bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of intercellular and extracellular synthesis of biogenic amines by the aquatic mossVesicularia dubyana
Authors: Belyshenko Alexander , Morgunova Maria , Malygina Ekaterina , Dmitrieva Maria , Imidoeva Natalia , Shelkovnikova Victoria , Telnova Tamara , Vlasova Anfisa , Vavilina Tatiana , Tretyakova Anastasia , Axenov-Gribanov Denis 
Published: July 2024

ABSTRACTNatural compounds of mosses are an understudied area of phytochemistry. Over the last 20 years, the amount of information on the chemistry of natural compounds in mosses has increased considerably, but is still underwhelming. Historically, only a few hundred natural products have been described for mosses, whereas the potential for bacteria or fungi is measured in hundreds of thousands of metabolites. Although metabolites with antimicrobial, antiviral, fungicidal, and cytotoxic activities have been discovered in mosses, only few studies have been devoted to compounds with neurogenic properties. In our study, the ability of the aquatic mossVesicularia dubyanato synthesize biogenic amines intercellularly and extracellularly has been evaluated.Aquatic moss was grown in laboratory conditions, and methanol extraction of cell biomass and moss-environment medium was conducted. The presence of biogenic amines was confirmed by UHPLC-MS-MRM analysis.The following compounds were revealed in the cellular biomass ofV. dubyana: histamine, kynurenine, kynurenic acid, tryptamine, and tyramine. Histamine was also detected in the moss-environment medium, indicating the extracellular synthesis of this natural compound. Methanol extracts of the studied moss showed low antibacterial and antioxidant activities. Thus, this study for the first time demonstrates biogenic amine synthesis by aquatic mosses.
Human ANP32A/B are SUMOylated and utilized by avian influenza virus NS2 protein to overcome species-specific restriction
Authors: Sun Liuke , Guo Xing , Yu Mengmeng , Wang Xue-Feng , Ren Huiling , Wang Xiaojun 
Published: July 2024

AbstractHuman ANP32A/B (huANP32A/B) poorly support the polymerase activity of avian influenza viruses (AIVs), thereby limiting interspecies transmission of AIVs from birds to humans. The SUMO-interacting motif (SIM) within NS2 promotes the adaptation of AIV polymerase to huANP32A/B via a yet undisclosed mechanism. Here we show that huANP32A/B are SUMOylated by the E3 SUMO ligase PIAS2α, and deSUMOylated by SENP1. SUMO modification of huANP32A/B results in the recruitment of NS2, thereby facilitating huANP32A/B-supported AIV polymerase activity. Such a SUMO-dependent recruitment of NS2 is mediated by its association with huANP32A/B via the SIM-SUMO interaction module, where K68/K153-SUMO in huANP32A or K68/K116-SUMO in huANP32B interacts with the NS2-SIM. The SIM-SUMO interactions between huANP32A/B and NS2 function to promote AIV polymerase activity by positively regulating AIV vRNP-huANP32A/B interactions and AIV vRNP assembly. Our study offers insights into the mechanism of NS2 SIM in facilitating AIVs adaptation to mammals.
High-throughput discovery of regulatory effector domains in human RNA-binding proteins
Authors: Thurm Abby R. , Finkel Yaara , Andrews Cecelia , Cai Xiangmeng S. , Benko Colette , Bintu Lacramioara 
Published: July 2024

SummaryRNA regulation plays an integral role in tuning gene expression and is controlled by thousands of RNA-binding proteins (RBPs). We develop and use a high-throughput recruitment assay (HT-RNA-Recruit) to identify regulatory domains within human RBPs by recruiting over 30,000 protein tiles from 367 RBPs to a reporter mRNA. We discover over 100 unique RNA-regulatory effectors in 86 distinct RBPs, presenting evidence that RBPs contain functionally separable domains that dictate their post-transcriptional control of gene expression, and identify some with unique activity at 5’ or 3’UTRs. We identify some domains that downregulate gene expression both when recruited to DNA and RNA, and dissect their mechanisms of regulation. Finally, we build a synthetic RNA regulator that can stably maintain gene expression at desired levels that are predictable by a mathematical model. This work serves as a resource for human RNA-regulatory effectors and expands the synthetic repertoire of RNA-based genetic control tools.Highlights-HT-RNA-Recruit identifies hundreds of RNA-regulatory effectors in human proteins.-Recruitment to 5’ and 3’ UTRs identifies regulatory domains unique to each position.-Some protein domains have both transcriptional and post-transcriptional regulatory activity.-We develop a synthetic RNA regulator and a mathematical model to describe its behavior.
Lactate-carried Mitochondrial Energy Overflow
Authors: Rauseo Daniela , Contreras-Baeza Yasna , Faurand Hugo , Cárcamo Nataly , Suárez Raibel , von Faber-Castell Alexandra , Silva Franco , Mora-González Valentina , Wyss Matthias T. , Baeza-Lehnert Felipe , Ruminot Iván , Alvarez-Navarro Carlos , Martín Alejandro San , Weber Bruno , Sandoval Pamela Y. , Barros L. Felipe 
Published: July 2024

