bluuebunny/crossref_metadata_2025 huggingface dataset:
ISWI chromatin remodeler SMARCA5 is essential for meiotic gene expression and male fertility in mammals
Authors: Kataruka Shubhangini , Malla Aushaq B , Rainsford Shannon R , Lesch Bluma J
Published: October 2024

Regulation of the transcriptome to promote meiosis is important for sperm development and fertility. However, how chromatin remodeling directs the transcriptome during meiosis in male germ cells is largely unknown. Here, we demonstrate that the ISWI family ATP-dependent chromatin remodeling factor SMARCA5 (SNF2H) plays a critical role in regulating meiotic prophase progression during spermatogenesis. Males with germ cell-specific depletion of SMARCA5 are infertile and unable to form sperm. Loss ofSmarca5results in failure of meiotic progression with abnormal spermatocytes beginning at the pachytene stage and an aberrant global increase in chromatin accessibility, especially at genes important for meiotic prophase.
Telomere length and cognitive function among middle-aged and older participants from communities underrepresented in aging research: A preliminary study
Authors: McLester-Davis Lauren W. Y. , Norton Derek , Papale Ligia A. , James Taryn T. , Salazar Hector , Asthana Sanjay , Johnson Sterling C. , Gooding Diane C. , Roy Trevor R. , Alisch Reid S. , Drury Stacy S. , Gleason Carey E. , Zuelsdorff Megan
Published: October 2024

Objective

Accelerated biological aging is a plausible and modifiable determinant of dementia burden facing minoritized communities, but is not well-studied in these historically underrepresented populations. Our objective was to preliminarily characterize relationships between telomere length and cognitive health among American Indian/Alaska Native (AI/AN) and Black/African American (B/AA) middle-aged and older adults.

Methods

This study included data on telomere length and cognitive test performance from 187 participants, enrolled in one of two community-based cognitive aging cohorts and who identified their primary race as AI/AN or B/AA.

Results

Nested multivariable regression models revealed preliminary evidence for associations between telomere length and cognitive performance, and these associations were partially independent of chronological age.

Discussion

Small sample size limited estimate precision, however, findings suggest future work on telomere length and cognitive health in underrepresented populations at high risk for dementia is feasible and valuable as a foundation for social and behavioral intervention research.
Epigenetic and 3D genome reprogramming during the aging of human hippocampus
Authors: Zemke Nathan R. , Lee Seoyeon , Mamde Sainath , Yang Bing , Berchtold Nicole , Garduño B. Maximiliano , Indralingam Hannah S. , Bartosik Weronika M. , Lau Pik Ki , Dong Keyi , Yang Amanda , Tani Yasmine , Chen Chumo , Zeng Qiurui , Ajith Varun , Tong Liqi , Seng Chanrung , Li Daofeng , Wang Ting , Xu Xiangmin , Ren Bing
Published: October 2024

Age-related cognitive decline is associated with altered physiology of the hippocampus. While changes in gene expression have been observed in aging brain, the regulatory mechanisms underlying these changes remain underexplored. We generated single-nucleus gene expression, chromatin accessibility, DNA methylation, and 3D genome data from 40 human hippocampal tissues spanning adult lifespan. We observed a striking loss of astrocytes, OPC, and endothelial cells during aging, including astrocytes that play a role in regulating synapses. Microglia undergo a dramatic switch from a homeostatic state to a primed inflammatory state through DNA methylome and 3D genome reprogramming. Aged cells experience erosion of their 3D genome architecture. Our study identifies age-associated changes in cell types/states and gene regulatory features that provide insight into cognitive decline during human aging.
An increase in reactive oxygen species underlies neonatal cerebellum repair
Authors: Pakula Anna , El Nagar Salsabiel , Bayin N. Sumru , Christensen Jens Bager , Stephen Daniel N. , Reid Adam James , Koche Richard , Joyner Alexandra L.
Published: October 2024

The neonatal mouse cerebellum shows remarkable regenerative potential upon injury at birth, wherein a subset of Nestin-expressing progenitors (NEPs) undergoes adaptive reprogramming to replenish granule cell progenitors that die. Here, we investigate how the microenvironment of the injured cerebellum changes upon injury and contributes to the regenerative potential of normally gliogenic-NEPs and their adaptive reprogramming. Single cell transcriptomic and bulk chromatin accessibility analyses of the NEPs from injured neonatal cerebella compared to controls show a temporary increase in cellular processes involved in responding to reactive oxygen species (ROS), a known damage-associated molecular pattern. Analysis of ROS levels in cerebellar tissue confirm a transient increased one day after injury at postanal day 1, overlapping with the peak cell death in the cerebellum. In a transgenic mouse line that ubiquitously overexpresses human mitochondrial catalase (mCAT), ROS is reduced 1 day after injury to the granule cell progenitors, and we demonstrate that several steps in the regenerative process of NEPs are curtailed leading to reduced cerebellar growth. We also provide preliminary evidence that microglia are involved in one step of adaptive reprogramming by regulating NEP replenishment of the granule cell precursors. Collectively, our results highlight that changes in the tissue microenvironment regulate multiple steps in adaptative reprogramming of NEPs upon death of cerebellar granule cell progenitors at birth, highlighting the instructive roles of microenvironmental signals during regeneration of the neonatal brain.
Multimodal predictions of end stage chronic kidney disease from asymptomatic individuals for discovery of genomic biomarkers
Authors: Rabinovici-Cohen Simona , Platt Daniel E , Iwamori Toshiya , Guez Itai , Dey Sanjoy , Bose Aritra , Kudo Michiharu , Cosmai Laura , Porta Camillo , Koseki Akira , Meyer Pablo
Published: October 2024

