bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-based reclassification of Paenibacillus panacisoli DSM 21345T as Paenibacillus massiliensis subsp. panacisoli subsp. nov. and description of Paenibacillus massiliensis subsp. massiliensis subsp. nov.
Authors: Tonial Fabiana , Guella Felipe , Passaglia Luciane Maria Pereira , Sant’Anna Fernando Hayashi
Published: July 2020

Bacteria of the genus

Paenibacillus

are relevant to humans, animals and plants. The species

Paenibacillus massiliensis

and

Paenibacillus panacisoli

are Gram-stain-positive and endospore-forming bacilli isolated from a blood culture of a leukemia patient and from soil of a ginseng field, respectively. Comparative analyses of their 16S rRNA genes revealed that the two

Paenibacillus

species could be synonyms (99.3% sequence identity). In the present study we performed different genomic analyses in order to evaluate the phylogenetic relationship of these micro-organisms.

Paenibacillus massiliensis

DSM 16942T and

P. panacisoli

DSM 21345T presented a difference in their G+C content lower than 1 mol%, overall genome relatedness index values higher than the species circumscription thresholds (average nucleotide identity, 95.57 %; genome-wide ANI, =96.51 %; and orthologous ANI, 96.25 %), and a monophyletic grouping pattern in the phylogenies of the 16S rRNA gene and the proteome core. Considering that these strains present differential biochemical capabilities and that their computed digital DNA–DNA hybridization value is lower than the cut-off for bacterial subspecies circumscription, we suggest that each of them form different subspecies of

P. massiliensis

,

Paenibacillus massiliensis

subsp. panacisoli subsp. nov. (type strain DSM 21345T) and

Paenibacillus massiliensis

subsp. massiliensis subsp. nov. (type strain DSM 16942T).
Sequential 3D OrbiSIMS and LESA-MS/MS-based metabolomics for prediction of brain tumor relapse from sample-limited primary tissue archives
Authors: Meurs Joris , Scurr David J. , Lourdusamy Arockia , Storer Lisa C.D. , Grundy Richard G. , Alexander Morgan R. , Rahman Ruman , Kim Dong-Hyun
Published: July 2020

We present here a novel surface mass spectrometry strategy to perform untargeted metabolite profiling of formalin-fixed paraffin-embedded (FFPE) pediatric ependymoma archives. Sequential Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) and liquid extraction surface analysis-tandem MS (LESA-MS/MS) permitted the detection of 887 metabolites (163 chemical classes) from pediatric ependymoma tumor tissue microarrays (diameter <1 mm; thickness: 4 μm). From these 163 classes, 60 classes were detected with both techniques, whilst LESA-MS/MS and 3D OrbiSIMS individually allowed the detection of another 83 and 20 unique metabolite classes, respectively. Through data fusion and multivariate analysis, we were able to identify key metabolites and corresponding pathways predictive of tumor relapse which were retrospectively confirmed using gene expression analysis with publicly available data. Altogether, this sequential mass spectrometry strategy has shown to be a versatile tool to perform high throughput metabolite profiling on sample-limited tissue archives.

Abstract Figure

For Table of Contents Only
Is population anxiety associated with COVID-19 related hospitalizations and deaths? A study protocol
Authors: Feys Frederik , Naser Abdallah
Published: July 2020

Abstract

BACKGROUND

The nocebo effect is any harmful reaction following a negative suggestion. Anxiety can be seen as a manifestation of a nocebo context. The psychological stress of the COVID-19 pandemic led some people to experience COVID-19 symptoms, which were not actually related to a COVID-19 infection. A fundamental goal during the COVID-19 pandemic is to limit the COVID-19 related demand on healthcare systems and to minimize COVID-19 related deaths. This exploratory study aims to determine to what extent the anxiety in the population is related to the number of covid-19 related hospitalizations and deaths.

METHODS

We will quantify the magnitude of the relationship between population anxiety and hospitalizations / deaths. Anxiety will be assessed using the results of the most frequently used anxiety measuring scale. Official websites of governments will be screened to determine hospitalizations and deaths.

Studies will be included if they had at least 100 respondents, used a validated anxiety scale, reported on the general population of a country, and were conducted during the Covid-19 pandemic. A search strategy will take into account the limited resources for this study and will be used to search Pubmed, MedRXiv and PsychRXiv. Screening will take place at two levels: abstracts and titles, followed by full text reports. One researcher will extract data which will be double checked by a second researcher.

We will perform weighted OLS regression to quantify the relationship of anxiety and covid-19 related hospitalizations / deaths.

DISCUSSION

Covid-19 related measures can carry a significant social cost and risk of unwanted effects; it is therefore important to assess the extent to which anxiety in the population is related to covid-19 related hospitalizations or deaths. If anxiety can be properly reduced in the population, health care will be safeguarded. Thus, any strategy that reduces anxiety can then be included in evidence-based decision making.
The properties of hot household hygroscopic materials and their potential use for non-medical facemask decontamination
Authors: Andreola Marie-Line , Becquart Fréderic , Jomaa Wahbi , Verhoeven Paul O. , Baldacchino Gérard , Hemour Simon , consortium D-Mask
Published: July 2020

The wide use of facemasks through the population to prevent SARS-CoV-2 virus transmission, and its resulting mis- or even non-decontamination are challenging the management of the epidemic at a large scale. As a complement to machine-wash that wastes significant amount of water and energy, hot hygroscopic materials could be used to decontaminate non-medical facemasks in household settings. We report the inactivation of a viral load on a facial mask for an exposure of 15 minutes, with the combined effect of heat and humidity under a decaying pattern suggesting straight-forward general public deployment towards a reliable implementation by the population.
A Contact-Explicit Covid-19 Epidemic and Response Assessment Model
Authors: Getz Wayne M. , Vissat Ludovica Luisa , Salter Richard
Published: July 2020

We formulate a refined SEIR epidemic model that explicitly includes a contact class C that either thwarts pathogen invasion and returns to the susceptible class S or progresses successively through latent, asymptomatic, and symptomatic classes L, A, and I. Individuals in both A and I may go directly to an immune class V, and in I to a dead class D. We extend this SCLAIV formulation by including a set of drivers that can be used to develop policy to manage current Covid-19 and similar type disease outbreaks. These drivers include surveillance, social distancing (rate and efficacy), social relaxation, quarantining (linked to contact tracing), patient treatment/isolation and vaccination processes, each of which can be represented by a non-negative constant or an s-shaped switching flow. The latter are defined in terms of onset and switching times, initial and final values, and abruptness of switching. We built a Covid-19NMB-DASA web app to generate both deterministic and stochastic solutions to our SCLAIV and drivers model and use incidence and mortality data to provide both maximum-likelihood estimation (MLE) and Bayesian MCMC fitting of parameters. In the context of South African and English Covid-19 incidence data we demonstrate how to both identify and evaluate the role of drivers in ongoing outbreaks. In particular, we show that early social distancing in South Africa likely averted around 80,000 observed cases (actual number is double if only half the cases are observed) during the months of June and July. We also demonstrated that incidence rates in South Africa will increase to between a conservative estimate of 15 and 30 thousand observed cases per day (at a 50% surveillance level) by the end of August if stronger social distancing measures are not effected during July and August, 2020. On different a note, we show that comparably good local MLE fits of the English data using surveillance, social distancing and social relaxation drivers can represent very different kinds of outbreaks—one with close to 90% and another with under 8% immune individuals. This latter result provides a cautionary tale of why fitting SEIR-like models to incidence or prevalence data can be extremely problematic when not anchored by other critical measures, such as levels of immunity in the population. Our presentation illustrates how our SCLAIV formulation can be used to carry out forensic and scenario analyses of disease outbreaks such as Covid-19 in well defined regions.
Early Repolarization Pattern is Associated with Schizophrenia: A Single Center Experience in Japan
Authors: Kameyama Hiroshi , Sugimoto Kenichi , Inamura Keisuke , Itoh Kyoko , Kodaka Fumitoshi , Matsuda Yuki , Nukariya Kazutaka , Kato Tomohiro , Shigeta Masahiro
Published: July 2020

Introduction

Recent studies have shown a high frequency of abnormal electrocardiograms in patients with schizophrenia. The objective of this study was to associate schizophrenia diagnoses with early repolarization patterns in a sample of hospitalized patients from a single hospital in Japan.

Methods

We conducted a retrospective age, sex and coronary risk factors matched case-control study on 85 patients with schizophrenia and 89 controls from medical checkups. First, we compared the presence of early repolarization patterns in both groups. Secondly, we elucidated an association between the presence of an early repolarization pattern and clinical findings in the patients’ groups. We also evaluated J-point elevation patterns.

Results

As a result, we found that both early repolarization patterns and J-point elevation patterns observed were significantly higher in the schizophrenic group than in the matched control group (early repolarization pattern 23;6 P < 0.001; J-point elevation pattern 34:12; P = 0.001). After multivariable logistic regression among the patients and controls, schizophrenia was the independent predictor for early repolarization pattern (P = 0.001) and J-point elevation (P < 0.001). Among the patients, the independent predictor for early repolarization pattern was psychiatric family history (P = 0.006), while older age (P = 0.038) and psychiatric family history (P = 0.014) were predictors for J-point elevation patterns.

Conclusion

These findings suggest that an association between early repolarization pattern or J-point elevation pattern and schizophrenia in a single Japanese center.
Epidemiological aspects of COVID-19 disease in India during nationwide lockdown phase-An empirical data-based analysis and its implications on interrupting the transmission
Authors: Perumal Vanamail
Published: July 2020

Background

Covid-19 disease is pandemic in more than 85% of the countries in the world, with about 10 million cases and 0.5 million deaths as on July 2, 2020. In India reporting of the first case was on January 30, 2020, and to prevent rapid community spread of the disease nationwide lockdown phase was imposed from March 25- June 1, 2020. Our objective was to assess various epidemiological measures during the lockdown phase.

Methods

We used daily reporting of confirmed cases by the Ministry of Health and Family Welfare, Government of India during the period March 19-June 1, 2020. Using statistical packages STATA and R-packages, we fitted three statistical distributions (Gamma, Weibull and Log-normal) to the daily recorded new cases. We estimated daily incidence rate and death rate per million population, generation time and Basic Reproduction numbers.

