bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort
Authors: Montanari Silvia , Jansen Rick , Schranner Daniela , Kastenmüller Gabi , Arnold Matthias , Janiri Delfina , Sani Gabriele , Bhattacharyya Sudeepa , Dehkordi Siamak Mahmoudian , Dunlop Boadie W , Rush A. John , Penninx Brenda W. H. J. , Kaddurah-Daouk Rima , Milaneschi Yuri 
Published: February 2024

ABSTRACTBackgroundAcylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Studies linking AC levels to depression are few and provide mixed findings. We examined the association of circulating ACs levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific symptom profiles.MethodsThe sample from the Netherlands Study of Depression and Anxiety included participants with current (n=1035) or remitted (n=739) MDD and healthy controls (n=800). Plasma levels of four ACs (short-chain: acetylcarnitine C2 and propionylcarnitine C3; medium-chain: octanoylcarnitine C8 and decanoylcarnitine C10) were measured. Overall depression severity as well as atypical/energy-related (AES), anhedonic and melancholic symptom profiles were derived from the Inventory of Depressive Symptomatology.ResultsAs compared to healthy controls, subjects with current or remitted MDD presented similarly lower mean C2 levels (Cohen’s d=0.2, p≤1e-4). Higher overall depression severity was significantly associated with higher C3 levels (ß=0.06, SE=0.02, p=1.21e-3). No associations were found for C8 and C10. Focusing on symptom profiles, only higher AES scores were linked to lower C2 (ß=-0.05, SE=0.02, p=1.85e-2) and higher C3 (ß=0.08, SE=0.02, p=3.41e-5) levels. Results were confirmed in analyses pooling data with an additional internal replication sample from the same subjects measured at 6-year follow-up (totaling 4195 observations).ConclusionsSmall alterations in levels of short-chain acylcarnitine levels were related to the presence and severity of depression, especially for symptoms reflecting altered energy homeostasis. Cellular metabolic dysfunctions may represent a key pathway in depression pathophysiology potentially accessible through AC metabolism.
Distinct impact modes of polygenic disposition to dyslexia in the adult brain
Authors: Soheili-Nezhad Sourena , Schijven Dick , Mars Rogier B. , Fisher Simon E. , Francks Clyde 
Published: February 2024

AbstractDyslexia is a common condition that impacts reading ability. Identifying affected brain networks has been hampered by limited sample sizes of imaging case-control studies. We focused instead on brain structural correlates of genetic disposition to dyslexia in large-scale population data. In over 30,000 adults (UK Biobank), higher polygenic disposition to dyslexia was associated with lower head and brain size, and especially reduced volume and/or altered fiber density in networks involved in motor control, language and vision. However, individual genetic variants disposing to dyslexia often had quite distinct patterns of association with brain structural features. Independent component analysis applied to brain-wide association maps for thousands of dyslexia-disposing genetic variants revealed multiple impact modes on the brain, that corresponded to anatomically distinct areas with their own genomic profiles of association. Polygenic scores for dyslexia-related cognitive and educational measures, as well as attention-deficit/hyperactivity disorder, showed similarities to dyslexia polygenic disposition in terms of brain-wide associations, with microstructure of the internal capsule consistently implicated. In contrast, lower volume of the primary motor cortex was only associated with higher dyslexia polygenic disposition among all traits. These findings robustly reveal heterogeneous neurobiological aspects of dyslexia genetic disposition, and whether they are shared or unique with respect to other genetically correlated traits.
Neuronal alpha-Synuclein Disease Integrated Staging System performance in PPMI, PASADENA, and SPARK baseline cohorts
Authors: Dam Tien , Pagano Gennaro , Brumm Michael C , Gochanour Caroline , Poston Kathleen L , Weintraub Daniel , Chahine Lana M. , Coffey Christopher , Tanner Caroline M. , Kopil Catherine M. , Xiao Yuge , Chowdhury Sohini , Concha-Marambio Luis , DiBiaso Peter , Foroud Tatiana , Frasier Mark , Jennings Danna , Kieburtz Karl , Merchant Kalpana , Mollenhauer Brit , Montine Thomas J , Nudelman Kelly , Seibyl John , Sherer Todd , Singleton Andrew , Stephenson Diane , Stern Matthew , Soto Claudio , Tolosa Eduardo , Siderowf Andrew , Dunn Billy , Simuni Tanya , Marek Kenneth ,   the Parkinson’s Progression Markers Initiative
Published: February 2024

