bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of Schools to Covid-19 Pandemic: Evidence from Czechia
Authors: Brom Cyril , Drbohlav Jakub , Šmíd Martin , Zajíček Milan 
Published: September 2021

AbstractPurposeIt is unclear how much opening of schools during Covid-19 pandemic contributes to new SARS-CoV-2 infections among children. We investigated the impact of school opening with various mitigation measures (masks, rotations, mass testing) on growth rate of new cases in child cohorts ranging from kindergartens to upper secondary in Czechia, a country heavily hit by Covid-19, since April 2020 to June 2021.MethodsOur primary method is comparison of the reported infections in age cohorts corresponding to school grades undergoing different regimes. When there is no opportunity for such a comparison, we estimate corresponding coefficients from a regression model. In both the cases, we assume that district-level infections in particular cohorts depend on the school attendance and the external environment in dependence on the current overall risk contact reduction.ResultsThe estimates of in-cohort growth rates were significantly higher for normally opened schools compared to closed schools. When prevalence is comparable in the cohorts and general population, and no further measures are applied, the in-cohort growth reduction for closed kindergartens is 29% (SE=11%); primary: 19% (7%); lower secondary: 39% (6%); upper secondary: 47% (6%). For secondary education, mitigation measures reduce school-related growth 2-6 times.ConclusionConsidering more infectious SARS-CoV-2 variants and the ‘long covid’ risk, mitigation measures in schools, especially in secondary levels, should be implemented for the next school year. Some infections, however, are inevitable, even in kindergartens (where mitigation measures are difficult to implement) and primary schools (where they may not work due to low adherence).
Reduced antibody activity against SARS-CoV-2 B.1.617.2 Delta virus in serum of mRNA-vaccinated patients receiving TNF-α inhibitors
Authors: Chen Rita E. , Gorman Matthew J. , Zhu Daniel Y. , Carreño Juan Manuel , Yuan Dansu , VanBlargan Laura A. , Burdess Samantha , Lauffenburger Douglas A. , Kim Wooseob , Turner Jackson S. , Droit Lindsay , Handley Scott A. , Chahin Salim , Deepak Parakkal , O’Halloran Jane A. , Paley Michael , Presti Rachel M. , Wu Gregory F. , Krammer Florian , Alter Galit , Ellebedy Ali H. , Kim Alfred H. J. , Diamond Michael S. 
Published: September 2021

SUMMARYAlthough vaccines effectively prevent COVID-19 in healthy individuals, they appear less immunogenic in individuals with chronic inflammatory diseases (CID) and/or under chronic immunosuppression, and there is uncertainty of their activity against emerging variants of concern in this population. Here, we assessed a cohort of 74 CID patients treated as monotherapy with chronic immunosuppressive drugs for functional antibody responses in serum against historical and variant SARS-CoV-2 viruses after immunization with Pfizer mRNA BNT162b2 vaccine. Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with TNF-α inhibitors, and this pattern appeared worse against the B.1.617.2 Delta virus. Within five months of vaccination, serum neutralizing titers of the majority of CID patients fell below the presumed threshold correlate for antibody-mediated protection. Thus, further vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) likely will be required to prevent SARS-CoV-2 infection in this susceptible population.
A Multidisciplinary Prematurity Research Cohort Study
Authors: Stout Molly J. , Chubiz Jessica , Raghuraman Nandini , Zhao Peinan , Tuuli Methodius G. , Wang Lihong V. , Cahill Alison G. , Cuculich Phillip S. , Wang Yong , Jungheim Emily S. , Herzog Erik D. , Fay Justin , Schwartz Alan L. , Macones George A. , England Sarah K. 
Published: September 2021

