bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination Respiratory Vaccine Containing Recombinant SARS-CoV-2 Spike and Quadrivalent Seasonal Influenza Hemagglutinin Nanoparticles with Matrix-M Adjuvant
Authors: Massare Michael J , Patel Nita , Zhou Bin , Maciejewski Sonia , Flores Rhonda , Guebre-Xabier Mimi , Tian Jing-Hui , Portnoff Alyse D. , Fries Louis , Shinde Vivek , Ellingsworth Larry , Glenn Gregory , Smith Gale 
Published: May 2021

AbstractThe 2019 outbreak of a severe respiratory disease caused by an emerging coronavirus, SARS-CoV-2, has spread globally with high morbidity and mortality. Co-circulating seasonal influenza has greatly diminished recently, but expected to return with novel strains emerging, thus requiring annual strain adjustments. We have developed a recombinant hemagglutinin (HA) quadrivalent nanoparticle influenza vaccine (qNIV) produced using an established recombinant insect cell expression system to produce nanoparticles. Influenza qNIV adjuvanted with Matrix-M was well-tolerated and induced robust antibody and cellular responses, notably against both homologous and drifted A/H3N2 viruses in Phase 1, 2, and 3 trials. We also developed a full-length SARS-CoV-2 spike protein vaccine which is stable in the prefusion conformation (NVX-CoV2373) using the same platform technology. In phase 3 clinical trials, NVX-CoV2373 is highly immunogenic and protective against the prototype strain and B.1.1.7 variant. Here we describe the immunogenicity and efficacy of a combination quadrivalent seasonal flu and COVID-19 vaccine (qNIV/CoV2373) in ferret and hamster models. The combination qNIV/CoV2373 vaccine produces high titer influenza hemagglutination inhibiting (HAI) and neutralizing antibodies against influenza A and B strains. The combination vaccine also elicited antibodies that block SARS-CoV-2 spike protein binding to the human angiotensin converting enzyme-2 (hACE2) receptor. Significantly, hamsters immunized with qNIV/CoV2373 vaccine and challenged with SARS-CoV-2 were protected against weight loss and were free of replicating SARS-CoV-2 in the upper and lower respiratory tract with no evidence of viral pneumonia. This study supports evaluation of qNIV/CoV2373 combination vaccine as a preventive measure for seasonal influenza and CoVID-19.HighlightsCombination qNIV/CoV2373 vaccine induced protective hemagglutination inhibition (HAI) responses to seasonal influenza A and B unchanged when formulated with recombinant spike.Combination qNIV/CoV2373 vaccine maintained clinical and virologic protection against experimental challenge with SARS-CoV-2.Combination qNIV/CoV2373 vaccine showed no clinical or histological sign of enhanced disease following experimental challenge with SARS-CoV-2.Combination qNIV/CoV2373 vaccine induced antibodies against SARS-CoV-2 neutralizing epitopes common between US-WA and B.1.352 variant.
Structural basis of RNA polymerase recycling by the Swi2/Snf2 ATPase RapA inEscherichia coli
Authors: Qayyum M. Zuhaib , Molodtsov Vadim , Renda Andrew , Murakami Katsuhiko S. 
Published: May 2021

ABSTRACTAfter transcription termination, cellular RNA polymerases (RNAPs) are occasionally trapped on DNA, impounded in an undefined Post-Termination Complex (PTC), limiting free RNAP pool and making transcription inefficient. InEscherichia coli, a Swi2/Snf2 ATPase RapA is involved in countering such inefficiency through RNAP recycling. To understand its mechanism of RNAP recycling, we have determined the cryo-electron microscopy (cryo-EM) structures of two sets ofE. coliRapA-RNAP complexes along with RNAP core enzyme and elongation complex (EC). The structures revealed the large conformational changes of RNAP and RapA upon their association implicated in the hindrance in PTC formation. Our study reveals that although RapA binds away from the DNA binding channel of RNAP, it can close the RNAP clamp allosterically thereby preventing its non-specific DNA binding. Together with DNA binding assays, we propose that RapA acts as a guardian of RNAP by which prevents non-specific DNA binding of RNAP without affecting the sigma factor binding to RNAP core enzyme, thereby enhancing RNAP recycling.
A lipid-based parallel processor for chemical signals
Authors: Cazimoglu Idil , Booth Michael J. , Bayley Hagan 
Published: May 2021

