bluuebunny/crossref_metadata_2025 huggingface dataset:
Association analyses reveal both anthropic and environmental selective events during eggplant domestication
Authors: Omondi Emmanuel , Barchi Lorenzo , Gaccione Luciana , Portis Ezio , Toppino Laura , Tassone Maria Rosaria , Alonso David , Prohens Jaime , Rotino Giuseppe Leonardo , Schafleitner Roland , van Zonneveld Maarten , Giuliano Giovanni
Published: November 2024

Eggplant (Solanum melongena) is one of the four most important Solanaceous crops, widely cultivated and consumed in Asia, the Mediterranean basin, and Southeast Europe. We studied the Genome-wide association (GWA) of historical genebank phenotypic data on a genotyped worldwide collection of 3,449 eggplant accessions. Overall, 334 significant associations for key agronomic traits were detected. Significant correlations were obtained between different types of phenotypic data, some of which were not obvious, such as between fruit size/yield and fruit color components, suggesting simultaneous anthropic selection for genetically unrelated traits. Anthropic selection of traits like leaf prickles, fruit color, and yield, acted on distinct genomic regions in the two domestication centers (India and Southeast Asia), further confirming the multiple domestication of eggplant. To discriminate anthropic from environmental selection in domestication centers, we conducted a Genotype-Environment Association (GEA) on a subset of georeferenced accessions from the Indian subcontinent. The population structure in this area revealed four genetic clusters, corresponding to a latitudinal gradient, and environmental factors explained 31% of the population structure when the effect of spatial distances was removed. GEA and outlier association (OA) identified 305 candidate regions under environmental selection, containing genes for abiotic stress responses, plant development, and flowering transition. Finally, in the Indian domestication center anthropic and environmental selection acted largely independently, and on different genomic regions. These data allow a better understanding of the different effects of environmental and anthropic selection during domestication of a crop, and the different world regions where some traits were initially selected by humans.
Sex Differences in Middle Cerebral Artery Reactivity and Hemodynamics Independent from Changes in Systemic Arterial Stiffness in Adult Sprague-Dawley Rats
Authors: Ray Jonathan W. , Sun Xuming , Diaz Nildris Cruz , Pulgar Victor M. , Yamaleyeva Liliya M.
Published: November 2024

Young women are protected against cerebrovascular disease compared with men. However, the underlying mechanisms of sex differences in cerebrovascular function are not well understood. In this study, we determined whether sex differences in middle cerebral artery (MCA) reactivity are accompanied with changes in cerebral or systemic arterial resistance and stiffness in adult 25-week-old Sprague-Dawley (SD) rats. No differences in systolic or diastolic blood pressures were observed between sexes. Heart rate was higher in the female versus male SD. Left MCA pulsatility index (PI) was lower in female versus male SD, while no differences in left intracranial internal carotid artery (ICA) PI was observed between sexes. There were no differences in thoracic aorta or left common carotid artery pulse wave velocity (PWV) between sexes. In isolated MCA segments, female left MCA had lower contraction to potassium, but similar maximal contraction and sensitivity to thromboxane A2 receptor agonist U46619. Pre-incubation with indomethacin lowered maximal response and sensitivity to U46619 in male MCA but not female MCA suggesting that vasoconstrictor prostaglandins may have a greater role in male MCA vs. female MCA. Endothelial nitric oxide synthase (eNOS) and vascular smooth muscle layer thromboxane A2 receptor immunoreactivity were greater in female versus male SD. We conclude that sex differences in the MCA reactivity are associated with a differential functional profile of MCA in adult SD rats independent from changes in systemic PWV.

NEW & NOTEWORTHY

Despite the debilitating effects of cerebrovascular disease in women, the basis for sex differences in cerebrovascular dysfunction remains incompletely understood. Our study demonstrated that middle cerebral artery reactivity and hemodynamics are not accompanied by changes in central pulse wave velocity in mature adult Sprague-Dawley rats suggesting different mechanisms underlying baseline vascular reactivity of cerebral versus systemic arterial beds.
White matter hyperintensities and microplastics
Authors: Bearer Elaine L. , Garcia Marcus A. , Adolphi Natalie , Campen Matthew J.
Published: November 2024

Synopsis

White matter hyperintensities are abnormalities that appear in MRI scans of living patients but are not apparent in MRI post-mortem.

Goal

Our goal is to understand the cellular/biological basis of white matter hyperintensities (WMH).

Approach

We aligned post-mortem MR scans with those collected ante-mortem and performed histopathology and pyrGC/MS for plastics on regions with WMH.

Result

PyrGC/MS detected large amounts of plastics and we determined their cellular locations with a novel optical imaging approach in regions with small vessel disease and Abeta plaques.

