http://www.rssboard.org/rss-specification 720 https://escholarship.org/uc/metx/rss Recent eScholarship items from Microbiology and Environmental Toxicology Sun, 28 Jun 2026 14:41:31 +0000 https://escholarship.org/uc/item/9ng999qt A measurement of the Higgs boson mass and width via its decay to two bosons is presented. Proton-proton collision data collected by the CMS experiment, corresponding to an integrated luminosity of at a center-of-mass energy of 13&nbsp;TeV, is used. The invariant mass distribution of four leptons in the on-shell Higgs boson decay is used to measure its mass and constrain its width. This yields the most precise single measurement of the Higgs boson mass to date, , and an upper limit on the width at 95%&nbsp;confidence level. A combination of the on- and off-shell Higgs boson production decaying to four leptons is used to determine the Higgs boson width, assuming that no new virtual particles affect the production, a premise that is tested by adding new heavy particles in the gluon fusion loop model. This result is combined with a previous CMS analysis of the off-shell Higgs boson production with decay to two leptons and two neutrinos, giving a measured Higgs boson width of ... https://escholarship.org/uc/item/9ng999qt Tue, 26 Aug 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Laer, T Van Mechelen, P Breugelmans, N D’Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Bilin, B Clerbaux, B Das, AK De Lentdecker, G Evard, H Favart, L Gianneios, P Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Mahdavikhorrami, M Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Amarilo, K Mota Samalan, A Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Wertz, S Alves, GA Pereira, M Alves Gallo Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Herrera, C Mora Moraes, A Teles, P Rebello Soeiro, M Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao https://escholarship.org/uc/item/7k7791cq A search is presented for the pair production of new heavy resonances, each decaying into a top quark (t) or antiquark and a gluon (g). The analysis uses data recorded with the CMS detector from proton–proton collisions at a center-of-mass energy of 13TeV$$\,\text {Te}\hspace{-.08em}\text {V}$$ at the LHC, corresponding to an integrated luminosity of 138fb-1$$\,\text {fb}^{-1}$$. Events with one muon or electron, multiple jets, and missing transverse momentum are selected. After using a deep neural network to enrich the data sample with signal-like events, distributions in the scalar sum of the transverse momenta of all reconstructed objects are analyzed in the search for a signal. No significant deviations from the standard model prediction are found. Upper limits at 95% confidence level are set on the product of cross section and branching fraction squared for the pair production of excited top quarks in the t∗→tg$$\text {t}^{*} \rightarrow {\text {t}} {\text {g}} $$ decay channel.... https://escholarship.org/uc/item/7k7791cq Mon, 21 Apr 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Benato, L Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Waltenberger, W Wulz, C-E Janssen, T Laer, T Van Mechelen, P Van Breugelmans, N D’Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Onsem, GP Van Putte, S Van Vannerom, D Bilin, B Clerbaux, B Das, AK De Bruyn, I De Lentdecker, G Evard, H Favart, L Gianneios, P Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Velde, C Vander Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Amarilo, K Mota Skovpen, K Bossche, N Van Den van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Favereau De Jeneret, J Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain, Sa Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Turkcapar, S Alves, GA Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Herrera, C Mora Teles, P Rebello Soeiro, M Manganote, EJ Tonelli Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM https://escholarship.org/uc/item/8t74756x The first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV, collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by hidden valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics. With no observed excess of events over the standard model expectation, limits are set on the cross section for production via gluon fusion of a scalar mediator with SUEP-like decays. https://escholarship.org/uc/item/8t74756x Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Mechelen, P Breugelmans, N D’Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Clerbaux, B Das, AK De Lentdecker, G Evard, H Favart, L Gianneios, P Hohov, D Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Mahdavikhorrami, M Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Mestdach, G Amarilo, K Mota Samalan, A Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Wertz, S Alves, GA Pereira, M Alves Gallo Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W https://escholarship.org/uc/item/8ks5b73d A search is performed for charged-lepton flavor violating processes in top quark ( ) production and decay. The data were collected by the CMS experiment from proton-proton collisions at a center-of-mass energy of 13&nbsp;TeV and correspond to an integrated luminosity of . The selected events are required to contain one opposite-sign electron-muon pair, a third charged lepton (electron or muon), and at least one jet of which no more than one is associated with a bottom quark. Boosted decision trees are used to distinguish signal from background, exploiting differences in the kinematics of the final states particles. The data are consistent with the standard model expectation. Upper limits at 95%&nbsp;confidence level are placed in the context of effective field theory on the Wilson coefficients, which range between depending on the flavor of the associated light quark and the Lorentz structure of the interaction. These limits are converted to upper limits on branching fractions... https://escholarship.org/uc/item/8ks5b73d Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Del Valle, A Escalante Hussain, PS Jeitler, M Krammer, N Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Mechelen, P Bols, ES D’Hondt, J Dansana, S De Moor, A Delcourt, M Faham, H El Lowette, S Makarenko, I Müller, D Sahasransu, AR Tavernier, S Tytgat, M Van Putte, S Vannerom, D Clerbaux, B De Lentdecker, G Favart, L Hohov, D Jaramillo, J Khalilzadeh, A Lee, K Mahdavikhorrami, M Malara, A Paredes, S Pétré, L Postiau, N Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Hong, Y Knolle, J Lambrecht, L Mestdach, G Rendón, C Samalan, A Skovpen, K Van Den Bossche, N Wezenbeek, L Benecke, A Bruno, G Caputo, C Delaere, C Donertas, IS Giammanco, A Jaffel, K Jain Lemaitre, V Lidrych, J Mastrapasqua, P Mondal, K Tran, TT Wertz, S Alves, GA Coelho, E Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM Da Silveira, GG De Jesus Damiao, D De Souza, S Fonseca Martins, J Herrera, C Mora Amarilo, K Mota Mundim, L https://escholarship.org/uc/item/84w4k34d The Higgs boson (H) trilinear self-coupling, λ 3 , is constrained via its measured properties and limits on the HH pair production using the proton-proton collision data collected by the CMS experiment at s = 13 TeV . The combination of event categories enriched in single-H and HH events is used to measure κ λ , defined as the value of λ 3 normalized to its standard model prediction, while simultaneously constraining the Higgs boson couplings to fermions and vector bosons. Values of κ λ outside the interval − 1.2 &lt; κ λ &lt; 7.5 are excluded at 2σ confidence level, which is compatible with the expected range of − 2.0 &lt; κ λ &lt; 7.7 under the assumption that all other Higgs boson couplings are equal to their standard model predicted values. Relaxing the assumption on the Higgs couplings to fermions and vector bosons the observed (expected) κ λ interval is constrained to be within − 1.4 &lt; κ λ &lt; 7.8 ( − 2.3 &lt; κ λ &lt; 7.8 ) at 2σ confidence level. https://escholarship.org/uc/item/84w4k34d Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Laer, T Van Mechelen, P Breugelmans, N D'Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Bilin, B Clerbaux, B Das, AK De Lentdecker, G Evard, H Favart, L Gianneios, P Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Mahdavikhorrami, M Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Amarilo, K Mota Samalan, A Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Wertz, S Alves, GA Pereira, M Alves Gallo Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W https://escholarship.org/uc/item/6x82z9st This paper describes the Combine software package used for statistical analyses by the CMS Collaboration. The package, originally designed to perform searches for a Higgs boson and the combined analysis of those searches, has evolved to become the statistical analysis tool presently used in the majority of measurements and searches performed by the CMS Collaboration. It is not specific to the CMS experiment, and this paper is intended to serve as a reference for users outside of the CMS Collaboration, providing an outline of the most salient features and capabilities. Readers are provided with the possibility to run Combine and reproduce examples provided in this paper using a publicly available container image. Since the package is constantly evolving to meet the demands of ever-increasing data sets and analysis sophistication, this paper cannot cover all details of Combine. However, the online documentation referenced within this paper provides an up-to-date and complete user guide. https://escholarship.org/uc/item/6x82z9st Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Mechelen, P Breugelmans, N D’Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Clerbaux, B Das, AK De Lentdecker, G Evard, H Favart, L Gianneios, P Hohov, D Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Mahdavikhorrami, M Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Mestdach, G Amarilo, K Mota Samalan, A Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Wertz, S Alves, GA Pereira, M Alves Gallo Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W https://escholarship.org/uc/item/6kp7s2b5 The first observation of the concurrent production of two mesons in proton-nucleus collisions is presented. The analysis is based on a proton-lead ( ) data sample recorded at a nucleon-nucleon center-of-mass energy of 8.16&nbsp;TeV by the CMS experiment at the CERN LHC and corresponding to an integrated luminosity of . The two mesons are reconstructed in their decay channels with transverse momenta and rapidity . Events where one of the mesons is reconstructed in the dielectron channel are also considered in the search. The process is observed with a significance of 5.3 standard deviations. The measured inclusive fiducial cross section, using the four-muon channel alone, is . A fit of the data to the expected rapidity separation for pairs of mesons produced in single (SPS) and double (DPS) parton scatterings yields and , respectively. This latter result can be transformed into a lower bound on the effective DPS cross section, closely related to the squared average... https://escholarship.org/uc/item/6kp7s2b5 Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Laer, T Van Mechelen, P Breugelmans, N D’Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Bilin, B Clerbaux, B Das, AK De Lentdecker, G Evard, H Favart, L Gianneios, P Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Mahdavikhorrami, M Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Amarilo, K Mota Samalan, A Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Wertz, S Alves, GA Pereira, M Alves Gallo Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W https://escholarship.org/uc/item/6ct533df This Letter presents the first search for bottom quark associated production of the standard model Higgs boson, in final states with leptons. Higgs boson decays to pairs of tau leptons and pairs of leptonically decaying W bosons are considered. The search is performed using data collected from 2016 to 2018 by the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 138 fb − 1 . Upper limits at the 95% confidence level are placed on the signal strength for Higgs boson production in association with bottom quarks; the observed (expected) upper limit is 3.7 (6.1) times the standard model prediction. https://escholarship.org/uc/item/6ct533df Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Waltenberger, W Wulz, C-E Janssen, T Van Laer, T Van Mechelen, P Breugelmans, N D'Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Bilin, B Clerbaux, B Das, AK De Lentdecker, G Evard, H Favart, L Gianneios, P Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Mahdavikhorrami, M Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Amarilo, K Mota Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Wertz, S Alves, GA Pereira, M Alves Gallo Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Herrera, C Mora Moraes, A Teles, P Rebello Soeiro, M Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM https://escholarship.org/uc/item/65r1f8q5 This Letter presents the first measurements of the groomed jet radius R g and the jet girth g in events with an isolated photon recoiling against a jet in lead-lead (PbPb) and proton-proton (pp) collisions at the LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. The observables R g and g provide a quantitative measure of how narrow or broad a jet is. The analysis uses PbPb and pp data samples with integrated luminosities of 1.7 &nbsp;nb − 1 and 301 &nbsp;pb − 1 , respectively, collected with the CMS experiment in 2018 and 2017. Events are required to have a photon with transverse momentum p T γ &gt; 100 &nbsp;GeV and at least one jet back-to-back in azimuth with respect to the photon and with transverse momentum p T jet such that p T jet / p T γ &gt; 0.4 . The measured R g and g distributions are unfolded to the particle level, which facilitates the comparison between the PbPb and pp results and with theoretical predictions. It is found that jets with p T jet / p T γ... https://escholarship.org/uc/item/65r1f8q5 Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Mechelen, P Bols, ES D'Hondt, J Dansana, S De Moor, A Delcourt, M Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Clerbaux, B Das, AK De Lentdecker, G Evard, H Favart, L Gianneios, P Hohov, D Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Mahdavikhorrami, M Malara, A Paredes, S Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Hong, Y Knolle, J Lambrecht, L Mestdach, G Amarilo, K Mota Rendón, C Samalan, A Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C Delaere, C Donertas, IS Giammanco, A Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Wertz, S Alves, GA Coelho, E Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM Da Silveira, GG De Jesus Damiao, D De Souza, S Fonseca De Souza, R Gomes Martins, J https://escholarship.org/uc/item/5dm688bn Measurements of the polarization and spin correlation in top quark pairs ( ) are presented using events with a single electron or muon and jets in the final state. The measurements are based on proton-proton collision data from the LHC at collected by the CMS experiment, corresponding to an integrated luminosity of . All coefficients of the polarization vectors and the spin correlation matrix are extracted simultaneously by performing a binned likelihood fit to the data. The measurement is performed inclusively and in bins of additional observables, such as the mass of the system and the top quark scattering angle in the rest frame. The measured polarization and spin correlation are in agreement with the standard model. From the measured spin correlation, conclusions on the spin entanglement are drawn by applying the Peres-Horodecki criterion. The standard model predicts entangled spins for states at the production threshold and at high masses of the system. Entanglement... https://escholarship.org/uc/item/5dm688bn Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Benato, L Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Waltenberger, W Wulz, C-E Janssen, T Van Laer, T Van Mechelen, P Breugelmans, N D’Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Bilin, B Clerbaux, B Das, AK De Bruyn, I De Lentdecker, G Evard, H Favart, L Gianneios, P Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Amarilo, K Mota Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Turkcapar, S Alves, GA Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Herrera, C Mora Teles, P Rebello Soeiro, M Manganote, EJ Tonelli Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM https://escholarship.org/uc/item/1d05p2b9 Searches for pair-produced multijet signatures using data corresponding to an integrated luminosity of 128  fb^{-1} of proton-proton collisions at sqrt[s]=13  TeV are presented. A data scouting technique is employed to record events with low jet scalar transverse momentum sum values. The electroweak production of particles predicted in R-parity violating supersymmetric models is probed for the first time with fully hadronic final states. This is the first search for prompt hadronically decaying mass-degenerate higgsinos, and extends current exclusions on R-parity violating top squarks and gluinos. https://escholarship.org/uc/item/1d05p2b9 Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Mechelen, P Breugelmans, N D’Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Clerbaux, B Das, AK De Lentdecker, G Evard, H Favart, L Gianneios, P Hohov, D Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Mahdavikhorrami, M Malara, A Paredes, S Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Mestdach, G Amarilo, K Mota Rendón, C Samalan, A Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Wertz, S Alves, GA Coelho, E Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Pereira, A Vilela Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J https://escholarship.org/uc/item/08t554tz Measurements at s = 13.6 TeV of the opposite-sign W boson pair production cross section in proton-proton collisions are presented. The data used in this study were collected with the CMS detector at the CERN LHC in 2022, and correspond to an integrated luminosity of 34.8 fb − 1 . Events are selected by requiring one electron and one muon of opposite charge. A maximum likelihood fit is performed on signal- and background-enriched data categories defined by the flavor and charge of the leptons, the number of jets, and number of jets originating from b quarks. The overall sensitivity is significantly better than that of previous results with a similar integrated luminosity. The improvement comes from a more refined control of experimental uncertainties and an improved fit strategy. An inclusive W + W − production cross section of 125.7 ± 5.6 pb is measured, in agreement with standard model predictions. Cross sections are also reported in a fiducial region close to that of the detector... https://escholarship.org/uc/item/08t554tz Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Waltenberger, W Wulz, C-E Janssen, T Van Laer, T Van Mechelen, P Breugelmans, N D'Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Bilin, B Clerbaux, B Das, AK De Lentdecker, G Evard, H Favart, L Gianneios, P Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Mahdavikhorrami, M Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Amarilo, K Mota Samalan, A Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Wertz, S Alves, GA Pereira, M Alves Gallo Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Herrera, C Mora Moraes, A Teles, P Rebello Soeiro, M Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J https://escholarship.org/uc/item/00f9n225 The CERN LHC provided proton and heavy ion collisions during its Run 2 operation period from 2015 to 2018. Proton-proton collisions reached a peak instantaneous luminosity of 2.1× 1034 cm-2s-1, twice the initial design value, at √(s)=13 TeV. The CMS experiment records a subset of the collisions for further processing as part of its online selection of data for physics analyses, using a two-level trigger system: the Level-1 trigger, implemented in custom-designed electronics, and the high-level trigger, a streamlined version of the offline reconstruction software running on a large computer farm. This paper presents the performance of the CMS high-level trigger system during LHC Run 2 for physics objects, such as leptons, jets, and missing transverse momentum, which meet the broad needs of the CMS physics program and the challenge of the evolving LHC and detector conditions. Sophisticated algorithms that were originally used in offline reconstruction were deployed online. Highlights... https://escholarship.org/uc/item/00f9n225 Tue, 4 Feb 2025 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Benato, L Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Waltenberger, W Wulz, C-E Janssen, T Van Laer, T Van Mechelen, P Breugelmans, N D'Hondt, J Dansana, S De Moor, A Delcourt, M Heyen, F Lowette, S Makarenko, I Müller, D Tavernier, S Tytgat, M Van Onsem, GP Van Putte, S Vannerom, D Beghin, D Bilin, B Brun, H Clerbaux, B Das, AK De Bruyn, I De Lentdecker, G Evard, H Favart, L Gianneios, P Jaramillo, J Khalilzadeh, A Khan, FA Lee, K Malara, A Paredes, S Shahzad, MA Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P Cornelis, T De Coen, M Dobur, D Gokbulut, G Hong, Y Knolle, J Lambrecht, L Marckx, D Amarilo, K Mota Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bethani, A Bruno, G Caputo, C De Jeneret, J De Favereau Delaere, C Donertas, IS Giammanco, A Guzel, AO Jain Lemaitre, V Lidrych, J Mastrapasqua, P Tran, TT Turkcapar, S Alves, GA Coelho, E Silva, G Correia Hensel, C De Oliveira, T Menezes Herrera, C Mora Teles, P Rebello Soeiro, M Manganote, EJ Tonelli Pereira, A Vilela Júnior, WL Aldá Filho, M Barroso Ferreira Malbouisson, H Brandao https://escholarship.org/uc/item/9ck8x5vn BackgroundThe burden of Aedes aegypti-transmitted viruses such as dengue, chikungunya, and Zika are increasing globally, fueled by urbanization and climate change, with some of the highest current rates of transmission in Asia. Local factors in the built environment have the potential to exacerbate or mitigate transmission.MethodsIn 24 informal urban settlements in Makassar, Indonesia and Suva, Fiji, we tested children under 5 years old for evidence of prior infection with dengue, chikungunya, and Zika viruses by IgG serology. We used a catalytic model using seroprevalence and mean age to estimate annual incidence of dengue in each country. We also conducted detailed questionnaires to evaluate environmental risk factors for a positive serology result. Dengue risk factors were evaluated for children by univariate and multivariable logistic regression accounting for settlement as a fixed effect. Trash and flooding were additionally evaluated as dengue risk factors at the settlement... https://escholarship.org/uc/item/9ck8x5vn Sat, 1 Feb 2025 00:00:00 +0000 Rosser, Joelle I Openshaw, John J Lin, Audrie Taruc, Ruzka R Tela, Autiko Tamodding, Nursehang Abdullah, Nurul Pausi Emelia Amiruddin, Murni Buyukcangaz, Esra Barker, S Fiona Turagabeci, Amelia Ansariadi Leder, Karin Wahid, Isra https://escholarship.org/uc/item/0t4781ct Antibiotics can trigger antimicrobial resistance and microbiome alterations. Reducing pathogen exposure and undernutrition can reduce infections and antibiotic use. We assess effects of water, sanitation, handwashing (WSH) and nutrition interventions on caregiver-reported antibiotic use in Bangladesh and Kenya, longitudinally measured at three timepoints among birth cohorts (ages 3–28 months) in a cluster-randomized trial. Over 50% of children used antibiotics at least once in the 90 days preceding data collection. In Bangladesh, the prevalence of antibiotic use was 10–14% lower in groups receiving WSH (prevalence ratio [PR] = 0.90 (0.82–0.99)), nutrition (PR = 0.86 (0.78–0.94)), and nutrition+WSH (PR = 0.86 (0.79–0.93)) interventions. The prevalence of using antibiotics multiple times was 26–35% lower in intervention arms. Reductions were largest when the birth cohort was younger. In Kenya, interventions did not affect antibiotic use. In this work, we show that improving WSH... https://escholarship.org/uc/item/0t4781ct Fri, 17 Jan 2025 00:00:00 +0000 Ercumen, Ayse Mertens, Andrew N https://orcid.org/0000-0002-1050-6721 Butzin-Dozier, Zachary Jung, Da Kyung Ali, Shahjahan Achando, Beryl S Rao, Gouthami Hemlock, Caitlin Pickering, Amy J https://orcid.org/0000-0001-6193-2221 Stewart, Christine P https://orcid.org/0000-0003-4575-8571 Tan, Sophia T Grembi, Jessica A Benjamin-Chung, Jade Wolfe, Marlene Ho, Gene G Rahman, Md Ziaur Arnold, Charles D https://orcid.org/0000-0001-6510-3172 Dentz, Holly N Njenga, Sammy M Meerkerk, Theodora Chen, Belinda Nadimpalli, Maya Islam, Mohammad Aminul Hubbard, Alan E https://orcid.org/0000-0002-3769-0127 Null, Clair Unicomb, Leanne Rahman, Mahbubur Colford, John M https://orcid.org/0000-0002-3288-6956 Luby, Stephen P Arnold, Benjamin F https://orcid.org/0000-0001-6105-7295 Lin, Audrie https://escholarship.org/uc/item/9m14t1jd <i>Helicobacter pylori</i> infects roughly half the world's population, causing gastritis, peptic ulcers, and gastric cancer in a subset. These pathologies occur in response to a chronic inflammatory state, but it is not fully understood how <i>H. pylori</i> controls this process. We characterized the inflammatory response of <i>H. pylori</i> mutants that cannot produce the quorum sensing molecule autoinducer 2 (AI-2) by deleting the gene for the AI-2 synthase, <i>luxS</i>. Our work shows that <i>H. pylori luxS</i> mutants colonize the stomach normally but recruit high numbers of CD4⁺ T cells to the stomach during chronic infection. This increase in the number of CD4⁺ T cells correlated with elevated expression of <i>CXCL9</i>, a chemokine important for T cell recruitment. Together, our results suggest that <i>H. pylori</i> may utilize AI-2 signaling to modulate the inflammatory response during chronic infection. IMPORTANCE: Many bacteria signal to each other... https://escholarship.org/uc/item/9m14t1jd Sat, 28 Dec 2024 00:00:00 +0000 Yang, Christina Rodriguez y Baena, Alessandra https://orcid.org/0000-0003-2510-7173 Manso, Bryce A https://orcid.org/0000-0002-4860-4888 Hu, Shuai Lopez-Magaña, Raymondo Ohanyan, Mané Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/2j1270w5 Dengue fever is a mosquito-transmitted disease of great public health importance. Dengue lacks adequate vaccine protection and insecticide-based methods of mosquito control are proving increasingly ineffective. Here we review the emerging use of mosquitoes transinfected with the obligate intracellular bacterium Wolbachia pipientis for vector control. Wolbachia often induces cytoplasmic incompatibility in its mosquito hosts, resulting in infertile progeny between an infected male and an uninfected female. Wolbachia infection also suppresses the replication of pathogens in the mosquito, a process known as "pathogen blocking". Two strategies have emerged. The first one releases Wolbachia carriers (both male and female) to replace the wild mosquito population, a process driven by cytoplasmic incompatibility and that becomes irreversible once a threshold is reached. This suppresses disease transmission mainly by pathogen blocking and frequently requires a single intervention. The second... https://escholarship.org/uc/item/2j1270w5 Thu, 26 Dec 2024 00:00:00 +0000 Montenegro, Diego Cortés-Cortés, Gerardo Balbuena-Alonso, María Guadalupe Warner, Caison Camps, Manel https://orcid.org/0000-0002-0467-4032 https://escholarship.org/uc/item/6v4667dn The circadian clock is a cell-autonomous process that regulates daily internal rhythms by interacting with environmental signals. Reports across species show that infection can alter the expression of circadian genes; however, in teleosts, these effects are influenced by light exposure. Currently, no reports analyze the direct effects of bacterial exposure on the zebrafish clock. Using zebrafish Z3 cells, we demonstrate that exposure to heat-killed Streptococcus pneumoniae (HK-Spn) augments the expression of core repressive factors in a light- and time-dependent manner. In constant darkness, HK-Spn highly upregulated cry1a, per3, and per1b expression. In the presence of light, HK-Spn exposure rapidly and strongly upregulated per2 and cry1a, and this was proportionally increased with light intensity. The combinatorial effect of light and HK-Spn on per2 and cry1a was not duplicated with H2O2, a known byproduct of light exposure. However, the ROS inhibitor N-acetyl cysteine was sufficient... https://escholarship.org/uc/item/6v4667dn Fri, 29 Nov 2024 00:00:00 +0000 Morales Fénero, Camila Sacksteder, Raina E Diamos, Andrew G Kimmey, Jacqueline M https://orcid.org/0000-0003-1330-8525 https://escholarship.org/uc/item/988907w5 BACKGROUND: Manganese (Mn) is both an essential and toxic metal, and associations with neurodevelopment depend on exposure timing. Prospective data examining early life Mn with adolescent cognition are sparse. METHODS: We enrolled 140 Italian adolescents (10-14&nbsp;years old) from the Public Health Impact of Metals Exposure study. Mn in deciduous teeth was measured using laser ablation-mass spectrometry to represent prenatal, postnatal and early childhood exposure. The California Verbal Learning Test for Children (CVLT-C) was administered to assess adolescent verbal learning and memory. Multivariable regression models estimated changes in CVLT-C scores and the odds of making an error per doubling in dentine Mn in each exposure period. Multiple informant models tested for differences in associations across exposure periods. RESULTS: A doubling in prenatal dentine Mn levels was associated with lower odds of making an intrusion error (OR&nbsp;=&nbsp;0.23 [95% CI: 0.09, 0.61]). This... https://escholarship.org/uc/item/988907w5 Wed, 13 Nov 2024 00:00:00 +0000 Friedman, Alexa Schildroth, Samantha Bauer, Julia A Coull, Brent A Smith, Donald R Placidi, Donatella Cagna, Giuseppa Krengel, Maxine H Tripodis, Yorghos White, Roberta F Lucchini, Roberto G Wright, Robert O Horton, Megan Austin, Christine Arora, Manish Claus Henn, Birgit https://escholarship.org/uc/item/3fc3x83h Antibiotic-resistant bacteria are an emerging global health threat. New antimicrobials are urgently needed. The injectisome type III secretion system (T3SS), required by dozens of Gram-negative bacteria for virulence but largely absent from nonpathogenic bacteria, is an attractive antimicrobial target. We previously identified synthetic cyclic peptomers, inspired by the natural product phepropeptin D, that inhibit protein secretion through the <i>Yersinia</i> Ysc and Pseudomonas aeruginosa Psc T3SSs but do not inhibit bacterial growth. Here, we describe the identification of an isomer, 4EpDN, that is 2-fold more potent (50% inhibitory concentration [IC₅₀] of 4 μM) than its parental compound. Furthermore, 4EpDN inhibited the <i>Yersinia</i> Ysa and the Salmonella SPI-1 T3SSs, suggesting that this cyclic peptomer has broad efficacy against evolutionarily distant injectisome T3SSs. Indeed, 4EpDN strongly inhibited intracellular growth of Chlamydia trachomatis in HeLa cells,... https://escholarship.org/uc/item/3fc3x83h Tue, 12 Nov 2024 00:00:00 +0000 Lam, Hanh N Lau, Tannia Lentz, Adam Sherry, Jessica Cabrera-Cortez, Alejandro Hug, Karen Lalljie, Annalyse Engel, Joanne Lokey, R Scott Auerbuch, Victoria https://escholarship.org/uc/item/77n188vq The intestinal lumen is a turbulent, semi-fluid landscape where microbial cells and nutrient-rich particles are distributed with high heterogeneity. Major questions regarding the basic physical structure of this dynamic microbial ecosystem remain unanswered. Most gut microbes are non-motile, and it is unclear how they achieve optimum localization relative to concentrated aggregations of dietary glycans that serve as their primary source of energy. In addition, a random spatial arrangement of cells in this environment is predicted to limit sustained interactions that drive co-evolution of microbial genomes. The ecological consequences of random versus organized microbial localization have the potential to control both the metabolic outputs of the microbiota and the propensity for enteric pathogens to participate in proximity-dependent microbial interactions. Here, we review evidence suggesting that several bacterial species adopt organized spatial arrangements in the gut via adhesion.... https://escholarship.org/uc/item/77n188vq Tue, 5 Nov 2024 00:00:00 +0000 Chiang, Bo Huey Vega, Giovanni Dunwoody, Sarah C Patnode, Michael L https://escholarship.org/uc/item/7mr1p2x6 Background: Motor function is critical for children's health, yet remains an understudied neurodevelopmental domain. Exposure to metals has been linked with motor function, but no study has examined the joint effects of metal mixtures. Methods: We evaluated cross-sectional associations between a metal mixture and motor function among 569 adolescents (10-14 years old) living near the ferroalloy industry. Concentrations of blood lead, hair manganese, hair copper, and hair chromium were quantified using inductively coupled plasma mass spectrometry. Neuropsychologists administered multiple fine motor function assessments: pursuit aiming, finger tapping, visual