AbstractWe addressed the question of mitochondrial lactate metabolism using genetically-encoded sensors. The organelle was found to contain a dynamic lactate pool that leads to dose- and time-dependent protein lactylation. In neurons, mitochondrial lactate reported blood lactate levels with high fidelity. The exchange of lactate across the inner mitochondrial membrane was found to be mediated by a high affinity H+-coupled transport system involving the mitochondrial pyruvate carrier MPC. Assessment of electron transport chain activity and determination of lactate flux showed that mitochondria are tonic lactate producers, a phenomenon driven by energization and stimulated by hypoxia. We conclude that an overflow mechanism caps the redox level of mitochondria, while saving energy in the form of lactate.One Sentence SummaryMitochondrial lactate production
Impact ofAPOE,Klothoand sex on cognitive decline with aging
Authors: Shibata Kengo , Chen Cheng , Tai Xin You , Manohar Sanjay G , Husain Masud 
Published: July 2024

AbstractThe effects ofAPOEandKlothogenes, both implicated in aging, on human cognition as a function of sex and age are yet to be definitively established. Here we showed in the largest cohort studied to date (N =320,861) thatAPOEhomozygous ε4 carriers had a greater decline in cognition with aging compared to ε3 carriers (ε4/ε3 & ε3/ε3) as well as smaller hippocampi and amygdala (N =37,976). Critically, sex and age differentially affected the decline in cognition. Younger (40 - 50 years) female homozygous ε4 carriers showed a cognitive advantage over female ε3 carriers, but this advantage was not present in males. By contrast,Klotho-VSheterozygosity did not affect cognition or brain volume, regardless ofAPOEgenotype, sex or age. These cognitive trajectories with aging demonstrate clear sex- dependent antagonistic pleiotropy effects ofAPOEε4, but no effects ofKlothogenotype on cognition and brain volume.
Still Not Sterile: Chlorhexidine gluconate treatment does not completely reduce skin microbial bioburden and promotes pathogen overabundance in patients undergoing elective surgeries
Authors: Townsend Elizabeth C. , Xu Kayla , De La Cruz Karinda , Huang Lynda , Sandstrom Shelby , Arend Delanie , Gromek Owen , Scarborough John , Huttenlocher Anna , Gibson Angela L.F. , Kalan Lindsay R. 
Published: July 2024

AbstractSurgical site infections (SSI) continue to occur despite widespread adoption of surgical antiseptics. The effects of chlorhexidine gluconate (CHG)-based antiseptics on the skin microbiome also remains undefined due to confounding effects of CHG persistence on skin. Patients undergoing elective surgery were enrolled to characterize the immediate and long-term impact of pre-surgical preparation with CHG antiseptic on skin microbial communities. Due to the broad-spectrum antimicrobial activity of CHG and its propensity to bind extracellular DNA, methods to selectively identify live microorganisms are critical to this process and to fully elucidate the effectiveness of pre-surgical protocols and potential disruptions to the healthy skin microbiome. Swabs of the surgical site skin microbiome were collected at multiple timepoints before and after surgery. Microbial bioburden and community compositions were evaluated with viability qPCR and 16S ribosomal RNA gene profiling. Pre-operative CHG induced a measurable reduction in the viable microbial bioburden at the surgical site. On the day of surgery, surgical sites displayed a significant increase in the relative abundance of several SSI associated bacterial genera, including, Acinetobacter, Bacillus, Escherichia-Shigella,andPseudomonas, compared to baseline. Bacillusspecies isolated from subjects at baseline showed resistance to CHG with MICs exceeding 1000 µg/ml. Despite major shifts in the skin microbiome upon exposure to CHG, they were transient in the majority of individuals. Skin microbial community structure recovered by the post-surgical follow-up. In short, this study shows that pre-surgical application of CHG can significantly reduce viable skin microbial bioburden, however, complete sterility is not achieved. While CHG induces temporary shifts in the skin microbiome, including enrichment for potentially pathogenic taxa, the skin microbiome recovers back to near baseline. Collectively, these findings identify tangible avenues for improving antiseptic formulations and offer further support that the skin microbiome is viable, stable, and resilient to chemical perturbation.
Secreted exosomes induce filopodia formation
Authors: McAtee Caitlin , Patel Mikin , Hoshino Daisuke , Sung Bong Hwan , von Lersner Ariana , Shi Mingjian , Hong Nan Hyung , Young Anna , Krystofiak Evan , Zijlstra Andries , Weaver Alissa M. 
Published: July 2024

