bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary Survey of Fungal Communities Across a Plastics/No Plastics Transition on an Oregon Beach
Authors: Cullings Ken , Arterbury Karisa Boyce , Arterbury Richard 
Published: January 2024

AbstractPlastics pose an increasing and significant threat to both human and environmental health. While many fungi can degrade a variety of organic polymers, investigations into which fungi possess the potential to remediate environmental plastics contamination have only recently become a priority. To help address this need, we tested the null hypothesis that chronic plastics contamination has no impact on the fungal communities across a plastics/no plastics transition in a beach sand in northern Oregon. We used sieving and binocular microscopy of microplastics (particle size, 12.6µm +/-5.5µm, detection range 1-5000µm) to confirm the plastics/no plastics transition. We used paired plot design to collect samples across this transition and analyzed the fungal communities using high-throughput DNA sequencing methods for fungal ITS-2. Results indicated that the beach sand contaminated with plastics held an extensive fungal community, while un-contaminated sand held no fungal community at all. System dominants includedAcremoniumandPenicillium, both free-living ascomycete fungi that have shown plastics-degrading capabilities in lab studies, and the ectomycorrhizal genus,Russulaa symbiotic fungus that has known plastics-degrading enzyme capabilities. Also amongst dominant genera was a human fungal pathogen (genusMalassezia) that causes chronic skin disease. These results provide new fungal models for further studies of fungal and ectomycorrhizal remediation of plastics contaminated contaminated beach sand.
Comparison of histological procedures and antigenicity of human post-mortem brains fixed with solutions used in gross anatomy laboratories
Authors: Frigon Eve-Marie , Gérin-Lajoie Amy , Dadar Mahsa , Boire Denis , Maranzano Josefina 
Published: January 2024

AbstractBackgroundBrain banks provide small tissue samples to researchers, while gross anatomy laboratories could provide larger samples, including complete brains to neuroscientists. However, they are preserved with solutions appropriate for gross-dissection, different from the classic neutral-buffered formalin (NBF) used in brain banks. Our previous work in mice showed that two gross-anatomy laboratory solutions, a saturated-salt-solution (SSS) and an alcohol-formaldehyde-solution (AFS), preserve antigenicity of the main cellular markers. Our goal is now to compare the quality of histology and antigenicity preservation of human brains fixed with NBF by immersion (practice of brain banks) vs. those fixed with a SSS and an AFS by whole body perfusion, practice of gross-anatomy laboratories.MethodsWe used a convenience sample of 42 brains (31 males, 11 females; 25-90 years old) fixed with NBF (N=12), SSS (N=13), and AFS (N=17). One cm3tissue blocks were cut, cryoprotected, frozen and sliced into 40 μm sections. The four cell populations were labeled using immunohistochemistry (neuronal-nuclei (NeuN), glial-fibrillary-acidic-protein (GFAP), ionized-calcium-binding-adaptor-molecule1 (Iba1) and myelin-proteolipid-protein (PLP)). We qualitatively assessed antigenicity and cell distribution, and compared the ease of manipulation of the sections, the microscopic tissue quality, and the quality of common histochemical stains (e.g., Cresyl violet, Luxol fast blue, etc.) across solutions.ResultsSections of SSS-fixed brains were more difficult to manipulate and showed poorer tissue quality than those from brains fixed with the other solutions. The four antigens were preserved, and cell labeling was more often homogenous in AFS-fixed specimens. NeuN and GFAP were not always present in the NBF and SSS samples. Some antigens were heterogeneously distributed in some specimens, independently of the fixative, but an antigen retrieval protocol successfully recovered them. Finally, the histochemical stains were of sufficient quality regardless of the fixative, although neurons were more often paler in SSS-fixed specimens.ConclusionAntigenicity was preserved in human brains fixed with solutions used in human gross-anatomy (albeit the poorer quality of SSS-fixed specimens). For some specific variables, histology quality was superior in AFS-fixed brains. Furthermore, we show the feasibility of frequently used histochemical stains. These results are promising for neuroscientists interested in using brain specimens from anatomy laboratories.
Effects of a school-based physical activity implementation program to reduce musculoskeletal pain frequency in children aged 9 to 12: a randomised clinical trial
Authors: Viana da Silva Priscilla , Kamper Steven J , Yamato Tiê Parma , Wolfenden Luke , Sutherland Rachel , McCarthy Nicole , Nolan Erin , Oldmeadow Christopher , Nathan Nicole , Williams Christopher M 
Published: January 2024