AbstractA key goal of bottom-up synthetic biology is to construct cell- and tissue-like structures. Underpinning cellular life is the ability to process several external chemical signals, often in parallel. Until now, however, cell- and tissue-like structures have only been constructed with one signalling pathway. Here, we construct a dual-signal processor from the bottom up in a modular fashion. The processor comprises three aqueous compartments bounded by lipid bilayers and operates in an aqueous environment. It can receive two chemical signals from the external environment, process them orthogonally, and then produce a distinct output for each signal. It is suitable for both sensing and enzymatic processing of environmental signals with fluorescence and molecular outputs. In the future, such processors could serve as smart drug delivery vehicles or as modules within synthetic tissues to control their behaviour in response to external chemical signals.
Mechanistic Insights of High Temperature-Interfered Meiosis in AutotetraploidArabidopsis thaliana
Authors: Fu Huiqi , Yang Ke , Zhang Xiaohong , Zhao Jiayi , Elesawi Ibrahim Eid , Liu Hong , Xia Jing , Yu Guanghui , Chen Chunli , Wang Chong , Liu Bing 
Published: May 2021

AbstractEnvironmental temperature has a huge impact on multiple meiosis processes in flowering plants. Polyploid plants derived from whole genome duplication are believed to have an enhanced abiotic stress tolerance. In this study, the impact of high temperatures on male meiosis in autotetraploidArabidopsis thalianawas investigated. We found that autotetraploid Columbia (Col-0) plants generate a subpopulation of aberrant meiotic products under normal temperature, which is significantly increased under heat stress. Cytological studies revealed that, as the case in diploidArabidopsis thaliana, assembly of microtubular cytoskeleton network, pairing and segregation of homologous chromosomes, and meiotic recombination in autotetraploid Arabidopsis are compromised under the high temperatures. Immunostaining of ɤH2A.X and recombinase DMC1 suggested that heat stress inhibits formation of DNA double-strand breaks; additionally, it specifically destabilizes ASY1 and ASY4, but not SYN1 on chromosomes. The loading defects of ASY1 and ASY4 overlap in thesyn1mutant, which supports that the building of lateral element of synaptonemal complex occurs downstream of a SYN1-ASY4-ASY3 stepwise assembly of axis. Remarkably, heat-induced abnormalities of ASY1 and ASY4 co-localize on chromosomes of both diploid and autotetraploid Arabidopsis, suggesting that high temperatures interfere with ASY1-associated SC via an impacted stability of chromosome axis. Furthermore, ZYP1-dependent transverse filament of SC is disrupted by heat stress. Taken together, these findings suggest that polyploidization negatively contributes to instability of chromosome axis and meiotic recombination inArabidopsis thalianaunder heat stress.
DNA methylation calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation
Authors: Liu Yang , Rosikiewicz Wojciech , Pan Ziwei , Jillette Nathaniel , Wang Ping , Taghbalout Aziz , Foox Jonathan , Mason Christopher , Carroll Martin , Cheng Albert , Li Sheng 
Published: May 2021

AbstractBackgroundNanopore long-read sequencing technology greatly expands the capacity of long-range single-molecule DNA-modification detection. A growing number of analytical tools have been actively developed to detect DNA methylation from Nanopore sequencing reads. Here, we examine the performance of different methylation calling tools to provide a systematic evaluation to guide practitioners for human epigenome-wide research.ResultsWe compare five analytic frameworks for detecting DNA modification from Nanopore long-read sequencing data. We evaluate the association between genomic context, CpG methylation-detection accuracy, CpG sites coverage, and running time using Nanopore sequencing data from natural human DNA. Furthermore, we provide an online DNA methylation database (https://nanome.jax.org) with which to display genomic regions that exhibit differences in DNA-modification detection power among different methylation calling algorithms for nanopore sequencing data.ConclusionsOur study is the first benchmark of computational methods for mammalian whole genome DNA-modification detection in Nanopore sequencing. We provide a broad foundation for cross-platform standardization, and an evaluation of analytical tools designed for genome-scale modified-base detection using Nanopore sequencing.
QSMxT: Robust Masking and Artefact Reduction for Quantitative Susceptibility Mapping
Authors: Stewart Ashley Wilton , Robinson Simon Daniel , O’Brien Kieran , Jin Jin , Widhalm Georg , Hangel Gilbert , Walls Angela , Goodwin Jonathan , Eckstein Korbinian , Tourell Monique , Morgan Catherine , Narayanan Aswin , Barth Markus , Bollmann Steffen 
Published: May 2021