Impact

Microplastics in the brains of people with cognitive impairment may be due to pre-existing vascular injury or contribute to it. Many questions remain: Where do they come from, do they impair function? Can they be diagnosed by MRI ante-mortem?
Evolutionary rescue model informs strategies for driving cancer cell populations to extinction
Authors: Dabi Amjad , Brown Joel S , Gatenby Robert A , Jones Corbin D , Schrider Daniel R
Published: November 2024

Cancers exhibit a remarkable ability to develop resistance to a range of treatments, often resulting in relapse following first-line therapies and significantly worse outcomes for subsequent treatments. While our understanding of the mechanisms and dynamics of the emergence of resistance during cancer therapy continues to advance, questions remain about how to minimize the probability that resistance will evolve, thereby improving long-term patient outcomes. Here, we present an evolutionary simulation model of a clonal population of cells that can acquire resistance mutations to one or more treatments. We leverage this model to examine the efficacy of a two-strike "extinction therapy" protocol, in which two treatments are applied sequentially to first contract the population to a vulnerable state and then push it to extinction, and compare it to a combination therapy protocol. We investigate how factors such as the timing of the switch between the two strikes, the rate of emergence of resistant mutations, the doses of the applied drugs, the presence of cross-resistance, and whether resistance is a binary or a quantitative trait affect the outcome. Our results show that the timing of switching to the second strike has a marked effect on the likelihood of driving the cancer to extinction, and that extinction therapy outperforms combination therapy when cross-resistance is present. We conduct anin silicotrial that reveals when and why a second strike will succeed or fail. Finally, we demonstrate that our conclusions hold whether we model resistance as a binary trait or as a quantitative, multi-locus trait.
An updated reference genome sequence and annotation reveals gene losses and gains underlying naked mole-rat biology
Authors: Sokolowski Dustin J , Miclăuş Mihai , Nater Alexander , Faykoo-Martinez Mariela , Hoekzema Kendra , Zuzarte Philip , Monis Simon , Alvi Sana Akhtar , Erdmann Jason , Erdmann Archana Lal , Kumaragurubaran Rathnakumar , Bayerl Jonathan , Yoo DongAhn , Karimpour Nadia , Ungerleider Kyra , Hou Huayun , Fergal Martin , Hourlier Thibaut , Clarke Zoe A , Lischer Heidi EL , Leordean Dragos V , Jiang Yiyue , Pugh Trevor J , Smith Ewan St. J , Haggerty Leanne , Laird Diana J , Lilue Jingtao , Holmes Melissa M , Eichler Evan E , Bruggmann Rémy , Simpson Jared T , Balmus Gabriel , Wilson Michael D
Published: November 2024

The naked mole-rat (NMR;Heterocephalus glaber) is a eusocial subterranean rodent with a highly unusual set of physiological traits that has attracted great interest amongst the scientific community. However, the genetic basis of most of these traits has not been elucidated. To facilitate our understanding of the molecular mechanisms underlying NMR physiology and behaviour, we generated a long-read chromosomal-level genome assembly of the NMR. This genome was subsequently annotated and incorporated into multiple whole genome alignments in the Ensembl database. Our long-read assembly identified thousands of repeats and genes that were previously unassembled in the NMR and improved the results of routinely used short-read sequencing-based experiments such as RNA-seq, snRNA-seq, and ATAC-seq. We identified several spermatozoa related gene losses that may underlie the unique degenerative sperm phenotype in NMRs (IRGC,FSCB,AKAP3,MROH2B,CATSPER1,DCDC2C,ATP1A4,TEKT5, andZAN), and an additional gene loss related to the established NK-cell absence in NMRs (PILRB). We resolved several tandem duplications in genes related to pathways underlying unique NMR adaptations including hypoxia tolerance, oxidative stress, and nervous system protection (TINF2,TCP1,KYAT1). Lastly, we describe our ongoing efforts to generate a reference telomere-to-telomere assembly in the NMR which includes the resolution of complex gene families. This new reference genome should accelerate the discovery of the genetic underpinnings of NMR physiology and adaptation.
pnetr: An R package for the PnET family of forest ecosystem models
Authors: Gao Xiaojie , Zhou Zaixing , Ollinger Scott V. , Matthes Jaclyn Hatala , Jiao Wenzhe , Thompson Jonathan R.
Published: November 2024

Ecosystem models offer a rigorous way to formalize scientific theories and are critical to evaluating complex interactions among ecological and biogeochemical processes. In addition to simulation and prediction, ecosystem models are a valuable tool for testing hypotheses about mechanisms and empirical findings because they reveal critical internal processes that are difficult to observe directly.

However, many ecosystem models are difficult to manage and apply by scientists who lack advanced computing skills due to complex model structures, lack of consistent documentation, and low-level programming implementation, which facilitates computing but reduces accessibility.

Here, we present the ‘pnetr’ R package, which is designed to provide an easy-to-manage ecosystem modeling framework and detailed documentation in both model structure and programming. The framework implements a family of widely used PnET (net photosynthesis, evapotranspiration) ecosystem models, which are relatively parsimonious but capture essential biogeochemical cycles of water, carbon, and nutrients. We chose the R programming language since it is familiar to many ecologists and has abundant statistical modeling resources. We showcase examples of model simulations and test the effects of phenology on carbon assimilation and wood production using data measured by the Environmental Measurement Station (EMS) eddy-covariance flux tower at Harvard Forest, MA.