ABSTRACTObjectiveTo estimate the effect of scheduling physical activity during the school day on pain outcomes (frequency, severity, and impact), quality of life, physical activity and sedentary time in school children with musculoskeletal pain.Design, setting, and participantsA preplanned secondary analysis of a cluster randomised trial in private elementary schools from Australia. Eligible participants were students aged 9 to 12 (grades 4 to 6) who reported having previous MSK pain.InterventionsIntervention schools received support to increase the scheduling of physical activity during the school day (with and without nutrition strategies). Control schools received either support to implement nutrition strategies or no active support.Main outcomes and measuresPain frequency reported at 9-months after randomisation over the last six months. Secondary outcomes: quality of life (PedsQL 4.0), pain severity (FSP-R), physical activity and sedentary times, the prevalence of recent pain, and pain-related impact on physical activity, usual activities, school absenteeism, and health care utilisation.ResultsWe included 633 students (mean age 10.5 years). Of those, 33% of students reported previous frequent pain at follow-up. We found no difference in pain frequency between groups (OR 1.0, 95% CI: 0.6 to 1.6). The intervention group had slightly higher physical activity levels (mean difference: 3.1 min/day, 95% CI: −0.02 to 6.2) and lower pain impact in usual activities (OR 0.7, 95% CI: 0.4 to 1.0).Conclusion and relevanceIncreased scheduling of physical activity in schools did not improve pain outcomes in children with MSK pain. However, results suggest that children can improve physical activity levels during school time despite experiencing pain.Trial registrationACTRN12616001228471SUMMARY BOXWhat is already known on this topicMusculoskeletal (MSK) pain is prevalent among children and adolescents. The relationship between physical activity and pain is complex, with evidence indicating that physical inactivity can contribute to MSK pain, but pain may also serve as a barrier to engaging in physical activities.What this study addsWe found that scheduling physical activity during school time did not improve pain outcomes of school-aged children with MSK pain. However, there appears to be a small benefit to improving physical activity levels and impact on usual activities in students with prior MSK pain.How this study might affect research, practice or policyThis study highlights that children with MSK pain might need a more comprehensive approach to school-based physical activity programs, combining strategies that not only promote physical activity but also address the unique challenges posed by MSK pain in this age group.
A Dynamical Systems Approach to Optimal Foraging
Authors: Chaturvedi Siddharth , El-Gazzar Ahmed , Gerven Marcel van 
Published: January 2024

