bluuebunny/crossref_metadata_2025_split huggingface dataset:
Probiotic effect of trichloroacetic acid on cervicovaginal microbiota in cervical intraepithelial neoplasia: A pilot study
Authors: Shibata Takeo , Ohno Ayumu , Murakami Isao , Takakura Masahiro , Sasagawa Toshiyuki , Imanishi Tadashi , Mikami Mikio 
Published: January 2024

AbstractSymbiosis of bacteria and human papillomavirus (HPV) in the cervicovaginal environment influences cervical intraepithelial neoplasia (CIN) progression or regression. In this case series, we enrolled all 10 patients who had resolved CIN after a cervical local treatment using trichloroacetic acid (TCA). Prominent changes in the cervicovaginal microbiota, such as an enrichment of the genusBifidobacteriumand genusLactobacillus, were observed in seven of 10 patients. A decrease in cervicovaginal bacterial alpha diversity was observed in 4 patients with high-risk HPV clearance. Differential abundance analysis revealed that genusBifidobacteriumincreased significantly after TCA. The dominance of a single bacteria can be characteristic of CIN cures after TCA. These results highlight the potential link of cervicovaginal bacteria such as genusBifidobacteriumand genusLactobacillusin the clearance of CIN and high-risk HPV. This pilot study guides future research questions that specific cervicovaginal bacteria may be promising candidates for probiotic therapy to treat CIN and HPV infections.
Lack of phosphatidylinositol 3-kinase VPS34 in regulatory T cells leads to a fatal lymphoproliferative disorder without affecting their development
Authors: Courreges Christina J.F. , Davenport Elizabeth C.M. , Bilanges Benoit , Rebollo-Gomez Elena , Hukelmann Jens , Schoenfelder Priya , Edgar James R. , Sansom David , Scudamore Cheryl , Roychudhuri Rahul , Garden Oliver A. , Vanhaesebroeck Bart , Okkenhaug Klaus 
Published: January 2024

AbstractRegulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Treg cells completely. However, VPS34-deficient Treg cells developed normally, populated the peripheral lymphoid organs and effectively supressed conventional T cellsin vitro.Our data suggest that VPS34 is required for the maturation of Treg cells or that mature Treg cells depend on VPS34 for survival. Functionally, we observed that lack of VPS34 activity impairs cargo processing upon transendocytosis, that defective autophagy contributes to, but is not sufficient to explain this lethal phenotype, and that loss of VPS34 activity induces a state of heightened metabolic activity that may interfere with metabolic networks required for maintenance or suppressive functions of Treg cells.
Pregnancy affects flight behavior in big brown bats (Eptesicus fuscus)
Authors: Calistri-Yeh Adrienne , Hilliard Young Vanessa K , Klingerman Michaele , Kloepper Laura N. 
Published: January 2024

ABSTRACTPregnancy involves increased body mass and decreased locomotor performance in many species and can be especially impactful on volant animals. To test the hypothesis that bats modify flight behavior to adjust for pregnancy-related increases in mass, we recorded thermal video from a maternity colony of big brown bats (Eptesicus fuscus) as they emerged from a roost, during periods associated with pregnancy and post-pregnancy. From video tracking, we calculated the vertical drop distance before upward motion (UM), time from emergence until UM, average speeds before and after UM, and average wingbeat rate per second (WBR). Bats recorded during the pregnancy period had a significantly larger drop distance, longer time until UM, faster flight speed before UM, and higher WBR compared to bats recorded during the non-pregnancy period. Our results suggest that pregnancy has a significant effect on flight in female bats, with a particularly strong impact on achieving UM after emergence. However, the higher WBR recorded from bats flying during the pregnancy period implies that bats acclimate to such changes in body mass by altering their flight behaviors to sustain UM while pregnant.
Efficient overexpression and purification of SARS-CoV-2 Nucleocapsid proteins inEscherichia coli
Authors: Brudenell Emma L , Pohare Manoj B , Zafred Domen , Phipps Janine , Hornsby Hailey R , Darby John , Dai Junxiao , Liggett Ellen , Cain Kathleen , Barran Perdita E. , de Silva Thushan I , Sayers Jon R 
Published: January 2024

