bluuebunny/crossref_metadata_2025_split huggingface dataset:
An autophagy adaptor TRIAD3A promotes tau fibrillation by phase separation
Authors: Zhou Jiechao , Chuang Yang ‘an , Redding-Ochoa Javier , Platero Alexander J. , Barrett Alexander H. , Troncoso Juan C. , Worley Paul F. , Zhang Wenchi 
Published: October 2023

AbstractMultiple neurodegenerative diseases are characterized by aberrant proteinaceous accumulations of tau. Here, we report an RBR-type E3 ligase TRIAD3A functions as a novel autophagy adaptor for tau.TRIAD3A(RNF216) is an essential gene with mutations causing ageprogressive neurodegeneration. Our studies reveal that TRIAD3A E3 ligase catalyzes a novel mixed K11/K63 polyubiquitin chain and self assembles into liquid-liquid phase separated (LLPS) droplets. Tau is ubiquitinated and accumulates within TRIAD3A LLPS droplets and via LC3 interacting regions targets tau for autophagic degradation. Unexpectedly, tau sequestered within TRIAD3A droplets rapidly converts to amyloid aggregates without the transitional liquid phase of tau. In vivo studies reveal TRIAD3A decreases the accumulation of phosphorylated tau in a tauopathy mouse model, and disease-associated mutation of TRIAD3A increases accumulation of phosphorylated tau, exacerbates gliosis, and increases pathological tau spreading. In human Alzheimer’s disease brain, TRIAD3A colocalizes with tau amyloid in multiple histological forms suggesting a role in tau homeostasis. TRIAD3A is the first autophagic adaptor that utilizes E3-ligase and LLPS as a mechanism to capture cargo and appears especially relevant to neurodegenerative diseases.
Human proton channels accumulate in cholesterol dependent membrane domains via direct interaction with stomatin
Authors: Ayuyan Artem G. , Cherny Vladimir V. , Chaves Gustavo , Musset Boris , Cohen Fredric S. , DeCoursey Thomas E. 
Published: October 2023

AbstractMany membrane proteins are modulated by cholesterol. Here we report strong effects of cholesterol depletion and restoration on the human voltage gated proton channel, hHV1 in excised patches but negligible effects in whole-cell configuration. Despite the presence of a putative cholesterol binding site, a CARC domain in the human voltage gated proton channel, hHV1, mutation of this domain did not affect cholesterol effects. The murine HV1 lacks a CARC sequence but displays similar cholesterol effects. These three results all argue against a direct effect of cholesterol on HV1. We propose that the data are explainable if HV1 preferentially associates with cholesterol-dependent lipid domains, or “rafts.” The rafts would be expected to concentrate in the membrane/glass interface and to be depleted from the electrically-accessible patch membrane. This idea is supported by evidence that HV1 channels can diffuse between seal and patch membranes when suction is applied. Suction pulls membrane constituents including HV1 into the patch. In whole-cell studies moderate osmotic stretch does not noticeably alter H+currents. Simultaneous truncation of the large intracellular N- and C-termini greatly attenuated the cholesterol effect, but C-truncation only did not. We conclude that the N-terminus is the region of attachment to lipid domains. Searching for abundant raft-associated molecules led to stomatin. Co-immunoprecipitation experiments showed that hHV1 binds to stomatin. The stomatin-mediated association of HV1 with cholesterol-dependent lipid domains provides a mechanism for cells to direct HV1 to subcellular location where it is needed, such as the phagosome in leukocytes.SignificanceMany membrane proteins are modulated by cholesterol. Here we explore effects of cholesterol on the human voltage-gated proton channel, hHV1. Although we find little evidence for a direct effect, cholesterol was found to exert a strong influence over H+current in excised membrane patches. These effects are explainable by hypothesizing that HV1 preferentially associates with cholesterol-dependent membrane lipid domains. We postulate that HV1 diffuses within the membrane and is concentrated in such domains that are anchored to the pipette glass by large membrane proteins. We find that HV1 co-immunoprecipitates with stomatin, a typical component of cholesterol dependent lipid domains. The association of HV1 with lipid domains provides a mechanism for directing HV1 to specific subcellular locations to perform specific functions.
Epidemiology and Nomogram Development for Chronic Eosinophilic Leukemia, Not Otherwise Specified (CEL-NOS): Insights from the SEER Database
Authors: Wang Fan 
Published: October 2023

