bluuebunny/crossref_metadata_2025_split huggingface dataset:
HuD (ELAVL4) gain-of-function impairs neuromuscular junctions and induces apoptosis inin vitroandin vivomodels of amyotrophic lateral sclerosis
Authors: Silvestri Beatrice , Mochi Michela , Mawrie Darilang , de Turris Valeria , Colantoni Alessio , Borhy Beatrice , Medici Margherita , Anderson Eric Nathaniel , Garone Maria Giovanna , Zammerilla Christopher Patrick , Pandey Udai Bhan , Rosa Alessandro 
Published: August 2023

ABSTRACTEarly defects at the neuromuscular junction (NMJ) are among the first hallmarks of the progressive neurodegenerative disease amyotrophic lateral sclerosis (ALS). According to the “dying back” hypothesis, disruption of the NMJ not only precedes, but is also a trigger for the subsequent degeneration of the motoneuron in both sporadic and familial ALS, including ALS caused by the severeFUSpathogenic variant P525L. However, the mechanisms linking genetic and environmental factors to NMJ defects remain elusive. By taking advantage of co-cultures of motoneurons and skeletal muscle derived from human induced pluripotent stem cells (iPSCs), we show that the neural RNA binding protein HuD (ELAVL4) may underlie NMJ defects and apoptosis in FUS-ALS. HuD overexpression in motoneurons phenocopies the severe FUSP525Lmutation, while HuD knockdown in FUSP525Lco-cultures produces phenotypic rescue. We validated these findingsin vivoin aDrosophilaFUS-ALS model. Neuronal-restricted overexpression of the HuD-related gene,elav, producesper sea motor phenotype, while neuronal-restrictedelavknockdown significantly rescues motor dysfunction caused by FUS. Finally, we show that HuD levels increase upon oxidative stress in human motoneurons and in sporadic ALS patients with an oxidative stress signature. On these bases, we propose HuD as an important player downstream of FUS mutation in familial ALS, with potential implications for sporadic ALS related to oxidative stress.
The loss-of-function of SOCS2 increases the inflammatory response toStaphylococcus aureusinfection
Authors: Guzylack-Piriou Laurence , Gausseres Blandine , Tasca Christian , Hassel Chervin , Tabouret Guillaume , Foucras Gilles 
Published: August 2023

AbstractThe involvement of suppressor of cytokine signaling (SOCS)2 in anti-infective bacterial immunity remains largely undetermined compared to other members of the SOCS family. We developed a mouse model expressing the loss of function R96C SOCS2 point mutation to characterize the response of macrophages toStaphylococcus aureusand its TLR-ligand derivatives. The model resumes observations of gigantism done in Socs2-/- mice. Stimulation of bone-marrow-derived macrophages with various TLR-2 ligands showed upregulation of the pro-inflammatory cytokines IL-6 and TNF-α production only in cytokine-modulating environments that promote SOCS2 expression. Using this model, we showed that SOCS2 protein reduces STAT-5 phosphorylation in a short time frame upon TLR engagement. When SOCS2 is ablated, neutrophil and F4/80intLy6C+inflammatory macrophage recruitment, as well as IFN-γ and IL-10 concentrations are significantly increased uponS. aureusperitoneal infection. By lowering the pro-inflammatory environment, SOCS2 favors better healing during a systemic infection caused byS. aureus.
Virulence is associated with daily rhythms in the within-host replication of the malaria parasitePlasmodium chabaudi
Authors: Owolabi Alíz T. Y. , Schneider Petra , Reece Sarah E. 
Published: August 2023

