bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle mitochondrial bioenergetic capacities is associated with multimorbidity burden in older adults: the Study of Muscle, Mobility and Aging (SOMMA)
Authors: Mau Theresa , Blackwell Terri L. , Cawthon Peggy M. , Molina Anthony J. A. , Coen Paul M. , Distefano Giovanna , Kramer Philip A. , Ramos Sofhia V. , Forman Daniel E. , Goodpaster Bret H. , Toledo Frederico G. S. , Duchowny Kate A. , Sparks Lauren M. , Newman Anne B. , Kritchevsky Stephen B. , Cummings Steven R. 
Published: November 2023

AbstractBackgroundThe geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity.MethodsThe Study of Muscle, Mobility and Aging (SOMMA) assessedex vivomuscle mitochondrial energetics in 764 older adults (mean age =76.4, 56.5% women, 85.9% non-Hispanic white) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95%CI]) for the likelihood of greater multimorbidity (four levels: 0 conditions, N=332; 1 condition, N=299; 2 conditions, N=98; or 3+ conditions, N=35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions.ResultsLower oxidative phosphorylation supported by fatty acids and/or complex-I and -II linked carbohydrates (e.g., Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR=1.32[1.13,1.54]) and separately with diabetes mellitus (OR=1.62[1.26,2.09]), depressive symptoms (OR=1.45[1.04,2.00]) and possibly chronic kidney disease (OR=1.57[0.98,2.52]) but not significantly with other conditions (e.g., cardiac arrhythmia, chronic obstructive pulmonary disease).ConclusionsLower muscle mitochondrial bioenergetic capacities was associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and is more strongly related to some conditions than others.(Words= 233)
Comparison of frailty instruments in acute coronary syndrome patients
Authors: Langsted Anne , Benatar Jocelyn , Kerr Andrew , Bloomfield Katherine , Devlin Gerry , Sasse Alex , Smythe David , To Andrew , Wilkins Gerry , White Harvey , Stewart Ralph 
Published: November 2023

AbstractBackgroundRecognising frailty is important to guide clinical decisions in older patients with cardiac disease. The relative strengths of different frailty instruments to predict mortality and hospitalization risk are uncertain.MethodsThe Edmonton Frail Scale (EFS), Fried Criteria (Fried), Clinical Frailty Scale (CFS), Katz score (Katz), GP Cognition test (GPCog), and Euroscore II a disease based risk score, were completed in 1174 clinically stable inpatients >70 years of age admitted with an acute coronary syndrome to 5 New Zealand hospitals. Associations with all cause mortality (n=353, 29%) during a median follow-up of 5.1 (IQR: 4.6-5.5) years and hospitalization for > 10 days in the next year (n=267, 22%) were evaluated.ResultsThere were graded associations between increasing frailty assessed by each tool and all cause mortality. For the EFS, which scores up to 17 points on different dimensions of frailty, hazard ratios for high (score 9-17, n=197) compared to low frailty (score 0-2, n=331) were 5.0 (95%CI: 3.4-7.4) for mortality, and 5.3 (3.4-8.3) for hospitalization. Discrimination for all-cause mortality according to Harrell’s C-index for each instrument were EFS 0.663, Euroscore II 0.654, Fried 0.648, CFS 0.640, GPCog 0.608, and Katz 0.593, P<0.001 for all. C-statistics for hospitalization >10 days were EFS 0.649, Fried 0.628, Katz 0.602, Euroscore II 0.589, CFS 0.584, and GPCog 0.552, P<0.001 for all. When combining tools integrated discrimination improvement for both mortality and hospitalization were greater for EFS than for other frailty instruments.ConclusionIn acute coronary syndrome patients aged >70 years greater ‘frailty’ assessed using all tools was associated with higher mortality and hospitalization. The Edmonton Frail Scale, which provides a graded measure of severity of frailty based on information relevant to clinical care, discriminated the risk of mortality and hospitalization as well or better than other frailty instruments.
Dissecting the Vascular-Cognitive Nexus: Energetic vs. Conventional Hemodynamic Parameters
Authors: Cheng Hao-Min , Wang Jiun-Jr , Chuang Shao-Yuan , Lin Chen-Hua , Mitchell Gary F. , Huang Chi-Jung , Wang Pei-Ning , Chung Chih-Ping , Chen Liang-Kung , Pan Wen-Harn , Peng Li-Ning , Chen Chen-Huan 
Published: November 2023