AbstractBackgroundChronic Eosinophilic Leukemia, Not Otherwise Specified (CEL-NOS), a rare and intricate hematological disorder characterized by uncontrolled eosinophilic proliferation, presents clinical challenges owing to its infrequency. This study aimed to investigate the epidemiology and develop a prognostic nomogram for CEL-NOS patients.MethodsUtilizing the Surveillance, Epidemiology and End Results (SEER) database, CEL-NOS cases diagnosed between 2001 and 2020 were analyzed for incidence rates, clinical profiles, and survival outcomes. Patients were randomly divided into training and validation cohorts (7:3 ratio). LASSO regression analysis and Cox regression analysis were performed to screen the prognostic factors for overall survival. A nomogram was then constructed and validated to predict the 3- and 5-year overall survival probability of CEL-NOS patients by incorporating these factors.ResultsThe incidence rate of CEL-NOS was very low, with an average of 0.033 per 100,000 person-years from 2001 to 2020. The incidence rate significantly increased with age and was higher in males than females. The mean age at diagnosis was 57 years. Prognostic analysis identified advanced age, specific marital statuses, and secondary CEL-NOS as independent and adverse predictors of overall survival (OS). To facilitate personalized prognostication, a nomogram was developed incorporating these factors, demonstrating good calibration and discrimination. Risk stratification using the nomogram effectively differentiated patients into low- and high-risk groups.ConclusionsThis study enhances our understanding of CEL-NOS, offering novel insights into its epidemiology, demographics, and prognostic determinants, while providing a possible prognostication tool for clinical use. However, further research is warranted to elucidate molecular mechanisms and optimize therapeutic strategies for CEL-NOS.
Prenatal exposure to THC vapor influences feeding, bodyweight and glucose metabolism under both basal conditions and following high fat diet
Authors: Hume Catherine , Baglot Samantha L. , Javorcikova Lucia , Lightfoot Savannah H.M. , Scheufen Jessica B.K. , Hill Matthew N. 
Published: October 2023

Abstract4-20% of people report using cannabis during pregnancy, thereby it is essential to assess the associated risks. There is some evidence that prenatal cannabis exposure (PCE) may be associated with increased risk for development of obesity and diabetes later in life, however this has not been well explored under controlled conditions. The aim of this study was to use a translational THC vapor model in rodents to characterize the effects of PCE on adiposity, glucose metabolism, and feeding patterns in adulthood, with focus on potential sex differences. Pregnant Sprague Dawley rats were exposed to vaporized THC (100mg/ml) or control (polyethylene glycol vehicle) across the entire gestational period. Adult offspring from PCE or control litters were subjected to measures of adiposity, glucose metabolism and feeding behavior. Rats were then placed onto special diets (60% high-fat diet [HFD] or control 10% low fat diet [LFD]) for 4-months, then re-subjected to adiposity, glucose metabolism and feeding behavior measurements. PCE did not influence maternal weight or food consumption but was associated with transient decreased pup weight. PCE did not initially influence bodyweight or adiposity, but PCE did significantly reduce the rate of bodyweight gain when animals were maintained on special diets (HFD/LFD), regardless of which diet. Further, PCE had complex effects on glucose metabolism and feeding behavior that were both sex and diet dependent. No effects of PCE were found on plasma leptin or insulin, or white adipose tissue mass. Overall, this data enhances current understanding of the potential impacts of PCE.
Accurate Identification of Motoneuron Discharges from Ultrasound Images Across the Full Muscle Cross-Section
Authors: Lubel Emma , Rohlén Robin , Sgambato Bruno Grandi , Barsakcioglu Deren Y , Ibáñez Jaime , Tang Meng-Xing , Farina Dario 
Published: October 2023

AbstractObjectiveNon-invasive identification of motoneuron (MN) activity is commonly done using (EMG). However, surface EMG (sEMG) signals detect only superficial sources, at less than approximately 10-mm depth. Intramuscular EMG can detect deep sources, but it is limited to sources within a few mm of the detection site. Conversely, ultrasound (US) images have high spatial resolution across the whole muscle cross-section. The activity of MNs can be extracted from US images due to the movements that MN activation generates in the innervated muscle fibers. Current US-based decomposition methods can accurately identify the location and average twitch induced by MN activity. However, they cannot accurately detect MN discharge times.MethodsHere, we present a method based on the convolutive blind source separation of US images to estimate MN discharge times with high accuracy. The method was validated across 10 participants using concomitant sEMG decomposition as the ground truth.Results140 unique MN spike trains were identified from US images, with a rate of agreement (RoA) with sEMG decomposition of 87.4 ± 10.3 %. Over 50% of these MN spike trains had a RoA greater than 90%. Furthermore, with US, we identified additional MUs well beyond the sEMG detection volume, at up to >30 mm below the skin.ConclusionThe proposed method can identify discharges of MNs innervating muscle fibers in a large range of depths within the muscle from US images.SignificanceThe proposed methodology can non-invasively interface with the outer layers of the central nervous system innervating muscles across the full cross-section.
A morphotype ofSaccolaimus saccolaimus(Chiroptera: Emballonuridae) from West Bengal, India with a comparative note of the species
Authors: Bhakat Somnath 
Published: October 2023

AbstractAn adultSaccolaimus saccolaimusTemminck, 1838 is described here with morphometric measurements in detail. The present species though showed morphological similarities with the species reported from India and abroad but it bears an exceptional character, a white oval pad at the base of the thumb. A comparative note of the species found in India and other countries are also presented here with a suggestion to rethink the IUCN status of the species “Least Concern” in India.
TreeArchTraits: an R package to analyse the architectural traits of trees using TLS data
Authors: Puletti Nicola , Innocenti Simone , Guasti Matteo , Alvites Cesar 
Published: October 2023

1AbstractThe architecture of trees is significantly influenced by their interactions, directly affecting their functioning and structural development. Different tree architectural indicators (TAT) have evolved, including these interactions’ measurements.Recent advances in Terrestrial Laser Scanning data collection make measuring the three-dimensional characteristics of trees more more efficient.The R packageTreeArchTraitsfacilitates the processing of three-dimensional tree characteristics obtained through Terrestrial Laser Scanning, enabling the computation of various indices.A set of trees belonging to different forest conditions was used to demonstrate theTreeArchTraitspotential for characterizing tree architectures.Abstract Figure
HIV-DRIVES: HIV Drug Resistance Identification, Variant Evaluation, & Surveillance Pipeline
Authors: Kanyerezi Stephen , Sserwadda Ivan , Ssemaganda Aloysius , Seruyange Julius , Ayitewala Alisen , Oundo Hellen , Tenywa Wilson , Kagurusi Brian , Tusabe Godwin , Were Stacy , Ssewanyana Isaac , Nabadda Susan , Namaganda Maria Magdalene , Mboowa Gerald 
Published: October 2023