AbstractAsexually replicating stages of most malaria (Plasmodiumspp.) parasite species replicate synchronously within the red blood cells of their vertebrate host. Rhythmicity in this intraerythrocytic developmental cycle (IDC) enables parasites to maximise exploitation of the host and align transmission activities with the time of day that mosquito vectors blood feed. The IDC is also responsible for the major pathologies associated with malaria, and plasticity in the parasite’s rhythm can confer tolerance to antimalarial drugs. Both the severity of infection (virulence) and synchrony of the IDC vary across species and between genotypes ofPlasmodium, yet this variation is poorly understood. Theory predicts that virulence and IDC synchrony are negatively correlated and we tested this hypothesis using two closely related genotypes of the rodent malaria modelPlasmodium chabaudithat differ markedly in virulence. We also test the predictions that in response to perturbations to the timing (phase) of the IDC schedule relative to the phase of host rhythms (misalignment), the virulent parasite genotype recovers the correct phase relationship faster, incurs less fitness loss, and so, hosts benefit less from misalignment of the virulent genotype. Our predictions are partially supported; the virulent parasite genotype was less synchronous in some circumstances and recovered faster from misalignment. While hosts were less anaemic when infected by misaligned parasites, the extent of this benefit did not depend on parasite virulence. Overall, our results suggest that interventions to perturb the alignment between the IDC schedule and host rhythms, and increase synchrony between parasites within each IDC, could alleviate disease symptoms. However, virulent parasites, which are better at withstanding conventional antimalarial treatment, would also be intrinsically better able to tolerate such interventions.
Interactions between temperature and nutrients determine the population dynamics of primary producers
Authors: Bieg Carling , Vasseur David 
Published: August 2023

AbstractGlobal change is rapidly and fundamentally altering many of the processes regulating the flux of energy throughout ecosystems and although researchers now understand the effect of temperature on key rates (such as aquatic primary productivity), the theoretical foundation needed to generate forecasts of biomass dynamics and extinction risk remains underdeveloped. We develop new theory that describes the interconnected effects of nutrients and temperature on phytoplankton populations and show that the thermal response of equilibrium biomass (i.e., carrying capacity) always peaks at a lower temperature than for productivity (i.e., growth rate). This difference results from trade-offs between the thermal responses of growth, death, and per-capita impact on the nutrient pool, making this thermal mismatch highly general and applicable to widely used population models. We further show that non-equilibrium dynamics depend on the pace of environmental change relative to underlying vital rates, and that populations respond to variable environments differently at high vs. low temperatures due to thermal asymmetries.
Logical model of human tolerogenic dendritic cells and their participation in autoimmune disease
Authors: Nuñez-Reza Karen J. , Lozano-Jiménez Isaac , Martínez-Hernández Leslie , Medina-Rivera Alejandra 
Published: August 2023

AbstractTolerogenic dendritic cells (tolDC) regulate the immune response, several clinical trials focused on autoimmune diseases use tolDC to promote immune tolerance response and Treg activation. Here we built a logical model for the tolerization cellular process of dendritic cells using IL10. By combining literature knowledge, microarray gene expression, and key tolDC markers, we ensembled a logical model that describes the obtention of tolDC using the IL10 signaling cascade that spawns the most tolerogenic phenotype. The model uses IL10 as input and the signaling cascade that trigger seven transcription factors (TFs), three previously known TFs in the IL10 response (STAT3, NFKB, STAT6), and four were incorporated based on our gene expression analysis (IRF8, TCF7L2, CEBPB, and TFCP2L1). Using our model, we generated mutantsin-silicoand identified that even when IL10 is present the single mutants for TCF7L2, IRF8, TFCP2L1, and STAT3 were not able to reach a tolDC stable state, highlighting the relevance of these TFs in the process. The current model sets a precedent that will help in the development of tolDC for future applications.
Control adjustment costs limit goal flexibility: Empirical evidence and a computational account
Authors: Grahek Ivan , Leng Xiamin , Musslick Sebastian , Shenhav Amitai 
Published: August 2023

AbstractA cornerstone of human intelligence is the ability to flexibly adjust our cognition and behavior as our goals change. For instance, achieving some goals requires efficiency, while others require caution. Different goals require us to engage different control processes, such as adjusting how attentive and cautious we are. Here, we show that performance incurs control adjustment costs when people adjust control to meet changing goals. Across four experiments, we provide evidence of these costs, and validate a dynamical systems model explaining the source of these costs. Participants performed a single cognitively demanding task under varying performance goals (e.g., being fast or accurate). We modeled control allocation to include a dynamic process of adjusting from one’s current control state to a target state for a given performance goal. By incorporating inertia into this adjustment process, our model accounts for our empirical finding that people under-shoot their target control state more (i.e., exhibit larger adjustment costs) when goals switch rather than remain fixed (Study 1). Further validating our model, we show that the magnitude of this cost is increased when: distances between target states are larger (Study 2), there is less time to adjust to the new goal (Study 3), and goal switches are more frequent (Study 4). Our findings characterize the costs of adjusting control to meet changing goals, and show that these costs emerge directly from cognitive control dynamics. In so doing, they shed new light on the sources of and constraints on flexibility of goal-directed behavior.
Redox-enabled Electronic Interrogation and Feedback Control of Hierarchical and Networked Biological Systems
Authors: Wang Sally , Chen Chen-Yu , Rzasa John R. , Tsao Chen-Yu , Li Jinyang , VanArsdale Eric , Kim Eunkyoung , Zakaria Fauziah Rahma , Payne Gregory F. , Bentley William E. 
Published: August 2023