ABSTRACTBackgroundWorldwide, 10% of babies are born preterm, defined as a live birth before 37 weeks of gestation. Preterm birth is the leading cause of neonatal death, and survivors face lifelong risks of adverse outcomes. New approaches with large sample sizes are needed to identify strategies to predict and prevent preterm birth. The primary aims of the Washington University Prematurity Research Cohort Study were to conduct three prospective projects addressing possible causes of preterm birth and provide data and samples for future research.Study DesignPregnant patients were recruited into the cohort between January 2017 and January 2020. Consenting patients were enrolled into the study before 20 weeks’ gestation and followed through delivery. Participants completed demographic and lifestyle surveys; provided maternal blood, placenta samples, and cord blood; and participated in up to three projects focused on underlying physiology of preterm birth: cervical imaging (Project 1), circadian rhythms (Project 2), and uterine magnetic resonance imaging and electromyometrial imaging (Project 3).ResultsA total of 1260 participants were enrolled and delivered during the study period. Of the participants, 706 (56%) were Black/African American, 494 (39%) were nulliparous, and 185 (15%) had a previous preterm birth. Of the 1260 participants, 1220 (97%) delivered a live infant. Of the 1220 with a live birth, 163 (14.1%) had preterm birth, of which 74 (6.1%) were spontaneous preterm birth. Of the 1220 participants with a live birth, 841 participated in cervical imaging, 1047 contributed data and/or samples on circadian rhythms, and 39 underwent uterine magnetic resonance imaging. Of the 39, 25 underwent electromyometrial imaging.ConclusionWe demonstrate feasibility of recruiting and retaining a diverse cohort in a complex prospective, longitudinal study throughout pregnancy. The extensive clinical, imaging, survey, and biologic data obtained will be used to explore cervical, uterine, and endocrine physiology of preterm birth and can be used to develop novel approaches to predict and prevent preterm birth.
HIV-specific CD8 T cells from elite controllers have an epigenetic imprint that preserves effector functions
Authors: Frias Adolfo B. , Rutishauser Rachel L. , Sharma Ashish A. , Mi Tian , Abdelsamed Hossam , Zebley Caitlin , Constantz Christian M. , Stone Mars , Busch Michael P. , Deeks Steven G. , Sékaly Rafick-Pierre , Youngblood Ben 
Published: September 2021

AbstractSeveral lines of evidence support a central role for CD8 T cells as key determinants in the control of HIV, particularly in rare “elite controllers” who control the virus to undetectable levels in the blood in the absence of antiretroviral therapy (ART). While HIV-specific CD8 T cells isolated from elite controllers have enhanced antiviral cytokine production and proliferative capacity in response to antigen stimulation when compared to cells isolated from viremic or even aviremic ART-suppressed non-controllers, the cell-intrinsic mechanisms underlying the enhanced T cell memory-like function of HIV-specific CD8 T cells in elite controllers remain largely undefined. To identify the transcriptional and epigenetic pathways that regulate functional capacity in HIV-specific CD8 T cells in elite controllers, we performed genome-wide transcriptional and DNA methylation analysis of MHC Class I multimer+ CD8 T cells sorted from aviremic elite controllers compared to aviremic non-controllers on suppressive ART. Co-omics analysis revealed enrichment for gene signatures that support a multipotent differentiation state, cell survival, and a long-lived effector cell fate in HIV-specific CD8 T cells from elite controllers. Specifically, we observed DNA methylation programs at the transcription factor binding sites of the stem-associated factors TCF-1 and LEF1 that delineate HIV-specific CD8 T cells from elite controllers versus ART-treated individuals. HIV-specific CD8 T cells in elite controllers also maintain T cell receptor and IL-12/STAT4 pathway signaling and have suppressed pro-apoptotic TNFα pathway signaling. These findings show that HIV-specific CD8 T cells from elite controllers have enhanced expression and DNA methylation programs that maintain developmental potential and in turn promote long-term survival, proliferative potential, and effector capacity. These data also provide new insights into the relationship between stem-associated transcription factors and stable epigenetic restriction of T cell developmental capacity.
Blind cavefish retain functional connectivity in the tectum despite loss of retinal input
Authors: Lloyd Evan , McDole Brittnee , Privat Martin , Jaggard James B. , Duboué Erik , Sumbre German , Keene Alex 
Published: September 2021

AbstractSensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus, consists of eyed river-dwelling surface populations, and multiple independent cave populations which have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Further, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye-loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution.
Spatial structure affects evolutionary dynamics and drives genomic diversity in experimental populations of Pseudomonas fluorescens
Authors: Bailey Susan F. , Trudeau Andrew , Tulowiecki Katherine , McGrath Morgan , Belle Aria , Fountain Herbert , Akter Mahfuza 
Published: September 2021

ABSTRACTMost populations live in spatially structured environments and that structure has the potential to impact the evolutionary dynamics in a number of important ways. Theoretical models tracking evolution in structured environments using a range of different approaches, suggest that local interactions and spatial heterogeneity can increase the adaptive benefits of motility, impact both the rate and extent of adaptation, and increase the probability of parallel evolution. We test these general predictions in a microbial evolution experiment tracking phenotypic and genomic changes in replicate populations of Pseudomonas fluorescens evolved in both well-mixed and spatially-structured environments, where spatial structure was generated through the addition of semi-solid agar. In contrast to the well-mixed environment, populations evolved in the spatially-structured environment adapted more slowly, retained the ability to disperse more rapidly, and had a greater putatively neutral population genomic diversity. The degree of parallel evolution measured at the gene-level, did not differ across these two types of experimental environments, perhaps because the populations had not evolved for long enough to near their fitness optima. These results confirm important general impacts of spatial structure on evolutionary dynamics at both the phenotypic and genomic level.
The helper NLR immune protein NRC3 mediates the hypersensitive cell death caused by the cell-surface receptor Cf-4
Authors: Kourelis Jiorgos , Contreras Mauricio P. , Harant Adeline , Adachi Hiroaki , Derevnina Lida , Wu Chih-Hang , Kamoun Sophien 
Published: September 2021

ABSTRACTCell surface pattern recognition receptors (PRRs) activate immune responses that can include the hypersensitive cell death. However, the pathways that link PRRs to the cell death response are poorly understood. Here, we show that the cell surface receptor-like protein Cf-4 requires the intracellular nucleotide-binding domain leucine-rich repeat containing receptor (NLR) NRC3 to trigger a confluent cell death response upon detection of the fungal effector Avr4 in leaves ofNicotiana benthamiana. This NRC3 activity requires an intact N-terminal MADA motif, a conserved signature of coiled-coil (CC)-type plant NLRs that is required for resistosome-mediated immune responses. A chimeric protein with the N-terminal α1 helix of Arabidopsis ZAR1 swapped into NRC3 retains the capacity to mediate Cf-4 hypersensitive cell death. Pathogen effectors acting as suppressors of NRC3 can suppress Cf-4-triggered hypersensitive cell-death. Our findings link the NLR resistosome model to the hypersensitive cell death caused by a cell surface PRR.
Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients: a retrospective cohort study in a Mediterranean area
Authors: Ventero Maria Paz , Moreno-Perez Oscar , Molina-Pardines Carmen , Paytuví-Gallart Andreu , Boix Vicente , Galan Irene , González-delaAleja Pilar , López-Pérez Mario , Sánchez-Martínez Rosario , Merino Esperanza , Rodríguez Juan Carlos 
Published: September 2021

AbstractBackgroundThere is mounting evidence suggesting that the microbiome composition could be different in COVID-19 patients. However, the relationship between microbiota and COVID-19 severity progression is still being assessed. This study aimed to analyse the diversity and taxonomic composition of the nasopharyngeal microbiota, to determine its association with COVID-19 clinical outcome.Methods and FindingsSamples came from a retrospective cohort of adult patients with COVID-19, hospitalised in a tertiary centre. To study the nasopharyngeal microbiota, we utilized 16S rRNA sequencing. Raw sequences were processed by QIIME2. The associations between the microbiota, invasive mechanical ventilation (IMV), and all-cause mortality were analysed by multiple logistic regression (OR; 95%CI), adjusted for age, gender, and comorbidity. 177 patients were included: median age 68.0 years, 57.6% males, 59.3% had a Charlson comorbidity index ≥3, and 89.2% with pneumonia. The microbiota α diversity indexes were lower in patients with a fatal outcome, and this association persisted after adjustment for the main confounders; whereas the β diversity analysis showed a significant clustering, grouping the patients with a fatal outcome. After multivariate adjustment, the presence of Selenomonas spp., Filifactor spp., Actinobacillus spp., or Chroococcidiopsis spp., was associated with a reduced risk of IMV (adjusted OR 0.06[95%CI 0.01–0.0.47], p = 0.007).ConclusionsThe microbiota diversity and taxonomic composition are related to COVID-19 severity. Higher diversity and the presence of certain genera in the nasopharyngeal microbiota seem to be early biomarkers of a favourable clinical evolution in hospitalised patients with moderate to severe SARS-CoV-2 infections.
A microfluidic platform for sequential assembly and separation of synthetic cell models
Authors: Tivony Ran , Fletcher Marcus , Nahas Kareem Al , Keyser Ulrich F 
Published: September 2021

AbstractCell-sized vesicles like giant unilamellar vesicles (GUVs) are established as a promising biomimetic model for studying cellular phenomena in isolation. However, the presence of residual components and by-products, generated during vesicles preparation and manipulation, severely limits the utility of GUVs in applications like synthetic cells. Therefore, with the rapidly growing field of synthetic biology, there is an emergent demand for techniques that can continuously purify cell-like vesicles from diverse residues, while GUVs are being simultaneously synthesized and manipulated. We developed a microfluidic platform capable of purifying GUVs through stream bifurcation, where a stream of vesicles suspension is partitioned into three fractions - purified GUVs, residual components, and a washing solution. Using our purification approach, we showed that giant vesicles can be separated from various residues – that range in size and chemical composition – with a very high efficiency (e = 0.99), based on size and deformability of the filtered objects. In addition, by incorporating the purification module with a microfluidic-based GUV-formation method, octanol-assisted liposome assembly (OLA), we established an integrated production-purification microfluidic unit that sequentially produces, manipulates, and purifies GUVs. We demonstrate the applicability of the integrated device to synthetic biology through sequentially fusing SUVs with freshly prepared GUVs and separating the fused GUVs from extraneous SUVs and oil droplets at the same time.
Ovipin: a new antimicrobial peptide from chicken eggsGallus gallus
Authors: dos Santos Sandra Regina , Miranda Antonio , da Silva Junior Pedro Ismael 
Published: September 2021

AbstractThe intensive and indiscriminate use of antibiotic has increased cases of microorganisms resistance and becoming a worldwide public health problem. In the last years, from natural sources such as hen’s egg, have received special attention in the discovery of new bioactive compounds. This study aims to identify and characterize a new peptide from chicken egg ofGallus gallus domesticus. The chicken egg was subjected the extraction acid, the supernatant was prefractionated in Sep- Pak column and fractionated peptide by reverse-phase high-performance liquid chromatography (RP-HPLC). The antimicrobial activity of the fractions were evaluated through liquid growth inhibition assays. The molecular weight and amino acid sequence was determined by mass spectrometry (MS/MS), the characaterization performed by bioinformatics analysis with Peaks® tool and comparision with the NCBI and UniProt-SwisProt database. The physicochemical parameters of the samples were evaluated with online programs. One fraction named Ovipin peptide, showed antimicrobial activity against Gram-positive bacteria (Micrococcus luteus– MIC 1.94 µM) and Filamentous fungus (Aspergillus niger- MIC 31.01 µM). The minimum inhibitory concentration againstCryptococcus neoformansVNI (WM 148) Yeast was 15.51 µM, this microorganism an opportunistic yeast and mainly binds in immunosuppressed or immunocompromissed people. Ovipin is a hydrophoic peptide and not cause significant hemolytic effect against human erythrocytes. Ovipin primary sequence is YVSPVAIVKGLNIPL and a molecular weight of 1,581.94 Da. Ovipin shows 100% and 93.3%, respectively, sequence similarity with the fragments Apolipoprotein B ofGallus gallusand Apolipoprotein B of five others species of Aves. Our data suggest that Ovipin peptide could be a potential therapeutic candidate to be used an alternative against infections developed by resistant microorganisms, mainly in the fight againstCryptococcus neoformansopportunistic yeast.
Effectiveness of the protected areas on the Mornington Peninsula for the common resident shorebird species using citizen science data
Authors: Wijewardhana Udani A. , Apputhurai Pragalathan , Jayawardana Madawa , Meyer Denny 
Published: September 2021