AbstractPurposeQuantitative Susceptibility Mapping (QSM) is a post-processing technique applied to gradient-echo phase data. QSM algorithms require a signal mask to delineate regions with reliable phase signal for subsequent susceptibility estimation. Existing masking techniques used in QSM have limitations that introduce artefacts, exclude anatomical detail, and rely on parameter tuning and anatomical priors that narrow their application. Here, a robust masking and reconstruction procedure is presented to overcome these limitations and enable automated QSM processing for a wide range of use-cases implemented in an open-source software framework:QSMxT.MethodsA robust masking technique that automatically separates reliable from less reliable phase regions was developed and combined with a two-pass reconstruction procedure that operates on the separated sources before combination, extracting more information while reducing the influence of artefacts.ResultCompared with standard masking and reconstruction procedures, the two-pass inversion reduces streaking artefacts caused by unreliable phase and high dynamic ranges of susceptibility sources. QSMxT is robust across a range of datasets at 3 T in healthy volunteers and phantoms, at 7 T in tumour patients, and in the QSM challenge 2.0 simulated brain dataset, with significant artefact and error reductions, greater anatomical detail, and minimal parameter tuning.ConclusionQSMxT generates masks for QSM that separate reliable from less reliable phase regions, enables a more accurate QSM reconstruction that mitigates artefacts, operates without anatomical priors, and requires minimal parameter tuning. QSMxT makes QSM processing more accessible, reliable and reproducible.
Cell-envelope synthesis is required for surface-to-mass coupling, which determines dry-mass density inBacillus subtilis
Authors: Kitahara Yuki , Oldewurtel Enno R. , Wilson Sean , Sun Yingjie , Garner Ethan C. , van Teeffelen Sven 
Published: May 2021

AbstractCells must increase their volumes in response to biomass growth to maintain intracellular mass density, the ratio of dry mass to cell volume, within physiologically permissive bounds. To increase volume, bacteria enzymatically expand their cell envelopes and insert new envelope material. Recently, we demonstrated that the Gram-negative bacteriumEscherichia coliexpands cell-surface area rather than volume in proportion to mass. Here, we investigate the regulation of cell-volume growth in the evolutionarily distantBacillus subtilis. First, we demonstrate that the coupling of surface growth to mass growth is conserved inB. subtilis. Therefore, mass density changes with cell shape at the single-cell level. Interestingly, mass density varies by more than 30% when we systematically change cell width by modulation of cell-wall insertion, without any effect on mass-growth rate. Second, we demonstrate that the coupling of surface- and mass growth is broken if peptidoglycan or membrane synthesis are inhibited. Once transient perturbations are relieved, the surface-to-mass ratio is rapidly restored. In conclusion, we demonstrate that surface-to-mass coupling is a conserved principle for volume regulation in bacteria, and that envelope synthesis provides an important link between surface growth and biomass growth inB. subtilis.
Somatic genetics analysis of sleep in adult mice
Authors: Wang Guodong , Li Qi , Xu Junjie , Zhao Shuai , Zhou Rui , Chen Zhenkang , Jiang Wentong , Gao Xue , Zhou Shuang , Chen Zhiyu , Sun Quanzhi , Ma Chengyuan , Chen Lin , Shi Bihan , Guo Ying , Wang Haiyan , Wang Xia , Li Huaiye , Cai Tao , Wang Yibing , Chen Zhineng , Wang Fengchao , Liu Qinghua 
Published: May 2021