AbstractWe enable microelectronic devices to interrogate biology’s molecular communication, perform computations, and in real time control biological systems, including at several hierarchical levels: proteins, cells, and cell consortia. A key driver is establishing electronic access to and from biology’s native redox networks. First, redox-mediated electro-biofabrication facilitates facile assembly of biological components onto microelectronic systems, then electrode-actuated redox allows digital programming of enzyme activity, and further, redox-mediated electrogenetics facilitates closed-loop electronic control of cellular function. Specifically, we show algorithm-based feedback control of enzyme activity, cellular genetic circuits (via eCRISPR) and cell consortia behavior, all enabled by electronic data transfer. We further demonstrate electronic switching of cell-cell quorum sensing communication from one autoinducer network to another, creating an electronically controlled “bilingual” cell. We suggest these methodologies will not only help us to better understand biological systems, but design and control those currently unimagined.
An insect’s view of a numerosity illusion: a simple strategy may explain complex numerical performance in bumblebees
Authors: Gatto Elia , Guan Cui , Christian Agrillo , Cutini Simone , Chittka Lars , Petrazzini Maria Elena Miletto 
Published: August 2023

SummaryDespite some similarities in numerical abilities among vertebrates, animals seem to differ with respect to the perceptual factors underlying numerical estimation. This is particularly evident in the case of numerosity illusions, a type of illusory phenomena elicited by the spatial arrangement of the elements that compose it. We investigated whether an insect experiences the most famous numerosity illusion, the Solitaire Illusion. Bumblebees (Bombus terrestris audax) presented with two mixed arrays containing magenta and yellow dots were trained to select the array containing the larger number of a target colour (either magenta or yellow). In the test phases, bumblebees were presented with sets of stimuli differing in the numerical ratio, including the illusory arrays: in one array, magenta dots were centrally located (yellow dots in the perimeter), whereas in the other one, magenta dots were located in the perimeter (yellow dots in the centre). Bees discriminated up to a ratio of 0.78 (14 vs. 18). Video analyses showed that bumblebees sequentially scanned the stimuli before making a choice. Bumblebees required longer scanning time for patterns with smaller numbers of reinforced colour dots, suggesting that bumblebees spent longer time on searching for more information or finding a reinforced arrangement of spatial dots before making an accurate decision. In the presence of the “illusion arrangement”, bees behaved in a manner consistent with misperception of numerosity, overestimating the number of centrally located dots. The spatial configuration of the stimuli influenced how the patterns were assessed: bees examined the clustered reinforced colour dots longer. Flying paths analysis suggested that bumblebees followed the paths formed by similar colour dots rather than counting each dot to make a numerical discrimination. These results challenge the notion that visual illusions can be inferred simply from evaluating choices of different visual patterns and reinforce the idea that multiple strategies can potentially be used to achieve seemingly similar cognitive outcomes. Detailed analyses of decision-making processes are essential to deduce the cognitive strategies underpinning discrimination tasks, whether they are numerical or other visual tasks.
Plant immunity activated and suppressed by a conserved effector protein family in mirid bugRiptortus pedestris
Authors: Zhou Jiangxuan , Yin Zhiyuan , Shen Danyu , Dong Yumei , Yang Yuxia , Zhang Qingsong , Ma Yurong , Pei Yong , Lu Wangshan , Zhang Yancong , Ai Gan , Yang Donglei , Wang Yuanchao , Dou Daolong , Xia Ai 
Published: August 2023