AbstractThe global prevalence of resistance to the Human Immunodeficiency Virus (HIV) combined antiretroviral therapy (cART) emphasizes the need to continuous monitoring to better understand the dynamics of drug-resistant mutations to guide treatment optimization and patient management as well as check the spread of resistant viral strains. We have recently, integrated next-generation sequencing (NGS) into routine HIV drug resistance (HIVDR) monitoring, with key challenges in the bioinformatic analysis and interpretation of the complex data generated while ensuring data security and privacy of patient information. To address these challenges, here, we present HIV-DRIVES (HIV Drug Resistance Identification, Variant Evaluation, and Surveillance), an NGS-HIVDR bioinformatics pipeline that has been developed and validated using Illumina short-reads, FASTA, and sanger ab1.seq files.Availability and implementationHIV-DRIVES source codes and operation manual freely available athttps://github.com/MicroBioGenoHub/HIV-DRIVES.
Default mode network shows distinct emotional and contextual responses yet common effects of retrieval demands across tasks
Authors: Souter Nicholas E. , de Freitas Antonia , Zhang Meichao , Shao Ximing , del Jesus Gonzalez Alam Tirso Rene , Engen Haakon , Smallwood Jonathan , Krieger-Redwood Katya , Jefferies Elizabeth 
Published: October 2023

AbstractThe default mode network (DMN) lies towards the heteromodal end of the principal gradient of intrinsic connectivity, maximally separated from sensory-motor cortex. It supports memory-based cognition, including the capacity to retrieve conceptual and evaluative information from sensory inputs, and to generate meaningful states internally; however, the functional organisation of DMN that can support these distinct modes of retrieval remains unclear. We used fMRI to examine whether activation within subsystems of DMN differed as a function of retrieval demands, or the type of information to be retrieved, or both. In a picture association task, participants retrieved two types of semantic features about contexts and emotions: in the generate phase, these associations were retrieved from a novel picture, while in a switch phase, participants retrieved a new association for the same image. Semantic context and emotion trials were associated with dissociable DMN subnetworks, indicating that a key dimension of DMN organisation relates to the type of information being accessed. The fronto-temporal and medial temporal DMN showed a preference for emotional and contextual associations, respectively. Relative to the generate phase, the switch phase recruited clusters closer to the heteromodal apex of the principal gradient – a cortical hierarchy separating unimodal and heteromodal regions. There were no differences in this effect between association types. Instead, memory switching was associated with a distinct subnetwork associated with controlled internal cognition. These findings delineatedistinctpatterns of DMN recruitment for different kinds of associations yetcommonresponses across tasks that reflect retrieval demands.Key pointsRetrieval of contextual and emotional features relies on distinct default mode subnetworks.Novelty of visual input has an equivalent effect across default mode subnetworks.Secondary associations retrieved from re-presented pictures activate heteromodal end of the principal gradient.
Antiepileptic medication strengthens excitatory neurotransmission in pyramidal neurons of the adult human neocortex
Authors: Lenz Maximilian , Kruse Pia , Eichler Amelie , Straehle Jakob , Hemeling Hanna , Stöhr Phyllis , Beck Jürgen , Vlachos Andreas 
Published: October 2023

ABSTRACTHomeostatic synaptic plasticity serves to maintain neuronal function within a dynamic range upon perturbations in network activity. While coordinated structural and functional changes at synaptic sites play a crucial role in adaptive processes, the specific regulatory mechanisms and biological relevance of homeostatic plasticity in the human brain warrant further investigation. In this study, we investigated the effects of neural network silencing, achieved through pharmacological inhibition of voltage-gated sodium channels or glutamatergic neurotransmission – common targets of antiepileptic medication – on functional and structural properties of murine and human cortical tissue. Using mouse entorhino-hippocampal tissue cultures, acute neocortical slices of adult mice, and human brain tissue, we characterize homeostatic synaptic plasticity across models, brain regions, and species. Our findings demonstrate local homeostatic synaptic plasticity in the adult human neocortex, highlighting the potential effects of antiepileptic medication in brain regions unaffected by the primary diseases, which might represent a mechanism for neuropsychiatric effects linked to these medications and increased seizure susceptibility upon discontinuation of antiepileptic medication.
A senescence-like state is beneficial for ovarian cancer treatment
Authors: Skulimowski Michael , Calvo Llilians , Cheng Shuofei , Clément Isabelle , Portelance Lise , Zhan Yu , Carmona Euridice , Lafontaine Julie , de Ladurantaye Manon , Rahimi Kurosh , Provencher Diane , Mes-Masson Anne-Marie , Rodier Francis 
Published: October 2023