AbstractForaging for resources in an environment is a fundamental activity that must be addressed by any biological agent. Modelling this phenomenon in simulations can enhance our understanding of the characteristics of natural intelligence. In this work, we present a novel approach to model foraging in-silico using a continuous coupled dynamical system. The dynamical system is composed of three differential equations, representing the position of the agent, the agent’s control policy, and the environmental resource dynamics. Crucially, the control policy is implemented as a parameterized differential equation which allows the control policy to adapt in order to solve the foraging task. Using this setup, we show that when these dynamics are coupled and the controller parameters are optimized to maximize the rate of reward collected, adaptive foraging emerges in the agent. We further show that the internal dynamics of the controller, as a surrogate brain model, closely resemble the dynamics of the evidence accumulation mechanism, which may be used by certain neurons of the dorsal anterior cingulate cortex region in non-human primates, for deciding when to migrate from one patch to another. We show that by modulating the resource growth rates of the environment, the emergent behaviour of the artificial agent agrees with the predictions of the optimal foraging theory. Finally, we demonstrate how the framework can be extended to stochastic and multi-agent settings.Author SummaryIntelligence is a phenomenon that arises due to the interactions of an agent’s dynamics with the environment’s dynamics under the assumption that the agent seeks optimization of certain objective. Modelling both these dynamics as a single coupled dynamical system can shed light on patterns of intelligence that unfold in time. This report aims to provide a minimal in-silico framework that models the main components involved in natural phenomena, like optimal foraging, as a coupled dynamical system. Interestingly, we observe similarities between the surrogate brain dynamics of the artificial agent with the evidence accumulation mechanism that can be responsible for decision-making in certain non-human primates performing a similar foraging task. We also observe similarities between trends prescribed by theories prevalent in behavioural ecology such as the optimal foraging theory and those shown by the artificial agent. Such similarities can increase the predictability and explainability of artificial systems. We can now expect them to mimic these natural decision-making mechanisms by replicating such trends and we can thus understand the reasoning behind their actions. They can also increase the confidence of researchers to consider using such artificial agent models as simulation tools to make predictions and test hypotheses about aspects of natural intelligence.
Spreading depolarization causes reversible neuronal mitochondria fragmentation and swelling in healthy, normally perfused neocortex
Authors: Sword Jeremy , Fomitcheva Ioulia V. , Kirov Sergei A. 
Published: January 2024

AbstractMitochondrial function is tightly linked to their morphology, and fragmentation of dendritic mitochondria during noxious conditions suggests loss of function. In the normoxic cortex, spreading depolarization (SD) is a phenomenon underlying migraine aura. It is unknown whether mitochondria structure is affected by normoxic SD.In vivotwo-photon imaging followed by quantitative serial section electron microscopy (ssEM) was used to monitor dendritic mitochondria in the normoxic cortex of urethane-anesthetized mature male and female mice during and after SD initiated by focal KCl microinjection. Structural dynamics of dendrites and their mitochondria were visualized by transfecting excitatory, glutamatergic neurons of the somatosensory cortex with bicistronic AAV, which induced tdTomoto labeling in neuronal cytoplasm and mitochondria labeling with roGFP. Normoxic SD triggered a rapid fragmentation of dendritic mitochondria alongside dendritic beading, both reversible; however, mitochondria took significantly longer to recover. Several rounds of SD resulted in transient mitochondrial fragmentation and dendritic beading without accumulating injury, as both recovered. SsEM corroborated normoxic SD-elicited dendritic and mitochondrial swelling and transformation of the filamentous mitochondrial network into shorter, swollen tubular and globular structures. Our results revealed normoxic SD-induced disruption of the dendritic mitochondrial structure that might impact mitochondrial bioenergetics during migraine with aura.
WHAMM functions in kidney reabsorption and polymerizes actin to promote autophagosomal membrane closure and cargo sequestration
Authors: Coulter Alyssa M , Cortés Valerie , Theodore Corey J , Cianciolo Rachel E , Korstanje Ron , Campellone Kenneth G 
Published: January 2024

ABSTRACTThe actin cytoskeleton is essential for many functions of eukaryotic cells, but the factors that nucleate actin assembly are not well understood at the organismal level or in the context of disease. To explore the function of the actin nucleation factor WHAMM in mice, we examined howWhamminactivation impacts kidney physiology and cellular proteostasis. We show that male WHAMM knockout mice excrete elevated levels of albumin, glucose, phosphate, and amino acids, and display abnormalities of the kidney proximal tubule, suggesting that WHAMM activity is important for nutrient reabsorption. In kidney tissue, the loss of WHAMM results in the accumulation of the lipidated autophagosomal membrane protein LC3, indicating an alteration in autophagy. In mouse fibroblasts and human proximal tubule cells, WHAMM and its binding partner the Arp2/3 complex control autophagic membrane closure and cargo receptor recruitment. These results reveal a role for WHAMM-mediated actin assembly in maintaining kidney function and promoting proper autophagosome membrane remodeling.
Evolution of a bistable genetic system in fluctuating and non-fluctuating environments
Authors: Fernández-Fernández Rocío , Olivenza David R. , Weyer Esther , Singh Abhyudai , Casadesús Josep , Sánchez-Romero María Antonia 
Published: January 2024

