bluuebunny/crossref_metadata_2025 huggingface dataset:
Viral zoonotic risk is homogenous among taxonomic orders of mammalian and avian reservoir hosts
Authors: Mollentze Nardus , Streicker Daniel G.
Published: April 2020

The notion that certain animal groups disproportionately maintain and transmit viruses to humans due to broad-scale differences in ecology, life history, and physiology currently influences global health surveillance and research in disease ecology, virology, and immunology. To directly test whether such “special reservoirs” of zoonoses exist, we used literature searches to construct the largest existing dataset of virus–reservoir relationships, consisting of the avian and mammalian reservoir hosts of 415 RNA and DNA viruses along with their histories of human infection. Reservoir host effects on the propensity of viruses to have been reported as infecting humans were rare and when present were restricted to one or two viral families. The data instead support a largely host-neutral explanation for the distribution of human-infecting viruses across the animal orders studied. After controlling for higher baseline viral richness in mammals versus birds, the observed number of zoonoses per animal order increased as a function of their species richness. Animal orders of established importance as zoonotic reservoirs including bats and rodents were unexceptional, maintaining numbers of zoonoses that closely matched expectations for mammalian groups of their size. Our findings show that variation in the frequency of zoonoses among animal orders can be explained without invoking special ecological or immunological relationships between hosts and viruses, pointing to a need to reconsider current approaches aimed at finding and predicting novel zoonoses.
RNA polymerase II stalls on oxidative DNA damage via a torsion-latch mechanism involving lone pair–π and CH–π interactions
Authors: Oh Juntaek , Fleming Aaron M. , Xu Jun , Chong Jenny , Burrows Cynthia J. , Wang Dong
Published: April 2020

Oxidation of guanine generates several types of DNA lesions, such as 8-oxoguanine (8OG), 5-guanidinohydantoin (Gh), and spiroiminodihydantoin (Sp). These guanine-derived oxidative DNA lesions interfere with both replication and transcription. However, the molecular mechanism of transcription processing of Gh and Sp remains unknown. In this study, by combining biochemical and structural analysis, we revealed distinct transcriptional processing of these chemically related oxidized lesions: 8OG allows both error-free and error-prone bypass, whereas Gh or Sp causes strong stalling and only allows slow error-prone incorporation of purines. Our structural studies provide snapshots of how polymerase II (Pol II) is stalled by a nonbulky Gh lesion in a stepwise manner, including the initial lesion encounter, ATP binding, ATP incorporation, jammed translocation, and arrested states. We show that while Gh can form hydrogen bonds with adenosine monophosphate (AMP) during incorporation, this base pair hydrogen bonding is not sufficient to hold an ATP substrate in the addition site and is not stable during Pol II translocation after the chemistry step. Intriguingly, we reveal a unique structural reconfiguration of the Gh lesion in which the hydantoin ring rotates ∼90° and is perpendicular to the upstream base pair planes. The perpendicular hydantoin ring of Gh is stabilized by noncanonical lone pair–π and CH–π interactions, as well as hydrogen bonds. As a result, the Gh lesion, as a functional mimic of a 1,2-intrastrand crosslink, occupies canonical −1 and +1 template positions and compromises the loading of the downstream template base. Furthermore, we suggest Gh and Sp lesions are potential targets of transcription-coupled repair.
Rcf2 revealed in cryo-EM structures of hypoxic isoforms of mature mitochondrial III-IV supercomplexes
Authors: Hartley Andrew M. , Meunier Brigitte , Pinotsis Nikos , Maréchal Amandine
Published: April 2020

The organization of the mitochondrial electron transport chain proteins into supercomplexes (SCs) is now undisputed; however, their assembly process, or the role of differential expression isoforms, remain to be determined. In
Saccharomyces cerevisiae
, cytochrome
c
oxidase (CIV) forms SCs of varying stoichiometry with cytochrome
bc
1
(CIII). Recent studies have revealed, in normoxic growth conditions, an interface made exclusively by Cox5A, the only yeast respiratory protein that exists as one of two isoforms depending on oxygen levels. Here we present the cryo-EM structures of the III
2
-IV
1
and III
2
-IV
2
SCs containing the hypoxic isoform Cox5B solved at 3.4 and 2.8 Å, respectively. We show that the change of isoform does not affect SC formation or activity, and that SC stoichiometry is dictated by the level of CIII/CIV biosynthesis. Comparison of the CIV
5B
- and CIV
5A
-containing SC structures highlighted few differences, found mainly in the region of Cox5. Additional density was revealed in all SCs, independent of the CIV isoform, in a pocket formed by Cox1, Cox3, Cox12, and Cox13, away from the CIII–CIV interface. In the CIV
5B
-containing hypoxic SCs, this could be confidently assigned to the hypoxia-induced gene 1 (Hig1) type 2 protein Rcf2. With conserved residues in mammalian Hig1 proteins and Cox3/Cox12/Cox13 orthologs, we propose that Hig1 type 2 proteins are stoichiometric subunits of CIV, at least when within a III-IV SC.
CD93 negatively regulates astrogenesis in response to MMRN2 through the transcriptional repressor ZFP503 in the developing brain
Authors: Liang Qingli , Su Libo , Zhang Dongming , Jiao Jianwei
Published: April 2020

Astrogenesis is repressed in the early embryonic period and occurs in the late embryonic period. A variety of external and internal signals contribute to the sequential differentiation of neural stem cells. Here, we discovered that immune-related CD93 plays a critical negative role in the regulation of astrogenesis in the mouse cerebral cortex. We show that CD93 expression is detected in neural stem cells and neurons but not in astrocytes and declines as differentiation proceeds.
Cd93
knockout increases astrogenesis at the expense of neuron production during the late embryonic period. CD93 responds to the extracellular matrix protein Multimerin 2 (MMRN2) to trigger the repression of astrogenesis. Mechanistically, CD93 delivers signals to β-Catenin through a series of phosphorylation cascades, and then β-Catenin transduces these signals to the nucleus to activate
Zfp503
transcription. The transcriptional repressor ZFP503 inhibits the transcription of
glial fibrillary acidic protein
(
Gfap
) by binding to the
Gfap
promoter with the assistance of Grg5. Furthermore,
Cd93
knockout mice exhibit autism-like behaviors. Taken together, our results reveal that CD93 is a negative regulator of the onset of astrogenesis and provide insight into therapy for psychiatric disorders.
Noninvasive hippocampal blood−brain barrier opening in Alzheimer’s disease with focused ultrasound
Authors: Rezai Ali R. , Ranjan Manish , D’Haese Pierre-François , Haut Marc W. , Carpenter Jeffrey , Najib Umer , Mehta Rashi I. , Chazen J. Levi , Zibly Zion , Yates Jennifer R. , Hodder Sally L. , Kaplitt Michael
Published: April 2020

The blood–brain barrier (BBB) presents a significant challenge for treating brain disorders. The hippocampus is a key target for novel therapeutics, playing an important role in Alzheimer’s disease (AD), epilepsy, and depression. Preclinical studies have shown that magnetic resonance (MR)-guided low-intensity focused ultrasound (FUS) can reversibly open the BBB and facilitate delivery of targeted brain therapeutics. We report initial clinical trial results evaluating the safety, feasibility, and reversibility of BBB opening with FUS treatment of the hippocampus and entorhinal cortex (EC) in patients with early AD. Six subjects tolerated a total of 17 FUS treatments with no adverse events and neither cognitive nor neurological worsening. Post-FUS contrast MRI revealed immediate and sizable hippocampal parenchymal enhancement indicating BBB opening, followed by BBB closure within 24 h. The average opening was 95% of the targeted FUS volume, which corresponds to 29% of the overall hippocampus volume. We demonstrate that FUS can safely, noninvasively, transiently, reproducibly, and focally mediate BBB opening in the hippocampus/EC in humans. This provides a unique translational opportunity to investigate therapeutic delivery in AD and other conditions.
Machine learning for learner English
Authors: Ballier Nicolas , Canu Stéphane , Petitjean Caroline , Gasso Gilles , Balhana Carlos , Alexopoulou Theodora , Gaillat Thomas
Published: April 2020

This paper discusses machine learning techniques for the prediction of Common European Framework of Reference (CEFR)
levels in a learner corpus. We summarise the CAp 2018 Machine Learning (ML) competition, a
classification task of the six CEFR levels, which map linguistic competence in a foreign language onto six reference levels. The goal of
this competition was to produce a machine learning system to predict learners’ competence levels from written productions comprising between
20 and 300 words and a set of characteristics computed for each text extracted from the French component of the EFCAMDAT data (Geertzen et al., 2013). Together with the description of the competition, we provide an analysis of
the results and methods proposed by the participants and discuss the benefits of this kind of competition for the learner corpus research
(LCR) community. The main findings address the methods used and lexical bias introduced by the task.
ACKR4 restrains antitumor immunity by regulating CCL21
Authors: Whyte Carly E. , Osman Maleika , Kara Ervin E. , Abbott Caitlin , Foeng Jade , McKenzie Duncan R. , Fenix Kevin A. , Harata-Lee Yuka , Foyle Kerrie L. , Boyle Sarah T. , Kochetkova Marina , Aguilera Amelia Roman , Hou Jiajie , Li Xian-Yang , Armstrong Mark A. , Pederson Stephen M. , Comerford Iain , Smyth Mark J. , McColl Shaun R.
Published: April 2020

Current immunotherapies involving CD8+ T cell responses show remarkable promise, but their efficacy in many solid tumors is limited, in part due to the low frequency of tumor-specific T cells in the tumor microenvironment (TME). Here, we identified a role for host atypical chemokine receptor 4 (ACKR4) in controlling intratumor T cell accumulation and activation. In the absence of ACKR4, an increase in intratumor CD8+ T cells inhibited tumor growth, and nonhematopoietic ACKR4 expression was critical. We show that ACKR4 inhibited CD103+ dendritic cell retention in tumors through regulation of the intratumor abundance of CCL21. In addition, preclinical studies indicate that ACKR4 and CCL21 are potential therapeutic targets to enhance responsiveness to immune checkpoint blockade or T cell costimulation.
The neonatal SCN2A mutant channel mimics adult channel properties
Authors: Muller Grace K.
Published: April 2020

SCN2A mutations can cause early-onset epilepsy. Thompson et al. examined these human mutations in neonatal versus adult channel isoforms.
Bifurcation of critical sets and relaxation oscillations in singular fast-slow systems
Authors: Nyman Karl H M , Ashwin Peter , Ditlevsen Peter D
Published: April 2020

Fast-slow dynamical systems have subsystems that evolve on vastly different timescales, and bifurcations in such systems can arise due to changes in any or all subsystems. We classify bifurcations of the critical set (the equilibria of the fast subsystem) and associated fast dynamics, parametrized by the slow variables. Using a distinguished parameter approach we are able to classify bifurcations for one fast and one slow variable. Some of these bifurcations are associated with the critical set losing manifold structure. We also conjecture a list of generic bifurcations of the critical set for one fast and two slow variables. We further consider how the bifurcations of the critical set can be associated with generic bifurcations of attracting relaxation oscillations under an appropriate singular notion of equivalence.
Strong pairing in two dimensions: pseudogaps, domes, and other implications
Authors: Wang Xiaoyu , Chen Qijin , Levin K
Published: April 2020

This paper addresses the transition from the normal to the superfluid state in strongly correlated two dimensional fermionic superconductors and Fermi gases. We arrive at the Berezinskii–Kosterlitz–Thouless (BKT) temperature T
BKT as a function of attractive pairing strength by associating it with the onset of ‘quasi-condensation’ in the normal phase. Our approach builds on a criterion for determining the BKT transition temperature for atomic gases which is based on a well established quantum Monte Carlo analysis of the phase space density. This latter quantity, when derived from BCS–BEC crossover theory for fermions, leads to non-monotonic behavior for T
BKT as a function of the attractive interaction or inverse scattering length. In Fermi gases, this implies a robust superconducting dome followed by a long tail from the flat BEC asymptote, rather similar to what is observed experimentally. For lattice systems we find that T
BKT has an absolute maximum of the order of 0.1E
F. We discuss how our results compare with those derived from the Nelson–Kosterlitz criterion based on the mean field superfluid density and the approach to the transition from below. While there is agreement in the strict mean-field BCS regime at weak coupling, we find that at moderate pairing strength bosonic excitations cause a substantial increase in T
BKT followed by an often dramatic decrease before the system enters the BEC regime.
Correlation between protein concentration and bacterial cell size can reveal mechanisms of gene expression
Authors: Nieto-Acuña César , Arias-Castro Juan Carlos , Vargas-García César , Sánchez Carlos , Pedraza Juan Manuel
Published: April 2020

Classically, gene expression is modeled as a chemical process with reaction rates dependent on the concentration of the reactants (typically, DNA loci, plasmids, RNA, enzymes, etc). Other variables like cell size are in general ignored. Size dynamics can become an important variable due to the low number of many of these reactants, imperfectly symmetric cell partitioning and molecule segregation. In this work we measure the correlation between size and protein concentration by observing the gene expression of the RpOD gene from a low-copy plasmid in Escherichia coli during balanced growth in different media. A positive correlation was found, and we used it to examine possible models of cell size dynamics and plasmid replication. We implemented a previously developed model describing the full gene expression process including transcription, translation, loci replication, cell division and molecule segregation. By comparing with the observed correlation, we determine that the transcription rate must be proportional to the size times the number of plasmids. We discuss how fluctuations in plasmid segregation, due to the low copy number, can impose limits in this correlation.
Neural decoding of electrocorticographic signals using dynamic mode decomposition
Authors: Shiraishi Yoshiyuki , Kawahara Yoshinobu , Yamashita Okito , Fukuma Ryohei , Yamamoto Shota , Saitoh Youichi , Kishima Haruhiko , Yanagisawa Takufumi
Published: April 2020

Objective. Brain-computer interfaces (BCIs) using electrocorticographic (ECoG) signals have been developed to restore the communication function of severely paralyzed patients. However, the limited amount of information derived from ECoG signals hinders their clinical applications. We aimed to develop a method to decode ECoG signals using spatiotemporal patterns characterizing movement types to increase the amount of information gained from these signals. Approach. Previous studies have demonstrated that motor information could be decoded using powers of specific frequency bands of the ECoG signals estimated by fast Fourier transform (FFT) or wavelet analysis. However, because FFT is evaluated for each channel, the temporal and spatial patterns among channels are difficult to evaluate. Here, we used dynamic mode decomposition (DMD) to evaluate the spatiotemporal pattern of ECoG signals and evaluated the accuracy of motor decoding with the DMD modes. We used ECoG signals during three types of hand movements, which were recorded from 11 patients implanted with subdural electrodes. From the signals at the time of the movements, the modes and powers were evaluated by DMD and FFT and were decoded using support vector machine. We used the Grassmann kernel to evaluate the distance between modes estimated by DMD (DMD mode). In addition, we decoded the DMD modes, in which the phase components were shuffled, to compare the classification accuracy. Main results. The decoding accuracy using DMD modes was significantly better than that using FFT powers. The accuracy significantly decreased when the phases of the DMD mode were shuffled. Among the frequency bands, the DMD mode at approximately 100 Hz demonstrated the highest classification accuracy. Significance. DMD successfully captured the spatiotemporal patterns characterizing the movement types and contributed to improving the decoding accuracy. This method can be applied to improve BCIs to help severely paralyzed patients communicate.
Elliptic solutions for higher order KdV equations
Authors: Hayashi Masahito , Shigemoto Kazuyasu , Tsukioka Takuya
Published: April 2020