ABSTRACTBackgroundBlood flow measurements are being studied in relation to vascular health and cognitive function, but their role is unclear.ObjectiveWe investigated whether energetic hemodynamic parameters, such as aortic and carotid mean and pulsatile energy, and energy pulsatility index (PI), provide a more nuanced understanding of the vascular-cognitive link, as assessed by the Montreal Cognitive Assessment (MoCA), than conventional flow and flow PI.MethodsCognitive evaluation and hemodynamic measurements, including aortic and carotid pressure and flow waves, were performed on 1858 MoCA participants. Energy was calculated by integrating pressure time flow. An asymmetric bifurcation model was used to calculate aortic and carotid mean, pulsatile energy, and hemodynamic parameters across the interface.ResultsAfter adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels, energetic hemodynamic parameters were more associated with MoCA score than aortic and carotid flow and flow PI. In particular, carotid mean energy was most significantly positively associated with MoCA (standardized beta = 0.053, P = 0.0253) and energy PI was most significantly negatively associated (standardized beta = -0.093, P = 0.0002), surpassing conventional metrics like carotid PI. Aortic pressure reflection coefficient at the aorta-carotid bifurcation was positively correlated with mean carotid energy and weakly negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy.ConclusionOur study shows that energetic hemodynamic parameters, particularly carotid mean energy and energy PI, better explain the vascular-cognitive nexus than conventional measures.
“In Vivo Imaging of Bone Collagen Dynamics in zebrafish”
Authors: Hino Hiromu , Kuroda Junpei , Kondo Shigeru 
Published: November 2023

AbstractType I collagen plays a pivotal role in shaping bone morphology and determining its physical properties by serving as a template for ossification. Nevertheless, the mechanisms underlying bone collagen formation, particularly the principles governing its orientation, remain unknown due to the lack of a method enabling continuous in vivo observation. To address this challenge, we constructed a method to visualize bone collagen by tagging with GFP in zebrafish and observed the interactions between the osteoblasts and collagen fiber during bone formation in vivo. When Col1a2-GFP was expressed under the control of the osteoblast-specific promotersosxoroscin zebrafish, bone collagen could be observed clearly enough to identify their localization, but collagen from other organs did not. Therefore, we determined that this method was of sufficient quality for detailed in vivo observation of bone collagen. Next, bone collagen in the scales, fin ray, and opercular bones was observed in detail in zebrafish, when bone formation is more active.By simultaneously observing bone collagen and osteoblasts, we successfully observed dynamic changes in the morphology and position of osteoblasts from the early stages of bone formation. It was also found that the localization pattern and orientation of bone collagen significantly differed depending on the choice of expression promoter. Both promoters (osxandosc) used in this study are osteoblast-specific, but their Col1a2-GFP localizing regions within bone are exclusive, withosxregion localizing mainly the outer edge of bone andoscregion localizing the central area of bone. This suggests the existence of distinct subpopulations of osteoblasts with various gene expression profiles, each of which may play a unique role in the osteogenic process.These findings would contribute to a better understanding of the mechanisms governing bone collagen formation by osteoblasts.
Neural representation of association strength and prediction error during novel symbol-speech sounds learning
Authors: Fraga-González Gorka , Haller Patrick , Willinger David , Gehrig Vanessa , Frei Nada , Brem Silvia 
Published: November 2023

