Somatic SNCA Copy Number Variants in Multiple System Atrophy Are Related to Pathology and Inclusions

BACKGROUND: Somatic α-synuclein (SNCA) copy number variants (CNVs, specifically gains) occur in multiple system atrophy (MSA) and Parkinson's disease brains. OBJECTIVE: The aim was to compare somatic SNCA CNVs in MSA subtypes (striatonigral degeneration [SND] and olivopontocerebellar atrophy [OPCA]) and correlate with inclusions. METHODS: We combined fluorescent in situ hybridization with immunofluorescence for α-synuclein and in some cases oligodendrocyte marker tubulin polymerization promoting protein (TPPP). RESULTS: We analyzed one to three brain regions from 24 MSA cases (13 SND, 11 OPCA). In a region preferentially affected in one subtype (putamen in SND, cerebellum in OPCA), mosaicism was higher in that subtype, and cells with CNVs were 4.2 times more likely to have inclusions. In the substantia nigra, nonpigmented cells with CNVs and TPPP were about six times more likely to have inclusions. CONCLUSIONS: The correlation between SNCA CNVs and pathology (at a regional level) and inclusions (at a single-cell level) suggests a role for somatic SNCA CNVs in MSA pathogenesis. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Virtual Friend: Tracking and Generating Natural Interactive Behaviours in Real Video

The aim of our research is to create a "virtual friend" i.e., a virtual character capable of responding to actions obtained from observing a real person in video in a realistic and sensible manner. In this paper, we present a novel approach for generating a variety of complex behavioural responses for a fully articulated "virtual friend" in three dimensional (3D) space. Our approach is model-based. First of all, we train a collection of dual hidden Markov models (HMMs) on 3D motion capture (MoCap) data representing a number of interactions between two people. Secondly, we track 3D articulated motion of a single person in ordinary 2D video. Finally, using the dual HMM, we generate a moving "virtual friend" reacting to the motion of the tracked person and place it in the original video footage. In this paper, we describe our approach in depth as well as present the results of experiments, which show that the produced behaviours are very close to those of real people

New Noncovalent Inhibitors of Penicillin-Binding Proteins from Penicillin-Resistant Bacteria

BACKGROUND: Penicillin-binding proteins (PBPs) are well known and validated targets for antibacterial therapy. The most important clinically used inhibitors of PBPs beta-lactams inhibit transpeptidase activity of PBPs by forming a covalent penicilloyl-enzyme complex that blocks the normal transpeptidation reaction; this finally results in bacterial death. In some resistant bacteria the resistance is acquired by active-site distortion of PBPs, which lowers their acylation efficiency for beta-lactams. To address this problem we focused our attention to discovery of novel noncovalent inhibitors of PBPs. METHODOLOGY/PRINCIPAL FINDINGS: Our in-house bank of compounds was screened for inhibition of three PBPs from resistant bacteria: PBP2a from Methicillin-resistant Staphylococcus aureus (MRSA), PBP2x from Streptococcus pneumoniae strain 5204, and PBP5fm from Enterococcus faecium strain D63r. Initial hit inhibitor obtained by screening was then used as a starting point for computational similarity searching for structurally related compounds and several new noncovalent inhibitors were discovered. Two compounds had promising inhibitory activities of both PBP2a and PBP2x 5204, and good in-vitro antibacterial activities against a panel of Gram-positive bacterial strains. CONCLUSIONS: We found new noncovalent inhibitors of PBPs which represent important starting points for development of more potent inhibitors of PBPs that can target penicillin-resistant bacteria.Eur-Intafa

Quantifying direct and indirect contacts for the potential transmission of infection between species using a multilayer contact network

Detecting opportunities for between-species transmission of pathogens can be challenging, particularly if rare behaviours or environmental transmission are involved. We present a multilayer network framework to quantify transmission potential in multi-host systems, incorporating environmental transmission, by using empirical data on direct and indirect contacts between European badgers Meles meles and domestic cattle. We identify that indirect contacts via the environment at badger latrines on pasture are likely to be important for transmission within badger populations and between badgers and cattle. We also find a positive correlation between the role of individual badgers within the badger social network, and their role in the overall badger-cattle-environment network, suggesting that the same behavioural traits contribute to the role of individual badgers in within- and between-species transmission. These findings have implications for disease management interventions in this system, and our novel network approach can provide general insights into transmission in other multi-host disease systems