SUMMARYClassical forward and reverse mouse genetics approaches require germline mutations and, thus, are unwieldy to study sleep functions of essential genes or redundant pathways. It is also time-consuming to conduct electroencephalogram/electromyogram-based mouse sleep screening owning to labor-intensive surgeries and genetic crosses. Here, we describe a highly accurate SleepV (video) system and adeno-associated virus (AAV)-based adult brain chimeric (ABC)- expression/knockout (KO) platform for somatic genetics analysis of sleep in adult mice. A pilot ABC-expression screen identifies CREB and CRTC1, of which constitutive or inducible expression significantly reduces quantity and quality of non-rapid eye movement sleep. Whereas ABC-KO of exon 13 ofSik3by AAV-Cre injection inSik3-E13flox/floxadult mice phenocopiesSleepy (Sik3Slp/+)mice, ABC-CRISPR ofSlp/Sik3reverses hypersomnia ofSleepymice, indicating a direct role of SLP/SIK3 kinase in sleep regulation. Multiplex ABC-CRISPR of both orexin/hypocretin receptors causes narcolepsy-like episodes, enabling one-step analysis of redundant genes in adult mice. Finally, ABC-expression/KO screen identifies Ankrd63 and NR1 as two potentially new sleep regulators. Therefore, this somatic genetics approach should facilitate high-throughput analysis of sleep regulatory genes, especially for essential or redundant genes, in adult mice by skipping the mouse development and genetic crosses.
Mechanical collaboration between the embryonic brain and the surrounding scalp tissues
Authors: Tsujikawa Koichiro , Saito Kanako , Nagasaka Arata , Miyata Takaki 
Published: May 2021

ABSTRACTDuring brain enlargement between embryonic day (E) 11 and E13, within the limited mouse cranial space enclosed by the scalp consisting of epidermal and preosteogenic mesenchymal layers, the angle between the pons and the medulla decreases. This raises the possibility that the scalp, upon being pushed outwardly by the brain and stretched, in return inwardly recoils to confine and fold the brain. Our stress-releasing tests showed that the scalp recoiled to shrink more extensively at E12~13 than at E15~16 and that thein vivopre-stretch prerequisite for this recoil response depended physically on the brain (pressurization at 77~93 Pa) and on actomyosin and elastin within the scalp layers. Under non-stretched conditions, scalp cell proliferation declined, while re-stretching of the shrunken scalp rescued proliferation. In scalp-removed heads, pons–medulla folding was reduced, and the spreading of ink from the lateral ventricle to the spinal cord that occurred in scalp-intact embryos (with >5 μl injection) was lost, suggesting that the scalp plays roles in brain morphogenesis and cerebrospinal fluid homeostasis. Thus, the brain and the scalp mechanically interact and collaborate.
Unbiased lexicometry analyses illuminate plague dynamics during the second pandemic
Authors: Barbieri Rémi , Nodari Riccardo , Signoli Michel , Epis Sara , Raoult Didier , Drancourt Michel 
Published: May 2021

AbstractKnowledge of the second plague pandemic that swept over Europe during the 14th-19th centuries, mainly relies on the exegesis of contemporary texts, prone to interpretive bias. Leveraging bioinformatic tools routinely used in biology, we here developed a quantitative lexicography of 32 texts describing two major plague outbreaks using contemporary plague-unrelated texts as negative controls. Nested, network and category analyses of a 207-word pan-lexicome over-represented in plague-related texts, indicated that “buboes” and “carbuncles” words were significantly associated with plague, signaling ectoparasite- borne plague. Moreover, plague-related words were associated with the words “merchandise”, “movable”, “tatters”, “bed” and “clothes”, while no association was found with rats and fleas. These results support the hypothesis that during the second plague pandemic, human ectoparasites were the major drivers of plague. Analyzing ancient texts using here reported method would certify plague-related historical records and indicate particularities of each plague outbreak, including sources of the causativeYersinia pestis.
Information-seeking behavior of female doctor shoppers: results from an interview study
Authors: Chen Shih-Chuan 
Published: May 2021

