Chromosome mapping of dragline silk genes in the genomes of widow spiders (araneae, theridiidae)

With its incredible strength and toughness, spider dragline silk is widely lauded for its impressive material properties. Dragline silk is composed of two structural proteins, MaSp1 and MaSp2, which are encoded by members of the spidroin gene family. While previous studies have characterized the genes that encode the constituent proteins of spider silks, nothing is known about the physical location of these genes. We determined karyotypes and sex chromosome organization for the widow spiders, Latrodectus hesperus and L. geometricus (Araneae, Theridiidae). We then used fluorescence in situ hybridization to map the genomic locations of the genes for the silk proteins that compose the remarkable spider dragline. These genes included three loci for the MaSp1 protein and the single locus for the MaSp2 protein. In addition, we mapped a MaSp1 pseudogene. All the MaSp1 gene copies and pseudogene localized to a single chromosomal region while MaSp2 was located on a different chromosome of L. hesperus. Using probes derived from L. hesperus, we comparatively mapped all three MaSp1 loci to a single region of a L. geometricus chromosome. As with L. hesperus, MaSp2 was found on a separate L. geometricus chromosome, thus again unlinked to the MaSp1 loci. These results indicate orthology of the corresponding chromosomal regions in the two widow genomes. Moreover, the occurrence of multiple MaSp1 loci in a conserved gene cluster across species suggests that MaSp1 proliferated by tandem duplication in a common ancestor of L. geometricus and L. hesperus. Unequal crossover events during recombination could have given rise to the gene copies and could also maintain sequence similarity among gene copies over time. Further comparative mapping with taxa of increasing divergence from Latrodectus will pinpoint when the MaSp1 duplication events occurred and the phylogenetic distribution of silk gene linkage patterns. © 2010 Zhao et al

Examining the impacts of drivers’ emotions on takeover readiness and performance in highly automated driving

SAE Level 3 automated vehicles often requires the driver to take control of the vehicle within a short period of time. Although this problem has received much attention the role of the driver's emotional state has still remained largely unexplored. To tackle this problem, a human subject experiment was conducted with 24 participants in a desktop driving simulator. The experiment adopted a within-subject design with four types of emotions: angry, sad, happy and calm. Results showed that emotions significantly affected drivers’ takeover readiness and performance in highly automated driving.McityPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149482/1/Extended abstract_2019-Annual-Meeting-Na Du.pdfDescription of Extended abstract_2019-Annual-Meeting-Na Du.pdf : Main Fil

The FDA-Approved Drug Cobicistat Synergizes with Remdesivir To Inhibit SARS-CoV-2 Replication In Vitro and Decreases Viral Titers and Disease Progression in Syrian Hamsters

Combinations of direct-acting antivirals are needed to minimize drug resistance mutations and stably suppress replication of RNA viruses. Currently, there are limited therapeutic options against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and testing of a number of drug regimens has led to conflicting results. Here, we show that cobicistat, which is an FDA-approved drug booster that blocks the activity of the drug-metabolizing proteins cytochrome P450-3As (CYP3As) and P-glycoprotein (P-gp), inhibits SARS-CoV-2 replication. Two independent cell-to-cell membrane fusion assays showed that the antiviral effect of cobicistat is exerted through inhibition of spike protein-mediated membrane fusion. In line with this, incubation with low-micromolar concentrations of cobicistat decreased viral replication in three different cell lines including cells of lung and gut origin. When cobicistat was used in combination with remdesivir, a synergistic effect on the inhibition of viral replication was observed in cell lines and in a primary human colon organoid. This was consistent with the effects of cobicistat on two of its known targets, CYP3A4 and P-gp, the silencing of which boosted the in vitro antiviral activity of remdesivir in a cobicistat-like manner. When administered in vivo to Syrian hamsters at a high dose, cobicistat decreased viral load and mitigated clinical progression. These data highlight cobicistat as a therapeutic candidate for treating SARS-CoV-2 infection and as a potential building block of combination therapies for COVID-19

Improvement of composition of CdTe thin films during heat treatment in the presence of CdCl2

