bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 Active Surveillance Simulation Case Study - Health and Economic Impacts of Active Surveillance in a School Environment
Authors: Saad Ali A. , Saad Malak , Boctor Emad M.
Published: November 2020

The COVID-19 pandemic has affected the lives of almost all human beings and has forced stay-at-home mandates across the world. Government and school officials are facing challenging decisions on how to start the new 2020/2021 school year. Almost every school system has chosen a remote learning model for the Fall of 2020 while many are facing financial and logistical challenges.

In this study, we explore the efficacy of an Active Surveillance testing model where a random number of students are tested daily for early detection of asymptomatic patients and for prevention of the infection among the student population. In addition to health impacts, we also analyze the financial impact of deploying the Active Surveillance system in schools while taking into consideration lost workdays of parents, hospitalization costs, and testing costs.

Under the given assumptions, initial modeling results indicate that low Active Surveillance testing rates (between 6-10% daily testing of student population) can help achieve low infection rates (≤10%) among students along with enforcing mitigation procedures, such as wearing masks and social distancing. Without enforcing mitigation procedures, the optimal Active Surveillance rate of 8-10% can also achieve (≤10%) infection rates among student population. The results also demonstrate that Active Surveillance can lower the financial burden of the pandemic by proactively lowering the infection rates among student populations.
Preventing COVID-19 Fatalities: State versus Federal Policies
Authors: Renne Jean-Paul , Roussellet Guillaume , Schwenkler Gustavo
Published: November 2020

Are COVID-19 fatalities large when a federal government does not enforce containment policies and instead allow states to implement their own policies? We answer this question by developing a stochastic extension of a SIRD epidemiological model for a country composed of multiple states. Our model allows for interstate mobility. We consider three policies: mask mandates, stay-at-home orders, and interstate travel bans. We fit our model to daily U.S. state-level COVID-19 death counts and exploit our estimates to produce various policy counterfactuals. While the restrictions imposed by some states inhibited a significant number of virus deaths, we find that more than two-thirds of U.S. COVID-19 deaths could have been prevented by late November 2020 had the federal government enforced federal mandates as early as some of the earliest states did. Our results quantify the benefits of early actions by a federal government for the containment of a pandemic.
Impacts of teaching modality on U.S. COVID-19 spread in fall 2020 semester
Authors: Badruddoza Syed , Amin Modhurima Dey
Published: November 2020

We study the impact of college reopening in Fall 2020 on county-level COVID-19 cases and deaths using the information of 1,076 randomly chosen four- and two-year undergraduate degree-granting colleges from the National Center for Education Statistics. These institutions include public, private nonprofit, and for profit schools from 50 US states and the District of Columbia. We match college and county characteristics using several methods and calculate the average treatment effects of three teaching modalities: in-person, online, and hybrid on COVID-19 outcomes up to two months after college reopening. In pairwise comparison, colleges reopened with in-person teaching mode were found to have about 35 percentage points more cases within 15 days of reopening, compared to those that reopened online, and the gap widens over time at a decreasing rate. Death rates follow the pattern with a time lag. However, colleges with hybrid mode reach up to the rates of in-person mode after some time. We also find that greater endowment and student population, bigger class size, and fewer Republican voters in the county are major predictors of choosing remote teaching modes over in-person.
Acquisition and carriage dynamics of fluoroquinolone resistant Enterobacteriaceae at individual and household levels
Authors: Musicha Patrick , Stewardson Andrew J. , Mo Yin , Vervoort Jascha , Adriaenssens Niels , Coenen Samuel , Godycki-Cwirko Maciek , Kowalczyk Anna , Lammens Christine , Malhotra-Kumar Surbhi , Goossens Herman , Harbarth Stephan , Cooper Ben S.
Published: November 2020

Carriage dynamics of drug-resistant bacteria, especially within households, are poorly understood. This limits the ability to develop effective interventions for controlling the spread of antimicrobial resistance in the community. Two groups consisting of: (i) patients with urinary tract infection requiring antimicrobial treatment; and (ii) patients who were not prescribed antimicrobial treatment were prospectively recruited at three European sites: Antwerp (Belgium), Geneva (Switzerland) and Lodz (Poland). Each index patient and up to three additional household members provided faecal samples at baseline, completion of antimicrobial therapy (or 7-10 days after the first sample for the non-exposed) and 28 days after the second sample. We analysed household-level and individual-level fluoroquinolone resistant Enterobacteriaceae (FQR-E) acquisition and carriage data using Bayesian multi-state Markov models. At the individual level, we estimated a median baseline FQR-E acquisition rate of 0.006 (95%CrI = [0.004, 0.01]) per day, and a median duration of carriage of 24.4 days (95% CrI=[15.23,41.38]). Nitrofurantoin exposure was associated with a reduced rate of FQR-E acquisition (HR=0.28, 95%CrI=[0.14,0.56]), while fluoroquinolone exposure had no clear association with rates of FQR-E acquisition (HR=1.43, 95% CrI=[0.81,2.53]) at individual level. There was evidence that rates of FQR-E acquisition varied by site, and coming from Lodz was associated with a higher acquisition rate (HR=3.56, 95% CrI=[1.92, 6.34]). Prolonged duration of carriage was associated with exposure to fluoroquinolone or nitrofurantoin during the study, use of any antimicrobial agent in the prior 12 months and travel to endemic regions. At household level, we found strong evidence of positive association between FQR-E acquisition and fluoroquinolone exposure (HR=3.43, 95% CrI=[1.51,7.74]). There was weak evidence of negative association between FQR-E acquisition and nitrofurantoin exposure (HR=0.42, 95%CrI=[0.12, 1.24]. Similar to the individual level, carriage duration was also associated with antimicrobial exposure at the household level. Our study has identified within household contacts as an important route for FQR-E transmission and highlights the need for prioritising household focused interventions to control FQR-E spread.
A Novel 3-Dimensional technique in measuring pericoronary epicardial adipose tissue radiodensity
Authors: Xu Lingyu , Hrybouski Stanislau , Xu Yuancheng , Coulden Richard , Sonnex Emer , Paterson D. Ian , Butler Craig
Published: November 2020

Objectives

This study aimed to investigate a novel semi-automated three-dimensional (3D) quantification of the pericoronary epicardial adipose tissue radiodensity (PCATrd).

Methods

Twenty-four subjects who previously underwent contrast-enhanced cardiac CT scans were retrospectively identified. The PCATrd was measured in ITK-SNAP imaging software using a Hounsfield unit threshold (−190,-3) to define epicardial adipose tissue (EAT). A spherical 3D brush tool was used on multiplanar reformatted images to segment the PCAT. We defined the PCATrd as EAT within the orthogonal distance from the coronary artery (CA) outer wall equal to the diameter of the corresponding CA segment. The segmentation followed the path of major CAs. Additionally, the PCAT of twenty-five calcified segments were segmented. Reliability of this novel segmentation protocol was assessed using Dice Similarity Coefficients (DSCs) and intraclass coefficient (ICC).

Results

The segmentation reproducibility for the PCAT was high, with intraobserver DSC 0.86±0.04 for the full length of major CAs and 0.85±0.07 for the calcified segments, and interobserver DSC 0.84±0.04 for the full length of major CAs and 0.83±0.05 for the calcified segments. The reproducibility of the PCATrd value assessed by ICC was also excellent, with intraobserver ICC 0.99 for the full length of major CAs and 0.99 for the calcified segments, and interobserver ICC 0.99 for the full length of major CAs and 0.99 for the calcified segments.

Conclusions

Our novel 3D PCATrd quantification technique is reliable and reproducible. The availability of the open source software and detailed image analysis pipeline will enable reliable replications and broad uptake of our technique.

Key points

We have produced a novel, semiautomated technique to comprehensively quantify pericoronary epicardial adipose tissue radiodensity (PCATrd) which is a novel imaging biomarker of coronary inflammation.

Our method of PCAT segmentation has excellent reproducibility.

We use open source software and provide detailed image analysis pipeline of quantifying PCATrd, which will allow easy replication and broad uptake of our technique.
Transmission routes of SARS-CoV-2 among healthcare workers of a French university hospital in Paris, France: a case-control study
Authors: Contejean Adrien , Leporrier Jérémie , Canouï Etienne , Fourgeaud Jacques , Mariaggi Alice-Andrée , Alby-Laurent Fanny , Lafont Emmanuel , Beaudeau Lauren , Rouzaud Claire , Lecieux Fabienne , Greffet Agnès , L’Honneur Anne-Sophie , Tréluyer Jean-Marc , Lanternier Fanny , Casetta Anne , Frange Pierre , Leruez-Ville Marianne , Rozenberg Flore , Lortholary Olivier , Kernéis Solen
Published: November 2020

In this case-control study on 564 healthcare workers of a university hospital in Paris (France), contacts without protection with COVID-19 patients or with colleagues were associated with infection with SARS-CoV-2, while working in a COVID-dedicated unit, using public transportation and having children kept in childcare facilities were not.
Preserved sensory processing but hampered conflict detection when stimulus input is task-irrelevant
Authors: Nuiten Stijn A. , Canales-Johnson Andrés , Beerendonk Lola , Nanuashvili Nutsa , Fahrenfort Johannes J. , Bekinschtein Tristan , van Gaal Simon
Published: November 2020

Conflict detection in sensory input is central to adaptive human behavior. Perhaps unsurprisingly, past research has shown that conflict may even be detected in absence of conflict awareness, suggesting that conflict detection is an automatic process that does not require attention. To test the possibility of conflict processing in the absence of attention, we manipulated task relevance and response overlap of potentially conflicting stimulus features across six behavioral tasks. Multivariate analyses on human electroencephalographic data revealed neural signatures of conflict only when at least one feature of a conflicting stimulus was attended, regardless of whether that feature was part of the conflict, or overlaps with the response. In contrast, neural signatures of basic sensory processes were present even when a stimulus was completely unattended. These data reveal an attentional bottleneck at the level of objects, suggesting that object-based attention is a prerequisite for cognitive control operations involved in conflict detection.
Effects of external stimulation on psychedelic state neurodynamics
Authors: Mediano Pedro A.M. , Rosas Fernando E. , Timmermann Christopher , Roseman Leor , Nutt David J. , Feilding Amanda , Kaelen Mendel , Kringelbach Morten L. , Barrett Adam B. , Seth Anil K. , Muthukumaraswamy Suresh , Bor Daniel , Carhart-Harris Robin L.
Published: November 2020

Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes such as personality changes. These findings are particularly intriguing given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g. from wakefulness to sleep). However, little is known about how context impacts the entropy-enhancing effect of psychedelics, which carries important implications for how it can be exploited in, for example, psychedelic psychotherapy. This article investigates how brain entropy is modulated by stimulus manipulation during a psychedelic experience, by studying participants under the effects of LSD or placebo, either with gross state changes (eyes closed vs. open) or different stimulus (no stimulus vs. music vs. video). Results show that while brain entropy increases with LSD in all the experimental conditions, it exhibits largest changes when subjects have their eyes closed. Furthermore, brain entropy changes are consistently associated with subjective ratings of the psychedelic experience, but this relationship is disrupted when participants are viewing video — potentially due to a “competition” between external stimuli and endogenous LSD-induced imagery. Taken together, our findings provide strong quantitative evidence for the role of context in modulating neural dynamics during a psychedelic experience, underlining the importance of performing psychedelic psychotherapy in a suitable environment. Additionally, our findings put into question simplistic interpretations of brain entropy as a direct neural correlate of conscious level.

Significance Statement

The effects of psychedelic substances on conscious experience can be substantially affected by contextual factors, which play a critical role in the outcomes of psychedelic therapy. This study shows how context can modulate not only psychological, but also neurophysiological phenomena during a psychedelic experience. Our findings reveal distinctive effects of having eyes closed after taking LSD, including a more pronounced change on the neural dynamics, and a closer correspondence between brain activity and subjective ratings. Furthermore, our results suggest a competition between external stimuli and internal psychedelic-induced imagery, which supports the practice of carrying out psychedelic therapy with patients having their eyes closed.
Rapid inactivation of SARS-CoV-2 with ozone water
Authors: Inagaki Hiroko , Saito Akatsuki , Sudaryatma Putu Eka , Sugiyama Hironobu , Okabayashi Tamaki , Fujimoto Shouichi
Published: November 2020

Although ozone water is one of the promising candidates for hand hygiene to prevent fomite infection, the detailed effects of ozone water on SARS-CoV-2 have not been clarified. We evaluated the inactivating effect of ozone water against SARS-CoV-2 by its concentration and exposure time. The reduction rates of virus titer after 5 sec treatment with ozone concentrations of 1, 4, 7, and 10 mg/L were 81.4%, 93.2%, 96.6%, and 96.6%, respectively. No further decrease in virus titer was observed by the extended exposure time over 5 sec. High-concentration ozone water was considered to be effective in promptly inactivating SARS-CoV-2 virus.
IceR improves proteome coverage and data completeness in global and single-cell proteomics
Authors: Kalxdorf Mathias , Müller Torsten , Stegle Oliver , Krijgsveld Jeroen
Published: November 2020

Label-free proteomics by data-dependent acquisition (DDA) enables the unbiased quantification of thousands of proteins, however it notoriously suffers from high rates of missing values, thus prohibiting consistent protein quantification across large sample cohorts. To solve this, we here present IceR, an efficient and user-friendly quantification workflow that combines high identification rates of DDA with low missing value rates similar to DIA. Specifically, IceR uses ion current information in DDA data for a hybrid peptide identification propagation (PIP) approach with superior quantification precision, accuracy, reliability and data completeness compared to other quantitative workflows. We demonstrate greatly improved quantification sensitivity on published plasma and single-cell proteomics data, enhancing the number of reliably quantified proteins, improving discriminability between single-cell populations, and allowing reconstruction of a developmental trajectory. IceR will be useful to improve performance of large scale global as well as low-input proteomics applications, facilitated by its availability as an easy-to-use R-package.
A long read mapping method for highly repetitive reference sequences
Authors: Jain Chirag , Rhie Arang , Hansen Nancy , Koren Sergey , Phillippy Adam M.
Published: November 2020

About 5-10% of the human genome remains inaccessible for functional analysis due to the presence of repetitive sequences such as segmental duplications and tandem repeat arrays. To enable high-quality resequencing of personal genomes, it is crucial to support end-to-end genome variant discovery using repeat-aware read mapping methods. In this study, we highlight the fact that existing long read mappers often yield incorrect alignments and variant calls within long, near-identical repeats, as they remain vulnerable toallelic bias. In the presence of a non-reference allele within a repeat, a read sampled from that region could be mapped to an incorrect repeat copy because the standard pairwise sequence alignment scoring system penalizes true variants.

To address the above problem, we propose a novel, long read mapping method that addresses allelic bias by making use ofminimal confidently alignable substrings(MCASs). MCASs are formulated as minimal length substrings of a read that have unique alignments to a reference locus with sufficient mapping confidence (i.e., a mapping quality score above a user-specified threshold). This approach treats each read mapping as a collection of confident sub-alignments, which is more tolerant of structural variation and more sensitive to paralog-specific variants (PSVs) within repeats. We mathematically define MCASs and discuss an exact algorithm as well as a practical heuristic to compute them. The proposed method, referred to as Winnowmap2, is evaluated using simulated as well as real long read benchmarks using the recently completed gapless assemblies of human chromosomes X and 8 as a reference. We show that Winnowmap2 successfully addresses the issue of allelic bias, enabling more accurate downstream variant calls in repetitive sequences. As an example, using simulated PacBio HiFi reads and structural variants in chromosome 8, Winnowmap2 alignments achieved the lowest false-negative and false-positive rates (1.89%, 1.89%) for calling structural variants within near-identical repeats compared to minimap2 (39.62%, 5.88%) and NGMLR (56.60%, 36.11%) respectively.

Winnowmap2 code is accessible athttps://github.com/marbl/Winnowmap
Correction of a Factor VIII genomic inversion with designer-recombinases
Authors: Lansing Felix , Mukhametzyanova Liliya , Rojo-Romanos Teresa , Iwasawa Kentaro , Kimura Masaki , Paszkowski-Rogacz Maciej , Karpinski Janet , Grass Tobias , Sonntag Jan , Schneider Paul Martin , Günes Ceren , Hoersten Jenna , Schmitt Lukas Theo , Rodriguez-Muela Natalia , Knöfler Ralf , Takebe Takanori , Buchholz Frank
Published: November 2020

Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct a 140 kb genomic inversion of the F8 gene, which is frequently found in patients diagnosed with severe Hemophilia A. Employing substrate-linked directed molecular evolution, we developed a fused heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells. Transient RecF8 treatment of endothelial cells, differentiated from patient derived induced pluripotent stem cells (iPSCs) of a hemophilic donor, resulted in prominent correction of the inversion and restored Factor VIII mRNA expression. Our data suggests that designer-recombinases may represent efficient and specific means towards treatment of monogenic diseases caused by large gene inversions.
Downstream of gasdermin D cleavage, a Ragulator-Rag-mTORC1 pathway promotes pore formation and pyroptosis
Authors: Evavold Charles L. , Hafner-Bratkovič Iva , Kagan Jonathan C.
Published: November 2020

The process of pyroptosis is mediated by inflammasomes and a downstream effector known as gasdermin D (GSDMD). Upon cleavage by inflammasome-associated caspases, the N-terminal domain of GSDMD forms membrane pores that promote cytolysis. Numerous proteins are recognized to promote GSDMD cleavage, but none are known to be required for pore formation after GSDMD cleavage. Herein, we report a forward genetic screen that was designed to identify regulators of pyroptosis that act downstream of GSDMD cleavage. This screen identified several components of the Ragulator-Rag complex, which is known for its metabolic control of mTOR. Mechanistic studies revealed that Ragulator-Rag is not necessary for GSDMD localization to the plasma membrane, but is necessary for pore formation and mitochondrial inactivation. Downstream of Ragulator-Rag is mTORC1, which we found to promote pyroptosis in response to diverse natural stimuli, including infection. GSDMD therefore requires a Ragulator-Rag-mTORC1 pathway in order to form pores and execute pyroptosis.
Microbiota functional activity biosensors for characterizing nutrient utilizationin vivo
Authors: Wesener Darryl A. , Beller Zachary W. , Peters Samantha L. , Rajabi Amir , Dimartino Gianluca , Giannone Richard J. , Hettich Robert L. , Gordon Jeffrey I.
Published: November 2020

Methods for measuring gut microbiota biochemical activitiesin vivoare needed to characterize its functional states in health and disease. To illustrate one approach, an arabinan-containing polysaccharide was purified from pea fiber, its structure defined, and forward genetic and proteomic analyses used to compare its effects, versus unfractionated pea fiber and sugar beet arabinan, on a human gut bacterial strain consortium in gnotobiotic mice. We produced ‘Microbiota Functional Activity Biosensors’ (MFABs) consisting of glycans covalently-linked to the surface of fluorescent paramagnetic microscopic glass beads. Three MFABs, each containing a unique glycan/fluorophore combination, were simultaneously orally gavaged into gnotobiotic mice, recovered from their intestines, and analyzed to directly quantify bacterial metabolism of structurally distinct arabinans in different human diet contexts. Colocalizing pea-fiber arabinan and another polysaccharide (glucomannan) on the bead surface enhancedin vivometabolism of glucomannan. MFABs represent a potentially versatile platform for developing new prebiotics and more nutritious foods.
Adipose Triglyceride Lipase is needed for homeostatic control of Sterol Element-Binding Protein-1c driven hepatic lipogenesis
Authors: Wieser Beatrix Irene , de la Sancha Paola Peña , Schauer Silvia , Reicher Helga , Sattler Wolfgang , Breinbauer Rolf , Schweiger Martina , Espenshade Peter John , Zechner Rudolf , Hoefler Gerald , Vesely Paul Willibald
Published: November 2020

Sterol Regulatory Element-Binding Protein-1c (SREBP-1c) is translated as an inactive precursor-protein that is proteolytically activated to promote fatty-acid (FA) biosynthesis, when unsaturated (u)FAs are scarce. During fasting, however, lipogenesis is low, and adipose-tissue lipolysis supplies the organism with FAs. Adipose TriGlyceride Lipase (ATGL) is the rate-limiting enzyme for lipolysis, and it preferentially hydrolyzes uFAs. Therefore, we hypothesized that ATGL-derived FAs may suppress the proteolytic activation of SREBP-1c in the liver. Here we show that (i) SREBP-1c is inactive during fasting but active after refeeding, (ii) uFA species liberated by ATGL suppress SREBP-1c activationin vitro, (iii) SREBP-1c is hyper-activated in livers of mice lacking ATGL, and (iv) pharmacological inhibition of ATGL selectively activates SREBP-1c in hepatocytes. Our findings highlight an ATGL/SREBP-1c axis, instrumental to coordinate lipogenesis and lipolysis, whose homeostatic regulation is crucial to avoid severe diseases including diabetes, cardiomyopathy, and even cancer.
The SARS-CoV-2 RNA interactome
Authors: Lee Sungyul , Lee Young-suk , Choi Yeon , Son Ahyeon , Park Youngran , Lee Kyung-Min , Kim Jeesoo , Kim Jong-Seo , Kim V. Narry
Published: November 2020

SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its ability to repurpose host RNA-binding proteins (RBPs) to form its own RNA interactome. Here, we developed and applied a robust ribonucleoprotein capture protocol to uncover the SARS-CoV-2 RNA interactome. We report 109 host factors that directly bind to SARS-CoV-2 RNAs including general antiviral factors such as ZC3HAV1, TRIM25, and PARP12. Applying RNP capture on another coronavirus HCoV-OC43 revealed evolutionarily conserved interactions between viral RNAs and host proteins. Network and transcriptome analyses delineated antiviral RBPs stimulated by JAK-STAT signaling and proviral RBPs responsible for hijacking multiple steps of the mRNA life cycle. By knockdown experiments, we further found that these viral-RNA-interacting RBPs act against or in favor of SARS-CoV-2. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.
Whole genome genetic variation and linkage disequilibrium in a diverse collection ofListeria monocytogenesisolates
Authors: Louha Swarnali , Meinersmann Richard J. , Glenn Travis C.
Published: November 2020

We performed whole-genome multi-locus sequence typing for 2554 genes in a large and heterogenous panel of 180Listeria monocytogenesstrains having diverse geographical and temporal origins. The subtyping data was used for characterizing genetic variation and evaluating patterns of linkage disequilibrium in the pan-genome ofL. monocytogenes. Our analysis revealed the presence of strong linkage disequilibrium inL. monocytogenes, with ∼99% of genes showing significant non-random associations with a large majority of other genes in the genome. Twenty-seven loci having lower levels of association with other genes were considered to be potential “hot spots” for horizontal gene transfer (i.e., recombination via conjugation, transduction, and/or transformation). The patterns of linkage disequilibrium inL. monocytogenessuggest limited exchange of foreign genetic material in the genome and can be used as a tool for identifying new recombinant strains. This can help understand processes contributing to the diversification and evolution of this pathogenic bacteria, thereby facilitating development of effective control measures.
Reducedech-6Expression Attenuates Fat-induced Premature Aging inC. elegans
Authors: Liu Yasmine J. , Gao Arwen W. , Smith Reuben L. , Janssens Georges E. , Panneman Daan M. , Jongejan Aldo , van Weeghel Michel , Vaz Frédéric M. , Silvestrini Melissa J. , Lapierre Louis R. , MacInnes Alyson W. , Houtkooper Riekelt H.
Published: November 2020

Deregulated energy homeostasis represents a hallmark of aging and results from complex gene-by-environment interactions. Here, we discovered that reducing the expression of the geneech-6encoding enoyl-CoA hydratase remitted fat diet-induced deleterious effects on lifespan inCaenorhabditis elegans, while a basal expression ofech-6was important for survival under normal dietary conditions. Lipidomics revealed that supplementation of fat inech-6-silenced worms had marginal effects on lipid profiles, suggesting an alternative fat utilization for energy production. Transcriptomics further suggest a causal relation between the lysosomal pathway, energy production, and the longevity effect conferred by the interaction betweenech-6and high-fat diets. Indeed, enhancing energy production from endogenous fat by overexpressing lysosomal lipaselipl-4recapitulated the lifespan effects of high-fat diets onech-6-silenced worms. Collectively, these results reveal that the geneech-6modulates metabolic flexibility and may be a target for promoting metabolic health and longevity.
Neutrophils encompass a regulatory subset suppressing T cells in apparently healthy cattle and mice
Authors: Rambault Marion , Doz-Deblauwe Émilie , Vern Yves Le , Carreras Florence , Cunha Patricia , Germon Pierre , Rainard Pascal , Winter Nathalie , Remot Aude
Published: November 2020

Neutrophils that reside in the bone marrow are switly recruited from circulating blood to fight infections. For a long time, these first line defenders were considered as microbe killers. However their role is far more complex as cross talk with T cells or dendritic cells have been described for human or mouse neutrophils. In cattle, these new roles are not documented yet. We identified a new subset of regulatory neutrophils that is present in the mouse bone marrow or circulate in cattle blood under steady state conditions. These regulatory neutrophils that display MHC-II on the surface are morphologically indistinguishable from classical MHC-IInegneutrophils. However MHC-IIposand MHC-IInegneutrophils display distinct transcriptomic profiles. While MHC-IInegand MHC-IIposneutrophils display similar bacterial phagocytosis or killing activity, MHC-IIposonly are able to suppress T cell proliferation under contact-dependent mechanisms. Regulatory neutrophils are highly enriched in lymphoid organs as compared to their MHC-IInegcounterparts and in the mouse they express PDL-1, an immune checkpoint involved in T-cell blockade. Our results emphasize neutrophils as true partners of the adaptive immune response, including in domestic species. They open the way for discovery of new biomarkers and therapeutic interventions to better control cattle diseases.
Common transcriptional programme of liver fibrosis in mouse genetic models and humans
Authors: Cokan Kaja Blagotinšek , Urlep Žiga , Moškon Miha , Mraz Miha , Kong Xiang Y. , Eskild Winnie , Rozman Damjana , Juvan Peter , Režen Tadeja
Published: November 2020

Multifactorial metabolic diseases, such as non-alcoholic fatty liver disease, are a major burden of modern societies and frequently present with no clearly defined molecular biomarkers. Herein we used systems medicine approaches to decipher signatures of liver fibrosis in mouse models with malfunction in genes from unrelated biological pathways. Enrichment analyses of KEGG, Reactome and TRANSFAC databases complemented with genome-scale metabolic modelling revealed fibrotic signatures highly similar to liver pathologies in humans. The diverse genetic models of liver fibrosis exposed a common transcriptional programme with activated ERα signalling, and a network of interactions between regulators of lipid metabolism and transcription factors from cancer pathways and immune system. The novel hallmarks of fibrosis are downregulated lipid pathways, including fatty acid, bile acid, and steroid hormone metabolism. Moreover, distinct metabolic subtypes of liver fibrosis were proposed, supported by unique enrichment of transcription factors based on the type of insult, disease stage, or sex.
Structural and functional plasticity in the dorsolateral geniculate nucleus of mice following bilateral enucleation
Authors: Bhandari Ashish , Ward Thomas W. , Smith Jennie , Van Hook Matthew J.
Published: November 2020

Within the nervous system, plasticity mechanisms attempt to stabilize network activity following disruption by injury, disease, or degeneration. Optic nerve injury and age-related diseases can induce homeostatic-like responses in adulthood. We tested this possibility in the thalamocortical (TC) neurons in the dorsolateral geniculate nucleus (dLGN) using patch-clamp electrophysiology, optogenetics, immunostaining, and single-cell dendritic analysis following loss of visual input via bilateral enucleation. We observed progressive loss of vGlut2-positive retinal terminals in the dLGN indicating degeneration post-enucleation that was coincident with changes in microglial morphology indicative of microglial activation. Consistent with the decline of vGlut2 puncta, we also observed loss of retinogeniculate (RG) synaptic function assessed using optogenetic activation of RG axons while performing whole-cell voltage clamp recordings from TC neurons in brain slices. Surprisingly, we did not detect any significant changes in the frequency of miniature post-synaptic currents (mEPSCs) or corticothalamic feedback synapses. Analysis of TC neuron dendritic structure from single-cell dye fills revealed a gradual loss of dendrites proximal to the soma, where TC neurons receive the bulk of RG inputs. Finally, analysis of action potential firing demonstrated that TC neurons have increased excitability following enucleation, firing more action potentials in response to depolarizing current injections. Our findings show that degeneration of the retinal axons/optic nerve and loss of RG synaptic inputs induces structural and functional changes in TC neurons, consistent with neuronal attempts at compensatory plasticity in the dLGN.
scCapsNet-mask: an automatic version of scCapsNet
Authors: Wang Lifei , Zhang Jiang , Cai Jun
Published: November 2020

Recently we developed scCapsNet, an interpretable deep learning cell type classifier for single cell RNA sequencing data, based on capsule network. However, the running process of scCapsNet is not fully automatic, in which a manual intervention is required for getting the final results. Here we present scCapsNet-mask, an updated version of scCapsNet that utilizes a mask to fully automate the running process of scCapsNet. scCapsNet-mask could constrain the internal parameter coupling coefficients and result in a one to one correspondence between the primary capsule and type capsule. Based on those bijective mapping between primary capsule and type capsule, the model could automatically extract the cell type related genes according to weight matrix connecting input and primary capsule, without a need for manual inspection of the relationship between primary capsules and type capsules. The scCapsNet-mask is evaluated on two single cell RNA sequence datasets. The results show that scCapsNet-mask not only retains the merits of the original scCapsNet with high classification accuracy and high interpretability, but also has the virtue of automatic processing.
Response ofProsopis farctato copper and cadmium stress and potential for accumulation and translocation of these heavy metals
Authors: Gishini Mohammad Fazel Soltani , Azizian Abolfazl , Alemzadeh Abbas , Shabani Marzieh , Amin Seifollah , Hildebrand David
Published: November 2020

Few studies have evaluated the effects of various levels of heavy metals on medicinal plants. The impact of gradually increased soil levels of copper (Cu) and cadmium (Cd) on the medicinal plant native to Southwest Asia and North Africa,Prosopis farcta, irrigated with metal-enriched water was determined. The exposure of plants to Cd or Cu decreased plant growth and increased Cd and Cu concentration in their shoots and roots. External Cd or Cu in the soil increased the uptake of both elements. Regression analysis showed that the weight of both shoots and roots decreased linearly with the increase of Cu and Cd contents in roots and shoots. Results showed that Cd was more toxic than Cu. The water content of shoots and roots decreased linearly with increased heavy metal levels.P. farctacould take up Cu and Cd in both Cu- and Cd-contaminated soils, however, it was more capable for transporting Cd from roots to shoots rather than Cu.P. farctais a natural accumulator for Cu and Cd under gradually increased levels of these metals in the soil.
An epithelialNfkb2pathway exacerbates intestinal inflammation by supplementing latent RelA dimers to the canonical NF-κB module
Authors: Chawla Meenakshi , Mukherjee Tapas , Deka Alvina , Chatterjee Budhaditya , Sarkar Uday Aditya , Singh Amit K. , Kedia Saurabh , Banoth Balaji , Biswas Subhra K , Ahuja Vineet , Basak Soumen
Published: November 2020

Aberrant inflammation associated with human ailments, including inflammatory bowel disease (IBD), is typically fuelled by the inordinate activity of RelA/NF-κB transcription factors. As such, the canonical NF-κB module mediates controlled nuclear activation of RelA dimers from the latent cytoplasmic complexes. What provokes pathological RelA activity in the colitogenic gut remains unclear. The noncanonical NF-κB pathway promotes immune organogenesis involvingNfkb2gene products. Because NF-κB pathways are intertwined, we asked if noncanonical signaling aggravated inflammatory RelA activity. Our investigation revealed frequent engagement of the noncanonical pathway in human IBD. In a mouse model, anNfkb2function exacerbated gut inflammation by amplifying the epithelial RelA activity induced upon intestinal injury. Our mechanistic studies clarified that cell-autonomousNfkb2signaling supplemented latent NF-κB dimers leading to hyperactive canonical RelA response in the inflamed colon. In sum, regulation of latent NF-κB dimers links noncanonical signaling to RelA-driven inflammatory pathologies and may provide for therapeutic targets.

In brief

Noncanonical NF-κB signals in intestinal epithelial cells supplement latent RelA dimers that, in turn, aggravated canonical NF-κB response in the colitogenic gut exacerbating intestinal inflammation.

Highlights

Human IBD involves the frequent engagement of the noncanonical NF-κB pathway.

Mice deficient in the noncanonical signal transducerNfkb2are resistant to experimental colitis.

Noncanonical NF-κB signaling supplements latent RelA NF-κB dimers.

Noncanonical NF-κB signaling amplifies canonical NF-κB response to TLR ligands.
Recurrent SPECC1L–NTRK fusions in pediatric sarcoma and brain tumors
Authors: Khuong-Quang Dong-Anh , Brown Lauren M. , Wong Marie , Mayoh Chelsea , Sexton-Oates Alexandra , Kumar Amit , Pinese Mark , Nagabushan Sumanth , Lau Loretta , Ludlow Louise E. , Gifford Andrew J. , Rodriguez Michael , Desai Jayesh , Fox Stephen B. , Haber Michelle , Ziegler David S. , Hansford Jordan R. , Marshall Glenn M. , Cowley Mark J. , Ekert Paul G.
Published: November 2020

The identification of rearrangements driving expression of neurotrophic receptor tyrosine kinase (NTRK) family kinases in tumors has become critically important because of the availability of effective, specific inhibitor drugs. Whole-genome sequencing (WGS) combined with RNA sequencing (RNA-seq) can identify novel and recurrent expressed fusions. Here we describe three SPECC1L–NTRK fusions identified in two pediatric central nervous system cancers and an extracranial solid tumor using WGS and RNA-seq. These fusions arose either through a simple balanced rearrangement or in the context of a complex chromoplexy event. We cloned the SPECC1L–NTRK2 fusion directly from a patient sample and showed that enforced expression of this fusion is sufficient to promote cytokine-independent survival and proliferation. Cells transformed by SPECC1L–NTRK2 expression are sensitive to a TRK inhibitor drug. We report here that SPECC1L–NTRK fusions can arise in a range of pediatric cancers. Although WGS and RNA-seq are not required to detect NTRK fusions, these techniques may be of benefit when NTRK fusions are not suspected on clinical grounds or not identified by other methods.
Crystal structures of 2-amino-2-oxoethyl 4-bromobenzoate, 2-amino-2-oxoethyl 4-nitrobenzoate and 2-amino-2-oxoethyl 4-aminobenzoate monohydrate
Authors: Sapayev F. A. , Okmanov R. Ya. , Kholikov T. S. , Tadjimukhamedov Kh. S. , Tashkhodjaev B.
Published: November 2020

The title molecules were synthesized by the reaction of 4-substituted sodium benzoates with chloroacetic acid amide in the presence of dimethylformamide. The yields of 2-amino-2-oxoethyl 4-bromobenzoate, C9H8BrNO3, I, 2-amino-2-oxoethyl 4-nitrobenzoate, C9H8N2O5, II, and 2-amino-2-oxoethyl 4-aminobenzoate monohydrate, C9H10N2O3·H2O, III, are 86, 78 and 88%, respectively. The low yield of II is explained by the reduced reactivity of the molecule in a nucleophilic exchange reaction because of the negative induction and negative mesomeric effects of the nitro group on the benzene ring. Single crystals were obtained from the products under the same (temperature and solvent) conditions. In the case of III, the crystals formed as a monohydrate. In all three crystal structures, the same type of intermolecular N—H...O hydrogen bonds are observed, but the molecules differ in some torsion angles as well as in the dihedral angles between the mean planes of the benzene rings and the amide groups.
Testing for the Marshall–Lerner condition in Egypt: an empirical analysis
Authors: Adams John , Metwally Ali
Published: November 2020

Purpose

The purpose of this paper is to examine to what extent evidence can be found for the presence of the Marshall–Lerner (ML) condition regarding the trade balances of Egypt. The theoretical basis of the ML is presented and then tested using Egyptian trade data from 1965 to 2017.

Design/methodology/approach

The data are analysed via standard ordinary least squares models subject to the constraints imposed by economic theory, specifically ML theory, in which the coefficients represent elasticities. A range of tests are undertaken to establish the validity of the models and the model results including multicollinearity, unit root and co-integration in order to avoid spurious regressions.

Findings

The export model strongly suggests that real exports of Egyptian goods and services are elastic with respect to changes in the real effective exchange rate (REER), with a coefficient weight of −1.64 and is significant at 1%. However, for the import model the coefficient weight of the REER −1.17 and is significant at 1%. This result contradicts ML theory, where an increase in the REER makes imports cheaper and thus causes them to increase.

Research limitations/implications

The limitations of the study are two in particular, the first is that the frequency of the data employed is annual, not monthly or even quarterly, which means that the sample size would have been larger, and the estimated parameters could have been more accurate in forecasting the future behaviour of exports and imports. There could be several other indicators that might have clear impacts on exports and imports. In other words, it is possible that a model with consumer spending and government spending as well as terms of trade, inflation, interest rate spread and taxes is going to capture more of the variation that occurs in Egypt's trade balance components.

Practical implications

The results suggest that the Egypt-International Monetary Fund plan (depreciation) is likely to have a positive effect on the economy. However, this does not mean that the deficit of the trade balance is going to change into a surplus once the policies of the plan are fully applied, but it does mean the deficit will reduce. Only in the long run is the trade balance likely to record a sustainable surplus. But the latter will heavily depend on the structure of exports and imports and maintaining price stability, both of which are key government policy areas.

Originality/value

The paper builds on previous theoretical and empirical work in this field and in particular is focussed on Egypt. There are extremely few analyses of the ML condition regarding Egypt. This paper provides new information on this and can also be utilized by researchers to further develop the analysis and method through identification of other potentially relevant variables within a single country ML study.
The power of diversification: Do African fixed-income investors have a chance in Malaysian Sukuk market?
Authors: Abdulkarim Fatima Muhammad , Tabash Mosab I.
Published: November 2020

Purpose

This study investigates the presence of portfolio diversification benefits for South African, Nigerian, Ghanaian and Kenyan fixed-income investors diversifying bond portfolios in the Malaysian sovereign Sukuk market.

Design/methodology/approach

The paper uses wavelet coherence and a multivariate generalized autoregressive conditional heteroscedastic (GARCH) model. The data cover the period from September 2013 to January 2019.

Findings

The findings obtained from the wavelet coherence model reveal evidence of portfolio diversification opportunities for African fixed-income investors in the Malaysian sovereign Sukuk market. These opportunities are more significant in the short- and medium-term investment horizons than in the long-term. Also, the results of multivariate GARCH show that the Malaysian Sukuk market has a negative unconditional correlation with the South African bond market, signifying better diversification benefits for these investors.

Practical implications

The findings have implications for both fund managers and investors intending to include Sukuk in a diversified portfolio to reduce their risks and maximize their return from bonds.

Originality/value

To the best knowledge of the authors, this is the first study to examine the opportunities for African investors in the Malaysian Sukuk market.
Entrepreneurship education and sustainable development: mediating role of entrepreneurial skills
Authors: Edokpolor James Edomwonyi
Published: November 2020

Purpose

This study aims to examine the mediating role of entrepreneurial skills developed by undergraduates (ESDU) in the relationship between entrepreneurship education (EE) and the core values of sustainable development (CVSD).

Design/methodology/approach

This is a correlational study that used a structured questionnaire for quantitative data collection from 399 purposively selected Nigerian university undergraduates.

Findings

The results confirmed the statistically significant and positive mediating role of ESDU on the relationship between EE and the CVSD.

Originality/value

This study has contributed to the mediating role of ESDU in the relationship between EE and the CVSD. This interrelationship can further provide a better understanding or insights into how ESDU can help mediate the relationship between EE and the CVSD.
Are consumers loyal to genetically modified food? Evidence from Australia
Authors: Rabbanee Fazlul K. , Afroz Tanzim , Naser Mostafa Mahmud
Published: November 2020

Purpose

Genetically modified (GM) food has received considerable interest from academics and practitioners. However, research on consumer loyalty towards GM food is relatively sparse. Guided by the theory of planned behaviour, this study aims to explore the factors that influence consumer repurchase intention and behavioural loyalty towards GM food.

Design/methodology/approach

Data were collected from 464 Australian consumer panel members surveyed through a nationwide online survey, with data analysed by structural equation modelling using AMOS (v. 22.0).

Findings

The findings reveal that consumer loyalty towards GM food is influenced by the interplay between awareness of benefits and risks, situational and social influences and attitude and repurchase intention. Female consumers are found to not only possess a relatively more favourable attitude and repurchase intention, but also are more loyal towards GM food compared to male consumers. Unlike older consumers, younger consumers' loyalty towards GM food is influenced by their attitude and repurchase intention. The relevant policy implications of the findings are discussed.

Practical implications

As consumers have contrasting views about GM food, to influence their loyalty, it is important for GM food industries as well as policy makers to better understand how to address consumers' varying concerns about GM food.

Originality/value

This study offers a parsimonious model for explaining the factors that influence consumer loyalty towards GM food.