We study higher order KdV equations from the GL(2,

R

) ≅ SO(2,1) Lie group point of view. We find elliptic solutions of higher order KdV equations up to the ninth order. We argue that the main structure of the trigonometric/hyperbolic/elliptic N-soliton solutions for higher order KdV equations is the same as that of the original KdV equation. Pointing out that the difference is only the time dependence, we find N-soliton solutions of higher order KdV equations can be constructed from those of the original KdV equation by properly replacing the time-dependence. We discuss that there always exist elliptic solutions for all higher order KdV equations.
A new insight on structural and some functional aspects of peri-endodermal thickenings, a specific layer in Noccaea caerulescens roots
Authors: Kováč Ján , Lux Alexander , Soukup Milan , Weidinger Marieluise , Gruber Daniela , Lichtscheidl Irene , Vaculík Marek
Published: April 2020

Background and Aims

Cell walls of the peri-endodermis, a layer adjacent to the endodermis in alpine pennycress (Noccaea caerulescens) roots, form C-shaped peri-endodermal thickenings (PETs). Despite its specific position close to the endodermis, the assumed similarity of PETs to phi thickenings in many other species, and the fact that N. caerulescens is a well-studied heavy-metal-hyperaccumulating plant, the PET as a root trait is still not understood.

Methods

Here, we characterized PET cell walls by histochemical techniques, Raman spectroscopy, immunolabelling and electron microscopy. Moreover, a role of PETs in solute transport was tested and compared with Arabidopsis thaliana plants, which do not form PETs in roots.

Key Results

Cell walls with PETs have a structured relief mainly composed of cellulose and lignin. Suberin, typical of endodermal cells, is missing but pectins are present on the inner surface of the PET. Penetrating dyes are not able to cross PETs either by the apoplasmic or the symplasmic pathway, and a significantly higher content of metals is found in root tissues outside of PETs than in innermost tissues.

Conclusions

Based on their development and chemical composition, PETs are different from the endodermis and closely resemble phi thickenings. Contrarily, the different structure and dye impermeability of PETs, not known in the case of phi thickenings, point to an additional barrier function which makes the peri-endodermis with PETs a unique and rare layer.
Monotocy and the evolution of plural breeding in mammals
Authors: Lukas Dieter , Clutton-Brock Tim
Published: April 2020

In many mammals, breeding females are intolerant of each other and seldom associate closely but, in some, they aggregate in groups that vary in size, stability, and kinship structure. Aggregation frequently increases competition for food, and interspecific differences in female sociality among mammals are commonly attributed to contrasts in ecological parameters, including variation in activity timing, the distribution of resources, as well as the risk of predation. However, there is increasing indication that differences in female sociality are also associated with phylogenetic relationships and with contrasts in life-history parameters. We show here that evolutionary transitions from systems where breeding females usually occupy separate ranges (“singular breeding”) to systems where breeding females usually aggregate (“plural breeding”) have occurred more frequently in monotocous lineages where females produce single young than in polytocous ones where they produce litters. A likely explanation of this association is that competition between breeding females for resources is reduced where they produce single young and is more intense where they produce litters. Our findings reinforce evidence that variation in life-history parameters plays an important role in shaping the evolution of social behavior.
ntJoin: Fast and lightweight assembly-guided scaffolding using minimizer graphs
Authors: Coombe Lauren , Nikolić Vladimir , Chu Justin , Birol Inanc , Warren René L
Published: April 2020

The ability to generate high-quality genome sequences is cornerstone to modern biological research. Even with recent advancements in sequencing technologies, many genome assemblies are still not achieving reference-grade. Here, we introduce ntJoin, a tool that leverages structural synteny between a draft assembly and reference sequence(s) to contiguate and correct the former with respect to the latter. Instead of alignments, ntJoin uses a lightweight mapping approach based on a graph data structure generated from ordered minimizer sketches. The tool can be used in a variety of different applications, including improving a draft assembly with a reference-grade genome, a short-read assembly with a draft long-read assembly and a draft assembly with an assembly from a closely related species. When scaffolding a human short-read assembly using the reference human genome or a long-read assembly, ntJoin improves the NGA50 length 23- and 13-fold, respectively, in under 13 m, using <11 GB of RAM. Compared to existing reference-guided scaffolders, ntJoin generates highly contiguous assemblies faster and using less memory.

Availability and implementation

ntJoin is written in C++ and Python and is freely available at https://github.com/bcgsc/ntjoin.

Supplementary information

Supplementary data are available at Bioinformatics online.
A novel normalization and differential abundance test framework for microbiome data
Authors: Ma Yuanjing , Luo Yuan , Jiang Hongmei
Published: April 2020

Motivation

Microbial communities have been proved to have close relationship with many diseases. The identification of differentially abundant microbial species is clinically meaningful for finding disease-related pathogenic or probiotic bacteria. However, certain characteristics of microbiome data have hurdled the accuracy and effectiveness of differential abundance analysis. The abundances or counts of microbiome species are usually on different scales and exhibit zero-inflation and over-dispersion. Normalization is a crucial step before the differential abundance test. However, existing normalization methods typically try to adjust counts on different scales to a common scale by constructing size factors with the assumption that count distributions across samples are equivalent up to a certain percentile. These methods often yield undesirable results when differentially abundant species are of low to medium abundance level. For differential abundance analysis, existing methods often use a single distribution to model the dispersion of species which lacks flexibility to catch a single species’ distinctiveness. These methods tend to detect a lot of false positives and often lack of power when the effect size is small.

