Tetrodotoxin-sensitive persistent sodium currents, INaP, that activate at subthreshold voltages, have been detected in numerous vertebrate and invertebrate neurons. These currents are believed to be critical for regulating neuronal excitability. However, the molecular mechanism underlying INaP is controversial. In this study, we identified an INaP with a broad range of voltage dependence, from -60mV to 20mV, in a Drosophila sodium channel variant expressed in Xenopus oocytes. Mutational analysis revealed that two variant-specific amino acid changes, I260T in the S4-S5 linker of domain I (ILS4-S5) and A1731V in the voltage sensor S4 of domain IV (IVS4), contribute to the INaP. I260T is critical for the portion of INaP at hyperpolarized potentials. The T260-mediated INaP is likely the result of window currents flowing in the voltage range where the activation and inactivation curves overlap. A1731V is responsible for impaired inactivation and contributes to the portion of INaP at depolarized potentials. Furthermore, A1731V causes enhanced activity of two site-3 toxins which induce persistent currents by inhibiting the outward movement of IVS4, suggesting that A1731V inhibits the outward movement of IVS4. These results provided molecular evidence for the involvement of distinct mechanisms in the generation of INaP: T260 contributes to INaP via enhancement of the window current, whereas V1731 impairs fast inactivation probably by inhibiting the outward movement of IVS4.

© 2015 Greninger et al. Background: Primary amoebic meningoencephalitis (PAM) is a rare, often lethal, cause of encephalitis, for which early diagnosis and prompt initiation of combination antimicrobials may improve clinical outcomes. Methods: In this stud

We summarize some of the work done by the P3 subgroup on Alternative Models and New Ideas. The working group covered a broad range of topics including a constrained Standard Model from an extra dimension, a discussion of recent ideas addressing the strong CP problem, searches for doubly charged higgs bosons in e gamma collisions, and an update on discovery limits for extra neutral gauge bosons at hadron colliders. The breadth of topics reflects the many ideas and approaches to physics beyond the Standard Model.

The NSF has chosen the site for the Deep Underground Science and Engineering Laboratory (DUSEL) to be in Lead, South Dakota. In fact, the state of South Dakota has already stepped up to the plate and contributed its own funding for the proposed lab, see http://www.sanfordlaboratoryathomestake.org/index.html. The final decision by NSF for funding the Initial Suite of Experiments for DUSEL will be made early in 2009. At that time the NSF Science Board must make a decision. Of order 200 experimentalists have already expressed an interest in performing experiments at DUSEL. In order to assess the interest of the theoretical community, the Center for Cosmology and Astro-Particle Physics (CCAPP) at The Ohio State University (OSU) organized a 3-day DUSEL Theory Workshop in Columbus, Ohio from April 4 - 6, 2008. The workshop focused on the scientific case for six proposed experiments for DUSEL: long baseline neutrino oscillations, proton decay, dark matter, astrophysical neutrinos, neutrinoless double beta decay and N-Nbar oscillations. The outcome of this workshop is the DUSEL Theory White paper addressing the scientific case at a level which may be useful in the decision making process for policy makers at the NSF and in the U.S. Congress. In order to assess the physics interest in the DUSEL project we have posted the DUSEL Theory White paper on the following CCAPP link http://ccapp.osu.edu/whitepaper.html . Please read the white paper and, if you are interested, use the link to show your support by co-signing the white paper.

Recent developments of transition-edge sensors (TESs), based on extensive experience in ground-based experiments, have been making the sensor techniques mature enough for their application on future satellite cosmic microwave background (CMB) polarization experiments. LiteBIRD is in the most advanced phase among such future satellites, targeting its launch in Japanese Fiscal Year 2027 (2027FY) with JAXA’s H3 rocket. It will accommodate more than 4000 TESs in focal planes of reflective low-frequency and refractive medium-and-high-frequency telescopes in order to detect a signature imprinted on the CMB by the primordial gravitational waves predicted in cosmic inflation. The total wide frequency coverage between 34 and 448 GHz enables us to extract such weak spiral polarization patterns through the precise subtraction of our Galaxy’s foreground emission by using spectral differences among CMB and foreground signals. Telescopes are cooled down to 5 K for suppressing thermal noise and contain polarization modulators with transmissive half-wave plates at individual apertures for separating sky polarization signals from artificial polarization and for mitigating from instrumental 1/f noise. Passive cooling by using V-grooves supports active cooling with mechanical coolers as well as adiabatic demagnetization refrigerators. Sky observations from the second Sun–Earth Lagrangian point, L2, are planned for 3 years. An international collaboration between Japan, the USA, Canada, and Europe is sharing various roles. In May 2019, the Institute of Space and Astronautical Science, JAXA, selected LiteBIRD as the strategic large mission No. 2.