bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD8+ T cell epitope variations suggest a potential antigen presentation deficiency for spike protein of SARS-CoV-2
Authors: Qiu Congling , Xiao Chanchan , Wang Zhigang , Chen Xiongfei , Gao Lijuan , Deng Jieping , Su Jun , Su Huanxing , Fang Evandro Fei , Zhang Zhang-Jin , Zhu Guodong , Zhang Jikai , Xie Caojun , Yuan Jun , Luo Oscar Junhong , Wang Pengcheng , Chen Guobing 
Published: January 2021

AbstractCOVID-19 is caused by a newly identified coronavirus, SARS-CoV-2, and has become a pandemic around the world. The illustration of the immune responses against SARS-CoV-2 is urgently needed for understanding the pathogenesis of the disease and its vaccine development. CD8+ T cells are critical for virus clearance and induce long lasting protection in the host. Here we identified specific HLA-A2 restricted T cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides (n-Sp1, 2, 6, 7, 11, 13, 14) were confirmed to bind with HLA-A2 and potentially be presented by antigen presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. In addition, these epitopes could activate and generate epitope-specific T cellsin vitro, and those activated T cells showed cytotoxicity to target cells. Meanwhile, all these epitopes exhibited high frequency of variations. Among them, n-Sp1 epitope variation5L>Fsignificantly decreased the proportion of specific T cell activation; n-Sp1 epitope8L>Vvariant showed significantly reduced binding to HLA-A2 and decreased the proportion of n-Sp1-specific CD8+ T cell, which potentially contributes to the immune escape of SAR-CoV-2.
Nuclear translocation of tagged endogenous ERK/MPK-1 MAP Kinase denotes a subset of activation events inC. elegansdevelopment
Authors: Rasmussen Neal R. , Reiner David J. 
Published: January 2021

ABSTRACTThe extracellular signal-regulated kinase (ERK) MAP kinase is utilized downstream of Ras>Raf>MEK signaling to control activation of a wide array of targets. Activation of ERK is elevated in Ras-driven tumors and RASopathies, and is thus a target for pharmacological inhibition. Regulatory mechanisms of ERK activation has been studied extensivelyin vitroand in cultured cells but little in living animals. We used CRISPR to tag the 3’ end of theC. elegansERK-encoding gene,mpk-1. Endogenous MPK-1 protein is ubiquitously expressed with elevated expression in certain tissues. We detected cytosol-to-nuclear translocation of MPK-1 in maturing oocytes and hence validated nuclear translocation as a reporter of some activation events. During developmental patterning of the six vulval precursor cells, MPK-1 is necessary and sufficient for the central cell, P6.p, to assume 1° fate. We observed MPK-1 to be recruited to the nuclei of all six VPCs in a temporal and concentration gradient centered on P6.p. This observation contrasts with previous results using the ERK-nKTR reporter of substrate activation, raising questions about mechanisms and indicators of MPK-1 activation. This system and reagent promise to provide critical insights into regulation of MPK-1 activation within a complex intercellular signaling network.
The CLASSY family controls tissue-specific DNA methylation patterns in Arabidopsis
Authors: Zhou Ming , Coruh Ceyda , Xu Guanghui , Bourbousse Clara , Lambolez Alice , Law Julie A. 
Published: January 2021

ABSTRACTDNA methylation shapes the epigenetic landscape of the genome, plays critical roles in regulating gene expression, and ensures transposon silencing. As evidenced by the numerous defects associated with aberrant DNA methylation landscapes, establishing proper tissue-specific methylation patterns is critical. Yet, how such differences arise remains a largely open question in both plants and animals. Here we demonstrate that CLASSY1-4 (CLSY1-4), four locus-specific regulators of DNA methylation that are differentially expressed during plant development, play major roles in controlling tissue-specific DNA methylation patterns. Depending on the tissue, the genetic requirements for specific CLSYs differ significantly and, on a global scale, certainclsymutants are sufficient to largely shift the epigenetic landscape between tissues. Together, these findings not only reveal substantial epigenetic diversity between tissues, but assign these changes to specific CLSY proteins, revealing how locus-specific targeting combined with tissue-specific expression enables the CLSYs to generate epigenetic diversity during plant development.
Remodeling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis
Authors: Tamamouna Vasilia , Rahman M. Mahidur , Petersson Monika , Charalambous Irini , Kux Kristina , Mainor Hannah , Bolender Verena , Isbilir Buse , Edgar Bruce A. , Pitsouli Chrysoula 
Published: January 2021