ABSTRACTThe Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson’s disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1,741 participants had SAA data and of these 1,030 (59%) were S+ consistent with NSD. Among sporadic PD, 683/736 (93%) were NSD, and the distribution for Stages 2B, 3, and 4 was 25%, 63%, and 9%, respectively. Median (95% CI) time to developing a clinically meaningful outcome was 8.3 (6.2, 10.1), 5.9 (4.1, 6.0), and 2.4 (1.0, 4.0) years for baseline stage 2B, 3, and 4, respectively.We propose pilot biologic and clinical anchors for NSD-ISS. Our results highlight the baseline heterogeneity of individuals currently defined as early PD. Baseline stage predicts time to progression to clinically meaningful milestones. Further research on validation of the anchors in longitudinal cohorts is necessary.
Outdoor Nighttime Light Exposure (Light Pollution) is Associated with Alzheimer’s Disease
Authors: Voigt Robin M , Ouyang Bichun , Keshavarzian Ali 
Published: February 2024

AbstractAlzheimer’s disease (AD) prevalence has increased in the last century which can be attributed to increased lifespan, but environment is also important. This study evaluated the relationship between outdoor nighttime light exposure and AD prevalence in the United States. Higher outdoor nighttime light was associated with higher prevalence of AD. While atrial fibrillation, diabetes, hyperlipidemia, hypertension, and stroke were associated more strongly with AD prevalence than nighttime light intensity, nighttime light was more strongly associated with AD prevalence than alcohol abuse, chronic kidney disease, depression, heart failure, and obesity. Startlingly, nighttime light exposure more strongly associated with AD prevalence in those under the age of 65 than any other disease factor examined. These data indicate a need to investigate how nighttime light exposure influences AD pathogenesis.One-Sentence SummaryThere is a positive association between Alzheimer’s disease prevalence and average outdoor nighttime light intensity in the United States.
Distinct hippocampal mechanisms support concept formation and updating
Authors: Mack Michael L. , Love Bradley C. , Preston Alison R. 
Published: February 2024

AbstractLearning systems must constantly decide whether to create new representations or update existing ones. For example, a child learning that a bat is a mammal and not a bird would be best served by creating a new representation, whereas updating may be best when encountering a second similar bat. Characterizing the neural dynamics that underlie these complementary memory operations requires identifying the exact moments when each operation occurs. We address this challenge by interrogating fMRI brain activation with a computational learning model that predicts trial-by-trial when memories are created versus updated. We found distinct neural engagement in anterior hippocampus and ventral striatum for model-predicted memory create and update events during early learning. Notably, the degree of this effect in hippocampus, but not ventral striatum, significantly related to learning outcome. Hippocampus additionally showed distinct patterns of functional coactivation with ventromedial prefrontal cortex and angular gyrus during memory creation and premotor cortex during memory updating. These findings suggest that complementary memory functions, as formalized in computational learning models, underlie the rapid formation of novel conceptual knowledge, with the hippocampus and its interactions with frontoparietal circuits playing a crucial role in successful learning.Significance statementHow do we reconcile new experiences with existing knowledge? Prominent theories suggest that novel information is either captured by creating new memories or leveraged to update existing memories, yet empirical support of how these distinct memory operations unfold during learning is limited. Here, we combine computational modeling of human learning behaviour with functional neuroimaging to identify moments of memory formation and updating and characterize their neural signatures. We find that both hippocampus and ventral striatum are distinctly engaged when memories are created versus updated; however, it is only hippocampus activation that is associated with learning outcomes. Our findings motivate a key theoretical revision that positions hippocampus is a key player in building organized memories from the earliest moments of learning.
Hippocampal area CA2 activity supports social investigation following an acute social stress
Authors: Radzicki Daniel , McCann Katharine E. , Alexander Georgia M. , Dudek Serena M. 
Published: February 2024

AbstractNeuronal activity in the hippocampus is critical for many types of memory acquisition and retrieval and influences an animal’s response to stress. Moreover, the molecularly distinct principal neurons of hippocampal area CA2 are required for social recognition memory and aggression in mice. To interrogate the effects of stress on CA2-dependent behaviors, we chemogenetically manipulated neuronal activityin vivoduring an acute, socially derived stressor and tested whether memory for the defeat was influenced. One day after an acute social defeat (aSD), defeated mice spent significantly less time investigating another mouse when compared to non-defeated control mice. We found that this avoidant phenotype persisted for up to one month following a single defeat encounter. When CA2 pyramidal neuron activity was inhibited with Gi-DREADD receptors during the defeat, subject mice exhibited a significantly higher amount of social avoidance one day later when compared to defeated littermates not expressing DREADDs. Moreover, CA2 inhibition during defeat caused a reduction in submissive defense behaviors in response to aggression.In vitroelectrophysiology and tracing experiments revealed a circuit wherein CA2 neurons connect to caudal CA1 projection neurons that, in turn, project to corticolimbic regions including the anterior cingulate cortex. Finally, socially avoidant, defeated mice exhibited significant reductions in cFos expression in caudal hippocampal and limbic brain areas during a social investigation task 24 hours after aSD. Taken together, these results indicate that CA2 neuronal activity is required to support behavioral resilience following an acute social stressor and that submissive defensive behavior during the defeat (vs. fleeing) is a predictor of future resilience to social stress. Furthermore, CA2 preferentially targets a population of caudal CA1 projection neurons that contact cortical brain regions where activity is modulated by an acute social stressor.
Resilience and Charge-Dependent Fibrillation of Functional Amyloids: Interactions ofPseudomonasBiofilm-Associated FapB and FapC
Authors: Golan Nimrod , Parizat Amit , Tabachnikov Orly , Barnea Eilon , Olsen William P. , Otzen Daniel E. , Landau Meytal 
Published: February 2024

AbstractFapC and FapB are biofilm-associated amyloids involved in the virulence ofPseudomonasand other bacteria. We herein demonstrate their exceptional thermal and chemical resilience, suggesting that biofilm structures might withstand standard sterilization, thereby contributing to the persistence ofP. aeruginosainfections. Our findings also underscore the impact of environmental factors on Fap proteins, suggesting that orthologs in differentPseudomonasstrains adapt to specific environments and roles. Challenging previous assumptions about a simple nucleation role for FapB in promoting FapC aggregation, the study shows a significant influence of FapC on FapB aggregation. The interaction between FapB and FapC is intricate: FapB stabilizes FapC fibrils, while FapC slows down FapB fibrillation but can still serve as a cross-seeding template. This complex interplay is key to understanding their roles in bacterial biofilms. Furthermore, the study highlights distinct differences between Fap andE. coli’s curli CsgA amyloid, where CsgB assumes a simple unidirectional role in nucleating CsgA fibrillation, emphasizing the importance of a comprehensive understanding of various amyloid systems. This knowledge is vital for developing effective intervention strategies against bacterial infections and leveraging the unique properties of these amyloids in technological applications such as novel bio-nanomaterials or protective coatings.
Mapping protein-metabolite interactions inE. coliby integrating chromatographic techniques and co-fractionation mass spectrometry
Authors: Wagner Mateusz , Kang Jieun , Mercado Catherine , Thirumalaikumar Venkatesh P. , Gorka Michal , Zillmer Hanne , Guo Jingzhe , Minen Romina I. , Plecki Caroline F. , Dehesh Katayoon , Schroeder Frank C. , Walther Dirk , Skirycz Aleksandra 
Published: February 2024

AbstractIn our pursuit of understanding the protein-metabolite interactome, we introduced PROMIS, a co-fractionation mass spectrometry (CF-MS) technique focusing on biosynthetic and regulatory processes. However, the challenge lies in distinguishing true interactors from coincidental co-elution when a metabolite co-fractionates with numerous proteins. To address this, we integrated two chromatographic techniques— size exclusion and ion exchange—to enhance the mapping of protein-metabolite interactions (PMIs) inEscherichia coli. This integration aims to refine the PMI network by considering size and charge characteristics, resulting in 994 interactions involving 51 metabolites and 465 proteins. The PMI network is enriched for known and predicted interactions validating our approach’s efficacy. Furthermore, the analysis of protein targets for different metabolites revealed novel functional insights, such as the connection between proteinogenic dipeptides and fatty acid biosynthesis. Notably, we uncovered an inhibitory interaction between the riboflavin degradation product lumichrome and orotate phosphoribosyltransferase (PyrE), a key enzyme inde novopyrimidine synthesis. Lumichrome supplementation mimicked the biofilm formation inhibition observed in aΔpyrEmutant strain, suggesting lumichrome role in integrating pyrimidine and riboflavin metabolism with quorum sensing and biofilm formation. In summary, our integrated chromatographic approach significantly advances PMI mapping, offering novel insights into functional associations and potential regulatory mechanisms inE. coli.
Covering the bases: population genomic structure ofLemna minorand the cryptic speciesL. japonicain Switzerland
Authors: Schmid Marc W. , Moradi Aboubakr , Leigh Deborah M. , Schuman Meredith C. , van Moorsel Sofia J. 
Published: February 2024

AbstractDuckweeds, including the common duckweedLemna minor, are increasingly used to test eco-evolutionary theories. Yet, despite its popularity and near-global distribution, the understanding of its population structure (and genetic variation therein) is still limited. It is essential that this is resolved, because of the impact genetic diversity has on experimental responses and scientific understanding.Through whole-genome sequencing, we assessed the genetic diversity and population genomic structure of 23 naturalLemnaspp. populations from their natural range in Switzerland. We used two distinct analytical approaches, a reference-free kmer approach and the classical reference-based one. Two genetic clusters were identified across the described species distribution ofL. minor, surprisingly corresponding to species-level divisions. The first cluster contained the targetedL. minorindividuals and the second contained individuals from a cryptic species:Lemna japonica. Within theL. minorcluster, we identified a well-defined population structure with little intra-population genetic diversity (i.e. within ponds) but high inter-population diversity (i.e. between ponds). InL. japonica, the population structure was significantly weaker and genetic variation between a subset of populations was as low as within populations.This study revealed thatLemna japonicais more widespread than previously thought. Our findings signify that thorough genotype-to-phenotype analyses are needed in duckweed experimental ecology and evolution.
Neural dynamics of shifting attention between perception and working-memory contents
Authors: Gresch Daniela , Boettcher Sage E.P. , Gohil Chetan , van Ede Freek , Nobre Anna C. 
Published: February 2024

AbstractIn everyday tasks, our focus of attention shifts seamlessly between contents in the sensory environment and internal memory representations. Yet, research has mainly considered external and internal attention in isolation. We used magnetoencephalography to compare the neural dynamics of shifting attention to visual contents within vs. between the external and internal domains. Participants performed a combined perception and working-memory task in which two sequential cues guided attention to upcoming (external) or memorised (internal) sensory information. Critically, the second cue could redirect attention to visual content within the same or alternative domain as the first cue. Multivariate decoding unveiled distinct patterns of human brain activity when shifting attention within vs. between domains. Brain activity distinguishing within- from between-domain shifts was broadly distributed and highly dynamic. Intriguingly, crossing domains did not invoke an additional stage prior to shifting. Alpha lateralisation, a canonical marker of shifting spatial attention, showed no delay when cues redirected attention to the same vs. alternative domain. Instead, evidence suggested that neural states associated with a given domain linger and influence subsequent shifts of attention within vs. between domains. Our findings provide the first insights into the neural dynamics that govern attentional shifts between perception and working memory.Significance StatementDuring almost every natural behaviour, our attention regularly shifts between sensory and memory contents. Although the systems and mechanisms of attentional control and modulation within the external and internal domains have been heavily studied in isolation, how attention crosses between these domains remains uncharted territory. Here, we provide the first study to investigate brain dynamics associated with shifting attention between contents in the sensory environment and memory representations. Using a novel experimental design, we isolated the patterns and dynamics of brain activity associated with shifting attention within vs. between the external and internal domains. Our findings reveal early, dynamic, and distributed patterns of activity that distinguish within- from between-domain shifts, offering fascinating initial insights, and opening new questions for investigation.
Toxicity of the model protein 3×GFP arises from degradation overload, not from aggregate formation
Authors: Namba Shotaro , Moriya Hisao 
Published: February 2024

AbstractWhile protein aggregation can cause cytotoxicity, it also forms to mitigate cytotoxicity from misfolded proteins, though the nature of these contrasting aggregates remains unclear. We previously found that overproduction (op) of a three green fluorescent protein linked protein (3×GFP) in yeast cells induces giant aggregates, and is detrimental to growth. Here, we investigated the mechanism of growth inhibition by 3×GFP-op using non-aggregative 3×MOX-op as a control. The 3×GFP aggregates were induced by misfolding, and 3×GFP-op had higher cytotoxicity than 3×MOX-op because it perturbs the ubiquitin-proteasome system. Static aggregates formed by 3×GFP-op dynamically trapped Hsp70, causing the heat shock response. Systematic analysis of mutants deficient in the protein quality control suggested that 3×GFP-op did not cause critical Hsp70 depletion and that the formation of aggregates functioned in the direction of mitigating toxicity. Artificial trapping of essential cell cycle regulators into 3×GFP aggregates caused abnormalities in the cell cycle. In conclusion, the formation of the giant 3×GFP aggregates itself is not cytotoxic, as it does not entrap and deplete essential proteins. Rather, it is productive, inducing the heat shock response while preventing an overload to the degradation system.
Genome sequence of the ornamental plantDigitalis purpureareveals the molecular basis of flower color and morphology variation
Authors: Horz Jakob Maximilian , Wolff Katharina , Friedhoff Ronja , Pucker Boas 
Published: February 2024

AbstractDigitalis purpurea(foxglove) is a widely distributed ornamental plant and the producer of the biomedical compound digoxin. Here, we present a long read sequencing-based genome sequence of a red floweringD. purpureaplant and a corresponding prediction of gene models. The high assembly continuity is indicated by the N50 of 4.3 Mbp and the completeness is supported by discovery of about 96% complete BUSCO genes. This genomic resource paves the way for an in-depth investigation of the flower pigmentation ofD. purpurea. Structural genes of the anthocyanin biosynthesis and the corresponding transcriptional regulators were identified. The comparison of red and white flowering plants revealed a large insertion in the anthocyanidin synthase gene in white flowering plants that most likely renders this gene non-functional and could explain the loss of anthocyanin pigmentation. In addition, the anthocyanin biosynthesis activatorMYB5shows a 18 bp deletion in white flowering plants that results in the loss of 6 amino acids in the protein. Furthermore, we found a large insertion in theDpTFL1/CENgene to be responsible for the development of large terminal flowers.