bluuebunny/crossref_metadata_2025_split huggingface dataset:
Making Sense of Neural Networks in the Light of Evolutionary Optimization
Authors: Sinitskiy Anton V. 
Published: November 2023

AbstractTo what extent can evolution be considered as the sole first principle that explains all properties of nervous systems? This paper proposes an innovative, mathematically rigorous perspective on understanding nervous systems from an evolutionary perspective, leveraging methods of nonequilibrium statistical physics. This approach allows for modeling an exhaustive evolutionary optimization of nervous systems irrespective of any specific molecular and cellular mechanisms, approximate neuronal models or evolutionary history events. This novel method may shed light on key properties of biological neural networks and may also have potential relevance for understanding artificial neural networks.
A multistage, dual voxel study of glutamate in the anterior cingulate cortex in schizophrenia supports a primary pyramidal dysfunction model of disorganization
Authors: Fan Lejia , Zhang Zhenmei , Ma Xiaoqian , Liang Liangbing , Wang Yujue , Yuan liu , Ouyang Lijun , Li Zongchang , Chen Xiaogang , He Ying , Palaniyappan Lena 
Published: November 2023

AbstractBackgroundSchizophrenia is an illness where glutamatergic dysfunction in the anterior cingulate cortex (ACC) has been long suspected; Recent in vivo evidence (Adams et al. 2022) has implicated pyramidal dysfunction (reduced glutamate tone) as the primary pathophysiology contributing to subtle features, with a secondary disinhibition effect (higher glutamate tone) resulting in the later emergence of prominent clinical symptoms. We investigate if genetic high risk (GHR) for schizophrenia reduces glutamatergic tone in ACC when compared to the states of clinical high risk (CHR) and first episode schizophrenia (FES) where symptoms are already prominent.MethodsWe recruited 302 individuals across multiple stages of psychosis (CHR, n=63; GHR, n=76; FES, n=96) and healthy controls (n=67) and obtained proton magnetic resonance spectroscopy of glutamate from perigenual ACC (pACC) and dorsal ACC (dACC) using 3-Tesla scanner.ResultsGHR had lower Glu compared to CHR while CHR had higher Glu compared to FES and HC. Higher disorganization burden, but not any other symptom domain, was predicted by lower levels of Glu in the GHR group (dACC and pACC) and in the CHR group (pACC only).ConclusionsThe reduction in glutamatergic tone in GHR supports the case for a pyramidal dysfunction contributing to higher disorganization, indicating disorganization to be the core domain in the pathophysiology of schizophrenia. Higher glutamate (likely due to disinhibition) is apparent when psychotic symptoms are raising to be prominent (CHR), though at the full-blown stage of psychosis, the relationship between glutamate and symptoms ceases to be a simple linear one.
The differing prevalences of propionate and butyrate-producing bacteria in the human gut microbiota
Authors: Christensen Rebecca , Wang Yu Han Daisy , Arnoldini Markus , Cremer Jonas 
Published: November 2023

AbstractPropionate and butyrate are major fermentation products released during the anaerobic growth of bacteria in the large intestine with strong implications on host health. While the different metabolic pathways leading to the release of these products are biochemically well characterized, less is known about their relative abundances across hosts and conditions. Here, we introduce a bioinformatics pipeline which connects pathway analyses, gene identification via sequence homology, and the screening of metagenomic samples to systematically identify the abundances of propionate producing pathways across individuals and in relation to butyrate producing pathways. We found that on average 36% of all genomes of a gut microbiota carried propionate producing pathways with the sodium-pumping succinate pathway being the most prevalent. This pathway abundance was anti-correlated to the abundance of butyrate pathways and greatly depended on host physiology. For example, propionate pathway abundance varied strongly among infants with a substantially higher abundance in vaginally than C-section born infants, increased in early adulthood, and decreased again with higher ages. This is in strong contrast to the known variation of butyrate pathway abundance, which is close to zero in infants and steadily increases with age. These results highlight the contrasting prevalence of both fermentation products at the individual level with shifts in microbiota composition resulting in strong consequences on the amount of butyrate and propionate available to the host.
Central corneal thickness and the risk of primary open-angle glaucoma: a Mendelian randomization mediation analysis
Authors: Katsimpris Andreas , Baumeister Sebastian-Edgar , Baurecht Hansjörg , Tatham Andrew J , Nolde Michael 
Published: November 2023

