Background and purpose

The bioactive monoamine 5-HT, implicated in the pathogenesis of functional gastrointestinal disorders, is abundantly synthesized and stored in rat proximal colonic mucosa and released to the gut lumen and subepithelial space. Despite much data regarding its expression and function, the effects of luminal 5-HT on colonic anion secretion have not been fully investigated.

Experimental approach

We measured short-circuit current (Isc ) as an indicator of ion transport in mucosa-submucosa or mucosa-only preparations of rat proximal colon. Total CO2 output was measured in vitro and in vivo. Immunohistochemistry was performed to investigate the localization of 5-HT4 , NOS1 and NOS2.

Key results

Luminal 5-HT gradually increased the amplitude and sustained the elevation of Isc . Luminal 5-HT-evoked ΔIsc was acetazolamide sensitive and HCO3 (-) dependent, consistent with cytosolic carbonic anhydrase-dependent electrogenic HCO3 (-) secretion, while not affected by tetrodotoxin (TTX), atropine or indomethacin. Pretreatment with the selective 5-HT4 antagonist GR113808, but not antagonists for 5-HT3 , 5-HT6 or 5-HT7 , inhibited luminal 5-HT-evoked ΔIsc . Furthermore, luminal cisapride and tegaserod increased Isc to the same extent as did 5-HT in the presence of indomethacin and TTX. Removal of the submucosa or pretreatment with NOS inhibitors enhanced luminal 5-HT-evoked ΔIsc , suggesting that NO synthesized in the submucosa suppresses mucosal anion secretion. NOS1 and NOS2 were immunostained in the submucosal neurons and glial cells respectively. Luminal 5-HT-evoked HCO3 (-) secretion was confirmed in vivo, inhibited by co-perfusion of GR113808, but not by ondansetron.

Conclusions and implications

A novel apical 5-HT4 -mediated HCO3 (-) secretory pathway and an NO-dependent inhibitory mechanism are present in the proximal colon. Luminal 5-HT-evoked HCO3 (-) secretion may be important for the maintenance of mucosal integrity by regulating luminal pH.

Short-chain fatty acids (SCFA) are microbial fermentation products absorbed by the colon. We recently reported that activation of the SCFA receptor termed free fatty acid receptor 3 (FFA3), expressed on cholinergic nerves, suppresses nicotinic acetylcholine receptor (nAChR)-mediated transepithelial anion secretion. This study aimed to clarify how activation of neurally expressed FFA3 affects colonic motor function. FFA3-expressing myenteric neurons were identified by immunostaining; contractions of isolated circular muscle strips obtained from rat proximal colon were measured by isometric transducers. The effect of FFA3 agonists on defecation in vivo was examined in an exogenous serotonin-induced defecation model. FFA3 immunoreactivity was located in nitrergic and cholinergic neurons in the myenteric plexus. In isolated circular muscle strips without mucosa and submucosa, the addition of nicotine (10 μM) or serotonin transiently relaxed the muscle through nitrergic neurons, whereas high concentrations of nicotine (100 μM) induced large-amplitude contractions that were mediated by cholinergic neurons. Pretreatment with FFA3 agonists inhibited nicotine- or serotonin-induced motility changes but had no effect on bethanechol-induced direct muscle contractions. The Gi/o inhibitor pertussis toxin reversed the inhibitory effect of an FFA3 agonist AR420626 on nicotine-evoked contractions, suggesting that FFA3 activation suppresses nAChR-mediated neural activity in myenteric neurons, consistent with an FFA3-mediated antisecretory effect. In conscious rats, exogenous serotonin increased the volume of fecal output, compared with the vehicle- or AR420626-treated groups. Pretreatment with AR420626 significantly suppressed serotonin-induced fecal output. FFA3 is a promising target for the treatment of neurogenic diarrheal disorders by suppressing nAChR-mediated neural pathways.

The polarization of the atmosphere has been a long-standing concern for ground-based experiments targeting cosmic microwave background (CMB) polarization. Ice crystals in upper tropospheric clouds scatter thermal radiation from the ground and produce a horizontally polarized signal. We report a detailed analysis of the cloud signal using a ground-based CMB experiment, Polarbear, located at the Atacama desert in Chile and observing at 150 GHz. We observe horizontally polarized temporal increases of low-frequency fluctuations ("polarized bursts," hereafter) of ≲0.1 K when clouds appear in a webcam monitoring the telescope and the sky. The hypothesis of no correlation between polarized bursts and clouds is rejected with >24σ statistical significance using three years of data. We consider many other possibilities including instrumental and environmental effects, and find no reasons other than clouds that can explain the data better. We also discuss the impact of the cloud polarization on future ground-based CMB polarization experiments.

Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.