We hope ‘pnetr’ can facilitate further development of ecological theory and increase the accessibility of ecosystem modeling and ecological forecasting.
Himalayan whole-genome sequences provide insight into population formation and adaptation
Authors: Arciero Elena , Almarri Mohamed A. , Mezzavilla Massimo , Xue Yali , Hallast Pille , Hammoud Cidra , Chen Yuan , Skov Laurits , Kraaijenbrink Thirsa , Ayub Qasim , Yang Huanming , van Driem George , Jobling Mark A. , de Knijff Peter , Tyler-Smith Chris , Asan  , Haber Marc
Published: November 2024

High-altitude environments pose substantial challenges for human survival and reproduction, attracting considerable attention to the demographic and adaptive histories of high-altitude populations. Previous work focused mainly on Tibetans, establishing their genetic relatedness to East Asians and their genetic adaptation to high altitude, especially at EPAS1. Here, we present 87 new whole-genome sequences from 16 Himalayan populations and the insight they provide into the genomic history of the region. We show that population structure in the Himalayas began to emerge as early as 10,000 years ago, predating archaeological evidence of permanent habitation above 2,500 meters by approximately 6,000 years. The high prevalence of the introgressed adaptive EPAS1 haplotype in all high-altitude populations today supports a shared genetic origin and its importance for survival in this region. We also identify additional selection signals in genes associated with hypoxia, physical activity, immunity and metabolism which could have facilitated adaptation to the harsh environment. Over time, increasing genetic structure led to the diverse and strongly differentiated ethnic groups observed today, most of which maintained small population sizes throughout their history or experienced severe bottlenecks. Between 6,000 and 3,000 years ago, a few uniparental lineages became predominant, likely coinciding with the advent of agriculture, although significant population growth was not observed in the Himalayas except in the Tibetans. In more recent times, we detect bidirectional gene flow between high-altitude and lowland groups, occurring on both sides of the Himalayan range. The timing of this admixture aligns with the rise and expansion of historical regional powers, particularly during the Tibetan Empire and the northern Indian Gupta Empire. In the past few centuries, migrations to the Himalayas seem to have occurred alongside conflicts and population displacements in nearby regions and show some sex bias.
Characterization of Soybean Vein Necrosis Virus (SVNV) Proteins: Sequence Analysis of Field Strains and Comparison of Localization Patterns in Differing Cell Types
Authors: Shehata Abdelaal H.A. , Mayfield Michael A. , Sikora Edward J. , Martin Kathleen M.
Published: November 2024

Soybean vein necrosis virus(SVNV) is a persistent, propagative, ambisense-ssRNA virus in the genus Orthotospovirus transmitted byNehydratothrips variabilis. In this study, five open reading frames (ORFs) (N, NSs, NSm, GN, and GC) were fused in frame to GFP for use in both plant and insect cells. N and NSs localize in plants to the cell periphery and nucleus. NSm causes cell death to plant cells but not in insect cells where cytoplasmic localization is seen. GNand GCglycoproteins localize to the membranes and accumulate with more cytoplasmic localization seen in insect cells. To understand SVNV in the field, we collected 33 samples expressing symptoms of SVNV. The N, NSs, and NSm ORFs were sequenced and amino acid mutations in each gene were seen. The findings of this study capture sequence changes which have occurred over the past fifteen years compared to the localization of proteins never before conducted.
A contextual fear conditioning paradigm in head-fixed mice exploring virtual reality
Authors: Krishnan Seetha , Dong Can , Ratigan Heather , Morales-Rodriguez Denisse , Cherian Chery , Sheffield Mark
Published: November 2024

Contextual fear conditioning is a classical laboratory task that tests associative memory formation and recall. Techniques such as multi-photon microscopy and holographic stimulation offer tremendous opportunities to understand the neural underpinnings of these memories. However, these techniques generally require animals to be head-fixed. There are few paradigms that test contextual fear conditioning in head-fixed mice, and none where the behavioral outcome following fear conditioning is freezing, the most common measure of fear in freely moving animals. To address this gap, we developed a contextual fear conditioning paradigm in head-fixed mice using virtual reality (VR) environments. We designed an apparatus to deliver tail shocks (unconditioned stimulus, US) while mice navigated a VR environment (conditioned stimulus, CS). The acquisition of contextual fear was tested when the mice were reintroduced to the shock-paired VR environment the following day. We tested three different variations of this paradigm and, in all of them, observed an increased conditioned fear response characterized by increased freezing behavior. This was especially prominent during the first trial in the shock-paired VR environment, compared to a neutral environment where the mice received no shocks. Our results demonstrate that head-fixed mice can be fear conditioned in VR, discriminate between a feared and neutral VR context, and display freezing as a conditioned response, similar to freely behaving animals. Furthermore, using a two-photon microscope, we imaged from large populations of hippocampal CA1 neurons before, during, and following contextual fear conditioning. Our findings reconfirmed those from the literature on freely moving animals, showing that CA1 place cells undergo remapping and show narrower place fields following fear conditioning. Our approach offers new opportunities to study the neural mechanisms underlying the formation, recall, and extinction of contextual fear memories. As the head-fixed preparation is compatible with multi-photon microscopy and holographic stimulation, it enables long-term tracking and manipulation of cells throughout distinct memory stages and provides subcellular resolution for investigating axonal, dendritic, and synaptic dynamics in real-time.
Physioxia-modulated mesenchymal stem cells secretome has higher capacity to preserve neuronal network and translation processes in hypoxic-ischemic encephalopathy in vitro model
Authors: Caramelo Inês , Anjo Sandra I. , Mendes Vera M. , Salazar Ivan L. , Dinis Alexandra , Cardoso Carla M.P. , Duarte Carlos B. , Grãos Mário , Manadas Bruno
Published: November 2024

Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of child death worldwide. Most of the survivors develop various neurological diseases, such as cerebral palsy, seizures, and/or motor and behavioral problems. HIE is caused by an episode of perinatal asphyxia, which interrupts the blood supply to the brain. Due to its high energy demands, this interruption initiates glutamate excitotoxic pathways, leading to cell death. Umbilical cord mesenchymal stem cells (UC-MSCs) are gaining attention as a promising complement to the current clinical approach, based on therapeutic hypothermia, which has shown limited efficacy. Previous data have shown that priming MSCs under physiological culture conditions, namely soft platforms (3kPa) – mechanomodulated – or physiological oxygen levels (5% O2) – physioxia – leads to changes in the cellular proteome and their secretome. To evaluate how exposing MSCs’ to these culture conditions could impact their therapeutic potential, physiologically primed UC-MSCs or their secretome were added to anin vitroHIE model using cortical neurons primary cultures subjected to oxygen and glucose deprivation (OGD) insult. By comparing the neuronal proteome of sham, OGD insulted, and OGD-treated neurons, it was possible to identify proteins whose levels were restored in the presence of UC-MSCs or their secretome. Despite the different approaches that differentially altered UC-MSCs’ proteome and secretome, the effects converged on the re-establishment of the levels of proteins involved in translation mechanisms (such as the 40S and 60s ribosomal subunits), possibly stabilizing proteostasis, which is known to be essential for neuronal recovery. Interestingly, treatment with the secretome of UC-MSC modulated under physioxic conditions sustained part of the neuronal network integrity and modulated several mitochondrial proteins, including those proteins involved in ATP production. This suggests that the unique composition of the physioxia-modulated secretome may offer a therapeutical advantage in restoring essential cellular processes that help neurons maintain their function, compared to traditionally expanded UC-MSCs. These findings suggest that both the presence of UC-MSCs and their secretome alone can influence multiple targets and signaling pathways, collectively promoting neuronal survival following an OGD insult.
Stage-Specific Transcriptome Landscape of Hepatocellular Carcinoma: Insights from Super and Poor Survivors with Prognostic Signature Identification
Authors: Xu Xiao-Qian , Wang Hao , Shi Li-Chen , Huang Cheng , You Hong , Jia Ji-Dong , He You-Wen , Kong Yuan-Yuan
Published: November 2024

Background

The prognosis for hepatocellular carcinoma (HCC) patients can vary significantly even within the same clinical stage. This study aims to characterize the stage-specific transcriptomic landscape of super survivors with HCC and identify a prognostic gene signature.

Methods

We analyzed data from The Cancer Genome Atlas (TCGA) for 76 matched super survivors (alive at 5 years) and poor survivors (deceased within 1 year) with HCC. Gene set enrichment analysis stratified by stage was conducted and a key prognostic gene signature was developed. The signature was then applied to the full TCGA cohort and independently validated in International Cancer Genome Consortium (ICGC) data.

Findings

Stage-specific transcriptomic profiling revealed distinct patterns in super survivors. Stage I and II showed positive enrichment in immune response pathways, while stage III exhibited enhanced catabolic activities and reduced glycolysis. Across all stages, cell cycle processes were less active in super survivors. A 19-gene signature, incorporating immune, metabolic, and cell cycle genes, accurately distinguished super from poor survivors with 91% accuracy (69/76). The signature reliably predicted overall survival in both the verification cohort (1-year, 3-year, and 5-year AUROCs of 0.82, 0.80, and 0.78) and the independent validation cohort (1-year and 3-year AUROCs of 0.80 and 0.83). Consistent AUROCs were observed across all tumor stages.

Interpretation

Our findings reveal a dynamic shift in HCC progression, with immune dominance in early stages and metabolic dominance in later stages, alongside reduced cell cycle activity across all stages. Integrating stage-specific transcriptomic profiles offers a promising approach to enhancing individualized management for HCC patients.
Insulin resistance, cognition, and functional brain network topology in older adults with obesity
Authors: McIntyre Clayton C. , Lyday Robert G. , Su Yixin , Nicklas Barbara , Simpson Sean L. , Deep Gagan , Macauley Shannon L. , Hugenschmidt Christina E.
Published: November 2024

Objective

Cross-sectional data from a sample of older adults with obesity was used to determine how peripheral and neuronal insulin resistance (IR) relate to executive function and functional brain network topology.

Methods

Older adults (n=71) with obesity but without type 2 diabetes were included. Peripheral IR was quantified by HOMA2-IR. Neuronal IR was quantified according to a proposed neuron-derived exosome-based method (NDE-IR). An executive function composite score, summed scores to the Auditory Verbal Learning Test (AVLT) trials 1-5, and functional brain networks generated from resting-state functional magnetic resonance imaging were outcomes in analyses. We used general linear models and a novel regression framework for brain network analysis to identify relationships between IR measures and brain-related outcomes.

Results

HOMA2-IR, but not NDE-IR, was negatively associated with executive function. Neither IR measure was associated with AVLT score. Peripheral IR was also related to hippocampal network topology in participants who had undergone functional neuroimaging. Neither peripheral nor neuronal IR were significantly related to network topology of the central executive network.