First Dating of a Recombination Event in Mammalian Tick-Borne Flaviviruses

The mammalian tick-borne flavivirus group (MTBFG) contains viruses associated with important human and animal diseases such as encephalitis and hemorrhagic fever. In contrast to mosquito-borne flaviviruses where recombination events are frequent, the evolutionary dynamic within the MTBFG was believed to be essentially clonal. This assumption was challenged with the recent report of several homologous recombinations within the Tick-borne encephalitis virus (TBEV). We performed a thorough analysis of publicly available genomes in this group and found no compelling evidence for the previously identified recombinations. However, our results show for the first time that demonstrable recombination (i.e., with large statistical support and strong phylogenetic evidences) has occurred in the MTBFG, more specifically within the Louping ill virus lineage. Putative parents, recombinant strains and breakpoints were further tested for statistical significance using phylogenetic methods. We investigated the time of divergence between the recombinant and parental strains in a Bayesian framework. The recombination was estimated to have occurred during a window of 282 to 76 years before the present. By unravelling the temporal setting of the event, we adduce hypotheses about the ecological conditions that could account for the observed recombination

Global Oceans

Global Oceans is one chapter from the State of the Climate in 2019 annual report and is avail-able from https://doi.org/10.1175/BAMS-D-20-0105.1. Compiled by NOAA’s National Centers for Environmental Information, State of the Climate in 2019 is based on contr1ibutions from scien-tists from around the world. It provides a detailed update on global climate indicators, notable weather events, and other data collected by environmental monitoring stations and instru-ments located on land, water, ice, and in space. The full report is available from https://doi.org /10.1175/2020BAMSStateoftheClimate.1

Abstracts from the NIHR INVOLVE Conference 2017

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Global Oceans, BAMS State of the Climate in 2021, Chapter 3

Patterns of variability in ocean properties are often closely related to large-scale climate pattern indices, and 2021 is no exception. The year 2021 started and ended with La Niña conditions, charmingly dubbed a “double-dip” La Niña. Hence, stronger-than-normal easterly trade winds in the tropical south Pacific drove westward surface current anomalies in the equatorial Pacific; reduced sea surface temperature (SST) and upper ocean heat content in the eastern tropical Pacific; increased sea level, upper ocean heat content, and salinity in the western tropical Pacific; resulted in a rim of anomalously high chlorophyll-a (Chla) on the poleward and westward edges of the anomalously cold SST wedge in the eastern equatorial Pacific; and increased precipitation over the Maritime Continent. The Pacific decadal oscillation remained strongly in a negative phase in 2021, with negative SST and upper ocean heat content anomalies around the eastern and equatorial edges of the North Pacific and positive anomalies in the center associated with low Chla anomalies. The South Pacific exhibited similar patterns. Fresh anomalies in the northeastern Pacific shifted towards the west coast of North America. The Indian Ocean dipole (IOD) was weakly negative in 2021, with small positive SST anomalies in the east and nearly-average anomalies in the west. Nonetheless, upper ocean heat content was anomalously high in the west and lower in the east, with anomalously high freshwater flux and low sea surface salinities (SSS) in the east, and the opposite pattern in the west, as might be expected during a negative phase of that climate index. In the Atlantic, the only substantial cold anomaly in SST and upper ocean heat content persisted east of Greenland in 2021, where SSS was also low, all despite the weak winds and strong surface heat flux anomalies into the ocean expected during a negative phase of the North Atlantic Oscillation. These anomalies held throughout much of 2021. An Atlantic and Benguela Niño were both evident, with above-average SST anomalies in the eastern equatorial Atlantic and the west coast of southern Africa. Over much of the rest of the Atlantic, SSTs, upper ocean heat content, and sea level anomalies were above average. Anthropogenic climate change involves long-term trends, as this year’s chapter sidebars emphasize. The sidebars relate some of the latest IPCC ocean-related assessments (including carbon, the section on which is taking a hiatus from our report this year). This chapter estimates that SST increased at a rate of 0.16–0.19°C decade−1 from 2000 to 2021, 0–2000-m ocean heat content warmed by 0.57–0.73 W m−2 (applied over Earth’s surface area) from 1993 to 2021, and global mean sea level increased at a rate of 3.4 ± 0.4 mm yr−1 from 1993 to 2021. Global mean SST, which is more subject to interannual variations than ocean heat content and sea level, with values typically reduced during La Niña, was ~0.1°C lower in 2021 than in 2020. However, from 2020 to 2021, annual average ocean heat content from 0 to 2000 dbar increased at a rate of ~0.95 W m−2, and global sea level increased by ~4.9 mm. Both were the highest on record in 2021, and with year-on-year increases substantially exceeding their trend rates of recent decades

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs