bluuebunny/crossref_metadata_2025_split huggingface dataset:
T-cell responses to acute cardiorespiratory or resistance exercise in cohorts of physically active or physically inactive older adults: A randomized complete crossover
Authors: Graff Rachel M. , Jennings Kristofer , LaVoy Emily C. , Warren Victoria E. , Macdonald Brad W. , Park Yoonjung , Markofski Melissa M. 
Published: April 2021

AbstractAging is associated with many chronic diseases that are maintained and perpetuated by immune dysregulation and chronic systemic inflammation. T-cells often undergo age-related changes, including an accumulation of memory cells, which places individuals at increased risk for novel infections and may predispose them to increased inflammation. Regular exercise training has been suggested to offset age-related changes in T-cells, but the majority of literature is derived from cardiorespiratory exercise (CRE) studies. Much less is understood about the T-cell response to resistance exercise (RE). The purpose of this study was to examine the effects of acute CRE and acute RE on the T-cell response among a cohort of physically active older adults (PA) compared to a cohort of physically inactive older adults (PI).METHODSTwenty-four healthy older adults (PA n=12; PI n=12; mean ± SD; age (yrs) PA 62 ± 5, PI 64 ± 5; height (cm) PA 170.9 ± 6.9, PI 162.9 ± 8.0; weight (kg) PA 69.3 ± 10.2, PI 68.2 ± 12.8; BMI (kg/m2) PA 23.9 ± 3.0, PI 25.6 ± 3.5) completed one bout of CRE and one bout of RE in a randomized order, both at a moderate intensity, and separated by at least 7 days. Blood samples drawn pre-exercise, post-exercise, and 1h post-exercise (recovery) were analyzed for CD4+ and CD8+ T-cells and their differentiation status using surface markers CD45RA, CD62L, and CD57, as well as for Th17 cells (CD4+ CD161+ CD196+) using flow cytometry.RESULTSPI had higher numbers of circulating CD57+ EMRA CD4+ T-cells (PA, mean ± SE, 1 ± 2 cells/uL; PI, 6 ± 2 cells/uL; p=0.01; z=2.32) than PA at pre-exercise. Both CRE and RE elicited a significant mobilization of highly-differentiated (CD45RA+ CD62L-; CD57+ CD45RA+ CD62L-) CD8+ T-cells into the circulation post-exercise in both PA and PI groups. Furthermore, CRE resulted in a decrease in the number of circulating Th17 cells post-exercise, while RE increased Th17 cell mobilization compared to the CRE response.CONCLUSIONTaken together, T-cells in PA and PI respond similarly to acute CRE and support previously reported data showing a significant mobilization of highly differentiated T-cells. The present study confirms that moderate intensity RE also elicits this response, but highlights potential differences between CRE and RE on the immune responses of T-cells, particularly in PI individuals.Clinical trial registrationThis research study was registered at clinicaltrials.gov NCT03794050
Developing RT-LAMP Assays for Detection of SARS-CoV-2 in Saliva
Authors: Huang Xin , Tang Gongyu , Ismail Nahed , Wang Xiaowei 
Published: April 2021