AbstractTheDrosophilatracheal system, as the functional equivalent of mammalian blood vessels, responds to hypoxia and transports oxygen throughout the body. Although the signaling pathways involved in tracheal development and the hypoxic response are well-studied, how adult tracheae interact with their target tissues is largely unknown. Here we show that the tracheae that serve the adult intestine are dynamic and respond to enteric infection, oxidative agents, and the development of gut tumors with increased terminal branching. Increased tracheation is necessary for efficient damage-induced intestinal stem cell (ISC)-mediated midgut regeneration and sufficient to drive ISC proliferation in the absence of damage. Gut damage or tumors induce Hif-1α/Sima, which, in turn, stimulates tracheole branching via the FGF(Brachless/Bnl)/FGFR(Breathless/Btl) signaling cascade. Bnl/Btl signaling is required both in the intestinal epithelium and the tracheal system for efficient damage-induced tracheal remodeling and ISC proliferation. We show that chemical orPseudomonas-generated ROS directly affect the trachea and are necessary for branching and intestinal regeneration. Similarly, tracheole branching and the resulting increase in oxygen supply are essential for tumor growth in the midgut. Thus, we have identified a novel mechanism of visceral tracheal-intestinal tissue communication, whereby oxidative damage and tumors induce neo-tracheogenesis in adultDrosophila.This process is reminiscent of cancer-induced neo-angiogenesis in mammals.
Anaerobic Benzene Biodegradation Linked to Growth of Highly Specific Bacterial Clades
Authors: Toth Courtney R. A. , Luo Fei , Bawa Nancy , Webb Jennifer , Guo Shen , Dworatzek Sandra , Edwards Elizabeth A. 
Published: January 2021

ABSTRACTReliance on bioremediation to remove benzene from anoxic environments has proven risky for decades but for unknown reasons. Years of research have revealed a strong link between anaerobic benzene biodegradation and the enrichment of highly specific microbes, namelyThermincolain the family Peptococcaceae and the deltaproteobacterial Candidate Sva0485 clade. Using aquifer material from Canadian Forces Base Borden, we compared five bioremediation approaches in batch microcosms. Under conditions simulating natural attenuation or sulfate biostimulation, benzene was not degraded after 1-2 years of incubation and no enrichment of known benzene-degrading microbes occurred. In contrast, nitrate-amended microcosms reported benzene biodegradation coincident with significant growth ofThermincolaspp., along with a functional gene presumed to catalyze anaerobic benzene carboxylation (abcA). Inoculation with 2.5% of a methanogenic benzene-degrading consortium containing Sva0485 (DeltaproteobacteriaORM2) resulted in benzene biodegradation in the presence of sulfate or under methanogenic conditions. The presence of other hydrocarbon co-contaminants decreased rates of benzene degradation by a factor of 2-4. Tracking the abundance of theabcAgene and 16S rRNA genes specific for benzene-degradingThermincolaand Sva0485 is recommended to monitor benzene bioremediation in anoxic groundwater systems to further uncover growth rate limiting conditions for these two intriguing phylotypes.SYNOPSISAnaerobic benzene biodegradation was accelerated by biostimulation with nitrate or by bioaugmentation under methanogenic or sulfate-reducing conditions.
Metabolic adaption to extracellular pyruvate triggers biofilm formation inClostridioides difficile
Authors: Tremblay Yannick D.N. , Durand Benjamin A.R. , Hamiot Audrey , Martin-Verstraete Isabelle , Oberkampf Marine , Monot Marc , Dupuy Bruno 
Published: January 2021

