bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polyfunctional IL-17A+ MAIT cells are expanded in the peripheral blood of patients with HLA-B27+ axial spondyloarthritis
Authors: Lefton Micah , Sharma Nihaarika , Patel Akash R. , Sparks Jeffrey A. , Ermann Joerg 
Published: January 2022

AbstractObjectivesStudies in axial spondyloarthritis (axSpA) have yielded conflicting results regarding the identity of the major IL-17A-producing lymphocyte populations. The goal of this study was to comprehensively assess the production of IL-17A and related cytokines by peripheral blood lymphocytes in axSpA.MethodsPeripheral blood mononuclear cells were isolated from patients with axSpA and healthy controls matched for age, sex and HLA-B27 status. Unstimulated cells and cells activated with PMA/Ionomycin were analyzed by 25-parameter fluorescent flow cytometry. Data were analyzed by hierarchical gating, UMAP and SPICE.ResultsExcept for a reduced frequency of mucosal-associated invariant T (MAIT) cells and natural killer (NK) cells, there were no other significant differences in abundance of major lymphocyte populations in axSpA patients compared with controls. Increased IL-17A production in axSpA was observed in total non-B lymphocytes and in MAIT cells. The fraction of MAIT cells expressing the tissue residency markers CD69 and CD103 was increased in axSpA. CD103 positive MAIT cells were enriched for IL-17A producers. axSpA patients demonstrated an expansion of MAIT cell subsets producing IL-17A, IL-17F, GM-CSF and TNF. This expansion was only observed in HLA-B27+ patients.ConclusionsWe document an expansion of polyfunctional IL-17A+ MAIT cells in the peripheral blood of HLA-B27+ patients with axSpA. These results are consistent with the implied role of intestinal dysbiosis or inflammation in axSpA pathogenesis.Key messagesWhat is already known about this subject?Various IL-17A-producing lymphocyte populations have been implicated in the pathogenesis of axSpA.What does this study add?Polyfunctional MAIT cells capable of producing IL-17A, IL-17F, GM-CSF and TNF are expanded in the peripheral blood of HLA-B27+ patients with axSpA.How might this impact on clinical practice or future developments?Overproduction of IL-17A by MAIT cells is the most consistent finding of peripheral blood lymphocyte studies in axSpA.Our data support the pathogenetic link between intestinal and axial inflammation in axSpA.
Impact of pre-breeding feeding practices on rabbit mammary gland development at mid-pregnancy
Authors: Hue-Beauvais C , Bébin K , Robert R , Gardan-Salmon D , Maupin M , Brun N , Aujean E , Jaffrezic F , Simon S , Charlier M , Le Provost F 
Published: January 2022

AbstractOptimizing rabbit does preparation during early life to improve reproductive potential is a major challenge for breeders. Does selected for reproduction have specific nutritional needs, which may not be supplied with the common practice of feed restriction during rearing in commercial rabbit production. Nutrition during early life was already known to influence metabolism, reproduction and mammary gland development later in life, in particular during pregnancy. The aim of this study was to analyze the impact of four different feeding strategies in the early life of rabbit females (combination of high or moderate feed restriction from 5 to 9 weeks of age with restricted or ad libitum feeding regime from 9 to 12 weeks of constituting the pubertal period) on their growth, reproductive capacities and mammary development at mid-pregnancy.Unlike food intake, which remains regular, mean body weight gain was inversely proportional to the dietary restriction applied over the considered periods. The feeding strategies in place for the four groups had no effect on the reproductive parameters of the females at mid-pregnancy, as opposed to certain metabolic parameters such as cholesterolemia, that decreased with dietary intake at puberty (p≤0.05). Furthermore, restriction programs have impacted mammary tissular structures at mid-pregnancy. The expression of lipid metabolism enzymes (Fatty acid synthase N and Stearoyl co-A desaturase) is also increased in mammary epithelial tissue at mid-pregnancy by the dietary strategies implemented (p≤0.05). Moreover, milk gene expression, used as differentiation markers, indicates a better mammary epithelial development regarding further lactation, in the case of the less restrictive strategies during early life period, especially the higher feeding allowance. Our results highlight the importance of investigating feeding conditions of young female rabbits and nutrition in early life rearing, in order to provide specific recommendations for optimizing lactation and thus preventing neonatal mortality of the offspring.
Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice
Authors: Gargareta Vasiliki-Ilya , Reuschenbach Josefine , Siems Sophie B. , Sun Ting , Piepkorn Lars , Mangana Carolina , Späte Erik , Goebbels Sandra , Huitinga Inge , Möbius Wiebke , Nave Klaus-Armin , Jahn Olaf , Werner Hauke B. 
Published: January 2022

AbstractHuman myelin disorders are commonly studied in mouse models. Since both clades evolutionarily diverged approximately 85 million years ago, it is critical to know to what extent the myelin protein composition has remained similar. Here we use quantitative proteomics to analyze myelin purified from human white matter and find that the relative abundance of the structural myelin proteins PLP, MBP, CNP and SEPTIN8 correlates well with that in C57Bl/6N- mice. Conversely, multiple other proteins were identified exclusively or predominantly in human or mouse myelin. This is exemplified by peripheral myelin protein-2 (PMP2), which was specific to human CNS myelin, while tetraspanin-2 (TSPAN2) and connexin-29 (CX29/GJC3) were confined to mouse myelin. Assessing published scRNA-seq-datasets, human and mouse oligodendrocytes display well-correlating transcriptome profiles but divergent expression of distinct genes includingPmp2, Tspan2andGjc3. Species-dependent diversity of oligodendroglial mRNA-expression and myelin protein composition can be informative when translating from mouse models to humans.
How Glutamate Promotes Liquid-liquid Phase Separation and DNA Binding Cooperativity ofE. coliSSB Protein
Authors: Kozlov Alexander G. , Cheng Xian , Zhang Hongshan , Shinn Min Kyung , Weiland Elizabeth , Nguyen Binh , Shkel Irina A. , Zytkiewicz Emily , Finkelstein Ilya J. , Thomas Record M. , Lohman Timothy M. 
Published: January 2022

AbstractE. colisingle-stranded-DNA binding protein (EcSSB) displays nearest-neighbor (NN) and non-nearest-neighbor (NNN)) cooperativity in binding ssDNA during genome maintenance. NNN cooperativity requires the intrinsically-disordered linkers (IDL) of the C-terminal tails. Potassium glutamate (KGlu), the primaryE. colisalt, promotes NNN-cooperativity, while KCl inhibits it. We find that KGlu promotes compaction of a single polymeric SSB-coated ssDNA beyond what occurs in KCl, indicating a link of compaction to NNN-cooperativity.EcSSB also undergoes liquid-liquid phase separation (LLPS), inhibited by ssDNA binding. We find that LLPS, like NNN-cooperativity, is promoted by increasing [KGlu] in the physiological range, while increasing [KCl] and/or deletion of the IDL eliminate LLPS, indicating similar interactions in both processes. From quantitative determinations of interactions of KGlu and KCl with protein model compounds, we deduce that the opposing effects of KGlu and KCl on SSB LLPS and cooperativity arise from their opposite interactions with amide groups. KGlu interacts unfavorably with the backbone (especially Gly) and side chain amide groups of the IDL and therefore promotes amide-amide interactions in LLPS and NNN-cooperativity. By contrast, KCl interacts favorably with these amide groups and therefore inhibits LLPS and NNN-cooperativity. These results highlight the importance of salt interactions in regulating the propensity of proteins to undergo LLPS.
Elevation of Clavibacter michiganensis subsp. californiensis to species level as Clavibacter californiensis sp. nov., merging and re-classification of Clavibacter michiganensis subsp. chilensis and Clavibacter michiganensis subsp. phaseoli as Clavibacter chilensis sp. nov. based on complete genome in-silico analyses
Authors: Arizala Dario , Dobhal Shefali , Alvarez Anne M. , Arif Mohammad 
Published: January 2022

ABSTRACTThe Gram-positive Clavibacter genus is currently divided into seven species (C. michiganensis, C. nebraskensis, C. capsici, C. sepedonicus, C. tessellarius, C. insidiosus and C. zhangzhiyongii) and three subspecies (C. michiganensis subsp. californiensis, C. michiganensis subsp. chilensis and C. michiganensis subsp. phaseoli). Recent studies have indicated that the taxonomic rank of the subspecies must be re-evaluated. In this research, we assessed the taxonomy position of the three C. michiganensis subspecies and clarified the taxonomic nomenclature of other 75 Clavibacter strains. The complete genomes of the type strains of the three Clavibacter subspecies, type strain of C. tessellarius and C. nebraskensis A6096 were sequenced using PacBio RSII technology. Application of whole-genome-based computational approaches such as average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), multi-locus sequence analysis (MLSA) of seven housekeeping genes (acnA, atpD, bipA, icdA, mtlD, recA and rpoB), phylogenomic tree reconstructed from 1,028 core genes, and ANI-based phylogeny pinpointed conclusive evidence to raise C. michiganensis subsp. californiensis to the species status. These results led us to propose the establishment of C. californiensis sp. nov. as a species with its type strain C55ᵀ (=CFBP 8216ᵀ=ATCC BAA-2691ᵀ). Moreover, the orthologous and in-silico dot plot analyses, along with the aforementioned bioinformatic strategies, revealed a high degree of homology between C. michiganensis subsp. chilensis and C. michiganensis subsp. phaseoli. Based on these outcomes, we proposed to combine both subspecies into a single taxon and elevate its rank to the species level as C. chilensis sp. nov., with ZUM3936ᵀ (= ATCC BAA-2690ᵀ = CFBP 8217ᵀ) as the type strain.
Development of an HIV reporter virus that identifies latently infected CD4+T cells
Authors: Kim Eun Hye , Manganaro Lara , Schotsaert Michael , Brown Brian D. , Mulder Lubbertus C.F. , Simon Viviana 
Published: January 2022

SUMMARYThere is no cure for HIV infection as the virus establishes a latent reservoir, which escapes highly active antiretroviral treatments. One major obstacle is the difficulty to identify cells that harbor latent proviruses. We devised a novel viral vector that carries a series of versatile reporter molecules that are expressed in an LTR-dependent or LTR-independent manner and allows to accurately distinguish productive from latent infection. Using primary human CD4+T cells, we show that transcriptionally silent proviruses make up over 50% of all infected cells. These latently infected cells harbor proviruses, but lack evidence for viral transcription. LTR silent integrations occurred to variable degrees in all CD4+T-subsets examined with CD4+TEMand CD4+Tregdisplaying the highest frequency. Viral vectors such as the one described here, permit interrogation HIV latency at a single-cell resolution, revealing mechanisms of latency establishment and allowing for the characterization of effective latency reversing agents.
MicroRNA Detection in Biological Media Using a Split Aptamer Platform
Authors: Wang Liming , Hast Kern , Aggarwal Tushar , Baci Melih , Hong Jonathan , Izgu Enver Cagri 
Published: January 2022

ABSTRACTIntercellular microRNA (miRNA)-based communication has been implicated in a wide array of functional and dysfunctional biological processes. This has raised attention to the potential use of miRNAs as biomarkers for disease diagnosis and prognosis and produced interest in their detection. Though the list of clinically significant miRNA biomarkers is rapidly expanding, it remains challenging to adapt current tools to investigate new targets in biological environments. Systematic approaches for the rapid development of miRNA biosensors are valuable to reduce this disparity. We describe here a methodology for developing aptamer-based fluorescent biosensors that can specifically detect miRNAs in biological environments, including culture medium from HeLa cells, human serum, and human plasma. This methodology includes the semi-rational design of the hybridization between a pair of split DNA aptamer oligonucleotides and the miRNA target to build a pool of potential sensor designs, and the screening of this pool for designs with high signal-to-background ratio and sequence selectivity. The method uses natural oligonucleotides without chemical modification, and is effective in buffer, 10%, and 30% (v/v) biological media. Following this approach, we developed sensors that detect three miRNA targets (miR-19b, miR-21, and miR-92a) at concentrations as low as 5 nM without amplification and are selective against single-nucleotide mutants. This work expands upon the current design principles of nucleic acid-based biosensors and provides a method to rapidly develop diagnostic tools for novel and niche miRNA targets of interest.
Omicron-associated changes in SARS-CoV-2 symptoms in the United Kingdom
Authors: Vihta Karina-Doris , Pouwels Koen B. , Peto Tim EA , Pritchard Emma , House Thomas , Studley Ruth , Rourke Emma , Cook Duncan , Diamond Ian , Crook Derrick , Clifton David A. , Matthews Philippa C. , Stoesser Nicole , Eyre David W. , Walker Ann Sarah ,   the COVID-19 Infection Survey team
Published: January 2022

ABSTRACTBackgroundThe SARS-CoV-2 Delta variant has been replaced by the highly transmissible Omicron BA.1 variant, and subsequently by Omicron BA.2. It is important to understand how these changes in dominant variants affect reported symptoms, while also accounting for symptoms arising from other co-circulating respiratory viruses.MethodsIn a nationally representative UK community study, the COVID-19 Infection Survey, we investigated symptoms in PCR-positive infection episodes vs. PCR-negative study visits over calendar time, by age and vaccination status, comparing periods when the Delta, Omicron BA.1 and BA.2 variants were dominant.ResultsBetween October-2020 and April-2022, 120,995 SARS-CoV-2 PCR-positive episodes occurred in 115,886 participants, with 70,683 (58%) reporting symptoms. The comparator comprised 4,766,366 PCR-negative study visits (483,894 participants); 203,422 (4%) reporting symptoms. Symptom reporting in PCR-positives varied over time, with a marked reduction in loss of taste/smell as Omicron BA.1 dominated, maintained with BA.2 (44%/45% 17 October 2021, 16%/13% 2 January 2022, 15%/12% 27 March 2022). Cough, fever, shortness of breath, myalgia, fatigue/weakness and headache also decreased after Omicron BA.1 dominated, but sore throat increased, the latter to a greater degree than concurrent increases in PCR-negatives. Fatigue/weakness increased again after BA.2 dominated, although to a similar degree to concurrent increases in PCR-negatives. Symptoms were consistently more common in adults aged 18-65 years than in children or older adults.ConclusionsIncreases in sore throat (also common in the general community), and a marked reduction in loss of taste/smell, make Omicron harder to detect with symptom-based testing algorithms, with implications for institutional and national testing policies.SummaryIn a UK community study, loss of taste/smell was markedly less commonly reported with Omicron BA.1/BA.2 than Delta SARS-CoV-2 infections, with smaller declines in reported shortness of breath, myalgia and fatigue/weakness, but increases in sore throat, challenging symptom-based testing algorithms.
Booster vaccination to curtail COVID-19 resurgence - population-level implications of the Israeli campaign
Authors: Gavish Nir , Yaari Rami , Huppert Amit , Katriel Guy 
Published: January 2022

AbstractIsrael was one of the first countries to administer mass vaccination. Consequently, it was among the first countries to experience significant breakthrough infections due to the waning of vaccine-induced immunity, which led to a resurgence of the epidemic. To mitigate the outbreak, Israel launched a pioneering booster campaign. Israel’s success in curtailing the Delta resurgence while imposing only mild non-pharmaceutical interventions has been instrumental in influencing the decision of many countries to initiate a booster campaign. By constructing a detailed mathematical model and calibrating it to the Israeli data, we expand our understanding of the impact of the booster campaign from the individual to the population level. We use the calibrated model to explore counterfactual scenarios in which the booster vaccination campaign is altered and to assess the direct and indirect effects in the different scenarios. Our results point to the vast benefits of vaccinating younger age groups that are not at a high risk of developing severe disease but play an important role in transmission. We further show that when the epidemic is exponentially growing the success of the booster campaign is highly sensitive to the timing of its initiation. Hence a rapid response is an important factor in reducing disease burden using booster vaccination.
Parallel evolution of amphioxus and vertebrate small-scale gene duplications
Authors: Brasó-Vives Marina , Marlétaz Ferdinand , Echchiki Amina , Mantica Federica , Acemel Rafael D. , Gómez-Skarmeta José L. , Hartasánchez Diego A. , Targa Lorlane L. , Pontarotti Pierre , Tena Juan J. , Maeso Ignacio , Escriva Hector , Irimia Manuel , Robinson-Rechavi Marc 
Published: January 2022