Conclusions

Cognitive and functional imaging effects were observed from HOMA2-IR, but not NDE-IR. The hippocampus may be particularly vulnerable to effects of peripheral IR.
Visualizing turnover of synaptic vesicle protein Synaptogyrin/SNG-1 in vivo using a new method, ARGO (Analysis of Red Green Offset)
Authors: Shiliaev Nikita , Baumberger Sophie , Richardson Claire E.
Published: November 2024

Proteostasis is critical for cellular function and longevity, especially in long-lived cells including neurons. A major component of proteostasis is the regulated degradation and replacement of proteins to ensure their quality and appropriate abundance. The regulation of synaptic vesicle protein turnover in neurons is important for understanding synaptic communication, yet it is incompletely understood, partly due to limited tools for assessing protein turnoverin vivo. Here, we present ARGO (Analysis of Red-Green Offset), a fully genetically encoded, ratiometric fluorescence imaging method that visualizes and quantifies protein turnover with subcellular resolutionin vivo. ARGO involves cell-specific labeling of the protein-of-interest with both RFP and GFP, followed by Cre/Lox-mediated removal of GFP (pulse) and periodic ratiometric imaging to track protein turnover (chase). This approach is inexpensive, modular, and scalable for use in genetically tractable experimental organisms. Using ARGO, we examined the turnover of Synaptogyrin/SNG-1, an evolutionarily conserved, integral SV protein, in adultCaenorhabditis elegansneurons. Our findings support the model that SV proteins are sorted for degradation at the synapse, then trafficked to the neuron cell body to complete degradation. We show that the rate of presynaptic SNG-1 turnover is consistent across synapses within a single neuron, indicating a cell-wide super-pool for SV protein degradation. Our results further suggest that, contrary to prevailing models, neither the surveillance nor the sorting of SV proteins for degradation is a rate-limiting step for SNG-1 turnover; rather, the rate-limiting step is the clearance of sorted-for-degradation SNG-1 from the presynapse.

Article Summary

How proteins are turned over within subcellular compartments is not well understood, in part because the phenomenon is difficult to quantify. The authors developed a simple, genetically encoded method to quantify the turnover of a protein-of-interest using fluorescence microscopy. They used this method to begin to assess synaptic vesicle protein turnoverin vivo, as this is important for synaptic function. They found that synaptic vesicle protein Synaptogyrin/SNG-1 is sorted for degradation at the synapse but degraded in the neuron cell body, and the turnover rate depends on animal age but is constant across presynapses within a neuron.
Analysis of publicly available transcriptomic data to identify key genes and pathways associated with osteosarcoma metastasis
Authors: Horak Iryna
Published: November 2024

Osteosarcoma is the most common bone tumor occurring in children and adolescents. The prognosis of osteosarcoma patients with metastasis is rather poor, availability of prognostic molecular markers would thereby help to distinguish patients with a worse prognosis and to choose appropriate treatment. This study aimed to analyze data from publicly available datasets to identify genes and pathways associated with osteosarcoma onset and metastasis.

A total of 8 datasets were analyzed (TARGET-OS, GSE220538, GSE21257, GSE9508, GSE87624, GSE14359, GSE19276, and GSE36001), and common deregulated genes and abundant pathways were searched. Three downregulated genes,TMBIM4, PKIBandIGKC, were common between metastatic and non-metastatic osteosarcoma tumors. Several abundant GO terms and pathways were identified, including Apoptotic Process (GO:0006915), Regulation Of Phosphatidylinositol 3-Kinase Signaling (GO:0014066), Regulation Of Cell Adhesion Molecule Production (GO:0060353), Positive Regulation Of MAP Kinase Activity (GO:0043406), and KEGG pathway Adherens junction.

Analysis of metastasisversusprimary tumor revealed 231 common deregulated genes, identified hub genes involved in the organization of cell-cell junctions and surfactant metabolism. Significant enrichment was found in tight junctions, actin cytoskeleton, focal adhesion, muscle contraction proteins, NF-κB, PIK3/Akt/mTOR, AMPK, TNF, and MAPK signaling.

335 common deregulated genes were found between tumor and normal bone, network analysis revealed two clusters involved in cell cycle progression and G2/M transition, and immune response regulation. Abundance was found in p53, TNF, MAPK, and JAK-STAT pathways.

Taken together, this study consolidated transcriptomic data from 8 publicly available datasets to identify common deregulated genes and pathways in osteosarcoma development and metastasis.
The Lifespan Evolution of Individualized Neurophysiological Traits
Authors: da Silva Castanheira Jason , Wiesman Alex I. , Taylor Margot J. , Baillet Sylvain
Published: November 2024

How do neurophysiological traits that characterize individuals evolve across the lifespan? To address this question, we analyzed brief, task-free magnetoencephalographic recordings from over 1,000 individuals aged 4-89. We found that neurophysiological activity is significantly more similar between individuals in childhood than in adulthood, though periodic patterns of brain activity remain reliable markers of individuality across all ages. The cortical regions most critical for determining individuality shift across neurodevelopment and aging, with sensorimotor cortices becoming increasingly prominent in adulthood. These developmental changes in neurophysiology align closely with the expression of cortical genetic systems related to ion transport and neurotransmission, suggesting a growing influence of genetic factors on neurophysiological traits across the lifespan. Notably, this alignment peaks in late adolescence, a critical period when genetic factors significantly shape brain individuality. Overall, our findings highlight the role of sensorimotor regions in defining individual brain traits and reveal how genetic influences on these traits intensify with age. This study advances our understanding of the evolving biological foundations of inter-individual differences.