Chronic kidney disease (CKD) is a complex condition where the kidneys are damaged and progressively lose their ability to filter blood, 10% of the world population have the disease that often goes undetected until it is too late for intervention. Using the UK Biobank (UKBB) we constructed a CKD cohort of patients (n=46,986) with genomic, clinical and demographic data available, a subset (n=2,151) having also whole body Magnetic Resonance Imaging (MRI) scans. We used this multimodal cohort to successfully predict, from initially healthy patients, their 5-year outcomes for End-Stage Renal Disease (ESRD, n=210, AUC=0.804 ± 0.03 with 5 fold cross-validation) and the larger cohort for validation to predict time-to ESRD and perform Genome-wide association studies (GWAS). Extracting important clinical, phenotypic and genetic features from the models, we were able to stratify the cohorts based on a novel set of significant previously unreported SNPs related to mitochondria/cell death, kidney development and function. In particular, we show that the risk allele of SNP rs1383063 present in 30% of the population irrespective of ancestry and putatively regulatingMAGI-1, a gene expressed in the podocyte slit diaphragm, is a strong predictor of ESRD and stratifies male populations of older age.
Association of HOXB13 G84E with prostate cancer among 592,158 men
Authors: Crawford Taylor B. , Nelson Tyler , Karunamuni Roshan , Desai Heena , Hausler Ryan , Teerlink Craig , Carter Hannah , Pagadala Meghana S. , Alba Patrick R. , DuVall Scott L. , Danowski Morgan E. , Brunette Charles A. , Ratner Dmitry , Garraway Isla P. , Rose Brent S. , Cooney Kathleen A. , Vassy Jason L. , Hauger Richard L. , Lynch Julie A. , Seibert Tyler M. , Maxwell Kara N.
Published: October 2024

The HOXB13 c.G251G>A:p.G84E (rs138213197) variant confers an increased risk of prostate cancer (PCa). Minimal data exist from population-based cohorts to guide genetic counseling. We identified men heterozygous for HOXB13 p.G84E or homozygous wild-type among 592,158 male participants in the Million Veteran Program (MVP). 1660 (0.3%) men in MVP were heterozygous for HOXB13 p.G84E. Results from Cox proportional hazards models demonstrated significant associations between HOXB13 p.G84E and risk of any PCa (HR 3.23, 95%CI 2.97-3.53, p<2.0E-16), metastatic PCa (HR 2.96, 95%CI 2.30-3.81, p<2.0E-16), and PCa death (HR 2.65, 95%CI 1.67-4.21, p=3.8E-05). In a subset of MVP participants who underwent prostate biopsy at VA (n=36,321), a multivariable logistic regression model controlling for known PCa risk factors showed that HOXB13 p.G84E heterozygotes had a higher risk of PCa diagnosis (OR 2.60, 95%CI 1.94-3.52, p<0.001). HOXB13 p.G84E heterozygotes had slightly younger age of PCa diagnosis but similar distribution of Gleason scores and rates of de novo, any, and castrate resistant metastatic disease. In the largest cohort of men with the HOXB13 p.G84E variant studied to date, we show this variant confers a moderately increased lifetime risk of PCa. Further work is needed to determine if early PCa screening in HOXB13 p.G84E heterozygotes improves outcomes.
Understanding Pain in Polycystic Ovary Syndrome: Health Risks and Treatment Effectiveness
Authors: Cherlin Tess , Mohammed Stephanie , Ottey Sasha , Sherif Katherine , Verma Shefali S.
Published: October 2024

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women, often accompanied by various symptoms including significant pain, such as dysmenorrhea, abdominal, and pelvic pain, which remains underexplored. This retrospective study examines electronic health records (EHR) data to assess the prevalence of pain in women with PCOS. Conducted on May 29, 2024, using data from 120 Health Care Organizations within the TriNetX Global Network, the study involved 76,859,666 women from diverse racial backgrounds. The analysis focused on the prevalence of pain among women with PCOS, both overall and in those prescribed PCOS-related medications. Relative risk ratios (RR) were calculated for future health outcomes and stratified by self-reported race. The study found that 19.21% of women with PCOS experienced pain, with the highest prevalence among Black or African American (32.11%) and White (30.75%) populations. Both the PCOS and PCOS and Pain cohorts exhibited increased RR for various health conditions, with significant differences noted across racial groups for infertility, ovarian cysts, obesity, and respiratory diseases. Additionally, women with PCOS who were treated with PCOS-related medications showed a decrease in pain diagnoses following treatment. In conclusion, this study highlights the critical need to address pain in the diagnosis and management of PCOS due to its significant impact on patient health outcomes.