AbstractThe coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has killed millions of people worldwide. The current crisis has created an unprecedented demand for rapid test of SARS-CoV-2 infection. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) is a fast and convenient method to amplify and identify the transcripts of a targeted pathogen. However, the sensitivity and specificity of RT-LAMP were generally regarded as inferior when compared with the gold standard RT-qPCR. To address this issue, we combined bioinformatic and experimental analyses to improve the assay performance for COVID-19 diagnosis. First, we developed an improved algorithm to design LAMP primers targeting the nucleocapsid (N), membrane (M), and spike (S) genes of SARS-CoV-2. Next, we rigorously validated these new assays for their efficacy and specificity. Further, we demonstrated that multiplexed RT-LAMP assays could directly detect as low as a few copies of SARS-CoV-2 RNA in saliva, without the need of RNA isolation. Importantly, further testing using saliva samples from COVID-19 patients indicated that the new RT-LAMP assays were in total agreement in sensitivity and specificity with standard RT-qPCR. In summary, our new LAMP primer design algorithm along with the validated assays provide a fast and reliable method for the diagnosis of COVID-19 cases.
The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models
Authors: Rozowsky Joel , Drenkow Jorg , Yang Yucheng T , Gursoy Gamze , Galeev Timur , Borsari Beatrice , Epstein Charles B , Xiong Kun , Xu Jinrui , Gao Jiahao , Yu Keyang , Berthel Ana , Chen Zhanlin , Navarro Fabio , Liu Jason , Sun Maxwell S , Wright James , Chang Justin , Cameron Christopher JF , Shoresh Noam , Gaskell Elizabeth , Adrian Jessika , Aganezov Sergey , Aguet François , Balderrama-Gutierrez Gabriela , Banskota Samridhi , Corona Guillermo Barreto , Chee Sora , Chhetri Surya B , Cortez Martins Gabriel Conte , Danyko Cassidy , Davis Carrie A , Farid Daniel , Farrell Nina P , Gabdank Idan , Gofin Yoel , Gorkin David U , Gu Mengting , Hecht Vivian , Hitz Benjamin C , Issner Robbyn , Kirsche Melanie , Kong Xiangmeng , Lam Bonita R , Li Shantao , Li Bian , Li Tianxiao , Li Xiqi , Lin Khine Zin , Luo Ruibang , Mackiewicz Mark , Moore Jill E , Mudge Jonathan , Nelson Nicholas , Nusbaum Chad , Popov Ioann , Pratt Henry E , Qiu Yunjiang , Ramakrishnan Srividya , Raymond Joe , Salichos Leonidas , Scavelli Alexandra , Schreiber Jacob M , Sedlazeck Fritz J , See Lei Hoon , Sherman Rachel M , Shi Xu , Shi Minyi , Sloan Cricket Alicia , Strattan J Seth , Tan Zhen , Tanaka Forrest Y , Vlasova Anna , Wang Jun , Werner Jonathan , Williams Brian , Xu Min , Yan Chengfei , Yu Lu , Zaleski Christopher , Zhang Jing , Ardlie Kristin , Cherry J Michael , Mendenhall Eric M , Noble William S , Weng Zhiping , Levine Morgan E , Dobin Alexander , Wold Barbara , Mortazavi Ali , Ren Bing , Gillis Jesse , Myers Richard M , Snyder Michael P , Choudhary Jyoti , Milosavljevic Aleksandar , Schatz Michael C , Guigó Roderic , Bernstein Bradley E , Gingeras Thomas R , Gerstein Mark 
Published: April 2021

ABSTRACTUnderstanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of personal epigenomes, for ∼25 tissues and >10 assays in four donors (>1500 open-access functional genomic and proteomic datasets, in total). Each dataset is mapped to a matched, diploid personal genome, which has long-read phasing and structural variants. The mappings enable us to identify >1 million loci with allele-specific behavior. These loci exhibit coordinated epigenetic activity along haplotypes and less conservation than matched, non-allele-specific loci, in a fashion broadly paralleling tissue-specificity. Surprisingly, they can be accurately modelled just based on local nucleotide-sequence context. Combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci and enables models for transferring known eQTLs to difficult-to-profile tissues. Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.
Eye movements reveal spatiotemporal dynamics of visually-informed planning in navigation
Authors: Zhu Seren L. , Lakshminarasimhan Kaushik J. , Arfaei Nastaran , Angelaki Dora E. 
Published: April 2021