Lay summary

This study examines how brain activity reflects the development of individuality across a person’s life. Using magnetoencephalography to capture brief recordings of spontaneous brain activity, the researchers distinguished between over 1,000 individuals, spanning ages 4 to 89. They found that the brain regions most associated with individuality change with age: sensory and motor regions become increasingly distinctive in early adulthood, highlighting their role in shaping a person’s unique characteristics of brain activity. The study also revealed that changes in brain activity across different ages correspond to specific patterns of gene expression, shedding light on how genetics influence brain individuality. These findings deepen our understanding of the biological foundations of inter-individual differences and how it evolves over the lifespan.
Rab2B promotes chaperonin-mediated actin folding and prevents developmental transcription reprogramming and quiescence in trypanosomes
Authors: Li Feng-Jun , Dong Xiaoduo , Huang Yameng , Hu Donghui , Chae Eunyoung , He Cynthia Y.
Published: November 2024

The Rab family of small GTPases are regulators of intracellular membrane trafficking. Rab2B, a Golgi-resident Rab GTPase, has been shown to function in ER-Golgi transport and autophagosome-lysosome fusion in mammalian cells andDrosophila. InTrypanosoma brucei, the autophagy-related function of Rab2B was conserved and depletion of Rab2B blocked autophagosome-lysosome fusion. Intriguingly, depletion of Rab2B induced differentiation ofT. bruceifrom a proliferative slender form to a quiescent stumpy form, a step crucial for parasite transmission. Chaperonin CCT/TRiC was identified as an effector of Rab2B. Depletion of CCT/TRiC subunits or actin (a known CCT/TRiC substrate), or blocking actin polymerisation with Latrunculin A all triggered differentiation, suggesting a role of Rab2B on CCT/TRiC-mediated actin folding. Using an actin chromobody, we identified a pool of nuclear actin that is crucial for transcription reprogramming and life cycle differentiation inT. brucei.The study revealed a function of Rab2B and actin inT. bruceitranscription reprogramming leading to cell differentiation, and an unexpected role of Rab2B and CCT/TRiC mediated actin folding.
Immortalized Intestinal Telocytes - A Stem Cell Niche In Vitro
Authors: Canella Marco , Gharbi Amal , Duran Deborah , Corem Noa , Ben-Neriah Yinon , Birimberg-Schwartz Liron , Ben-Porath Ittai , Grunewald Myriam , Shoshkes-Carmel Michal
Published: November 2024

Telocytes, a distinct type of mesenchymal cell, have recently emerged as crucial components of the intestinal stem cell niche, primarily by providing essential Wnt proteins that drive stem cell function. However, their detailed biology and the specific mechanisms by which they regulate stem cell activity remain largely unexplored. Here, we established an immortalized intestinal telocyte cell line that retains the key cellular and molecular characteristics of native telocytes. Remarkably, this cell line, unlike telocyte-depleted immortalized mesenchyme, supports the growth of both mouse and human organoids in co-culture without the need for external factor supplementation. These findings indicate that telocytes are not only essential but are also sufficient to maintain stem cell activity. This immortalized telocyte line provides a valuable source of factors that support stem cell activity in vitro, offering a powerful tool for advancing our understanding of telocyte biology and the reciprocal communication between stem cells and their niche.
White matter microstructure links with brain, bodily and genetic attributes in adolescence, mid- and late life
Authors: Korbmacher Max , Tranfa Mario , Pontillo Giuseppe , van der Meer Dennis , Wang Meng-Yun , Andreassen Ole A. , Westlye Lars T. , Maximov Ivan I.
Published: November 2024

Advanced diffusion magnetic resonance imaging (dMRI) allows one to probe and assess brain white matter (WM) organization and microstructurein vivo. Various dMRI models with different theoretical and practical assumptions have been developed, representing partly overlapping characteristics of the underlying brain biology with potentially complemen-tary value in the cognitive and clinical neurosciences. To which degree the different dMRI metrics relate to clinically relevant geno-and phenotypes is still debated. Hence, we inves-tigate how tract-based and whole WM skeleton parameters from different single- and multi-compartment dMRI approaches associate with clinically relevant and white matter-related phenotypes (sex, age, pulse pressure (PP), body-mass-index (BMI), brain asymmetry) and genetic markers in the UK Biobank (UKB, n=52, 140) and the Adolescent Brain Cognitive Development (ABCD) Study (n=5, 844). Multi-compartment dMRI approaches provided the strongest WM associations with age, and unique insights into brain asymmetry. Kurto-sis was most indicative of PP and BMI. WM-based sex classifications and polygenic score associations for common psychiatric disorders and Alzheimer’s disease were similar across diffusion approaches. We conclude that WM microstructure is differentially associated with clinically relevant pheno- and genotypes at different points in life. Multi-compartment dMRI approaches, and particularly the examined Bayesian approach, provide additional information to conventional approaches in such examinations.
Individual differences in the effects of musical familiarity and musical features on brain activity during relaxation
Authors: Scarratt Rebecca Jane , Dietz Martin , Vuust Peter , Kleber Boris , Jespersen Kira Vibe
Published: November 2024