Impact Statement

Insufficient data exist on the prevalence of pain in women with a PCOS diagnosis, and its associations with future health outcomes. Among, 444,348 women with PCOS in the TriNextX Global Network, 19.21% have dysmenorrhea, abdominal, and pelvic pain. Women with PCOS and Pain are at increased risk for developing ovarian cysts, infertility, T2D, and fatty liver disease and are at further risk when stratified by self-reported race groups.
Mortality and lost to follow-up among Tuberculosis patients on treatment in Meru County, Kenya: a retrospective cohort study
Authors: Ngari Moses M. , Mberia Jane K. , Kanana Eunice , Sanga Deche , Ngari Martin K. , Nyagah David N. , Abdullahi Osman A.
Published: October 2024

Tuberculosis (TB) remains a leading cause of death globally. Patients who get lost-to-follow-up (LTFU) during TB treatment have high risk of relapse, mortality, treatment failure and developing Multidrug resistant TB. Empirical data to monitor long-term TB treatment outcomes in low-and-middle income countries (LMICs) are sparse. We determined proportion of TB patients who die or are LTFU during six months of treatment and identified factors independently associated with mortality or LTFU. A retrospective cohort using data from routine Meru County TB surveillance system. We included 38020 records of TB patients aged ≥15 years on treatment 2012 to 2022. TB treatment outcomes of interest were LTFU or death within six months of treatment. Survival analyses accounting for competing events were performed. Among the 38020 patients included, 27608 (73%) were male and the median (IQR) age was 32 [25‒42] years. 26599 (70%) had bacteriologically confirmed TB while 11421 (30%) were clinically diagnosed. During 16531 person-years of follow-up, 2385 (6.3%, 95%CI 6.0‒6.5) and 1942 (5.1%, 95%CI 4.9‒5.3) patients were LTFU and died respectively. In the multivariable model, patients on re-treatment after LTFU or after failure and those previously treated compared to new TB patients were positively associated with LTFU. Patients coinfected with HIV and those with unknown HIV status were positively associated with LTFU. In contrast, females, clinically diagnosed, extra-pulmonary TB and older patients were negatively associated with LTFU. Patients HIV infected on ARVs, not on ARVs and unknown HIV status versus not infected were positively associated with mortality. Other comorbidities (not HIV), clinically diagnosed, undernourished and older patients were positively associated with mortality. More than 10% of TB patients either die or are LTFU before completing treatment. TB patients on re-treatment, HIV infected, clinically diagnosed, undernourished and the elderly needs more targeted interventions to improve survival and successfully treatment.
Prevalence and Risk Factors for Non-Communicable Chronic Diseases in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis
Authors: Xavier Sancho Pedro , Gotine Ana Raquel Manuel , Vasco Melsequisete Daniel , Victor Audêncio
Published: October 2024

Background

Non-communicable chronic diseases (NCDs) have become increasingly prominent in low- and middle-income countries (LMIC), driven by a rapid rise in their incidence. Current estimates suggest that these conditions account for approximately 80% of deaths in these regions. This study aimed to analyze the prevalence of NCDs and their associated risk factors in LMIC.

Methods

Electronic searches were conducted in the PubMed, Embase, Scopus, Cochrane, and Virtual Health Library (VHL) databases between June and July 2023. Studies on the prevalence of NCDs, with or without associated risk factor analysis, were included. The quality of these studies was assessed using NIH tools, and a meta-analysis was conducted using the random-effects model.

Results

A total of 34 studies on hypertension and 22 studies on diabetes were included in the systematic review and meta-analysis. The estimated prevalence of hypertension was 24% (95% CI: 21.0; 28.0) and diabetes mellitus (DM) was 11% (95% CI: 10.0; 13.0), with future predictions for similar populations ranging from 11.0-46.0% for hypertension and 6.0-21.0% for DM. Geographic analysis revealed a lower prevalence of hypertension in Latin America and the Caribbean (7.0%) with no statistically significant differences compared to other regions (p-value = 0.101). The prevalence of DM was lower in Sub-Saharan Africa (5.0%; p-value < 0.001). The identified risk factors for hypertension included increased age, male sex, elevated BMI, alcohol consumption, excessive salt intake, and stress. For diabetes, the risk factors were increased age, lack of religious affiliation, elevated BMI, family history of DM, hypertension, high hemoglobin concentration (HbA1c), waist-to-hip ratio, smoking, and infection with Taenia spp.

Conclusion

NCDs such as hypertension and DM pose a growing public health challenge in low- and middle-income countries. Our findings may assist policymakers in identifying high-risk groups and recommending appropriate prevention strategies.

Systematic Review Registration

The protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number: CRD42024520601).
Spontaneous formation of different forms of alpha-synuclein fibrils from a recombinant protein
Authors: Egorov V.V. , Grudinina N.A. , Polyakov D.S. , Zabrodskaya Y.A. , Gavrilova N.V. , Shavlovsky M.M.
Published: October 2024

Alpha-synuclein is a protein, the conformational changes of which lead to the development of such socially significant diseases as Parkinson’s disease and amyotrophic lateral sclerosis. The methods for differential diagnostics of these diseases based on the use of alpha-synuclein in a non-native conformation obtained from patients as a seed for inducing fibrillogenesis and studying the morphology of the resulting amyloid-like fibrils were described in a number of studies. The authors associate such properties of the seed with the presence of post-translational modifications in the protein obtained from patients. At the same time, the production of fibrils differing in morphology from recombinant alpha-synuclein under various conditions of fibrillogenesis is also described. In this work, we show that the formation of morphologically distinct fibril types from recombinant alpha-synuclein lacking post-translational modifications is possible under the same conditions, and that spontaneously arising different fibril types, when used as a seed for fibrillogenesis, lead to the formation of recombinant protein fibrils morphological similar to the parental seed. The results of the work can be used both in studying the fundamental mechanisms of conformation transfer and in developing test systems for synucleinopathies.
Microbial iCLIP2: Enhanced mapping of RNA-Protein interaction by promoting protein and RNA stability
Authors: Stoffel Nina Kim , Sankaranarayanan Srimeenakshi , Müntjes Kira , Körtel Nadine , Busch Anke , Zarnack Kathi , König Julian , Feldbrügge Michael
Published: October 2024

The entire RNA lifecycle, spanning from transcription to decay, is intricately regulated by RNA-binding proteins (RBPs). To understand their precise functions, it is crucial to identify direct targets, pinpoint their exact binding sites, and unravel the underlying specificityin vivo. Individual-nucleotide resolution UV crosslinking and immunoprecipitation 2 (iCLIP2) is a state-of-the-art technique that enables the identification of RBP binding sites at single-nucleotide resolution. However, in the field of microbiology, optimized iCLIP protocols compared to mammalian systems are lacking. Here, we present the first microbial iCLIP2 approach using the multi-RRM domain protein Rrm4 from the fungusUstilago maydisas an example. Key challenges such as inherently high RNase and protease activity in fungi were addressed by improving mechanical cell disruption and lysis buffer composition. Our modifications increased the yield of crosslink events and improved the identification of Rrm4 binding sites. Thus, we were able to pinpoint that Rrm4 binds the stop codons of nuclear-encoded mRNAs of mitochondrial respiratory complex I, III and V – revealing an intimate link between endosomal mRNA transport and mitochondrial physiology. Thus, our study serves as a paradigm for optimizing iCLIP2 procedures in challenging organisms or tissues under high RNase/ protease conditions.
Strong segregation promotes self-destructive cooperation
Authors: Wen Lingling , Bai Yang , Lan Yunquan , Shen Yaxin , She Xiaoyi , Dong Peng , Wang Teng , Fu Xiongfei , Huang Shuqiang
Published: October 2024

Self-destructive cooperator (SDC), where individuals sacrifice themselves for others, poses significant personal costs yet is widespread in nature. Traditional group selection theory struggles to explain its persistence, as the extreme cost of self-destruction typically exceeds the benefit to these individuals. Here, we predict that this behavior can endure in structured environments with strong segregation, where populations are divided into homogenous groups originating from one or two founding members. In such contexts, the benefits derived from SDC are primarily confined within the homogenous SDC groups, thus preserving the value of this altruistic sacrifice and ensuring its maintenance. To validate our hypothesis, we employ a synthetic system with engineered bacteria to mimic both SDC and non-sacrificing cheaters. We then conduct automated experiments facilitated by biofoundry technology to monitor and operate the subgroups with diverse growth behaviors stemming from a restricted number of initial cells because of strong segregation. Eventually, we demonstrate that SDC indeed maintains under strong segregation, and high stress benefits SDC because it reduces the benefits received by cheaters in heterogenous subgroups. This study extends the group selection theory to encompass even the most extreme manifestations of altruism and highlights the potential of automation in evolutionary research.
RNAi epimutations conferring antifungal drug resistance are inheritable
Authors: Pérez-Arques Carlos , Navarro-Mendoza María Isabel , Xu Ziyan , Walther Grit , Heitman Joseph
Published: October 2024

Epimutations modify gene expression and lead to phenotypic variation while the encoding DNA sequence remains unchanged. Epimutations mediated by RNA interference (RNAi) and/or chromatin modifications can confer antifungal drug resistance and may impact virulence traits in fungi. However, whether these epigenetic modifications can be transmitted across generations following sexual reproduction was unclear. This study demonstrates that RNAi epimutations conferring antifungal drug resistance are transgenerationally inherited in the human fungal pathogenMucor circinelloides. Our research revealed that RNAi-based antifungal resistance follows a DNA sequenceindependent, non-Mendelian inheritance pattern. Small RNAs (sRNAs) are the exclusive determinants of inheritance, transmitting drug resistance independently of other known repressive epigenetic modifications. Unique sRNA signature patterns can be traced through inheritance from parent to progeny, further supporting RNA as an alternative molecule for transmitting information across generations. Understanding how epimutations occur, propagate, and confer resistance may enable their detection in other eukaryotic pathogens, provide solutions for challenges posed by rising antimicrobial drug resistance (AMR), and also advance research on phenotypic adaptability and its evolutionary implications.
Prefrontal orchestration: a cortical network for rodent motor inhibition
Authors: Jäckel Zoe , Schwaderlapp Niels , Adzemovic Ahmed , Steenbergen Florian , Hardung Stefanie , Fuchs Katharina , Leibold Christian , Zaitsev Maxim , Diester Ilka
Published: October 2024

Goal-directed action control and behavioral flexibility are prerequisites for effective, adaptive behavior. Both abilities rely on functional motor inhibition, which is linked to the prefrontal cortex (PFC), where distinct subsections collaborate in functional networks. How these PFC subsections interact and which roles they play during motor inhibition remains incompletely understood. In this study, we employed an action-preparation task in rats, combined with bidirectional optogenetic interventions, opto-fMRI, single unit electrophysiology and local field potential synchrony measurements across PFC subsections. Our findings support a clear and simple model of action inhibition within the prefrontal network. This model suggests prelimbic cortex (PL) as an input-dependent switch between motor inhibition and execution, modulated by an infralimbic cortex (IL)-dominated network. This distribution of tasks allows the PL to mediate goal-directed action while the IL ensures behavioral flexibility.

Abstract Figure

Graphical Abstract:

Behavioral measurements were conducted alongside optogenetic modulation of PL, IL or VO. Inhibitory modulation led to varying effects on performance, while excitatory ChR2 stimulation of PL, IL or VO led to analogous effects on proactive motor inhibition. To identify shared nodes recruited by ChR2 stimulation of distinct PFC subareas, we performed whole-brain mapping with opto-fMRI. This revealed an overlapping activation volume spanning PFC, BF, Fr, Cg2, and M2. Notably, this common activation volume closely outlined the entirety of the IL-recruited regions; IL excitation also produced robust behavioral effects. Multisite recordings revealed task performance-dependent PL-IL delta synchrony. PCA of single-unit activity during behavior revealed varied neural patterns among PFC subsections, highlighting PL to have the most the homogenous input-driven activity. The findings can be interpreted as PL acting as an input-dependent switch between motor inhibition and execution, modulated by IL to maintain behavioral flexibility.
A role for class I PAKs in the regulation of the excitability of the actin cytoskeleton
Authors: Tyler Joe J. , Davidson Anthony , Poxon Megan E. , Martinez Montserrat Llanses , Hume Pete , King Jason S. , Koronakis Vassilis
Published: October 2024

P21 activated kinases (PAKs) are involved in a wide range of functions from the regulation of the cytoskeleton to the control of apoptosis and proliferation. Although many PAK substrates identified are implicated in the regulation of the actin cytoskeleton, a coherent picture of the total effect of PAK activation on the state of the actin cytoskeleton is unclear. We therefore set out to observe and quantify the effect of PAK inhibition on the actin cytoskeleton in greater detail. In Mouse Embryonic Fibroblasts, inhibition of PAK kinase activity, either by treatment with small molecule inhibitors or overexpression of mutant PAK constructs leads to the constitutive production of patches of the phosphoinositide PIP3 on the ventral surface of the cell. The formation of these patches remodels the actin cytoskeleton and polarises the cell. From the overexpression of truncated and mutant PAK constructs as well as anin vitromodel of PAK recruitment to small GTPases we propose that this is due to a hyper recruitment of PAK and PAK binding partners in the absence of PAK kinase activity. This aberrant production of PIP3 suggests that, by limiting its own recruitment, the kinase activity of class I PAKs acts to downregulate PI3K activity, further highlighting class I PAKs as regulators of PI3K activity and therefore the excitability of the actin cytoskeleton.
Genomic and structural insights into Jyvaskylavirus, the first giant virus isolated from Finland
Authors: de Freitas Almeida Gabriel Magno , Arriaga Iker , de Azevedo Bruna Luiza , Leppänen Miika , Abrahao Jonatas Santos , Andreani Julien , Zabeo Davide , Ravantti Janne , Abrescia Nicola GA , Sundberg Lotta-Riina
Published: October 2024

Giant viruses of protists are a diverse and likely ubiquitous group of organisms. Here, we describe Jyvaskylavirus, the first giant virus isolated from Finland. This clade B marseillevirus was found inAcanthamoeba castellaniifrom a composting soil sample in Jyväskylä, Central Finland. Its genome shares similarities with other marseilleviruses. Helium ion microscopy and electron microscopy of infected cells unraveled stages of the Jyvaskylavirus lifecycle. We reconstructed the Jyvaskylavirus particle to 6.3 Å resolution using cryo-EM. The ∼2,500 Å diameter virion displays structural similarities to otherMarseilleviridaegiant viruses. The capsid comprises of 9,240 copies of the major capsid protein ORF184, which possesses a double jellyroll fold arranged in trimers forming pseudo-hexameric capsomers. Below the capsid shell, the internal membrane vesicle encloses the genome. Through cross-structural and -sequence comparisons with otherMarseilleviridaeusing AI-based software in model building and prediction, we elucidated ORF142 as the penton protein, which plugs the twelve vertices of the capsid. Five additional ORFs were identified, with models predicted and fitted into densities that either cap the capsomers externally or stabilize them internally. The isolation of Jyvaskylavirus suggests that these viruses may be widespread in the boreal environment and provide structural insights extendable to other marseilleviruses.
Accurate and flexible estimation of effective population size history
Authors: Huang Zhendong , Chan Yao-ban , Balding David
Published: October 2024

Current methods for inferring historical population sizes from DNA sequences often impose a heavy computational burden, or relieve that burden by imposing a fixed parametric form. In addition, they can be marred by sequencing errors or uncertainty about recombination rates, and the quality of inference is often poor in the recent past. We propose “InferNo” for flexible, nonparametric inference of effective population sizes. It requires modest computing resources and little prior knowledge of the recombination and mutation maps, and is robust to sequencing error and gene conversion. We illustrate the statistical and computational advantages of InferNo over previous approaches using a range of simulation scenarios. In particular, we demonstrate the ability of InferNo to exploit biobank-scale datasets for accurate inference of rapid population size changes in the recent past. We also apply InferNo to worldwide human data, finding remarkable similarities in inferences from different populations in the same region. Unlike previous studies, we show two historic bottlenecks for most of the non-African populations.
Understanding Neuronal Diversity: Role of Input Dynamics and Filtering
Authors: Joshi Nishant , van der Burg Sven , Celikel Tansu , Zeldenrust Fleur
Published: October 2024