AbstractGoal-oriented navigation is widely understood to depend upon internal maps. Although this may be the case in many settings, humans tend to rely on vision in complex, unfamiliar environments. To study the nature of gaze during visually-guided navigation, we tasked humans to navigate to transiently visible goals in virtual mazes of varying levels of difficulty, observing that they took near-optimal trajectories in all arenas. By analyzing participants’ eye movements, we gained insights into how they performed visually-informed planning. The spatial distribution of gaze revealed that environmental complexity mediated a striking trade-off in the extent to which attention was directed towards two complimentary aspects of the world model: the reward location and task-relevant transitions. The temporal evolution of gaze revealed rapid, sequential prospection of the future path, evocative of neural replay. These findings suggest that the spatiotemporal characteristics of gaze during navigation are significantly shaped by the unique cognitive computations underlying real-world, sequential decision making.
Trypanosoma bruceiTim50 Plays a Critical Role in Cell Cycle Regulation and Parasite Infectivity
Authors: Tripathi Anuj , Singha Ujjal K , Cooley Ayorinde , Gillyard Taneisha , Krystofiak Evan , Pratap Siddharth , Davis Jamaine , Chaudhuri Minu 
Published: April 2021

AbstractTim50 is a receptor subunit of the preprotein-translocase of the mitochondrial inner membrane, TIM23.Trypanosoma brucei, the infective agent for African trypanosomiasis, possesses a homologue of Tim50 (TbTim50) with a pair of characteristic DXDX(T/V) phosphatase signature motifs. Here, we demonstrated that besides its protein phosphatase activity, the recombinant TbTim50 binds and hydrolyzes phosphatidic acid in a concentration-dependent manner.In silicostructural homology models identify the putative binding interfaces that may accommodate different phospho-substrates. Interestingly, TbTim50 depletion in the bloodstream form (BF) ofT. bruceireduced cardiolipin (CL) levels and decreased mitochondrial membrane potential (ΔΨ). TbTim50 knockdown (KD) also reduced the population of G2 phase and increased G1 phase; thus, BF cell growth was reduced. Confocal and electron microscopy revealed a defect in regulation of kinetoplast (kDNA) replication due to TbTim50 KD. Depletion of TbTim50 increased the levels of AMPK phosphorylation, and parasite morphology was changed to stumpy-like with upregulation of few stumpy marker gene expressions. Importantly, we observed that TbTim50-depleted parasites were unable to establish infection in mice and rats. Proteomics analysis showed reductions of the translation factors, flagellar transport proteins, and many proteasomal subunits, including the mitochondrial HslVU that is known to play a role in kDNA replication. Reduction of the level of HslV in TbTim50 KD cells was further validated by immunoblot analysis. Altogether, our results showed that TbTim50 is essential for mitochondrial function, regulation of kDNA replication, and cell cycle in the BF. Therefore, TbTim50 is an important target for structure-based drug design to combat African trypanosomiasis.ImportanceAfrican trypanosomiasis, a neglected tropical disease caused by parasitic protozoanTrypanosoma brucei, is transmitted by the tsetse fly prevalent in sub-Saharan Africa. During its digenetic life cycle,T. bruceiundergoes multiple developmental changes to adapt in different environments.T. bruceiBF, dwelling in mammalian blood, generates ATP from glycolysis and hydrolyzes ATP in mitochondria for inner membrane potential. We found that TbTim50, a HAD-family phosphatase, is critical forT. bruceiBF survivalin vitroandin vivo. Depletion of TbTim50 in BF reduced CL levels and mitochondrial ΔΨ and caused a detrimental effect on many cellular functions. Cells accumulated in G1-S phase, and kinetoplast was over-replicated due to depletion of mitochondrial proteasomes, HslVU, a master-regulator of kDNA replication. Cell growth inhibition was accompanied by changes in morphology, AMPK phosphorylation, and upregulation of stumpy-specific gene expression. TbTim50 is essential forT. bruceisurvival and an importantT. bruceitherapeutic target.
Relative Mutant N501Y SARS-CoV-2 Spike Protein RBD Inhibition of Anti-Spike Protein IgG and ACE-2 Binding to Spike Protein Species
Authors: Klegerman Melvin E. , Cirillo Jeffrey D. , McPherson David D. 
Published: April 2021

