bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic changes regulating the epithelial-mesenchymal transition in human trophoblast differentiation
Authors: Ackerman William E. , Rigo Mauricio M. , DaSilva-Arnold Sonia C. , Do Catherine , Tariq Mariam , Salas Martha , Castano Angelica , Zamudio Stacy , Tycko Benjamin , Illsley Nicholas P. 
Published: July 2024

AbstractThe phenotype of human placental extravillous trophoblast (EVT) at the end of pregnancy reflects both first trimester differentiation from villous cytotrophoblast (CTB) and later gestational changes, including loss of proliferative and invasive capacity. Invasion abnormalities are central to two major placental pathologies, preeclampsia and placenta accreta spectrum, so characterization of the corresponding normal processes is crucial. In this report, our gene expression analysis, using purified human CTB and EVT cells, highlights an epithelial- mesenchymal transition (EMT) mechanism underlying CTB-EVT differentiation and provides a trophoblast-specific EMT signature. In parallel, DNA methylation profiling shows that CTB cells, already hypomethylated relative to non-trophoblast cell lineages, show further genome- wide hypomethylation in the transition to EVT. However, a small subgroup of genes undergoes gains of methylation (GOM) in their regulatory regions or gene bodies, associated with differential mRNA expression (DE). Prominent in this GOM-DE group are genes involved in the EMT, including multiple canonical EMT markers and the EMT-linked transcription factorRUNX1, for which we demonstrate a functional role in modulating the migratory and invasive capacities of JEG3 trophoblast cells. This analysis of DE associated with locus-specific GOM, together with functional studies of an important GOM-DE gene, highlights epigenetically regulated genes and pathways acting in human EVT differentiation and invasion, with implications for obstetric disorders in which these processes are dysregulated.
Alcohol induces p53-mediated apoptosis in neural crest by stimulating an AMPK-mediated suppression of TORC1, S6K, and ribosomal biogenesis
Authors: Huang Yanping , Flentke George R. , Smith Susan M. 
Published: July 2024

AbstractPrenatal alcohol exposure is a leading cause of permanent neurodevelopmental disability and can feature distinctive craniofacial deficits that partly originate from the apoptotic deletion of craniofacial progenitors, a stem cell lineage called the neural crest (NC). We recently demonstrated that alcohol causes nucleolar stress in NC through its suppression of ribosome biogenesis (RBG) and this suppression is causative in their p53/MDM2-mediated apoptosis. Here, we show that this nucleolar stress originates from alcohol’s activation of AMPK, which suppresses TORC1 and the p70/S6K-mediated stimulation of RBG. Alcohol-exposed cells of the pluripotent, primary cranial NC line O9-1 were evaluated with respect to their S6K, TORC1, and AMPK activity. The functional impact of these signals with respect to RBG, p53, and apoptosis were assessed using gain-of-function constructs and small molecule mediators. Alcohol rapidly (<2hr) increased pAMPK, pTSC2, and pRaptor, and reduced both total and pS6K in NC cells. These changes persisted for at least 12hr to 18hr following alcohol exposure. Attenuation of these signals via gain- or loss-of-function approaches that targeted AMPK, S6K, or TORC1 prevented alcohol’s suppression of rRNA synthesis and the induction of p53-stimulated apoptosis. We conclude that alcohol induces ribosome dysbiogenesis and activates their p53/MDM2-mediated apoptosis via its activation of pAMPK, which in turn activates TSC2 and Raptor to suppress the TORC1/S6K-mediated promotion of ribosome biogenesis. This represents a novel mechanism underlying alcohol’s neurotoxicity and is consistent with findings that TORC1/S6K networks are critical for cranial NC survival.
Biomolecular condensates are characterized by interphase electric potentials
Authors: Posey Ammon E. , Bremer Anne , Erkamp Nadia A. , Pant Avnika , Knowles Tuomas P.J. , Dai Yifan , Mittag Tanja , Pappu Rohit V. 
Published: July 2024

ABSTRACTBiomolecular condensates form via processes that combine phase separation and reversible associations of multivalent macromolecules. Condensates can be two- or multi-phase systems defined by coexisting dense and dilute phases. Here, we show that solution ions can partition asymmetrically across coexisting phases defined by condensates formed by intrinsically disordered proteins or homopolymeric RNA molecules. Our findings were enabled by direct measurements of the activities of cations and anions within coexisting phases of protein and RNA condensates. Asymmetries in ion partitioning between coexisting phases vary with protein sequence, condensate type, salt concentration, and ion type. The Donnan equilibrium set up by asymmetrical partitioning of solution ions generates interphase electric potentials known as Donnan and Nernst potentials. Our measurements show that the interphase potentials of condensates are of the same order of magnitude as membrane potentials of membrane-bound organelles. Interphase potentials quantify the degree to which microenvironments of coexisting phases are different from one another. Importantly, and based on condensate-specific interphase electric potentials, which are membrane-like potentials of membraneless bodies, we reason that condensates are mesoscale capacitors that store charge. Interphase potentials lead to electric double layers at condensate interfaces. This helps explain recent observations of condensate interfaces being electrochemically active.
Familiarity of an environment prevents song suppression in isolated zebra finches
Authors: Zai A.T. , Rodrigues D. I. , Stepien A.E. , Lorenz C. , Giret N. , Adam Iris , Hahnloser R.H.R. 
Published: July 2024

AbstractDespite the wide use of zebra finches as an animal model to study vocal learning and production, little is known about impacts on their welfare caused by routine experimental manipulations such as changing their social context. Here we conduct a post-hoc analysis of singing rate, an indicator of positive welfare, to gain insights into stress caused by social isolation, a common experimental manipulation. We find that isolation in an unfamiliar environment reduces singing rate for several days, indicating the presence of an acute stressor. However, we find no such decrease when social isolation is caused by either removal of a social companion or by transfer to a familiar environment. Furthermore, during repeated brief periods of isolation, singing rate remains high when isolation is induced by removal of social companions, but it fails to recover from a suppressed state when isolation is induced by recurrent transfer to an unknown environment. These findings suggest that stress from social isolation is negligible compared to stress caused by environmental changes and that frequent short visits of an unfamiliar environment are detrimental rather than beneficial. Together, these insights can serve to refine experimental studies and design paradigms maximizing the birds’ wellbeing and vocal output.
The Role of Coenzyme Q10 in Cardiovascular Disease Treatment: An Updated 2024 Systematic Review and Meta-Analysis of Prospective Cohort Studies (1990-2024)
Authors: Borges Julian Yin Vieira 
Published: July 2024

AbstractBackground and ObjectivesWith the increasing need for clinicians to develop novel treatment strategies for the treatment of CVDs, the future lies in developing personalized nutrient recommendations based on an individual’s needs. CoQ10, a key component of the mitochondrial electron transport chain, has emerged as a potential ally with proven cardioprotective effects. This study investigates the efficacy of Coenzyme Q10 (CoQ10) nutrient supplementation in improving mitochondrial function, systolic performance and other parameters in patients with cardiovascular diseases (CVDs).MethodsA systematic review and meta-analysis included data from PubMed, Embase, and the Cochrane Library up to January 2024. Inclusion criteria were randomized controlled trials (RCTs) involving adults with CVDs, comparing CoQ10 with placebo or standard care. Data extraction and quality assessment were performed using PRISMA guidelines, the Cochrane Collaboration’s RoB2 tool, AMSTAR 2, and GRADE. Primary outcome: mitochondrial function (ATP production, respiratory capacity). Secondary outcome: systolic function (ejection fraction).FindingsFrom initial reference list of 46 selected studies, 22 were extracted presenting the encompassing a total sum of 11,372 subjects that were included in the meta-analysis with a total follow-up time ranging from 2 to 144 months (12 years). The results revealed that CoQ10 supplementation significantly improved ejection fraction (mean difference: 5.6%, 95% CI: 3.2% to 8.0%, p<0.001, I²=25%). The I² statistic for ejection fraction was 25%, indicating low heterogeneity among the studies included in the meta-analysis. Mitochondrial function showed increased ATP production (SMD: 0.82, 95% CI: 0.60 to 1.04, p<0.001, I²=30%) and enhanced respiratory capacity (SMD: 0.75, 95% CI: 0.53 to 0.97, p<0.001, I²=28%). The I² statistics for ATP production and mitochondrial respiratory capacity were 30% and 28%, respectively, suggesting low to moderate heterogeneity among the included studies. Sensitivity analyses confirmed the robustness of the results, with consistent effect sizes and confidence intervals across both fixed-effect and random-effects models, and no significant changes upon excluding high-risk studies. Publication bias was low, as indicated by funnel plots and Egger’s test (p=0.12).LimitationsLarger-scale RCTs are needed to confirm findings and determine the optimal dosage and duration of CoQ10 therapy.ConclusionCoQ10 has demonstrated to improve mitochondrial function, systolic performance, and other important cardiovascular health parameters in CVD patients. The evidence here presented strongly supports clinicians in the prescription of CoQ10 supplementation due to its proven efficacy in improving treatment outcomes and mitochondrial function in patients with CVDs.
Incidence, symptoms and medical care for influenza virus and respiratory syncytial virus illnesses among older adults in Eastern China: Findings from the China Ageing Respiratory Infections Study (CARES), 2015-2017
Authors: Leung Nancy H. L. , Zhang Hongjun , Zhang Jun , Tang Fenyang , Luan Lin , Zheng Benfeng , Chen Guoqing , Li Changcheng , Dai Qigang , Xu Cuiling , Chen Yuyun , Chu Daniel K. W. , Song Ying , Zhang Ran , Kim Lindsay , Wendlandt Rachael , Zhu Huachen , Havers Fiona , Yu Hongjie , Shifflett Pat , Greene Carolyn M. , Cowling Benjamin J. , Thompson Mark G. , Iuliano A. Danielle 
Published: July 2024

SUMMARYIntroductionFew studies have examined the incidence of virologic-confirmed influenza virus and respiratory syncytial virus (RSV) infections in community-dwelling older adults.MethodsWe enrolled adults aged 60–89 years in Jiangsu Province, China and followed them weekly from December 2015–September 2017 to identify acute respiratory illnesses (ARI), collect illness information and respiratory specimens for laboratory testing.Results1,527 adults were enrolled, 0·4% reported ever receiving influenza vaccination. 95 PCR-confirmed influenza ARIs and 22 RSV ARIs were identified, among whom 4–5% required hospitalization. One death associated with RSV ARI while none for influenza ARIs was observed. From December 2015-August 2016, the cumulative incidences of influenza and RSV ARIs were 0·8% (95% CI:0·3–1·4) and 0·5% (95% CI:0·1–1·0), respectively. From September 2016-August 2017, the cumulative incidences were 6·1% (95% CI:4·7–7·7) and 1·0% (95% CI:0·5–1·6); the influenza and RSV ARI-associated hospitalization incidences were 0·3% (95% CI:0–0·8) and 0·1% (95% CI:0–0·2). Feverishness was more common in influenza (55%) than RSV ARIs (30%, p=0·03). Influenza (12·5 days, p=0·02) and RSV ARI symptoms (14·1 days, p=0·15) lasted longer compared to PCR-negative/other ARIs (11·0 days). Antibiotic use was more common for influenza (65%, p=0·02) and RSV (70%, p=0·04) ARIs than other ARIs (51%).ConclusionsWe observed a higher incidence of influenza relative to RSV infections among community-dwelling older adults compared to prior studies. Our findings suggest older adults may benefit from receiving influenza and RSV vaccines to reduce the occurrence of illnesses.
A Systematic Review of Mendelian Randomization Studies on Celiac Disease
Authors: Omar Mahmud , Agbareia Reem , Nassar Salih , Omar Mohammad , Naffaa Mohammad E. , Lahat Adi , Sharif Kassem 
Published: July 2024

AbstractBackground and ObjectiveMendelian randomization (MR) has become an important tool in epidemiology, used to infer causal relationships diseases. This review aims to consolidate existing MR evidence concerning celiac disease (CeD).MethodsWe systematically searched major databases up to May 2024, adhering to PRISMA guidelines. Only MR studies explicitly investigating CeD were included. We assessed the quality of each study based on the strength, independence, and exclusivity of the instrumental variables used.ResultsFrom an initial pool of 207 articles, 35 met our inclusion criteria. These studies frequently addressed the relationship between CeD and autoimmune diseases like inflammatory bowel disease (IBD) and explored connections with gut microbiota, various cancers, and metabolic disorders. Significant findings highlight a robust bi-directional association between IBD and CeD and complex interactions with gut microbiota. Notably, many associations reported were near the threshold of clinical significance.ConclusionThis systematic review highlights the dual nature of current MR evidence on CeD. On one hand, we observe consistent associations between CeD, IBDs, and gut microbiota. On the other, there is a plethora of weaker associations that raise critical questions about their clinical and research significance. This work lays a solid foundation for deeper investigations into these weaker links, particularly in relation to lymphomas and psychiatric conditions. It calls for an expanded use of MR and other methodologies to explore under-researched areas.
Type 1 diabetes risk and severity after SARS-CoV-2 infection or vaccination
Authors: Stene Lars C. , Ruiz Paz Lopez-Doriga , Ljung Rickard , Bøås Håkon , Gulseth Hanne L. , Pihlström Nicklas , Sundström Anders , Zethelius Björn , Størdal Ketil , Gani Osman , Lund-Blix Nicolai A. , Skrivarhaug Torild , Tapia German 
Published: July 2024

AbstractAimTo clarify whether SARS-CoV-2 infection or vaccination contribute to risk of type 1 diabetes or more severe diabetes onset in children and young adults.MethodsWe analysed cohorts of population-wide registries of young individuals from Norway (N=1,986,970) and Sweden (N=2,100,188). We used regression models to estimate adjusted rate ratios (aRR), treating exposures as time-varying, starting 30 days after registered SARS-CoV-2 positive test or vaccination.FindingsPooled results from Norway and Sweden and age-groups 12-17 and 18-29 years showed no significant increase in type 1 diabetes after documented infections (aRR 1.06, 95%CI:0.77-1.45). There was moderate heterogeneity, with a suggestive increased risk among children in Norway after infection. Pooled results for Norway and Sweden and age-groups 12-17 years and 18-29 years showed no significant association between SARS-CoV-2 vaccination and risk of type 1 diabetes (aRR 1.09, 95%CI: 0.81, 1.48). There was significant heterogeneity, primarily driven by a positive association among children and an inverse association in young adults in Sweden. While the type 1 diabetes incidence increased and diabetes ketoacidosis decreased over time during 2016-2023, no significant break in time-trends were seen after March 2020 for HbA1c, risk or severity of diabetic ketoacidosis, or islet autoantibodies, at diagnosis of type 1 diabetes.InterpretationTaken together, these results do not indicate any consistent, large effects of SARS-CoV-2 infection or -vaccination on risk of type 1 diabetes or severity at disease onset. Suggestive associations in sub-groups should be investigated further in other studies.FundingThe work was done as part of regular work at the institutions where the authors had their primary affiliation, and no specific funding was obtained for these studies.
WITHDRAWN: AID-SLR: A Generative Artificial Intelligence-Driven Automated System for Systematic Literature Review
Authors: Lee Kyeryoung , Datta Surabhi , Paek Hunki , Rastegar-Mojarad Majid , Huang Liang-Chin , He Long , Wang Siwei , Wang Jingqi , Wang Xiaoyan 
Published: July 2024

Withdrawal StatementThe authors have withdrawn their manuscript owing to [Internal Revision]. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Unexpected diversity and ecological significance of uncultivable large virus-like particles in aquatic environments
Authors: Billard Hermine , Fuster Maxime , Enault François , Carrias Jean-François , Fargette Léa , Carrouée Margot , Desmares Perrine , Delmont Tom O. , Bigeard Estelle , Tanguy Gwenn , Nogaret Pauline , Baudoux Anne-Claire , Christaki Urania , Sime-Ngando Télesphore , Colombet Jonathan 
Published: July 2024