Neurons exhibit diverse morphological, electrophysiological, and transcriptomic properties. Their role as spatiotemporal filters suggests that the interaction between input dynamics and postsynaptic neuronal properties should be crucial for shaping this diversity. To test this, barrel cortex neurons were studied using two input types: a “step-and-hold” stimulus and a dynamic input mimicking presynaptic activity. It was found that stimulus type strongly influenced neuronal classification. Neuronal heterogeneity under a dynamic stimulus was further analyzed using four attribute sets: action potential attributes, passive biophysical attributes, adaptation current, and linear input filters via the Spike Triggered Average (STA). Multi-set factor analysis revealed that the linear input filter explained the most private variance, making it the most informative attribute for neuronal heterogeneity. These findings highlight the interplay between input dynamics and neuron’s linear filtering properties as key to understanding functional neuronal diversity, emphasizing the need to go beyond static intrinsic features for understanding neuronal heterogeneity.
White Matter Microstructural Alterations in Autism Localized with Bundle Analytics
Authors: Kim Gaon S. , Chandio Bramsh Q. , Benavidez Sebastian M. , Thompson Paul M. , Lawrence Katherine E.
Published: October 2024

Previous diffusion magnetic resonance imaging research in autism has reported altered microstructure in the corpus callosum (CC), the major commissure connecting the two brain hemispheres. However, the CC consists of many fibers connecting various brain regions, and the precise localization of these differences in autism remains unclear. Additionally, the conventional diffusion tensor imaging (DTI) model cannot resolve complex fiber configurations and may miss subtle alterations. In this study, we investigated CC microstructure in 365 participants (5-25 years; 34.0% female; 195 with autism) from 10 sites/scanners by using a novel along-tract mapping method, BUndle ANalytics (BUAN), and advanced microstructure model, the tensor distribution function (TDF). Autism was associated with regionally specific reductions in white matter integrity and elevations in diffusivity. The TDF model detected CC microstructure differences more sensitively than DTI. Taken together, BUAN and TDF allow for precise and rigorous white matter analyses, enhancing the detection of subtle neural differences.
Relational integration demands are tracked by temporally delayed neural representations in alpha and beta rhythms within higher-order cortical networks
Authors: Robinson Conor N , Cocchi Luca , Ito Takuya , Hearne Luke J
Published: October 2024

Relational reasoning is the ability to infer and understand the relations between multiple elements. In humans, this ability supports higher cognitive functions and is linked to fluid intelligence. Relational complexity (RC) is a cognitive framework that offers a generalisable method for classifying the complexity of reasoning problems. To date, increased RC has been linked to static patterns of brain activity supported by the frontoparietal system, but limited work has assessed the multivariate spatiotemporal dynamics that code for RC. To address this, we conducted representational similarity analysis in two independent neuroimaging datasets (Dataset 1 fMRI, n=40; Dataset 2 EEG, n=45), where brain activity was recorded while participants completed a visuospatial reasoning task that included different levels of RC (Latin Square Task). Our findings revealed that, spatially, RC representations were widespread, peaking in brain networks associated with higher-order cognition (frontoparietal, dorsal-attention, and cingulo-opercular). Temporally, RC was represented in the 2.5 - 4.1 seconds post-stimuli window and emerged in the alpha and beta frequency range. Finally, multimodal fusion analysis demonstrated that shared variability within EEG-fMRI signals within higher-order cortical networks were better explained by the theorised RC model, relative to a model of cognitive effort (CE). Altogether, the results further our understanding of the neural representations supporting relational processing, highlight the spatially distributed coding of RC and CE across cortical networks, and emphasise the importance of late-stage, frequency-specific neural dynamics in resolving RC.
Integrated single cell functional-proteomic profiling of human skeletal muscle reveals a shift in cellular specificity in nemaline myopathy
Authors: Seaborne Robert A.E. , Moreno-Justicia Roger , Laitila Jenni , Lewis Chris T. A. , Savoure Lola , Zanoteli Edmar , Lawlor Michael W , Jungbluth Heinz , Deshmukh Atul S. , Ochala Julien
Published: October 2024

Skeletal muscle is a complex syncytial arrangement of an array of cell types and, in the case of muscle specific cells (myofibers), sub-types. There exists extensive heterogeneity in skeletal muscle functional behaviour and molecular landscape, at the cell composition, myofiber sub-type and intra-myofiber sub-type level. This heterogeneity highlights limitations in currently applied methodological approaches, which has stagnated our understanding of fundamental skeletal muscle biology in both healthy and myopathic contexts. Here, we developed a novel approach that combines a fluorescence based assay for the biophysical examination of the sarcomeric protein, myosin, coupled with same-myofiber high sensitivity proteome profiling, termed Single Myofiber Protein Function-Omics (SMPFO). Successfully applying this approach to healthy human skeletal muscle tissue, we identify the integrate relationship between myofiber functionality and the underlying proteomic landscape that guides divergent, but physiologically important, behaviour in myofiber sub-types. By applying SMPFO to two forms of human nemaline myopathy (ACTA1andTNNT1mutations), we reveal significant reduction in the divergence of myofiber sub-types, across both biophysical and proteomic behaviour. Collectively, we develop SMPFO as a novel approach to study skeletal muscle with greater specificity, accuracy and resolution then currently applied methods, facilitating that advancement in understanding of SkM tissue in both healthy and diseased states.
Circadian de(regulation) in physiology: implications for disease and treatment
Authors: de Assis Leonardo Vinicius Monteiro , Kramer Achim
Published: October 2024

Time plays a crucial role in the regulation of physiological processes. Without a temporal control system, animals would be unprepared for cyclic environmental changes, negatively impacting their survival. Experimental studies have demonstrated the essential role of the circadian system in the temporal coordination of physiological processes. Translating these findings to humans has been challenging. Increasing evidence suggests that modern lifestyle factors such as diet, sedentarism, light exposure, and social jet lag can stress the human circadian system, contributing to misalignment; i.e., loss of phase coherence across tissues. An increasing body of evidence supports the negative impact of circadian disruption on several human health parameters. This review aims to provide a comprehensive overview of how circadian disruption influences various physiological processes, its long-term health consequences, and its association with various diseases. To illustrate the relevant consequences of circadian disruption, we focused on describing the many physiological consequences faced by shift workers, a population known to experience high levels of circadian disruption. We also discuss the emerging field of circadian medicine, its founding principles, and its potential impact on human health.
Intensive
γ
-ray light sources based on oriented single crystals
Authors: Sushko Gennady B. , Korol Andrei V. , Solov’yov Andrey V.
Published: October 2024

The feasibility of gamma-ray light sources based on the channeling phenomenon of ultrarelativistic electrons and positrons in oriented single crystals is demonstrated using rigorous numerical modeling. Case studies are presented for 10 GeV and sub-GeV e−/e+ beams incident on 10−1−100  mm thick diamond and silicon crystals. It is shown that for moderate values of the beam average current (≲10  μA), the average photon flux in the energy range of 100–102  MeV emitted within the 101–103  μrad cone and 1% bandwidth can be on the level of 1010  photon/s for electrons and 1010–1012  photon/s for positrons. These values are higher than the fluxes available at modern laser-Compton gamma-ray light sources.

Published by the American Physical Society
2024
Generalized measurements on qubits in quantum randomness certification and expansion
Authors: Mironowicz Piotr , Grünfeld Marcus , Bourennane Mohamed
Published: October 2024

Quantum mechanics has greatly impacted our understanding of microscopic nature. One of the key concepts of this theory is generalized measurements, which have proven useful in various quantum information processing tasks. However, despite their significance, they have not yet been shown empirically to provide an advantage in quantum randomness certification and expansion protocols. This investigation explores scenarios where generalized measurements can yield more than 1 bit of certified randomness with a single-qubit system measurement on untrusted devices and against a quantum adversary. We compare the robustness of several protocols to exhibit the advantage of exploiting generalized measurements. In our analysis of experimental data, we were able to obtain 1.21 bits of min-entropy from a measurement taken on one qubit of an entangled state. We also obtained 1.07 bits of min-entropy from an experiment with quantum state preparation and generalized measurement on a single qubit. We also provide finite data analysis for a protocol using generalized measurements and the Entropy Accumulation Theorem. Our exploration demonstrates the potential of generalized measurements to improve the certification of quantum sources of randomness and enhance the security of quantum cryptographic protocols and other areas of quantum information.

Published by the American Physical Society
2024
Phase diagram of a generalized Stephanov model for finite-density QCD
Authors: Baranka György , Giordano Matteo
Published: October 2024

We solve a random matrix model for QCD at finite chemical potential, obtained by generalizing the Stephanov model by modifying the random-matrix integration measure with a one-parameter trace deformation. This allows one to check how important the integration measure is for the qualitative features of random matrix models, as well as to test the robustness and universality of the qualitative picture of the original model. While for a small trace deformation the phase diagram is identical to that of the Stephanov model, for a large deformation an exotic phase with spontaneous charge-conjugation breaking appears.

Published by the American Physical Society
2024
Gemini dark matter
Authors: Cheek Andrew , Qiu Yu-Cheng , Tan Liang
Published: October 2024

The S8/σ8 tension in the large-scale structure can be explained by decaying dark matter with an almost degenerate spectrum and small enough decay width. Here we propose the Gemini dark matter model, which contains a heavy mother particle χ3 and two twins χ1/2, which are almost degenerate in mass and are produced at the same time. The dark sector is charged under the same Froggatt-Nielsen symmetry that can explain the hierarchy of the Standard Model Yukawa couplings. The slightly heavier χ2 decays into χ1 and the axionic component of the flavon, which washes out the small-scale structure and resolves S8/σ8 tension. We present the production mechanism of Gemini dark matter and viable parameter regions. We find that, despite the preferred dark matter mass being O(1)–O(100)  keV, they constitute cold dark matter. The Gemini dark matter model predicts an abundance of dark radiation that will be probed in future measurements of the cosmic microwave background.

Published by the American Physical Society
2024
Three-point functions of higher-spin supercurrents in 4D
N=1
SCFT: General formalism for arbitrary superspins
Authors: Buchbinder Evgeny I. , Hutomo Jessica , Stone Benjamin J.
Published: October 2024

We analyze the general structure of the three-point functions involving conserved higher-spin “vectorlike” supercurrents Js(z)≔Jα(s)α˙(s)(z) in four-dimensional N=1 superconformal field theory. Using the constraints of superconformal symmetry and superfield conservation equations, we utilize a computational approach to analyze the general structure of the three-point function ⟨Js1(z1)Js2′(z2)Js3′′(z3)⟩ and provide a general classification of the results. We demonstrate that the three-point function is fixed up to 2  min(si)+2 independent conserved structures, which we propose to hold for arbitrary superspins. In addition, we show that the conserved structures can be classified as parity-even or parity-odd in superspace based on their transformation properties under superinversion.

Published by the American Physical Society
2024
Multiphase field model of cells on a substrate: From three dimensional to two dimensional
Authors: Chiang Michael , Hopkins Austin , Loewe Benjamin , Marenduzzo Davide , Marchetti M. Cristina
Published: October 2024

Multiphase field models have emerged as an important computational tool for understanding biological tissue while resolving single-cell properties. While they have successfully reproduced many experimentally observed behaviors of living tissue, the theoretical underpinnings have not been fully explored. We show that a two-dimensional version of the model, which is commonly employed to study tissue monolayers, can be derived from a three-dimensional version in the presence of a substrate. We also show how viscous forces, which arise from friction between different cells, can be included in the model. Finally, we numerically simulate a tissue monolayer and find that intercellular friction tends to solidify the tissue.

Published by the American Physical Society
2024
Electrical Excitation and Detection of Chiral Magnons in a Compensated Ferrimagnetic Insulator
Authors: Wang Ledong , Shen Laichuan , Bai Hao , Zhou Heng-An , Shen Ka , Jiang Wanjun
Published: October 2024

Magnon chirality refers to the precessional handedness of magnetization around the external magnetic field, which is fixed as right-handed in ferromagnets. Compensated ferrimagnets accommodate parallel and antiparallel configurations of net magnetization and angular momentum, and thus serve as an ideal platform for studying magnon chirality. Through performing spin-torque ferromagnetic resonance experiments, we experimentally study the reversal of low-frequency magnon chirality across the magnetization and angular momentum compensation temperatures in a Gd3Fe5O12/Pt bilayer. In particular, we demonstrate that dampinglike spin torque could sensitively excite and detect the reversal of low-frequency magnon chirality. By solving the coupled Landau-Lifshitz-Gilbert equations, the close correlation between the reversal of low-frequency magnon chirality and the sign of net angular momenta is established. The electrical excitation and detection of low-frequency magnon chirality in compensated ferrimagnetic insulators could be useful for building chiral spintronics.

Published by the American Physical Society
2024
Unsupervised learning of effective quantum impurity models
Authors: Rigo Jonas B. , Mitchell Andrew K.
Published: October 2024

Generalized quantum impurity models—which feature a few localized and strongly correlated degrees of freedom coupled to itinerant conduction electrons—describe diverse physical systems, from magnetic moments in metals to nanoelectronics quantum devices such as quantum dots or single-molecule transistors. Correlated materials can also be understood as self-consistent impurity models through dynamical mean-field theory. Accurate simulation of such models is challenging, especially at low temperatures, due to many-body effects from electronic interactions, resulting in strong renormalization. In particular, the interplay between local impurity complexity and Kondo physics is highly nontrivial. A common approach, which we further develop in this work, is to consider instead a simpler effective impurity model that still captures the low-energy physics of interest. The mapping from a bare to an effective model is typically done perturbatively, but even this can be difficult for complex systems, and the resulting effective model parameters can nevertheless be quite inaccurate. Here we develop a nonperturbative, unsupervised machine learning approach to systematically obtain low-energy effective impurity-type models, based on the renormalization-group framework. The method is shown to be general and flexible, as well as accurate and systematically improvable. We benchmark the method against exact results for the Anderson impurity model, and we provide an outlook for more complex models beyond the reach of existing methods.

Published by the American Physical Society
2024
Axion Clouds around Neutron Stars
Authors: Noordhuis Dion , Prabhu Anirudh , Weniger Christoph , Witte Samuel J.
Published: October 2024

Recent work has shown that axions can be efficiently produced via nonstationary pair plasma discharges in the polar cap region of pulsars. Here, we point out that for axion masses 10−9≲ma≲10−4  eV a sizable fraction of the sourced axion population will be gravitationally confined to the neutron star. These axions accumulate over astrophysical timescales, thereby forming a dense “axion cloud” around the star. We argue that the existence of such a cloud, with densities reaching and potentially exceeding O(1022)  GeV cm−3, is a generic expectation across a wide range of parameter space. For axion masses ma≳10−7  eV, energy is primarily radiated from the axion cloud via resonant axion-photon mixing, generating a number of distinctive signatures that include a sharp line in the radio spectrum of each pulsar (located at the axion mass, and with an order percent-level width) and transient events arising from the reconfiguration of charge densities in the magnetosphere. While a deeper understanding of the systematic uncertainties in these systems is required, our current estimates suggest that existing radio telescopes could improve sensitivity to the axion-photon coupling by more than an order of magnitude.

Published by the American Physical Society
2024