AbstractFilopodia are dynamic adhesive cytoskeletal structures that are critical for directional sensing, polarization, cell-cell adhesion, and migration of diverse cell types. Filopodia are also critical for neuronal synapse formation. While dynamic rearrangement of the actin cytoskeleton is known to be critical for filopodia biogenesis, little is known about the upstream extracellular signals. Here, we identify secreted exosomes as potent regulators of filopodia formation. Inhibition of exosome secretion inhibited the formation and stabilization of filopodia in both cancer cells and neurons and inhibited subsequent synapse formation by neurons. Rescue experiments with purified small and large extracellular vesicles (EVs) identified exosome-enriched small EVs (SEVs) as having potent filopodia-inducing activity. Proteomic analyses of cancer cell-derived SEVs identified the TGF-β family coreceptor endoglin as a key SEV-enriched cargo that regulates filopodia. Cancer cell endoglin levels also affected filopodia-dependent behaviors, including metastasis of cancer cells in chick embryos and 3D migration in collagen gels. As neurons do not express endoglin, we performed a second proteomics experiment to identify SEV cargoes regulated by endoglin that might promote filopodia in both cell types. We discovered a single SEV cargo that was altered in endoglin-KD cancer SEVs, the transmembrane protein Thrombospondin Type 1 Domain Containing 7A (THSD7A). We further found that both cancer cell and neuronal SEVs carry THSD7A and that add-back of purified THSD7A is sufficient to rescue filopodia defects of both endoglin-KD cancer cells and exosome-inhibited neurons. We also find that THSD7A induces filopodia formation through activation of the Rho GTPase, Cdc42. These findings suggest a new model for filopodia formation, triggered by exosomes carrying THSD7A.
Standardizing and Scaffolding Healthcare AI-Chatbot Evaluation
Authors: Hua Yining , Xia Winna , Bates David W. , Hartstein George Luke , Kim Hyungjin Tom , Li Michael Lingzhi , Nelson Benjamin W. , Stromeyer Charles , King Darlene , Suh Jina , Zhou Li , Torous John 
Published: July 2024

AbstractThe rapid rise of healthcare chatbots, valued at $787.1 million in 2022 and projected to grow at 23.9% annually through 2030, underscores the need for robust evaluation frameworks. Despite their potential, the absence of standardized evaluation criteria and rapid AI advancements complicate assessments. This study addresses these challenges by developing the first comprehensive evaluation framework inspired by health app regulations and integrating insights from diverse stakeholders. Following PRISMA guidelines, we reviewed 11 existing frameworks, refining 271 questions into a structured framework encompassing three priority constructs, 18 second-level constructs, and 60 third-level constructs. Our framework emphasizes safety, privacy, trustworthiness, and usefulness, aligning with recent concerns about AI in healthcare. This adaptable framework aims to serve as the initial step in facilitating the responsible integration of chatbots into healthcare settings.
Epigenome-wide association study of pregnancy exposure to green space and placental DNA methylation
Authors: Aguilar-Lacasaña Sofía , Cosin-Tomas Marta , Raimbault Bruno , Gómez Laura , Sánchez Olga , Zanini Maria Julia , Capdevila Rosalia Pascal , Foraster Maria , Gascon Mireia , Rivas Ioar , Llurba Elisa , Gómez-Roig Maria Dolores , Sunyer Jordi , Vrijheid Martine , Bustamante Mariona , Dadvand Payam 
Published: July 2024

AbstractMaternal exposure to green space during pregnancy has been associated with lower risk for adverse birth outcomes; however, the underlying biological mechanisms remain largely unknown. Epigenetic changes, such as DNA methylation (DNAm), might be one of the molecular mechanisms contributing to this association. The placenta is the key organ for foetal growth and development, but studies of prenatal green space exposure and placental DNAm are scarce and have not been conducted on a genome-wide scale. Here, we aimed to investigate the association between exposure to green space during pregnancy and epigenome-wide placental DNAm.This study was conducted in 550 mother-child pairs from the Barcelona Life Study Cohort (BiSC), a population-based birth cohort in Spain (2018-2021). We comprehensively assessed green space exposure during pregnancy as (i) residential surrounding greenness (satellite-based Normalized Difference Vegetation Index (NDVI) in buffers of 100m, 300m and 500m), (ii) residential distance to the nearest major green space (meters), iii) use of green space (hours/week), and iv) visual access to greenery through home window (≥half of the view). Placental DNAm was measured with the EPIC array. To identify differentially methylated positions (DMPs), we fitted robust linear regression models adjusted for relevant covariates, while differentially methylated regions (DMRs) were identified using thedmrffmethod.After Bonferroni (BN) correction, cg14852540, annotated toSLC25A10gene, was inversely associated with residential surrounding greenness within 500m buffer. Additionally, ten unique DMRs were associated with surrounding greenness within 300m and 500m, distance or visual access to green space. No associations were found for surrounding greenness within 100m or use of green space. Genes annotated to these loci are involved in transcriptional regulation, metabolism and mitochondrial respiration.Overall, we identified associations between prenatal green space exposure and DNAm levels in placenta. Further research is needed to validate these results and understand the underlying biological pathways.
Meiosis-specific decoupling of the pericentromere from the kinetochore
Authors: Pan Bo , Bruno Melania , Macfarlan Todd S , Akera Takashi 
Published: July 2024

AbstractThe primary constriction site of the M-phase chromosome is an established marker for the kinetochore position, often used to determine the karyotype of each species. Underlying this observation is the concept that the kinetochore is spatially linked with the pericentromere where sister-chromatids are most tightly cohered. Here, we found an unconventional pericentromere specification with sister chromatids mainly cohered at a chromosome end, spatially separated from the kinetochore inPeromyscusmouse oocytes. This distal locus enriched cohesin protectors, such as the Chromosomal Passenger Complex (CPC) and PP2A, at a higher level compared to its centromere/kinetochore region, acting as the primary site for sister-chromatid cohesion. Chromosomes with the distal cohesion site exhibited enhanced cohesin protection at anaphase I compared to those without it, implying that these distal cohesion sites may have evolved to ensure sister-chromatid cohesion during meiosis. In contrast, mitotic cells enriched CPC only near the kinetochore and the distal locus was not cohered between sister chromatids, suggesting a meiosis-specific mechanism to protect cohesin at this distal locus. We found that this distal locus corresponds to an additional centromeric satellite block, located far apart from the centromeric satellite block that builds the kinetochore. SeveralPeromyscusspecies carry chromosomes with two such centromeric satellite blocks. Analyses on threePeromyscusspecies revealed that the internal satellite consistently assembles the kinetochore in both mitosis and meiosis, whereas the distal satellite selectively enriches cohesin protectors in meiosis to promote sister-chromatid cohesion at that site. Thus, our study demonstrates that pericentromere specification is remarkably flexible and can control chromosome segregation in a cell-type and context dependent manner.
AQuaRef: Machine learning accelerated quantum refinement of protein structures
Authors: Zubatyuk Roman , Biczysko Malgorzata , Ranasinghe Kavindri , Moriarty Nigel W. , Gokcan Hatice , Kruse Holger , Poon Billy K. , Adams Paul D. , Waller Mark P. , Roitberg Adrian E. , Isayev Olexandr , Afonine Pavel V. 
Published: July 2024

ABSTRACTCryo-EM and X-ray crystallography provide crucial experimental data for obtaining atomic-detail models of biomacromolecules. Refining these models relies on library- based stereochemical restraints, which, in addition to being limited to known chemical entities, do not include meaningful noncovalent interactions relying solely on nonbonded repulsions. Quantum mechanical (QM) calculations could alleviate these issues but are too expensive for large molecules. We present a novel AI-enabled Quantum Refinement (AQuaRef) based on AIMNet2 neural network potential mimicking QM at substantially lower computational costs. By refining 41 cryo-EM and 30 X-ray structures, we show that this approach yields atomic models with superior geometric quality compared to standard techniques, while maintaining an equal or better fit to experimental data.
Trajectory of severe COVID anxiety and predictors for recovery in an 18-month cohort
Authors: King Jacob D , McQuaid Aisling , Barnicot Kirsten , Bassett Paul , Leeson Verity C , Di Simplicio Martina , Tyrer Peter , Tyrer Helen , Watt Richard G , Crawford Mike J 
Published: July 2024

AbstractBackgroundPeople with severe COVID anxiety have significant fears of contagion, physiological symptoms of anxiety in response to a COVID stimuli, and employ safety behaviours which are often in excess of health guidelines and at the expense of other life priorities. The natural course of severe COVID anxiety is not known.MethodsThis prospective cohort study followed 285 people with severe COVID anxiety in United Kingdom over 18-months. Descriptive statistics and linear regression models identified factors associated with change in COVID anxiety.ResultsMost participants experienced major reductions in COVID anxiety over time (69.8% relative cohort mean decrease; p<0.001), but a quarter of people (23.7%, 95% CI 17.8 to 30.1) continued to worry about COVID every day. Increasing age, being from an ethnic background which conferred greater risk from COVID-19, and the persistence of high levels of health anxiety and depressive symptoms predicted significantly slower improvements in severe COVID anxiety adjusting for other clinical and demographic factors.ConclusionsFor most people severe COVID anxiety significantly improves with time. However established interventions treating depression or health anxiety, and targeting older people and people from at-risk minority groups who appear to recover at slower rates, might be clinically indicated in future pandemics.HighlightsMost people with severe COVID anxiety reported large improvements in symptoms 18-months later.Levels of co-occurring poor mental health and social functioning also improved for most people.More than 1 in 10 continued to have severe COVID anxiety symptoms 18 months later.Age, ethnic background, and high levels of health anxiety and depression predict slower improvements.People with these risk characteristics could be considered for targeted support.
Association of polyunsaturated fatty acids with cholelithiasis risk and the role of plasma lipid mediators: insights from NHANES 2017-2020 and Mendelian randomization
Authors: Chen Yuxuan , Chen Wei , Qian Jin , Jin Xuanchen , Wang Congying , Zheng Yihu 
Published: July 2024

AbstractBackground & aimsPrevious studies have suggested a potential link between polyunsaturated fatty acid (PUFA) intake and the risk of cholelithiasis. Omega-3 fatty acids, a key subfamily of PUFAs, have been identified in observational studies as playing a role in lipid regulation and potentially serving as a protective factor against cholelithiasis. In this study, we aim to investigate this association further by analyzing data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) and conducting Mendelian randomization (MR) analyses.MethodsWe employed weighted multivariate-adjusted logistic regression analyses to examine the association between PUFAs and cholelithiasis risk using data from NHANES 2017-2020. Additionally, a two-sample Mendelian randomization (MR) study was conducted utilizing pooled data from Genome-Wide Association Studies (GWAS) to establish the causal relationship between PUFAs and cholelithiasis. Following this, we performed two-step MR mediation analyses to investigate the mediating role of plasma lipids in the pathway, focusing on the strongly positive subfamily of PUFAs, Omega-3, in relation to plasma circulating lipids and cholelithiasis.ResultsOur observational study in NHANES included 7,527 participants. Weighted multivariate-adjusted logistic regression analyses initially revealed a negative association between PUFAs, their subclasses, and cholelithiasis. However, this association became nonsignificant after adjusting for multiple covariates. In contrast, MR analyses identified a significant negative association between PUFAs (OR=0.75 [95% CI, 0.58∼0.98]) and Omega-3 (OR=0.79 [95% CI, 0.7∼0.9]) and the risk of cholelithiasis. Specifically, Omega-3 was associated with a reduced risk of developing cholelithiasis (OR=0.77 [95% CI, 0.65∼0.91]), possibly due to the upregulation of LDL-C levels (Beta=0.24 [95% CI, 0.1∼0.38]). This upregulation of LDL-C subsequently lowered the risk of cholelithiasis (OR=0.77 [95% CI, 0.65∼0.91]), with the mediating effect of LDL-C accounting for 28% of the overall association.ConclusionsBoth cross-sectional observational analyses and Mendelian randomization (MR) analyses demonstrated a negative correlation between polyunsaturated fatty acids (PUFAs) and cholelithiasis. Omega-3 fatty acids seem to play a key role in this association by increasing plasma LDL-C levels, which in turn may help reduce the risk of cholelithiasis.