AbstractThe association of central corneal thickness (CCT) with primary open-angle glaucoma (POAG) remains uncertain. Although, several observational studies assessing this relationship, have reported an inverse association between CCT and POAG, this could be the result of collider bias. In this study, we leveraged human genetic data to assess through Mendelian randomization (MR) the effect of CCT on POAG risk, and whether this effect is mediated by intraocular pressure (IOP) changes. We used 24 single-nucleotide polymorphisms (SNPs) associated with CCT (P-value < 5×10-8) from a genome-wide association study (GWAS) (N = 17,803) provided by the International Glaucoma Genetics Consortium and 53 SNPs associated with IOP (P-value < 5×10-8) from a GWAS of UK Biobank (UKBB) (N = 97,653). We related these instruments with POAG using a GWAS meta-analysis of 8,283 POAG cases and 753,827 controls from UKBB and FinnGen. MR analysis suggested a positive association between CCT and POAG (odds ratio of POAG per 50μm increase in CCT: 1.38; 95% confidence interval: 1.18 to 1.61; p-value < 0.01). MR mediation analysis showed that 28.4% of the total effect of CCT on POAG risk was mediated through changes in IOP. The primary results were consistent with estimates of pleiotropy-robust MR methods. In conclusion, contrary to most observational studies, our results support a positive effect of CCT on the risk of POAG.
Brain network connectivity underlying remission in early psychosis: a whole brain model approach
Authors: Mana Ludovica , López-González Ane , Alemán-Gómez Yasser , Baumann Philipp S. , Jenni Raoul , Alameda Luis , Abrahamyan Empson Lilith , Klauser Paul , Conus Philippe , Hagmann Patric , Vila-Vidal Manel , Deco Gustavo 
Published: November 2023

ABSTRACTBackgroundAlterations in brain connectivity occur early during psychosis and underlie the clinical manifestations of the illness as well as patient functioning and outcome. After a first episode of psychosis (FEP), different trajectories are possible and best described by the clinical-staging model that places the patient along a continuum of conditions: from non-remitting chronic symptoms to full-remission, often followed by relapses. However, little is known about the differences in brain connectivity that could underlie these differences in clinical outcome.MethodsIn this study, we included resting-state fMRI and DSI data from a cohort of 128 healthy controls (HC) and 88 patients with early psychosis (EP) stratified based on their ability to remit after the FEP. In particular we focused on differences between stage IIIb,c remitting-relapsing (EP3R) and stage IIIa non-remitting (EP3NR) patients. We investigated alterations in resting-state functional connectivity (FC), and combined information derived from fMRI and DSI into generative whole-brain models of each condition to explore the underlying mechanisms.ResultsOpposite alterations in FC could be found in patients as compared to HC, depending on their stage. In non-remitting patients (EP3NR), we observed a reduction of FC, aligned with the reduced structural connectivity found in previous studies, while remitting-relapsing patients (EP3R) showed increased FC, potentially indicating a relevant compensatory mechanism. By means of a whole-brain network model, we showed that in HC a subset of areas is characterized by increased stability to prevent an oversynchronisation of the network, while in EP3 patients such property is lost. This alteration was more relevant in the EP3R than in EP3NR patients, probably indicating a compensatory response to the reduced effective conductivity (global coupling) highlighted by the model in both EP3 conditions as compared to controls.ConclusionsThese findings highlight the significance of categorizing patients into subgroups based on the progression of their psychotic disorders, providing insights into the factors contributing to heterogeneity in functional alterations. They enhance our understanding of the interplay between structural and functional properties, shedding light on the mechanisms of psychosis emergence, remission and progression, with potential implications for future therapeutic advancements.
Enrichable consortia of microbial symbionts degrade macroalgal polysaccharides inKyphosusfish
Authors: Oliver Aaron , Podell Sheila , Kelly Linda Wegley , Sparagon Wesley J. , Plominsky Alvaro M. , Nelson Robert S. , Laurens Lieve M. L. , Augyte Simona , Sims Neil A. , Nelson Craig E. , Allen Eric E. 
Published: November 2023

AbstractCoastal herbivorous fishes consume macroalgae, which is then degraded by microbes along their digestive tract. However, there is scarce foundational genomic work on the microbiota that perform this degradation. This study explores the potential ofKyphosusgastrointestinal microbial symbionts to collaboratively degrade and ferment polysaccharides from red, green, and brown macroalgae throughin silicostudy of carbohydrate-active enzyme and sulfatase sequences. Recovery of metagenome-assembled genomes (MAGs) reveals differences in enzymatic capabilities between the major microbial taxa inKyphosusguts. The most versatile of the recovered MAGs were from the Bacteroidota phylum, whose MAGs house enzymes able to decompose a variety of algal polysaccharides. Unique enzymes and predicted degradative capacities of genomes from theBacillota(genusVallitalea) andVerrucomicrobiota(order Kiritimatiellales) suggest the potential for microbial transfer between marine sediment andKyphosusdigestive tracts. Few genomes contain the required enzymes to fully degrade any complex sulfated algal polysaccharide alone. The distribution of suitable enzymes between MAGs originating from different taxa, along with the widespread detection of signal peptides in candidate enzymes, is consistent with cooperative extracellular degradation of these carbohydrates. This study leverages genomic evidence to reveal an untapped diversity at the enzyme and strain level amongKyphosussymbionts and their contributions to macroalgae decomposition. Bioreactor enrichments provide a genomic foundation for degradative and fermentative processes central to translating the knowledge gained from this system to the aquaculture and bioenergy sectors.ImportanceSeaweed has long been considered a promising source of sustainable biomass for bioenergy and aquaculture feed, but scalable industrial methods for decomposing terrestrial compounds can struggle to break down seaweed polysaccharides efficiently due to their unique sulfated structures. Fish of the genusKyphosusfeed on seaweed by leveraging gastrointestinal bacteria to degrade algal polysaccharides into simple sugars. This study is the first to build genomes for these gastrointestinal bacteria to enhance our understanding of herbivorous fish digestion and fermentation of algal sugars. Investigations at the gene level identifyKyphosusguts as an untapped source of seaweed-degrading enzymes ripe for further characterization. These discoveries set the stage for future work incorporating marine enzymes and microbial communities in the industrial degradation of algal polysaccharides.
The human voice aligns with whole-body kinetics
Authors: Pouw Wim , Raphael Werner , Burchardt Lara S. , Selen Luc P.J. 
Published: November 2023

AbstractHumans often vocalize while concurrently gesturing with their hands. Fluctuations in the intensity and tone of the voice have been shown to synchronize with gestural upper limb movement. This research provides direct evidence that interactions between arm movements and postural muscle activity cause these voicing fluctuations. We show that specific muscles (e.g., pectoralis major, erector spinae), associated with upper limb movement and their postural anticipations, are especially likely to interact with the voice. Adding mass to the upper limb increased this interaction. Ground-reaction forces were also found to relate to postural muscles, and these measurements also directly covaried with fluctuations in the voice during some movement conditions. These results show that the voice co-patterns with whole-body kinetics, i.e. forces. We thereby go beyond kinematic analyses in studying interactions between gesturing and vocalization, invoking several implications for biomechanical modeling. We conclude that human voicing has evolved in a dynamical interaction with the whole-body motor system.
GPRC5A regulates keratinocyte adhesion and migration through nuclear translocation of its C-terminus region
Authors: Chanteloube Sarah , Ya Choua , Provost Gabrielle Le , Berthier Aurore , Dieryckx Cindy , Goff Sandrine Vadon-Le , Nadal Florence , Fromy Bérengère , Debret Romain 
Published: November 2023

ABSTRACTG-Protein Coupled Receptor, Class C, Group 5, Member A (GPRC5A) is well-documented in lung and various epithelial cancers. However, its role in the skin remains unexplored. In this study, we investigated the function of this receptor in skin biology and our research demonstrated that its expression responds to mechanical substrate changes in human primary keratinocytes. Furthermore, we observed GPRC5A reinduction during wound healing at the leading edges in anex vivoburn model, coinciding with the translocation of its C-terminal region into the nucleus. We identified the cleavage site of GPRC5A by N-TAILS analysis, and cathepsin G was characterized as responsible for proteolysis in cultured cells.To gain a deeper understanding of GPRC5A’s role in keratinocyte, we performed GPRC5A knockdown in N/TERT-1 cells using short-hairpin RNA. Our findings strongly suggest a close association between GPRC5A and adhesion regulation pathways, but also demonstrate that GPRC5AKDenhanced cell adhesion while reducing cell migration and differentiation. Importantly, these effects were reversed by adding a recombinant polypeptide mimicking the C-terminal region of GPRC5A.Overall, our study reveals an unexpected role of GPRC5A in regulating keratinocyte behavior, implicating its C-terminal region translocation into the nucleus. These results open up interesting strategic pathways for wound healing.
DNA methylation by CcrM contributes to genome maintenance in theAgrobacterium tumefaciensplant pathogen
Authors: Martin Sandra , Fournes Florian , Ambrosini Giovanna , Iseli Christian , Bojkowska Karolina , Marquis Julien , Guex Nicolas , Collier Justine 
Published: November 2023

ABSTRACTThecellcycle-regulated DNAmethyltransferase CcrM is conserved in mostAlphaproteobacteria, but its role in bacteria with complex or multicentric genomes remains unexplored. Here, we compare the methylome, the transcriptome and the phenotypes of wild-type and CcrM-depletedAgrobacterium tumefacienscells with a dicentric genome with two essential replication origins. We find that DNA methylation has a pleiotropic impact on motility, biofilm formation and viability. Remarkably, CcrM promotes the expression of therepABCCh2operon, encoding proteins required for replication initiation/partitioning atori2, and inhibitsgcrA, encoding a conservedglobalcell cycle regulator. Imagingori1andori2in live cells, we show that replication fromori2is often delayed in cells with a hypo-methylated genome, whileori2over-initiates in cells with a hyper-methylated genome. We thus propose that methylation by CcrM stimulates RepABC-dependent chromosomal origins, uncovering a novel and original connection between CcrM-dependent DNA methylation and genome maintenance in anAlphaproteobacterialpathogen.
Allosteric Competition and Inhibition in AMPA Receptors
Authors: Hale W. Dylan , Romero Alejandra Montaño , Gonzalez Cuauhtemoc U. , Jayaraman Vasanthi , Lau Albert Y. , Huganir Richard L. , Twomey Edward C. 
Published: November 2023

AbstractExcitatory neurotransmission is principally mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). Dysregulation of AMPARs is the cause of many neurological disorders and how therapeutic candidates such as negative allosteric modulators inhibit AMPARs is unclear. Here, we show that non-competitive inhibition desensitizes AMPARs to activation and prevents positive allosteric modulation. We dissected the noncompetitive inhibition mechanism of action by capturing AMPARs bound to glutamate and the prototypical negative allosteric modulator, GYKI-52466, with cryo-electron microscopy. Noncompetitive inhibition by GYKI-52466, which binds in the transmembrane collar region surrounding the ion channel, negatively modulates AMPARs by decoupling glutamate binding in the ligand binding domain from the ion channel. Furthermore, during allosteric competition between negative and positive modulators, negative allosteric modulation by GKYI-52466 outcompetes positive allosteric modulators to control AMPAR function. Our data provide a new framework for understanding allostery of AMPARs and foundations for rational design of therapeutics targeting AMPARs in neurological diseases.
Competition for shared resources increases dependence on initial population size during coalescence of gut microbial communities
Authors: Goldman Doran A. , Xue Katherine S. , Parrott Autumn B. , Jeeda Rashi R. , Franzese Lauryn R. , Lopez Jaime G. , Vila Jean C. C. , Petrov Dmitri A. , Good Benjamin H. , Relman David A. , Huang Kerwyn Casey 
Published: November 2023

AbstractThe long-term success of introduced populations depends on their initial size and ability to compete against existing residents, but it remains unclear how these factors collectively shape colonization. Here, we investigate how initial population (propagule) size and resource competition interact during community coalescence by systematically mixing eight pairs ofin vitromicrobial communities at ratios that vary over six orders of magnitude, and we compare our results to a neutral ecological model. Although the composition of the resulting co-cultures deviated substantially from neutral expectations, each co-culture contained species whose relative abundance depended on propagule size even after ∼40 generations of growth. Using a consumer-resource model, we show that this dose-dependent colonization can arise when resident and introduced species have high niche overlap and consume shared resources at similar rates. This model predicts that propagule size will have larger, longer-lasting effects in diverse communities in which niche overlap is higher, and we experimentally confirm that strain isolates show stronger dose dependence when introduced into diverse communities than in pairwise co-culture. This work shows how neutral-like colonization dynamics can emerge from non-neutral resource competition and have lasting effects on the outcomes of community coalescence.
Coevolution-induced stabilizing and destabilizing selection shapes species richness in clade co-diversification
Authors: Zeng Yichao , Hembry David H. 
Published: November 2023

ABSTRACTCoevolution can occur as a result of species interactions. However, it remains unclear how coevolutionary processes translate into the accumulation of species richness over macroevolutionary timescales. Assuming speciation occurs in a metacommunity as a result of genetic differentiation across communities due to dispersal limitation, we examine the effects of coevolution-induced stabilizing and destabilizing selection of a single quantitative trait on species diversification. We propose and test two hypotheses. (1) Stabilizing selection within communities enhances species diversification through strengthened dispersal limitation. (2) Destabilizing selection within communities impedes species diversification through weakened dispersal limitation. Here, we simulate clade co-diversification using an individual-based model, considering scenarios where phenotypic evolution is shaped by neutral dynamics, mutualistic coevolution, or antagonistic coevolution, where coevolution operates through trait matching or trait difference, and where the strength of coevolutionary selection is symmetrical or asymmetrical. Our assumption that interactions occur between an independent party (whose individuals can establish or persist in a community independently, e.g. hosts) and a dependent party (whose individuals cannot establish or persist in a community without the independent party, e.g. parasites or obligate mutualists) yields two contrasting results. Stabilizing selection within communities enhances species diversification in the dependent clade but not in the independent clade. Conversely, destabilizing selection within communities impedes species diversification in the independent clade but not in the dependent clade. These results are partially corroborated by empirical dispersal data, suggesting that these mechanisms might explain the diversification of some of the most species-rich clades in the Tree of Life.
Assessment of photosynthetic activity in dense microalgae cultures using oxygen production
Authors: Vera-Vives Antoni Mateu , Michelberger Tim , Morosinotto Tomas , Perin Giorgio 
Published: November 2023

AbstractMicroalgae are photosynthetic microorganisms playing a pivotal role in primary production in aquatic ecosystems, sustaining the entry of carbon in the biosphere. Microalgae have also been recognized as sustainable source of biomass to complement crops. For this objective they are cultivated in photobioreactors or ponds at high cell density to maximize biomass productivity and lower the cost of downstream processes.Photosynthesis depends on light availability, that is often not constant over time. In nature, sunlight fluctuates over diurnal cycles and weather conditions. In high-density microalgae cultures of photobioreactors outdoors, on top of natural variations, microalgae are subjected to further complexity in light exposure. Because of the high-density cells experience self-shading effects that heavily limit light availability in most of the mass culture volume. This limitation strongly affects biomass productivity of industrial microalgae cultivation plants with important implication on economic feasibility.Understanding how photosynthesis responds to cell density is informative to assess functionality in the inhomogeneous light environment of industrial photobioreactors. In this work we exploited a high-sensitivity Clark electrode to measure microalgae photosynthesis and compare cultures with different densities, usingNannochloropsisas model organism. We observed that cell density has a substantial impact on photosynthetic activity, and demonstrated the reduction of the cell’s light-absorption capacity by genetic modification is a valuable strategy to increase photosynthetic functionality of dense microalgae cultures.HighlightsMicroalgae biomass is a promising alternative to crops.The impact of cultivation at scale on photosynthesis is still under-investigated.The Photosynthesis-Irradiance (PI) relationship is informative.High-sensitivity oxygen measurements for PI investigation was validated.The effect of cell density on PI was studied inNannochloropsispale mutants.