AbstractBackgroundAmphioxus are non-vertebrate chordates characterized by a slow morphological and molecular evolution. They share the basic chordate body-plan and genome organization with vertebrates but lack their 2R whole-genome duplications and their developmental complexity. For these reasons, amphioxus are frequently used as an outgroup to study vertebrate genome evolution and Evo-Devo. Aside from whole-genome duplications, genes continuously duplicate on a smaller scale. Small-scale duplicated genes can be found in both amphioxus and vertebrate genomes, while only the vertebrate genomes have duplicated genes product of their 2R whole-genome duplications. Here, we explore the history of small-scale gene duplications in the amphioxus lineage and compare it to small- and large-scale gene duplication history in vertebrates.ResultsWe present a study of the European amphioxus (Branchiostoma lanceolatum) gene duplications thanks to a new, high-quality genome reference. We find that, despite its overall slow molecular evolution, the amphioxus lineage has had a history of small-scale duplications similar to the one observed in vertebrates. We find parallel gene duplication profiles between amphioxus and vertebrates, and conserved functional constraints in gene duplication. Moreover, amphioxus gene duplicates show levels of expression and patterns of functional specialization similar to the ones observed in vertebrate duplicated genes. We also find strong conservation of gene synteny between two distant amphioxus species, B. lanceolatum and B. floridae, with two major chromosomal rearrangements.ConclusionsIn contrast to their slower molecular and morphological evolution, amphioxus’ small-scale gene duplication history resembles that of the vertebrate lineage both in quantitative and in functional terms.
Enhancing Uterine Receptivity for Embryo Implantation through Controlled Collagenase Intervention
Authors: Zehorai Eldar , Gross Tamar , Shimshoni Elee , Hadas Ron , Adir Idan , Golani Ofra , Molodij Guillaume , Eitan Ram , Kadler Karl E. , Kollet Orit , Neeman Michal , Dekel Nava , Solomonov Inna , Sagi Irit 
Published: January 2022

AbstractSuccessful embryo implantation within the uterine wall requires intricate endometrial remodeling. Impaired endometrial receptivity, a common cause of infertility, often results from ineffective remodeling processes. Here, we demonstrate that a single dose of human collagenase-1 administered into the mouse uterus enhances embryo implantation rates. Mechanistically, collagenase-1 induces remodeling of the endometrial extracellular matrix (ECM), leading to the degradation of collagen fibers and proteoglycans. This process releases matrix-bound bioactive factors, such as VEGF, which facilitates local vascular permeability and angiogenesis. Furthermore, collagenase-1 treatment increases NK cell infiltration and elevates levels of the cytokine LIF, a key factor in embryo implantation. Remarkably, the overall structural integrity of the uterine tissue remains uncompromised, even in the presence of reduced tension in endometrial collagen fibers. To assess pre-clinical potential, in-uteri application of collagenase-1 successfully rescued implantation in mouse models subjected to heat stress and embryo transfer, conditions known for their adverse impact on implantation rates. Importantly, ex-vivo exposure of human uterine tissue to collagenase-1 induced collagen de-tensioning and the release of VEGF, demonstrating similar processes observed in the mouse settings, and the potential relevance of this treatment to human conditions. Our findings underscore the immense clinical potential and feasibility of collagenase treatment to enhance uterine receptivity for embryo implantation, offering a controlled and minimally invasive intervention. This innovative approach not only demonstrates the potential to enhance efficiency in livestock breeding but, more importantly, signifies a substantial promise in supporting medical interventions for human reproduction in clinical settings.
Fam49b dampens TCR signal strength to regulate survival of positively selected thymocytes
Authors: Park Chan-Su , Guan Jian , Rhee Peter , Gonzalez Federico , Coscoy Laurent , Robey Ellen A. , Shastri Nilabh , Sadegh-Nasseri Scheherazade 
Published: January 2022

AbstractThe fate of developing T cells is determined by the strength of T cell receptor (TCR) signal they receive in the thymus. This process is finely regulated through tuning of positive and negative regulators in thymocytes. The Family with sequence similarity 49 member B (Fam49b) protein is a newly discovered negative regulator of TCR signaling that has been shown to suppress Rac-1 activity in vitro in cultured T cell lines. However, the contribution of Fam49b to thymic development of T cells is unknown. To investigate this important issue, we generated a novel mouse line deficient in Fam49b (Fam49b-KO). We observed that Fam49b-KO double positive (DP) thymocytes underwent excessive negative selection, whereas the positive selection stage was unaffected. This altered development process resulted in significant reductions in CD4 and CD8 single positive thymocytes as well as peripheral T cells. Interestingly, a large proportion of the TCRγδ+ and CD8αα+TCRαβ+ gut intraepithelial T lymphocytes were absent in Fam49b-KO mice. Our results demonstrate that Fam49b dampens thymocytes TCR signaling in order to escape negative selection during development, uncovering the function of Fam49b as a critical regulator of selection process to ensure normal thymocyte development.