We report an improved measurement of the cosmic microwave background B-mode polarization power spectrum with the Polarbear experiment at 150 GHz. By adding new data collected during the second season of observations (2013-2014) to re-analyzed data from the first season (2012-2013), we have reduced twofold the band-power uncertainties. The band powers are reported over angular multipoles 500 ≤ ℓ ≤ 2100, where the dominant B-mode signal is expected to be due to the gravitational lensing of E-modes. We reject the null hypothesis of no B-mode polarization at a confidence of 3.1σ including both statistical and systematic uncertainties. We test the consistency of the measured B-modes with the Λ Cold Dark Matter (ΛCDM) framework by fitting for a single lensing amplitude parameter A L = 0.60 +0.26-0.24(stat)+0.00-0.04 (inst) ± 0.14(foreground) ± 0.04(multi), where A L = 1 relative to the Planck 2015 best-fit model prediction. We obtain ±0.14(foreground) ±0.04(multi), where is the fiducial ΛCDM value.

We present an overview of the design and status of the Polarbear-2 and the Simons Array experiments. Polarbear-2 is a cosmic microwave background polarimetry experiment which aims to characterize the arc-minute angular scale B-mode signal from weak gravitational lensing and search for the degree angular scale B-mode signal from inflationary gravitational waves. The receiver has a 365 mm diameter focal plane cooled to 270 mK. The focal plane is filled with 7588 dichroic lenslet–antenna-coupled polarization sensitive transition edge sensor (TES) bolometric pixels that are sensitive to 95 and 150 GHz bands simultaneously. The TES bolometers are read-out by SQUIDs with 40 channel frequency domain multiplexing. Refractive optical elements are made with high-purity alumina to achieve high optical throughput. The receiver is designed to achieve noise equivalent temperature of 5.8 μ KCMBs in each frequency band. Polarbear-2 will deploy in 2016 in the Atacama desert in Chile. The Simons Array is a project to further increase sensitivity by deploying three Polarbear-2 type receivers. The Simons Array will cover 95, 150, and 220 GHz frequency bands for foreground control. The Simons Array will be able to constrain tensor-to-scalar ratio and sum of neutrino masses to σ(r) = 6 × 10 - 3 at r= 0.1 and ∑ mν(σ= 1) to 40 meV.

We present on the status of POLARBEAR-2 A (PB2-A) focal plane fabrication. The PB2-A is the first of three telescopes in the Simons Array, which is an array of three cosmic microwave background polarization-sensitive telescopes located at the POLARBEAR site in Northern Chile. As the successor to the PB experiment, each telescope and receiver combination is named as PB2-A, PB2-B, and PB2-C. PB2-A and -B will have nearly identical receivers operating at 90 and 150 GHz while PB2-C will house a receiver operating at 220 and 270 GHz. Each receiver contains a focal plane consisting of seven close-hex packed lenslet-coupled sinuous antenna transition edge sensor bolometer arrays. Each array contains 271 dichroic optical pixels, each of which has four TES bolometers for a total of 7588 detectors per receiver. We have produced a set of two types of candidate arrays for PB2-A. The first we call Version 11 (V11) uses a silicon oxide (SiOx) for the transmission lines and crossover process for orthogonal polarizations. The second we call Version 13 (V13) uses silicon nitride (SiNx) for the transmission lines and cross-under process for orthogonal polarizations. We have produced enough of each type of array to fully populate the focal plane of the PB2-A receiver. The average wirebond yield for V11 and V13 arrays is 93.2% and 95.6%, respectively. The V11 arrays had a superconducting transition temperature (Tc) of 452±15 mK, a normal resistance (Rn) of 1.25±0.20Ω, and saturation powers of 5.2 ± 1.0 pW and 13 ± 1.2 pW for the 90 and 150 GHz bands, respectively. The V13 arrays had a superconducting transition temperature (Tc) of 456 ± 6 mK, a normal resistance (Rn) of 1.1±0.2Ω, and saturation powers of 10.8 ± 1.8 pW and 22.9 ± 2.6 pW for the 90 and 150 GHz bands, respectively. Production and characterization of arrays for PB2-B are ongoing and are expected to be completed by the summer of 2018. We have fabricated the first three candidate arrays for PB2-C but do not have any characterization results to present at this time.

LiteBIRD is a proposed CMB polarization satellite project to probe the inflationary B-mode signal. The satellite is designed to measure the tensor-to-scalar ratio with a 68 % confidence level uncertainty of σr< 10 - 3, including statistical, instrumental systematic, and foreground uncertainties. LiteBIRD will observe the full sky from the second Lagrange point for 3 years. We have a focal plane layout for observing frequency coverage that spans 40–402 GHz to characterize the galactic foregrounds. We have two detector candidates, transition-edge sensor bolometers and microwave kinetic inductance detectors. In both cases, a telecentric focal plane consists of approximately 2 × 10 3 superconducting detectors. We will present the mission overview of LiteBIRD, the project status, and the TES focal plane layout.

Particle production and correlation functions from Au+Au reactions have been measured as a function of both beam energy (2-10.7AGeV) and impact parameter. These results are used to probe the dynamics of heavy-ion reactions, confront hadronic models over a wide range of conditions and to search for the onset of new phenomena.