bluuebunny/crossref_metadata_2025_split huggingface dataset:
The earliest allopolyploidization in tracheophytes revealed by phylotranscriptomics and morphology of Selaginellaceae
Authors: Kang Jong-Soo , Yu Ji-Gao , Xiang Qiao-Ping , Zhang Xian-Chun 
Published: January 2024

AbstractSelaginellaceae exhibit extraordinary evolutionary history in which they survived and thrived during the Permian–Triassic extinction and did not undergo polyploidization. Here, we reconstructed the phylogenetic relationships of Selaginellaceae by applying large-scale nuclear genes from RNA-seq, and found that each group showed phylogenetic incongruences among single-gene trees with different frequencies. In particular, three different phylogenetic positions of thesanguinolentagroup were recovered by different nuclear gene sets. We evaluated the factors that might lead to the phylogenetic incongruence of thesanguinolentagroup and concluded that hybridization between each ancestor of two superclades is the most likely cause. We presented the supporting evidence from gene flow test, species network inference, and plastome-based phylogeny. Furthermore, morphological characters and chromosomal evidence also lend support to the hybrid origin of this group. The divergence time estimations, using two gene sets respectively, indicated the splits between thesanguinolentagroup and each related superclade happened around the same period, implying that the hybridization event probably occurred during the Early Triassic. This study reveals an ancient allopolyploidization with integrative evidence and robust analyses, which sheds new light on the recalcitrant phylogenetic problem of thesanguinolentagroup and reports the polyploidization in the basal vascular plants, Selaginellaceae.
The ventral hippocampus and nucleus accumbens underlie long-term social memory about female conspecifics in male mice
Authors: Watarai Akiyuki , Ishida Kiyoshi , Okuyama Teruhiro 
Published: January 2024

AbstractFor many social animals, including humans, the ability to remember and recognize conspecifics (i.e., having social memory), especially a mating partner, is essential for adaptive reproductive strategies. Our previous studies have shown that social memory about same-sex conspecifics, namely male-to-male social memory, is stored in hippocampal ventral CA1 (vCA1) neurons and that neural projections from the vCA1 to the nucleus accumbens (NAc) are crucial for social discriminatory behavior. However, how the memory of an opposite-sex conspecific, specifically male-to-female social memory, and how the social memory modulates sexual behavior in males remain unknown. Herein, we investigated the ultrasonic vocalizations (USVs) and socially approaching behavior of males toward a female before and after social memory formation. We found that the total duration of USVs was reduced when the male mice interacted with a familiar female. This reduction in USV emission was blocked by optogenetic inhibition of vCA1 neurons, as well as D1- and D2-dopamine receptor (D1R and D2R) expressing neurons in the NAc. Furthermore, fiber photometry recordings in the NAc revealed that the activities of both D1R and D2R neuronal populations were altered during social interaction with familiar or novel females after the process of familiarization. The response of D1R-neurons was reduced only when interacting with familiar females. In contrast, although responses of D2R-neurons were reduced toward both familiar and novel females after social memory formation, the reduction towards novel females was significantly more pronounced compared to that towards familiar females. Our findings suggested that the activities of both vCA1 neurons and D1R- and D2R-expressing NAc neurons in males were differentially modulated by the presence of social memory about females during adaptive reproductive strategies.Significance StatementLong-term social memory about females modulates male sexual behavior, specifically ultrasonic vocalization emissions, mediated by hippocampal ventral CA1 and dopamine receptor expressing neurons in the nucleus accumbens.
Primary oocytes with cellular senescence features are involved in ovarian aging in mice
Authors: Yan Hao , Diaz Miranda Edgar Andres , Jin Shiying , Wilson Faith , An Kang , Godbee Brooke , Zheng Xiaobin , Brau-Rodríguez Astrid Roshealy , Lei Lei 
Published: January 2024

AbstractIn mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging. In the present study, we report that some quiescent primary oocytes in primordial follicles become senescent in adult mouse ovaries. The senescent primary oocytes share senescence markers characterized in senescent somatic cells. The senescent primary oocytes were observed in young adult mouse ovaries, remained at approximately 15% of the total primary oocytes during ovarian aging from 6 months to 12 months, and accumulated in aged ovaries. Administration of a senolytic drug ABT263 to 3-month-old mice reduced the percentage of senescent primary oocytes and the transcription of the SASP cytokines in the ovary. In addition, led to increased numbers of primordial and total follicles and a higher rate of oocyte maturation and female fertility. Our study provides experimental evidence that primary oocytes, a germline cell type that is arrested in meiosis, become senescent in adult mouse ovaries and that senescent cell clearance reduced primordial follicle loss and mitigated ovarian aging phenotypes.
Nationwide Inclusive Facilitator Training: Mindsets, Practices and Growth
Authors: Codding Diane , Yen Alexandria H. , Lewis Haley , Johnson-Ojeda Vanessa , Frey Regina F. , Hokanson Sarah Chobot , Goldberg Bennett B. 
Published: January 2024

AbstractAdvancing diversity in STEM requires competent and confident faculty and staff who can lead local professional development in inclusive teaching to improve classroom instruction and support all learners. This paper examines how a facilitator training model designed to promote inclusive facilitation impacted inclusive learning community facilitator self-reported confidence and practices. This mixed methods study reports on survey data from project trained facilitators (n=71) collected over four course runs. Facilitators reported significant increases in confidence, with the largest effect sizes in areas related to diversity, equity, and inclusion (DEI) and identity. Qualitative findings indicate the training model effectively aligned facilitators with our approach to inclusive facilitation. Findings demonstrate that professional development in inclusive teaching, and by extension in other equity and diversity topics, can be successfully done at a national scale by centering identity, power, and positionality while upholding ‘do no harm.’ This paper provides a strategy for how DEI-focused faculty development efforts can select, train, and support facilitators on a national scale while maintaining high fidelity to project values and goals.
Concordance of high blood pressure among middle-aged and older same-sex couples in the USA
Authors: Varghese Jithin Sam , Curtis Michael G. , Opara Samuel C.O. , Patel Shivani A. , Sheth Anandi N. , Hussen Sophia A. 
Published: January 2024

AbstractHeterosexual couples in romantic relationships are known to influence each other’s hypertension risk. However, the role of partners on an individual’s hypertension status in same-sex relationships is less understood. Our objective is to characterize the burden of high blood pressure among middle-aged and older couples consisting of men who have sex with men (MSM) and women who have sex with women (WSW) living in the US. Among 81 same-sex couples from the Health and Retirement Study 2006-18, 72.4% (95%CI: 23.4-95.7) MSM couples and 61.0% (95%CI: 30.4-84.8) WSW couples consisted of both partners with hypertension. Same-sex couples demonstrate high concordance of hypertension and related risk factors, suggesting a need to develop novel interventions targeting MSM and WSW couples
Protection afforded by post-infection SARS-CoV-2 vaccine doses: a cohort study in Shanghai
Authors: Zheng Bo , Gonçalves Bronner , Deng Pengfei , Wang Weibing , Tian Jie , Liang xueyao , Yao Ye , Xue Caoyi 
Published: January 2024