AbstractClostridioides difficileinfections are associated with gut microbiome dysbiosis and are the leading cause of hospital acquired diarrhoea. The infectious process is strongly influenced by the microbiota and successful infection relies on the absence of specific microbiota-produced metabolites. Deoxycholic acid (DOC) and short chain fatty acids are microbiota-produced metabolites that limit the growth ofC. difficileand protect the host against this infection. In a previous study, we showed that DOC causesC. difficileto form strongly adherent biofilms after 48 h. Here, our objectives were to identify and characterize key molecules and events required for biofilm formation in the presence of DOC. We applied time-course transcriptomics and genetics to identify sigma factors, metabolic processes and type IV pili that drive biofilm formation. These analyses revealed that extracellular pyruvate induces biofilm formation in the presence of DOC. In the absence of DOC, pyruvate supplementation was sufficient to induce biofilm formation in a process that was dependent on pyruvate uptake by the membrane protein CstA. In the context of the human gut, microbiota-generated pyruvate is a metabolite that limits pathogen colonization. Taken together our results suggest that pyruvate-induced biofilm formation might act as a key process drivingC. difficilepersistence in the gut.
Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination
Authors: Zarnitsyna Veronika I. , Akondy Rama S. , Ahmed Hasan , McGuire Don J. , Zarnitsyn Vladimir G. , Moore Mia , Johnson Philip L. F. , Ahmed Rafi , Li Kelvin , Hellerstein Marc , Antia Rustom 
Published: January 2021

AbstractUnderstanding how immunological memory lasts a lifetime requires quantifying changes in the number of memory cells as well as how their division and death rates change over time. We address these questions by using a statistically powerful mixed-effects differential equations framework to analyze data from two human studies that follow CD8 T cell responses to the yellow fever vaccine (YFV-17D). Models were first fit to the frequency and division rates of YFV-specific memory CD8 T cells 42 days to 1 year post-vaccination. A different dataset, on the loss of YFV-specific CD8 T cells over three decades, was used to assess out of sample predictions of our models. The commonly used exponential and bi-exponential decline models performed relatively poorly. Models with the cell loss following a power law (exactly or approximately) were most predictive. Notably, using only the first year of data, these models accurately predicted T cell frequencies up to 30 years post-vaccination. Our analyses suggest that division rates of these cells drop and plateau at a low level (0.001 per day, ~double estimates for naive T cells) within one year following vaccination, whereas death rates continue to decline for much longer. Our results show that power laws can be predictive for T cell memory, a finding that may be useful for vaccine evaluation and epidemiological modeling. Moreover, since power laws asymptotically decline more slowly than any exponential decline, our results help explain the longevity of immune memory phenomenologically.Author summaryImmunological memory, generated in response to infection or vaccination, may provide complete or partial protection from antigenically similar infections for the lifetime. Memory CD8 T cells are important players in protection from secondary viral infections but quantitative understanding of their dynamics in humans is limited. We analyze data from two studies where immunization with the yellow fever virus vaccine (YFV-17D) generates a mild acute infection and long-term memory. We find that: (i) the division rate of YFV-17D-specific CD8 T cells drops and stabilizes at ~ 0.1% per day during the first year following vaccination whereas the death rate declines more gradually, and (ii) the number of these cells declines approximately in accordance with a power law (∝time−0.82) for at least several decades following vaccination.
Probing mechanotransduction in living cells by optical tweezers and FRET-based molecular force microscopy
Authors: Sergides M. , Perego L. , Galgani T. , Arbore C. , Pavone F.S. , Capitanio M 
Published: January 2021

AbstractCells sense mechanical signals and forces to probe the external environment and adapt to tissue morphogenesis, external mechanical stresses, and a wide range of diverse mechanical cues. Here, we propose a combination of optical tools to manipulate single cells and measure the propagation of mechanical and biochemical signals inside them. Optical tweezers are used to trap microbeads that are used as handles to manipulate the cell plasma membrane; genetically encoded FRET-based force sensors inserted in F-actin and alpha-actinin are used to measure the propagation of mechanical signals to the cell cytoskeleton; while fluorescence microscopy with single molecule sensitivity can be used with a huge array of biochemical and genetic sensors. We describe the details of the setup implementation, the calibration of the basic components and preliminary characterization of actin and alpha-actinin FRET-based force sensors.
SARS-CoV-2 infection in Ivory Coast: a serosurveillance survey among gold mine workers
Authors: Milleliri Jean Marie , Coulibaly Daouda , Nyobe Blaise , Rey Jean-Loup , Lamontagne Franck , Hocqueloux Laurent , Giaché Susanna , Valery Antoine , Prazuck Thierry 
Published: January 2021

