X-ray phase contrast imaging of biological specimens with tabletop synchrotron radiation

Since their discovery in 1896, x-rays have had a profound impact on science, medicine and technology. Here we show that the x-rays from a novel tabletop source of bright coherent synchrotron radiation can be applied to phase contrast imaging of biological specimens, yielding superior image quality and avoiding the need for scarce or expensive conventional sources

Revealing the cosmic evolution of boxy/peanut-shaped bulges from HST COSMOS and SDSS

Abstract Vertically thickened bars, observed in the form of boxy/peanut (B/P) bulges, are found in the majority of massive barred disc galaxies in the local Universe, including our own. B/P bulges indicate that their host bars have suffered violent bending instabilities driven by anisotropic velocity distributions. We investigate for the first time how the frequency of B/P bulges in barred galaxies evolves from z = 1 to z ≈ 0, using a large sample of non-edge-on galaxies with masses M⋆ > 1010 M⊙, selected from the HST COSMOS survey. We find the observed fraction increases from $0^{+3.6}_{-0.0}\%$ at z = 1 to $37.8^{+5.4}_{-5.1}$% at z = 0.2. We account for problems identifying B/P bulges in galaxies with low inclinations and unfavourable bar orientations, and due to redshift-dependent observational biases with the help of a sample from the Sloan Digital Sky Survey, matched in resolution, rest-frame band, signal-to-noise ratio and stellar mass and analysed in the same fashion. From this, we estimate that the true fraction of barred galaxies with B/P bulges increases from ∼10% at z ≈ 1 to $\sim 70\%$ at z = 0. In agreement with previous results for nearby galaxies, we find a strong dependence of the presence of a B/P bulge on galaxy stellar mass. This trend is observed in both local and high-redshift galaxies, indicating that it is an important indicator of vertical instabilities across a large fraction of the age of the Universe. We propose that galaxy formation processes regulate the thickness of galaxy discs, which in turn affect which galaxies experience violent bending instabilities of the bar

Analysis of host response to bacterial infection using error model based gene expression microarray experiments

A key step in the analysis of microarray data is the selection of genes that are differentially expressed. Ideally, such experiments should be properly replicated in order to infer both technical and biological variability, and the data should be subjected to rigorous hypothesis tests to identify the differentially expressed genes. However, in microarray experiments involving the analysis of very large numbers of biological samples, replication is not always practical. Therefore, there is a need for a method to select differentially expressed genes in a rational way from insufficiently replicated data. In this paper, we describe a simple method that uses bootstrapping to generate an error model from a replicated pilot study that can be used to identify differentially expressed genes in subsequent large-scale studies on the same platform, but in which there may be no replicated arrays. The method builds a stratified error model that includes array-to-array variability, feature-to-feature variability and the dependence of error on signal intensity. We apply this model to the characterization of the host response in a model of bacterial infection of human intestinal epithelial cells. We demonstrate the effectiveness of error model based microarray experiments and propose this as a general strategy for a microarray-based screening of large collections of biological samples

Iterative focused screening with biological fingerprints identifies selective Asc-1 inhibitors distinct from traditional high throughput screening

N-methyl-d-aspartate receptors (NMDARs) mediate glutamatergic signaling that is critical to cognitive processes in the central nervous system, and NMDAR hypofunction is thought to contribute to cognitive impairment observed in both schizophrenia and Alzheimer’s disease. One approach to enhance the function of NMDAR is to increase the concentration of an NMDAR coagonist, such as glycine or d-serine, in the synaptic cleft. Inhibition of alanine–serine–cysteine transporter-1 (Asc-1), the primary transporter of d-serine, is attractive because the transporter is localized to neurons in brain regions critical to cognitive function, including the hippocampus and cortical layers III and IV, and is colocalized with d-serine and NMDARs. To identify novel Asc-1 inhibitors, two different screening approaches were performed with whole-cell amino acid uptake in heterologous cells stably expressing human Asc-1: (1) a high-throughput screen (HTS) of 3 M compounds measuring 35S l-cysteine uptake into cells attached to scintillation proximity assay beads in a 1536 well format and (2) an iterative focused screen (IFS) of a 45 000 compound diversity set using a 3H d-serine uptake assay with a liquid scintillation plate reader in a 384 well format. Critically important for both screening approaches was the implementation of counter screens to remove nonspecific inhibitors of radioactive amino acid uptake. Furthermore, a 15 000 compound expansion step incorporating both on- and off-target data into chemical and biological fingerprint-based models for selection of additional hits enabled the identification of novel Asc-1-selective chemical matter from the IFS that was not identified in the full-collection HTS

Evc2 is a positive modulator of Hedgehog signalling that interacts with Evc at the cilia membrane and is also found in the nucleus