Results

During the lockdown phase, the daily per cent increase in the cumulative number of cases showed negative exponential growth with 0.022 as an instantaneous rate of decrease. The average incidence rate with a 95% confidence interval (CI) was 1.84 (1.43-2.25). Day specific incidence rate per million (revealed the exponential pattern with 0.069 as the instantaneous rate of increase per day, which accounted for the doubling time of the disease (10 days; 95% CI: 9.25-10.93). Case fatality rate (2.92%; 95% CI: 2.82% −3.02%) and overall death rate was 1.14 (95% CI: 0.87-1.41) per million. were abysmally low. Statistical distribution fitting of new cases found to be satisfactory with Gamma distribution. Basic reproduction numbers 1.83 (95% CI: 1.82-1.83) was less.

Conclusion

In India, with a population density of about 450 per Km2, the virulent of COVID-19 transmission was interrupted significantly with 70 days lockdown during the early transmission stage. We observed a considerable decline in all the epidemiological indices compared to the corresponding indices recorded during the same period in the severely affected countries.
Development of a simplein vitroassay to identify and evaluate nucleotide analogs against SARS-CoV-2 RNA-dependent RNA polymerase
Authors: Lu Gaofei , Zhang Xi , Zheng Weinan , Sun Jialei , Hua Lan , Xu Lan , Chu Xin-jie , Ding Sheng , Xiong Wen
Published: July 2020

Nucleotide analogs targeting viral RNA polymerase have been approved to be an effective strategy for antiviral treatment and are attracting antiviral drugs to combat the current SARS-CoV-2 pandemic. In this report, we develop a robustin vitrononradioactive primer extension assay to evaluate the incorporation efficiency of nucleotide analog by SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) quantitively. Our results show that many nucleotide analogs can be incorporated into RNA by SARS-CoV-2 RdRp, and that the incorporation of some of them leads to chain termination. The discrimination values of nucleotide analog over those of natural nucleotide were measured to evaluate the incorporation efficiency of nucleotide analog by RdRp. We found that the incorporation efficiency of Remdesivir-TP is higher than ATP, and we did not observe chain termination or delayed chain termination caused by single Remdesivir-TP incorporation, while multiple incorporations of Remdesivir-TP caused chain termination in our assay condition. The incorporation efficiency of Ribavirin-TP and Favipiravir-TP is very low either as ATP or GTP analogs, which suggested that mutagenesis may not be the mechanism of action of those two drugs against SARS-CoV-2. Incorporation of Sofosbuvir-TP is also very low suggesting that sofosbuvir may not be very effective in treating SARS-CoV-2 infection. As a comparison, 2’-C-Methyl-GTP can be incorporated into RNA efficiently, and the derivative of 2’-C-Methyl-GTP may have therapeutic application in treating SARS-CoV-2 infection. This report provides a simple screening method that should be useful in evaluating nucleotide-based drugs targeting SARS-CoV-2 RdRp, and for studying the mechanism of action of selected nucleotide analog.
Loss ofNupr1promotes engraftment by tuning the quiescence threshold of hematopoietic stem cell repository via regulating p53-checkpoint pathway
Authors: Wang Tongjie , Xia Chengxiang , Weng Qitong , Wang Kaitao , Dong Yong , Hao Sha , Dong Fang , Liu Xiaofei , Liu Lijuan , Geng Yang , Guan Yuxian , Du Juan , Cheng Tao , Cheng Hui , Wang Jinyong
Published: July 2020

Hematopoietic stem cells (HSCs) are dominantly quiescent under homeostasis, which is a key mechanism of maintaining the HSC pool for life-long hematopoiesis. Dormant HSCs poise to be immediately activated on urgent conditions and can return to quiescence after regaining homeostasis. To date, the molecular networks of regulating the threshold of HSC dormancy, if exist, remain largely unknown. Here, we unveiled that deletion ofNupr1, a gene preferentially expressed in HSCs, activated the quiescence HSCs under homeostatic status, which conferred engraftment competitive advantage on HSCs without compromising their stemness and multi-lineage differentiation abilities in serial transplantation settings. Following an expansion protocol, theNupr1-/-HSCs proliferate more robustly than their wild type counterpartsin vitro. Nupr1inhibits the expression of p53 and the rescue of which offsets the engraftment advantage. Our data unveil thede novorole ofNupr1as an HSC quiescence-regulator, which provides insights into accelerating the engraftment efficacy of HSC transplantation by targeting the HSC quiescence-controlling network.
Piezo1 potentially mediates inflammation in balloon-inflated rat brain and its bidirectional mechanosensitivity
Authors: Zhang Yichi , Wang Gang , Xie Minjie , Lian Lifei , Xiong Yongjie , Xu Feng , Li Guo , Tang Zhouping , Wang Furong , Zhu Suiqiang
Published: July 2020

Brain injury after intracerebral hemorrhage is extremely complicated, and the exact mechanism remains puzzling. Piezo1, a novel mammalian mechanosensitive ion channel, has been identified to play important roles in several pathologic and physiologic procedures that involve cellular mechanotransduction. However, the role of Piezo1 in hematoma compression after intracerebral hemorrhage is still unclear. In the present study, we established a balloon-inflated rat brain model mimicking the pure mechanical compression of a hematoma and detected balloon compression in the basal ganglia region of the brain, resulting in abnormal behaviors and a significant increase in the expression of Piezo1 and proinflammatory cytokines. These effects were reversed by GsMTx4, an antagonist of Piezo1. Additionally, the balloon deflation time affected behavioral function and the levels of Piezo1 and proinflammatory cytokines. These results establish the firstin vivoevidence for the role of Piezo1 in blood-brain neuroinflammation after hematoma compression. Piezo1 may therefore be a potential therapeutic target for the treatment of intracerebral hemorrhage.
Interactive effects of aging and aerobic capacity on energy metabolism-related metabolites of serum, skeletal muscle, and white adipose tissue
Authors: Zhuang Haihui , Karvinen Sira , Zhang Xiaobo , Ojanen Xiaowei , Törmakangas Timo , Velagapudi Vidya , Alen Markku , Britton Steven L. , Koch Lauren G. , Kainulainen Heikki , Cheng Sulin , Wiklund Petri
Published: July 2020

Aerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging and their interaction on metabolism, we utilized rat models of low and high intrinsic aerobic capacity (LCRs/HCRs) and assessed the metabolomics of serum, muscle, and white adipose tissue (WAT). We compared LCRs and HCRs at two time points: Young rats were sacrificed at 9 months, and old rats were sacrificed at 21 months. Targeted and semi-quantitative metabolomics analysis was performed on ultra-pressure Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS) platform. Interaction of aerobic capacity and aging was studied via regression analysis. Our results showed at young age, metabolites linked to amino acid metabolism differed in serum and muscle with aerobic capacity, whereas no difference were observed in WAT. In aged animals, most prominent changes in metabolites occurred in WAT. Aerobic capacity and aging interactively affected seven metabolites linked to energy metabolism. Our results support previous findings that high aerobic capacity is associated with more efficient amino acid metabolism in muscle. While impaired branched chain amino acids (BCAAs) and fatty acid metabolism in the muscle may associate to the high risk of metabolic disorders and shorter lifespan previously observed in LCRs. The interactive effects of aging and aerobic capacity on energy metabolism-related metabolites were largely driven by HCRs, reflecting the importance of inherited aerobic capacity in the aging process. Our results highlight that dysfunctional mitochondrial β-oxidation in WAT may be one key mechanism related to aging.
A genomic link in China roses: and they all lived prickly but water deficient ever after?
Authors: Zhong Mi-Cai , Jiang Xiao-Dong , Yang Guo-Qian , Cui Wei-Hua , Suo Zhi-Quan , Wang Wei-Jia , Sun Yi-Bo , Wang Dan , Cheng Xin-Chao , Li Xu-Ming , Dong Xue , Tang Kai-Xue , Li De-Zhu , Hu Jin-Yong
Published: July 2020

Prickles act against herbivores, pathogens or mechanical injury, while also prevent water loss. However, whether prickles have new function and the molecular genetics of prickle patterning remains poorly explored. Here, we generated a high-quality reference genome assembly for ‘Basye’s Thornless’ (BT), a prickle-free cultivar ofRosa wichuraiana,to identify genetic elements related to stem prickle development. The BT genome harbors a high level of sequence diversity in itself and between cultivar ‘Old Blush’ (R. chinensis), a founder genotype in rose domestication. Inheritance of stem prickle density was determined and two QTL were identified. Differentially expressed genes in QTL were involved in water-related functions, suggesting that prickle density may hitchhike with adaptations to moist environments. While the prickle-related gene-regulatory-network (GRN) was highly conserved, the expression variation of key candidate genes was associated with prickle density. Our study provides fundamental resources and insights for genome evolution in the Rosaceae. Ongoing efforts on identification of the molecular bases for key rose traits may lead to the improvement of horticultural markets.
Probabilistic approaches for classifying highly variable anti-SARS-CoV-2 antibody responses
Authors: Dopico Xaquin C , Hanke Leo , Sheward Daniel J. , Muschiol Sandra , Aleman Soo , Grinberg Nastasiya F. , Adori Monika , Christian Murray , Vidakovics Laura Perez , Kim Changil , Khoenkhoen Sharesta , Pushparaj Pradeepa , Morro Ainhoa Moliner , Mandolesi Marco , Ahl Marcus , Forsell Mattias , Coquet Jonathan , Corcoran Martin , Rorbach Joanna , Dillner Joakim , Bogdanovic Gordana , McInerney Gerald M. , Allander Tobias , Murrell Ben , Wallace Chris , Albert Jan , Karlsson Hedestam Gunilla B.
Published: July 2020

Antibody responses vary widely between individuals1, complicating the correct classification of low-titer measurements using conventional assay cut-offs. We found all participants in a clinically diverse cohort of SARS-CoV-2 PCR+ individuals (n=105) – and n=33 PCR+ hospital staff – to have detectable IgG specific for pre-fusion-stabilized spike (S) glycoprotein trimers, while 98% of persons had IgG specific for the receptor-binding domain (RBD). However, anti-viral IgG levels differed by several orders of magnitude between individuals and were associated with disease severity, with critically ill patients displaying the highest anti-viral antibody titers and strongest in vitro neutralizing responses. Parallel analysis of random healthy blood donors and pregnant women (n=1,000) of unknown serostatus, further demonstrated highly variable IgG titers amongst seroconverters, although these were generally lower than in hospitalized patients and included several measurements that scored between the classical 3 and 6SD assay cut-offs. Since the correct classification of seropositivity is critical for individual- and population-level metrics, we compared different probabilistic algorithms for their ability to assign likelihood of past infection. To do this, we used tandem anti-S and -RBD IgG responses from our PCR+ individuals (n=138) and a large cohort of historical negative controls (n=595) as training data, and generated an equal-weighted learner from the output of support vector machines and linear discriminant analysis. Applied to test samples, this approach provided a more quantitative way to interpret anti-viral titers over a large continuum, scrutinizing measurements overlapping the negative control background more closely and offering a probability-based diagnosis with potential clinical utility. Especially as most SARS-CoV-2 infections result in asymptomatic or mild disease, these platform-independent approaches improve individual and epidemiological estimates of seropositivity, critical for effective management of the pandemic and monitoring the response to vaccination.
Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome
Authors: Pandolfi Laura , Fossali Tommaso , Frangipane Vanessa , Bozzini Sara , Morosini Monica , D’Amato Maura , Lettieri Sara , Urtis Mario , Di Toro Alessandro , Saracino Laura , Percivalle Elena , Tomaselli Stefano , Cavagna Lorenzo , Cova Emanuela , Mojoli Francesco , Bergomi Paola , Ottolina Davide , Lilleri Daniele , Corsico Angelo Guido , Arbustini Eloisa , Colombo Riccardo , Meloni Federica
Published: July 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. We conducted a prospective study to assess deep lung inflammatory status in patients with moderate to severe COVID-19.

Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n=28) and to the Intermediate Medicine Ward (IMW) (n=5). We analyze the differential cell count, ultrastructure of cells and Interleukin(IL)6, 8 and 10 levels.

ICU patients showed a marked increase in neutrophils (72%, 60-81), lower lymphocyte (8%, 4-12) and macrophages fractions (17%, 11-27) compared to IMW patients (3%, 2-17, 15%, 6-26 and 74%, 58-90, respectively) (p<0.01). Ultrastructural study from ICU patients showed viral-like particles in cytopathic mononuclear cells however extensive cytopathic damage in all cell lineages. Immunostaining with anti-viral capsid and spike antibodies specifically immunoreacted with BAL cells, mostly cytopathic ones. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p<0.01, IL8 p<0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p<0.1) or antivirals (p<0.05).

Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome.
Assessing the effects of non-pharmaceutical interventions on SARS-CoV-2 transmission in Belgium by means of an extended SEIQRD model and public mobility data
Authors: Alleman Tijs W. , Vergeynst Jenna , De Visscher Lander , Rollier Michiel , Torfs Elena , Nopens Ingmar , Baetens Jan M.
Published: July 2020

We present a compartmental extended SEIQRD metapopulation model for SARS-CoV-2 spread in Belgium. We demonstrate the robustness of the calibration procedure by calibrating the model using incrementally larger datasets and dissect the model results by computing the effective reproduction number at home, in workplaces, in schools, and during leisure activities. We find that schools are an important transmission pathway for SARS-CoV-2, with the potential to increase the effective reproduction number from Re = 0.66 ± 0.04 (95 % CI) to Re = 1.09 ± 0.05 (95 % CI) under lockdown measures. The model accounts for the main characteristics of SARS-CoV-2 transmission and COVID-19 disease and features a detailed representation of hospitals with parameters derived from a dataset consisting of 22 136 hospitalized patients. Social contact during the pandemic is modeled by scaling pre-pandemic contact matrices with Google Community Mobility data and with effectivity-of-contact parameters inferred from hospitalization data. The calibrated social contact model with its publically available mobility data, although coarse-grained, is a readily available alternative to social-epidemiological contact studies under lockdown measures, which were not available at the start of the pandemic.
The psychological impact of ‘mild lockdown’ in Japan during the COVID-19 pandemic: a nationwide survey under a declared state of emergency
Authors: Yamamoto Tetsuya , Uchiumi Chigusa , Suzuki Naho , Yoshimoto Junichiro , Murillo-Rodriguez Eric
Published: July 2020

This study examined the psychological distress caused by non-coercive lockdown (mild lockdown) in Japan. An online survey was conducted with 11,333 people (52.4% women; mean age = 46.3 ± 14.6 years, range = 18-89 years) during the mild lockdown in the seven prefectures most affected by COVID-19 infection. Over one-third (36.6%) of participants experienced mild-to-moderate psychological distress (Kessler Psychological Distress Scale [K6] score 5-12), while 11.5% reported serious psychological distress (K6 score ≥ 13). The estimated prevalence of depression (Patient Health Questionnaire-9 score ≥ 10) was 17.9%. Regarding the distribution of K6 scores, the proportion of individuals displaying psychological distress in this study was significantly higher compared to previous national survey data from 2010, 2013, 2016 and 2019. Healthcare workers, those with a history of treatment for mental illness, and younger participants (aged 18-19 or 20-39 years) were particularly vulnerable. Psychological distress severity was influenced by specific interactional structures of risk factors: high loneliness, poor interpersonal relationships, COVID-19-related sleeplessness and anxiety, deterioration of household economy, and work and academic difficulties. Flexible approaches that are optimised for the difficulties specific to each individual through cross-disciplinary public-private initiatives are important to combat lockdown-induced mental health problems.
Multisectoral collaboration for pandemic response and operational support of critical care and emergency departments
Authors: Christofferson RC , O’Neal Hollis R. , Jagneaux Tonya , O’Neal Catherine , Walsh Christine S. , Mayton E. Handly , Vu Luan D. , Fish Abigail I. , Phan Anh , Stoufflet Thaya E. , Schroeder Jonathan R. , Walker Morgan , Turner Erik A. , Pierce Christi G. , Wester K. Scott , DeLeo Connie , Tenreiro Edgardo , Ogden Beverly W. , Cormier Stephania A.
Published: July 2020

Background

In March 2020, an influx of admissions in COVID-19 positive patients threatened to overwhelm healthcare facilities in East Baton Rouge Parish, Louisiana. Exacerbating this problem was a shortage of diagnostic testing capability, resulting in a delay in time-to-result return. An improvement in diagnostic testing availability and timeliness was necessary to improve the allocation of resources and ultimate throughput of patients. The management of a COVID-19 positive patient or patient under investigation requires infection control measures that can quickly consume personal protective equipment (PPE) stores and personnel available to treat these patients. Critical shortages of both PPE and personnel also negatively impact care in patients admitted with non-COVID-19 illnesses.

Methods

A multisectoral partnership of healthcare providers, facilities and academicians created a molecular diagnostic lab within an academic research facility dedicated to testing inpatients and healthcare personnel for SARS-CoV-2. The purpose of the laboratory was to provide a temporary solution to the East Baton Rouge Parish healthcare community until individual facilities were self-sustaining in testing capabilities. We describe the partnership and the impacts of this endeavor by developing a model derived from a combination of data sources, including electronic health records, hospital operations, and state and local resources.

Findings

Our model demonstrates two important principles: the impact of reduced turnaround times (TAT) on potential differences in inpatient population numbers for COVID-19 and savings in PPE attributed to the more rapid TAT.

Interpretation

Overall, we provide rationale for and demonstration of the utility of multisectoral partnerships when responding to public health emergencies.
Calm on the surface, dynamic on the inside. Molecular homeostasis in response to regulatory and metabolic perturbation ofAnabaenasp. PCC 7120 nitrogen metabolism
Authors: Perin Giorgio , Fletcher Tyler , Sagi-Kiss Virag , Gaboriau David C. A. , Carey Mathew R. , Bundy Jacob G. , Jones Patrik R.
Published: July 2020

Nitrogen is a key macro-nutrient required for the metabolism and growth of biological systems. Although multiple nitrogen sources can serve this purpose, they are all converted into ammonium/ammonia as a first step of assimilation. It is thus reasonable to expect that molecular parts involved in the transport of ammonium/ammonia across biological membranes (i.e. catalysed by AMT transporters) connect with the regulation of both nitrogen and central carbon metabolism. In order to test this hypothesis, we applied both (1) genetic (i.e. Δamtmutation) and (2) environmental treatments to a target biological system, the cyanobacterium Anabaena sp. PCC 7120. Cyanobacteria have a key role in the global nitrogen cycle and thus represent a useful model system. The aim was to both (1) perturb sensing and low-affinity uptake of ammonium/ammonia and (2) induce multiple inner N states, followed by targeted quantification of key proteins, metabolites and enzyme activities, with experiments intentionally designed over a longer time-scale than the available studies in literature. We observed that the absence of AMT transporters triggered a substantial response at a whole-system level, affecting enzyme activities and the quantity of both proteins and metabolites, spanning both N and C metabolism. Moreover, the absence of AMT transporters left a molecular fingerprint indicating N-deficiency even under N replete conditions (i.e. greater GS activity, lower 2-OG content and faster nitrogenase activation upon N deprivation). Contrasting with all of the above dynamic adaptations was the striking near-complete lack of any externally measurable phenotype (i.e. growth, photosynthesis, pigments, metabolites). We thus conclude that this species evolved a highly robust and adaptable molecular network to maintain homeostasis, resulting in substantial internal but minimal external perturbations. The analytical data highlights several internal adaptations, including increased N assimilation (i.e. greater GS activity) and nitrogenase activity (i.e. faster activation upon N deprivation) together with altered amino acids metabolism, as indicated by changes in Gln, Glu and 2-OG, indicating an altered C/N balance. The analyses provides evidence for an active role of AMT transporters in the regulatory/signalling network of N metabolism in this biological system, and the existence of a novel fourth IF7A-independent regulatory mechanism controlling GS activity.
The enrichment of breakpoints in late-replicating chromatin provides novel insights into chromoanagenesis mechanisms
Authors: Chatron Nicolas , Giannuzzi Giuliana , Rollat-Farnier Pierre-Antoine , Diguet Flavie , Porcu Eleonora , Yammine Tony , Uguen Kevin , Bellil Zohra-Lydia , Zillhardt Julia Lauer , Sorlin Arthur , Ader Flavie , Afenjar Alexandra , Andrieux Joris , Bardel Claire , Calpena Eduardo , Chantot-Bastaraud Sandra , Callier Patrick , Chelloug Nora , Chopin Emilie , Cordier Marie-Pierre , Dubourg Christèle , Faivre Laurence , Girard Françoise , Heide Solveig , Herenger Yvan , Jaillard Sylvie , Keren Boris , Knight Samantha J. L. , Lespinasse James , Lohmann Laurence , Marle Nathalie , Maroofian Reza , Masurel-Paulet Alice , Mathieu-Dramard Michèle , Metay Corinne , Pagnamenta Alistair T. , Portnoï Marie-France , Prieur Fabienne , Rio Marlène , Siffroi Jean-Pierre , Valence Stéphanie , Taylor Jenny C. , Wilkie Andrew O. M. , Edery Patrick , Reymond Alexandre , Sanlaville Damien , Schluth-Bolard Caroline
Published: July 2020

The rise of pangenomic molecular assays allowed uncovering complex rearrangements namedchromoanagenesisthat were hypothesized to result from catastrophic shattering events. Constitutional cases have typically been reported individually preventing identification of common features and uncovering the mechanisms at play. We characterized 20 newchromoanagenesisand discovered yet undescribed features. While literature differentiateschromothripsisand its shattering event repaired through non-homologous end joining fromchromoanasynthesisborn to aberrant replicative processes, we identified shattered chromosomes repaired through a combination of mechanisms. In particular, three samples present with “rearrangement hubs” comprising a fragmented kilobase-long sequence threaded throughout the rearrangement.

To assess the mechanisms at play, we merged our data with those of 20 published constitutional complex chromosomal rearrangement cases. We evaluated if the distribution of their 1032 combined breakpoints was distinctive using bootstrap simulations and found that breakpoints tend to keep away from haplosensitive genes suggesting selective pressure. We then compared their distribution with that of 13,310 and 468 breakpoints of cancer complex chromosomal rearrangements and constitutional simple rearrangement samples, respectively. Both complex rearrangement groups showed breakpoint enrichment in late replicating regions suggesting similar origins for constitutional and cancer cases. Simple rearrangement breakpoints but not complex ones were depleted from lamina-associated domains (LADs), possibly as a consequence of reduced mobility of DNA ends bound to lamina.

The enrichment of breakpoints in late-replicating chromatin for both constitutional and cancerchromoanagenesisprovides an orthogonal support to the premature chromosome condensation hypothesis that was put forward to explainchromoanagenesis.
Delineation of a molecularly distinct terminally differentiated memory CD8 T cell population
Authors: Milner J. Justin , Nguyen Hongtuyet , Omilusik Kyla , Reina-Campos Miguel , Tsai Matthew , Toma Clara , Delpoux Arnaud D. , Boland Brigid S. , Hedrick Stephen M. , Chang John T. , Goldrath Ananda W.
Published: July 2020

Memory CD8 T cells provide durable protection against diverse intracellular pathogens and can be broadly segregated into distinct circulating and tissue-resident populations. Paradigmatic studies have demonstrated circulating memory cells can be further divided into effector memory (Tem) and central memory (Tcm) populations based on discrete functional characteristics. Following resolution of infection, we identified a persisting antigen-specific CD8 T cell population that was simultaneously terminally-fated with potent effector function but maintained memory T cell qualities and conferred robust protection against reinfection. Notably, this terminally-differentiated effector memory CD8 T cell population (terminal-Tem) was conflated within the conventional Tempopulation, prompting redefinition of the classical characteristics of Temcells. Murine terminal-Temwere transcriptionally, functionally, and developmentally unique compared to Temcells. Through mass cytometry and single-cell RNAseq analyses of human peripheral blood from healthy individuals, we also identified an analogous terminal-Tempopulation of CD8 T cells that was transcriptionally distinct from Temand Tcm. A key finding of this study was that parsing of terminal-Temfrom conventionally defined Temchallenges classical characteristics of Tembiology, including enhanced presence in lymphoid tissues, robust IL-2 production and recall potential, greater than expected homeostatic fitness, refined transcription factor dependencies, and a distinct molecular phenotype. Classification of terminal-Temand clarification of Tembiology hold broad implications for understanding the molecular regulation of memory cell states and harnessing immunological memory to improve immunotherapies.
ADAM protease inhibition overcomes resistance of breast cancer stem-like cells to γδ T cell immunotherapy
Authors: Dutta Indrani , Dieters-Castator Dylan , Papatzimas James W. , Medina Anais , Schueler Julia , Derksen Darren J. , Lajoie Gilles , Postovit Lynne-Marie , Siegers Gabrielle M.
Published: July 2020

Breast cancer stem cells (BCSC) are highly resistant to current therapies, and are responsible for metastatic burden and relapse. Gamma delta T cells (γδTc) are immunosurveillance cells with tremendous anti-tumoral activity, and a growing number of clinical trials have confirmed the safety of γδTc immunotherapy for various malignancies. Herein, we demonstrate that γδTc can kill BCSC, but to a lesser extent than non-cancer stem cells (NSC). Immune evasion was orchestrated by several mechanisms. The BCSC secretome rendered γδTc hypo-responsive by reducing proliferation, cytotoxicity and IFN-γ production, while increasing expression of co-inhibitory receptors on γδTc. BCSC and target cells surviving γδTc cytotoxicity had higher PD-L1 co-inhibitory ligand expression, and blocking PD-1 on γδTc significantly overcame BCSC resistance to γδTc killing. Fas/FasL signaling was dysfunctional in BCSC due to upregulation of the anti-apoptotic protein MCL-1, which could be partially overcome using dMCL1-2, an MCL-1 degrader. Moreover, the BCSC fraction shed higher levels of the NKG2D ligand MICA compared to NSC. Inhibiting MICA shedding using the ADAM inhibitor GW280264X overcame BCSC resistance to γδTc killing, rendering BCSC as sensitive to γδTc cytotoxicity as NSC. Collectively, our data unravel multiple mechanisms exploited by BCSC to evade γδTc killing, which may also come into play in BCSC resistance to other cytotoxic lymphocytes. Developing strategies to overcome this resistance will increase the efficacy of cancer immunotherapy and lead to improved outcomes for cancer patients.

One Sentence Summary

Breast cancer stem-like cells are resistant to γδ T cell targeting, which can be overcome by inhibiting ADAM proteases that facilitate MICA/B shedding.
Time-dependent inhibition of covert shift of attention
Authors: Buonocore Antimo , Dietze Niklas , McIntosh Robert D.
Published: July 2020

Visual transients can interrupt overt orienting by abolishing the execution of a planned eye movement due about 90 ms later, a phenomenon known as saccadic inhibition (SI). It is not known if the same inhibitory process might influence covert orienting in the absence of saccades, and consequently alter visual perception. In Experiment 1 (n=14), we measured orientation discrimination during a covert orienting task in which an uninformative exogenous visual cue preceded the onset of an oriented probe by 140 to 290 ms. In half of the trials the onset of the probe was accompanied by a brief irrelevant flash, a visual transient that would normally induce SI. We report a time-dependent inhibition of covert orienting in which the irrelevant flash impaired orientation discrimination accuracy when the probe followed the cue by 190 and 240 ms. The interference was more pronounced when the cue was incongruent with the probe location, suggesting an impact on the reorienting component of the attentional shift. In Experiment 2 (n=12), we tested whether the inhibitory effect of the flash could occur within an earlier time range, or only within the later, reorienting range. We presented probes at congruent cue locations in a time window between 50 to 200 ms. Similarly to Experiment 1, discrimination performance was altered at 200 ms after the cue. We suggest that covert attention may be susceptible to similar inhibitory mechanisms that generate SI, especially in later stages of attentional shifting (> 200ms after a cue), typically associated with reorienting.
Biodiversity and niche partitioning in an anaerobic benzene degrading culture
Authors: Melkonian Chrats , Fillinger Lucas , Atashgahi Siavash , da Rocha Ulisses Nunes , Kuiper Esther , Olivier Brett , Braster Martin , Gottstein Willi , Helmus Rick , Parsons John , Smidt Hauke , van der Waals Marcelle , Gerritse Jan , Brandt Bernd W , Molenaar Douwe , van Spanning Rob
Published: July 2020

A key question in microbial ecology is what the driving forces behind the persistence of large biodiversity in natural environments are. We studied a microbial community with more than 100 different types of species which evolved in a 15-years old bioreactor with benzene as the main carbon and free energy source and nitrate as the electron acceptor. We demonstrate that only a few community members are able to degrade benzene, and that most of the others feed on the metabolic left-overs or on the contents of dead cells making up a food web with different trophic levels. As a result of niche partitioning, a high species richness is maintained and the complexity of a natural community is stabilized in a relatively simple environment. This view highlights the importance of species interactions and interdependencies, which drive microbial community structure and function. These mechanisms may well be conserved across ecosystems.
Transcriptional Signatures of Synaptic Vesicle Genes Define Myotonic Dystrophy Type I Neurodegeneration
Authors: Jimenez-Marin Antonio , Diez Ibai , Labayru Garazi , Sistiaga Andone , Sepulcre Jorge , Lopez de Munain Adolfo , Cortes Jesus M.
Published: July 2020

Despite significant research, the biological mechanisms underlying the brain degeneration in Myotonic Dystrophy Type I (DM1) remain largely unknown. Here we have assessed brain degeneration by measuring the volume loss (VL) and cognitive deficits (CD) in two cohorts of DM1 patients, and associating them to the large-scale brain transcriptome maps provided by the Allen Human Brain Atlas (AHBA). From a list of preselected hypothesis-driven genes, three of them appear to play a major role in degeneration: dystrophin (DMD), alpha-synuclein (SNCA)and the microtubule-associated protein tau (MAPT). Moreover, a purely data-driven strategy identified gene clusters enriched for key biological processes in the central nervous system, such as synaptic vesicle recycling, localization, endocytosis and exocytosis, and the serotonin and dopamine neurotransmitter pathways. Therefore, by combining large-scale transcriptome interactions with brain imaging and cognitive function, we provide a new more comprehensive understanding of DM1 that might help define future therapeutic strategies and research into this condition.