bluuebunny/crossref_metadata_2025_split huggingface dataset:
Durability of mRNA-1273-induced antibodies against SARS-CoV-2 variants
Authors: Pegu Amarendra , O’Connell Sarah , Schmidt Stephen D , O’Dell Sijy , Talana Chloe A. , Lai Lilin , Albert Jim , Anderson Evan , Bennett Hamilton , Corbett Kizzmekia S. , Flach Britta , Jackson Lisa , Leav Brett , Ledgerwood Julie E. , Luke Catherine J. , Makowski Mat , Roberts Paul C. , Roederer Mario , Rebolledo Paulina A. , Rostad Christina A. , Rouphael Nadine G. , Shi Wei , Wang Lingshu , Widge Alicia T. , Yang Eun Sung ,   the mRNA-1273 Study Group, Beigel John H. , Graham Barney S. , Mascola John R , Suthar Mehul S. , McDermott Adrian , Doria-Rose Nicole A. 
Published: May 2021

AbstractSARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, and the durability of such responses has not been previously reported. Here, we present a comprehensive assessment of the impact of variants B.1.1.7, B.1.351, P.1, B.1.429, and B.1.526 on binding, neutralizing, and ACE2-blocking antibodies elicited by the vaccine mRNA-1273 over seven months. Cross-reactive neutralizing responses were rare after a single dose of mRNA-1273. At the peak of response to the second dose, all subjects had robust responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of mRNA-1273. Across all assays, B.1.351 had the greatest impact on antibody recognition, and B.1.1.7 the least. These data complement ongoing studies of clinical protection to inform the potential need for additional boost vaccinations.One-Sentence SummaryMost mRNA-1273 vaccinated individuals maintained binding and functional antibodies against SARS-CoV-2 variants for 6 months.
A large majority of awake hippocampal sharp-wave ripples feature spatial trajectories with momentum
Authors: Krause Emma L. , Drugowitsch Jan 
Published: May 2021

AbstractDuring periods of rest, hippocampal place cells feature bursts of activity called sharp-wave ripples (SWRs). Heuristic approaches to their analysis have revealed that a small fraction of SWRs appear to “simulate” trajectories through the environment—called awake hippocampal replay—while the functional role of a majority of these SWRs remains unclear. Applying a novel probabilistic approach to characterize the spatio-temporal dynamics embedded in SWRs, we instead show that almost all SWRs of foraging rodents simulate such trajectories through the environment. Furthermore, these trajectories feature momentum, that is, inertia in their velocities, that mirrors the animals’ natural movement. This stands in contrast to replay events during sleep which seem to follow Brownian motion without such momentum. Lastly, interpreting the replay trajectories in the context of navigational planning revealed that similar past analyses were biased by the heuristic SWR sub-selection. Overall, our approach provides a more complete characterization of the spatio-temporal dynamics within SWRs, highlights qualitative differences between sleep and awake replay, and ought to support future, more detailed, and less biased analysis of the role of awake replay in navigational planning.
Introduction of Surface Loops as a Tool for Encapsulin Functionalization
Authors: Michel-Souzy Sandra , Hamelmann Naomi M. , Zarzuela-Pura Sara , Paulusse Jos M. J. , Cornelissen Jeroen J. L. M. 
Published: May 2021

ABSTRACTEncapsulin based protein cages are nanoparticles with different biomedical applications, such as targeted drug delivery or imaging agents. These particles are biocompatible and can be produced in bacteria, allowing large scale production and protein engineering. In order to use these bacterial nanocages in different applications, it is important to further explore the potential of their surface modification and optimize their production. In this study we design and show new surface modifications of the Thermotoga maritima (Tm) and Brevibacterium linens (Bl) encapsulins. Two new loops on Tm encapsulin with a His-tag insertion after the residue 64 and the residue 127, and the modification of the C-terminal on Bl encapsulin, are reported. The multi-modification of the Tm encapsulin enables up to 240 different functionalities on the cage surface, resulting from 4 potential modifications per protein subunit. We furthermore report an improved protocol giving a better stability and providing a notable increase of the production yield of the cages. Finally, we tested the stability of different encapsulin variants over a year and the results show a difference in stability arising from the tag insertion position. These first insights in the structure-property relationship of encapsulins, with respect to the position of a function loop, allow for further study of the use of these protein nanocages in biomedical applications.Abstract Figure
Rapid Screening of COVID-19 Disease Directly from Clinical Nasopharyngeal Swabs using the MasSpec Pen Technology
Authors: Garza Kyana Y. , Silva Alex Ap. Rosini , Rosa Jonas R. , Keating Michael F. , Povilaitis Sydney C. , Spradlin Meredith , Sanches Pedro H. Godoy , Moura Alexandre Varão , Gutierrez Junier Marrero , Lin John Q. , Zhang Jialing , DeHoog Rachel J. , Bensussan Alena , Badal Sunil , Cardoso Danilo , Garcia Pedro Henrique Dias , de Oliveira Negrini Lisamara Dias , Antonio Marcia Ap. , Canevari Thiago C. , Eberlin Marcos N. , Tibshirani Robert , Eberlin Livia S. , Porcari Andreia M. 
Published: May 2021

AbstractThe outbreak of COVID-19 has created an unprecedent global crisis. While PCR is the gold standard method for detecting active SARS-CoV-2 infection, alternative high-throughput diagnostic tests are of significant value to meet universal testing demands. Here, we describe a new design of the MasSpec Pen technology integrated to electrospray ionization (ESI) for direct analysis of clinical swabs and investigate its use for COVID-19 screening. The redesigned MasSpec Pen system incorporates a disposable sampling device refined for uniform and efficient analysis of swab tips via liquid extraction directly coupled to a ESI source. Using this system, we analyzed nasopharyngeal swabs from 244 individuals including symptomatic COVID-19 positive, symptomatic negative, and asymptomatic negative individuals, enabling rapid detection of rich lipid profiles. Two statistical classifiers were generated based on the lipid information aquired. Classifier 1 was built to distinguish symptomatic PCR-positive from asymptomatic PCR-negative individuals, yielding cross-validation accuracy of 83.5%, sensitivity of 76.6%, and specificity of 86.6%, and validation set accuracy of 89.6%, sensitivity of 100%, and specificity of 85.3%. Classifier 2 was built to distinguish symptomatic PCR-positive patients from negative individuals including symptomatic PCR-negative patients with moderate to severe symptoms and asymptomatic individuals, yielding a cross-validation accuracy of 78.4% accuracy, specificity of 77.21%, and sensitivity of 81.8%. Collectively, this study suggests that the lipid profiles detected directly from nasopharyngeal swabs using MasSpec Pen-ESI MS allows fast (under a minute) screening of COVID-19 disease using minimal operating steps and no specialized reagents, thus representing a promising alternative high-throughput method for screening of COVID-19.
Liquid-Liquid Phase Separation Protects Amyloidogenic and Aggregation-Prone Peptides in Heterologous Expression Systems
Authors: Gabryelczyk Bartosz , Philips Margaret , Low Kimberly , Venkatraman Anandalakshmi , Kannaian Bhuvaneswari , Alag Reema , Linder Markus , Pervushin Konstantin , Miserez Ali 
Published: May 2021

ABSTRACTStudying pathogenic effects of amyloids requires homogeneous amyloidogenic peptide samples. Recombinant production of these peptides is challenging due to their susceptibility to aggregation and chemical modifications. Thus, chemical synthesis is primarily used to produce amyloidogenic peptides suitable for high resolution structural studies. Here, we exploited the shielded environment of protein condensates formed via liquid-liquid phase separation (LLPS) as a protective mechanism against premature aggregation. We designed a fusion protein tag undergoing LLPS in E. coli and linked it to highly amyloidogenic peptides, including Aβ amyloid. We find that the fusion proteins form membraneless organelles during overexpression and remain soluble. We also developed a facile purification method of functional Aβ peptides free of chromatography steps. The strategy exploiting LLPS can be applied to other amyloidogenic, hydrophobic, and repetitive peptides that are otherwise difficult to produce.
Specific bacterial cell wall components influence the stability of Coxsackievirus B3
Authors: Dhalech Adeeba H. , Fuller Tara D. , Robinson Christopher M. 
Published: May 2021

AbstractEnteric viruses infect the mammalian gastrointestinal tract and lead to significant morbidity and mortality worldwide. Data indicate that enteric viruses can utilize intestinal bacteria to promote viral replication and pathogenesis. However, the precise interactions between enteric viruses and bacteria are unknown. Here we examined the interaction between bacteria and Coxsackievirus B3, an enteric virus from the picornavirus family. We found that bacteria enhance the infectivity of Coxsackievirus B3 (CVB3) in vitro. Notably, specific bacteria are required as gram-negative Salmonella enterica, but not Escherichia coli, enhanced CVB3 infectivity and stability. Investigating the cell wall components of both S. enterica and E. coli revealed that structures in the O-antigen or core of lipopolysaccharide, a major component of the gram-negative bacterial cell wall, were required for S. enterica to enhance CVB3. To determine if these requirements were necessary for similar enteric viruses, we investigated if S. enterica and E. coli enhanced infectivity of poliovirus, another enteric virus in the picornavirus family. We found that, in contrast to CVB3, these bacteria enhanced the infectivity of poliovirus in vitro. Overall, these data indicate that distinct bacteria enhance CVB3 infectivity and stability, and specific enteric viruses may have differing requirements for their interactions with specific bacterial species.ImportancePrevious data indicate that several enteric viruses utilize bacteria to promote intestinal infection and viral stability. Here we show that specific bacteria and bacterial cell wall components are required to enhance infectivity and stability of Coxsackievirus B3 in vitro. These requirements are likely enteric virus-specific as the bacteria for CVB3 differs from poliovirus, a closely related virus. Therefore, these data indicate that specific bacteria and their cell wall components dictate the interaction with various enteric viruses in distinct mechanisms.
Zika virus infection of pregnant Ifnar1−/− mice triggers strain-specific differences in fetal outcomes
Authors: Bohm Ellie K. , Vangorder-Braid Jennifer T. , Jaeger Anna S. , Moriarty Ryan V. , Baczenas John J. , Bennett Natalie C. , O’Connor Shelby L. , Fritsch Michael K. , Fuhler Nicole A. , Noguchi Kevin K. , Aliota Matthew T. 
Published: May 2021

ABSTRACTZika virus (ZIKV) is a flavivirus that causes a constellation of adverse fetal outcomes collectively termed Congenital Zika Syndrome (CZS). However, not all pregnancies exposed to ZIKV result in an infant with apparent defects. During the 2015-2016 American outbreak of ZIKV, CZS rates varied by geographic location. The underlying mechanisms responsible for this heterogeneity in outcomes have not been well defined. Therefore, we sought to characterize and compare the pathogenic potential of multiple Asian/American-lineage ZIKV strains in an established Ifnar1−/− pregnant mouse model. Here, we show significant differences in the rate of fetal demise following maternal inoculation with ZIKV strains from Puerto Rico, Panama, Mexico, Brazil, and Cambodia. Rates of fetal demise broadly correlated with maternal viremia but were independent of fetus and placenta virus titer, indicating that additional underlying factors contribute to fetus outcome. Our results, in concert with those from other studies, suggest that subtle differences in ZIKV strains may have important phenotypic impacts. With ZIKV now endemic in the Americas, greater emphasis needs to be placed on elucidating and understanding the underlying mechanisms that contribute to fetal outcome.IMPORTANCEZika virus (ZIKV) actively circulates in 89 countries and territories around the globe. ZIKV infection during pregnancy is associated with adverse fetal outcomes including birth defects, microcephaly, neurological complications, and even spontaneous abortion. Rates of adverse fetal outcomes vary between regions, and not every pregnancy exposed to ZIKV results in birth defects. Not much is known about how or if the infecting ZIKV strain is linked to fetal outcomes. Our research provides evidence of phenotypic heterogeneity between Asian/American-lineage ZIKV strains and provides insight into the underlying causes of adverse fetal outcomes. Understanding ZIKV strain-dependent pathogenic potential during pregnancy and elucidating underlying causes of diverse clinical sequelae observed during human infections is critical to understanding ZIKV on a global scale.
Human norovirus infection of primary B cells triggers immune activationin vitro
Authors: Mirabelli Carmen , Jones Melissa K. , Young Vivienne , Kolawole Abimbola O. , Owusu Irene , Shan Mengrou , Abuaita Basel , Grigorova Irina , Lundy Steven K. , Lyssiotis Costas A. , Ward Vernon K. , Karst Stephanie M. , Wobus Christiane E. 
Published: May 2021

AbstractHuman norovirus (HNoV) is a global health and socio-economic burden, estimated to infect every individual at least five times during their lifetime. The underlying mechanism for the potential lack of long-term immune protection from HNoV infections is not understood and prompted us to investigate HNoV susceptibility of primary human B cells and its functional impact. Primary B cells isolated from whole-blood were infected with HNoV-positive stool samples and harvested 3 days post infection (dpi) to assess viral RNA yield by RT-qPCR. A 3-18 fold increase in HNoV RNA yield was observed in 50-60% donors. Infection was further confirmed in B cells derived from splenic and lymph node biopsies. Next, we characterized infection of whole-blood derived B cells by flow cytometry in specific functional B cell subsets (naïve CD27-IgD+, memory switched CD27+IgD-, memory unswitched CD27+IgD+and double-negative CD27-IgD-). While susceptibility of subsets was similar, we observed changes in B cell subsets distribution upon infection that were recapitulated after treatment with HNoV virus-like particles and mRNA encoding for HNoV NS1-2 protein. Importantly, treatment of immortalized BJAB B cell lines with the predicted recombinant NS1 protein triggered cell proliferation, increased ATP production, and induced metabolic changes, as detected by means of CFSE/Ki67 staining, seahorse analysis and metabolomics, respectively. These data demonstrate the susceptibility of primary B cells to HNoV infection and suggest that the secreted NS1 protein affects B cell function, proliferation and metabolismin vitro, which could have implications for viral pathogenesis and immune responsein vivo.ImportanceHuman norovirus (HNoV) is the most prevalent causative agent of gastroenteritis worldwide. Infection results in a self-limiting disease that can become chronic and severe in the immunocompromised, elderly and infants. There are currently no approved therapeutic and preventative strategies to limit the health and socio-economic burden associated with HNoV infections. Moreover, HNoV does not elicit life-long immunity as repeat infections are common, presenting a challenge for vaccine development. Given the importance of B cells for humoral immunity, we investigated susceptibility and impact of HNoV infection on human B cells. We found that HNoV replicates in human primary B cells derived from blood, spleen and lymph nodes specimens and induces functional changes in B cells, mediated in part by the non-structural protein NS1. Because of the secreted nature of NS1, we put forward the hypothesis that HNoV infection can modulate bystander B cell function with potential implications in systemic immune response.
Potent neutralization of SARS-CoV-2 variants of concern by an antibody with a unique genetic signature and structural mode of spike recognition
Authors: Kramer Kevin J. , Johnson Nicole V. , Shiakolas Andrea R. , Suryadevara Naveenchandra , Periasamy Sivakumar , Raju Nagarajan , Williams Jazmean K. , Wrapp Daniel , Zost Seth J. , Holt Clinton M. , Hsieh Ching-Lin , Sutton Rachel E. , Paulo Ariana , Davidson Edgar , Doranz Benjamin J. , Crowe James E. , Bukreyev Alexander , Carnahan Robert H. , McLellan Jason S. , Georgiev Ivelin S. 
Published: May 2021

AbstractThe emergence of novel SARS-CoV-2 lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of COVID-19. Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the LIBRA-seq technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 showed potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryo-EM structure of 54042-4 in complex with the SARS-CoV-2 spike revealed an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses unique genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings motivate 54042-4 as a lead candidate for clinical development to counteract current and future SARS-CoV-2 VOCs.
Virtually in Synch: A Pilot Study on Affective Dimensions of Dancing with Parkinson’s during COVID-19
Authors: Ghanai Katayoun , Barnstaple Rebecca E. , DeSouza Joseph FX 
Published: May 2021

AbstractLoss of social supports and community programs due to lockdowns and other measures associated with COVID-19 has been linked with concerns over mental health and feelings of isolation. These challenges can be particularly acute for the elderly and people living with chronic or pervasive health conditions. Dance for PD, a program specifically developed for people living with Parkinson’s Disease, formerly offered in hundreds of locations around the globe, either halted or shifted to a virtual format. Our study investigates the transition of these dance-based programs to an online environment, with the aim of determining the extent to which a virtual format provides affective support or other benefits. Given the increased incidence of mental health problems and social isolation associated with COVID-19, this investigation aims to contribute to the development of better supports for vulnerable populations while helping us understand the specific contributions of dance-based programs in a virtual environment.
Remote, unsupervised functional motor task evaluation in older adults across the United States using the MindCrowd electronic cohort
Authors: Hooyman Andrew , Talboom Joshua S. , DeBoth Matthew D. , Ryan Lee , Huentelman Matt , Schaefer Sydney Y. 
Published: May 2021

AbstractThe COVID-19 pandemic has impacted the ability to evaluate motor function in older adults, as motor assessments typically require face-to-face interaction. This study tested whether motor function can be assessed at home. One hundred seventy-seven older adults nationwide (recruited through the MindCrowd electronic cohort) completed a brief functional upper-extremity assessment at home and unsupervised. Performance data were compared to data from an independent sample of community-dwelling older adults (N=250) assessed by an experimenter in-lab. The effect of age on performance was similar between the in-lab and at-home groups for both the dominant and non-dominant hand. Practice effects were also similar between the groups. Assessing upper-extremity motor function remotely is feasible and reliable in community-dwelling older adults. This test offers a practical solution in response to the COVID-19 pandemic and telehealth practice and other research involving remote or geographically isolated individuals.
FOCUS: Forecasting COVID-19 in the United States
Authors: Nagraj VP , Hulme-Lowe Chris , Guertin Stephanie L. , Turner Stephen D. 
Published: May 2021

AbstractInfectious disease forecasting has been a useful tool for public health planning and messaging during the COVID-19 pandemic. In partnership with the CDC, the organizers of the COVID-19 Forecast Hub have created a mechanism for forecasters from academia, industry, and government organizations to submit weekly near-term predictions of COVID-19 targets in the United States. Here we describe our efforts to participate in the COVID-19 Forecast Hub through theForecastingCOVID-19 in theUnitedStates (FOCUS) project. The effort led to more than three months of weekly submissions and development of an automated pipeline to generate forecasts. The models used in FOCUS yielded forecasts that ranked relatively well in terms of precision and accuracy.
Representation of Racial and Ethnic Minority Populations in Dementia Prevention Trials: A Systematic Review
Authors: Shaw Ashley R. , Perales-Puchalt Jaime , Johnson Ellie , Espinoza-Kissell Paul , Acosta-Rullan Mariola , Frederick Sarah , Lewis Anneka , Chang Huan , Mahnken Jonathan , Vidoni Eric D. 
Published: May 2021

ABSTRACTDespite older racial and ethnic minorities (REMs) being more likely to develop dementia they are underrepresented in clinical trials focused on neurological disorders. Inclusion of REMs in dementia prevention studies is vital to reducing the impact of disparities in dementia risk. We conducted a systematic review to characterize the number of REM enrolled in brain health and prevention randomized controlled trials (RCTs). RTCs published from January 1, 2004 to April 21, 2020 were included. Participants were normal cognitive adults aged 45 years and older who participated in a Phase II or Phase III U.S. based preventative trial. Analyses were performed to examine differences in trial characteristics between RCTs that did and those that did not report race/ethnicity and to calculate the pooled proportion of each racial/ethnic group in randomized brain healthy prevention trials. A total of 42 studies consisting of 100,748 participants were included in the final analyses. A total of 26 (62%) reported some racial/ethnic identity data. The pooled proportion of REM participants was 0.256 (95% CI, 0.191, 0.326). There is a lack of racial/ethnic reporting of participants and REMs remain underrepresented in brain health prevention RCTs.
UMGAP: the Unipept MetaGenomics Analysis Pipeline
Authors: Van der Jeugt Felix , Maertens Rien , Steyaert Aranka , Verschaffelt Pieter , De Tender Caroline , Dawyndt Peter , Mesuere Bart 
Published: May 2021

AbstractShotgun metagenomics is now commonplace to gain insights into communities from diverse environments, but fast, memory-friendly, and accurate tools are needed for deep taxonomic analysis of the metagenome data. To meet this need we developed UMGAP, a highly versatile open source command line tool implemented in Rust for taxonomic profiling of shotgun metagenomes. It differs from state-of-the-art tools in its use of protein code regions identified in short reads for robust taxonomic identifications, a broad-spectrum index that can identify both archaea, bacteria, eukaryotes and viruses, a non-monolithic design, and support for interactive visualizations of complex biodiversities.