<p>Abstract</p> <p>Background</p> <p>Evc is essential for Indian Hedgehog (Hh) signalling in the cartilage growth plate. The gene encoding Evc2 is in close proximity in divergent orientation to <it>Evc </it>and mutations in both human genes lead to the chondrodysplasia Ellis-van Creveld syndrome.</p> <p>Results</p> <p>Bioinformatic analysis reveals that the <it>Evc </it>and <it>Evc2 </it>genes arose through a duplication event early in metazoan evolution and were subsequently lost in arthropods and nematodes. Here we demonstrate that Evc2 is essential for Hh pathway activation in response to the Smo agonist purmorphamine. A yeast two-hybrid screen using Evc as bait identified Evc2 as an Evc binding partner and we confirmed the interaction by immunoprecipitation. We developed anti-Evc2 antibodies and show that Evc2 and Evc co-localize at the basal body and also on primary cilia. In transfected cells, basal body and cilia localization is observed when Evc and Evc2 constructs are co-transfected but not when either construct is transfected individually. We show that Evc and Evc2 are cilia transmembrane proteins, the C-terminus for both being intracellular and Evc2, but not Evc, having an extracellular portion. Furthermore, Evc is absent at the basal body in Evc2 null cells. Using Western blots of cytoplasmic and nuclear protein, we also demonstrate that full length Evc2 but not Evc, is located in the nucleus.</p> <p>Conclusions</p> <p>We demonstrate for the first time that Evc2 is a positive regulator of the Hh signalling pathway and that it is located at the basal body of primary cilia. We show that the presence of Evc and Evc2 at the basal body and cilia membrane is co-dependent. In addition, Evc2, but not Evc, is present in the cell nucleus suggesting movement of Evc2 between the cilium and nucleus.</p

Probing the Interactions of Thiazole Abietane Inhibitors with the Human Serine Hydrolases ABHD16A and ABHD12

Peer reviewe

Development of the Arizona Robotic Telescope Network

The Arizona Robotic Telescope Network (ARTN) project is a long term effort to develop a system of telescopes to carry out a flexible program of PI observing, survey projects, and time domain astrophysics including monitoring, rapid response, and transient/target-of-opportunity followup. Steward Observatory operates and shares in several 1-3m class telescopes with quality sites and instrumentation, largely operated in classical modes. Science programs suited to these telescopes are limited by scheduling flexibility and people-power of available observers. Our goal is to adapt these facilities for multiple co-existing queued programs, interrupt capability, remote/robotic operation, and delivery of reduced data. In the long term, planning for the LSST era, we envision an automated system coordinating across multiple telescopes and sites, where alerts can trigger followup, classification, and triggering of further observations if required, such as followup imaging that can trigger spectroscopy. We are updating telescope control systems and software to implement this system in stages, beginning with the Kuiper 61'' and Vatican Observatory 1.8-m telescopes. The Kuiper 61'' and its Mont4K camera can now be controlled and queue-scheduled by the RTS2 observatory control software, and operated from a remote room at Steward. We discuss science and technical requirements for ARTN, and some of the challenges in adapting heterogenous legacy facilities, scheduling, data pipelines, and maintaining capabilities for a diverse user base.Comment: Proceedings of SPIE Astronomical Telescopes & Instrumentation 2018, Observatory Operations: Strategies, Processes, and Systems VI

Association between recent overnight travel and use of long-lasting insecticidal nets in rural Uganda: a prospective cohort study in Tororo.

BACKGROUND: The burden of malaria in Uganda remains high, but has become increasingly heterogenous following intensified malaria control. Travel within Uganda is recognized as a risk factor for malaria, but behaviours associated with travel are not well-understood. To address this knowledge gap, malaria-relevant behaviours of cohort participants were assessed during travel and at home in Uganda. METHODS: Residents from 80 randomly selected households in Nagongera sub-county, Tororo district were enrolled into a cohort to study malaria in rural Uganda. All participants were given long-lasting insecticidal nets (LLINs) at enrolment and were evaluated every 4 weeks at the study clinic. Participants were asked if they had travelled overnight from their home, and if so, a questionnaire was administered to capture information on travel details and behaviours. Behaviour while travelling was assessed within 4 weeks following travel during the study clinic visit. Behaviour while at home was assessed using a similar questionnaire during two-weekly home visits. Behaviours while travelling vs at home were compared using log binomial regression models with generalized estimating equations adjusting for repeated measures in the same individual. Analysis of factors associated with LLIN adherence, such as destination and duration of travel, time to bed during travel, gender and age at time of travel, were assessed using log binomial regression models with generalized estimating equations adjusting for repeated measures in the same individual. RESULTS: Between October 2017 and October 2019, 527 participants were enrolled and assessed for travel. Of these, 123 (23.2%) reported taking 211 overnight trips; 149 (70.6%) trips were within Tororo. Participants were less likely to use LLINs when travelling than when at home (41.0% vs. 56.2%, relative risk [RR] 0.73, 95% CI 0.60-0.89, p = 0.002); this difference was noted for women (38.8% vs 59.2%, RR 0.66, 95% CI 0.52-0.83, p = 0.001) but not men (48.3% vs 46.6%, RR 0.96, 95% CI 0.67-1.40, p = 0.85). In an adjusted analysis, factors associated with LLIN use when travelling included destination (travelling to districts not receiving indoor residual spraying [IRS] 65.8% vs Tororo district 32.2%, RR 1.80, 95% CI 1.31-2.46, p  7 nights 60.3% vs one night 24.4%, RR 1.97, 95% CI 1.07-3.64, p = 0.03). CONCLUSIONS: Travellers, particularly women, were less likely to use LLINs when travelling than when at home. LLIN adherence was higher among those who travelled to non-IRS districts and for more than 1 week, suggesting that perceived malaria risk influences LLIN use. Strategies are needed to raise awareness of the importance of using LLINs while travelling