BackgroundEight months after the detection of the first COVID-19 case in Africa, 1,262,476 cases have been reported in African countries compared to 72 million worldwide. The real burden of SARS-CoV-2 infection in West Africa is not clearly defined. The aim of the study was to evaluate the seroprevalence of SARS-CoV-2 in half of the 3,380 workers of several mining companies operating in two mines in the Ivory Coast and having its headquarters in the economic capital Abidjan.MethodsFrom 15th July to 13th October 2020, a voluntary serological test campaign was performed in the 3 sites where the companies operate: two mines, and the headquarters in Abidjan.We performed a COVID-PRESTO rapid test for the detection of IgG and IgM on capillary blood. A multivariate analysis was performed to identify independent sociodemographic characteristics associated with a higher SARS-CoV-2 seroprevalence rate.ResultsA total of 1,687 subjects were tested. 91% were male (n= 1,536) and mean age was 37 years old. The overall crude seroprevalence rate was 25.1% (n=422), but differing significantly between different sites, rising from 13.6% (11.2%-16.1%) in mine A to 34.4% (31.1%-37.7%) in mine B and 34.7% (26.2%-43.2%) in Abidjan. Non-resident workers in mines had a significantly lower prevalence rate than those living full-time in mines. Seroprevalence was 26.5% in natives of the Ivory Coast, while people coming from countries other than Africa were less likely to be SARS-CoV-2 seropositive. Among the 422 positive subjects, 74 reported mild symptoms in the three previous months and one was hospitalized for a severe COVID-19 infection.ConclusionThe prevalence of SARS-CoV-2 infection among mine workers in Ivory Coast is high. The low morbidity observed has probably led to an underestimation of the burden of this infection in West Africa. The high prevalence reported in subjects living in Abidjan, who have not any close contact with mine workers, may be indicative of the real seroprevalence in the Ivory Coast capital.
Induction of labour during the COVID-19 pandemic: a national survey of impact on practice in the UK
Authors: Harkness M , Yuill C , Cheyne H , Stock SJ , McCourt C 
Published: January 2021

AbstractBackgroundInduction of labour (IOL) is one of the most commonly performed interventions in maternity care, with outpatient cervical ripening increasingly offered as an option for women undergoing IOL. The COVID-19 pandemic has changed the context of practice and the option of returning home for cervical ripening may now assume greater significance. This work aimed to examine whether and how the COVID-19 pandemic has changed practice around IOL in the UK.MethodWe used an online questionnaire to survey senior obstetricians and midwives at all 156 UK NHS Trusts and Boards that currently offer maternity services. Responses were analysed to produce descriptive statistics, with free text responses analysed using a conventional content analysis approach.FindingsResponses were received from 92 of 156 UK Trusts and Boards, a 59% response rate. Many Trusts and Boards reported no change to their IOL practice, however 23% reported change in methods used for cervical ripening; 28% a change in criteria for home cervical ripening; 28% stated that more women were returning home during cervical ripening; and 24% noted changes to women’s response to recommendations for IOL. Much of the change was reported as happening in response to attempts to minimise hospital attendance and restrictions on birth partners accompanying women.ConclusionsThe pandemic has changed practice around induction of labour, although this varied significantly between NHS Trusts and Boards. There is a lack of formal evidence to support decision-making around outpatient cervical ripening: the basis on which changes were implemented and what evidence was used to inform decisions is not clear.
Allosteric Regulation of the EphA2 Receptor Intracellular Region by Serine/Threonine Kinases
Authors: Lechtenberg Bernhard C. , Gehring Marina P. , Light Taylor P. , Matsumoto Mike W. , Hristova Kalina , Pasquale Elena B. 
Published: January 2021