ABSTRACTIn the SARS-CoV-2 coronavirus pandemic of 2019 (COVID-19), it has become evident that the ACE-2 receptor-binding domain (RBD) of the viral spike protein (SP) is the target of neutralizing antibodies that comprise a critical element of protective immunity to the virus. The most definitive confirmation of this contention is that the two mRNA COVID-19 vaccines in general use, which elicit antibodies specific for the RBD, exhibit approximately 95% protective efficacy against COVID-19. A potential challenge to vaccine efficacy is the emergence of SARS-CoV-2 variants possessing multiple mutations affecting amino acid residues in the RBD. Of concern are variants that arose in the United Kingdom, Brazil and South Africa. One of the variants, designated B.1.351, has shown a higher transmissibility due to greater affinity for the ACE-2 receptor and decreased neutralization by convalescent plasma, therapeutic monoclonal antibodies, and post-vaccination plasma. Common to several of the variants is the N501Y mutation in the RBD, which may be responsible for at least part of the observed variant properties. To test this hypothesis, we measured the ability of the Y501 RBD to inhibit binding of the wild type RBD and full SP (S1 + S2) to the ACE-2 protein and a human monoclonal IgG antibody elicited to the wild type RBD, relative to the wild type RBD in two enzyme-linked immunosorbent assays (ELISAs). We found no significant difference in the IC50of the two RBD species’ inhibition of ACE-2 binding, but unexpectedly found that the IC50of the wild type RBD inhibition of antibody binding was nearly twice that of the Y501 RBD, reflecting a lower affinity. These results suggest that the individual N501Y mutation does not contribute to altered viral properties by itself, but may contribute to a collective conformational shift produced by multiple mutations.
Understanding double descent through the lens of principal component regression
Authors: Lind Christine H. , Yu Angela J. 
Published: April 2021

AbstractA number of recent papers have studied the double-descent phenomenon: as the number of parameters in a supervised learning model increasingly exceeds that of data points (“second-descent”), the empirical risk curve has been observed to not overfit, instead decreasing monotonically, sometimes to a level even better than the best “first-descent” model (using a subset of features not exceeding the number of data points). Understanding exactly when this happens and why it happens is an important theoretical problem. Focusing on the over-parameterized linear regression setting, a commonly chosen case study in the double-descent literature, we present two theoretical results: 1) final second-descent (regression using all of the predictor variables) and principal component (PC) regression without dimensionality reduction are equivalent; 2) the PCR risk curve can be expected to lower bound not only all linearly transformed first-descent models, but also all linearly transformed second-descent models (including the elimination of features as a special case); 3) if the smallest singular value of the design matrix is “large enough” (we will define mathematically), final second-descent can be expected to outperform any first-descent or second-descent model. These insights have important ramifications for a type of semi-supervised learning problem, a scenario which can explain why a face representation trained on unlabeled faces from one race would be better for later supervised-learning tasks on the same race of faces than for faces from another race – this can both provide a scientific explanation for the other-race effect seen in humans and give hints for how to mitigate similar issues in the domain of ethical AI.
Socio-demographic influences on various consumer food safety indices: an empirical study of ethnic Goan pork sausage consumers
Authors: Rajkumar Solomon , Nayar Renuka , Rajagopal Kavitha , Chakurkar Eaknath B. , Venkatesh Vismitha Shree , Nambiar Prejit , Paramesh Venkatesh 
Published: April 2021