reaction time (VRT), and subtests from the Luria Nebraska battery. We estimated associations between motor function and the metal mixture using quantile-based g-computation and multivariable linear regression, adjusting for child age, sex, and socioeconomic status. We explored sex-specific associations in stratified models. Results:... https://escholarship.org/uc/item/7mr1p2x6 Sat, 17 Aug 2024 00:00:00 +0000 Friedman, Alexa Schildroth, Samantha Fruh, Victoria Krengel, Maxine H Tripodis, Yorghos Placidi, Donatella White, Roberta F Lucchini, Roberto G Smith, Donald R Wright, Robert O Horton, Megan K Henn, Birgit Claus https://escholarship.org/uc/item/75b8x71r A search for the production of a top quark in association with a photon and additional jets via flavor changing neutral current interactions is presented. The analysis uses proton-proton collision data recorded by the CMS detector at a center-of-mass energy of 13&nbsp;TeV, corresponding to an integrated luminosity of . The search is performed by looking for processes where a single top quark is produced in association with a photon, or a pair of top quarks where one of the top quarks decays into a photon and an up or charm quark. Events with an electron or a muon, a photon, one or more jets, and missing transverse momentum are selected. Multivariate analysis techniques are used to discriminate signal and standard model background processes. No significant deviation is observed over the predicted background. Observed (expected) upper limits are set on the branching fractions of top quark decays: ( ) and ( ) at 95%&nbsp;confidence level, assuming a single nonzero coupling at... https://escholarship.org/uc/item/75b8x71r Wed, 7 Aug 2024 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Del Valle, A Escalante Hussain, PS Jeitler, M Krammer, N Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Mechelen, P Bols, ES D’Hondt, J Dansana, S De Moor, A Delcourt, M Faham, H El Lowette, S Makarenko, I Müller, D Sahasransu, AR Tavernier, S Tytgat, M Van Putte, S Vannerom, D Clerbaux, B De Lentdecker, G Favart, L Hohov, D Jaramillo, J Khalilzadeh, A Lee, K Mahdavikhorrami, M Malara, A Paredes, S Pétré, L Postiau, N Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Hong, Y Knolle, J Lambrecht, L Mestdach, G Rendón, C Samalan, A Skovpen, K Van Den Bossche, N Wezenbeek, L Benecke, A Bruno, G Caputo, C Delaere, C Donertas, IS Giammanco, A Jaffel, K Jain Lemaitre, V Lidrych, J Mastrapasqua, P Mondal, K Tran, TT Wertz, S Alves, GA Coelho, E Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM Da Silveira, GG De Jesus Damiao, D De Souza, S Fonseca Martins, J Herrera, C Mora Amarilo, K Mota Mundim, L https://escholarship.org/uc/item/35m4g718 A search is presented for charged, long-lived supersymmetric particles in final states with one or more disappearing tracks. The search is based on data from proton-proton collisions at a center-of-mass energy of 13&nbsp;TeV collected with the CMS detector at the CERN LHC between 2016 and 2018, corresponding to an integrated luminosity of . The search is performed over final states characterized by varying numbers of jets, -tagged jets, electrons, and muons. The length of signal-candidate tracks in the plane perpendicular to the beam axis is used to characterize the lifetimes of wino- and Higgsino-like charginos produced in the context of the minimal supersymmetric standard model. The energy loss of signal-candidate tracks is used to increase the sensitivity to charginos with a large mass and thus a small Lorentz boost. The observed results are found to be statistically consistent with the background-only hypothesis. Limits on the pair-production cross section of gluinos and... https://escholarship.org/uc/item/35m4g718 Wed, 7 Aug 2024 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Del Valle, A Escalante Hussain, PS Jeitler, M Krammer, N Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Mechelen, P Bols, ES D’Hondt, J Dansana, S De Moor, A Delcourt, M Faham, H El Lowette, S Makarenko, I Müller, D Sahasransu, AR Tavernier, S Tytgat, M Van Putte, S Vannerom, D Clerbaux, B De Lentdecker, G Favart, L Hohov, D Jaramillo, J Khalilzadeh, A Lee, K Mahdavikhorrami, M Malara, A Paredes, S Pétré, L Postiau, N Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Hong, Y Knolle, J Lambrecht, L Mestdach, G Rendón, C Samalan, A Skovpen, K Van Den Bossche, N Wezenbeek, L Benecke, A Bruno, G Caputo, C Delaere, C Donertas, IS Giammanco, A Jaffel, K Jain Lemaitre, V Lidrych, J Mastrapasqua, P Mondal, K Tran, TT Wertz, S Alves, GA Coelho, E Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM Da Silveira, GG De Jesus Damiao, D De Souza, S Fonseca Martins, J Herrera, C Mora Amarilo, K Mota Mundim, L https://escholarship.org/uc/item/70w1n7kj Sibling rivalry among the ZBTB transcription factor family: homo vs heterodimerization https://escholarship.org/uc/item/70w1n7kj Thu, 1 Aug 2024 00:00:00 +0000 Piepoli, Sofia https://orcid.org/0000-0002-3891-9464 Akkose, Umit Nogay, Liyne Taskiran, Hakan Tolay, Nazife Gezen, Melike Adebali, Ogun Atilgan, Canan Erman, Batu https://escholarship.org/uc/item/9g15583q The azimuthal anisotropy of Image 1 mesons in high-multiplicity proton-lead collisions is studied using data collected by the CMS experiment at a nucleon-nucleon center-of-mass energy of 8.16 TeV . The Image 1 mesons are reconstructed using their dimuon decay channel. The anisotropy is characterized by the second Fourier harmonic coefficients, found using a two-particle correlation technique, in which the Image 1 mesons are correlated with charged hadrons. A large pseudorapidity gap is used to suppress short-range correlations. Nonflow contamination from the dijet background is removed using a low-multiplicity subtraction method, and the results are presented as a function of Image 1 transverse momentum. The azimuthal anisotropies are smaller than those found for charmonia in proton-lead collisions at the same collision energy, but are consistent with values found for Image 1 mesons in lead-lead interactions at a nucleon-nucleon center-of-mass energy of 5.02 TeV. https://escholarship.org/uc/item/9g15583q Wed, 24 Jul 2024 00:00:00 +0000 Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Del Valle, A Escalante Hussain, PS Jeitler, M Krammer, N Lechner, L Liko, D Mikulec, I Paulitsch, P Pitters, FM Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Kello, T Sfar, H Rejeb Van Mechelen, P Bols, ES D'Hondt, J De Moor, A Delcourt, M Faham, H El Lowette, S Moortgat, S Morton, A Müller, D Sahasransu, AR Tavernier, S Van Doninck, W Vannerom, D Clerbaux, B De Lentdecker, G Favart, L Hohov, D Jaramillo, J Lee, K Mahdavikhorrami, M Makarenko, I Malara, A Paredes, S Pétré, L Postiau, N Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P Dobur, D Knolle, J Lambrecht, L Mestdach, G Niedziela, M Rendón, C Roskas, C Samalan, A Skovpen, K Tytgat, M Van Den Bossche, N Vermassen, B Wezenbeek, L Benecke, A Bruno, G Bury, F Caputo, C David, P Delaere, C Donertas, IS Giammanco, A Jaffel, K Jain Lemaitre, V Mondal, K Taliercio, A Tran, TT Vischia, P Wertz, S Alves, GA Coelho, E Hensel, C Moraes, A Teles, P Rebello Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM Da Silveira, GG De Jesus Damiao, D https://escholarship.org/uc/item/8sq3n3c6 A search is presented for new Higgs bosons in proton-proton (pp) collision events in which a same-sign top quark pair is produced in association with a jet, via the p p → t H / A → t t c ‾ and p p → t H / A → t t u ‾ processes. Here, H and A represent the extra scalar and pseudoscalar boson, respectively, of the second Higgs doublet in the generalized two-Higgs-doublet model (g2HDM). The search is based on pp collision data collected at a center-of-mass energy of 13 TeV with the CMS detector at the LHC, corresponding to an integrated luminosity of 138fb−1. Final states with a same-sign lepton pair in association with jets and missing transverse momentum are considered. New Higgs bosons in the 200–1000 GeV mass range and new Yukawa couplings between 0.1 and 1.0 are targeted in the search, for scenarios in which either H or A appear alone, or in which they coexist and interfere. No significant excess above the standard model prediction is observed. Exclusion limits are derived in... https://escholarship.org/uc/item/8sq3n3c6 Wed, 24 Jul 2024 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Hussain, PS Jeitler, M Krammer, N Li, A Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Mechelen, P Bols, ES D'Hondt, J Dansana, S De Moor, A Delcourt, M Faham, H El Lowette, S Makarenko, I Müller, D Sahasransu, AR Tavernier, S Tytgat, M Van Putte, S Vannerom, D Clerbaux, B De Lentdecker, G Favart, L Hohov, D Jaramillo, J Khalilzadeh, A Lee, K Mahdavikhorrami, M Malara, A Paredes, S Pétré, L Postiau, N Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Hong, Y Knolle, J Lambrecht, L Mestdach, G Rendón, C Samalan, A Skovpen, K Van Den Bossche, N van der Linden, J Wezenbeek, L Benecke, A Bruno, G Caputo, C Delaere, C Donertas, IS Giammanco, A Jaffel, K Jain Lemaitre, V Lidrych, J Mastrapasqua, P Mondal, K Tran, TT Wertz, S Alves, GA Coelho, E Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM Da Silveira, GG De Jesus Damiao, D De Souza, S Fonseca Martins, J Herrera, C Mora Amarilo, K Mota https://escholarship.org/uc/item/80x0308b Vibrio vulnificus is an opportunistic pathogen that causes gastroenteritis and septicemia in humans. The V. vulnificus multifunctional-autoprocessing repeats-in-toxin (MARTX) toxin is a pore-forming toxin that translocates multiple functionally independent effector domains into target cells and an essential virulence factor for fatal disease. The effector repertoire delivered and thus the mechanism of action of the toxin can differ dramatically across V. vulnificus isolates. Here, we utilize a strain of V. vulnificus that carries an F-type MARTX toxin that delivers an actin cross-linking domain (ACD) and four other effector domains. We demonstrate that ACD is the primary driver of virulence following intragastric infection and of bacterial dissemination to distal organs. We additionally show that ACD activates the transcription of intermediate early response genes in cultured intestinal epithelial cells (IECs). However, the genes activated by ACD are suppressed, at least in part,... https://escholarship.org/uc/item/80x0308b Wed, 24 Jul 2024 00:00:00 +0000 Woida, Patrick J Kitts, Giordan Shee, Stephanie Godzik, Adam Satchell, Karla JF https://escholarship.org/uc/item/7w04z1kv The identification of prompt and isolated muons, as well as muons from heavy-flavour hadron decays, is an important task. We developed two multivariate techniques to provide highly efficient identification for muons with transverse momentum greater than 10 GeV. One provides a continuous variable as an alternative to a cut-based identification selection and offers a better discrimination power against misidentified muons. The other one selects prompt and isolated muons by using isolation requirements to reduce the contamination from nonprompt muons arising in heavy-flavour hadron decays. Both algorithms are developed using 59.7 fb-1 of proton-proton collisions data at a centre-of-mass energy of √(s)=13 TeV collected in 2018 with the CMS experiment at the CERN LHC. https://escholarship.org/uc/item/7w04z1kv Wed, 24 Jul 2024 00:00:00 +0000 Hayrapetyan, A Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Del Valle, A Escalante Hussain, PS Jeitler, M Krammer, N Liko, D Mikulec, I Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Van Mechelen, P Bols, ES D'Hondt, J Dansana, S De Moor, A Delcourt, M Faham, H El Lowette, S Makarenko, I Müller, D Sahasransu, AR Tavernier, S Tytgat, M Van Putte, S Vannerom, D Clerbaux, B De Lentdecker, G Favart, L Hohov, D Jaramillo, J Khalilzadeh, A Lee, K Mahdavikhorrami, M Malara, A Paredes, S Pétré, L Postiau, N Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P De Coen, M Dobur, D Hong, Y Knolle, J Lambrecht, L Mestdach, G Rendón, C Samalan, A Skovpen, K Van Den Bossche, N Wezenbeek, L Benecke, A Bruno, G Caputo, C Delaere, C Donertas, IS Giammanco, A Jaffel, K Jain Lemaitre, V Lidrych, J Mastrapasqua, P Mondal, K Tran, TT Wertz, S Alves, GA Coelho, E Hensel, C De Oliveira, T Menezes Moraes, A Teles, P Rebello Soeiro, M Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM Da Silveira, GG De Jesus Damiao, D De Souza, S Fonseca Martins, J Herrera, C Mora Amarilo, K Mota Mundim, L https://escholarship.org/uc/item/7kw0g7vh Measurements of the elliptic ( v 2 ) and triangular ( v 3 ) azimuthal anisotropy coefficients are presented for Image 1 mesons produced in Image 2 hadron decays (nonprompt Image 1 mesons) in lead-lead collisions at s NN = 5.02 TeV . The results are compared with previously published charm meson anisotropies measured using prompt Image 1 mesons. The data were collected with the CMS detector in 2018 with an integrated luminosity of 0.58 nb − 1 . Azimuthal anisotropy is sensitive to the interactions of quarks with the hot and dense medium created in heavy ion collisions. Comparing results for prompt and nonprompt Image 1 mesons can assist in understanding the mass dependence of these interactions. The nonprompt results show lower magnitudes of v 2 and v 3 and weaker dependences on the meson transverse momentum and collision centrality than those found for prompt Image 1 mesons. The results are in agreement with theoretical predictions that include a mass dependence in the interactions... https://escholarship.org/uc/item/7kw0g7vh Wed, 24 Jul 2024 00:00:00 +0000 Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Del Valle, A Escalante Hussain, PS Jeitler, M Krammer, N Lechner, L Liko, D Mikulec, I Paulitsch, P Pitters, FM Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Kello, T Sfar, H Rejeb Van Mechelen, P Bols, ES D'Hondt, J De Moor, A Delcourt, M Faham, H El Lowette, S Moortgat, S Morton, A Müller, D Sahasransu, AR Tavernier, S Van Doninck, W Vannerom, D Clerbaux, B De Lentdecker, G Favart, L Hohov, D Jaramillo, J Lee, K Mahdavikhorrami, M Makarenko, I Malara, A Paredes, S Pétré, L Postiau, N Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P Dobur, D Knolle, J Lambrecht, L Mestdach, G Rendón, C Samalan, A Skovpen, K Tytgat, M Van Den Bossche, N Vermassen, B Wezenbeek, L Benecke, A Bruno, G Bury, F Caputo, C David, P Delaere, C Donertas, IS Giammanco, A Jaffel, K Jain Lemaitre, V Mondal, K Taliercio, A Tran, TT Vischia, P Wertz, S Alves, GA Coelho, E Hensel, C Moraes, A Teles, P Rebello Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM Da Silveira, GG De Jesus Damiao, D Dos Santos Sousa, V De Souza, S Fonseca https://escholarship.org/uc/item/48t3m7m6 Pandemic and endemic strains of Vibrio cholerae arise from toxigenic conversion by the CTXφ bacteriophage, a process by which CTXφ infects nontoxigenic strains of V.&nbsp;cholerae. CTXφ encodes the cholera toxin, an enterotoxin responsible for the watery diarrhea associated with cholera infections. Despite the critical role of CTXφ during infections, signals that affect CTXφ‐driven toxigenic conversion or expression of the CTXφ‐encoded cholera toxin remain poorly characterized, particularly in the context of the gut mucosa. Here, we identify mucin polymers as potent regulators of CTXφ‐driven pathogenicity in V.