AbstractHigh-grade serous ovarian carcinoma (HGSOC) commonly responds to initial therapy, but this response is rarely durable. Understanding cell fate decisions taken by HGSOC cells in response to treatment could guide new therapeutic opportunities. Here we find that tissue-derived primary HGSOC epithelial cultures reflecting the original disease primarily undergo therapy-induced senescence in response to DNA damage and first-line carboplatin/paclitaxel chemotherapy. Unlike previous observations using cell lines, primary HGSOC cell TIS displays a stable senescence proliferation arrest and p16INK4A expression, and is accompanied by persistent DNA damage, an inflammatory secretome, and senolytic sensitivity, suggesting new avenues for selective pharmacological manipulation of these cells. Whether cell senescence induced by cancer therapy is beneficial or detrimental to clinical outcomes remains unknown. Single cell comparison of pre- and post-chemotherapy patient HGSOC tissue samples revealed changes in physio-pathological senescence biomarkers supporting a post-treatment senescence-like state. Importantly, patients with stronger senescence signatures post-chemotherapy displayed better 5-year survival suggesting that senescence accounts, at least in part, for beneficial cellular responses to treatment. Given that ovarian cancer epithelial cells almost universally retain the capacity to undergo senescence and that senescence appears beneficial in this context, HGSOC senescence-centric therapeutic avenues should be further explored.Author SummaryWhether cancer therapy-induced cell fate decisions like senescence are good or bad for patient treatment outcome is unknown. We find that ovarian cancer cells almost universally retain senescence competence and that senescence in treated cancer tissues correlate with good clinical outcomes. This reveals that senescence is a relevant drug target in ovarian cancer.
Torpor energetics are related to the interaction between body mass and climate in bats of the family Vespertilionidae
Authors: Ayala-Berdon Jorge , Medina-Bello Kevin I. 
Published: October 2023

AbstractTorpor is an adaptive strategy that allows animals to cope with energy limitations under adverse environmental conditions. In birds and mammals, intrinsic and extrinsic factors such as body mass (Mb) and ambient temperature (Ta) are well established triggers of torpor. Interestingly, the interplay betweenMband climate with differentTaon torpor traits in bats remains unexplored. Using open flow respirometry, we calculatedTaupon entering torpor (Tat), the reduction in torpid metabolic rate relative to the basal metabolic rate (TMRred), theTaat which torpor metabolic rate reached its minimum (Taadjust), and minimum torpid metabolic rate (TMRmin) in 11 bat species of the family Vespertilionidae that differ inMbfrom warm and cold climates. We also includedTMRmindata retrieved through a bibliography review. We tested the effects ofMband climate on torpor traits using mixed-effect phylogenetic models. All models showed a significant interaction betweenMband climate. This interaction was inversely related toTat,TMRred,Taadjust, and positively related toTMRmin. These results are likely explained by the differences inMband the metabolic rate of bats from different climates, which may allow individuals to express torpor in places with differentTa. Further studies to assess torpor use in bats of different climates are proposed.Summary statementThe interaction between body mass and climate influences torpor energetics in bats of the family Vespertilionidae. As a result, torpid traits change based on body mass and climate.
ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline
Authors: Alavattam Kris G. , Esparza Jasmine M. , Hu Mengwen , Shimada Ryuki , Kohrs Anna R. , Abe Hironori , Munakata Yasuhisa , Otsuka Kai , Yoshimura Saori , Kitamura Yuka , Yeh Yu-Han , Hu Yueh-Chiang , Kim Jihye , Andreassen Paul R. , Ishiguro Kei-ichiro , Namekawa Satoshi H. 
Published: October 2023

AbstractH3K9 tri-methylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that, in male meiosis, ATF7IP2 amasses on autosomal and X pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein’s essential roles in the maintenance of MSCI, suppression of retrotransposons, and global upregulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition.