bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superagers resist typical age-related white matter structural changes
Authors: Garo-Pascual Marta , Zhang Linda , Valentí-Soler Meritxell , Strange Bryan A. 
Published: January 2024

ABSTRACTSuperagers are elderly individuals with the memory ability of people 30 years younger and provide evidence that age-related cognitive decline is not inevitable. In a sample of 64 superagers (mean age 81.9; 59% women) and 55 typical older adults (mean age 82.4; 64% women) from the Vallecas Project, we studied, cross-sectionally and longitudinally over 5 years with yearly follow-ups, the global cerebral white matter status as well as region-specific white matter microstructure assessment derived from diffusivity measures. Superagers and typical older adults showed no difference in global white matter health (total white matter volume, Fazekas score, and lesions volume) cross-sectionally or longitudinally. However, analyses of diffusion parameters revealed better white matter microstructure in superagers than in typical older adults. Cross-sectional differences showed higher fractional anisotropy (FA) in superagers mostly in frontal fibres and lower mean diffusivity (MD) in most white matter tracts, expressed as an anteroposterior gradient with greater group differences in anterior tracts. FA decrease over time is slower in superagers than in typical older adults in all white matter tracts assessed, which is mirrored by MD increases over time being slower in superagers than in typical older adults in all white matter tracts except for the corticospinal tract, the uncinate fasciculus and the forceps minor. The better preservation of white matter microstructure in superagers relative to typical older adults supports resistance to age-related brain structural changes as a mechanism underpinning the remarkable memory capacity of superagers, while their regional ageing pattern is in line with the last-in-first-out hypothesis.SIGNIFICANCE STATEMENTEpisodic memory is one of the cognitive abilities most vulnerable to ageing. Although memory normally declines with age, some older people may have memory performance similar to that of people 30 years younger, and this phenomenon is often conceptualised as superageing. Understanding the superager phenotype can provide insights into mechanisms of protection against age-related memory loss and dementia. We studied the white matter structure of a large sample of 64 superagers over the age of 80 and 55 age-matched typical older adults during 5 years with yearly follow-ups showing evidence of slower age-related changes in the brains of superagers especially in protracted maturation tracts, indicating resistance to age-related changes and a regional ageing pattern in line with the last-in-first-out hypothesis.
Rbpms2 promotes female fate upstream of the nutrient sensing Gator2 complex component, Mios
Authors: Wilson Miranda L. , Romano Shannon N. , Khatri Nitya , Aharon Devora , Liu Yulong , Kaufman Odelya H. , Draper Bruce W. , Marlow Florence L. 
Published: January 2024

AbstractReproductive success relies on proper establishment and maintenance of biological sex. In many animals, including mammals, the primary gonad is initially ovary in character. We previously showed the RNA binding protein (RNAbp), Rbpms2, is required for ovary fate in zebrafish. Here, we identified Rbpms2 targets in oocytes(Rbpms2-bound oocyte RNAs; rboRNAs). We identify Rbpms2 as a translational regulator ofrboRNAs, which include testis factors and ribosome biogenesis factors. Further, genetic analyses indicate that Rbpms2 promotes nucleolar amplification via the mTorc1 signaling pathway, specifically through the mTorc1-activating Gap activity towards Rags 2 (Gator2) component, Missing oocyte (Mios). Cumulatively, our findings indicate that early gonocytes are in a dual poised, bipotential state in which Rbpms2 acts as a binary fate-switch. Specifically, Rbpms2 represses testis factors and promotes oocyte factors to promote oocyte progression through an essential Gator2-mediated checkpoint, thereby integrating regulation of sexual differentiation factors and nutritional availability pathways in zebrafish oogenesis.
MRCK-1 activates non-muscle myosin for outgrowth of a unicellular tube inCaenorhabditis elegans
Authors: Popiel Evelyn M. , Derry W. Brent 
Published: January 2024