AbstractEpigenetic mechanisms can generate bacterial lineages capable of spontaneously switching between distinct phenotypes. Currently, mathematical models and simulations propose epigenetic switches as a mechanism of adaptation to deal with fluctuating environments. However, bacterial evolution experiments for testing these predictions are lacking. Here, we exploit an epigenetic switch inSalmonella enterica,theopvABoperon, to show clear evidence that OpvAB bistability persists in changing environments but not in stable conditions. Epigenetic control of transcription in theopvABoperon produces OpvABOFF(phage-sensitive) and OpvABON(phage-resistant) cells in a reversible manner and may be interpreted as an example of bet-hedging to preadaptSalmonellapopulations to the encounter with phages. Our experimental observations and computational simulations illustrate the adaptive value of epigenetic variation as evolutionary strategy for mutation avoidance in fluctuating environments. In addition, our study provides experimental support to game theory models predicting that phenotypic heterogeneity is advantageous in changing and unpredictable environments.
Structure-Guided Mutagenesis Targeting Interactions between pp150 Tegument Protein and Small Capsid Protein Identify Five Lethal and Two Live Attenuated HCMV Mutants
Authors: Stevens Alex , Cruz-cosme Ruth , Armstrong Najealicka , Tang Qiyi , Zhou Z. Hong 
Published: January 2024

AbstractHuman cytomegalovirus (HCMV) replication relies on a nucleocapsid coat of the 150kDa, subfamily-specific tegument phosphoprotein (pp150) to regulate cytoplasmic virion maturation. While recent structural studies revealed pp150-capsid interactions, the role of specific amino-acids involved in these interactions have not been established experimentally. In this study, pp150 and the small capsid protein (SCP), one of pp150’s binding partners found atop the major capsid protein (MCP), were subjected to mutational and structural analyses. Mutations to clusters of polar or hydrophobic residues along the pp150-SCP interface abolished viral replication, with no replication detected in mutant virus-infected cells. Notably, a single point mutation at the pp150-MCP interface significantly attenuated viral replication, unlike the situation of pp150-deletion mutation where capsids degraded outside host nuclei. These functionally significant mutations targeting pp150-capsid interactions, particularly the pp150 K255E replication-attenuated mutant, can be explored to overcome the historical challenges of developing effective antivirals and vaccines against HCMV infection.
TDP-43 dysregulation of polyadenylation site selection is a defining feature of RNA misprocessing in ALS/FTD and related disorders
Authors: Arnold Frederick J. , Cui Ya , Michels Sebastian , Colwin Michael R. , Stockford Cameron , Ye Wenbin , Tam Oliver H. , Menon Sneha , Situ Wendy G. , Ehsani Kean C. K. , Howard Sierra , Hammell Molly Gale , Li Wei , La Spada Albert R. 
Published: January 2024

AbstractNuclear clearance and cytoplasmic aggregation of the RNA-binding protein TDP-43 are observed in many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and fronto- temporal dementia (FTD). Although TDP-43 dysregulation of splicing has emerged as a key event in these diseases, TDP-43 can also regulate polyadenylation; yet, this has not been adequately studied. Here, we applied the dynamic analysis of polyadenylation from RNA-seq (DaPars) tool to ALS/FTD transcriptome datasets, and report extensive alternative polyadenylation (APA) upon TDP-43 alteration in ALS/FTD cell models and postmortem ALS/FTD neuronal nuclei. Importantly, many identified APA genes highlight pathways implicated in ALS/FTD pathogenesis. To determine the functional significance of APA elicited by TDP-43 nuclear depletion, we examined microtubule affinity regulating kinase 3 (MARK3). Nuclear loss of TDP-43 yielded increased expression of MARK3 transcripts with longer 3’UTRs, resulting in greater transcript stability and elevated MARK3 protein levels, which promotes increased neuronal tau S262 phosphorylation. Our findings define changes in polyadenylation site selection as a previously unrecognized feature of TDP-43-driven disease pathology in ALS/FTD and highlight a potentially novel mechanistic link between TDP-43 dysfunction and tau regulation.
Birth of new protein folds and functions in the virome
Authors: Nomburg Jason , Price Nathan , Doudna Jennifer A. 
Published: January 2024