AbstractIn the absence of comprehensive survey data this study used citizen science bird counts, extracted from the Atlas of Living Australia, to assess which species benefit most from protected areas. This was done by fitting temporal models using the Integrated Laplace Approximation (INLA) method.The trends for five resident shorebird species were compared to the Australian Pied Oystercatcher, with significantly steeper upward trends identified for the Black-fronted Dotterel, Red-capped Dotterel and Red-kneed Dotterel. Steeper upward trends were observed in protected than unprotected areas for the Black-fronted Dotterel, Masked Lapwing and Red-kneed Dotterel.This work suggests that, with some limitations, statistical models can be used with citizen science data for monitoring the persistence of resident shorebirds and for investigating factors that are impacting these data. The results for the Dotterel species in protected areas are particularly encouraging.
Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody
Authors: Torres Jonathan L. , Ozorowski Gabriel , Andreano Emanuele , Liu Hejun , Copps Jeffrey , Piccini Giulia , Donnici Lorena , Conti Matteo , Planchais Cyril , Planas Delphine , Manganaro Noemi , Pantano Elisa , Paciello Ida , Pileri Piero , Bruel Timothée , Montomoli Emanuele , Mouquet Hugo , Schwartz Olivier , Sala Claudia , De Francesco Raffaele , Wilson Ian A. , Rappuoli Rino , Ward Andrew B. 
Published: September 2021

AbstractAs the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of a previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryo-EM. We show that mAb J08 has low nanomolar affinity against VoCs, binds high on the receptor binding domain (RBD) ridge and is therefore unaffected by most mutations, and can bind in the RBD-up and -down conformations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.One Sentence SummaryPotent neutralizing monoclonal antibody J08 binds SARS-CoV-2 spike independent of known escape mutations.
The evolution of splicing: transcriptome complexity and transcript distances implemented inTranD
Authors: Nanni Adalena , Titus-McQuillan James , Moskalenko Oleksandr , Pardo-Palacios Francisco , Liu Zihao , Conesa Ana , Rogers Rebekah L. , McIntyre Lauren M 
Published: September 2021

AbstractAlternative splicing contributes to organismal complexity. Comparing transcripts between and within species is an important first step toward understanding questions about how evolution of transcript structure changes between species and contributes to sub-functionalization. These questions are confounded with issues of data quality and availability. The recent explosion of affordable long read sequencing of mRNA has considerably widened the ability to study transcriptional variation in non-model species. In this work, we develop a computational framework that uses nucleotide resolution distance metrics to compare transcript models for structural phenotypes: total transcript length, intron retention, donor/acceptor site variation, alternative exon cassettes, alternative 5’/3’ UTRs are each scored qualitatively and quantitatively in terms of number of nucleotides. For a single annotation file, all differences among transcripts within a gene are summarized and transcriptome-level complexity metrics: number of variable nucleotides, unique exons per gene, exons per transcript, and transcripts per gene are calculated. To compare two transcriptomes on the same co-ordinates, a weighted total distance between pairs of transcripts for the same gene is calculated. The weight function proposed has larger penalties for intron retention and exon skipping than alternative donor/acceptor sites. Minimum distances can be used to identify both transcript pairs and transcripts missing structural elements in either of the two annotations. This enables a broad range of functionality from comparing sister species to comparing different methods of building and summarizing transcriptomes. Importantly, the philosophy here is to output metrics, enabling others to explore the nucleotide-level distance metrics. Single transcriptome annotation summaries and pairwise comparisons are implemented in a new tool,TranD,distributed as aPyPipackage and in the open-source web-based Galaxy (www.galaxyproject.org) platform.