bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-throughput TCRB enrichment sequencing of human cord blood exhibited a distinct fetal T cell repertoire in the third trimester of pregnancy
Authors: Dong Yan , Chen Wei , Wang Jinmin , Wu Xiaolei , Zhao Yangyu , Cai Yuhang , Han Yingxin , Wang Yuqi , Li Hongmei , Qiao Jie , Wei Yuan 
Published: September 2022

AbstractStudy questionWhat are the molecular characteristics during the maturation process of the human fetal immune system in the third trimester of pregnancy?Summary answerBoth the diversity and length of complementarity determining region 3 (CDR3s) in the fetal TCRB repertoire were less than those of adult CDR3s, and the fetal CDR3 length increased with gestation weeks in late pregnancy.What is known alreadyThe adaptive immune system recognizes various pathogens based on a large repertoire of T-cell receptors (TCR repertoire), but the maturation dynamics of the fetal TCR repertoire in the third trimester are largely unknown. The CDR3is the most diversified segment in the T-cell receptor β chain (TCRB) that binds and recognizes the antigen.Study design, size, and durationThis was a basic research to assess the composing characteristics of TCRBs in core blood and the dynamic pattern with fetal development in the third trimester of pregnancy.Participants/materials, setting methodsHigh-throughput TCRB-enrichment sequencing was utilized to characterize the TCRB repertoire of cord blood at 24~38 weeks of gestational age (WGA) with nonpreterm fetuses and to investigate their difference compared with that of adult peripheral blood.Main results and the role of chanceCompared to the adult control, the fetal TCRB repertoire had a 4.8-fold lower number of unique CDR3s, a comparable Shannon diversity index (p=0.7387), a lower mean top clone rate (p< 0.001) and a constrictive top 1000 unique clone rates. Although all kinds of TCRBV and TCRBJ genes present in adult CDR3s were identified in fetuses, nearly half of these fragments showed a significant difference in usage. Moreover, the fetal TCRB repertoire held a shorter CDR3 length, and the CDR3 length showed a progressive increase with fetal development. Jensen–Shannon (JS) divergences of TCRBV and TCRBJ gene usage in dizygotic twins were much lower than those in unrelated pairs. In the parental-fetal pair, JS divergence of TCRBV gene usage was not obviously different, while that of TCRBJ gene usage was only slightly lower.Limitations, reasons for cautionThe sample size is limited due to the limited accessibility to cord blood in late pregnancy with healthy nonpreterm fetuses.Wider implications of the findingsOur findings reveal the unique properties of fetal TCRB repertoires in the third trimester, fill the gap in our understanding of the maturation process of prenatal fatal immunity, and deepen our understanding of the immunologically relevant problems in neonates.Study funding/competing interest(s)This work was supported by the National Natural Science Foundation of China (82171661) and Tianjin Municipal Science and Technology Special Funds for Enterprise Development (NO. 14ZXLJSY00320). The authors declare that they have no competing interests.
Near-anoxia induces immobilisation and sustains viability of sperm in ant queens: Novel insights into mechanisms of prolonged sperm storage
Authors: Gotoh Ayako , Takeshima Mika , Mizutani Ken-ichi 
Published: September 2022

AbstractInsect females store sperm in a spermatheca after copulation for some duration to use it later for fertilisation. At the beginning of their adult lives, ant queens can preserve numerous viable sperm cells from copulation for over ten years. However, the key factors influencing long-term sperm storage have not been identified. Here we show that the spermathecal environment is near anoxic, which induces sperm immobilisation. Furthermore, mitochondrial respiratory inhibitors suppress sperm motility, suggesting that sperm immobilisation may be caused by a shortage of ATP generated from only glycolysis under near anoxic condition. Sperm immobilisation is not induced by acidification via glycolytic metabolism because the spermathecal fluid is not acidic. Finally, we show that artificial anoxic conditions rather than aerobic conditions sustain viable sperm cells. Therefore, near-anoxia is a key factor influencing long-term sperm storage in ant queens. The viability of sperm cells under artificial anoxia, however, is lower than of those dissected immediately from queens. Moreover, the immotile sperm cells under more than 4 h of anoxia do not begin swimming after aerobic exposure, unlike those that were in anoxic conditions for less than 2 h. This indicates that factors other than anoxia are also necessary for long-term sperm preservation.
A common humanMLKLpolymorphism confers resistance to negative regulation by phosphorylation
Authors: Garnish Sarah E. , Martin Katherine R. , Kauppi Maria , Jackson Victoria , Ambrose Rebecca , Eng Vik Ven , Chiou Shene , Meng Yanxiang , Frank Daniel , Tovey Crutchfield Emma C. , Patel Komal M. , Jacobsen Annette V. , Atkin-Smith Georgia K. , Rago Ladina Di , Doerflinger Marcel , Horne Christopher R. , Hall Cathrine , Young Samuel N. , Athanasopoulos Vicki , Vinuesa Carola G. , Lawlor Kate E. , Wicks Ian P. , Ebert Gregor , Ng Ashley P. , Slade Charlotte A. , Pearson Jaclyn S. , Samson Andre L. , Silke John , Murphy James M. , Hildebrand Joanne M. 
Published: September 2022