CdCl2 treatment is a crucial step in development of CdS/CdTe solar cells. Although this rocessing step has been used over a period of three decades, full understanding is not yet achieved. This paper reports the experimental evidence for improvement of composition of CdTe layers during CdCl2 treatment. This investigation makes use of four selected analytical techniques; Photo-electro-chemical (PEC) cell, X-ray diffraction (XRD), Raman spectroscopy and Scanning electron microscopy (SEM). CdTe layers used were electroplated using three Cd precursors; CdSO4, Cd(NO3)2 and CdCl2. Results show the improvement of stoichiometry of CdTe layers during CdCl2 treatment through chemical reaction between Cd from CdCl2 and elemental Te that usually precipitate during CdTe growth, due to its natural behaviour. XRD and SEM results show that the low-temperature (~85ºC) electroplated CdTe layers consist of ~(20-60) nm size crystallites, but after CdCl2 treatment, the layers show drastic recrystallisation with grains becoming a few microns in size. These CdCl2 treated layers are then comparable to high temperature grown CdTe layers by the size of grains

Aggregation and settling in aqueous polydisperse alumina nanoparticle suspensions

Nanoparticle suspensions (also called nanofluids) are often polydisperse and tend to settle with time. Settling kinetics in these systems are known to be complex and hence challenging to understand. In this work, polydisperse spherical alumina (Al2O3) nanoparticles in the size range of ~10-100nm were dispersed in water and examined for aggregation and settling behaviour near its isoelectric point (IEP). A series of settling experiments were conducted and the results were analysed by photography and by Small Angle X-ray Scattering (SAXS). The settling curve obtained from standard bed height measurement experiments indicated two different types of behaviour, both of which were also seen in the SAXS data. But the SAXS data were remarkably able to pick out the rapid settling regime as a result of the high temporal resolution (10s) used. By monitoring the SAXS intensity, it was further possible to record the particle aggregation process for the first time. Optical microscopy images were produced on drying and dried droplets extracted from the suspension at various times. Dried deposits showed the rapid decrease in the number of very large particles with time which qualitatively validates the SAXS prediction, and therefore its suitability as a tool to study unstable polydisperse colloids. Keywords: Nanoparticles, nanofluids, polydisperse, aggregation, settling, alumina, microscopy, SAX

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Composition and Hierarchical Organisation of a Spider Silk

Albeit silks are fairly well understood on a molecular level, their hierarchical organisation and the full complexity of constituents in the spun fibre remain poorly defined. Here we link morphological defined structural elements in dragline silk of Nephila clavipes to their biochemical composition and physicochemical properties. Five layers of different make-ups could be distinguished. Of these only the two core layers contained the known silk proteins, but all can vitally contribute to the mechanical performance or properties of the silk fibre. Understanding the composite nature of silk and its supra-molecular organisation will open avenues in the production of high performance fibres based on artificially spun silk material

Nicotinamide Inhibits Alkylating Agent-Induced Apoptotic Neurodegeneration in the Developing Rat Brain

BACKGROUND: Exposure to the chemotherapeutic alkylating agent thiotepa during brain development leads to neurological complications arising from neurodegeneration and irreversible damage to the developing central nerve system (CNS). Administration of single dose of thiotepa in 7-d postnatal (P7) rat triggers activation of apoptotic cascade and widespread neuronal death. The present study was aimed to elucidate whether nicotinamide may prevent thiotepa-induced neurodegeneration in the developing rat brain. METHODOLOGY/PRINCIPAL FINDINGS: Neuronal cell death induced by thiotepa was associated with the induction of Bax, release of cytochrome-c from mitochondria into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1). Post-treatment of developing rats with nicotinamide suppressed thiotepa-induced upregulation of Bax, reduced cytochrome-c release into the cytosol and reduced expression of activated caspase-3 and cleavage of PARP-1. Cresyl violet staining showed numerous dead cells in the cortex hippocampus and thalamus; post-treatment with nicotinamide reduced the number of dead cells in these brain regions. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) and immunohistochemical analysis of caspase-3 show that thiotepa-induced cell death is apoptotic and that it is inhibited by nicotinamide treatment. CONCLUSION: Nicotinamide (Nic) treatment with thiotepa significantly improved neuronal survival and alleviated neuronal cell death in the developing rat. These data demonstrate that nicotinamide shows promise as a therapeutic and neuroprotective agent for the treatment of neurodegenerative disorders in newborns and infants