SummaryRapid virus evolution generates proteins essential to infectivity and replication but with unknown function due to extreme sequence divergence1. Using a database of 67,715 newly predicted protein structures from 4,463 eukaryotic viral species, we found that 62% of viral proteins are evolutionarily young and lack homologs in the Alphafold database2,3. Among the 38% of more ancient viral proteins, many have non-viral structural homologs that revealed surprising similarities between human pathogens and their eukaryotic hosts. Structural comparisons suggested putative functions for >25% of unannotated viral proteins, including those with roles in the evasion of innate immunity. In particular, RNA ligase T- (ligT) like phosphodiesterases were found to resemble phage-encoded proteins that hydrolyze the host immune-activating cyclic dinucleotides 3’3’ and 2’3’ cyclic G-A monophosphate (cGAMP). Experimental analysis showed that ligT homologs encoded by avian poxviruses likewise hydrolyze 2’3’ cGAMP, showing that ligT-mediated targeting of cGAMP is an evolutionarily conserved mechanism of immune evasion present in both bacteriophage and eukaryotic viruses. Together, the viral protein structural database and analytics presented here afford new opportunities to identify mechanisms of virus-host interactions that are common across the virome.
A neural correlate of learning fails to predict foraging efficiency inBombus terrestris
Authors: Pasquier Grégoire , Pull Christopher D. , Ott Swidbert R. , Leadbeater Ellouise 
Published: January 2024

AbstractThe mushroom bodies (MB) are integrative structures in the insect brain that, in social bees, contribute to both visual and olfactory learning. Changes in the density of presynaptic boutons (or microglomeruli) within the calyx region of the MB have been repeatedly linked to various aspects of foraging, including forms of learning that are thought to be key to support foraging efficiency. Here we set out to directly test the relationship between foraging efficiency and microglomerulus density in a bumblebee model,Bombus terrestris.We found no evidence that microglomerulus density predicted real-world foraging performance, nor any relationship with foraging experience. Instead, our data suggest a potential non-linear relationship between individual age, independent of foraging experience, and microglomerulus density in the lip region of the calyx, which is associated with olfactory processing. Our findings suggest that in real-world scenarios there is no simple direct relationship between microglomerular density, learning ability and foraging efficiency in bumblebees, highlighting the gap in knowledge regarding the relationships between learning abilities, neuroanatomy and foraging efficiency.
Encoding of task regularities links grid-like signals to human timing behavior
Authors: Polti Ignacio , Nau Matthias , Kaplan Raphael , van Wassenhove Virginie , Doeller Christian F. 
Published: January 2024

AbstractGrid cells have been proposed to encode task regularities that allow predicting future states. Entorhinal grid-like signals might therefore mirror behavioral biases associated with relying on task regularities, like regression-to-the-mean biases in time estimation. Here, we tested this proposal using functional magnetic resonance imaging and a rapid timing task in humans. Indeed, trial-wise entorhinal activity reflected task accuracy and the degree to which interval estimates regressed towards the mean of all tested intervals. Grid-like signals were observed exclusively for the interval closest to the mean, which was explained by differences in temporal stability across intervals. Finally, both behavioral and entorhinal results were explained by a Bayesian observer model that assumes the integration of current-trial sensory evidence with prior expectations. Together, we find that entorhinal activity and grid-like signals reflect behavioral performance in a timing task, supporting the proposed role of grid cells in encoding task structure for predictive coordination of behavior.