PurposeThis study aims to explore the information-seeking behavior of female patients engaged in doctor shopping. An investigation was conducted on the following aspects: the reasons for doctor-shopping behavior (DSB), patients’ information needs and sources, patients’ use of the obtained information and the degree of satisfaction with the information collected.Design/methodology/approachIn-depth interviews were conducted in this study. In total, 30 female participants who lived or worked in the Taipei metropolitan area, Taiwan, were recruited.FindingsDissatisfaction with treatment, confirmation of illness conditions, inconvenient treatment locations and hours and dissatisfaction with doctor’s attitude were the main reasons for DSB. Family members, friends, the internet and mass media were sources of information for participants when they sought second and successive doctors. In most cases, the degree of satisfaction toward the obtained information increased after each visit to a doctor during the doctor-shopping journey. However, not all participants shared information with doctors. The participants suggested that detailed explanations provided by doctors and better communication with doctors may reduce the occurrence of doctor shopping.Originality/valueThe findings of this study help medical personnel better understand DSB. The findings revealed the significance of information to patients and indicated that the information collected during doctor shopping is beneficial for patients.
Addressing the double burden of the COVID-19 and noncommunicable disease pandemics: a new global governance challenge
Authors: Collins Tea , Tello Juan , Van Hilten Menno , Mahy Lina , Banatvala Nicholas , Fones Guy , Akselrod Svetlana , Bull Fiona , Cieza Alarcos , Farrington Jill , Fisher Jack , Gonzalez Cristina , Guerra Jaimie , Hanna Fahmy , Jakab Zsuzsanna , Kulikov Alexey , Saeed Khalid , Abdel Latif Nisreen , Mikkelsen Bente , Pourghazian Nasim , Troisi Giuseppe , Willumsen Juana 
Published: May 2021

PurposeAs the coronavirus disease 2019 (COVID-19) continues to spread across countries, it is becoming increasingly clear that the presence of pre-existing noncommunicable diseases (NCDs) dramatically increases the risk of aggravation in persons who contract the virus. The neglect in managing NCDs during emergencies may result in fatal consequences for individuals living with comorbidities. This paper aims to highlight the need for a paradigm shift in the governance of public health emergencies to simultaneously address NCD and noncommunicable disease (CD) pandemics while taking into account the needs of high-risk populations, underlying etiological factors, and the social, economic, and environmental determinants that are relevant for both CDs and NCDs.Design/methodology/approachThe paper reviews the available global frameworks for pandemic preparedness to highlight the governance challenges of addressing the dual agenda of NCDs and CDs during a public health emergency. It proposes key strategies to strengthen multilevel governance in support of countries to better prepare for public health emergencies through the engagement of a wide range of stakeholders across sectors.FindingsAddressing both CD and NCD pandemics during public health emergencies requires (1) a new framework that unites the narratives and overcomes service and system fragmentations; (2) a multisectoral and multistakeholder governance mechanism empowered and resourced to include stakeholders across sectors and (3) a prioritized research agenda to understand the political economy of pandemics, the role played by different political systems and actors and implementation challenges, and to identify combined strategies to address the converging agendas of CDs and NCDs.Research limitations/implicationsThe article is based on the review of available published evidence.Practical implicationsThe uptake of the strategies proposed will better prepare countries to respond to NCD and CD pandemics during public health emergencies.Originality/valueThe article is the first of its kind addressing the governance challenges of the dual pandemic of NCDs and CDs in emergencies.
Towards a more effective strategy to detect community-dwelling frail older adults: validation of risk factors
Authors: Van der Elst Michaël , Schoenmakers Birgitte , Dierckx Eva , De Roeck Ellen , van der Vorst Anne , Lambotte Deborah , De Lepeleire Jan , De Donder Liesbeth 
Published: May 2021

PurposeIn the context of early detection of frail older people, prior research found several risk factors of multidimensional frailty. The current study aims to validate these risk factors.Design/methodology/approachTwo data sets, Belgian Ageing Studies and Detection, Support and Care for older people: Prevention and Empowerment (BAS and D-SCOPE), in three Belgian municipalities (Ghent, Knokke-Heist and Thienen) were used and compared. The BAS data set (N = 1496) is a representative sample of community-dwelling older adults (60+), while the recruitment of the D-SCOPE sample (validation sample, N = 869) is based on risk factors (e.g. age, marital status, moved in the past 10 years). Frailty was measured with the comprehensive frailty assessment instrument (CFAI). The validity was examined by means of prevalence rates, distribution and the odds rates within both data sets.FindingsThe validation sample had an increase in the percentage of elderly who were mildly and highly frail for physical frailty (men: +17.0 percent point, women: +20.7 percent point), for psychological frailty (men: +13.4 percent point, women: +13.7 percent point), for social frailty (men: +24.8 percent point, women: +4.8 percent point) and environmental frailty (men: +24.2 percent point, women: +6.8 percent point). The present results indicate that the risk of being mildly or highly frail was higher in the validation sample in comparison with the BAS data.Originality/valueThe present study proved the validity of aforementioned risk factors. Selecting older people based on these risk factors proved to be an effective strategy for detecting frail older people.