AbstractThe formation and patterning of unicellular biological tubes is essential for metazoan development. It is well established that vascular tubes and neurons use similar guidance cues to direct their development, but the downstream mechanisms that promote the outgrowth of biological tubes are not well characterized. We show that the conserved kinase MRCK-1 and its substrate the regulatory light chain of non-muscle myosin, MLC-4, are required for outgrowth of the unicellular excretory canal inC. elegans. Structure-function analysis of MRCK-1 indicates that the kinase domain, but not the small GTPase-binding CRIB domain, is required for canal outgrowth. Expression of a phosphomimetic form of MLC-4 rescues canal truncations inmrck-1mutants and shows enrichment at the growing canal tip. Specific depletion of MRCK-1 or MLC-4 in the canal causes severe truncations, with unlumenized projections of the basal membrane. Moreover, our work reveals a novel function for non-muscle myosin downstream of MRCK-1 in excretory canal outgrowth that may be conserved in the development of seamless tubes in other organisms.
Active prokaryotic and eukaryotic viral ecology across spatial scale in a deep-sea brine pool
Authors: Minch Benjamin , Chakraborty Morgan , Purkis Sam , Rodrigue Mattie , Moniruzzaman Mohammad 
Published: January 2024

AbstractDeep-sea brine pools represent rare, extreme environments that focus biodiversity at bathyal to abyssal depths. Despite their small size and distribution, brine pools represent important ecosystems to study because they provide unique insight into the limits of life on Earth, and by analogy, the plausibility of life beyond it. A distinguishing feature of many brine pools is the presence of thick benthic microbial mats which develop at the brine-seawater interface. While these bacterial and archaeal communities have received moderate attention, little is known about the viral communities and their interactions with host populations in these environments. To bridge this knowledge gap, we leveraged metagenomic and metatranscriptomic data from three distinct zones within the NEOM brine pool system (Gulf of Aqaba) to gain insights into the active viral ecology around the pools. Here, we report a remarkable diversity and activity of viruses of all nucleic acid types and genome sizes that infect prokaryotic and eukaryotic hosts in this environment. These include giant viruses (phylum:Nucleocytoviricota), RNA viruses, jumbo phages, and polinton-like viruses (PLVs). Many of these appeared to form distinct clades showing the possibility of untapped viral diversity in the brine pool ecosystem. Zone-specific differences in viral community composition and infection strategy were also observed with lysogenic phages seeming to dominate the bacterial mat further away from the pool’s center. Through host matching, viruses infecting metabolically important bacteria and archaea were observed – including a linkage between a jumbo phage and a key manganese-oxidizing and arsenic-metabolizing bacterium. Our findings shed light on the role of viruses in modulating the brine pool microbial community dynamics and biogeochemistry through revealing novel viral diversity, host-virus associations, and spatial-scale heterogeneity in viral dynamics in these extreme environments. These results will provide crucial foundation for further investigation into the adaptations of viruses and their microbial hosts in extreme habitats in the marine ecosystem.
Coupled metalipidomics-metagenomics reveal structurally diverse sphingolipids produced by a wide variety of marine bacteria
Authors: Ding Su , von Meijenfeldt F. A. Bastiaan , Bale Nicole J. , Damsté Jaap S. Sinninghe , Villanueva Laura 
Published: January 2024

ABSTRACTMicrobial lipids, used as taxonomic markers and physiological indicators, have mainly been studied through cultivation. However, this approach is limited due to the scarcity of cultures of environmental microbes, thereby restricting insights into the diversity of lipids and their ecological roles. Addressing this limitation, here we apply for the first time metalipidomics combined with metagenomics in the Black Sea, classifying and tentatively identifying 1,623 lipid-like species across 18 lipid classes. We discovered over 200 novel, abundant, and structurally diverse sphingolipids in euxinic waters, including unique 1-deoxysphingolipids with long-chain fatty acids and sulfur-containing groups. Genomic analysis revealed that members of 38 bacterial phyla in the Black Sea can synthesize sphingolipids, representing a fourfold increase from previously known capabilities and accounting for up to 25% of the microbial community. These sphingolipids appear to be involved in oxidative stress response and cell wall remodeling. Our findings underscore the effectiveness of multi-omics approaches in exploring microbial chemical ecology.
Inhibitory control of gait initiation in humans: an electroencephalography study
Authors: Ziri D. , Hugueville L. , Olivier C. , Boulinguez P. , Gunasekaran H. , Lau B. , Welter M-L. , George N. 
Published: January 2024

AbstractResponse inhibition is a crucial component of executive control. Although mainly studied in upper limb tasks, it is fully implicated in gait initiation. Here, we assessed the influence of proactive and reactive inhibitory control during gait initiation in healthy adult participants. For this purpose, we measured kinematics and electroencephalography (EEG) activity (event-related potential [ERP] and time-frequency data) during a modified Go/NoGo gait initiation task in 23 healthy adults. The task comprised Go-certain, Go-uncertain, and NoGo conditions. Each trial included preparatory and imperative stimuli. Our results showed that go-uncertainty resulted in delayed reaction time (RT), without any difference for the other parameters of gait initiation. Proactive inhibition, i.e. Go uncertain versus Go certain conditions, influenced EEG activity as soon as the preparatory stimulus. Moreover, both proactive and reactive inhibition influenced the amplitude of the ERPs (central P1, occipito-parietal N1, and N2/P3) and theta and alpha/low beta band activities in response to the imperative—Go-uncertain versus Go-certain and NoGo versus Go-uncertain—stimuli. These findings demonstrate that the uncertainty context induced proactive inhibition, as reflected in delayed gait initiation. Proactive and reactive inhibition elicited extended and overlapping modulations of ERP and time-frequency activities. This study shows protracted influence of inhibitory control in gait initiation.
Synaptic vesicle release regulates pre-myelinating oligodendrocyte-axon interactions in a neuron subtype-specific manner
Authors: Gronseth James R. , Nelson Heather N. , Johnson Taylor L. , Mallon Taryn A. , Martell Madeline R. , Pfaffenbach Katrina A. , Duxbury Bailey B. , Henke John T. , Treichel Anthony J. , Hines Jacob H. 
Published: January 2024

AbstractOligodendrocyte-lineage cells are central nervous system (CNS) glia that perform multiple functions including the selective myelination of some but not all axons. During myelination, synaptic vesicle release from axons promotes sheath stabilization and growth on a subset of neuron subtypes. In comparison, it is unknown if pre-myelinating oligodendrocyte process extensions selectively interact with specific neural circuits or axon subtypes, and whether the formation and stabilization of these neuron-glia interactions involves synaptic vesicle release. In this study, we used fluorescent reporters in the larval zebrafish model to track pre-myelinating oligodendrocyte process extensions interacting with spinal axons utilizing in vivo imaging. Monitoring motile oligodendrocyte processes and their interactions with individually labeled axons revealed that synaptic vesicle release regulates the behavior of subsets of process extensions. Specifically, blocking synaptic vesicle release decreased the longevity of oligodendrocyte process extensions interacting with reticulospinal axons. Furthermore, blocking synaptic vesicle release increased the frequency that new interactions formed and retracted. In contrast, tracking the movements of all process extensions of singly-labeled oligodendrocytes revealed that synaptic vesicle release does not regulate overall process motility or exploratory behavior. Blocking synaptic vesicle release influenced the density of oligodendrocyte process extensions interacting with reticulospinal and serotonergic axons, but not commissural interneuron or dopaminergic axons. Taken together, these data indicate that alterations to synaptic vesicle release cause changes to oligodendrocyte-axon interactions that are neuron subtype specific.
Association between allostatic load and accelerated white matter brain aging: findings from the UK Biobank
Authors: Feng Li , Ye Zhenyao , Du Zewen , Pan Yezhi , Canida Travis , Ke Hongjie , Liu Song , Chen Shuo , Hong L. Elliot , Kochunov Peter , Chen Jie , Lei David K.Y. , Shenassa Edmond , Ma Tianzhou 
Published: January 2024

AbstractWhite matter (WM) brain age, a neuroimaging-derived biomarker indicating WM microstructural changes, helps predict dementia and neurodegenerative disorder risks. The cumulative effect of chronic stress on WM brain aging remains unknown. In this study, we assessed cumulative stress using a multi-system composite allostatic load (AL) index based on inflammatory, anthropometric, respiratory, lipidemia, and glucose metabolism measures, and investigated its association with WM brain age gap (BAG), computed from diffusion tensor imaging data using a machine learning model, among 22 951 European ancestries aged 40 to 69 (51.40% women) from UK Biobank. Linear regression, Mendelian randomization, along with inverse probability weighting and doubly robust methods, were used to evaluate the impact of AL on WM BAG adjusting for age, sex, socioeconomic, and lifestyle behaviors. We found increasing one AL score unit significantly increased WM BAG by 0.29 years in association analysis and by 0.33 years in Mendelian analysis. The age- and sex-stratified analysis showed consistent results among participants 45-54 and 55-64 years old, with no significant sex difference. This study demonstrated that higher chronic stress was significantly associated with accelerated brain aging, highlighting the importance of stress management in reducing dementia and neurodegenerative disease risks.
HistoPlexer: Histopathology-based Protein Multiplex Generation using Deep Learning
Authors: Andani Sonali , Chen Boqi , Ficek-Pascual Joanna , Heinke Simon , Casanova Ruben , Hild Bernard , Sobottka Bettina , Bodenmiller Bernd ,   Tumor Profiler Consortium, Koelzer Viktor H , Rätsch Gunnar 
Published: January 2024

AbstractMultiplexed imaging technologies provide crucial insights into interactions between tumors and their surrounding tumor microenvironment (TME), but their widespread adoption is limited by cost, time, and tissue availability. We introduce HistoPlexer, a deep learning (DL) framework that generates spatially-resolved protein multiplexes directly from histopathology images. HistoPlexer employs the conditional generative adversarial networks with custom loss functions that mitigate slice-to-slice variations and preserve spatial protein correlations. In a comprehensive evaluation on metastatic melanoma samples, HistoPlexer consistently outperforms existing approaches, achieving superior Multiscale Structural Similarity Index and Peak Signal-to-Noise Ratio. Qualitative evaluation by domain experts demonstrates that the generated protein multiplexes closely resemble the real ones, evidenced by Human Eye Perceptual Evaluation error rates exceeding the 50% threshold for perceived realism. Importantly, HistoPlexer preserves crucial biological relationships, accurately capturing spatial co-localization patterns among proteins. In addition, the spatial distribution of cell types derived from HistoPlexer-generated protein multiplex enables effective stratification of tumors into immune hot versus cold subtypes. When applied to an independent cohort, incorporating additional features from HistoPlexergenerated multiplexes enhances the performance of the DL model for survival prediction and immune subtyping, outperforming the model reliant solely on Hematoxylin & Eosin (H&E) image features. By enabling the generation of whole-slide protein multiplex from the H&E image, HistoPlexer offers a cost- and time-effective approach to understanding the TME, and holds promise for advancing precision oncology.
Definition of viroIogical endpoints improving the design of HIV cure strategies using analytical antiretroviral treatment interruption
Authors: Alexandre Marie , Prague Mélanie , Lhomme Edouard , Lelievre Jean-Daniel , Wittkop Linda , Richert Laura , Lévy Yves , Thiébaut Rodolphe 
Published: January 2024

AbstractBackgroundAnalytical treatment interruption (ATI) is the gold standard in HIV research to validate the ability of novel therapeutic strategies to long-term control viremia without antiretroviral treatment (ART). Viral setpoint is commonly used as endpoint to evaluate their efficacy. However, to mitigate higher viremia risk without ART, trials use short ATI phases and strict virological ART re-start criteria, compromising the observation of the setpoint.MethodsWe analyzed viral dynamics in 235 HIV-infected participants from three trials, examining various virological criteria during ATI phases. Time-related (e.g. time to rebound, peak and setpoint) and VL magnitude-related criteria (peak, setpoint and time-averaged AUC [nAUC]) were described. Spearman correlations were analyzed to identify surrogate endpoints for setpoints. Additional correlation analyzes were performed to identify optimal virological ART re-start criteria mitigating the risks of ART interruption and the evaluation of viral control.ResultsComparison of virological criteria between trials showed strong dependencies on ATI design. Similar correlations were found across trials, with nAUC identified as the criterion most strongly correlated with the setpoint, with correlations higher than 0.70. A threshold of at least 100,000 copies/mL for two consecutive VL measurements is requested as virological ART re-start criteria to keep strong correlations between the setpoint and nAUC.ConclusionsOur results emphasize the benefits of an ATI phase longer than 12 weeks, with regular monitoring, and a VL threshold of 100,000 copies/mL as virological ART re-start criteria to limit the risk for patients while capturing enough information to keep nAUC as an optimal proxy for the setpoint.
Aberrant fast spiking interneuronal activity precedes seizure transitions in humans
Authors: Merricks Edward M. , Deshpande Sarita S. , Agopyan-Miu Alexander H. , Smith Elliot H. , Schlafly Emily D. , McKhann Guy M. , Goodman Robert R. , Sheth Sameer A. , Greger Bradley , House Paul A. , Eskandar Emad N. , Madsen Joseph R. , Cash Sydney S. , Trevelyan Andrew J. , van Drongelen Wim , Schevon Catherine A. 
Published: January 2024

AbstractThere is active debate regarding how GABAergic function changes during seizure initiation and propagation, and whether interneuronal activity drives or impedes the pathophysiology. Here, we track cell-type specific firing during spontaneous human seizures to identify neocortical mechanisms of inhibitory failure. Fast-spiking interneuron activity was maximal over 1 second before equivalent excitatory increases, and showed transitions to out-of-phase firing prior to local tissue becoming incorporated into the seizure-driving territory. Using computational modeling, we linked this observation to transient saturation block as a precursor to seizure invasion, as supported by multiple lines of evidence in the patient data. We propose thattransientblocking of inhibitory firing due to selective fast-spiking interneuron saturation—resulting from intense excitatory synaptic drive—is a novel mechanism that contributes to inhibitory failure, allowing seizure propagation.
Impact of Remote Cholecystectomy on Clinical Outcomes FollowingPseudomonas aeruginosaBloodstream Infection: A Retrospective Cohort Study
Authors: Bertucci Hanna K. , Heise Lyndsey R. , Angarone Michael P. , Hauser Alan R. , Scheetz Marc H. , Bachta Kelly E. R. 
Published: January 2024

ABSTRACTPurposeMortality associated withPseudomonas aeruginosabloodstream infection (PABSI) remains high despite advances in clinical care and therapeutics. In a recent study using mice to model PABSI, the gallbladder (GB) was identified as a reservoir for bacterial expansion. Furthermore, bile exposure has been linked to increased antimicrobial resistance (AMR). Therefore, we asked whether patients with retained gallbladders might suffer from more antimicrobial resistantP. aeruginosa(Pa) infections, extended culture positivity, and worsened clinical outcomes.MethodsRetrospective cohort study of adults hospitalized over a five-year period with PABSI. PABSI cases were defined as patients with ≥ 1 positivePabacterial culture from the blood. Patients were categorized as either those retaining a gallbladder (no cholecystectomy) or those without (cholecystectomy). Cholecystectomy was defined as a history of cholecystectomy ≥ 1 year prior to the index episode of PABSI. Inferential statistics were used to identify associations between remote cholecystectomy and antimicrobial resistance profile, length of blood culture positivity, and in-hospital and 90-day mortality.ResultsThe final study population included 336 patients, 262 (78%) with retained gallbladder and 74 (22%) without. We observed no difference in 90-day or in-hospital mortality between groups. Overall, composite 90-day mortality was 30.1%. Furthermore, no robust differences were observed in the antimicrobial resistance profile ofPaisolates between the groups.ConclusionsIn our study, neither PABSI AMR pattern nor clinical outcome was affected by remote cholecystectomy. However, we do demonstrate that mortality for patients with PABSI in the modern era remains high despite advances in anti-pseudomonal therapeutics.
Efficient Inference on a Network of Spiking Neurons using Deep Learning
Authors: Baldy Nina , Breyton Martin , Woodman Marmaduke M. , Jirsa Viktor K. , Hashemi Meysam 
Published: January 2024

AbstractThe process of making inference on networks of spiking neurons is crucial to decipher the underlying mechanisms of neural computation. Mean-field theory simplifies the interactions between neurons to produce macroscopic network behavior, facilitating the study of information processing and computation within the brain. In this study, we perform inference on a mean-field model of spiking neurons to gain insight into likely parameter values, uniqueness and degeneracies, and also to explore how well the statistical relationship between parameters is maintained by traversing across scales. We benchmark against state-of-the-art optimization and Bayesian estimation algorithms to identify their strengths and weaknesses in our analysis. We show that when confronted with dynamical noise or in the case of missing data in the presence of bistability, generating probability distributions using deep neural density estimators outperforms other algorithms, such as adaptive Monte Carlo sampling. However, this class of deep generative models may result in an overestimation of uncertainty and correlation between parameters. Nevertheless, this issue can be improved by incorporating time-delay embedding. Moreover, we show that training deep Neural ODEs on spiking neurons enables the inference of system dynamics from microscopic states. In summary, this work demonstrates the enhanced accuracy and efficiency of inference on networks of spiking neurons when deep learning is harnessed to solve inverse problems in neural computation.