AbstractRiptortus pedestris(Fabricius) a major soybean pest migrates into soybean fields during pod filling stage resulting in a leaf and stem staygreen while pods without beans syndrome. Given the agricultural importance of this species and the lack of characterized HAMP from piercing-sucking insects we performed a large scale of screening by expression of 87R. pedestrissalivary proteins with signal peptides inNicotiana benthamianaobtaining a candidate HAMP RPH1. RPH1 activated a series of PTI responses including ROS burst upregulation of defense marker genes such as PR1 WRKY7 WRKY8 Acre31 and CYP71D20 MAPK activation and biosynthesis of phytohormones in plants. RPH1 significantly enhances soybean resistance againstR. pedestrisfeeding. PRR coreceptors BAK1 and SOBIR1 were required for RPH1-induced PTI responses. Remarkably RPH1 homologs were widely distributed in herbivorous insects and majority of homologs from selected species induced cell death or ROS. Thus our results demonstrated that RPH1 is a conserved HAMP within chewing and piercing-sucking insects. We also discovered thatR. pedestrisevolved four paralogs to overcome the plant immunity triggered by RPH1. This study filled a major gap of HAMP identification from piercing-sucking insect and also deciphered a novel evasion strategy of plant immunity exploited by herbivorous insects.One sentence summaryRiptortus pedestrisRPH1, a conserved HAMP in herbivores, activates a variety of PTI responses in plants. To couterdefense,R. pedestrisevolved four paralogs to suppress RPH1-induced PTI responses.The author(s) responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (https://academic.oup.com/plcell/pages/General-Instructions) is: Ai Xia (xia@njau.edu.edu).
Connecting Thiamine Availability to the Microbial Community Composition in Chinook Salmon Spawning Habitats of the Sacramento River Basin
Authors: Suffridge Christopher P. , Shannon Kelly C. , Matthews H. , Johnson R. , Jeffres C. , Mantua N. , Ward Abigail E. , Holmes E. , Kindopp J. , Aidoo M. , Colwell F. 
Published: August 2023

AbstractThiamine Deficiency Complex (TDC) is a major emerging threat to global populations of culturally and economically important populations of salmonids. Salmonid eggs and embryos can assimilate exogenous thiamine, and evidence suggests that microbial communities in benthic environments can produce substantial amounts of thiamine. We therefore hypothesize that microbially produced thiamine in both riverine surface water and hyporheic zones could serve to rescue early life stages of salmonids suffering from TDC. The distributions of thiamine and its metabolically related compounds (dTRCs) have never been determined in freshwater systems. Similarly, the microbial cycling of these compounds has never been investigated. Here we determine that all dTRCs are present in femto-picomolar concentrations across diverse salmon spawning habitats in California’s Sacramento River system. We observed that thiamine concentrations in the Sacramento River are orders of magnitude lower than marine environments, indicating substantial differences in thiamine cycling between these two environments. Our data suggest that the hyporheic zone is likely the source of thiamine to the overlying surface water. Temporal variations in dTRC concentration were observed where highest concentrations were seen when Chinook salmon were actively spawning. Significant correlations were identified between the richness of differentially abundant ASVs and dTRC concentrations. The influence of these ASVs on dTRC concentrations provide evidence of dTRC cycling by microbes in the hyporheic zone, which would influence the conditions where embryonic salmon incubate. Together, these results indicate a connection between microbial communities in freshwater habitats and the availability of thiamine to spawning TDC-impacted California Central Valley Chinook salmon.
A Continuous Extension of Gene Set Enrichment Analysis using the Likelihood Ratio Test Statistics Identifies VEGF as a Candidate Pathway for Alzheimer’s disease
Authors: Mahzarnia Ali , Lutz Michael W. , Badea Alexandra 
Published: August 2023

AbstractBackgroundAlzheimer’s disease involves brain pathologies such as amyloid plaque depositions and hyperphosphorylated tau tangles and is accompanied by cognitive decline. Identifying the biological mechanisms underlying disease onset and progression based on quantifiable phenotypes will help understand the disease etiology and devise therapies.ObjectiveOur objective was to identify molecular pathways associated with AD biomarkers (Amyloid-β and tau) and cognitive status (MMSE) accounting for variables such as age, sex, education, and APOE genotype.MethodsWe introduce a novel pathway-based statistical approach, extending the gene set likelihood ratio test to continuous phenotypes. We first analyzed independently each of the three phenotypes (Amyloid-β, tau, cognition), using continuous gene set likelihood ratio tests to account for covariates, including age, sex, education, and APOE genotype. The analysis involved a large sample size with data available for all three phenotypes, allowing for the identification of common pathways.ResultsWe identified 14 pathways significantly associated with Amyloid-β, 5 associated with tau, and 174 associated with MMSE. Surprisingly, the MMSE outcome showed a larger number of significant pathways compared to biomarkers. A single pathway, vascular endothelial growth factor receptor binding (VEGF-RB), exhibited significant associations with all three phenotypes.ConclusionsThe study’s findings highlight the importance of the VEGF signaling pathway in aging in AD. The complex interactions within the VEGF signaling family offer valuable insights for future therapeutic interventions.
Employing Machine Learning Techniques to Detect Protein-Protein Interaction: A Survey, Experimental, and Comparative Evaluations
Authors: Taha Kamal 
Published: August 2023

ABSTRACTThis survey paper provides an in-depth analysis of various machine learning techniques and algorithms that are utilized in the detection of PPI (Protein-Protein Interactions). For every technique examined, the paper evaluates its efficiency, shortcomings, possibilities for enhancement, and outlook for the future. A major challenge in current survey papers focusing on machine learning algorithms for PPI identification is the successful categorization of these algorithms. To overcome this challenge, the paper introduces a novel hierarchical taxonomy that organizes algorithms into more intricate categories and distinct techniques. The proposed taxonomy is constructed on a four-tier structure, beginning with the broad methodology category, and ending with specific sub-techniques. This structure facilitates a more systematic and exhaustive categorization of algorithms, aiding researchers in grasping the connections between different algorithms and techniques. Included in the paper are both empirical and experimental assessments to classify the various techniques. The empirical assessment judges the techniques according to four standards. The experimental evaluations carry out the following rankings: (1) the algorithms that employ the same specific sub-technique, (2) the different sub-techniques that employ the same technique, (3) the different techniques that employ the same methodology sub-category, and (4) the different methodology sub-categories within the same methodology category. By merging the new methodological taxonomy, empirical analyses, and experimental evaluations, the paper provides a multifaceted and thorough comprehension of the machine learning methods and algorithms for PPI detection. This synthesis helps researchers make well-informed decisions. In its conclusion, the paper furnishes crucial insights into the future possibilities of machine learning techniques for PPI identification, underscoring potential advancements and areas ripe for continued exploration and development.
PreventingE. colibiofilm formation with antimicrobial peptide surface coatings: recognizing the dependence on the bacterial binding mode using live-cell microscopy
Authors: Hansson Adam , Karlsen Eskil André , Stensen Wenche , Svendsen John-Sigurd , Berglin Mattias , Lundgren Anders 
Published: August 2023

AbstractAntimicrobial peptides (AMPs) can kill bacteria by destabilizing their membranes, yet, to translate these molecules’ properties into a covalently attached coating is challenging. Standard microbiology methods do not work well for grafted AMPs, particularly it is difficult to distinguish the AMPs’ bactericidal potency from factors relating to bacteria’s binding behavior, e.g., which type of and how persistent bacteria-surface contacts that is necessary. Here we present a method combining live-cell microscopy and microfluidics to study the response ofE. colichallenged by the same small AMP either in solution or grafted to the surface through click chemistry. The AMP coating initially suppressed bacterial growth as strongly as AMPs in solution. While AMPs in solution eventually killed theE. colibacteria, those binding to the AMP coating changed contact mode one hour after binding and then became insensitive to it. The transition depended on binding-induced expression of Type 1 fimbriae, which limits contact between the AMPs and theE. coliouter membrane. By quantifying several different factors contributing to the antibacterial efficacy, these measurements provide a holistic understanding of how antibacterial surface coatings function. We therefore expect this tool to be important for the design of elaborate antibacterial coatings that can reduce the need for antibiotics and thus contribute to slower spreading of antibiotic resistance genes.