Characterization of the mrgRS locus of the opportunistic pathogen Burkholderia pseudomallei: temperature regulates the expression of a two-component signal transduction system

BACKGROUND: Burkholderia pseudomallei is a saprophyte in tropical environments and an opportunistic human pathogen. This versatility requires a sensing mechanism that allows the bacterium to respond rapidly to altered environmental conditions. We characterized a two-component signal transduction locus from B. pseudomallei 204, mrgR and mrgS, encoding products with extensive homology with response regulators and histidine protein kinases of Escherichia coli, Bordetella pertussis, and Vibrio cholerae. RESULTS: The locus was present and expressed in a variety of B. pseudomallei human and environmental isolates but was absent from other Burkholderia species, B. cepacia, B. cocovenenans, B. plantarii, B. thailandensis, B. vandii, and B. vietnamiensis. A 2128 bp sequence, including the full response regulator mrgR, but not the sensor kinase mrgS, was present in the B. mallei genome. Restriction fragment length polymorphism downstream from mrgRS showed two distinct groups were present among B. pseudomallei isolates. Our analysis of the open reading frames in this region of the genome revealed that transposase and bacteriophage activity may help explain this variation. MrgR and MrgS proteins were expressed in B. pseudomallei 204 cultured at different pH, salinity and temperatures and the expression was substantially reduced at 25°C compared with 37°C or 42°C but was mostly unaffected by pH or salinity, although at 25°C and 0.15% NaCl a small increase in MrgR expression was observed at pH 5. MrgR was recognized by antibodies in convalescent sera pooled from melioidosis patients. CONCLUSION: The results suggest that mrgRS regulates an adaptive response to temperature that may be essential for pathogenesis, particularly during the initial phases of infection. B. pseudomallei and B. mallei are very closely related species that differ in their capacity to adapt to changing environmental conditions. Modifications in this region of the genome may assist our understanding of the reasons for this difference

BICEP3: a 95 GHz refracting telescope for degree-scale CMB polarization

BICEP3 is a 550 mm-aperture refracting telescope for polarimetry of radiation in the cosmic microwave background at 95 GHz. It adopts the methodology of BICEP1, BICEP2 and the Keck Array experiments - it possesses sufficient resolution to search for signatures of the inflation-induced cosmic gravitational-wave background while utilizing a compact design for ease of construction and to facilitate the characterization and mitigation of systematics. However, BICEP3 represents a significant breakthrough in per-receiver sensitivity, with a focal plane area 5$\times$ larger than a BICEP2/Keck Array receiver and faster optics ($f/1.6$ vs. $f/2.4$). Large-aperture infrared-reflective metal-mesh filters and infrared-absorptive cold alumina filters and lenses were developed and implemented for its optics. The camera consists of 1280 dual-polarization pixels; each is a pair of orthogonal antenna arrays coupled to transition-edge sensor bolometers and read out by multiplexed SQUIDs. Upon deployment at the South Pole during the 2014-15 season, BICEP3 will have survey speed comparable to Keck Array 150 GHz (2013), and will significantly enhance spectral separation of primordial B-mode power from that of possible galactic dust contamination in the BICEP2 observation patch.Comment: 12 pages, 5 figures. Presented at SPIE Astronomical Telescopes and Instrumentation 2014: Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VII. To be published in Proceedings of SPIE Volume 915

BICEP2 / Keck Array VIII: Measurement of gravitational lensing from large-scale B-mode polarization

We present measurements of polarization lensing using the 150 GHz maps which include all data taken by the BICEP2 & Keck Array CMB polarization experiments up to and including the 2014 observing season (BK14). Despite their modest angular resolution ($\sim 0.5^\circ$), the excellent sensitivity ($\sim 3\mu$K-arcmin) of these maps makes it possible to directly reconstruct the lensing potential using only information at larger angular scales ($\ell\leq 700$). From the auto-spectrum of the reconstructed potential we measure an amplitude of the spectrum to be $A^{\phi\phi}_{\rm L}=1.15\pm 0.36$ (Planck $\Lambda$CDM prediction corresponds to $A^{\phi\phi}_{\rm L}=1$), and reject the no-lensing hypothesis at 5.8$\sigma$, which is the highest significance achieved to date using an EB lensing estimator. Taking the cross-spectrum of the reconstructed potential with the Planck 2015 lensing map yields $A^{\phi\phi}_{\rm L}=1.13\pm 0.20$. These direct measurements of $A^{\phi\phi}_{\rm L}$ are consistent with the $\Lambda$CDM cosmology, and with that derived from the previously reported BK14 B-mode auto-spectrum ($A^{\rm BB}_{\rm L}=1.20\pm 0.17$). We perform a series of null tests and consistency checks to show that these results are robust against systematics and are insensitive to analysis choices. These results unambiguously demonstrate that the B-modes previously reported by BICEP / Keck at intermediate angular scales ($150\lesssim\ell\lesssim 350$) are dominated by gravitational lensing. The good agreement between the lensing amplitudes obtained from the lensing reconstruction and B-mode spectrum starts to place constraints on any alternative cosmological sources of B-modes at these angular scales.Comment: 12 pages, 8 figure

Diet-Induced Obesity Impairs Endothelium-Derived Hyperpolarization via Altered Potassium Channel Signaling Mechanisms

BACKGROUND: The vascular endothelium plays a critical role in the control of blood flow. Altered endothelium-mediated vasodilator and vasoconstrictor mechanisms underlie key aspects of cardiovascular disease, including those in obesity. Whilst the mechanism of nitric oxide (NO)-mediated vasodilation has been extensively studied in obesity, little is known about the impact of obesity on vasodilation to the endothelium-derived hyperpolarization (EDH) mechanism; which predominates in smaller resistance vessels and is characterized in this study. METHODOLOGY/PRINCIPAL FINDINGS: Membrane potential, vessel diameter and luminal pressure were recorded in 4(th) order mesenteric arteries with pressure-induced myogenic tone, in control and diet-induced obese rats. Obesity, reflecting that of human dietary etiology, was induced with a cafeteria-style diet (∼30 kJ, fat) over 16-20 weeks. Age and sexed matched controls received standard chow (∼12 kJ, fat). Channel protein distribution, expression and vessel morphology were determined using immunohistochemistry, Western blotting and ultrastructural techniques. In control and obese rat vessels, acetylcholine-mediated EDH was abolished by small and intermediate conductance calcium-activated potassium channel (SK(Ca)/IK(Ca)) inhibition; with such activity being impaired in obesity. SK(Ca)-IK(Ca) activation with cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) and 1-ethyl-2-benzimidazolinone (1-EBIO), respectively, hyperpolarized and relaxed vessels from control and obese rats. IK(Ca)-mediated EDH contribution was increased in obesity, and associated with altered IK(Ca) distribution and elevated expression. In contrast, the SK(Ca)-dependent-EDH component was reduced in obesity. Inward-rectifying potassium channel (K(ir)) and Na(+)/K(+)-ATPase inhibition by barium/ouabain, respectively, attenuated and abolished EDH in arteries from control and obese rats, respectively; reflecting differential K(ir) expression and distribution. Although changes in medial properties occurred, obesity had no effect on myoendothelial gap junction density. CONCLUSION/SIGNIFICANCE: In obese rats, vasodilation to EDH is impaired due to changes in the underlying potassium channel signaling mechanisms. Whilst myoendothelial gap junction density is unchanged in arteries of obese compared to control, increased IK(Ca) and Na(+)/K(+)-ATPase, and decreased K(ir) underlie changes in the EDH mechanism

2022 Upgrade and Improved Low Frequency Camera Sensitivity for CMB Observation at the South Pole

Constraining the Galactic foregrounds with multi-frequency Cosmic Microwave Background (CMB) observations is an essential step towards ultimately reaching the sensitivity to measure primordial gravitational waves (PGWs), the sign of inflation after the Big-Bang that would be imprinted on the CMB. The BICEP Array telescope is a set of multi-frequency cameras designed to constrain the energy scale of inflation through CMB B-mode searches while also controlling the polarized galactic foregrounds. The lowest frequency BICEP Array receiver (BA1) has been observing from the South Pole since 2020 and provides 30 GHz and 40 GHz data to characterize the Galactic synchrotron in our CMB maps. In this paper, we present the design of the BA1 detectors and the full optical characterization of the camera including the on-sky performance at the South Pole. The paper also introduces the design challenges during the first observing season including the effect of out-of-band photons on detectors performance. It also describes the tests done to diagnose that effect and the new upgrade to minimize these photons, as well as installing more dichroic detectors during the 2022 deployment season to improve the BA1 sensitivity. We finally report background noise measurements of the detectors with the goal of having photon noise dominated detectors in both optical channels. BA1 achieves an improvement in mapping speed compared to the previous deployment season.Comment: Proceedings of SPIE Astronomical Telescopes + Instrumentation 2022 (AS22

Results and Limits of Time Division Multiplexing for the BICEP Array High Frequency Receivers

Time-Division Multiplexing is the readout architecture of choice for many ground and space experiments, as it is a very mature technology with proven outstanding low-frequency noise stability, which represents a central challenge in multiplexing. Once fully populated, each of the two BICEP Array high frequency receivers, observing at 150GHz and 220/270GHz, will have 7776 TES detectors tiled on the focal plane. The constraints set by these two receivers required a redesign of the warm readout electronics. The new version of the standard Multi Channel Electronics, developed and built at the University of British Columbia, is presented here for the first time. BICEP Array operates Time Division Multiplexing readout technology to the limits of its capabilities in terms of multiplexing rate, noise and crosstalk, and applies them in rigorously demanding scientific application requiring extreme noise performance and systematic error control. Future experiments like CMB-S4 plan to use TES bolometers with Time Division/SQUID-based readout for an even larger number of detectors.Comment: 10 pages, 7 figures, Submitted to Journal of Low Temperature Physic