AbstractThe discovery of Jumbo phages and giant viruses of microeukaryotes has transformed our perception of the virosphere. Metagenomic and metatranscriptomic data further highlight their diversity and ecological impact. Nevertheless, sequence-based approaches fail to take into account the morphological diversity of non-cultivated viruses, resulting in our fragmented understanding of their nature and role in the environment. Here, we combined flow cytometry and electron microscopy to uncover both previously unsuspected morphological diversity as well as significant abundances of large viruses in aquatic environments. We discovered four new viral morphotypes, all of which were associated with microeukaryotes. We also obtained insights into the multi-year dynamics of the abundances of both giant microeukaryotic viruses and Jumbo phages. This work deepens our understanding of large viruses and reveals their key role as regulators of microbial communities.
Innate immune system signaling and CD11b+CD11c+CD103+cell migration to the brain underlie changes in mouse behavior after microbial colonization
Authors: Philip Vivek , Kraimi Narjis , Zhang Hailong , Lu Jun , De Palma Giada , Shimbori Chiko , McCoy Kathy D. , Hapfelmeier Siegfried , Schären Olivier P. , Macpherson Andrew J , Chirdo Fernando , Surette Michael G. , Verdu Elena F. , Liu Fang , Collins Stephen M , Bercik Premysl 
Published: July 2024

AbstractBackground and AimsAccumulating evidence suggests the microbiota is a key factor in disorders of gut-brain interaction (DGBI), by affecting host immune and neural systems. However, the underlying mechanisms remain elusive due to their complexity and clinical heterogeneity of patients with DGBIs. We aimed to identify neuroimmune pathways that are critical in microbiota-gut-brain communication during de novo gut colonization.MethodsWe employed a combination of gnotobiotic and state-of-the-art microbial tools, behavioral analysis, immune and pharmacological approaches. Germ-free wild type, MyD88−/−Ticam1−/−and SCID mice were studied before and after colonization with specific pathogen-free microbiota, Altered Schaedler Flora, E. coli or S. typhimurium (permanent or transient colonizers). TLR agonists and antagonists, CCR7 antagonist or immunomodulators were used to study immune pathways. We assessed brain c-Fos, brain-derived neurotrophic factor, and dendritic and glial cells by immunofluorescence, expression of neuroimmune genes by NanoString and performed brain proteomics.ResultsBacterial monocolonization, conventionalization or administration of microbial products to germ-free mice altered mouse behavior similarly, acting through Toll-like receptor or nucleotide-binding oligomerization domain signaling. The process required CD11b+CD11c+CD103+cell activation and migration into the brain. The change in behavior did not require the continued presence of bacteria and was associated with activation of multiple neuro-immune networks in the gut and the brain.ConclusionsChanges in neural plasticity occur rapidly upon initial gut microbial colonization and involve innate immune signaling to the brain, mediated by CD11b+CD11c+CD103+cell migration. The results identify a new target with therapeutic potential for DGBIs developing in context of increased gut and blood-brain barrier permeability.HighlightsMicrobiota impairment is a key factor in disorders of gut-brain interaction (DGBI)Microbial colonization induces changes in brain and behavior via innate immunityMicrobial colonization activates multiple neuro-immune networks in gut and brainBehavioral change is mediated by CD11b+CD11c+CD103+cells migration to the brain
Spatial proteomic mapping of human nuclear bodies reveals new functional insights into RNA regulation
Authors: Dyakov Boris J.A. , Kobelke Simon , Ahmed B. Raktan , Wu Mingkun , Roth Jonathan F. , Kasmaeifar Vesal , Lin Zhen-Yuan , Youn Ji-Young , Thivierge Caroline , Campbell Kieran R. , Duchaine Thomas F. , Blencowe Benjamin J. , Fox Archa H. , Gingras Anne-Claude 
Published: July 2024

AbstractNuclear bodies are diverse membraneless suborganelles with emerging links to development and disease. Explaining their structure, function, regulation, and implications in human health will require understanding their protein composition; however, isolating nuclear bodies for proteomic analysis remains challenging. We present the first comprehensive proximity proteomics-based map of nuclear bodies, featuring 140 bait proteins (encoded by 119 genes) and 1,816 unique prey proteins. We identified 641 potential nuclear body components, including 131 paraspeckle proteins and 147 nuclear speckle proteins. After validating 31 novel paraspeckle and nuclear speckle components, we discovered regulatory functions for the poorly characterised nuclear speckle- and RNA export-associated proteins PAXBP1, PPIL4, and C19ORF47, and revealed that QKI regulates paraspeckle size. This work provides a systematic framework of nuclear body composition in live cells that will accelerate future research into their organisation and roles in human health and disease.