ABSTRACTAcross the globe, 2-3% of humans carry thep.Ser132Prosingle nucleotide polymorphism inMLKL, the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. We show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKLS132Pin biological membranes and MLKLS132Poverriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalentMlkl S131Pmutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells.In vivo,MlklS131Phomozygosity reduces the capacity to clearSalmonellafrom major organs and retards recovery of hematopoietic stem cells. Thus, by dysregulating necroptosis, the S131P substitution impairs the return to homeostasis after systemic challenge. Present day carriers of theMLKL S132Ppolymorphism may be the key to understanding how MLKL and necroptosis modulate the progression of complex polygenic human disease.
DOTA chelation through click chemistry enables favorable biodistribution of89Zr-radiolabeled antibodies: A comparison with DFO chelation
Authors: Imura Ryota , Kumakura Yoshitaka , Yan Lin , Shimoura Yuki , Takahashi Hiroyuki , Ida Hiroyuki , Wada Youichiro , Akimitsu Nobuyoshi 
Published: September 2022

AbstractCurrently, the DFO chelator is commonly used to conjugate monoclonal antibodies (mAbs) and89Zr, whereas the DOTA chelator is commonly used to conjugate mAbs and alpha- and beta-emitting metal radionuclides. However, if the degradation of [89Zr]Zr-DFO-mAb is not negligible, the in vivo biodistribution of89Zr might not reflect that of metal radionuclides conjugated with DOTA-mAb. We hypothesized that [89Zr]Zr-DOTA-mAb as a new imaging counterpart would accurately predict the biodistribution of therapeutic metal radionuclides delivered by DOTA-mAb. In this study, we prepared [89Zr]Zr-DOTA-trastuzumab for the first time by a two-step reaction using click chemistry and then investigated the differences in biodistribution profiles between two chelating approaches for89Zr.MethodsWe prepared [89Zr]Zr-DOTA-trastuzumab from DOTA-tetrazine conjugates (DOTA-Tz) and transcyclooctene-trastuzumab conjugates (TCO-trastuzumab). We first radiolabeled DOTA-Tz with89Zr in a reaction solution of MeOH and HEPES buffer and then used a click reaction to obtain [89Zr]Zr-DOTA-Tz/TCO-trastuzumab. We performed biodistribution studies and PET imaging with [89Zr]Zr-DOTA-trastuzumab in a mouse model of HER2-positive ovarian cancer, SKOV3 xenograft mice at 24, 72, and 144 hours post-injection and compared these data with those of [89Zr]Zr-DFO-trastuzumab.ResultsTCO-trastuzumab was radiolabeled with [89Zr]Zr-DOTA-Tz in the two-step reaction in good radiochemical yield (57.8 ± 17.6%). HER2-positive tumors were clearly visualized with [89Zr]Zr-DOTA-trastuzumab in PET imaging studies. The temporal profile changes of89Zr radioactivity in SKOV3 tumors and bone marrow were sufficiently different between [89Zr]Zr-DOTA-trastuzumab and [89Zr]Zr-DFO-trastuzumab (P < 0.05). Conclusion: [89Zr]Zr-DOTA-trastuzumab can be produced by the two-step radiolabeling reaction based on the Tz/TCO click reaction. Presumably,89Zr released from DFO is not negligible. In contrast, [89Zr]Zr-DOTA-mAb would better predict the biodistribution of [177Lu]Lu- or [225Ac]Ac-DOTA-mAb than [89Zr]Zr-DFO-mAb, thus avoiding the use of different chelator for89Zr at the expense of the click chemistry step.Graphical Abstract
Progression Analysis of Disease with Survival (PAD-S) by SurvMap identifies different prognostic subgroups of breast cancer in a large combined set of transcriptomics and methylation studies
Authors: Forés-Martos Jaume , Suay-García Beatriz , Bosch-Romeu Raquel , Sanfeliu-Alonso Maria Carmen , Falcó Antonio , Climent Joan 
Published: September 2022

AbstractProgression analysis of disease (PAD) is a methodology that incorporates the output of Disease-Specific Genomic Analyses (DSGA) to an unsupervised classification scheme based on Topological Data Analysis (TDA). PAD makes use of data derived from healthy individuals to split individual diseased samples into healthy and disease components. Then, the shape characteristics of the disease component are extracted trough the generation of a combinatioral graph by means of the Mapper algorithm. In this paper we introduce a new filtering function for the Mapper algorithm that naturally integrates information on genes linked to disease-free or overall survival. We propose a new PAD-extended methodology termed Progression Analysis of Disease with Survival (PAD-S) and implement it in an R package called SurvMap which allows users to carry out all the steps involved in PAD-S, as well as in traditional PAD analyses. We tested PAD-S methodology using SurvMap on a large combined transcriptomics breast cancer dataset demonstrating its capacity to identify sets of samples displaying highly significant differences in terms of disease free survival (p = 8 × 10−14) and idiosyncratic biological features. PAD-S and SurvMap were also able to identify sets of samples with significantly different relapse-free survivals and molecular profiles inside breast cancer intrinsic subgroups (luminal A, luminal B, Her2, and basal). Finally, to illustrate that PAD-S and SurvMap are general-purpose analysis tools that can be applied to different types of omics data, we also carried out analyses in a breast cancer methylation dataset derived from The Cancer Genome Atlas (TCGA) identifying groups of patients with significant differences in terms of overall survival and methylation profiles.
High diversity and sharing of strongylid nematodes in humans and great apes co-habiting unprotected area in Cameroon
Authors: Ilík Vladislav , Kreisinger Jakub , Modrý David , Schwarz Erich M. , Tagg Nikki , Mbohli Donald , Irène Charmance Nkombou , Petrželková Klára J. , Pafčo Barbora 
Published: September 2022

ABSTRACTRapid increases in human populations and environmental changes of past decades have led to intensified contact with wildlife and significantly contributed to pathogen transmission in both directions, especially between humans and non-human primates, whose close phylogenetic relationship facilitates cross-infection. Using high-throughput sequencing, we studied strongylid communities in sympatric western lowland gorillas, central chimpanzees and humans co-occurring in an unprotected area in the northern periphery of the Dja Faunal Reserve, Cameroon. We identified 65 strongylid ITS-2 amplicon sequencing variants (ASVs) in humans and great apes. Great apes exhibited higher strongylid diversity than humans. Necator and Oesophagostomum were the most prevalent genera, and we commonly observed mixed infections of more than one strongylid species. Human strongylid nematodes were dominated by the human hookworm N. americanus, while great apes were mainly infected with N. gorillae, O. stephanostomum and trichostrongylids. We were also able to detect rare strongylid taxa (such as Ancylostoma and Ternidens). We detected eight ASVs shared between humans and great apes (four N. americanus variants, two N. gorillae variants, one O. stephanostomum type I and one Trichostrongylus sp. type II variant). Our results show that knowledge of strongylid communities in primates, including humans, is still limited. Sharing the same habitat, especially outside protected areas (where access to the forest is not restricted), can enable mutual exchange of parasites and can even override host phylogeny or conserved patterns.
A systematic review of the effects of recreation on mammals and birds in mountains: Insights and future research directions
Authors: Hochreutener Adrian , Rupf Reto , Pickering Catherine , Signer Claudio 
Published: September 2022

AbstractMountainous areas are popular destinations for outdoor recreation, which can have environmental impacts on wildlife. We assessed research studies about the impacts of recreation on mammals and birds in montane, subalpine and alpine zones using a systematic literature review methodology to identify trends and gaps. We found that research on this topic so far has concentrated on specific regions, seasons, infrastructure, activities and taxa. Most of the 67 articles revived were from Europe (52%) or Northern America (37%) and mainly from subalpine habitats (49%), focused on recreation infrastructure (51%) and mainly done either in summer (47%) or winter (25%). Research was not taxonomically representative but focused on cervids (Cervidae, 21%), bovids (Bovidae, 17%) and grouse (Phasianidae, 8%). It included few species of high conservation value. Almost all research (91%) found significant effects, which were predominantly negative (82%). Infrastructure, such as trails, had the most evidence for negative effects, followed by activities such as hiking and backcountry skiing. Much of the research looked at impacts at individual (42%) or population level (40%) responses, such as changes in behaviour or reductions in habitat, with limited research on communities (7%) or for popular activities such as mountain biking. We invite researchers to make use of emerging technologies, such as remote sensing, and to address research gaps including more regions, taxa and activities. Utilizing current research, land managers can implement more evidence-based strategies to minimise impacts of recreation and mitigate human-wildlife conflicts.
Comparative RNA-seq analysis of resistant and susceptible banana genotypes reveals molecular mechanisms in response toBanana bunchy top virus(BBTV)
Authors: Lantican Darlon V. , Nocum Jen Daine L. , Manohar Anand Noel C. , Mendoza Jay-Vee S. , Gardoce Roanne R. , Lachica Grace C. , Gueco Lavernee S. , Dela Cueva Fe M. 
Published: September 2022

ABSTRACTBanana is a major fruit crop in the Philippines and remains to be a large contributor to the country’s dollar reserve. Among the main hindrances in global banana production, diseases such as Banana bunchy top disease (BBTD) caused by BBTV can bring catastrophic loss to any banana plantation. To elucidate the resistance mechanism and understand the interplay of host factors in the presence of the invading pathogen, we implemented RNA-seq-based comparative transcriptomics analyses of mock- and BBTV-inoculated resistant (wildM. balbisiana) and susceptible (M. acuminata‘Lakatan’) banana genotypes. Similar patterns of expression for 119 differentially expressed genes (DEGs) were observed on both genotypes, representing the typical defense response of banana to BBTV. A set of 173 DEGs specific to the susceptible ‘Lakatan’ banana cultivar revealed potential host factors and susceptibility mechanisms involved in successful BBTV infection. Further, differential transcriptomic analysis revealed 268 DEGs exclusive to the resistant wildM. balbisiana, unraveling insights into the complex resistance mechanisms involved in BBTV defense such as pathogen perception, phytohormone action, reactive oxygen species (ROS), hypersensitive response (HR), production of secondary metabolites and cell wall modification. The DEGs identified in this study will aid in the design of foreground markers for the precise integration of resistance genes during marker-assisted breeding programs. Furthermore, the application of these results will also enable the foreseen deployment of genome-edited banana cultivars targeting the resistance and host factor genes towards a future-proof banana industry.
Multilayer Networks of Plasmid Genetic Similarity Reveal Potential Pathways of Gene Transmission
Authors: Shapiro Julie Teresa , Zorea Alvah , Brown Kav Aya , Ontiveros Vicente J. , Mizrahi Itzak , Pilosof Shai 
Published: September 2022

AbstractAntimicrobial resistance (AMR) is a major threat to public health. Plasmids are principal vectors of antimicrobial resistance genes, greatly contributing to their spread and mobility across hosts. Nevertheless little is known about the dynamics of plasmid genetic exchange across animal hosts. The cow rumen ecosystem is an excellent model system because it hosts diverse plasmid communities which interact and exchange genes. Here, we use theory and methodology from network and disease ecology to investigate the potential of gene transmission between plasmids using a data-set of 21 plasmidomes from a single dairy cow population. We constructed a multilayer network based on pairwise genetic similarity between plasmids serving as a signature for past genetic exchange to identify potential routes and mechanisms of gene transmission within and between cows. The transmission network was dominated by links between cows. Modularity analysis unraveled a major cross-cow transmission pathway with additional small pathways. Plasmid functions influenced network structure: plasmids containing mobility genes were more connected; those with the same AMR genes formed their own modules. We find signatures of gene superspreading in which a few plasmids and cows are responsible for most gene exchange. An agent-based transmission model showed that a new gene invading the cow population is likely to reach all cows. Finally, we showed that link weights contain a non-random signature for the mechanisms of gene transmission allowing us to differentiate between dispersal and genetic exchange. These results provide insights into the mechanisms by which genes, including those providing AMR, spread across animal hosts.
Selection Of Models For The Regression Problems In Biology Using Chi-Square Test
Authors: Gupta Aaditya Prasad 
Published: September 2022

ABSTRACTBiological systems, at all scales of organization from nucleic acids to ecosystems, are inherently complex and variable. Therefore mathematical models have become an essential tool in systems biology, linking the behavior of a system to the interaction between its components. Parameters in empirical mathematical models for biology must be determined using experimental data, a process called regression because the experimental data are noisy and incomplete. The term “regression” dates back to Galton’s studies in the 1890s. Considering all this, biologists, therefore, use statistical analysis to detect signals from the system noise. Statistical analysis is at the core of most modern biology and many biological hypotheses, even deceptively. Regression analysis is used to demonstrate association among the variables believed to be biologically related and fit the model to give the best model. There are two types of regression, linear and nonlinear regression to determine the best fit of the model. In this manuscript, we perform a least squares error fit to different models and select the best fit model using theχ2-test, and determine the p-value of the selected model to data that was collected when various doses of a drug were injected into three animals, and the change in blood pressure for each animal was recorded.
Sedimentary DNA can reveal the past population dynamics of a pelagic copepod
Authors: Nakane Kai , Liu Xin , Doi Hideyuki , Dur Gaël , Kuwae Michinobu , Ban Syuhei , Tsugeki Narumi 
Published: September 2022

SummaryCopepods play a key trophic role as secondary producers, transferring primary production to higher trophic levels such as fish. Copepod production contributes significantly to successful fish recruitment. Despite their importance, knowledge of copepod dynamics over several decades remains limited due to the lack of long-term data series with adequate sampling and analysis. However, an understanding of long-term copepod dynamics is urgently required to strive toward better management for sustainable aquatic ecosystems and fish recruitment.Sedimentary DNA (sedDNA) has been developing as a useful tool for reconstructing past plankton dynamics. This study evaluates whether sedDNA targeting the pelagic copepod,Eodiaptomus japonicus, in Lake Biwa (Japan) can be an effective tool for elucidating its past population dynamics.We applied a quantitative polymerase chain reaction method targeting the mitochondrial cytochrome c oxidase subunit I gene on two sediment cores and compared the detected sedDNA concentrations with the unique long-term dataset of demographic traits, biomass, specific growth rate, production, subitaneous eggs, and resting eggs ofE. japonicus.The sedDNA concentration ofE. japonicusrecovered from sediment layers correlated significantly within situproduction, biomass, and production of immediately hatching eggs but not with resting eggs or specific growth rate. Our study provides evidence for the effective use of sedDNA as a tracking tool for assessing past copepod production dynamics.
Targeting extracellular vesicle delivery to the lungs by microgel encapsulation
Authors: Cober Nicholas D. , Rowe Katelynn , Deng Yupu , Benavente-Babace Ainara , Courtman David W. , Godin Michel , Stewart Duncan J. 
Published: September 2022

AbstractExtracellular vesicles (EVs) secreted by stem and progenitor cells have significant potential as cell-free ‘cellular’ therapeutics. Yet, small EVs (<200 nm) are rapidly cleared after systemic administration, mainly by the liver, presenting challenges targeting EVs to a specific organ or tissue. Microencapsulation using natural nano-porous hydrogels (microgels) has been shown to enhance engraftment and increase the survival of transplanted cells. We sought to encapsulate EVs within microgels to target their delivery to the lung by virtue of their size-based retention within the pulmonary microcirculation. Mesenchymal stromal cell (MSC) derived EVs were labelled with the lipophilic dye (DiR) and encapsulated within agarose-gelatin microgels. Endothelial cells and bone marrow derived macrophages were able to take up EVs encapsulated in microgelsin vitro, but less efficiently than the uptake of free EVs. Following intrajugular administration, microgel encapsulated EVs were selectively retained within the lungs for 72 hours, while free EVs were rapidly cleared by the liver. Furthermore, microgel loaded EVs demonstrated greater uptake by lung cells, in particular CD45+ immune cells, as assessed by flow cytometry compared to free EVs. Microencapsulation of EVs may be a novel tool for enhancing targeted delivery of EVs for future therapeutic applications.