PurposeThe purpose of this paper is to assess food safety knowledge, choice behavior and health hazard concerns of ethnic Goan pork sausage consumers through various consumer food safety indices and also to evaluate socio-demographic influences on various consumer food safety indices.Design/methodology/approachPrimary data in the form of 210 questionnaire responses were collected from Goan pork sausage consumers. Based on the responses, seven various consumer food safety indices were derived. The cumulative score of all the indices were normalized (0–1). The association between socio-demographic variables and consumer indices were evaluated using linear regression analysis, Pearson's correlation matrix, principal component analysis (PCA) and correspondence analysis (CA).FindingsThe results of the analysis indicate that the consumption of Goan pork sausages is most prevalent amongst younger people with high education having higher income. A majority of consumers have high score for the four consumer indices. The results of correlation analysis, regression analysis, PCA and CA revealed a significant association of consumer indices with socio-demographic variables.Originality/valueThe results of this study will provide a way forward for the evaluation of existing overall food safety concerns in the target population and in the future would be used for the promotion of good handling practices and health of Goan pork sausage consumers.
Developing a framework for sacred grove management using stakeholder analysis: evidence from sacred groves in Gujarat, India
Authors: Pandey Amit , Sardana Kavita , Gupta Sandeep Kumar 
Published: April 2021

PurposeThe purpose of this study is to use the framework of stakeholder analysis in a participatory democracy, used in forest management planning, for arriving at the best management option for selected sacred groves of Kachchh. This is achieved by accounting for economic, cultural and ecological values and the resulting outcomes in the complex institutional mechanism. Additionally, this study provides a framework for complex decision-making that characterizes the management of sacred groves involving multiple criteria and options accounting for multiple stakeholders that involve conflicting interests.Design/methodology/approachThe analytical hierarchy process was used to calculate the global priorities of management options using the relative importance of stakeholders, weights of different decision criteria to arrive at the best management practice for selected groves of Kachchh. The global priorities of management options rank management practices based on stakeholders' values and their effects on the choice of management strategy as well as on the potential to attain a compromise between competing interests. For this purpose, survey responses of 141 individuals belonging to seven different stakeholder categories were analyzed. Along with focus group discussions, and personal interviews, a stratified random sampling technique was used to survey respondents.FindingsBased on the global priority weights of the alternatives, it is determined that the restoration management option (guggal is restored by planting new guggal sapplings, cattle grazing is prohibited and high levels of ecosystem goods and services are provided) had the highest score, followed by the preservation management option (grazing is allowed on the periphery, juvenile guggal is preserved and moderate ecosystem goods and services are provided). Therefore, restoration of sacred groves is the best management practice of sacred groves in West Kachchh, offering a compromise between maximizing provision of ecosystem services and economic benefits in terms of allowing cattle grazing.Originality/valueThough there are several studies on best management practices for community-owned forests, irrigation systems, and pasture lands, and the role of local institutions in sustaining these common-pool resources; such studies for sacred groves are absent, despite sacred groves being one of the longest surviving common-pool resources that has sustained it over several decades. This is the first study that uses the framework of stakeholder analysis to arrive at the best management practice for sacred groves. The uniqueness of the study lies in a comprehensive evaluation of ecological–economic–cultural interests of multiple stakeholders toward management of sacred groves.
Working with emotions: cultural employee perspectives to service management expectations
Authors: Babatunde Akanji , Mordi Chima , Ajonbadi Hakeem Adeniyi , Oruh Emeka Smart 
Published: April 2021

PurposeDrawing on the emotional labour theory, the purpose of this paper is to explore the effects of cultural orientation on emotion regulation and display processes for service employees.Design/methodology/approachBased on a Nigerian study where literature is scarce, data were gathered from semi-structured interviews conducted with 40 call centre service agents.FindingsThe findings identified three key values around reinforcing social cohesion, anticipated self-curtailment, hierarchy and expressions of servility based on broader societal needs to promote relational harmony when managing customer relations during inbound calls into the call centre.Research limitations/implicationsThe extent to which the findings can be generalised is constrained by the limited and selected sample size. However, the study makes contributions to the service work theory by identifying the extent to which communication of emotions is informed in large parts by local culture and seeks to incite scholarly awareness on the differences of emotional display rules from a developing country other than western contexts.Originality/valueThis paper is among the first to focus on the interface between culture and emotional labour from a Sub-Saharan African context.