ABSTRACTThe fundamental biology of Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (Ncap), its use in diagnostic assays and its potential application as a vaccine component have received considerable attention since the outbreak of the Covid19 pandemic in late 2019. Here we report the scalable expression and purification of soluble, immunologically active, SARS-CoV-2 Ncap inEscherichia coli. Codon-optimised synthetic genes encoding the original Ncap sequence and four common variants with an N-terminal 6His affinity tag (sequence MHHHHHHG) were cloned into an inducible expression vector carrying a regulated bacteriophage T5 synthetic promoter controlled bylacoperator binding sites. The constructs were used to express Ncap proteins and protocols developed which allow efficient production of purified Ncap with yields of over 200 mg per litre of culture media. These proteins were deployed in ELISA assays to allow comparison of their responses to human sera. Our results suggest that there was no detectable difference between the 6His-tagged and untagged original Ncap proteins but there may be a slight loss of sensitivity of sera to other Ncap isolates.
Annotations of four high-quality indigenous chicken genomes identify more than one thousand missing genes in sub-telomeric regions with high G/C contents
Authors: Wu Siwen , Dou Tengfei , Yuan Sisi , Yan Shixiong , Xu Zhiqiang , Liu Yong , Jian Zonghui , Zhao Jingying , Zhao Rouhan , Zi Xiannian , Gu Dahai , Liu Lixian , Li Qihua , Wu Dong-Dong , Su Zhengchang , Jia Junjing , Ge Changrong , Wang Kun 
Published: January 2024

AbstractBackgroundAlthough multiple chicken genomes have been assembled and annotated, the number of protein-coding genes in chicken genomes is still uncertain due to the low quality of these genome assemblies and limited resources used in gene annotations.ResultsTo fill the gap, we annotated our four recently assembled high-quality genomes of four indigenous chickens with distinct traits using a combination of RNA-seq- and homology-based approach. Our annotated genes in the four chickens recovered 51 of the 274 “missing” genes in birds in general and 36 of the 174 “missing” genes in chickens in particular. Intriguingly, based on deeply sequenced RNA-seq data collected in multiple tissues in each chicken breed, we found a total of 1,420 new protein-coding genes in the four chicken genomes, which were missed in the reference chicken genome annotations. These newly annotated genes (NAGs) tend to have high G/C contents and be located in sub-telomeric regions of almost all assembled chromosomes and some unplaced contigs. The NAGs showed tissue-specific expression and we were able to verify 39 (92.9%) of 42 randomly selected ones in various tissues of the four chicken breeds using RT-qPCR experiments. We found that most of the NAGs also are encoded in previously assembled chicken genomes. The NAGs form functional modules with homology-supported genes that are involved in many important biological pathways. We also identified numerous unique genes in each indigenous chicken genome that might be related to the unique traits of each breed.ConclusionThe ubiquitous presence of the NAGs in various chicken genomes indicate that they might play critical roles in chicken physiology. Counting these new genes, chicken genomes harbor more genes than originally thought.
Membrane cliffs are giant, recursive platforms that drive calcium and protein kinase signaling for cell growth
Authors: Trerotola Marco , Relli Valeria , Tripaldi Romina , Simeone Pasquale , Guerra Emanuela , Sacchetti Andrea , Ceci Martina , Pantalone Ludovica , Ciufici Paolo , Moschella Antonino , Caiolfa Valeria R. , Zamai Moreno , Alberti Saverio 
Published: January 2024

AbstractThe transmembrane glycoproteins Trop-1/EpCAM and Trop-2 independently trigger Ca2+and kinase signals for cell growth and tumor progression. We discovered that Trop-1 and Trop-2 are recruited at overlapping sites at free cell edges. Z-stack analysis and three-dimensional reconstruction of these sites revealed previously unrecognized, protruding membrane regions ≥20 µm-long, up to 1.5 µm high, then named ‘cliffs’. Cliffs appeared confined to essentially immobile sites of the cell membrane, where they recursively assembled over hundreds of seconds. Cliffs were shown to recruit growth-driving kinases and downstream cytoplasmic effectors. Trop-2 stimulates cell growth through a membrane super-complex that comprises CD9 and PKCα. Our findings indicated that the growth-driving Trop-2 super-complex assembles at cliffs. Cliffs acted as sites of phosphorylation/activation of growth-driving kinases and as origins of Ca2+signaling waves, indicating cliffs as novel signaling platforms for drivers of cell growth. Cliffs were induced by growth factors and disappeared upon growth factor deprivation, suggesting cliffs as pivotal platforms for signaling for cell growth.
Preferential apical infection of intestinal cell monolayers by SARS-CoV-2 is associated with damage to cellular barrier integrity: Implications for the physiopathology of COVID-19
Authors: Garrec Clémence , Arrindell Jeffrey , Andrieu Jonatane , Desnues Benoit , Mege Jean-Louis , Osman Ikram Omar , Devaux Christian A. 
Published: January 2024

AbstractSARS-CoV-2 can infect different organs, including the intestine. In Caco-2 intestinal cell line, SARS-CoV-2 modulates the ACE2 receptor expression and affects the expression of molecules involved in intercellular junctions. To further explore the possibility that the intestinal epithelium serves as an alternative infection route for SARS-CoV-2, we used a model of polarised intestinal cell monolayers grown on the polycarbonate membrane of Transwell inserts, inoculated with the virus either in the upper or lower chamber of culture. In both polarised Caco-2 cell monolayers and co-culture Caco-2/HT29 cell monolayer, apical SARS-CoV-2 inoculation was found to be much more effective in establishing infection than basolateral inoculation. In addition, apical SARS-CoV-2 infection triggers monolayer degeneration, as shown by histological examination, measurement of trans-epithelial electronic resistance, and cell adhesion molecule expression. During this process, the infectious viruses reach the lower chamber, suggesting either a transcytosis mechanism from the apical side to the basolateral side of cells, a paracellular trafficking of the virus after damage to intercellular junctions in the epithelial barrier, or both. Taken together, these data highlight a preferential tropism of SARS-CoV-2 for the apical side of the human intestinal tract and suggests that infection via the intestinal lumen leads to a systemic infection.
Effectiveness of a network Open House model to recruit trainees to post-baccalaureate STEM programs
Authors: Aoki Scott Takeo , Lewellyn Lindsay , Justice Sarah , Mordan-McCombs Sarah , Tewari Neetu , Cantu Jorge , Seiser Robert , Lakhani Ahmed , Kowalski Jennifer R. 
Published: January 2024

AbstractPost-baccalaureate (post-bac) programs can have a positive impact on science training and STEM career opportunities for junior trainees. A goal for many of these sponsored programs is to increase research exposure for underrepresented minorities, a group that can include African American, Hispanic, Native American, and first-generation college students, among others. Recruiting underrepresented minorities to post-bac programs can be challenging, for reasons that include a lack of available research opportunities, time to pursue these experiences, and awareness of available programs. To this end, an Open House event was created to inform and excite potential students for future post-bac programs. Students were recruited from partnering Minority Serving Institutions (MSIs) to attend a two-day event at a primarily undergraduate institution (PUI) and a research-intensive R1 institution. The students visited both campuses, were informed about post-bac programs and potential research opportunities, and met with faculty, current graduate students, and a former post-bac scholar. Transportation, lodging, and meals were provided. Visiting students completed voluntary pre- and post-surveys. Results indicated that attendees, the majority of whom were underrepresented minorities in STEM, left the event with an increased understanding about post-bac programs and their benefits to a career in STEM and that their attendance at the event made it more likely they would apply to available post-bac programs. Thus, this work demonstrates that in-person events involving integrative partnerships across multiple universities are effective strategies for increasing awareness of opportunities available to students post-graduation and for recruiting underrepresented groups in STEM to post-bac programs.
Coordinated molecular and ecological adaptations underlie a highly successful parasitoid
Authors: Pang Lan , Fang Gangqi , Liu Zhiguo , Dong Zhi , Chen Jiani , Feng Ting , Zhang Qichao , Sheng Yifeng , Lu Yueqi , Wang Ying , Zhang Yixiang , Li Guiyun , Chen Xuexin , Zhan Shuai , Huang Jianhua 
Published: January 2024

AbstractThe success of an organism depends on the molecular and ecological adaptations that promote its beneficial fitness. Parasitoids are valuable biocontrol agents for successfully managing agricultural pests, and they have evolved diversified strategies to adapt to both the physiological condition of hosts and the competition of other parasitoids. Here, we deconstructed the parasitic strategies in a highly successful parasitoid,Trichopria drosophilae, which parasitizes a broad range ofDrosophilahosts, including the globally invasive speciesD. suzukii. We found thatT. drosophilaehad developed specialized venom proteins that arrest host development to obtain more nutrients via secreting tissue inhibitors of metalloproteinases (TIMPs), as well as a unique type of cell— teratocytes—that digest host tissues for feeding by releasing trypsin proteins. In addition to the molecular adaptations that optimize nutritional uptake, this pupal parasitoid has evolved ecologically adaptive strategies including the conditional tolerance of intraspecific competition to enhance parasitic success in older hosts and the obligate avoidance of interspecific competition with larval parasitoids. Our study not only demystifies how parasitoids weaponize themselves to colonize formidable hosts but also provided empirical evidence of the intricate coordination between the molecular and ecological adaptations that drive evolutionary success.
HUB-DT: A tool for unsupervised behavioural discovery and analysis
Authors: Lindsay Adrian , Seamans Jeremy K 
Published: January 2024

AbstractThere has been an expansion in the diversity of tools used to measure various aspects of brain function in behaving animals. While these tools have great potential to transform our understanding of brain function, they are of little value if the behavior of interest is poorly defined or quantified. Traditional methods of behavioural labelling focus on easily quantified gross measure, such as velocity, gate crossing, nosepokes, etc. While these measures are specific and reproducible, they are crude descriptions of behaviour at best. Manually defined behaviours, while providing increased granularity and descriptive power over specific gross measures, suffer from being inexact and somewhat arbitrary. Consistent labelling between human observers is often difficult, and even if manually defined behaviours are subsequently labelled in an automated fashion (via a supervised learning algorithm) these behaviours need to be defined ahead of time, possibly biasing the range of behaviours of interest for a given task.Here we present HUB-DT, a behavioural discovery pipeline built on the frameworks of several existing tools and methods in the space of behavioural categorisation, the specifics of which will be highlighted in this report, and designed to address the requirements of behavioral discovery.
Metatranscriptomic analysis reveals synergistic activities of comammox and anammox bacteria in full-scale attached growth nitrogen removal system
Authors: Johnston Juliet , Vilardi Katherine , Cotto Irmarie , Sudarshan Ashwin , Bian Kaiqin , Klaus Stephanie , Bachmann Megan , Parsons Mike , Wilson Christopher , Bott Charles , Pinto Ameet 
Published: January 2024

0-AbstractLeveraging comammoxNitrospiraand anammox bacteria for shortcut nitrogen removal can drastically lower the carbon footprint of wastewater treatment facilities by decreasing aeration energy, carbon, alkalinity, and tank volume requirements while also potentially reducing nitrous oxide emissions. However, their co-occurrence as dominant nitrifying bacteria is rarely reported in full-scale wastewater treatment. As a result, there is poor understanding of how operational parameters, in particular dissolved oxygen, impact their activity and synergistic behavior. Here, we report the impact of dissolved oxygen concentration (DO = 2, 4, 6 mg/L) on the microbial community’s transcriptomic expression in a full-scale integrated fixed film activated sludge (IFAS) municipal wastewater treatment facility predominantly performed by comammoxNitrospiraand anammox bacterial populations. 16S rRNA transcript compositions revealed anammox bacteria andNitrospirawere significantly more active in IFAS biofilms compared to suspended sludge biomass. In IFAS biofilms, anammox bacteria significantly increasedhzoexpression at lower dissolved oxygen concentrations and this increase was highly correlated with theamoAexpression levels of comammox bacteria. Interestingly, the genes involved in nitrite oxidation by comammox bacteria were significantly more upregulated relative to the genes involved in ammonia oxidation with decreasing dissolved oxygen concentrations. Ultimately, our findings suggest that comammoxNitrospirasupply anammox bacteria with nitrite via ammonia oxidation and that this synergistic behavior is dependent on dissolved oxygen concentrations.SynopsisComammox bacteria differentially regulate ammonia and nitrite oxidation in response to dissolved oxygen concentration suggesting dissolved oxygen dependence of their synergistic nitrogen removal with anammox bacteria in IFAS biofilms.
CD271 restrains the B1b cell antibody response in a T cell dependent manner
Authors: Lebel Marie-Ève , Bonkoungou Carole A. , Thibault Jade , Rauch Joyce , Alugupalli Kishore R. , Melichar Heather J. 
Published: January 2024

AbstractCo-signaling molecules modulate T cell function and are essential to control the duration and amplitude of immune responses. These molecules belong to the immunoglobulin and tumor necrosis factor receptor (TNFR) superfamilies and have been extensively studied; however, the immunomodulatory role of several family members remains unknown. We show that CD271 (also known as p75 or NGFR), a TNFR superfamily member, is highly expressed on peritoneal B1 B cells, but not on conventional (B2) B cells at steady state. CD271 expression by B cells specifically restrains the response to T cell-independent type 2 antigens (TI-2). B1 cell-expressed CD271 maintains peritoneal CD4+T cell quiescence, and augmented antibody responses to TI-2 antigens in CD271-deficient mice are dependent on CD4+T cells. This increase in antibody production correlates with improved bacterial neutralizationin vitroand survival after bacterial challengein vivo. Further, our results suggest that CD271 can directly inhibit mouse and human T cell activity to the same extent as PD-L1, a known, negative regulator of T cell function. These results establish CD271 as a co-inhibitory molecule that could be targeted to improve the efficacy of vaccines against pathogenic encapsulated bacteria and to broadly modulate the T cell response in therapeutic contexts.eTOC summaryLebel et al. identify an unexpected role for CD271, a neurotrophin receptor, in directly inhibiting T cell function. B1 cell-expressed CD271 maintains CD4+T cell quiescence; in the absence of CD271, T cells bolster antibody production to T-independent antigens, enhancing the response to encapsulated bacteria.
Spatial Transcriptomics Sequencing of Mouse Liver at 2µm Resolution Using a Novel Spatial DNA Chip
Authors: Ding Xun , Hoff Kendall , Swaminathan Radha , Koutrouli Mikaela , Pollom Scott , Huang Tianlong , Li Xiaochi , Zhou Guoqiang , Bai Zhicong , Yu Shizhe , Xia Zongping , Jensen Lars Juhl , Crnogorac Filip , Yu Su , McGall Glenn , Edwards Jeremy , Zhou Wei 
Published: January 2024

AbstractSpatial transcriptomics enables analysis of gene expression that is spatially resolved within a tissue section, making it possible to elucidate the relationship between individual cells within the context of the tissue. This transformative technology enables researchers to better understand gene function within the context of health tissue, developmental processes, and disease. In this study, we present an innovative spatial transcriptomics technology and data using a high-resolution DNA chip with a total capture region size of 6.5 x 6.5 mm containing 2 x 2 µm features for spatial barcoding with no gaps between the features, thereby maximizing the capture area. These chips are manufactured at wafer scale using photolithography and are transferred to hydrogels, making them compatible with existing workflows for fresh frozen or paraffin-embedded samples. Herein, we examined a fresh frozen sample from an adult mouse liver. To analyze the data, we binned 10 x 10 features to represent a 20 µm x 20 µm capture area. We obtained 1.3 billion unique mapped reads, 68.78% sequencing saturation, with a median of 16,967 unique reads per region, indicating the potential for more unique reads with deeper sequencing. This high-resolution mapping of liver cell types and the visualization of gene expression patterns illustrate significant advancements in spatial sequencing technology.
The spatial landscape of glial pathology and T-cell response in Parkinson’s disease substantia nigra
Authors: Jakubiak Kelly , Paryani Fahad , Kannan Adithya , Lee Jaeseung , Madden Nacoya , Li Juncheng , Chen David , Mahajan Aayushi , Xia Shengnan , Flowers Xena , Menon Vilas , Sulzer David , Goldman James , Sims Peter A. , Al-Dalahmah Osama 
Published: January 2024

AbstractParkinson’s Disease (PD) is a progressive neurodegenerative disease that leads to debilitating movement disorders and often dementia. Recent evidence, including identification of specific peripheral T-cell receptor sequences, indicates that the adaptive immune response is associated with disease pathogenesis. However, the properties of T-cells in the brain regions where neurons degenerate are not well characterized. We have analyzed the identities and interactions of T-cells in PD in post-mortem brain tissue using single nucleus RNA sequencing, spatial transcriptomics and T-cell receptor sequencing. We found that T-cells in the substantia nigra of PD brain donors exhibit a CD8+ resident memory phenotype, increased clonal expansion, and altered spatial relationships with astrocytes, myeloid cells, and endothelial cells. We also describe regional differences in astrocytic responses to neurodegeneration. Our findings nominate potential molecular and cellular candidates that allow a deeper understanding of the pathophysiology of neurodegeneration in PD. Together, our work represents a major single nucleus and spatial transcriptional resource for the fields of neurodegeneration and PD.