ABSTRACTBackground:In many settings, a large fraction of the population has both been vaccinated against and infected by SARS-CoV-2. Hence, quantifying the protection provided by post-infection vaccination has become critical for policy. We aimed to estimate the protective effect against SARS-CoV-2 reinfection of an additional vaccine dose after an initial Omicron variant infection.Methods:We report a retrospective, population-based cohort study performed in Shanghai, China, using electronic databases with information on SARS-CoV-2 infections and vaccination history. We compared reinfection incidence by post-infection vaccination status in individuals initially infected during the April-May 2022 Omicron variant surge in Shanghai and who had been vaccinated before that period. Cox models were fit to estimate adjusted hazard ratios (aHR).Results:275,896 individuals were diagnosed with RT-PCR-confirmed SARS-CoV-2 infection in April-May 2022; 199,312/275,896 were included in analyses on the effect of a post-infection vaccine dose. Post-infection vaccination provided protection against reinfection (aHR 0.82; 95% CI 0.79-0.85). For patients who had received one, two or three vaccine doses before their first infection, hazard ratios for the post-infection vaccination effect were 0.84 (0.76-0.93), 0.87 (0.83-0.90) and 0.96 (0.74-1.23), respectively. Vaccination within 30 and 90 days before the second Omicron wave provided different degrees of protection (in aHR): 0.51 (0.44-0.58), and 0.67 (0.61-0.74), respectively. Moreover, for all vaccine types, but to different extents, a post-infection dose given to individuals who were fully vaccinated before first infection was protective.Conclusions:In previously vaccinated and infected individuals, an additional vaccine dose provided protection against Omicron variant reinfection. These observations will inform future policy decisions on COVID-19 vaccination in China and other countries.
Hippocampus Glutathione S Reductase Potentially Confers Genetic Resilience to Cognitive Decline in the AD-BXD Mouse Population
Authors: Saul Michael C. , Litkowski Elizabeth M. , Hadad Niran , Dunn Amy R. , Boas Stephanie M. , Wilcox Jon A. L. , Robbins Julia E. , Wu Yiyang , Philip Vivek M. , Merrihew Gennifer E. , Park Jea , De Jager Philip L. , Bridges Dave E. , Menon Vilas , Bennett David A. , Hohman Timothy J. , MacCoss Michael J. , Kaczorowski Catherine C. 
Published: January 2024

AbstractAlzheimer’s disease (AD) is a prevalent and costly age-related dementia. Heritable factors account for 58-79% of variation in late-onset AD, but substantial variation remains in age-of- onset, disease severity, and whether those with high-risk genotypes acquire AD. To emulate the diversity of human populations, we utilized the AD-BXD mouse panel. This genetically diverse resource combines AD genotypes with multiple BXD strains to discover new genetic drivers of AD resilience. Comparing AD-BXD carriers to noncarrier littermates, we computed a novel quantitative metric for resilience to cognitive decline in the AD-BXDs. Our quantitative AD resilience trait was heritable and genetic mapping identified a locus on chr8 associated with resilience to AD mutations that resulted in amyloid brain pathology. Using a hippocampus proteomics dataset, we nominated the mitochondrial glutathione S reductase protein (GR or GSHR) as a resilience factor, finding that the DBA/2J genotype was associated with substantially higher GR abundance. By mapping protein QTLs (pQTLs), we identified synaptic organization and mitochondrial proteins coregulated in trans with a cis-pQTL for GR. We found four coexpression modules correlated with the quantitative resilience score in aged 5XFAD mice using paracliques, which were related to cell structure, protein folding, and postsynaptic densities. Finally, we found significant positive associations between humanGSRtranscript abundance in the brain and better outcomes on AD-related cognitive and pathology traits in the Religious Orders Study/Memory and Aging project (ROSMAP). Taken together, these data support a framework for resilience in which neuronal antioxidant pathway activity provides for stability of synapses within the hippocampus.
SURF2 is a MDM2 antagonist in triggering the nucleolar stress response
Authors: Tagnères Sophie , Santo Paulo Espirito , Radermecker Julie , Rinaldi Dana , Froment Carine , Provost Quentin , Capeille Solemne , Watkins Nick , Marcoux Julien , Gleizes Pierre-Emmanuel , Marcel Virginie , Plisson-Chastang Célia , Lebaron Simon 
Published: January 2024

AbstractCancer cells are addicted to strong ribosome production to sustain their proliferation rate. Many chemotherapies impede ribosome production which is perceived by cells as “nucleolar stress” (NS), triggering p53-dependent and independent response pathways leading to cell cycle arrest and/or apoptosis. The 5S RNP particle, a sub-ribosomal particle, is instrumental to NS response. Upon ribosome assembly defects, the 5S RNP accumulate as free form. This free form is able to sequester and inhibit MDM2, thus promoting p53 stabilization. To investigate how cancer cells can resist to NS, we purified free-5S RNP and uncovered a new interaction partner, SURF2. Functional characterization of SURF2 shows that its depletion increases cellular sensitivity to NS, while its overexpression promotes their resistance to it. Consistently, SURF2 expression level negatively correlates with the overall survival in adrenocortical and head and neck squamous cell carcinomas. Our data demonstrate that SURF2 buffers free-5S RNP particles, and can modulate their activity. SURF2 regulates NS responses, and is a key player in both ribosomopathies and oncogenic mechanisms.
Lupus-associated innate receptors drive extrafollicular evolution of autoreactive B cells
Authors: Zhu Danni Yi-Dan , Maurer Daniel P. , Castrillon Carlos , Deng Yixiang , Mohamed Faez Amokrane Nait , Ma Minghe , Schmidt Aaron G. , Lingwood Daniel , Carroll Michael C. 
Published: January 2024

SummaryIn systemic lupus erythematosus, recent findings highlight the extrafollicular (EF) pathway as prominent origin of autoantibody-secreting cells (ASCs). CD21loCD11c+B cells, associated with aging, infection, and autoimmunity, are contributors to autoreactive EF ASCs but have an obscure developmental trajectory. To study EF kinetics of autoreactive B cell in tissue, we adoptively transferred WT and gene knockout B cell populations into the 564Igi mice - an autoreactive host enriched with autoantigens and T cell help. Time-stamped analyses revealed TLR7 dependence in early escape of peripheral B cell tolerance and establishment of a pre-ASC division program. We propose CD21locells as precursors to EF ASCs due to their elevated TLR7 sensitivity and proliferative nature. Blocking receptor function reversed CD21 loss and reduced effector cell generation, portraying CD21 as a differentiation initiator and a possible target for autoreactive B cell suppression. Repertoire analysis further delineated proto-autoreactive B cell selection and receptor evolution toward self-reactivity. This work elucidates receptor and clonal dynamics in EF development of autoreactive B cells, and establishes modular, native systems to probe mechanisms of autoreactivity.
Plasmodium falciparummitochondrial complex III, the target of atovaquone, is essential for progression to the transmissible sexual stages
Authors: Sheokand Pradeep Kumar , Mühleip Alexander , Sheiner Lilach 
Published: January 2024

AbstractThe Plasmodium mitochondrial electron transport chain (mETC) is responsible for essential metabolic pathways such as de novo pyrimidine synthesis and ATP synthesis. The mETC complex III (cytochrome bc1 complex) is responsible for transferring electrons from ubiquinol to cytochrome c and generating a proton gradient across the inner mitochondrial membrane, which is necessary for the function of ATP synthase. Recent studies revealed that the composition of Plasmodium complex III is divergent from human, highlighting its suitability as a target for specific inhibition. Indeed, complex III is the target of the clinically used anti-malarial atovaquone and of several inhibitors undergoing pre-clinical trials, yet its role in parasite biology have not been thoroughly studied. We provide evidence that the universally conserved subunit, PfRieske, and the new parasite subunit, PfC3AP2, are part of Plasmodium falciparum complex III (PfCIII), with the latter providing support for the prediction of its divergent composition. Using inducible depletion, we show that PfRieske, and therefore PfCIII as a whole, is essential for asexual blood stage parasite survival, in line with previous observations. We further found that depletion of PfCIII results in gametocyte maturation defect. These phenotypes are linked to defects in mitochondrial functions upon PfRieske depletion, including increased sensitivity to mETC inhibitors in asexual stages and decreased cristae abundance alongside abnormal mitochondrial morphology in gametocytes. This is the first study which explores the direct role of the PfCIII in gametogenesis via genetic disruption, paving the way for a better understanding of the role of mETC in the complex life cycle of these important parasites and providing further support for the focus of antimalarial drug development on this pathway.
Kernel-smoothed permutation for extreme P-value estimation in genetic association studies
Authors: Bian Jiayi , Li Caifeng , Wu Jingjing , Long Quan 
Published: January 2024

ABSTRACTIn genetic studies, permutation tests serve as a cornerstone to estimate P-values. This is because researchers may design new test statistics without a known closed-form distribution, or the assumption of a well-established test may not hold. However, permutation tests require vast number of permutations which is proportional to the magnitude of the actual P-values. When it comes to genome-wide association studies where multiple-test corrections are routinely conducted, the actual P-values are extremely small, requiring a daunting number of permutations that may be beyond the available computational resources. Existing models that reduce the required number of permutations all assume a specific format of the test statistic to exploit its specific statistical properties. We propose Kernel-smoothed permutation which is a model-free method universally applicable to any statistic. Our tool forms the null distribution of test statistics using a kurtosis-driven transformation, followed by a kernel-based density estimation (KDE). We compared our Kernel-smoothed permutation to Naïve permutation using statistics from known closed-form null distributions. Based on three frequently used test statistics in association studies, i.e., t-test, sequence kernel association test (SKAT), and chi-squared test, we demonstrated that our model reduced the required number of permutations by a magnitude with the same or higher accuracy.
The astrovirus N-terminal nonstructural protein anchors replication complexes to the perinuclear ER membranes
Authors: Ali Hashim , Noyvert David , Hankinson Jacqueline , Lindsey Gemma , Lulla Valeria 
Published: January 2024

AbstractAn essential aspect of viral replication is the anchoring of the replication complex (RC) to cellular membranes. Positive-sense RNA viruses employ diverse strategies, including co-translational membrane targeting through signal peptides and co-opting cellular membrane trafficking components. Often, N-terminal nonstructural proteins play a crucial role in linking the RC to membranes, facilitating the early association of the replication machinery. Astroviruses utilize a polyprotein strategy to synthesize nonstructural proteins, relying on subsequent processing to form replication-competent complexes. In this study, we provide evidence for the perinuclear ER membrane association of RCs in five distinct human astrovirus strains. Using tagged recombinant classical human astrovirus 1 and neurotropic MLB2 strains, we establish that the N-terminal domain guides the ER membrane association. Through mutational analysis of the N-terminal domain in replicon and reverse genetics systems, we identified di-arginine motifs responsible for the perinuclear ER retention and formation of functional RCs. Our findings highlight the intricate virus-ER interaction mechanism employed by astroviruses, potentially leading to the development of novel antiviral intervention strategies.Author SummaryHuman astroviruses are a significant cause of acute gastroenteritis, accounting for up to 9% of cases in young children. Immunocompromised individuals and infants experience more critical symptoms, such as severe and persistent diarrhea, as well as sporadic systemic and even fatal diseases. To date, no drugs have been developed to protect against astrovirus infection. Our study provides the first evidence that the integrity of the N-terminal domain of nsP1a is essential for establishing early replication. Central to this process, the di-arginine motifs in the N-terminal domain are responsible for ER retention, the formation of functional replication complexes, and viral replication. Therefore, selectively targeting N-terminal domain-mediated ER retention could be a promising therapeutic strategy to effectively control astrovirus infection.
PIRCHE application versions 3 and 4 lead to equivalent T cell epitope mismatch scores in solid organ and stem cell transplantation modules
Authors: Matern Benedict M , Niemann Matthias 
Published: January 2024

AbstractElevated PIRCHE scores between recipient and donor in organ and stem cell transplantation have been shown to correlate with increased risk of donor-specific HLA antibodies and graft-versus-host disease, respectively. With each revision of the PIRCHE application server, it is critical to completely evaluate the predicted scores, and compare with previous revisions. This manuscript compares the newly introduced PIRCHE version 4.2 with its predecessor version 3.3, which has been widely used in retrospective studies, using a virtual cohort of 10,000 transplant pairs. In the stem cell transplantation module, both versions yield identical results for 100% of the test population. In the solid organ transplantation module, 97% of the test population has identical PIRCHE scores in both versions. The deviating cases could be attributed to a refinement in the PIRCHE algorithm’s specification. For the 3% of cases with deviations, the determined magnitude of the difference is likely to be below the detection limit for clinical effects. We hereby confirm the equivalence in PIRCHE scores generated by the application server versions 3.3 and 4.2.