Finding a way to relax is increasingly difficult in our overstimulating modern society and chronic stress can have severe psychological and physiological consequences. Music is a promising tool to promote relaxation by lowering heart rate, modulating mood and thoughts, and providing a sense of safety. Here, we used functional magnetic resonance imaging (fMRI) to investigate how music influence brain activity during relaxation with a particular focus on the participants’ experience of different types of music. In a 2×2 design, 57 participants were scanned while rating how relaxed they felt after listening to 28-second excerpts of either familiar or unfamiliar relaxation music with calm or energetic features. Behaviourally, calm music was the strongest predictor of relaxation, followed by familiar music. fMRI results revealed activations of auditory, motor, emotion, and memory areas, for listening to familiar compared to unfamiliar music. This suggests increased audio-motor synchronization and participant engagement of known music. Listening to unfamiliar music was correlated with attention-related brain activity, suggesting increased attentional load for this music. Behaviourally, we identified four clusters of participants based on their relaxation response to the different types of music. These groups also displayed distinct auditory and motor activity patterns, suggesting that the behavioural responses are linked to changes in music processing. Interestingly, some individuals found energetic music to be relaxing if it is familiar, whereas others only found calm music to be relaxing. Such individual behavioural and neurological differences in relaxation responses to music emphasise the importance of developing personalised music-based interventions.

Graphical Abstract

Highlights:

- Participants listen to relaxation tracks varying in familiarity and energy levels

- Sedative music followed by familiar music increased relaxation ratings the most

- Auditory, motor, memory and attention activations depending on the music type

- 4 distinct clusters of behavioural responses to familiar or sedative music

- These groups are also present in brain activity
Pupil size variations reveal Bayesian inference in cognitive arithmetic
Authors: Zénon Alexandre , Salvaggio Samuel , Andres Michael
Published: November 2024

The assumption that the brain relies on Bayesian inference has been successful in accounting for many behavioural and neurophysiological observations, but to date, dependence on such mechanism has not been assessed in the context of arithmetic. Bayesian inference implies the representation of uncertainty and reliance on prior beliefs. In arithmetic problem solving, it would consist in refining prior knowledge about the response range as the system progressively integrates the numerical information conveyed by the operands. Within this framework, the amount of information needed to progress from a prior to a posterior probability distribution over responses can be quantified by the information gain, which would relate to the cognitive workload of the task. To test this hypothesis, we designed three experiments in which participants computed the sum of two numbers presented one after another through headphones. In each experiment, the information about response predictability conveyed by the first operand was manipulated. The first operand was either highly informative and contributed to narrow down the response range, or poorly informative and conveyed little information about a plausible response. Throughout all experiments, we found that pupil-related arousal signalled the information gain associated with the first operand, indicating that participants already updated the probability distribution of possible responses upon hearing that first stimulus. This finding shows that Bayesian inference is central to arithmetic problem solving and that information gains consecutive to the integration of the operands can be tracked over time through pupillometry.

Public significance statement

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This study suggests that when we do arithmetic, our brain uses Bayesian inference, a method similar to how scientists update their theories based on new evidence. This means that when doing math, we start with hypotheses about the result and progressively narrow down possible solutions.

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By observing the eye of the participants while they were solving arithmetic problems, the authors showed that their pupil size increased in proportion to the amount of processed information.

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The authors also found that when participants received more informative first operands in the math problem, and when their pupil size increased more during this presentation, they were also faster to respond, indicating that greater initial information processing facilitated quicker problem-solving.
Born Connected: Do Infants Already Have Adult-Like Multi-Scale Connectivity Networks?
Authors: Bajracharya Prerana , Mirzaeian Shiva , Fu Zening , Calhoun Vince , Shultz Sarah , Iraji Armin
Published: November 2024

The human brain undergoes remarkable development with the first six postnatal months witnessing the most dramatic structural and functional changes, making this period critical for in-depth research. rsfMRI studies have identified intrinsic connectivity networks (ICNs), including the default mode network, in infants. Although early formation of these networks has been suggested, the specific identification and number of ICNs reported in infants vary widely, leading to inconclusive findings. In adults, ICNs have provided valuable insights into brain function, spanning various mental states and disorders. A recent study analyzed data from over 100,000 subjects and generated a template of 105 multi-scale ICNs enhancing replicability and generalizability across studies. Yet, the presence of these ICNs in infants has not been investigated.

This study addresses this significant gap by evaluating the presence of these multi-scale ICNs in infants, offering critical insight into the early stages of brain development and establishing a baseline for longitudinal studies. To accomplish this goal, we employ two sets of analyses. First, we employ a fully data-driven approach to investigate the presence of these ICNs from infant data itself. Towards this aim, we also introduce burst independent component analysis (bICA), which provides reliable and unbiased network identification. The results reveal the presence of these multi-scale ICNs in infants, showing a high correlation with the template (rho > 0.5), highlighting the potential for longitudinal continuity in such studies.

We next demonstrate that reference-informed ICA-based techniques can reliably estimate these ICNs in infants, highlighting the feasibility of leveraging the NeuroMark framework for robust brain network extraction. This approach not only enhances cross-study comparisons across lifespans but also facilitates the study of brain changes across different age ranges.