&nbsp;cholerae. Our results indicate that mucin‐associated O‐glycans block toxigenic conversion by CTXφ and suppress the expression of CTXφ‐related virulence factors, including the toxin co‐regulated pilus and cholera toxin, by interfering with the TcpP/ToxR/ToxT virulence pathway. By synthesizing individual mucin glycan structures de novo, we identify the Core 2 motif as... https://escholarship.org/uc/item/48t3m7m6 Wed, 24 Jul 2024 00:00:00 +0000 Wang, Benjamin X Takagi, Julie McShane, Abigail Park, Jin Hwan https://orcid.org/0000-0001-8384-7909 Aoki, Kazuhiro Griffin, Catherine Teschler, Jennifer Kitts, Giordan Minzer, Giulietta Tiemeyer, Michael Hevey, Rachel Yildiz, Fitnat Ribbeck, Katharina https://escholarship.org/uc/item/1tj5h0dh The facultative human pathogen, Vibrio cholerae, employs two-component signal transduction systems (TCS) to sense and respond to environmental signals encountered during its infection cycle. TCSs consist of a sensor histidine kinase (HK) and a response regulator (RR); the V. cholerae genome encodes 43 HKs and 49 RRs, of which 25 are predicted to be cognate pairs. Using deletion mutants of each HK gene, we analyzed the transcription of vpsL, a biofilm gene required for Vibrio polysaccharide and biofilm formation. We found that a V. cholerae TCS that had not been studied before, now termed Rvv, controls biofilm gene transcription. The Rvv TCS is part of a three-gene operon that is present in 30% of Vibrionales species. The rvv operon encodes RvvA, the HK; RvvB, the cognate RR; and RvvC, a protein of unknown function. Deletion of rvvA increased transcription of biofilm genes and altered biofilm formation, while deletion of rvvB or rvvC lead to no changes in biofilm gene transcription.... https://escholarship.org/uc/item/1tj5h0dh Wed, 24 Jul 2024 00:00:00 +0000 Kitts, Giordan Rogers, Andrew Teschler, Jennifer K Park, Jin Hwan https://orcid.org/0000-0001-8384-7909 Trebino, Michael A Chaudry, Issac Erill, Ivan Yildiz, Fitnat H https://escholarship.org/uc/item/1nf9p7zh The assembly status of the V. cholerae flagellum regulates biofilm formation, suggesting that the bacterium senses a lack of movement to commit to a sessile lifestyle. Motility and biofilm formation are inversely regulated by the second messenger molecule cyclic dimeric guanosine monophosphate (c-di-GMP). Therefore, we sought to define the flagellum-associated c-di-GMP-mediated signaling pathways that regulate the transition from a motile to a sessile state. Here we report that elimination of the flagellum, via loss of the FlaA flagellin, results in a flagellum-dependent biofilm regulatory (FDBR) response, which elevates cellular c-di-GMP levels, increases biofilm gene expression, and enhances biofilm formation. The strength of the FDBR response is linked with status of the flagellar stator: it can be reversed by deletion of the T ring component MotX, and reduced by mutations altering either the Na+ binding ability of the stator or the Na+ motive force. Absence of the stator also... https://escholarship.org/uc/item/1nf9p7zh Wed, 24 Jul 2024 00:00:00 +0000 Wu, Daniel C Zamorano-Sánchez, David Pagliai, Fernando A Park, Jin Hwan https://orcid.org/0000-0001-8384-7909 Floyd, Kyle A Lee, Calvin K Kitts, Giordan Rose, Christopher B Bilotta, Eric M Wong, Gerard CL Yildiz, Fitnat H https://escholarship.org/uc/item/0w18t2n1 Two-particle Bose–Einstein momentum correlation functions are studied for charged-hadron pairs in lead-lead collisions at a center-of-mass energy per nucleon pair of . The data sample, containing minimum bias events corresponding to an integrated luminosity of 0.607 , was collected by the CMS experiment in 2018. The experimental results are discussed in terms of a Lévy-type source distribution. The parameters of this distribution are extracted as functions of particle pair average transverse mass and collision centrality. These parameters include the Lévy index or shape parameter , the Lévy scale parameter , and the correlation strength parameter . The source shape, characterized by , is found to be neither Cauchy nor Gaussian, implying the need for a full Lévy analysis. Similarly to what was previously found for systems characterized by Gaussian source radii, a hydrodynamical scaling is observed for the Lévy parameter. The parameter is studied in terms of the core-halo... https://escholarship.org/uc/item/0w18t2n1 Wed, 24 Jul 2024 00:00:00 +0000 Tumasyan, A Adam, W Andrejkovic, JW Bergauer, T Chatterjee, S Damanakis, K Dragicevic, M Del Valle, A Escalante Hussain, PS Jeitler, M Krammer, N Lechner, L Liko, D Mikulec, I Paulitsch, P Schieck, J Schöfbeck, R Schwarz, D Sonawane, M Templ, S Waltenberger, W Wulz, C-E Darwish, MR Janssen, T Kello, T Sfar, H Rejeb Van Mechelen, P Bols, ES D'Hondt, J De Moor, A Delcourt, M Faham, H El Lowette, S Morton, A Müller, D Sahasransu, AR Tavernier, S Van Doninck, W Van Putte, S Vannerom, D Clerbaux, B Dansana, S De Lentdecker, G Favart, L Hohov, D Jaramillo, J Lee, K Mahdavikhorrami, M Makarenko, I Malara, A Paredes, S Pétré, L Postiau, N Thomas, L Bemden, M Vanden Vander Velde, C Vanlaer, P Dobur, D Knolle, J Lambrecht, L Mestdach, G Rendón, C Samalan, A Skovpen, K Tytgat, M Van Den Bossche, N Vermassen, B Wezenbeek, L Benecke, A Bruno, G Bury, F Caputo, C David, P Delaere, C Donertas, IS Giammanco, A Jaffel, K Jain Lemaitre, V Mondal, K Taliercio, A Tran, TT Vischia, P Wertz, S Alves, GA Coelho, E Hensel, C Moraes, A Teles, P Rebello Júnior, WL Aldá Pereira, M Alves Gallo Filho, M Barroso Ferreira Malbouisson, H Brandao Carvalho, W Chinellato, J Da Costa, EM Da Silveira, GG De Jesus Damiao, D Dos Santos Sousa, V De Souza, S Fonseca https://escholarship.org/uc/item/72r3v1xw The BTB domain is an oligomerization domain found in over 300 proteins encoded in the human genome. In the family of BTB domain and zinc finger-containing (ZBTB) transcription factors, 49 members share the same protein architecture. The N-terminal BTB domain is structurally conserved among the family members and serves as the dimerization site, whereas the C-terminal zinc finger motifs mediate DNA binding. The available BTB domain structures from this family reveal a natural inclination for homodimerization. In this study, we investigated the potential for heterodimer formation in the cellular environment. We selected five BTB homodimers and four heterodimer structures. We performed cell-based binding assays with fluorescent protein-BTB domain fusions to assess dimer formation. We tested the binding of several BTB pairs, and we were able to confirm the heterodimeric physical interaction between the BTB domains of PATZ1 and PATZ2, previously reported only in an interactome mapping... https://escholarship.org/uc/item/72r3v1xw Fri, 19 Jul 2024 00:00:00 +0000 Piepoli, Sofia https://orcid.org/0000-0002-3891-9464 Barakat, Sarah Nogay, Liyne Şimşek, Büşra Akkose, Umit Taskiran, Hakan Tolay, Nazife Gezen, Melike Yeşilada, Canberk Yarkın Tuncay, Mustafa Adebali, Ogün Atilgan, Canan Erman, Batu https://escholarship.org/uc/item/5f2721tq PATZ1 is a ubiquitously expressed transcriptional repressor belonging to the ZBTB family that is functionally expressed in T lymphocytes. PATZ1 targets the CD8 gene in lymphocyte development and interacts with the p53 protein to control genes that are important in proliferation and in the DNA-damage response. PATZ1 exerts its activity through an N-terminal BTB domain that mediates dimerization and co-repressor interactions and a C-terminal zinc-finger motif-containing domain that mediates DNA binding. Here, the crystal structures of the murine and zebrafish PATZ1 BTB domains are reported at 2.3 and 1.8 Å resolution, respectively. The structures revealed that the PATZ1 BTB domain forms a stable homodimer with a lateral surface groove, as in other ZBTB structures. Analysis of the lateral groove revealed a large acidic patch in this region, which contrasts with the previously resolved basic co-repressor binding interface of BCL6. A large 30-amino-acid glycine- and alanine-rich central... https://escholarship.org/uc/item/5f2721tq Fri, 19 Jul 2024 00:00:00 +0000 Piepoli, Sofia https://orcid.org/0000-0002-3891-9464 Alt, Aaron Oliver Atilgan, Canan Mancini, Erika Jazmin Erman, Batu https://escholarship.org/uc/item/4534r5qh Structure and Function of the LRBA Protein https://escholarship.org/uc/item/4534r5qh Thu, 18 Jul 2024 00:00:00 +0000 Ezen, Ege Çatak, Mehmet Cihangir Çatak, Feyza Bayram Piepoli, Sofia Zahedimaram, Pegah Ultanır, Ecem Barış, Safa Erman, Batu https://escholarship.org/uc/item/2tv1q28j <i>Streptococcus pneumoniae,</i> a common cause of community-acquired bacterial pneumonia, can cross the respiratory epithelial barrier to cause lethal septicemia and meningitis. <i>S. pneumoniae</i> pore-forming toxin pneumolysin (PLY) triggers robust neutrophil (PMN) infiltration that promotes bacterial transepithelial migration <i>in vitro</i> and disseminated disease in mice. Apical infection of polarized respiratory epithelial monolayers by <i>S. pneumoniae</i> at a multiplicity of infection (MOI) of 20 resulted in recruitment of PMNs, loss of 50% of the monolayer, and PMN-dependent bacterial translocation. Reducing the MOI to 2 decreased PMN recruitment two-fold and preserved the monolayer, but apical-to-basolateral translocation of <i>S. pneumoniae</i> remained relatively efficient. At both MOI of 2 and 20, PLY was required for maximal PMN recruitment and bacterial translocation. Co-infection by wild-type <i>S. pneumoniae</i> restored translocation by a PLY-deficient mutant,... https://escholarship.org/uc/item/2tv1q28j Thu, 18 Jul 2024 00:00:00 +0000 Xu, Shuying Mo, Devons Rizvi, Fatima Z Rosa, Juan P Ruiz, Jorge Tan, Shumin Tweten, Rodney K Leong, John M Adams, Walter https://escholarship.org/uc/item/9gt4g9jg Two-component signal transduction systems (TCSs), typically composed of a sensor histidine kinase (HK) and a response regulator (RR), are the primary mechanism by which pathogenic bacteria sense and respond to extracellular signals. The pathogenic bacterium <i>Vibrio cholerae</i> is no exception and harbors 52 RR genes. Using in-frame deletion mutants of each RR gene, we performed a systematic analysis of their role in <i>V. cholerae</i> biofilm formation. We determined that 7 RRs impacted the expression of an essential biofilm gene and found that the recently characterized RR, VxrB, regulates the expression of key structural and regulatory biofilm genes in <i>V. cholerae</i><i>vxrB</i> is part of a 5-gene operon, which contains the cognate HK <i>vxrA</i> and three genes of unknown function. Strains carrying Δ<i>vxrA</i> and Δ<i>vxrB</i> mutations are deficient in biofilm formation, while the Δ<i>vxrC</i> mutation enhances biofilm formation. The overexpression of VxrB led to a... https://escholarship.org/uc/item/9gt4g9jg Tue, 16 Jul 2024 00:00:00 +0000 Teschler, Jennifer K Cheng, Andrew T Yildiz, Fitnat H https://escholarship.org/uc/item/8wp195m0 The biofilm growth mode is important in both the intestinal and environmental phases of the <i>Vibrio cholerae</i> life cycle. Regulation of biofilm formation involves several transcriptional regulators and alternative sigma factors. One such factor is the alternative sigma factor RpoN, which positively regulates biofilm formation. RpoN requires bacterial enhancer-binding proteins (bEBPs) to initiate transcription. The <i>V. cholerae</i> genome encodes seven bEBPs (LuxO, VC1522, VC1926 [DctD-1], FlrC, NtrC, VCA0142 [DctD-2], and PgtA) that belong to the NtrC family of response regulators (RRs) of two-component regulatory systems. The contribution of these regulators to biofilm formation is not well understood. In this study, we analyzed biofilm formation and the regulation of <i>vpsL</i> expression by RpoN activators. Mutants lacking NtrC had increased biofilm formation and <i>vpsL</i> expression. NtrC negatively regulates the expression of core regulators of biofilm formation... https://escholarship.org/uc/item/8wp195m0 Tue, 16 Jul 2024 00:00:00 +0000 Cheng, Andrew T Zamorano-Sánchez, David Teschler, Jennifer K Wu, Daniel Yildiz, Fitnat H https://escholarship.org/uc/item/36g0h445 The presence of the Lon protease in all three domains of life hints at its biological importance. The prokaryotic Lon protease is responsible not only for degrading abnormal proteins but also for carrying out the proteolytic regulation of specific protein targets. Posttranslational regulation by Lon is known to affect a variety of physiological traits in many bacteria, including biofilm formation, motility, and virulence. Here, we identify the regulatory roles of LonA in the human pathogen Vibrio cholerae. We determined that the absence of LonA adversely affects biofilm formation, increases swimming motility, and influences intracellular levels of cyclic diguanylate. Whole-genome expression analysis revealed that the message abundance of genes involved in biofilm formation was decreased but that the message abundances of those involved in virulence and the type VI secretion system were increased in a lonA mutant compared to the wild type. We further demonstrated that a lonA mutant... https://escholarship.org/uc/item/36g0h445 Tue, 16 Jul 2024 00:00:00 +0000 Rogers, Andrew Townsley, Loni Gallego-Hernandez, Ana L Beyhan, Sinem Kwuan, Laura Yildiz, Fitnat H https://escholarship.org/uc/item/31t576n2 Motility promotes biofilm initiation during the early steps of this process: microbial surface association and attachment. Motility is controlled in part by chemotaxis signaling, so it seems reasonable that chemotaxis may also affect biofilm formation. There is a gap, however, in our understanding of the interactions between chemotaxis and biofilm formation, partly because most studies analyzed the phenotype of only a single chemotaxis signaling mutant, e.g., <i>cheA</i>. Here, we addressed the role of chemotaxis in biofilm formation using a full set of chemotaxis signaling mutants in <i>Helicobacter pylori</i>, a class I carcinogen that infects more than half the world's population and forms biofilms. Using mutants that lack each chemotaxis signaling protein, we found that chemotaxis signaling affected the biofilm initiation stage, but not mature biofilm formation. Surprisingly, some chemotaxis mutants elevated biofilm initiation, while others inhibited it in a manner that was... https://escholarship.org/uc/item/31t576n2 Tue, 16 Jul 2024 00:00:00 +0000 Liu, Xiaolin Lertsethtakarn, Paphavee Mariscal, Vanessa T Yildiz, Fitnat Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/52q3j3pv VxrA and VxrB are cognate histidine kinase (HK) - response regulator (RR) pairs of a two-component signaling system (TCS) found in <i>Vibrio cholerae</i>, a bacterial pathogen that causes cholera. The VxrAB TCS positively regulates virulence, the Type VI Secretion System, biofilm formation, and cell wall homeostasis in <i>V. cholerae</i>, providing protection from environmental stresses and contributing to the transmission and virulence of the pathogen. The VxrA HK has a unique periplasmic sensor domain (SD) and, remarkably, lacks a cytoplasmic linker domain between the second transmembrane helix and the dimerization and histidine phosphotransfer (DHp) domain, indicating that this system may utilize a potentially unique signal sensing and transmission TCS mechanism. In this study, we have determined several crystal structures of VxrA-SD and its mutants. These structures reveal a novel structural fold forming an unusual β hairpin-swapped dimer. A conformational change caused by... https://escholarship.org/uc/item/52q3j3pv Mon, 8 Jul 2024 00:00:00 +0000 Tan, Kemin Teschler, Jennifer K Wu, Ruiying Jedrzejczak, Robert P Zhou, Min Shuvalova, Ludmilla A Endres, Michael J Welk, Lucas F Kwon, Keehwan Anderson, Wayne F Satchell, Karla JF Yildiz, Fitnat H Joachimiak, Andrzej https://escholarship.org/uc/item/9vx331fd The ability to sense and adapt to temperature fluctuation is critical to the aquatic survival, transmission, and infectivity of Vibrio cholerae, the causative agent of the disease cholera. Little information is available on the physiological changes that occur when V. cholerae experiences temperature shifts. The genome-wide transcriptional profile of V. cholerae upon a shift in human body temperature (37°C) to lower temperatures, 15°C and 25°C, which mimic those found in the aquatic environment, was determined. Differentially expressed genes included those involved in the cold shock response, biofilm formation, type VI secretion, and virulence. Analysis of a mutant lacking the cold shock gene cspV, which was upregulated &gt;50-fold upon a low-temperature shift, revealed that it regulates genes involved in biofilm formation and type VI secretion. CspV controls biofilm formation through modulation of the second messenger cyclic diguanylate and regulates type VI-mediated interspecies... https://escholarship.org/uc/item/9vx331fd Sat, 6 Jul 2024 00:00:00 +0000 Townsley, Loni Mangus, Marilou P Sison Mehic, Sanjin Yildiz, Fitnat H https://escholarship.org/uc/item/1620853x The dinucleotide second messenger c-di-GMP has emerged as a central regulator of reversible cell attachment during bacterial biofilm formation. A prominent cell adhesion mechanism first identified in pseudomonads combines two c-di-GMP-mediated processes: transcription of a large adhesin and its cell surface display via posttranslational proteolytic control. Here, we characterize an orthologous c-di-GMP effector system and show that it is operational in <i>Vibrio cholerae</i>, where it regulates two distinct classes of adhesins. Through structural analyses, we reveal a conserved autoinhibition mechanism of the c-di-GMP receptor that controls adhesin proteolysis and present a structure of a c-di-GMP-bound receptor module. We further establish functionality of the periplasmic protease controlled by the receptor against the two adhesins. Finally, transcription and functional assays identify physiological roles of both c-di-GMP-regulated adhesins in surface attachment and biofilm formation.... https://escholarship.org/uc/item/1620853x Sat, 6 Jul 2024 00:00:00 +0000 Kitts, Giordan Giglio, Krista M Zamorano-Sánchez, David Park, Jin Hwan https://orcid.org/0000-0001-8384-7909 Townsley, Loni Cooley, Richard B Wucher, Benjamin R Klose, Karl E Nadell, Carey D Yildiz, Fitnat H Sondermann, Holger https://escholarship.org/uc/item/0093j2xd The ability to form biofilms is critical for environmental survival and transmission of Vibrio cholerae, a facultative human pathogen responsible for the disease cholera. Biofilm formation is controlled by several transcriptional regulators and alternative sigma factors. In this study, we report that the two main positive regulators of biofilm formation, VpsR and VpsT, bind to nonoverlapping target sequences in the regulatory region of vpsL in vitro. VpsR binds to a proximal site (the R1 box) as well as a distal site (the R2 box) with respect to the transcriptional start site identified upstream of vpsL. The VpsT binding site (the T box) is located between the R1 and R2 boxes. While mutations in the T and R boxes resulted in a decrease in vpsL expression, deletion of the T and R2 boxes resulted in an increase in vpsL expression. Analysis of the role of H-NS in vpsL expression revealed that deletion of hns resulted in enhanced vpsL expression. The level of vpsL expression was higher... https://escholarship.org/uc/item/0093j2xd Sat, 6 Jul 2024 00:00:00 +0000 Zamorano-Sánchez, David Fong, Jiunn CN Kilic, Sefa Erill, Ivan Yildiz, Fitnat H https://escholarship.org/uc/item/1mq9f7f7 <i>Vibrio cholerae</i> biofilm formation and associated motility suppression are correlated with increased concentrations of cyclic diguanylate monophosphate (c-di-GMP), which are in turn driven by increased levels and/or activity of diguanylate cyclases (DGCs). To further our understanding of how c-di-GMP modulators in <i>V. cholerae</i> individually and collectively influence motility with cellular resolution, we determined how DGCs CdgD and CdgH impact intracellular c-di-GMP levels, motility, and biofilm formation. Our results indicated that CdgH strongly influences swim speed distributions; cells in which <i>cdgH</i> was deleted had higher average swim speeds than wild-type cells. Furthermore, our results suggest that CdgD, rather than CdgH, is the dominant DGC responsible for postattachment c-di-GMP production in biofilms. Lipopolysaccharide (LPS) biosynthesis genes were found to be extragenic bypass suppressors of the motility phenotypes of strains Δ<i>cdgD</i> and Δ<i>cdgH</i>... https://escholarship.org/uc/item/1mq9f7f7 Wed, 3 Jul 2024 00:00:00 +0000 Zamorano-Sánchez, David Xian, Wujing Lee, Calvin K Salinas, Mauro Thongsomboon, Wiriya Cegelski, Lynette Wong, Gerard CL Yildiz, Fitnat H https://escholarship.org/uc/item/9wx8c7hc BACKGROUND: Biomarker concentrations of metals are associated with neurodevelopment, and these associations may be modified by nutritional status (e.g., iron deficiency). No prior study on associations of metal mixtures with neurodevelopment has assessed effect modification by iron status. OBJECTIVES: We aimed to quantify associations of an industry-relevant metal mixture with verbal learning and memory among adolescents, and to investigate the modifying role of iron status on those associations. METHODS: We used cross-sectional data from 383 Italian adolescents (10-14 years) living in proximity to ferroalloy industry. Verbal learning and memory was assessed using the California Verbal Learning Test for Children (CVLT-C), and metals were quantified in hair (manganese, copper, chromium) or blood (lead) using inductively coupled plasma mass spectrometry. Serum ferritin, a proxy for iron status, was measured using immunoassays. Covariate-adjusted associations of the metal mixture... https://escholarship.org/uc/item/9wx8c7hc Sat, 11 May 2024 00:00:00 +0000 Schildroth, Samantha Friedman, Alexa White, Roberta F Kordas, Katarzyna Placidi, Donatella Bauer, Julia A Webster, Thomas F Coull, Brent A Cagna, Giuseppa Wright, Robert O Smith, Donald Lucchini, Roberto G Horton, Megan Claus Henn, Birgit https://escholarship.org/uc/item/8pd189zd The bacterial chemotaxis system is a well-understood signaling pathway that promotes bacterial success. Chemotaxis systems comprise chemoreceptors and the CheA kinase, linked by CheW or CheV scaffold proteins. Scaffold proteins provide connections between chemoreceptors and CheA and also between chemoreceptors to create macromolecular arrays. Chemotaxis is required for host colonization by many microbes, including the stomach pathogen <i>Helicobacter pylori</i>. This bacterium builds chemoreceptor-CheA contacts with two distinct scaffold proteins, CheW and CheV1. <i>H. pylori cheW</i> or <i>cheV1</i> deletion mutants both lose chemoreceptor array formation, but show differing semisolid agar chemotaxis assay behaviors: ∆<i>cheW</i> mutants exhibit total migration failure, whereas ∆<i>cheV1::cat</i> mutants display a 50% reduction. On investigating these varied responses, we found that both mutants initially struggle with migration. However, over time, ∆<i>cheV1::cat</i> mutants... https://escholarship.org/uc/item/8pd189zd Tue, 23 Apr 2024 00:00:00 +0000 Sagoo, Jashwin Abedrabbo, Samar Liu, Xiaolin Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/52w1q0zn Loss-of-function mutations in SLC30A10 induce hereditary manganese (Mn)-induced neuromotor disease in humans. We previously identified SLC30A10 to be a critical Mn efflux transporter that controls physiological brain Mn levels by mediating hepatic and intestinal Mn excretion in adolescence/adulthood. Our studies also revealed that in adulthood, SLC30A10 in the brain regulates brain Mn levels when Mn excretion capacity is overwhelmed (e.g. after Mn exposure). But, the functional role of brain SLC30A10 under physiological conditions is unknown. We hypothesized that, under physiological conditions, brain SLC30A10 may modulate brain Mn levels and Mn neurotoxicity in early postnatal life because body Mn excretion capacity is reduced in this developmental stage. We discovered that Mn levels of pan-neuronal/glial Slc30a10 knockout mice were elevated in specific brain regions (thalamus) during specific stages of early postnatal development (postnatal day 21), but not in adulthood. Furthermore,... https://escholarship.org/uc/item/52w1q0zn Tue, 9 Apr 2024 00:00:00 +0000 Taylor, Cherish A Grant, Stephanie M Jursa, Thomas Melkote, Ashvini Fulthorpe, Rebecca Aschner, Michael Smith, Donald R Gonzales, Rueben A Mukhopadhyay, Somshuvra https://escholarship.org/uc/item/3fk0n3p9 NON-TECHNICAL SUMMARY: Antibiotic resistance is a global human health problem. We partnered with Dignity Health Mercy Medical Center to study antibiotic resistance in clinical isolates. We tested whether growth rates, a sensitive assay used to measure the fitness of bacterial samples, correlate with a clinical test to measure antibiotic resistance. We found a strong correlation between these two methods suggesting that growth rates could be reliably applied to evolutionary studies of clinically relevant problems. Moreover, the sensitivity of the growth rates assay enabled us to identify fitness effects of specific antibiotic resistance genes. https://escholarship.org/uc/item/3fk0n3p9 Sun, 7 Apr 2024 00:00:00 +0000 Santiago, Fabian Doscher, Evin Kim, Jay Camps, Manel https://orcid.org/0000-0002-0467-4032 Meza, Juan https://orcid.org/0000-0003-4543-0349 Sindi, Suzanne Barlow, Miriam https://escholarship.org/uc/item/10b516pk The link between E. coli strains contaminating foods and human disease is unclear, with some reports supporting a direct transmission of pathogenic strains via food and others highlighting their role as reservoirs for resistance and virulence genes. Here we take a genomics approach, analyzing a large set of fully-assembled genomic sequences from E. coli available in GenBank. Most of the strains isolated in food are more closely related to each other than to clinical strains, arguing against a frequent direct transmission of pathogenic strains from food to the clinic. We also provide strong evidence of genetic exchanges between food and clinical strains that are facilitated by plasmids. This is based on an overlapped representation of virulence and resistance genes in plasmids isolated from these two sources. We identify clusters of phylogenetically-related plasmids that are largely responsible for the observed overlap and see evidence of specialization, with some food plasmid... https://escholarship.org/uc/item/10b516pk Fri, 8 Mar 2024 00:00:00 +0000 Balbuena-Alonso, María G Cortés-Cortés, Gerardo Kim, Jay W Lozano-Zarain, Patricia Camps, Manel https://orcid.org/0000-0002-0467-4032 Del Carmen Rocha-Gracia, Rosa https://escholarship.org/uc/item/8sf9w9s2 The World Health Organization (WHO) considers antimicrobial resistance to be one of the critical global public health priorities to address. <i>Escherichia coli</i> is a commensal bacterium of the gut microbiota in humans and animals; however, some strains cause infections and are resistant to antibiotics. One of the most common ways of acquiring pathogenic <i>E. coli</i> strains is through food. This review analyzes multidrug-resistant <i>E. coli</i> isolated from food, emphasizing Latin America and Mexico, and the mobile genetic elements (MGEs) responsible for spreading antibiotic resistance determinants among bacteria in different environments and hosts. We conducted a systematic search of the literature published from 2015 to 2022 in open access databases and electronic repositories. The prevalence of 11 <i>E. coli</i> pathotypes was described, with diarrheagenic <i>E. coli</i> pathotypes being the most frequently associated with foodborne illness in different Latin American... https://escholarship.org/uc/item/8sf9w9s2 Mon, 26 Feb 2024 00:00:00 +0000 Babines-Orozco, Lorena Balbuena-Alonso, María Guadalupe Barrios-Villa, Edwin Lozano-Zarain, Patricia Martínez-Laguna, Ygnacio Del Carmen Rocha-Gracia, Rosa Cortés-Cortés, Gerardo https://escholarship.org/uc/item/2q36s8xt Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor... https://escholarship.org/uc/item/2q36s8xt Tue, 13 Feb 2024 00:00:00 +0000 Liu, XF Onda, M Schlomer, J Bassel, L Kozlov, S Tai, C-H Zhou, Q Liu, W Tsao, H-E Hassan, R Ho, M Pastan, I https://escholarship.org/uc/item/5014h21f IMPORTANCE: Manipulating the genomes of bacteria is critical to many fields. Such manipulations are made by genetic engineering, which often requires new pieces of DNA to be added to the genome. Bacteria have robust systems for identifying and degrading new DNA, some of which rely on restriction enzymes. These enzymes cut DNA at specific sequences. We identified a set of DNA sequences that are missing normally from a bacterium's genome, more than would be expected by chance. Eliminating these sequences from a new piece of DNA allowed it to be incorporated into the bacterial genome at a higher frequency than new DNA containing the sequences. Removing such sequences appears to allow the new DNA to fly under the bacterial radar in "stealth" mode. This transformation improvement approach is straightforward to apply and likely broadly applicable. https://escholarship.org/uc/item/5014h21f Wed, 10 Jan 2024 00:00:00 +0000 Hu, Shuai Giacopazzi, Stefani Modlin, Ryan Karplus, Kevin Bernick, David L Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/3z1357mw The cytotoxin-associated gene (Cag) pathogenicity island is a strain-specific constituent of Helicobacter pylori (H. pylori) that augments cancer risk. CagA translocates into the cytoplasm where it stimulates cell signaling through the interaction with tyrosine kinase c-Met receptor, leading cellular proliferation. Identified as a potential gastric stem cell marker, cluster-of-differentiation (CD) CD44 also acts as a co-receptor for c-Met, but whether it plays a functional role in H. pylori-induced epithelial proliferation is unknown. We tested the hypothesis that CD44 plays a functional role in H. pylori-induced epithelial cell proliferation. To assay changes in gastric epithelial cell proliferation in relation to the direct interaction with H. pylori, human- and mouse-derived gastric organoids were infected with the G27 H. pylori strain or a mutant G27 strain bearing cagA deletion (∆CagA::cat). Epithelial proliferation was quantified by EdU immunostaining. Phosphorylation of... https://escholarship.org/uc/item/3z1357mw Sun, 24 Dec 2023 00:00:00 +0000 Bertaux-Skeirik, Nina Feng, Rui Schumacher, Michael A Li, Jing Mahe, Maxime M Engevik, Amy C Javier, Jose E Peek, Richard M Ottemann, Karen https://orcid.org/0000-0001-6265-7401 Orian-Rousseau, Veronique Boivin, Gregory P Helmrath, Michael A Zavros, Yana https://escholarship.org/uc/item/48v3g243 Background: Early-life environmental exposures during critical windows (CWs) of development can impact life course health. Exposure to neuroactive metals such as manganese (Mn) during prenatal and early postnatal CWs may disrupt typical brain development, leading to persistent behavioral changes. Males and females may be differentially vulnerable to Mn, presenting distinctive CWs to Mn exposure. Methods: We used magnetic resonance imaging to investigate sex-specific associations between early-life Mn uptake and intrinsic functional connectivity in adolescence. A total of 71 participants (15-23 years old; 53% female) from the Public Health Impact of Manganese Exposure study completed a resting-state functional magnetic resonance imaging scan. We estimated dentine Mn concentrations at prenatal, postnatal, and early childhood periods using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses to investigate the moderating effect... https://escholarship.org/uc/item/48v3g243 Mon, 13 Nov 2023 00:00:00 +0000 Rechtman, Elza Navarro, Esmeralda de Water, Erik Tang, Cheuk Y Curtin, Paul Papazaharias, Demetrios M Ambrosi, Claudia Mascaro, Lorella Cagna, Giuseppa Gasparotti, Roberto Invernizzi, Azzurra Reichenberg, Abraham Austin, Christine Arora, Manish Smith, Donald R Lucchini, Roberto G Wright, Robert O Placidi, Donatella Horton, Megan K https://escholarship.org/uc/item/7zn8b3gk Introduction: Adolescent exposure to neurotoxic metals adversely impacts cognitive, motor, and behavioral development. Few studies have addressed the underlying brain mechanisms of these metal-associated developmental outcomes. Furthermore, metal exposure occurs as a mixture, yet previous studies most often consider impacts of each metal individually. In this cross-sectional study, we investigated the relationship between exposure to neurotoxic metals and topological brain metrics in adolescents. Methods: In 193 participants (53% females, ages: 15-25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of four metals (manganese, lead, copper, and chromium) in multiple biological media (blood, urine, hair, and saliva) and acquired resting-state functional magnetic resonance imaging scans. Using graph theory metrics, we computed global and local efficiency (global:GE; local:LE) in 111 brain areas (Harvard Oxford Atlas). We used... https://escholarship.org/uc/item/7zn8b3gk Sat, 11 Nov 2023 00:00:00 +0000 Invernizzi, Azzurra Rechtman, Elza Oluyemi, Kristie Renzetti, Stefano Curtin, Paul Colicino, Elena Ambrosi, Claudia Mascaro, Lorella Patrono, Alessandra Corbo, Daniele Cagna, Giuseppa Gasparotti, Roberto Reichenberg, Abraham Tang, Cheuk Y Smith, Donald R Placidi, Donatella Lucchini, Roberto G Wright, Robert O Horton, Megan K https://escholarship.org/uc/item/87j1v8br BACKGROUND: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development. OBJECTIVES: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). METHODS: At enrollment, we determined women's (n&nbsp;=&nbsp;400) specific-gravity corrected urinary pesticide (μg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (μg/g) and blood (MnB) (μg/L), and blood lead (PbB) (μg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n&nbsp;=&nbsp;400), and about ten weeks afterwards (n&nbsp;=&nbsp;245). We assessed associations between exposures and... https://escholarship.org/uc/item/87j1v8br Fri, 10 Nov 2023 00:00:00 +0000 Corrales Vargas, Andrea Peñaloza Castañeda, Jorge Rietz Liljedahl, Emelie Mora, Ana María Menezes-Filho, Jose Antonio Smith, Donald R Mergler, Donna Reich, Brian Giffin, Andrew Hoppin, Jane A Lindh, Christian H van Wendel de Joode, Berna https://escholarship.org/uc/item/8t5887ms Food contamination with pathogenic <i>Escherichia coli</i> can cause severe disease. Here, we report the isolation of a multidrug resistant strain (A23EC) from fresh spinach. A23EC belongs to subclade C2 of ST131, a virulent clone of Extraintestinal Pathogenic <i>E. coli</i> (ExPEC). Most A23EC virulence factors are concentrated in three pathogenicity islands. These include PapGII, a fimbrial tip adhesin linked to increased virulence, and <i>CsgA</i> and <i>CsgB</i>, two adhesins known to facilitate spinach leaf colonization. A23EC also bears Tn<i>MB1860</i>, a chromosomally-integrated transposon with the demonstrated potential to facilitate the evolution of carbapenem resistance among non-carbapenemase-producing enterobacterales. This transposon consists of two IS<i>26</i>-bound modular translocatable units (TUs). The first TU carries <i>aac(6')-lb-cr</i>, <i>bla</i> _OXA-1, <i>ΔcatB3</i>, <i>aac(3)-lle</i>, and <i>tmrB</i>, and the second one harbors <i>bla</i> _CXT-M-15.... https://escholarship.org/uc/item/8t5887ms Tue, 7 Nov 2023 00:00:00 +0000 Balbuena-Alonso, Maria G Camps, Manel https://orcid.org/0000-0002-0467-4032 Cortés-Cortés, Gerardo Carreón-León, Eder A Lozano-Zarain, Patricia del Carmen Rocha-Gracia, Rosa https://escholarship.org/uc/item/9972b6rw The enteropathogen Yersinia pseudotuberculosis and the related plague agent Y. pestis require the Ysc type III secretion system (T3SS) to subvert phagocyte defense mechanisms and cause disease. Yet type III secretion (T3S) in Yersinia induces growth arrest and innate immune recognition, necessitating tight regulation of the T3SS. Here we show that Y. pseudotuberculosis T3SS expression is kept low under anaerobic, iron-rich conditions, such as those found in the intestinal lumen where the Yersinia T3SS is not required for growth. In contrast, the Yersinia T3SS is expressed under aerobic or anaerobic, iron-poor conditions, such as those encountered by Yersinia once they cross the epithelial barrier and encounter phagocytic cells. We further show that the [2Fe-2S] containing transcription factor, IscR, mediates this oxygen and iron regulation of the T3SS by controlling transcription of the T3SS master regulator LcrF. IscR binds directly to the lcrF promoter and, importantly, a mutation... https://escholarship.org/uc/item/9972b6rw Mon, 23 Oct 2023 00:00:00 +0000 Hooker-Romero, Diana Mettert, Erin Schwiesow, Leah Balderas, David Alvarez, Pablo A Kicin, Anadin Gonzalez, Azuah L Plano, Gregory V Kiley, Patricia J Auerbuch, Victoria https://escholarship.org/uc/item/88f2519h Retained lead fragments from nonfatal firearm injuries pose a risk of lead poisoning. While chelation is well-established as a lead poisoning treatment, it remains unclear whether chelation mobilizes lead from embedded lead fragments. Here, we tested whether 1) DMSA/succimer or CaNa₂EDTA increases mobilization of lead from fragments in vitro, and 2) succimer is efficacious in chelating fragment lead in vivo, using stable lead isotope tracer methods in a rodent model of embedded fragments. DMSA was &gt;&nbsp;10-times more effective than CaNa₂EDTA in mobilizing fragment lead in vitro. In the rodent model, succimer chelation on day 1 produced the greatest blood lead reductions, and fragment lead was not mobilized into blood. However, with continued chelation and over 3-weeks post-chelation, blood lead levels rebounded with mobilization of lead from the fragments. These findings suggest prolonged chelation will increase fragment lead mobilization post-chelation,... https://escholarship.org/uc/item/88f2519h Thu, 12 Oct 2023 00:00:00 +0000 Twardy, Shannon M Hanson, Sarah M Jursa, Thomas Gaitens, Joanna M Kalinich, John M McDiarmid, Melissa A Smith, Don R https://escholarship.org/uc/item/8cq8k5s3 Elevated exposure to multiple trace metals can be neurotoxic even at relatively low levels. These findings are primarily evident from adult occupational studies as well as in children exposed prenatally or in early childhood. Less research has focused on the neurodevelopmental impacts of exposure to metals among school-aged children. We examined associations between exposure to a mixture of four metals (arsenic, cadmium, manganese, lead) measured in hair and markers of cognition, attention, and behavior among 222 6-12 year old children who participated in a 2009-2010 neurodevelopmental follow-up to the C8 Health Project. Using quantile-based g-computation we estimated the adjusted overall metal mixture effect ψ (95 % CI) as the change in outcome per decile increase in all metals in the mixture. Hair metal levels varied by metal, with cadmium being lowest (median 0.007, interquartile range (IQR) 0.013&nbsp;μg/g) and lead the highest concentration (median 0.152, IQR 0.252&nbsp;μg/g).... https://escholarship.org/uc/item/8cq8k5s3 Tue, 10 Oct 2023 00:00:00 +0000 Stein, Cheryl R Wu, Haotian Bellinger, David C Smith, Donald R Wolff, Mary S Savitz, David A https://escholarship.org/uc/item/3122c9dn Studies have established associations between environmental and occupational manganese (Mn) exposure and executive and motor function deficits in children, adolescents, and adults. These health risks from elevated Mn exposure underscore the need for effective exposure biomarkers to improve exposure classification and help detect/diagnose Mn-related impairments. Here, neonate rats were orally exposed to 0, 25, or 50&nbsp;mg Mn/kg/day during early life (PND 1-21) or lifelong through&nbsp;∼&nbsp;PND 500 to determine the relationship between oral Mn exposure and blood, brain, and bone Mn levels over the lifespan, whether Mn accumulates in bone, and whether elevated bone Mn altered the local atomic and mineral structure of bone, or its biomechanical properties. Additionally, we assessed levels of bone Mn compared to bone lead (Pb) in aged humans (age 41-91) living in regions impacted by historic industrial ferromanganese activity. The animal studies show that blood, brain, and bone... https://escholarship.org/uc/item/3122c9dn Tue, 19 Sep 2023 00:00:00 +0000 Conley, Travis E Richardson, Cardius Pacheco, Juan Dave, Neil Jursa, Thomas Guazzetti, Stefano Lucchini, Roberto G Fendorf, Scott Ritchie, Robert O https://orcid.org/0000-0002-0501-6998 Smith, Donald R https://escholarship.org/uc/item/7s8709r1 Zinc Finger DNA-binding domain-containing proteins are the most populous family among eukaryotic transcription factors. Among these, members of the BTB domain-containing ZBTB sub-family are mostly known for their transcriptional repressive functions. In this Viewpoint article, we explore molecular mechanisms that potentially diversify the function of ZBTB proteins based on their homo and heterodimerization, alternative splicing and post-translational modifications. We describe how the BTB domain is as much a scaffold for the assembly of co-repressors, as a domain that regulates protein stability. We highlight another mechanism that regulates ZBTB protein stability: phosphorylation in the zinc finger domain. We explore the non-transcriptional, structural roles of ZBTB proteins and highlight novel findings that describe the ability of ZBTB proteins to associate with poly adenosine ribose in the nucleus during the DNA damage response. Herein, we discuss the contribution of BTB domain... https://escholarship.org/uc/item/7s8709r1 Mon, 18 Sep 2023 00:00:00 +0000 Barakat, Sarah Ezen, Ege Devecioğlu, İzem Gezen, Melike Piepoli, Sofia https://orcid.org/0000-0002-3891-9464 Erman, Batu https://escholarship.org/uc/item/3qw0s88d Type I interferons (IFNs) are critical mediators of antiviral defense, but their elicitation by bacterial pathogens can be detrimental to hosts. Many intracellular bacterial pathogens, including Mycobacterium tuberculosis, induce type I IFNs following phagosomal membrane perturbations. Cytosolic M. tuberculosis DNA has been implicated as a trigger for IFN production, but the mechanisms remain obscure. We report that the cytosolic DNA sensor, cyclic GMP-AMP synthase (cGAS), is required for activating IFN production via the STING/TBK1/IRF3 pathway during M. tuberculosis and L. pneumophila infection of macrophages, whereas L. monocytogenes short-circuits this pathway by producing the STING agonist, c-di-AMP. Upon sensing cytosolic DNA, cGAS also activates cell-intrinsic antibacterial defenses, promoting autophagic targeting of M. tuberculosis. Importantly, we show that cGAS binds M. tuberculosis DNA during infection, providing direct evidence that this unique host-pathogen interaction... https://escholarship.org/uc/item/3qw0s88d Sun, 17 Sep 2023 00:00:00 +0000 Watson, Robert O Bell, Samantha L MacDuff, Donna A Kimmey, Jacqueline M https://orcid.org/0000-0003-1330-8525 Diner, Elie J Olivas, Joanna Vance, Russell E Stallings, Christina L Virgin, Herbert W Cox, Jeffery S https://escholarship.org/uc/item/3n04d8wj Mycobacterium tuberculosis has evolved various mechanisms by which the bacterium can maintain homeostasis under numerous environmental assaults generated by the host immune response. M. tuberculosis harbors enzymes involved in the oxidative stress response that aid in survival during the production of reactive oxygen species in activated macrophages. Previous studies have shown that a dye-decolorizing peroxidase (DyP) is encapsulated by a bacterial nanocompartment, encapsulin (Enc), whereby packaged DyP interacts with Enc via a unique C-terminal extension. M. tuberculosis also harbors an encapsulin homolog (CFP-29, Mt-Enc), within an operon with M. tuberculosis DyP (Mt-DyP), which contains a C-terminal extension. Together these observations suggest that Mt-DyP interacts with Mt-Enc. Furthermore, it has been suggested that DyPs may function as either a heme-dependent peroxidase or a deferrochelatase. Like Mt-DyP, M. tuberculosis iron storage ferritin protein, Mt-BfrB, and an M.... https://escholarship.org/uc/item/3n04d8wj Sun, 17 Sep 2023 00:00:00 +0000 Contreras, Heidi Joens, Matthew S McMath, Lisa M Le, Vincent P Tullius, Michael V Kimmey, Jaqueline M https://orcid.org/0000-0003-1330-8525 Bionghi, Neda Horwitz, Marcus A https://orcid.org/0000-0001-6525-7147 Fitzpatrick, James AJ Goulding, Celia W https://orcid.org/0000-0001-5582-0565 https://escholarship.org/uc/item/7z5030f9 The <i>Pseudomonas aeruginosa</i> genome can change to adapt to different ecological niches. We compared four genomes from a Mexican hospital and 59 genomes from GenBank from different niches, such as urine, sputum, and environmental. The ST analysis showed that high-risk STs (ST235, ST773, and ST27) were present in the genomes of the three niches from GenBank, and the STs of Mexican genomes (ST167, ST2731, and ST549) differed from the GenBank genomes. Phylogenetic analysis showed that the genomes were clustering according to their ST and not their niche. When analyzing the genomic content, we observed that environmental genomes had genes involved in adapting to the environment not found in the clinics and that their mechanisms of resistance were mutations in antibiotic resistance-related genes. In contrast, clinical genomes from GenBank had resistance genes, in mobile/mobilizable genetic elements in the chromosome, except for the Mexican genomes that carried them mostly in plasmids.... https://escholarship.org/uc/item/7z5030f9 Sat, 16 Sep 2023 00:00:00 +0000 Gómez-Martínez, Jessica del Carmen Rocha-Gracia, Rosa Bello-López, Elena Cevallos, Miguel Angel Castañeda-Lucio, Miguel Sáenz, Yolanda Jiménez-Flores, Guadalupe Cortés-Cortés, Gerardo López-García, Alma Lozano-Zarain, Patricia https://escholarship.org/uc/item/8pj8c0qx Inhibition of actin remodeling in nerves modulates action potential propagation and therefore could be used to treat acute pain. N-001 is a novel protein analgesic engineered from several C. Botulinum toxins. N-001 targets sensory neurons through ganglioside GT1b binding and ADP-ribosylates G-actin reducing actin remodeling. The activity and efficacy of N-001 was evaluated previously in vitro and in a mouse inflammatory pain model. To assess the relevance of N-001 for treatment of acute post-surgical pain, the current study evaluated the efficacy of N-001 in a mouse hind-paw incision model by peri-incisional and popliteal nerve block administration combined with mechanical testing. N-001 provided relief of pain-like behavior over 3&nbsp;days and 2&nbsp;days longer than the conventional long-acting anesthetic bupivacaine. Preclinical safety studies of N-001 indicated the drug produced no toxic or adverse immunological reactions over multiple doses in mice. These results combined... https://escholarship.org/uc/item/8pj8c0qx Sat, 2 Sep 2023 00:00:00 +0000 Allen, Derek Hanumantharao, Samerender Nagam McDonell, Rylie Irvine, Karen-Amanda Sahbaie, Peyman Clark, David Blum, Paul https://escholarship.org/uc/item/6rq4q1hx This presentation summarizes several of the rodent and non-human studies that we have conducted to help inform the efficacy and clinical utility of succimer (meso-2,3-dimercaptosuccincinic acid) chelation treatment. We address the following questions: (1) What is the extent of body lead, and in particular brain lead reduction with chelation, and do reductions in blood lead accurately reflect reductions in brain lead? (2) Can succimer treatment alleviate the neurobehavioral impacts of lead poisoning? And (3) does succimer treatment, in the absence of lead poisoning, produce neurobehavioral deficits? Results from our studies in juvenile primates show that succimer treatment is effective at accelerating the elimination of lead from the body, but chelation was only marginally better than the complete cessation of lead exposure alone. Studies in lead-exposed adult primates treated with a single 19-day course of succimer showed that chelation did not measurably reduce brain lead levels... https://escholarship.org/uc/item/6rq4q1hx Sat, 2 Sep 2023 00:00:00 +0000 Smith, Donald Strupp, Barbara J https://escholarship.org/uc/item/12j4k95h The complement system has long been appreciated for its role in bloodborne infections, but its activities in other places, including the gastrointestinal tract, remain elusive. Here, we report that complement restricts gastric infection by the pathogen Helicobacter pylori. This bacterium colonized complement-deficient mice to higher levels than wild-type counterparts, particularly in the gastric corpus region. H. pylori uses uptake of the host molecule L-lactate to create a complement-resistant state that relies on blocking the deposition of the active complement C4b component on H. pylori’s surface. H. pylori mutants unable to achieve this complement-resistant state have a significant mouse colonization defect that is largely corrected by mutational removal of complement. This work highlights a previously unknown role for complement in the stomach, and has revealed an unrecognized mechanism for microbial-derived complement resistance. https://escholarship.org/uc/item/12j4k95h Fri, 14 Jul 2023 00:00:00 +0000 Hu, Shuai Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/87d364sp Behavioral disorders involving attention and impulse control dysfunction, such as ADHD, are among the most prevalent disorders in children and adolescents, with significant impact on their lives. The etiology of these disorders is not well understood, but is recognized to be multifactorial, with studies reporting associations with polygenic and environmental risk factors, including toxicant exposure. Environmental epidemiological studies, while good at establishing associations with a variety of environmental and genetic risk factors, cannot establish causality. Animal models of behavioral disorders, when properly designed, can play an essential role in establishing causal relationships between environmental risk factors and a disorder, as well as provide model systems for elucidating underlying neural mechanisms and testing therapies. Here, we review how animal model studies of developmental lead or manganese exposure have been pivotal in (1) establishing a causal relationship... https://escholarship.org/uc/item/87d364sp Wed, 12 Jul 2023 00:00:00 +0000 Smith, Donald R Strupp, Barbara J https://escholarship.org/uc/item/2fn826qv The flagellar motor protein FliL is conserved across many microbes, but its exact role has been obscured by varying <i>fliL</i> mutant phenotypes. We reanalyzed results from <i>fliL</i> studies and found they utilized alleles that differed in the amount of N- and C-terminal regions that were retained. Alleles that retain the N-terminal cytoplasmic and transmembrane helix (TM) regions in the absence of the C-terminal periplasmic domain result in loss of motility, while alleles that completely lack the N-terminal region, independent of the periplasmic domain, retain motility. We then tested this prediction in Helicobacter pylori <i>fliL</i> and found support for the idea. This analysis suggests that FliL function may be more conserved across bacteria than previously thought, that it is not essential for motility, and that the N-terminal region has the negative ability to regulate motor function. <b>IMPORTANCE</b> FliL is a protein found in the flagellar motor of bacteria, but what... https://escholarship.org/uc/item/2fn826qv Wed, 12 Jul 2023 00:00:00 +0000 Liu, Xiaolin Roujeinikova, Anna Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/6cq2m53c Helicobacter pylori colonizes half of the world's population and is responsible for a significant disease burden by causing gastritis, peptic ulcers, and gastric cancer. The development of host inflammation drives these diseases, but there are still open questions in the field about how H. pylori controls this process. We characterized H. pylori inflammation using an 8-month mouse infection time course and comparison of the wild type (WT) and a previously identified mutant lacking the TlpA chemoreceptor that causes elevated inflammation. Our work shows that H. pylori chronic-stage corpus inflammation undergoes surprising fluctuations, with changes in Th17 and eosinophil numbers. The H. pylori <i>tlpA</i> mutant changed the inflammation temporal characteristics, resulting in different inflammation from the wild type at some time points. <i>tlpA</i> mutants have equivalent total and gland colonization in late-stage infections. During early infection, in contrast, they show elevated... https://escholarship.org/uc/item/6cq2m53c Sat, 8 Jul 2023 00:00:00 +0000 Johnson, Kevin S Yang, Christina Carter, J Elliot Worthington, Atesh K Robinson, Elektra K Lopez-Magaña, Raymond Salgado, Frida Arnold, Isabelle Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/0rv5j6w7 Multiple mutations often have non-additive (epistatic) phenotypic effects. Epistasis is of fundamental biological relevance but is not well understood mechanistically. Adaptive evolution, i.e., the evolution of new biochemical activities, is rich in epistatic interactions. To better understand the principles underlying epistasis during genetic adaptation, we studied the evolution of TEM-1 β-lactamase variants exhibiting cefotaxime resistance. We report the collection of a library of 487 observed evolutionary trajectories for TEM-1 and determine the epistasis status based on cefotaxime resistance phenotype for 206 combinations of 2-3 TEM-1 mutations involving 17 positions under adaptive selective pressure. Gain-of-function (GOF) mutations are gatekeepers for adaptation. To see if GOF phenotypes can be inferred based solely on sequence data, we calculated the enrichment of GOF mutations in the different categories of epistatic pairs. Our results suggest that this is possible because... https://escholarship.org/uc/item/0rv5j6w7 Fri, 7 Jul 2023 00:00:00 +0000 Standley, Melissa Blay, Vincent Guthrie, Violeta Beleva Kim, Jay Lyman, Audrey Moya, Andrés Karchin, Rachel Camps, Manel https://orcid.org/0000-0002-0467-4032 https://escholarship.org/uc/item/646044gh Many biological processes depend on very few copies of intervening elements, which makes such processes particularly susceptible to the stochastic fluctuations of these elements. The intrinsic stochasticity of certain processes is propagated across biological levels, causing genotype- and environment-independent biological variation which might permit populations to better cope with variable environments. Biological variations of stochastic nature might also allow the accumulation of variations at the genetic level that are hidden from natural selection, which might have a great potential for population diversification. The study of any mechanism that resulted in the modulation of stochastic variation is, therefore, of potentially wide interest. I propose that sex might be an important modulator of the stochastic variation in gene expression, i.e., gene expression noise. Based on known associations between different patterns of gene expression variation, I hypothesize that in... https://escholarship.org/uc/item/646044gh Wed, 5 Jul 2023 00:00:00 +0000 Díaz-Castillo, Carlos https://escholarship.org/uc/item/8m45s4xj Circadian clocks are universally used to coordinate biological processes with the Earth's 24-h solar day and are critical for the health and environmental success of an organism. Circadian rhythms in eukaryotes are driven by a cell-intrinsic transcription-translation feedback loop that controls daily oscillations in gene expression which regulate diverse physiological functions. Substantial evidence now exists demonstrating that immune activation and inflammatory responses during infection are under circadian control, however, the cellular mechanisms responsible for this are not well understood. The zebrafish (Danio rerio) is a powerful model organism to study vertebrate circadian biology and immune function. Zebrafish contain homologs of mammalian circadian clock genes which, to our current knowledge, function similarly to impart timekeeping ability. Consistent with studies in mammalian models, several studies in fish have now demonstrated a bidirectional relationship between... https://escholarship.org/uc/item/8m45s4xj Tue, 4 Jul 2023 00:00:00 +0000 Sacksteder, Raina E Kimmey, Jacqueline M https://orcid.org/0000-0003-1330-8525 https://escholarship.org/uc/item/60r9m6fm The type III secretion system (T3SS) is an appendage used by many bacterial pathogens, such as pathogenic Yersinia, to subvert host defenses. However, because the T3SS is energetically costly and immunogenic, it must be tightly regulated in response to environmental cues to enable survival in the host. Here we show that expression of the Yersinia Ysc T3SS master regulator, LcrF, is orchestrated by the opposing activities of the repressive H-NS/YmoA histone-like protein complex and induction by the iron and oxygen-regulated IscR transcription factor. While deletion of iscR or ymoA has been shown to decrease and increase LcrF expression and type III secretion, respectively, the role of H-NS in this system has not been definitively established because hns is an essential gene in Yersinia. Using CRISPRi knockdown of hns, we show that hns depletion causes derepression of lcrF. Furthermore, we find that while YmoA is dispensable for H-NS binding to the lcrF promoter, YmoA binding to... https://escholarship.org/uc/item/60r9m6fm Tue, 4 Jul 2023 00:00:00 +0000 Balderas, David Ohanyan, Mané Alvarez, Pablo A Mettert, Erin Tanner, Natasha Kiley, Patricia J Auerbuch, Victoria https://escholarship.org/uc/item/1dd6q7s8 Many bacteria and archaea rely on chemotaxis signal transduction systems for optimal fitness. These complex, multiprotein signaling systems have core components found in all chemotactic microbes, as well as variable proteins found in only some species. We do not yet understand why these variations exist or whether there are specific niches that favor particular chemotaxis signaling organization. One variation is in the presence/absence of the chemotaxis methylation adaptation enzymes CheB and CheR. Genes for CheB and CheR are missing in the gastric pathogen Helicobacter pylori but present in related Helicobacter that colonize the liver or intestine. In this work, we asked whether there was a general pattern of CheB/CheR across multiple Helicobacter species. Helicobacter spp. all possess chemotactic behavior, based on the presence of genes for core signaling proteins CheA, CheW, and chemoreceptors. Genes for the CheB and CheR proteins, in contrast, were variably present. Niche... https://escholarship.org/uc/item/1dd6q7s8 Tue, 4 Jul 2023 00:00:00 +0000 Liu, Xiaolin Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/3f34j8x6 <h4>Background</h4>Neonates and children are particularly vulnerable to the toxic effects of excess manganese (Mn), but studies of Mn exposure during these developmental periods are hampered by a lack of validated biomarkers. Deciduous teeth may be used to assess Mn exposure during these developmental periods but require further validation to determine the relationship between tooth Mn, Mn in target tissues, and exposure.<h4>Objectives</h4>To determine the relationship of tooth Mn concentrations with: (i) exposure dose, (ii) the timing/duration of exposure, and (iii) with Mn concentrations in blood, brain and bone.<h4>Methods</h4>Rats in different treatment groups were orally exposed to 0, 25 or 50µg/g/day Mn either from postnatal day (PND) 1 - 21 and culled at PND 24, from PND 1 - 21 and culled as adults (&gt;PND 290), or from PND 1 - throughout life and culled at &gt;290 PND. Mn was measured in second molars, femurs, brain and blood by ICP-MS.<h4>Results</h4>Tooth Mn increased... https://escholarship.org/uc/item/3f34j8x6 Thu, 29 Jun 2023 00:00:00 +0000 Austin, Christine Richardson, Cardius Smith, Donald Arora, Manish https://escholarship.org/uc/item/3rq901jp The current obesity epidemic is calling for action in the determination of contributing factors. Although social and life-style factors have been traditionally associated with metabolic disruption, a subset of endocrine-disrupting chemicals (EDCs), called obesogens are garnering increasing attention for their ability to promote adipose tissue differentiation and accumulation. For some chemicals, such as tributyltin, there is conclusive evidence regarding their ability to promote adipogenesis and their mechanism of action. In recent years, the list of chemicals that exert obesogenic potential is increasing. In this chapter, we review current knowledge of the most recent developments in the field of emerging obesogens with a specific focus on food additives, surfactants, and sunscreens, for which the mechanism of action remains unclear. We also review new evidence relative to the obesogenic potential of environmentally relevant chemical mixtures and point to potential therapeutic... https://escholarship.org/uc/item/3rq901jp Sat, 24 Jun 2023 00:00:00 +0000 Chamorro-Garcia, Raquel Veiga-Lopez, Almudena https://escholarship.org/uc/item/0h27m9dx It has been long known that the environment plays a critical role in the etiology of disease. However, it is still unclear how the large variety of environmental factors humans are exposed to interact with each other to lead to disease. Metabolic disorders are just one example of human disorders that have been associated with environmental exposures. Obesity and type 2 diabetes have become a health and economic burden worldwide as the number of affected people has tripled in the last 40&nbsp;years. Animal and human studies have shown a strong association between exposure to environmental chemicals during critical windows of susceptibility such as periconception, prenatal, and early life, whose effect can persist through development and across generations. However, little is known about the mechanisms driving this persistence. Here, we review historical and current knowledge on the effect of exposure to environmental factors during <i>in utero</i> development and discuss mechanisms... https://escholarship.org/uc/item/0h27m9dx Fri, 23 Jun 2023 00:00:00 +0000 Davis, Daniel D Diaz-Castillo, Carlos https://orcid.org/0000-0001-5099-3619 Chamorro-Garcia, Raquel https://escholarship.org/uc/item/9wk786jx Greater understanding of the spatial relationships between members of the human gut microbiota and available nutrients is needed to gain deeper insights about community dynamics and expressed functions. Therefore, we generated a panel of artificial food particles with each type composed of microscopic paramagnetic beads coated with a fluorescent barcode and one of 60 different dietary or host glycan preparations. Analysis of 160 Bacteroides and Parabacteroides strains disclosed diverse strain-specific and glycan-specific binding phenotypes. We identified carbohydrate structures that correlated with binding by specific bacterial strains in&nbsp;vitro and noted strain-specific differences in the catabolism of glycans that mediate adhesion. Mixed in&nbsp;vitro cultures revealed that these adhesion phenotypes are maintained in more complex communities. Additionally, orally administering glycan beads to gnotobiotic mice confirmed specificity in glycan binding. This approach should... https://escholarship.org/uc/item/9wk786jx Fri, 16 Jun 2023 00:00:00 +0000 Patnode, Michael L Guruge, Janaki L Castillo, Juan J Couture, Garret A Lombard, Vincent Terrapon, Nicolas Henrissat, Bernard Lebrilla, Carlito B https://orcid.org/0000-0001-7190-5323 Gordon, Jeffrey I https://escholarship.org/uc/item/994563kh Streptococcus pneumoniae is an opportunistic human pathogen that causes invasive diseases, including pneumonia, with greater health risks upon influenza A virus (IAV) co-infection. To facilitate pathogenesis studies in&nbsp;vivo, we developed an inducible CRISPR interference system that enables genome-wide fitness testing in one sequencing step (CRISPRi-seq). We applied CRISPRi-seq to assess bottlenecks and identify pneumococcal genes important in a murine pneumonia model. A critical bottleneck occurs at 48&nbsp;h with few bacteria causing systemic infection. This bottleneck is not present during IAV superinfection, facilitating identification of pneumococcal pathogenesis-related genes. Top in&nbsp;vivo essential genes included purA, encoding adenylsuccinate synthetase, and the cps operon required for capsule production. Surprisingly, CRISPRi-seq indicated no fitness-related role for pneumolysin during superinfection. Interestingly, although metK (encoding S-adenosylmethionine... https://escholarship.org/uc/item/994563kh Tue, 13 Jun 2023 00:00:00 +0000 Liu, Xue Kimmey, Jacqueline M https://orcid.org/0000-0003-1330-8525 Matarazzo, Laura de Bakker, Vincent Van Maele, Laurye Sirard, Jean-Claude Nizet, Victor Veening, Jan-Willem https://escholarship.org/uc/item/8381p07t <i>Helicobacter pylori</i> is a chronic bacterial pathogen that thrives in several regions of the stomach, causing inflammation that can vary by site and result in distinct disease outcomes. Whether the regions differ in terms of host-derived metabolites is not known. We thus characterized the regional variation of the metabolomes of mouse gastric corpus and antrum organoids and tissue. The uninfected secreted organoid metabolites differed between the corpus and antrum in only seven metabolites as follows: lactic acid, malic acid, phosphoethanolamine, alanine, uridine, glycerol, and isoleucine. Several of the secreted chemicals were depleted upon <i>H. pylori</i> infection in both regions, including urea, cholesterol, glutamine, fumaric acid, lactic acid, citric acid, malic acid, and multiple nonessential amino acids. These results suggest a model in which <i>H. pylori</i> preferentially uses carboxylic acids and amino acids in complex environments, and these are found in both... https://escholarship.org/uc/item/8381p07t Tue, 13 Jun 2023 00:00:00 +0000 Keilberg, Daniela Steele, Nina Fan, Sili Yang, Christina Zavros, Yana Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/3xt3c8gt The cytokine IL-10 antagonizes pathways that control <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) infection. Nevertheless, the impact of IL-10 during <i>Mtb</i> infection has been difficult to decipher because loss-of-function studies in animal models have yielded only mild phenotypes. We have discovered that the transcription factor basic helix-loop-helix family member e40 (Bhlhe40) is required to repress <i>Il10</i> expression during <i>Mtb</i> infection. Loss of Bhlhe40 in mice results in higher <i>Il10</i> expression, higher bacterial burden, and early susceptibility similar to that observed in mice lacking IFN-γ. Deletion of <i>Il10</i> in <i>Bhlhe40</i>^-/- mice reverses these phenotypes. Bhlhe40 deletion in T cells or CD11c⁺ cells is sufficient to cause susceptibility to <i>Mtb</i> Bhlhe40 represents the first transcription factor found to be essential during <i>Mtb</i> infection to specifically regulate <i>Il10</i> expression, revealing the importance... https://escholarship.org/uc/item/3xt3c8gt Sat, 10 Jun 2023 00:00:00 +0000 Huynh, Jeremy P Lin, Chih-Chung Kimmey, Jacqueline M https://orcid.org/0000-0003-1330-8525 Jarjour, Nicholas N Schwarzkopf, Elizabeth A Bradstreet, Tara R Shchukina, Irina Shpynov, Oleg Weaver, Casey T Taneja, Reshma Artyomov, Maxim N Edelson, Brian T Stallings, Christina L https://escholarship.org/uc/item/2xb0019d Research in recent years has focused significantly on the role of selective macroautophagy in targeting intracellular pathogens for lysosomal degradation, a process termed xenophagy. In this review we evaluate the proposed roles for xenophagy in controlling bacterial infection, highlighting the concept that successful pathogens have evolved ways to subvert or exploit this defense, minimizing the actual effectiveness of xenophagy in innate immunity. Instead, studies in animal models have revealed that autophagy-associated proteins often function outside of xenophagy to influence bacterial pathogenesis. In light of current efforts to manipulate autophagy and the development of host-directed therapies to fight bacterial infections, we also discuss the implications stemming from the complicated relationship that exists between autophagy and bacterial pathogens. https://escholarship.org/uc/item/2xb0019d Sat, 10 Jun 2023 00:00:00 +0000 Kimmey, Jacqueline M https://orcid.org/0000-0003-1330-8525 Stallings, Christina L https://escholarship.org/uc/item/1sf6s51m Mycobacterium tuberculosis (Mtb) is one of the world's most successful pathogens. Millions of new cases of tuberculosis occur each year, emphasizing the need for better methods of treatment. The design of novel therapeutics is dependent on our understanding of factors that are essential for pathogenesis. Many bacterial pathogens use pili and other adhesins to mediate pathogenesis. The recently identified Mycobacterium tuberculosis pilus (MTP) and the hypothetical, widely conserved Flp pilus have been speculated to be important for Mtb virulence based on in vitro studies and homology to other pili, respectively. However, the roles for these pili during infection have yet to be tested. We addressed this gap in knowledge and found that neither MTP nor the hypothetical Flp pilus is required for Mtb survival in mouse models of infection, although MTP can contribute to biofilm formation and subsequent isoniazid tolerance. However, differences in mtp expression did affect lesion architecture... https://escholarship.org/uc/item/1sf6s51m Sat, 10 Jun 2023 00:00:00 +0000 Mann, Katherine M Pride, Aaron C Flentie, Kelly Kimmey, Jacqueline M https://orcid.org/0000-0003-1330-8525 Weiss, Leslie A Stallings, Christina L https://escholarship.org/uc/item/0nb380km Mycobacterium tuberculosis infection results in 1.5 million deaths annually. Type I interferon (IFN) signaling through its receptor IFNAR correlates with increased severity of disease, although how this increases susceptibility to M. tuberculosis remains uncertain. ISG15 is one of the most highly induced interferon stimulated genes (ISGs) during M. tuberculosis infection. ISG15 functions by conjugation to target proteins (ISGylation), by noncovalent association with intracellular proteins, and by release from the cell. Recent studies indicated that ISG15 can function via conjugation-independent mechanisms to suppress the type I IFN response. These data raised the question of whether ISG15 may have diverse and sometimes opposing functions during M. tuberculosis infection. To address this, we analyzed ISGylation during M. tuberculosis infection and show that ISGylated proteins accumulate following infection in an IFNAR-dependent manner. Type I IFN and ISG15 both play transient roles... https://escholarship.org/uc/item/0nb380km Sat, 10 Jun 2023 00:00:00 +0000 Kimmey, Jacqueline M https://orcid.org/0000-0003-1330-8525 Campbell, Jessica A Weiss, Leslie A Monte, Kristen J Lenschow, Deborah J Stallings, Christina L https://escholarship.org/uc/item/3wv9p9p0 Prenatal arsenic exposure has been associated with reduced fetal growth and increased risk for preterm birth, but most studies have been conducted in highly exposed populations outside the U.S. or in non-Hispanic populations in the rural U.S. The objectives of the current study were to: 1) examine the impact of early pregnancy exposure to arsenic on birth weight and gestational age at birth in a predominately lower income Hispanic pregnancy cohort in urban Los Angeles and 2) compare multiple biomarkers of arsenic exposure (blood, urine, and hair) assessed in early pregnancy (mean&nbsp;±&nbsp;SD gestational age at biospecimen collection: 14&nbsp;±&nbsp;4 weeks). Total arsenic (blood, hair) was measured by ICP-MS and speciated arsenic (urine) was measured by HPLC coupled to ICP-MS. Associations between log₂-transformed arsenic measures and birth outcomes were evaluated using multivariable linear regression. A doubling in hair arsenic was associated with a 72.2&nbsp;g... https://escholarship.org/uc/item/3wv9p9p0 Wed, 7 Jun 2023 00:00:00 +0000 Howe, Caitlin G Farzan, Shohreh F Garcia, Erika Jursa, Thomas Iyer, Ramsunder Berhane, Kiros Chavez, Thomas A Hodes, Tahlia L Grubbs, Brendan H Funk, William E Smith, Donald R Bastain, Theresa M Breton, Carrie V https://escholarship.org/uc/item/0jz4d5vq Studies have reported associations between environmental manganese (Mn) exposure and impaired cognition, attention, impulse control, and fine motor function in children. Our recent rodent studies established that elevated Mn exposure causes these impairments. Here, rats were exposed orally to 0, 25, or 50&nbsp;mg Mn&nbsp;kg^-1 &nbsp;day^-1 during early postnatal life (PND 1-21) or lifelong to determine whether early life Mn exposure causes heightened behavioral reactivity in the open field, lasting changes in the catecholaminergic systems in the medial prefrontal cortex (mPFC), altered dendritic spine density, and whether lifelong exposure exacerbates these effects. We also assessed astrocyte reactivity (glial fibrillary acidic protein, GFAP), and astrocyte complement C3 and S100A10 protein levels as markers of A1 proinflammatory or A2 anti-inflammatory reactive astrocytes. Postnatal Mn exposure caused heightened behavioral reactivity during the first 5-10&nbsp;min... https://escholarship.org/uc/item/0jz4d5vq Sat, 3 Jun 2023 00:00:00 +0000 Conley, Travis E Beaudin, Stephane A Lasley, Stephen M Fornal, Casimir A Hartman, Jasenia Uribe, Walter Khan, Tooba Strupp, Barbara J Smith, Donald R https://escholarship.org/uc/item/7d69w81n Growing evidence from studies with children and animal models suggests that elevated levels of manganese during early development lead to lasting cognitive and fine motor deficits. This study was performed to assess presynaptic biogenic amine function in forebrain of adult Long-Evans rats exposed orally to 0, 25, or 50 mg Mn/kg/day over postnatal day 1-21 or continuously from birth to the end of the study (approximately postnatal day 500). Intracerebral microdialysis in awake rats quantified evoked outflow of biogenic amines in the right medial prefrontal cortex and left striatum. Results indicated that brain manganese levels in the early life exposed groups (postnatal day 24) largely returned to control levels by postnatal day 66, whereas levels in the lifelong exposed groups remained elevated 10%-20% compared with controls at the same ages. Manganese exposure restricted to the early postnatal period caused lasting reductions in cortical potassium-stimulated extracellular norepinephrine,... https://escholarship.org/uc/item/7d69w81n Thu, 1 Jun 2023 00:00:00 +0000 Lasley, Stephen M Fornal, Casimir A Mandal, Shyamali Strupp, Barbara J Beaudin, Stephane A Smith, Donald R https://escholarship.org/uc/item/61f5t429 <i>Helicobacter pylori</i> is a pathogen that chronically colonizes the stomachs of approximately half of the world's population and contributes to the development of gastric inflammation. We demonstrated previously <i>in vivo</i> that <i>H. pylori</i> uses motility to preferentially colonize injury sites in the mouse stomach. However, the chemoreceptor responsible for sensing gastric injury has not yet been identified. In this study, we utilized murine gastric organoids (gastroids) and mutant <i>H. pylori</i> strains to investigate the components necessary for <i>H. pylori</i> chemotaxis. High-intensity 730-nm light (two-photon photodamage) was used to cause single-cell damage in gastroids, and repair of the damage was monitored over time; complete repair occurred within ∼10 min in uninfected gastroids. Wild-type <i>H. pylori</i> accumulated at the damage site after gastric damage induction. In contrast, mutants lacking motility (Δ<i>motB</i>) or chemotaxis (Δ<i>cheY</i>) did... https://escholarship.org/uc/item/61f5t429 Tue, 30 May 2023 00:00:00 +0000 Hanyu, Hikaru Engevik, Kristen A Matthis, Andrea L Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 Montrose, Marshall H Aihara, Eitaro https://escholarship.org/uc/item/5pv7g59p The epithelial cell layer of the major organs of the mammalian gastrointestinal (GI) tract is extensively invaginated into thousands of gland and crypt structures. These are lined by distinct sets of epithelial cells and may comprise discrete niches. The host maximizes the distance between the epithelial cell layer and GI-inhabiting microbes to limit inflammation, and these strategies also likely keep bacteria out of the glands and crypts. We discuss here the specific host processes that have been shown to restrict bacterial presence in the glands and crypts, specifically the immune system, acid, mucin, oxygen, and reactive oxygen species. Not surprisingly, microbes have evolved sophisticated strategies to overcome these host factors and reside close to the epithelium in the glands and crypts. Bacterial properties important for gland and crypt colonization include bacterial immunomodulatory molecules, chemotaxis, and the use of certain metabolites. Overall, these as-yet limited... https://escholarship.org/uc/item/5pv7g59p Wed, 24 May 2023 00:00:00 +0000 Yang, Christina Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/75r166f1 Bacterial flagella are rotary nanomachines that contribute to bacterial fitness in many settings, including host colonization. The flagellar motor relies on the multiprotein flagellar motor-switch complex to govern flagellum formation and rotational direction. Different bacteria exhibit great diversity in their flagellar motors. One such variation is exemplified by the motor-switch apparatus of the gastric pathogen <i>Helicobacter pylori</i>, which carries an extra switch protein, FliY, along with the more typical FliG, FliM, and FliN proteins. All switch proteins are needed for normal flagellation and motility in <i>H. pylori</i>, but the molecular mechanism of their assembly is unknown. To fill this gap, we examined the interactions among these proteins. We found that the C-terminal SpoA domain of FliY (FliY_C) is critical to flagellation and forms heterodimeric complexes with the FliN and FliM SpoA domains, which are β-sheet domains of type III secretion system proteins.... https://escholarship.org/uc/item/75r166f1 Sat, 20 May 2023 00:00:00 +0000 Lam, Kwok Ho Xue, Chaolun Sun, Kailei Zhang, Huawei Lam, Wendy Wai Ling Zhu, Zeyu Ng, Juliana Tsz Yan Sause, William E Lertsethtakarn, Paphavee Lau, Kwok Fai Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 Au, Shannon Wing Ngor https://escholarship.org/uc/item/5sb1v49w Despite decades of effort, <i>Helicobacter pylori</i> infections remain difficult to treat. Over half of the world's population is infected by <i>H. pylori</i>, which is a major cause of duodenal and gastric ulcers as well as gastric cancer. During chronic infection, <i>H. pylori</i> localizes within the gastric mucosal layer, including deep within invaginations called glands; thanks to its impressive ability to survive despite the harsh acidic environment, it can persist for the host's lifetime. This ability to survive and persist in the stomach is associated with urease production, chemotactic motility, and the ability to adapt to the fluctuating environment. Additionally, biofilm formation has recently been suggested to play a role in colonization. Biofilms are surface-associated communities of bacteria that are embedded in a hydrated matrix of extracellular polymeric substances. Biofilms pose a substantial health risk and are key contributors to many chronic and recurrent... https://escholarship.org/uc/item/5sb1v49w Fri, 19 May 2023 00:00:00 +0000 Hathroubi, Skander Servetas, Stephanie L Windham, Ian Merrell, D Scott Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/02c469j7 The epithelial layer of the gastrointestinal tract contains invaginations, called glands or crypts, which are colonized by symbiotic and pathogenic microorganisms and may function as designated niches for certain species. Factors that control gland colonization are poorly understood, but bacterial chemotaxis aids occupation of these sites. We report here that a <i>Helicobacter pylori</i> cytoplasmic chemoreceptor, TlpD, is required for gland colonization in the stomach. <i>tlpD</i> mutants demonstrate gland colonization defects characterized by a reduction in the percentage of glands colonized but not in the number of bacteria per gland. Consistent with TlpD's reported role in reactive oxygen species (ROS) avoidance, <i>tlpD</i> mutants showed hallmarks of exposure to high ROS. To assess the role of host-generated ROS in TlpD-dependent gland colonization, we utilized mice that lack either the ability to generate epithelial hydrogen peroxide or immune cell superoxide. <i>tlpD</i>... https://escholarship.org/uc/item/02c469j7 Wed, 17 May 2023 00:00:00 +0000 Collins, Kieran D Hu, Shuai Grasberger, Helmut Kao, John Y Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/68q7q514 The consumption of one meal of seafood containing domoic acid (DA) at levels high enough to induce seizures can cause gross histopathological lesions in hippocampal regions of the brain and permanent memory loss in humans and marine mammals. Seafood regulatory limits have been set at 20mgDA/kg shellfish to protect human consumers from symptomatic acute exposure, but the effects of repetitive low-level asymptomatic exposure remain a critical knowledge gap. Recreational and Tribal-subsistence shellfish harvesters are known to regularly consume low levels of DA. The aim of this study was to determine if chronic low-level DA exposure, at doses below those that cause overt signs of neurotoxicity, has quantifiable impacts on cognitive function. To this end, female C57BL/6NJ mice were exposed to asymptomatic doses of DA (≈0.75mg/kg) or vehicle once a week for several months. Spatial learning and memory were tested in a radial water maze paradigm at one, six and 25 weeks of exposure,... https://escholarship.org/uc/item/68q7q514 Thu, 11 May 2023 00:00:00 +0000 Lefebvre, Kathi A Kendrick, Preston S Ladiges, Warren Hiolski, Emma M Ferriss, Bridget E Smith, Donald R Marcinek, David J https://escholarship.org/uc/item/6xd7684p Although it is appreciated that bacterial chemotaxis systems rely on coupling, also called scaffold, proteins to both connect input receptors with output kinases and build interkinase connections that allow signal amplification, it is not yet clear why many systems use more than one coupling protein. We examined the distinct functions for multiple coupling proteins in the bacterial chemotaxis system of <i>Helicobacter pylori</i>, which requires two nonredundant coupling proteins for chemotaxis: CheW and CheV1, a hybrid of a CheW and a phosphorylatable receiver domain. We report that CheV1 and CheW have largely redundant abilities to interact with chemoreceptors and the CheA kinase, and both similarly activated CheA's kinase activity. We discovered, however, that they are not redundant for formation of the higher order chemoreceptor arrays that are known to form via CheA-CheW interactions. In support of this possibility, we found that CheW and CheV1 interact with each other and... https://escholarship.org/uc/item/6xd7684p Wed, 10 May 2023 00:00:00 +0000 Abedrabbo, Samar Castellon, Juan Collins, Kieran D Johnson, Kevin S Ottemann, Karen M https://orcid.org/0000-0001-6265-7401 https://escholarship.org/uc/item/471614mn Recent studies from our lab have demonstrated that postnatal manganese (Mn) exposure in a rodent model can cause lasting impairments in fine motor control and attention, and that oral methylphenidate (MPH) treatment can effectively treat the dysfunction in fine motor control. However, it is unknown whether MPH treatment can alleviate the impairments in attention produced by Mn exposure. Here we used a rodent model of postnatal Mn exposure to determine whether (1) oral MPH alleviates attention and impulse control deficits caused by postnatal Mn exposure, using attention tasks that are variants of the 5-choice serial reaction time task, and (2) whether these treatments affected neuronal dendritic spine density in the medial prefrontal cortex (mPFC) and dorsal striatum. Male Long-Evans rats were exposed orally to 0 or 50Mn/kg/d throughout life starting on PND 1, and tested as young adults (PND 107-115) on an attention task that specifically tapped selective attention and impulse... https://escholarship.org/uc/item/471614mn Wed, 10 May 2023 00:00:00 +0000 Beaudin, Stephane A Strupp, Barbara J Uribe, Walter Ysais, Lauren Strawderman, Myla Smith, Donald R