Results

We develop a novel framework for differential abundance analysis on sparse high-dimensional marker gene microbiome data. Our methodology relies on a novel network-based normalization technique and a two-stage zero-inflated mixture count regression model (RioNorm2). Our normalization method aims to find a group of relatively invariant microbiome species across samples and conditions in order to construct the size factor. Another contribution of the paper is that our testing approach can take under-sampling and over-dispersion into consideration by separating microbiome species into two groups and model them separately. Through comprehensive simulation studies, the performance of our method is consistently powerful and robust across different settings with different sample size, library size and effect size. We also demonstrate the effectiveness of our novel framework using a published dataset of metastatic melanoma and find biological insights from the results.

Availability and implementation

The R package ‘RioNorm2’ can be installed from Github athttps://github.com/yuanjing-ma/RioNorm2.

Supplementary information

Supplementary data are available at Bioinformatics online.
Metabolism of JQ1, an inhibitor of bromodomain and extra terminal bromodomain proteins, in human and mouse liver microsomes†
Authors: Li Feng , MacKenzie Kevin R , Jain Prashi , Santini Conrad , Young Damian W , Matzuk Martin M
Published: April 2020

JQ1 is a small-molecule inhibitor of the bromodomain and extra terminal (BET) protein family that potently inhibits the bromodomain testis-specific protein (BRDT), which is essential for spermatogenesis. JQ1 treatment produces a reversible contraceptive effect by targeting the activity of BRDT in mouse male germ cells, validating BRDT as a male contraceptive target. Although JQ1 possesses favourable physical properties, it exhibits a short half-life. Because the details of xenobiotic metabolism play important roles in the optimization of drug candidates and in determining the role of metabolism in drug efficacy, we investigated the metabolism of JQ1 in human and mouse liver microsomes. We present the first comprehensive view of JQ1 metabolism in liver microsomes, distinguishing nine JQ1 metabolites, including three monohydroxylated, one de-tert-butylated, two dihydroxylated, one monohydroxylated/dehydrogenated, one monohydroxylated-de-tert-butylated and one dihydroxylated/dehydrogenated variant of JQ1. The dominant metabolite (M1) in both human and mouse liver microsomes is monohydroxylated on the fused three-ring core. Using recombinant cytochrome P450 (CYP) enzymes, chemical inhibitors and the liver S9 fraction of Cyp3a-null mice, we identify enzymes that contribute to the formation of these metabolites. Cytochrome P450 family 3 subfamily A member 4 (CYP3A4) is the main contributor to the production of JQ1 metabolites in vitro, and the CYP3A4/5 inhibitor ketoconazole strongly inhibits JQ1 metabolism in both human and mouse liver microsomes. Our findings suggest that JQ1 half-life and efficacy might be improved in vivo by co-administration of a selective CYP inhibitor, thereby impacting the use of JQ1 as a probe for BRDT activity in spermatogenesis and as a probe or therapeutic in other systems.
Contribution of senescence in human endometrial stromal cells during proliferative phase to embryo receptivity†
Authors: Tomari Hiroyuki , Kawamura Teruhiko , Asanoma Kazuo , Egashira Katsuko , Kawamura Keiko , Honjo Ko , Nagata Yumi , Kato Kiyoko
Published: April 2020

Successful assisted reproductive technology pregnancy depends on the viability of embryos and endometrial receptivity. However, the literature has neglected effects of the endometrial environment during the proliferative phase on implantation success or failure. Human endometrial stromal cells (hESCs) were isolated from endometrial tissues sampled at oocyte retrieval during the proliferative phase from women undergoing infertility treatment. Primary hESC cultures were used to investigate the relationship between stemness and senescence induction in this population and embryo receptivity. Patients were classified as receptive or non-receptive based on their pregnancy diagnosis after embryo transfer. Biomarkers of cellular senescence and somatic stem cells were compared between each sample. hESCs from non-receptive patients exhibited significantly higher (P < 0.01) proportions of senescent cells, mRNA expressions of CDKN2A and CDKN1A transcripts (P < 0.01), and expressions of genes encoding the senescence-associated secretory phenotype (P < 0.05). hESCs from receptive patients had significantly higher (P < 0.01) mRNA expressions of ABCG2 and ALDH1A1 transcripts. Our findings suggest that stemness is inversely associated with senescence induction in hESCs and, by extension, that implantation failure in infertility treatment may be attributable to a combination of senescence promotion and disruption of this maintenance function in this population during the proliferative phase of the menstrual cycle. This is a promising step towards potentially improving the embryo receptivity of endometrium. The specific mechanism by which implantation failure is prefigured by a loss of stemness among endometrial stem cells, and cellular senescence induction among hESCs, should be elucidated in detail in the future.
Onset of hippocampal network aberration and memory deficits in P301S tau mice are associated with an early gene signature
Authors: Przybyla Magdalena , van Eersel Janet , van Hummel Annika , van der Hoven Julia , Sabale Miheer , Harasta Anne , Müller Julius , Gajwani Mehul , Prikas Emmanuel , Mueller Thomas , Stevens Claire H , Power John , Housley Gary D , Karl Tim , Kassiou Michael , Ke Yazi D , Ittner Arne , Ittner Lars M
Published: April 2020

Hyperphosphorylation and deposition of tau in the brain characterizes frontotemporal dementia and Alzheimer’s disease. Disease-associated mutations in the tau-encoding MAPT gene have enabled the generation of transgenic mouse models that recapitulate aspects of human neurodegenerative diseases, including tau hyperphosphorylation and neurofibrillary tangle formation. Here, we characterized the effects of transgenic P301S mutant human tau expression on neuronal network function in the murine hippocampus. Onset of progressive spatial learning deficits in P301S tau transgenic TAU58/2 mice were paralleled by long-term potentiation deficits and neuronal network aberrations during electrophysiological and EEG recordings. Gene-expression profiling just prior to onset of apparent deficits in TAU58/2 mice revealed a signature of immediate early genes that is consistent with neuronal network hypersynchronicity. We found that the increased immediate early gene activity was confined to neurons harbouring tau pathology, providing a cellular link between aberrant tau and network dysfunction. Taken together, our data suggest that tau pathology drives neuronal network dysfunction through hyperexcitation of individual, pathology-harbouring neurons, thereby contributing to memory deficits.
Longitudinal evaluation of the natural history of amyloid-β in plasma and brain
Authors: Burnham Samantha C , Fandos Noelia , Fowler Christopher , Pérez-Grijalba Virginia , Dore Vincent , Doecke James D , Shishegar Rosita , Cox Timothy , Fripp Jurgen , Rowe Christopher , Sarasa Manuel , Masters Colin L , Pesini Pedro , Villemagne Victor L
Published: April 2020

Plasma amyloid-β peptide concentration has recently been shown to have high accuracy to predict amyloid-β plaque burden in the brain. These amyloid-β plasma markers will allow wider screening of the population and simplify and reduce screening costs for therapeutic trials in Alzheimer’s disease. The aim of this study was to determine how longitudinal changes in blood amyloid-β track with changes in brain amyloid-β. Australian Imaging, Biomarker and Lifestyle study participants with a minimum of two assessments were evaluated (111 cognitively normal, 7 mild cognitively impaired, 15 participants with Alzheimer’s disease). Amyloid-β burden in the brain was evaluated through PET and was expressed in Centiloids. Total protein amyloid-β 42/40 plasma ratios were determined using ABtest® assays. We applied our method for obtaining natural history trajectories from short term data to measures of total protein amyloid-β 42/40 plasma ratios and PET amyloid-β. The natural history trajectory of total protein amyloid-β 42/40 plasma ratios appears to approximately mirror that of PET amyloid-β, with both spanning decades. Rates of change of 7.9% and 8.8%, were observed for total protein amyloid-β 42/40 plasma ratios and PET amyloid-β, respectively. The trajectory of plasma amyloid-β preceded that of brain amyloid-β by a median value of 6 years (significant at 88% confidence interval). These findings, showing the tight association between changes in plasma and brain amyloid-β, support the use of plasma total protein amyloid-β 42/40 plasma ratios as a surrogate marker of brain amyloid-β. Also, that plasma total protein amyloid-β 42/40 plasma ratios has potential utility in monitoring trial participants, and as an outcome measure.
Clinical Test Performance of a Rapid Point-of-Care Syphilis Treponemal Antibody Test: A Systematic Review and Meta-analysis
Authors: Bristow Claire C , Klausner Jeffrey D , Tran Anthony
Published: April 2020

We reviewed relevant syphilis diagnostic literature and conducted a meta-analysis to address the question, “What is the sensitivity and specificity of the Syphilis Health Check, a rapid qualitative test for the detection of human antibodies to Treponema pallidum.” The Syphilis Health Check is the only rapid syphilis test currently cleared by the Food and Drug Administration (FDA). We conducted a systematic review and a meta-analysis using Bayesian bivariate random-effects and fixed-effect models to create pooled estimates of sensitivity and specificity of the Syphilis Health Check. We identified 5 test evaluations published in the literature and 10 studies submitted to the FDA and for a Clinical Laboratory Improvement Amendments waiver application. The pooled sensitivity (95% CI) from the laboratory evaluations (n = 5) was 98.5% (92.1–100%), while pooled specificity was 95.9% (81.5–100.0%). The pooled sensitivity for prospective studies (n = 10) was 87.7% ( 71.8–97.2%), while pooled specificity was 96.7% (91.9–99.2%). Using nontreponemal supplemental testing, the sensitivity improved to a pooled sensitivity of 97.0% (94.8–98.6%). The Syphilis Health Check may provide accurate detection of treponemal antibody.
CRF01_AE and CRF01_AE Cluster 4 Are Associated With Poor Immune Recovery in Chinese Patients Under Combination Antiretroviral Therapy
Authors: Ge Zhangwen , Feng Yi , Li Kang , Lv Bowen , Zaongo Silvere D , Sun Jia , Liang Yanling , Liu Dan , Xing Hui , Wei Min , Ma Ping , Shao Yiming
Published: April 2020

Background

Human immunodeficiency virus type 1 (HIV-1) clades and clusters have different epidemic patterns and phenotypic profiles. It is unclear if they also affect patients’ immune recovery (IR) in combination antiretroviral therapy (cART).

Methods

We conducted a cohort study on 853 patients under cART for evaluating the impacts of viral factor on host IR. We used generalized estimating equations for factors affecting CD4 recovery, Kaplan-Meier curves for probability of achieving IR, and Cox hazards model for factors influencing IR capability.

Results

Besides low baseline CD4 and old age, CRF01_AE and its cluster 4 were independently associated with lower CD4 cell level (P ≤ .003), slower IR (P ≤ .022), fewer patients (P < .001), and longer time achieving IR (P < .001), compared with CRF07_BC and CRF01_AE cluster 5. Higher percentage of CXCR4 (X4) viruses in the CRF01_AE and cluster 4–infected patients, compared with their respective counterparts (P < .001), accounted for the poor IR in infected patients (P < .001). Finally, we revealed that greater X4 receptor binding propensity of amino acids was exhibited in CRF01_AE clade (P < .001) and its cluster 4 (P ≤ .004).

Conclusions

Our study demonstrates that the CRF01_AE clade and cluster are associated with poor IR in patients under cART, which is ascribed to a high proportion of viruses with X4 tropism. HIV-1 genotyping and phenotyping should be used as a surveillance tool for patients initiating cART. CCR5 inhibitors should be used with caution in regions with high prevalence of X4 viruses.
Pulmonary Tuberculosis Disease Among Immigrant Detainees: Rapid Disease Detection, High Prevalence of Asymptomatic Disease, and Implications for Tuberculosis Prevention
Authors: Boardman Nicole J , Moore Tiffany , Freiman Jennifer , Tagliaferri Geri , McMurray Dakota , Elson Diana , Lederman Edith
Published: April 2020

Background

Rapid screening for tuberculosis (TB) disease at intake into immigrant detention facilities allows for early detection and treatment. Detention facilities with United States Immigration and Customs Enforcement (ICE) Health Service Corps (IHSC) medical staffing utilize chest radiography and symptom screening as the primary screening for pulmonary TB (PTB) disease. This analysis describes the demographic, clinical, and microbiological characteristics of individuals identified with TB disease at these facilities.

Methods

We conducted a retrospective analysis to describe the population of immigrant detainees identified via chest radiography with PTB disease between 1 January 2014 and 31 December 2016 at facilities with IHSC medical staffing. We collected demographic variables, clinical presentation, diagnostic testing results, and microbiological findings. We generated descriptive statistics and examined univariate and multivariate associations between the variables collected and symptomatic status.

Results

We identified 327 patients with confirmed PTB disease (incidence rate, 92.8 per 100 000); the majority of patients were asymptomatic (79.2%) at diagnosis. Adjusting for all other variables in the model, the presence of cavitary lesions, acid-fast bacillus smear positivity, and multilobar presentation were significantly associated with symptomatic status. Among all patients identified with TB disease who had a tuberculin skin test (TST) result recorded, 27.2% were both asymptomatic and TST negative, including those with smear-positive disease.

Conclusions

Asymptomatic PTB disease is a significant clinical entity among immigrant detainees and placement in a congregate setting calls for aggressive screening to prevent transmission. Early identification, isolation, and treatment of TB disease benefit not only the health of the patient, but also the surrounding community.
A Tool for Early Prediction of Severe Coronavirus Disease 2019 (COVID-19): A Multicenter Study Using the Risk Nomogram in Wuhan and Guangdong, China
Authors: Gong Jiao , Ou Jingyi , Qiu Xueping , Jie Yusheng , Chen Yaqiong , Yuan Lianxiong , Cao Jing , Tan Mingkai , Xu Wenxiong , Zheng Fang , Shi Yaling , Hu Bo
Published: April 2020

Background

Because there is no reliable risk stratification tool for severe coronavirus disease 2019 (COVID-19) patients at admission, we aimed to construct an effective model for early identification of cases at high risk of progression to severe COVID-19.

Methods

In this retrospective multicenter study, 372 hospitalized patients with nonsevere COVID-19 were followed for > 15 days after admission. Patients who deteriorated to severe or critical COVID-19 and those who maintained a nonsevere state were assigned to the severe and nonsevere groups, respectively. Based on baseline data of the 2 groups, we constructed a risk prediction nomogram for severe COVID-19 and evaluated its performance.

Results

The training cohort consisted of 189 patients, and the 2 independent validation cohorts consisted of 165 and 18 patients. Among all cases, 72 (19.4%) patients developed severe COVID-19. Older age; higher serum lactate dehydrogenase, C-reactive protein, coefficient of variation of red blood cell distribution width, blood urea nitrogen, and direct bilirubin; and lower albumin were associated with severe COVID-19. We generated the nomogram for early identifying severe COVID-19 in the training cohort (area under the curve [AUC], 0.912 [95% confidence interval {CI}, .846–.978]; sensitivity 85.7%, specificity 87.6%) and the validation cohort (AUC, 0.853 [95% CI, .790–.916]; sensitivity 77.5%, specificity 78.4%). The calibration curve for probability of severe COVID-19 showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analyses indicated that nomogram conferred high clinical net benefit.

Conclusions

Our nomogram could help clinicians with early identification of patients who will progress to severe COVID-19, which will enable better centralized management and early treatment of severe disease.
Physiological indicators of habitat quality for a migratory songbird breeding in a forest invaded by non-native Japanese barberry (Berberis thunbergii)
Authors: Seewagen Chad L , Slayton Eric J , Smith Pagano Susan
Published: April 2020

Non-native, invasive plants can impact birds by altering food sources, nesting substrates and other critical resources. Japanese barberry (Berberis thunbergii) is one of the most invasive, non-native woody plants in in the northeastern USA, and yet almost nothing is known about its effects on birds or other wildlife. To investigate individual-level impacts of Japanese barberry on a forest-breeding bird, we compared food abundance (leaf-litter arthropod biomass) and the physiological condition of territorial male ovenbirds (Seiurus aurocapilla) between areas of a forest preserve in New York State that had high or low densities of Japanese barberry. We used haemoglobin and plasma triglyceride concentrations to indicate energetic condition, plasma uric acid and total plasma protein levels to indicate diet quality, and heterophil to lymphocyte ratios to indicate chronic stress. We found no difference in arthropod biomass between ovenbird territories that were heavily invaded by or relatively free of Japanese barberry. Perhaps largely as a result, we found no relationship between Japanese barberry density and any of our five haematological condition indices. There was also no difference in body mass, body size or age ratio between ovenbirds nesting in areas with low or high densities of Japanese barberry to suggest that relatively uninvaded forest patches were in greater demand and acquired by the most dominant individuals. Our results indicate that Japanese barberry does not reduce habitat quality for breeding male ovenbirds in a way that affects their prey abundance or physiological condition, but we caution that other species of birds and other aspects of habitat quality could be affected differently. We encourage future research on additional bird species and the effects of Japanese barberry on factors such as diet composition, pairing and nesting success and post-fledging survival to improve science-based decision-making about the extent to which conservation resources should be applied towards Japanese barberry control.
The Risk of SARS-CoV-2 in Immunosuppressed IBD Patients
Authors: Higgins Peter D R , Ng Siew , Danese Silvio , Rao Krishna
Published: April 2020

This is a rapid review of the risk of infection with SARS-CoV-2, the risk of symptomatic cases of COVID-19, and the severity of these cases in IBD patients. Guidance on how to manage IBD patients at risk for infection, and IBD patients after infection is provided. The prevention of infection in both patients and health care providers by reducing elective visits and procedures, utilizing telemedicine, and social isolation is also emphasized to maintain health care services for IBD patients during a growing pandemic.
Agricultural Returns to Labour and the Origins of Work Ethics
Authors: Fouka Vasiliki , Schläpfer Alain
Published: April 2020

We examine the historical determinants of differences in preferences for work across societies today. Our hypothesis is that a society’s work ethic depends on the role that labour has played in it historically, as an input in agricultural production: societies that have for centuries depended on the cultivation of crops with high marginal returns to labour effort will work longer hours and develop a preference for working hard. We formalise this prediction in the context of a model of endogenous preference formation, with altruistic parents who can invest in reducing their offsprings’ disutility from work. To empirically found our model, we construct an index of potential agricultural labour intensity, that captures the suitability of a location for the cultivation of crops with high estimated marginal returns to labour in their production. We find that this index positively predicts work hours and attitudes towards work in contemporary European regions. We investigate various mechanisms of persistence, including cultural transmission, as well as a society’s production structure and institutions.
Sex Chromosome Evolution: So Many Exceptions to the Rules
Authors: Furman Benjamin L S , Metzger David C H , Darolti Iulia , Wright Alison E , Sandkam Benjamin A , Almeida Pedro , Shu Jacelyn J , Mank Judith E
Published: April 2020

Genomic analysis of many nonmodel species has uncovered an incredible diversity of sex chromosome systems, making it possible to empirically test the rich body of evolutionary theory that describes each stage of sex chromosome evolution. Classic theory predicts that sex chromosomes originate from a pair of homologous autosomes and recombination between them is suppressed via inversions to resolve sexual conflict. The resulting degradation of the Y chromosome gene content creates the need for dosage compensation in the heterogametic sex. Sex chromosome theory also implies a linear process, starting from sex chromosome origin and progressing to heteromorphism. Despite many convergent genomic patterns exhibited by independently evolved sex chromosome systems, and many case studies supporting these theoretical predictions, emerging data provide numerous interesting exceptions to these long-standing theories, and suggest that the remarkable diversity of sex chromosomes is matched by a similar diversity in their evolution. For example, it is clear that sex chromosome pairs are not always derived from homologous autosomes. In addition, both the cause and the mechanism of recombination suppression between sex chromosome pairs remain unclear, and it may be that the spread of recombination suppression is a more gradual process than previously thought. It is also clear that dosage compensation can be achieved in many ways, and displays a range of efficacy in different systems. Finally, the remarkable turnover of sex chromosomes in many systems, as well as variation in the rate of sex chromosome divergence, suggest that assumptions about the inevitable linearity of sex chromosome evolution are not always empirically supported, and the drivers of the birth–death cycle of sex chromosome evolution remain to be elucidated. Here, we concentrate on how the diversity in sex chromosomes across taxa highlights an equal diversity in each stage of sex chromosome evolution.
Homological Stability for Spaces of Commuting Elements in Lie Groups
Authors: Ramras Daniel A , Stafa Mentor
Published: April 2020

In this paper, we study homological stability for spaces $\textrm{Hom}({{\mathbb{Z}}}^n,G)$ of pairwise commuting $n$-tuples in a Lie group $G$. We prove that for each $n\geqslant 1$, these spaces satisfy rational homological stability as $G$ ranges through any of the classical sequences of compact, connected Lie groups, or their complexifications. We prove similar results for rational equivariant homology, for character varieties, and for the infinite-dimensional analogues of these spaces, $\textrm{Comm}(G)$ and $B_{\textrm{com}} G$, introduced by Cohen–Stafa and Adem–Cohen–Torres-Giese, respectively. In addition, we show that the rational homology of the space of unordered commuting $n$-tuples in a fixed group $G$ stabilizes as $n$ increases. Our proofs use the theory of representation stability—in particular, the theory of $\textrm{FI}_W$-modules developed by Church–Ellenberg–Farb and Wilson. In all of the these results, we obtain specific bounds on the stable range, and we show that the homology isomorphisms are induced by maps of spaces.