In summary, our study highlights the novel discovery that the infant brain already possesses ICNs that are widely observed in older cohorts.
Changes in interlimb coordination induced by within-stride changes in treadmill speed
Authors: Hall Brooke L. , Roemmich Ryan T. , Banks Caitlin L.
Published: November 2024

During walking, interlimb coordination involves the right and left legs working together to achieve a desired movement. Previously, dynamic treadmill walking has been shown to drive asymmetric gait changes in healthy young adults through selectively changing the speed of the whole treadmill. Currently, the coordination demands of this novel walking environment are unknown and must be understood prior to assessing dynamic treadmill walking in clinical populations. We investigated the interlimb coordination requirements of dynamic treadmill walking in ten healthy young adults. We quantified interlimb coordination changes as phase shift (timing of maximum cross-correlation between limb angle trajectories of the left and right legs), center of oscillation (limb angle at midstance), and center of oscillation difference (oscillation angle difference between legs). We found that phase shift in the Fast trial (i.e., 1.0m/s treadmill speed in first 50% of gait cycle, 0.5m/s in latter 50%) was significantly more positive (i.e., the right leg oscillates ahead of the left leg in time) than in the Slow, Accelerate, and Decelerate trials (all p<0.01). The Fast trial produced significantly positive center of oscillation values on the right leg, indicating that the right leg is oscillating about a more flexed axis than the left. Center of oscillation difference was similarly more positive during the Fast trial than in the Decelerate (p<0.01) and Slow (p<0.01) trials. These results exemplify that some forms of dynamic treadmill walking change interlimb coordination to a greater extent than others. After several minutes of dynamic treadmill walking, interlimb coordination is changed relative to baseline walking in the spatial domain (Fast and Decelerate conditions) and the temporal domain (Fast and Slow). Therefore, dynamic treadmill walking is tunable in both biomechanical and interlimb coordination parameters, creating a variety of options for restoring gait symmetry in asymmetric populations.
p300/CBP-catalyzed acetylation safeguards minor zygotic genome activation via activating DUX
Authors: Xiao Lieying , Jin Hao , Dang Yanna , Zhao Panpan , Li Shuang , Shi Yan , Wang Shaohua , Zhang Kun
Published: November 2024

Zygotic genome activation (ZGA), the first transcriptional event at the onset of life, is crucial for early embryonic development. However, the mechanisms that initiate and regulate ZGA in mammals remain poorly understood. In this study, we demonstrate that p300/CBP-catalyzed acetylation plays a vital role in regulating ZGA. Inhibition of p300/CBP acetyltransferase activity results in impaired minor ZGA and a subsequent 2-cell arrest. By profiling the dynamic landscape of p300 during the ZGA stage, we elucidate the distinct patterns of p300 establishment in promoter and enhancer regions. Moreover, p300 recruits RNA polymerase (Pol II) to pre-configure in the promoter regions of ZGA genes, and orchestrates the gradual establishment of enhancer activity during the early 2-cell stage to activate ZGA. Furthermore, p300 enhances minor ZGA by promoting the expression of DUX. Restoring DUX levels, which are diminished due to p300/CBP inhibition, rescues ZGA and embryonic development by re-establishing Pol II enrichment on minor ZGA genes. Overall, our findings elucidate the mechanism by which p300/CBP regulates ZGA through acetylation and activation of the key transcription factor DUX.

Highlights

p300/CBP plays a stage-specific role during preimplantation development phase.

p300 displays distinctive dynamic changes in promoter and enhancer regions during ZGA stage.

p300/CBP-catalyzed acetylation facilitates the pre-configuration and elongation of Pol II at ZGA gene regions.

DUX recruits p300 and Pol II to activate minor ZGA genes independently of p300’s catalytic activity.
The inflammasome sensor NLRP3 interacts with REV7 to maintain genome integrity through homologous recombination
Authors: Burlet Delphine , Khan Md Muntaz , Hacot Sabine , Buthmann Hannes , Bardoulet Léa , Huber Anne-Laure , Gorry Julie , Lopez Bernard S , Couté Yohann , Geyer Matthias , Tissier Agnès , Petrilli Virginie
Published: November 2024

DNA double strand break (DSB) is a highly toxic lesion that can generate genome instability, a major source of tumorigenesis. DSBs are mainly repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). The selection of the DSB repair pathway primarily depends on the DNA resection of the DSB ends. Indeed, HR is initiated by resection at the DSB generating 3’ single stranded extension. The shieldin complex prevents resection fostering DSB repair toward NHEJ. Here, we reveal that the inflammasome sensor NLRP3 facilitates DNA end resection to promote the HR pathway in an inflammasome-independent manner. Strikingly, NLRP3 silencing decreases HR efficiency, as evidenced by RAD51 foci and functional HR assays. Mechanistically, we describe that NLRP3 interacts with REV7, a subunit of the shieldin complex, and its depletion increases REV7 recruitment to IR-induced DSBs. Similar to cancer cells harboring HR mutated genes, we find that NLRP3 deficient cells are sensitive to PARP inhibitors (PARPi) and exhibit an epistatic relationship with BRCA1 deficiency. Remarkably, loss of REV7 in NLRP3-depleted cells induces PARPi resistance by restoring HR. This study unravels the crucial role of the innate immune receptor NLRP3 in regulating the selection of DSB repair pathways to maintain genome integrity.