AbstractEfficient learning of letters-speech sound associations leads to specialization of visual and audiovisual brain regions and is necessary to develop adequate reading skills. We still do not understand the brain dynamics of this learning process, and the involvement of learning and performance monitoring networks is still underexplored. Here we examined a feedback learning task with two mutually dependent parts in which novel symbol-speech sound associations were learned by 39 healthy adults. We used functional magnetic resonance (fMRI) and a reinforcement learning drift diffusion model that described learning across trials. The model-based analysis showed that posterior-occipital activations during stimulus processing were positively modulated by the trial-by-trial learning, described by the increase in association strength of each audiovisual pair. Prediction errors, describing the update mechanism to learn with feedback across trials, modulated activations in several mid-frontal, striatal and cingulate regions. The two task parts yielded a similar pattern of results although they varied in their relative difficulty. This study demonstrates which processes during audiovisual learning contribute to the rapid visual specialization within an experimental session and delineates a set of coactivated regions engaged in learning from feedback. Our paradigm provides a framework to advance our understanding of the neurobiology of learning and reading development.
coRIC map: a framework for the exploration of multifaceted subcellular RNA-binding proteins
Authors: Lv Yuan , Guo Xiangpeng , Hu Jieyi , Kanwal Shahzina , Yuan Jianwen , Tariq Muqddas , Zheng Jingxia , Sun Mingwei , Lu Yuanyuan , Wang Jingjing , Jiang Mengling , Wang Aiping , Castells-Garcia Alvaro , Zheng Xiyuan , Peng Bin , Wang Dongye , Volpe Giacomo , Wu Liang , Mazid Md. Abdul , Li Wenjuan , Lai Yiwei , Aguilo Francesca , Zhou Yu , Cosma Maria Pia , Xu Xingzhi , Lundberg Emma , Mulder Jan , Hutchins Andrew P. , Maxwell Patrick H. , Croce Luciano Di , Zhang Xiaofei , Esteban Miguel A. 
Published: November 2023

AbstractThe ability of RNA-binding proteins (RBPs) to form complexes with other biomolecules underpins a broad range of functions and remarkable structural properties. Understanding the precise spatiotemporal dynamics of RBPs and their interacting partners in the steady state and upon perturbation is key to deciphering these aspects. Here, we present the coRIC (compartmentalizedRNA InteractomeCapture) map, an experimental resource and analytical pipeline to study the subcellular dynamics of RBPs through multimodal dataset integration and machine learning. Using this approach, we have generated an atlas comprising 1,768 RBPs distributed in a broad panel of subcellular compartments and delineated their intermolecular and intercompartmental relationships. We have also defined the hierarchy of RBP-containing complexes at multiple scales across the cell, uncovering previously unknown functions of multiple RBPs. Furthermore, we have investigated the changes in RBP complex composition and subcellular distribution in response toC9ORF72amyotrophic lateral sclerosis/frontotemporal dementia dipeptide repeats and DNA damage stress. The coRIC map provides a valuable new approach for defining the roles of RBPs in homeostasis and disease.
Linking place and view: Organizing space through saccades and fixations between primate posterior parietal cortex and hippocampus
Authors: Vericel Marie , Baraduc Pierre , Duhamel Jean René , Wirth Sylvia 
Published: November 2023

AbstractHumans primarily rely on vision to explore and guide actions in spatial environments. The parietal cortex is thought to withhold a unified representation of the visual space allowing to direct saccades to salient cues, while the hippocampus provides a memory-based cognitive place map of the environment. Understanding how these two representations interact during navigation is a key question. To probe the link between view and place, we compared neural activity in the posterior parietal cortex and hippocampus of macaques navigating in a virtual maze. When analyzed as a function of the animal’s position in the virtual environment, more neurons in the parietal cortex displayed spatial selectivity compared to the hippocampus. We hypothesized that such modulation by self-position in the parietal cortex might stem from processing visual cues of the environment through exploratory saccades and fixations. However, we established that position-selectivity was not solely correlated with simple oculomotor dynamics. Rather, spatial selectivities in the PPC and the HPC originated from cells driven by direct fixations of maze paths or landmarks. However, while a substantial proportion of PPC and HPC cells displayed selectivity towards landmarks’ features, such as their side of appearance or their identity, we also revealed different task-related maze segmentation between regions. Indeed, when animal gazed at paths, activity in parietal cortex revealed anticipation of reward while that of the hippocampus suggested reward outcome processing. On the other hand, when animals gazed at a landmark already present in the field of view, parietal activity tended to occur close to intersections, while that of hippocampus was more spatially distributed. Finally, at the population level, neurons in both regions anticipated landmarks before they appeared in the field of view, suggesting a shared knowledge of the spatial layout and a collective active role in memory-guided visual exploration across regions. Taken together, these findings shed light on the neural processes that link place and view, through action- and memory-driven exploration of objects in space.
Cytokinin Dehydrogenase in Xylem Sap Reveals A Direct Link Between Cytokinin Metabolism and Long-Distance Transport
Authors: Nedvěd Daniel , Motyka Václav , Raimanová Ivana , Dobrev Petre I. , Kopečný David , Briozzo Pierre , Brunoni Federica , Müller Karel , Hoyerová Klára 
Published: November 2023

