bluuebunny/crossref_metadata_2025 huggingface dataset:
Michael Denis Gale. 25 August 1943—18 July 2009
Authors: Flavell Richard B. , Snape John W.
Published: August 2020

Michael (Mike) Gale was an internationally well-known crop geneticist with a career devoted mostly to wheat genetics. However, he also studied rice, maize, pearl millet and fox millet for the benefit of agriculture in developing countries. He brought new knowledge and techniques into plant breeding that made a difference to crop improvement worldwide. Noteworthy is his team's leadership in (i) defining the genetic basis of dwarfism in wheat, the major genetic innovation underlying the previously achieved ‘green revolution’ in wheat production; (ii) expanding knowledge of ‘pre-harvest sprouting’, which occurs in many wheat varieties growing in temperate climates, which reduces their flour quality and value; (iii) developing the first comprehensive genetic maps of wheat based on isozymic and DNA-based molecular markers; and (iv) developing the comparative genetics of grasses based on the conserved order of genes on chromosome segments, consistent with the evolution of the species from a common ancestor. These discoveries had a major impact in plant genetics. His team also provided the worldwide cereal geneticists and breeding communities with technologies and genetic markers that accelerated the development of cereal genetics and facilitated more efficient plant breeding. He made major and influential contributions to international agricultural research, particularly targeted at developing countries, through his participation on international and national committees, including those of the Consultative Group for International Agricultural Research. His contribution helped to drive the international research agenda for crop genetics, plant breeding and plant science generally.
David Roderick Curtis. 3 June 1927—11 December 2017
Authors: Redman S. J. , Porter R.
Published: August 2020

David Curtis was a pioneer in the identification of excitatory and inhibitory transmitters released at synapses in the central nervous system. He made major contributions to the identification of gamma-amino butyric acid (GABA) and glycine as inhibitory transmitters released at inhibitory synapses. His work laid the foundation for the subsequent acceptance that
l
-glutamate was the major excitatory transmitter. David's scientific work led to him receiving many accolades and honours, including fellowships of the Australian Academy of Sciences and the Royal Society and a Companion of the Order of Australia.

Note: This memoir was commissioned by the
Historical Records of Australian Science
and is published here with minor amendments. It was published in June 2020 and is available at
https://doi.org/10.1071/HR19016
.
Zoogloea dura sp. nov., a N2-fixing bacterium isolated from forest soil and emendation of the genus Zoogloea and the species Zoogloea oryzae and Zoogloea ramigera
Authors: Dahal Ram Hari , Chaudhary Dhiraj Kumar , Kim Dong-Uk , Kim Jaisoo
Published: August 2020

A motile, Gram-stain-negative, rod-shaped bacterium, designated G-4-1-14T, was obtained from forest soil sampled at Gwanggyo mountain, Gyeonggi-do, Republic of Korea. Cells were colourless, aerobic, grew optimally at 28–35 °C and hydrolysed DNA and casein. Phylogenetic analysis based on its 16S rRNA gene sequence revealed that strain G-4-1-14T formed a lineage within the genus

Zoogloea

. The closest members were

Zoogloea resiniphila

ATCC 70068T (98.6 % sequence similarity),

Zoogloea caeni

EMB43T (98.2 %),

Zoogloea oryzae

A-7T (97.7 %),

Zoogloea ramigera

IAM 12136T (96.9 %) and

Zoogloea oleivorans

BucT (96.2 %). The major respiratory quinone was ubiquinone-8 and the principal polar lipids were phosphatidylethanolamine, phosphatidyl-N-methylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The predominant cellular fatty acids were summed feature 3 (iso-C15 :0 2-OH/C16  : 1
ω7c) and C16 : 0. The DNA G+C content was 65.9 mol%. The average nucleotide identity and digital DNA–DNA hybridization relatedness values between strain G-4-1-14T and other type strains were ≤81.6 and ≤24.9 %, respectively, which are below the species demarcation thresholds. Based on the results of phenotypic, phylogenetic and genomic analyses, strain G-4-1-14T represents a novel species in the genus

Zoogloea

, for which the name Zoogloea dura sp. nov. is proposed. The type strain is G-4-1-14T (=KACC 21618T=NBRC 114358T). In addition, we propose emendation of the genus

Zoogloea

and the species

Zoogloea oryzae

and

Zoogloea ramigera

.
ICTV Virus Taxonomy Profile: Finnlakeviridae
Authors: Mäntynen Sari , Laanto Elina , Sundberg Lotta-Riina , Poranen Minna M. , Oksanen Hanna M. , Report Consortium ICTV
Published: August 2020

Finnlakeviridae is a family of icosahedral, internal membrane-containing bacterial viruses with circular, single-stranded DNA genomes. The family includes the genus, Finnlakevirus, with the species, Flavobacterium virus FLiP. Flavobacterium phage FLiP was isolated with its Gram-negative host bacterium from a boreal freshwater habitat in Central Finland in 2010. It is the first described single-stranded DNA virus with an internal membrane and shares minimal sequence similarity with other known viruses. The virion organization (pseudo T=21 dextro) and major capsid protein fold (double-β-barrel) resemble those of Pseudoalteromonas phage PM2 (family Corticoviridae), which has a double-stranded DNA genome. A similar major capsid protein fold is also found in other double-stranded DNA viruses in the kingdom Bamfordvirae. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) report on the family Finnlakeviridae, which is available at ictv.global/report/finnlakeviridae.
Comprehensive genome data analysis establishes a triple whammy of carbapenemases, ICEs and multiple clinically relevant bacteria
Authors: Botelho João , Mourão Joana , Roberts Adam P. , Peixe Luísa
Published: August 2020

Carbapenemases inactivate most β-lactam antibiotics, including carbapenems, and have frequently been reported among

Enterobacteriaceae

,

Acinetobacter

spp. and

Pseudomonas

spp. Traditionally, the horizontal gene transfer of carbapenemase-encoding genes (CEGs) has been linked to plasmids. However, given that integrative and conjugative elements (ICEs) are possibly the most abundant conjugative elements among prokaryotes, we conducted an in silico analysis to ascertain the likely role of ICEs in the spread of CEGs among all bacterial genomes (n=182 663). We detected 17 520 CEGs, of which 66 were located within putative ICEs among several bacterial species (including clinically relevant bacteria, such as

Pseudomonas aeruginosa

,

Klebsiella pneumoniae

and

Escherichia coli

). Most CEGs detected within ICEs belong to the IMP, NDM and SPM metallo-beta-lactamase families, and the serine beta-lactamase KPC and GES families. Different mechanisms were likely responsible for acquisition of these genes. The majority of CEG-bearing ICEs belong to the MPFG, MPFT and MPFF classes and often encode resistance to other antibiotics (e.g. aminoglycosides and fluoroquinolones). This study provides a snapshot of the different CEGs associated with ICEs among available bacterial genomes and sheds light on the underappreciated contribution of ICEs to the spread of carbapenem resistance globally.
Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study
Authors: Ip Andrew , Ahn Jaeil , Zhou Yizhao , Goy Andre H. , Hansen Eric , Pecora Andrew L , Sinclaire Brittany A , Bednarz Urszula , Marafelias Michael , Mathura Shivam , Sawczuk Ihor S , Underwood Joseph P. , Walker David M. , Prasad Rajiv , Sweeney Robert L. , Ponce Marie G. , Capra Samuel La , Cunningham Frank J. , Calise Arthur G. , Pulver Bradley L. , Ruocco Dominic , Mojares Greggory E. , Eagan Michael P. , Ziontz Kristy L. , Mastrokyriakos Paul , Goldberg Stuart L
Published: August 2020

Background

Hydroxychloroquine has not been associated with improved survival among hospitalized COVID-19 patients in the majority of observational studies and similarly was not identified as an effective prophylaxis following exposure in a prospective randomized trial. We aimed to explore the role of hydroxychloroquine therapy in mildly symptomatic patients diagnosed in the outpatient setting.

Methods

We examined the association between outpatient hydroxychloroquine exposure and the subsequent progression of disease among mildly symptomatic non-hospitalized patients with documented SARS-CoV-2 infection. The primary outcome assessed was requirement of hospitalization. Data was obtained from a retrospective review of electronic health records within a New Jersey USA multi-hospital network. We compared outcomes in patients who received hydroxychloroquine with those who did not applying a multivariable logistic model with propensity matching.

Results

Among 1274 outpatients with documented SARS-CoV-2 infection 7.6% were prescribed hydroxychloroquine. In a 1067 patient propensity matched cohort, 21.6% with outpatient exposure to hydroxychloroquine were hospitalized, and 31.4% without exposure were hospitalized. In the primary multivariable logistic regression analysis with propensity matching there was an association between exposure to hydroxychloroquine and a decreased rate of hospitalization from COVID-19 (OR 0.53; 95% CI, 0.29, 0.95). Sensitivity analyses revealed similar associations. QTc prolongation events occurred in 2% of patients prescribed hydroxychloroquine with no reported arrhythmia events among those with data available.

Conclusions

In this retrospective observational study of SARS-CoV-2 infected non-hospitalized patients hydroxychloroquine exposure was associated with a decreased rate of subsequent hospitalization. Additional exploration of hydroxychloroquine in this mildly symptomatic outpatient population is warranted.

Lay Summary

In this observational study of 1,274 COVID-19 patients, hydroxychloroquine given as an outpatient treatment was associated with a 47% reduction in the hazard of hospitalization. Adverse events were not increased (2% QTc prolongation events, 0% arrhythmias). Further validation is required. Use of hydroxychloroquine to treat COVID-19 in the outpatient setting should be reserved for a clinical trial or after discussion with a physician regarding risks and benefits.
The analysis of the long-term impact of SARS-CoV-2 on the cellular immune system in individuals recovering from COVID-19 reveals a profound NKT cell impairment
Authors: Liu Jia , Yang Xuecheng , Wang Hua , Li Ziwei , Deng Hui , Liu Jing , Xiong Shue , He Junyi , Guo Chunxia , Wang Weixian , Zelinskyy Gennadiy , Trilling Mirko , Dittmer Ulf , Lu Mengji , Sutter Kathrin , Senff Tina , Menne Christopher , Timm Joerg , Zhang Yanfang , Deng Fei , Feng Xuemei , Lu Yinping , Wu Jun , Yang Dongliang , Wang Baoju , Zheng Xin
Published: August 2020

Thecoronavirus disease 2019(COVID-19) pandemic caused by thesevere acute respiratory syndrome coronavirus 2(SARS-CoV-2) affects millions of people and killed hundred-thousands of individuals. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remained to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19 convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2 unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of Annexin V and 7-AAD double positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies, TIM-3 expression on CD4 and CD8 T cells, as well as PD-L1 expression on B cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by GzmB expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully capable to proliferate and produce effector cytokines upon TCR stimulation. Collectively, we provide the first comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.
A CAR RNA FISH assay to study functional and spatial heterogeneity of chimeric antigen receptor T cells in tissue
Authors: Eichholz Karsten , Li Alvason Zhenhua , Diem Kurt , Jensen Michael C. , Zhu Jia , Corey Lawrence
Published: August 2020

Chimeric antigen receptor (CAR) T cells are engineered cells used in cancer therapy and are studied to treat infectious diseases. Trafficking and persistence of CAR T cells is an important requirement for efficacy to target cancer. Here, we describe a CAR RNA FISH histo-cytometry platform combined with a random reaction seed image analysis algorithm to quantitate spatial distribution and in vivo functional activity of a CAR T cell population at a single cell resolution for preclinical models. In situ, CAR T cell exhibited a heterogenous effector gene expression and this was related to the distance from tumor cells, allowing a quantitative assessment of the potential in vivo effectiveness. The platform offers the potential to study immune functions of genetically engineered cells in situ with their target cells in tissues with high statistical power and thus, can serve as an important tool for preclinical assessment of CAR T cell effectiveness.

Brief summary

We developed an imaging platform and analysis pipeline to study large populations of engineered cells at a single cell level in situ.

One Sentence Summary

We developed a CAR RNA FISH assay to study chimeric antigen receptor T cell trafficking and function in mouse tissue.
Association of Medicaid Expansion Under the Affordable Care Act with Insurance Status and Clinical Characteristics of Low-Income Patients with Newly Diagnosed Melanoma
Authors: Puri Pranav , Pittelkow Mark R. , Mi Lanyu , Mangold Aaron R.
Published: August 2020

Importance

The Affordable Care Act expanded Medicaid eligibility in participating states to individuals with incomes up to 138% of the federal poverty line. The effects of this policy on the diagnosis and treatment of melanoma in low-income populations has yet to be described.

Objective

To evaluate the effect of Medicaid expansion on changes in insurance status and clinical characteristics of low-income patients with newly diagnosed melanoma.

Design, Setting, and Participants

This cross-sectional study included patients younger than 65 with a new diagnosis of malignant melanoma from January 1, 2011 to December 31, 2016, in the US National Cancer Institute’s Surveillance Epidemiology and End Results database.

Exposures

Residence in a state that expanded Medicaid on January 1, 2014.

Main Outcomes and Measures

The primary outcomes were insurance status, melanoma staging, and overall survival.

Results

In Medicaid expansion states, there were 1,719 low-income patients with newly diagnosed melanoma during the pre-expansion time period and 1,984 (15% increase) during the post-expansion time period. In nonexpansion states, there were 326 low-income patients with newly diagnosed melanoma during the pre-expansion time period, and 288 during the post-expansion time period (12% decrease). Compared with nonexpansion states, expansion states had a significantly greater reduction in percentage of uninsured patients following Medicaid expansion (adjusted odds ratio, 6.27 [95% CI, 4.83 to 8.14]). Overall survival was not statistically different between expansion and nonexpansion states (HR, 0.89 [95% CI, 0.74 to 1.06]). There were no statistically significant differences in melanoma staging at diagnosis between the expansion and nonexpansion groups (p = 0.05).

Conclusions and Relevance

Medicaid expansion was associated with increased melanoma diagnoses in low-income patients and a decreased proportion of uninsured patients. However, our study did not identify differences in clinical outcomes associated with Medicaid expansion.

Key Points

Question

Was Medicaid expansion associated with changes in insurance status and clinical characteristics of low-income melanoma patients?

Findings

Medicaid expansion was associated with increased diagnoses of melanoma in low-income populations and reductions in the proportion of uninsured melanoma patients. However, there were no statistically significant changes in staging at diagnosis or overall survival associated with Medicaid expansion.

Meaning

Increased health insurance coverage associated with Medicaid expansion could potentially improve timely detection and treatment of melanoma for low-income populations.
SARS-CoV-2 transmission and control in a hospital setting: an individual-based modelling study
Authors: Huang Qimin , Mondal Anirban , Jiang Xiaobing , Horn Mary Ann , Fan Fei , Fu Peng , Wang Xuan , Zhao Hongyang , Ndeffo-Mbah Martial , Gurarie David
Published: August 2020

Background

Development of strategies for mitigating the severity of COVID-19 is now a top global public health priority. We sought to assess strategies for mitigating the COVID-19 outbreak in a hospital setting via the use of non-pharmaceutical interventions such as social distancing, self-isolation, tracing and quarantine, wearing facial masks/ personal protective equipment.

Methods

We developed an individual-based model for COVID-19 transmission among healthcare workers in a hospital setting. We calibrated the model using data of a COVID-19 outbreak in a hospital unit in Wuhan in a Bayesian framework. The calibrated model was used to simulate different intervention scenarios and estimate the impact of different interventions on outbreak size and workday loss.

Results

We estimated that work-related stress increases susceptibility to COVID-19 infection among healthcare workers by 52% (90% Credible Interval (CrI): 16.4% – 93.0%). The use of high efficacy facial masks was shown to be able to reduce infection cases and workday loss by 80% (90% CrI: 73.1% – 85.7%) and 87% (CrI: 80.0% – 92.5%), respectively. The use of social distancing alone, through reduced contacts between healthcare workers, had a marginal impact on the outbreak. A strict quarantine policy with the isolation of symptomatic cases and a high fraction of pre-symptomatic/ asymptomatic cases (via contact tracing or high test rate), could only prolong outbreak duration with minimal impact on the outbreak size. Our results indicated that a quarantine policy should be coupled with other interventions to achieve its effect. The effectiveness of all these interventions was shown to increase with their early implementation.

Conclusions

Our analysis shows that a COVID-19 outbreak in a hospital’s non-COVID-19 unit can be controlled or mitigated by the use of existing non-pharmaceutical measures.
Seroprevalence of anti-SARS-CoV-2 IgG antibodies in hospitalized patients at a tertiary referral center in North India
Authors: Ray Animesh , Singh Komal , Chattopadhyay Souvick , Mehdi Farha , Batra Gaurav , Gupta Aakansha , Agarwal Ayush , Bhavesh M , Sahni Shubham , Chaithra R , Agarwal Shubham , Nagpal Chitrakshi , Gagantej B H , Arora Umang , Sharma Kartikeya Kumar , Jadon Ranveer Singh , Upadhyay Ashish Datt , Nischal Neeraj , Vikram Naval K , Soneja Manish , Pandey R M , Wig Naveet
Published: August 2020

Background

Seroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate the true extent of infection in a population. However, seroprevalence studies have been scarce in South East Asia including India, which, as of now, carries the third largest burden of confirmed cases in the world. The present study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among hospitalized patients at one of the largest government hospital in India.

Method

This cross-sectional study, conducted at a tertiary care hospital in North India, recruited consecutive patients who were negative for SARS-CoV-2 by RT-PCR or CB-NAAT. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the ELISA method.

Results

A total of 212 hospitalized patients were recruited in the study with mean age (±SD) of 41.2 (±15.4) years and 55% male population. Positive serology against SARS CoV-2 was detected in 19.8% patients(95% CI 14.7-25.8). Residency in Delhi conferred a higher frequency of seropositivity 26.5% (95% CI 19.3-34.7) as compared to that of other states 8% (95% CI 3.0-16.4) with p value 0.001. No particular age groups or socio-economic strata showed a higher proportion of seropositivity.

Conclusion

Around, one-fifth of hospitalized patients, who were not diagnosed with COVID-19 before, demonstrated seropositivity against SARS-CoV-2. While there was no significant difference in the different age groups and socio-economic classes; residence in Delhi was associated with increased risk (relative risk of 3.62, 95% CI 1.59-8.21)
Impacts of K-12 school reopening on the COVID-19 epidemic in Indiana, USA
Authors: España Guido , Cavany Sean , Oidtman Rachel , Barbera Carly , Costello Alan , Lerch Anita , Poterek Marya , Tran Quan , Moore Annaliese Wieler Sean , Perkins T. Alex
Published: August 2020

In the United States, schools closed in March 2020 due to COVID-19 and began reopening in August 2020, despite continuing transmission of SARS-CoV-2. In states where in-person instruction resumed at that time, two major unknowns were the capacity at which schools would operate, which depended on the proportion of families opting for remote instruction, and adherence to face-mask requirements in schools, which depended on cooperation from students and enforcement by schools. To determine the impact of these conditions on the statewide burden of COVID-19 in Indiana, we used an agent-based model calibrated to and validated against multiple data types. Using this model, we quantified the burden of COVID-19 on K-12 students, teachers, their families, and the general population under alternative scenarios spanning three levels of school operating capacity (50%, 75%, and 100%) and three levels of face-mask adherence in schools (50%, 75%, and 100%). Under a scenario in which schools operated remotely, we projected 45,579 (95% CrI: 14,109-132,546) infections and 790 (95% CrI: 176-1680) deaths statewide between August 24 and December 31. Reopening at 100% capacity with 50% face-mask adherence in schools resulted in a proportional increase of 42.9 (95% CrI: 41.3-44.3) and 9.2 (95% CrI: 8.9-9.5) times that number of infections and deaths, respectively. In contrast, our results showed that at 50% capacity with 100% face-mask adherence, the number of infections and deaths were 22% (95% CrI: 16%-28%) and 11% (95% CrI: 5%-18%) higher than the scenario in which schools operated remotely. Within this range of possibilities, we found that high levels of school operating capacity (80-95%) and intermediate levels of face-mask adherence (40-70%) resulted in model behavior most consistent with observed data. Together, these results underscore the importance of precautions taken in schools for the benefit of their communities.
ANALYSIS OF SARS-COV-2 GENOME SEQUENCES FROM THE PHILIPPINES: GENETIC SURVEILLANCE AND TRANSMISSION DYNAMICS
Authors: Tablizo Francis A. , Lapid Carlo M. , Maralit Benedict A. , Yap Jan Michael C. , Destura Raul V. , Alejandria Marissa M. , Petronio-Santos Joy Ann , Morado El King D. , Dizon Joshua Gregor A. , Llames Jo-Hannah S. , Araiza Shiela Mae M. , Punayan Kris P. , Velasco John Mark S. , Mejia Julius Aaron , Dollete Maribell , Salamat Sonia , Tan Christina , Gabriel Kristianne Arielle D. , Fabilloren Shebna Rose D. , Demot Bernard , Genavia Shana F. , Nipales Jarvin E. , Sanchez Alessandra C. , Gaza Haifa L. , Arevalo Geraldine M. , Pangilinan Coleen M. , Acosta Shaira A. , Salinas Melanie V. , Schwem Brian E. , Dela Tonga Angelo D. , Galarion Ma. Jowina H. , Dungca Niña Theresa P. , Geganzo Stessi G. , Bascos Neil Andrew D. , Cutiongco-de la Paz Eva Maria , Saloma Cynthia P.
Published: August 2020

The spread of the corona virus around the world has spurred travel restrictions and community lockdowns to manage the transmission of infection. In the Philippines, with a large population of overseas Filipino contract workers (OFWs), as well as foreign workers in the local online gaming industry and visitors from nearby countries, the first reported cases were from a Chinese couple visiting the country in mid-January 2020. Three months on, by mid-March, the COVID-19 cases in the Philippines had reached its first 100, before it exploded to the present 178,022 cases (as of August 20, 2020). Here, we report a genomic survey of six (6) whole genomes of the SARS-CoV-2 virus collected from COVID-19 patients seen at the Philippine General Hospital, the major referral hospital for COVID-19 cases in Metro Manila at about the time the Philippines had over a hundred cases. Analysis of commonly observed variants did not reveal a clear pattern of the virus evolving towards a more infectious and severe strain. When combined with other available viral sequences from the Philippines and from GISAID, phylogenomic analysis reveal that the sequenced Philippine isolates can be classified into three primary groups based on collection dates and possible infection sources: (1) January samples collected in the early phases of the pandemic that are closely associated with isolates from Wuhan, China; (2) March samples that are mainly linked to the M/V Diamond Princess Cruise Ship outbreak; and (3) June samples that clustered with European isolates, one of which already harbor the globally prevalent D614G mutation which initially circulated in Europe. The presence of community-acquired viral transmission amidst compulsory and strict quarantine protocols, particularly for repatriated Filipino workers, highlights the need for a refinement of the quarantine, testing, and tracing strategies currently being implemented to adapt to the current pandemic situation.
Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination
Authors: Elias George , Meysman Pieter , Bartholomeus Esther , De Neuter Nicolas , Keersmaekers Nina , Suls Arvid , Jansens Hilde , Souquette Aisha , De Reu Hans , Smits Evelien , Lion Eva , Thomas Paul G. , Mortier Geert , Van Damme Pierre , Beutels Philippe , Laukens Kris , Van Tendeloo Viggo , Ogunjimi Benson
Published: August 2020

Antigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts. In this study, we use high-throughput sequencing of memory CD4 TCRβ repertoire and machine learning to show that individuals with preexisting vaccine-reactive memory CD4 T cell clonotypes elicited earlier and higher antibody titers and mounted a more robust CD4 T cell response to hepatitis B vaccine. In addition, integration of TCRβ sequence patterns into a hepatitis B vaccine specific model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination.
BDNF/TrkB signaling endosomes in axons coordinate CREB/mTOR activation and protein synthesis in the cell body to induce dendritic growth in cortical neurons
Authors: Moya-Alvarado Guillermo , Guerra Miguel V. , Wu Chengbiao , Mobley William C. , Perlson Eran , Bronfman Francisca C
Published: August 2020

Brain-derived neurotrophic factor (BDNF) and its receptors tyrosine kinase receptor B (TrkB) and the p75 neurotrophin receptor (p75) are the primary regulators of dendritic growth in the central nervous system (CNS). After being bound by BDNF, TrkB and p75 are endocytosed into endosomes and continue signaling within the cell soma, dendrites, and axons. We studied the functional role of BDNF axonal signaling in cortical neurons derived from different transgenic mice using compartmentalized cultures in microfluidic devices. We found that axonal BDNF increased dendritic growth from the neuronal cell body in a cAMP response element-binding protein (CREB)-dependent manner. These effects were dependent on axonal TrkB but not p75 activity. Dynein-dependent BDNF-TrkB-containing endosome transport was required for long-distance induction of dendritic growth. Axonal signaling endosomes increased CREB and mTOR kinase activity in the cell body, and this increase in the activity of both proteins was required for general protein translation and the expression of Arc, a plasticity-associated gene, indicating a role for BDNF-TrkB axonal signaling endosomes in coordinating the transcription and translation of genes whose products contribute to learning and memory regulation.
Mask Wearing and Control of SARS-CoV-2 Transmission in the United States
Authors: Rader Benjamin , White Laura F. , Burns Michael R. , Chen Jack , Brilliant Joe , Cohen Jon , Shaman Jeffrey , Brilliant Larry , Hawkins Jared B. , Scarpino Samuel V. , Astley Christina M. , Brownstein John S.
Published: August 2020

Introduction

Cloth face coverings and surgical masks have become commonplace across the United States in response to the SARS-CoV-2 epidemic. While evidence suggests masks help curb the spread of respiratory pathogens, research is limited. Face masks have quickly become a topic of public debate as government mandates have started requiring their use. Here we investigate the association between self-reported mask wearing, social distancing and community SARS-CoV-2 transmission in the United States, as well as the effect of statewide mandates on mask uptake.

Methods

Serial cross-sectional surveys were administered June 3 through July 27, 2020 via web platform. Surveys queried individuals’ likelihood to wear a face mask to the grocery store or with family and friends. Responses (N=378,207) were aggregated by week and state and combined with measures of the instantaneous reproductive number (Rt), social distancing proxies, respondent demographics and other potential sources of confounding. We fit multivariate logistic regression models to estimate the association between mask wearing and community transmission control (Rt <1) for each state and week. Multiple sensitivity analyses were considered to corroborate findings across mask wearing definitions, Rt estimators and data sources. Additionally, mask wearing in 12 states was evaluated two weeks before and after statewide mandates.

Results

We find an upward trend in mask usage across the U.S., although uptake varies by geography and demographic groups. A multivariate logistic model controlling for social distancing and other variables found a 10% increase in mask wearing was associated with a 3.53 (95% CI: 2.03, 6.43) odds of transmission control (Rt <1). We also find that communities with high mask wearing and social distancing have the highest predicted probability of a controlled epidemic. These positive associations were maintained across sensitivity analyses. Segmented regression analysis of mask wearing found no statistical change following mandates, however the positive trend of increased mask wearing over time was preserved.

Conclusion

Widespread utilization of face masks combined with social distancing increases the odds of SARS-CoV-2 transmission control. Mask wearing rose separately from government mask mandates, suggesting supplemental public health interventions are needed to maximize mask adoption and disrupt the spread of SARS-CoV-2, especially as social distancing measures are relaxed.
SARS-CoV-2 specific memory B cells frequency in recovered patient remains stable while antibodies decay over time
Authors: Vaisman-Mentesh A. , Dror Y. , Tur-Kaspa R. , Markovitch D. , Kournos Tatiana , Dicker D. , Wine Y.
Published: August 2020

The breadth of the humoral immune response following SARS-CoV-2 infection was indicated to be important for recovery from COVID-19. Recent studies have provided valuable insights regarding the dynamics of the antibody response in symptomatic COVID-19 patients. However, the information regarding the dynamics of the serological and cellular memory in COVID-19 recovered patients in scarce. It is imperative to determine the persistence of humoral memory in COVID-19 recovered patients as it will help to evaluate the susceptibility of recovered patients to re-infection. Here, we describe the dynamics of both the SARS-CoV-2 specific serological and B cell response in COVID-19 recovered patients. We found that symptomatic SARS-CoV-2 patients mount a robust antibody response following infection however, the serological memory decays in recovered patients over the period of 6 months. On the other hand, the B cell response as observed in the SARS-CoV-2 specific memory B cell compartment, was found to be stable over time. Moreover, the frequency of SARS-CoV-2 specific B cell plasmablasts was found to be associated with the SARS-CoV-2 specific antibody levels. These data, suggests that the differentiation of short-lived plasmablasts to become long-lived plasma cells is impaired and the main contributor of antibody production are the short-lived plasmablasts.

Overall, our data provides insights regarding the humoral memory persistence in recovered COVID-19 patients. Notwithstanding the insights from this study, it is still to be determined if the persistence of SARS-CoV-2 memory B cells can be considered as a correlate of protection in the absence of serological memory.
Impact of nonpharmaceutical governmental strategies for prevention and control of COVID-19 in São Paulo State, Brazil
Authors: Fortaleza Cristiane Ravagnani , Vilches Thomas Nogueira , Berg de Almeida Gabriel , Ferreira Claudia Pio , Grotto Rejane Maria Tommasini , Guimarães Raul Borges , Souza Lenice do Rosário de , Fortaleza Carlos Magno Castelo Branco
Published: August 2020

Interrupted time series analyses (ITSA) were performed to measure the impact of social distancing policies (instituted 22/03/2020) and subsequent mandatory masking in the community (instituted 04/05/2020) on the incidence and effective reproductive number (Rt) of COVID-19 in São Paulo State, Brazil. Overall, the impact of social distancing both on incidence and Rt was greater than the incremental effect of mandatory masking. Those findings may reflect either a small impact of face masking or the loosening of social distancing after mandatory use of masks.
Epidemiologically most successful SARS-CoV-2 variant: concurrent mutations in RNA-dependent RNA polymerase and spike protein
Authors: Ilmjärv Sten , Abdul Fabien , Acosta-Gutiérrez Silvia , Estarellas Carolina , Galdadas Ioannis , Casimir Marina , Alessandrini Marco , Gervasio Francesco Luigi , Krause Karl-Heinz
Published: August 2020

The D614G mutation of the Spike protein is thought to be relevant for SARS-CoV-2 infection. Here we report biological and epidemiological aspects of this mutation. Using pseudotyped lentivectors, we were able to confirm that the G614 variant of the Spike protein is markedly more infectious than the ancestral D614 variant. We demonstrate by molecular modelling that the replacement of aspartate by glycine in position 614 facilitates the transition towards an open state of the Spike protein. To understand whether the increased infectivity of the D614 variant explains its epidemiological success, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. There was no significant correlation between reported COVID mortality in different countries and the prevalence of the Wuhan versus G/L variant. However, when comparing the speed of emergence and the ultimate predominance in individual countries, the G/L variant displays major epidemiological supremacy. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase (RdRp), is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2.
Bayesian Estimation of the Seroprevalence of Antibodies to SARS-CoV-2
Authors: Dong Qunfeng , Gao Xiang
Published: August 2020

Accurately estimating the seroprevalence of antibodies to SARS-CoV-2 requires the use of appropriate methods. Bayesian statistics provides a natural framework for considering the variabilities of specificity and sensitivity of the antibody tests, as well as for incorporating prior knowledge of viral infection prevalence. We present a full Bayesian approach for this purpose, and we demonstrate the utility of our approach using a recently published large-scale dataset from the U.S. CDC.
Antiviral activity of lambda-carrageenan against influenza viruses in mice and severe acute respiratory syndrome coronavirus 2in vitro
Authors: Jang Yejin , Shin Heegwon , Lee Myoung Kyu , Kwon Oh Seung , Shin Jin Soo , Kim Yongil , Kim Meehyein
Published: August 2020

Influenza virus and coronavirus, belonging to enveloped RNA viruses, are major causes of human respiratory diseases. The aim of this study was to investigate the broad spectrum antiviral activity of a naturally existing sulfated polysaccharide, lambda-carrageenan (λ-CGN), purified from marine red algae. Cell culture-based assays revealed that the macromolecule efficiently inhibited both influenza A and B viruses, as well as currently circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with EC50values ranging from 0.3–1.4 μg/ml. No toxicity to host cells was observed at concentrations up to 300 μg/ml. Plaque titration and western blot analysis verified that λ-CGN reduced expression of viral proteins in cell lysates and suppressed progeny virus production in culture supernatants in a dose-dependent manner. This polyanionic compound exerts antiviral activity by targeting viral attachment to cell surface receptors and preventing entry. Moreover, intranasal administration to mice during influenza A viral challenge not only alleviated infection-mediated reductions in body weight but also protected 60% of mice from virus-induced mortality. Thus, λ-CGN could be a promising antiviral agent for preventing infection by several respiratory viruses.
Training Infrastructure as a Service
Authors: Rasche Helena , Grüning Björn
Published: August 2020

Background

Hands-on training, whether it is in Bioinformatics or other scientific domains, requires significant resources and knowledge to setup and run. Trainers must have access to infrastructure that can support the sudden spike in usage, with classes of 30 or more trainees simultaneously running resource intensive tools. For efficient classes, the jobs must run quickly, without queuing delays, lest they disrupt the timetable set out for the class. Often times this is achieved via running on a private server where there is no contention for the queue, and therefore no or minimal waiting time. However, this requires the teacher or trainer to have the technical knowledge to manage compute infrastructure, in addition to their didactic responsibilities. This presents significant burdens to potential training events, in terms of infrastructure cost, person-hours of preparation, technical knowledge, and available staff to manage such events.

Findings

Galaxy Europe has developed Training Infrastructure as a Service (TIaaS) which we provide to the scientific commnuity as a service built on top of the Galaxy Platform. Training event organisers request a training and Galaxy administrators can allocate private queues specifically for the training. Trainees are transparently placed in a private queue where their jobs run without delay. Trainers access the dashboard of the TIaaS Service and can remotely follow the progress of their trainees without in-person interactions.

Conclusions

TIaaS on Galaxy Europe provides reusable and fast infrastructure for Galaxy training. The instructor dashboard provides visibility into class progress, making in-person trainings more efficient and remote training possible. In the past 24 months, > 110 trainings with over 3000 trainees have used this infrastructure for training, across scientific domains, all enjoying the accessibility and reproducibility of Galaxy for training the next generation of bioinformaticians. TIaaS itself is an extension to Galaxy which can be deployed by any Galaxy administrator to provide similar benefits for their users.https://galaxyproject.eu/tiaas
Drosophilamacrophage self-renewal is regulated by transient expression of PDGF- and VEGF-related factor 2
Authors: Bakopoulos Daniel , Whisstock James C. , Warr Coral G. , Johnson Travis K.
Published: August 2020

Macrophages are an ancient animal blood cell lineage critical for tissue homeostasis and defence against pathogens. Until recently, their numbers were thought to be sustained solely by specialised hematopoietic organs. It is now clear that many macrophages are instead replenished by self-renewal, yet the signals that regulate this remain poorly understood. InDrosophila melanogaster, macrophages (known as plasmatocytes) undergo a phase of rapid population expansion via self-renewal, makingDrosophilaan attractive model for revealing the signals and regulatory mechanisms involved. However, no central self-renewal pathway has been identified inDrosophila. Here, we investigated the PDGF-/VEGF-receptor pathway as a candidate for playing this role. Analysis of larvae deficient for each of the three PDGF-/VEGF-receptor ligands Pvf1-3 revealed Pvf2 as a major driver of macrophage self-renewal inDrosophila. We further found that only a small proportion of blood cells expressPvf2, and knockdown experiments implicate these cells as a major source ofPvf2in self-renewal. Lineage tracing studies support the idea thatPvf2expression in blood cells occurs transiently throughout the macrophage self-renewal period, and in response to an as yet unidentified cue. These data define the regulation ofPvf2expression in blood cells as a central mechanism by which macrophage self-renewal is controlled. Given the strong parallels that exist betweenDrosophilaand vertebrate macrophage systems, it is likely that similar mechanisms are at play across animal phyla.
Avalanche criticality in individuals, fluid intelligence and working memory
Authors: Xu Longzhou , Yu Lianchun , Feng Jianfeng
Published: August 2020

The critical brain hypothesis suggests that efficient neural computation can be realized through dynamics of the brain characterized by scale-free avalanche activities. However, the relation between human cognitive performance and the avalanche criticality in large-scale brain networks remains unclear. In this study, we analyzed the mean synchronization and synchronization entropy of blood oxygenation level signals from resting-state fMRI. We found that the scale-free avalanche activity was associated with intermediate synchronization and maximal synchronization entropy. The complexity of functional connectivity, as well as structure-function coupling, is maximized by criticality, which is consistent with theoretical predictions. We observed order-disorder phase transitions in resting-state brain dynamics and found that there were longer times spent in the subcritical regime. These results support the hypothesis that large-scale brain networks lie in the vicinity of a critical point. Finally, we showed evidence that the neural dynamics of human participants with higher fluid intelligence and working memory scores are closer to criticality. We identified brain regions whose critical dynamics showed significant positive correlations with fluid intelligence performance, and found these regions were located in the prefrontal cortex and inferior parietal cortex, which are believed to be important nodes of brain networks underlying human intelligence. Our results reveal the role that avalanche criticality plays in cognitive performance, and provide a simple method to identify the critical point and map cortical states on a spectrum of neural dynamics, ranging from subcriticality to supercriticality.
On the diversity of F420-dependent oxidoreductases: a sequence- and structure-based classification
Authors: Mascotti María Laura , Ayub Maximiliano Juri , Fraaije Marco W.
Published: August 2020

The F420deazaflavin cofactor is an intriguing molecule as it structurally resembles the canonical flavin cofactor, although biochemically behaves as a nicotinamide cofactor. Since its discovery, numerous enzymes relying on it have been described. The known deazaflavoproteins are taxonomically restricted to Archaea and Bacteria. The biochemistry of the deazaflavoenzymes is diverse and they exhibit some degree of structural variability as well. In this study a thorough sequence and structural homology evolutionary analysis was performed in order to generate an overarching classification of all known F420-dependent oxidoreductases. Five different superfamilies are described: Superfamily I, TIM-barrel F420-dependent enzymes; Superfamily II, Rossmann fold F420-dependent enzymes; Superfamily III, β-roll F420-dependent enzymes; Superfamily IV, SH3 barrel F420-dependent enzymes and Superfamily V, 3 layer ββα sandwich F420-dependent enzymes. This classification aims to be the framework for the identification, the description and the understanding the biochemistry of novel deazaflavoenzymes.
Tumor genotype dictates radiosensitization afterAtmdeletion in brainstem gliomas
Authors: Deland Katherine M. , Starr Bryce F. , Mercer Joshua S. , Byemerwa Jovita , Crabtree Donna M. , Williams Nerissa T. , Luo Lixia , Ma Yan , Chen Mark , Becher Oren J. , Kirsch David G.
Published: August 2020

Diffuse intrinsic pontine glioma (DIPG) kills more children than any other type of brain tumor. Despite clinical trials testing many chemotherapeutic agents, radiotherapy remains the standard treatment. Here, we utilized Cre/loxP technology to show that deletingAtaxia telangiectasia mutated(Atm) in primary mouse models of DIPG can enhance tumor radiosensitivity. Genetic deletion ofAtmimproved survival of mice withp53deficient but notp53wild-type gliomas following radiotherapy. Similar to patients with DIPG, mice withp53wild-type tumors had improved survival after radiotherapy independent ofAtmdeletion.p53wild-type tumor cell lines induced proapoptotic genes after radiation and repressed the NRF2 target,Nqo1. Tumors lackingp53andInk4a/Arfexpressed the highest level ofNqo1and were most resistant to radiation, but deletion ofAtmenhanced the radiation response. These results suggest that tumor genotype may determine whether inhibition of ATM during radiotherapy will be an effective clinical approach to treat DIPGs.