ABSTRACTEph receptor tyrosine kinases play a key role in cell-cell communication. However, lack of structural information on the entire multi-domain intracellular region of any Eph receptor has hindered detailed understanding of their signaling mechanisms. Here, we use an integrative structural biology approach combining X-ray crystallography, small-angle X-ray scattering and hydrogen-deuterium exchange mass spectrometry, to gain the first insights into the structure and dynamics of the entire EphA2 intracellular region. EphA2 promotes cancer malignancy through a poorly understood non-canonical form of signaling that depends on serine/threonine phosphorylation of the linker connecting the EphA2 kinase and SAM domains. We uncovered two distinct molecular mechanisms that may function in concert to mediate the effects of linker phosphorylation through an orchestrated allosteric regulatory network. The first involves a shift in the equilibrium between a “closed” configuration of the EphA2 intracellular region and an “open” more extended configuration induced by the accumulation of phosphorylation sites in the linker. This implies that cooperation of multiple serine/threonine kinase signaling networks is necessary to promote robust EphA2 non-canonical signaling. The second involves allosteric rearrangements in the kinase domain and juxtamembrane segment induced by phosphorylation of some linker residues, suggesting a link between EphA2 non-canonical signaling and canonical signaling through tyrosine phosphorylation. Given the key role of EphA2 in cancer malignancy, this new knowledge can inform therapeutic strategies.
Intraspecific variations in leaf traits, productivity and resource use efficiencies in the dominant species of subalpine evergreen coniferous and deciduous broad‐leaved forests along the altitudinal gradient
Authors: Hikosaka Kouki , Kurokawa Hiroko , Arai Takahisa , Takayanagi Sakino , Tanaka Hiroshi O. , Nagano Soichiro , Nakashizuka Tohru 
Published: January 2021

Abstract

Many studies have reported intraspecific variations in leaf functional traits, but their contribution to plant performance and ecosystem function are poorly understood. We studied altitudinal gradients of intraspecific variations in leaf traits, productivity and resource use efficiency in the dominant species of subalpine evergreen coniferous and deciduous broad‐leaved forests in Japan.

We addressed three hypotheses, which are exclusive to each other. (1) Leaf traits vary along the leaf economics spectrum (LES). Plants that grow at lower and higher altitudes have fast‐ and slow‐return strategies, respectively, which improve productivity or resource use efficiency in the respective habitat. (2) Leaf trait variations are not consistent with the LES, but they contribute to improving productivity or resource use efficiency in the respective habitat. (3) Leaf trait variations do not contribute to improving productivity or resource use efficiency at higher altitudes.

On the studied mountain range, Fagus crenata, a deciduous broad‐leaved tree, and Abies mariesii, an evergreen conifer, are the dominant species at lower and higher altitudes respectively. In F. crenata, leaf mass per area (LMA) and nitrogen concentrations were higher at higher altitudes. The net assimilation rate and light use efficiency during the growing season were greater at higher altitudes, which compensated for the shorter growing season in terms of annual productivity. In A. mariesii, the LMA was lower and the leaf life span was unchanged at higher altitudes. Productivity and resource use efficiency decreased with altitude.

Synthesis. We conclude that F. crenata improves its productivity and resource use efficiency at higher altitudes by altering its leaf functional traits (Hypothesis 2), whereas alterations to leaf traits in A. mariesii are not associated with any improvement at higher altitudes (Hypothesis 3), which may result from the negative impact of environmental stress. Hence, the ecological significance of altitudinal variations in leaf traits depends on species and environment.
Critical seed transfer distances for selected tree species in eastern North America
Authors: Pedlar John H. , McKenney Daniel W. , Lu Pengxin 
Published: January 2021

Abstract

Forest planting events present key opportunities to enhance forest adaptation and growth through the selection of appropriate growing materials (seeds and seedlings). Critical to such efforts is knowledge of the climatic distance that seed sources can be moved before significant growth forfeitures are incurred. These limits, referred to here as critical seed transfer distances (CSTD), can be used to identify a potential seed procurement region for any given planting site and can readily incorporate climate change projections.

We assembled provenance trial data from a variety of sources and employed transfer functions to derive CSTDs for five major tree species in eastern North America.

Optimal height growth at test sites was associated with modest warm‐to‐cold (i.e. northward) seed transfers of 1.6°C on average. Calculated transfer limits were large, indicating that seed sources could be moved significant climatic distances before height growth was less than 90% relative to that of the local seed source. These broad relationships, which were relatively consistent across species, would allow considerable flexibility in resulting seed transfer systems; however, given the significant uncertainty surrounding climate change—particularly in the location and timing of extreme weather events—prudent application of seed transfer limits may be appropriate.

Synthesis: We assembled and analysed a significant amount of provenance data to derive novel information on seed movement limits for five tree species in eastern North America. This information will support forest managers in ongoing efforts to incorporate climate change into forest regeneration operations.