AbstractMetabolic degradation of plant hormones cytokinins (CKs) co-regulates their homeostasis and signalling. In this work, we employed a large-scale bioinformatical analysis to address a diversity of cytokinin oxidase/dehydrogenase (CKX) substrate specificities previously described in several case studies. We present a three-way correlation of the entire CKX amino acid sequences, a variable motif involved in substrate binding, and subcellular localizations predicted by a deep learning model. This correlation is conserved in monocotyledonous plants, suggesting that the CKX diversity in a single species allows a precise tuning of the CK homeostasis. Following these findings, we detected CKX activity in xylem sap for the first time, using the oat (Avena sativa) as a model plant. Further investigation of the substrate specificity and glycosylation of this xylem-located CKX suggested that it originates in roots. We have identified 27 putative CKXs in oats and attributed the xylem-located activity to the extracellular isoforms AsCKX1a,c,d. Finally, we show that the xylem-located CKX activity responds to the nitrate supply, highlighting its physiological relevance. Taken together, we show that CKX directly modulates root-to-shoot CK translocation through metabolic degradation of the transported CKs.
Entorhinal cortex vulnerability to human APP expression promotes hyperexcitability and tau pathology
Authors: Goettemoeller Annie M , Banks Emmie , Kumar Prateek , Olah Viktor J , McCann Katharine E , South Kelly , Ramelow Christina C , Eaton Anna , Duong Duc M , Seyfried Nicholas T , Weinshenker David , Rangaraju Srikant , Rowan Matthew JM 
Published: November 2023

AbstractPreventative treatment for Alzheimer’s Disease is of dire importance, and yet, cellular mechanisms underlying early regional vulnerability in Alzheimer’s Disease remain unknown. In human patients with Alzheimer’s Disease, one of the earliest observed pathophysiological correlates to cognitive decline is hyperexcitability. In mouse models, early hyperexcitability has been shown in the entorhinal cortex, the first cortical region impacted by Alzheimer’s Disease. The origin of hyperexcitability in early-stage disease and why it preferentially emerges in specific regions is unclear. Using cortical-region and cell-type-specific proteomics coupled withex vivoandin vivoelectrophysiology, we uncovered differential susceptibility to human-specific amyloid precursor protein (hAPP) in a model of sporadic Alzheimer’s. Unexpectedly, our findings reveal that early entorhinal hyperexcitability may result from intrinsic vulnerability of parvalbumin (PV) interneurons, rather than the suspected layer II excitatory neurons. This vulnerability of entorhinal PV interneurons is specific to hAPP, as it could not be recapitulated with increased murine APP expression. However, partial replication of the findings could be seen after introduction of a murine APP chimera containing a humanized amyloid-beta sequence. Surprisingly, neurons in the Somatosensory Cortex showed no such vulnerability to adult-onset hAPP expression. hAPP-induced hyperexcitability in entorhinal cortex could be ameliorated by enhancing PV interneuron excitabilityin vivo.Co-expression of human Tau with hAPP decreased circuit hyperexcitability, but at the expense of increased pathological tau species. This study suggests early disease interventions targeting non-excitatory cell types may protect regions with early vulnerability to pathological symptoms of Alzheimer’s Disease and downstream cognitive decline.
Shared representations of human actions across vision and language
Authors: Dima Diana C. , Janarthanan Sugitha , Culham Jody C. , Mohsenzadeh Yalda 
Published: November 2023

AbstractHumans can recognize and communicate about many actions performed by others. How are actions organized in the mind, and is this organization shared across vision and language? We collected similarity judgments of human actions depicted through naturalistic videos and sentences, and tested four models of action categorization, defining actions at different levels of abstraction ranging from specific (action verb) to broad (action target: whether an action is directed towards an object, another person, or the self). The similarity judgments reflected a shared organization of action representations across videos and sentences, determined mainly by the target of actions, even after accounting for other semantic features. Language model embeddings predicted the behavioral similarity of action videos and sentences, and captured information about the target of actions alongside unique semantic information. Together, our results show how action concepts are organized in the human mind and in large language model representations.
Pauperization of Emerin from nuclear envelope during chromatin bridge resolution drives prostate cancer cell migration and invasiveness
Authors: Popęda Marta , Kowalski Kamil , Wenta Tomasz , Beznoussenko Galina V. , Rychłowski Michał , Mironov Alexander , Lavagnino Zeno , Barozzi Sara , Richert Julia , Bertolio Rebecca , Szade Jolanta , Miszewski Kevin , Matuszewski Marcin , Żaczek Anna J. , Braga Luca , Sal Giannino Del , Bednarz-Knoll Natalia , Maiuri Paolo , Nastały Paulina 
Published: November 2023

AbstractMicronuclei (MN) can arise from many causes, including the breakage of aberrant cytokinetic chromatin bridge. The frequent observation of MN in tumors raises the specter that they might not merely be passive elements but could instead play active roles in tumor progression. Here, we test the hypothesis that the presence of micronuclei could induce specific phenotypic and functional changes to the cell and lead to increased cancer invasive potential. With a variety of imaging and molecular methodsin vitroand in clinical samples from prostate cancer (PCa) patients, we show that chromosome bridge resolution can lead to EMD accumulation and formation of EMD-rich MN. Such structure is negative for Lamin A/C and positive for LBR and Sec6β. It can cause EMD pauperization from NE affecting migratory and invasive properties of a cell and can be translated to PCa patient’s poor prognosis.
Genome assembly of the dyeing poison frog provides insights into the dynamics of transposable element and genome-size evolution
Authors: Dittrich Carolin , Hölzl Franz , Smith Steve , Fouilloux Chloe A. , Parker Darren J. , O’Connell Lauren A. , Knowles Lucy S. , Hughes Margaret , Fewings Ade , Morgan Rhys , Rojas Bibiana , Comeault Aaron A. 
Published: November 2023

AbstractGenome size varies greatly across the tree of life and transposable elements are an important contributor to this variation. Among vertebrates, amphibians display the greatest variation in genome size, making them ideal models to explore the causes and consequences of genome size variation. However, high-quality genome assemblies for amphibians have, until recently, been rare. Here, we generate a high-quality genome assembly for the dyeing poison frog,Dendrobates tinctorius. We compare this assembly to publicly-available frog genomes and find evidence for both large-scale conserved synteny and widespread rearrangements between frog lineages. Comparing conserved orthologs annotated in these genomes revealed a strong correlation between genome size and gene size. To explore the cause of gene-size variation, we quantified the location of transposable elements relative to gene features and find that the accumulation of transposable elements in introns has played an important role in the evolution of gene size inD. tinctorius, while estimates of insertion times suggest that many insertion events are recent and species-specific. Finally, we show that the diversity and abundance of transposable elements in poison frog genomes can complicate genotyping efforts that rely on repetitive elements as sequence anchors. Our results show that transposable elements have clearly played an important role in the evolution of large genome size inD. tinctorius. Future studies are needed to fully understand the dynamics of transposable element evolution and to optimise primer or bait design for cost-effective population-level genotyping in species with large, repetitive genomes.SignificanceAmphibians display more variation in genome size than any other vertebrate lineage. Complexities associated with large genomes frequently hamper genome assembly and population genetic studies. Here we use long-read HiFi sequences to generate a high-quality 6.3 Gbp genome assembly of the poison frogDendrobates tinctorius. We use this genome and leverage comparative genomics andde novoannotations to quantify aspects of genome evolution driven by repetitive transposable genetic elements. Our results provide support for the dynamic role that transposable elements play in driving the evolution of “genomic gigantism” in amphibians. We also show how transposable elements can be leveraged for cost-efficient population genetic studies using limited input material.