bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thioether-functionalized cellulose for the fabrication of oxidation-responsive biomaterial coatings and films
Authors: DuBois Eric M. , Herrema Kate E. , Simkulet Matthew G. , Hassan Laboni F. , O’Connor Payton R. , Sen Riya , O’Shea Timothy M. 
Published: July 2024

AbstractBiomaterial coatings and films can prevent premature failure and enhance performance of chronically implanted medical devices. However, current hydrophilic polymer coatings and films have significant drawbacks, including swelling and delamination. To address these issues, we modified hydroxyethyl cellulose with thioether groups to generate an oxidation-responsive polymer, HECMTP. HECMTPreadily dissolves in green solvents and can be fabricated as coatings or films with tunable thicknesses. HECMTPcoatings effectively scavenge hydrogen peroxide, resulting in conversion of thioether groups to sulfoxide groups on the polymer chain. Oxidation-driven, hydrophobic-to-hydrophilic transitions that are isolated to the surface of HECMTPcoating under physiologically relevant conditions increase wettability, decrease stiffness, and reduce protein adsorption to generate a non-fouling interface with minimal coating delamination or swelling. HECMTPcan be used in diverse optical applications and permits oxidation-responsive, controlled drug release. HECMTPfilms are non-resorbablein vivoand evoke minimal foreign body responses. These results highlight the versatility of HECMTPand support its incorporation into chronically implanted medical devices.
Host-derived CEACAM-laden vesicles engage enterotoxigenicE. colifor elimination and toxin neutralization
Authors: Sheikh Alaullah , Ganguli Debayan , Vickers Tim J. , Singer Bernhard , Foulke-Abel Jennifer , Akhtar Marjahan , Khatoon Nazia , Setu Bipul , Basu Supratim , Harro Clayton , Maier Nicole , Beatty Wandy L. , Chakraborty Subhra , Bhuiyan Tafiqur R. , Qadri Firdausi , Donowitz Mark , Fleckenstein James M. 
Published: July 2024

abstractEnterotoxigenicEscherichia coli(ETEC) cause hundreds of millions of diarrheal illnesses annually ranging from mildly symptomatic cases to severe, life-threatening cholera-like diarrhea. Although ETEC are associated with long-term sequelae including malnutrition, the acute diarrheal illness is largely self-limited. Recent studies indicate that in addition to causing diarrhea, the ETEC heat-labile toxin (LT) modulates the expression of many genes in intestinal epithelia, including carcinoembryonic cell adhesion molecules (CEACAMs) which ETEC exploit as receptors, enabling toxin delivery. Here however, we demonstrate that LT also enhances the expression of CEACAMs on extracellular vesicles (EV) shed by intestinal epithelia and that CEACAM-laden EV increase in abundance during human infections, mitigate pathogen-host interactions, scavenge free ETEC toxins, and accelerate ETEC clearance from the gastrointestinal tract. Collectively, these findings indicate that CEACAMs play a multifaceted role in ETEC pathogen-host interactions, transiently favoring the pathogen, but ultimately contributing to innate responses that extinguish these common infections.Significance statementEnterotoxigenicE. coli,characterized by the production of heat-labile (LT) and heat-stable (ST) toxins, are a very common cause of diarrhea in low-income regions responsible for hundreds of millions of infections each year, and the major cause of diarrhea in travelers to endemic areas. Although these infections may be severe and cholera-like, they are typically self-limited. These studies demonstrate that extracellular vesicles produced by host intestinal cells can capture the bacteria and its secreted toxins at a distance from the cell surface, potentially acting as molecular decoys to neutralize the enterotoxins and extinguish the infection.
Similar won’t make it: Coexistence, habitat availability and suboptimal restoration
Authors: Urioste Felipe Maresca , Borthagaray Ana Inés , Cunillera-Montcusí David , Soutullo Álvaro , Arim Matias 
Published: July 2024

AbstractIn the context of the looming biodiversity crisis, adding patches of habitat has been proposed as a restoration strategy in several ecosystems. However, these interventions rarely mimic the conditions of the natural habitats precisely. Consequently, not all species equally benefit from the restored habitat, fostering a difference in species fitness that could generate an imbalance in the equalizing and stabilizing mechanisms that enable species coexistence, leading to competitive exclusion. Using a metapopulation model, we explore how the introduction of habitat patches with biased fitness advantages affects species coexistence. We show that while adding habitat patches generally increases species occupancy, suboptimal patches can favor one species, disrupting the stabilizing and equalizing mechanisms that enable coexistence, leading to competitive exclusion. This impact on the coexistence regime is particularly pronounced in species with high niche overlap and high colonization-extinction ratios. Our results highlight the double-edged sword effect of suboptimal restoration, revealing potential unintended consequences that could exacerbate biodiversity loss. On the other hand, restoration favoring endangered species is also identified as a conservation tool. The present study advances in the mechanistic comprehension of habitat restoration, a necessary endeavor in the face of the challenges posed by global change.
Motor Cortical Neuronal Hyperexcitability Associated with α-Synuclein Aggregation
Authors: Chen Liqiang , Chehade Hiba Douja , Chu Hong-Yuan 
Published: July 2024

AbstractDysfunction of the cerebral cortex is thought to underlie motor and cognitive impairments in Parkinson disease (PD). While cortical function is known to be suppressed by abnormal basal ganglia output following dopaminergic degeneration, it remains to be determined how the deposition of Lewy pathology disrupts cortical circuit integrity and function. Moreover, it is also unknown whether cortical Lewy pathology and midbrain dopaminergic degeneration interact to disrupt cortical function in late-stage. To begin to address these questions, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. Using this model system, we reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern. Particularly, intratelencephalic neurons (ITNs) showed earlier accumulation and greater extent of αSyn aggregates relative to corticospinal neurons (CSNs). Moreover, we demonstrated that the intrinsic excitability and inputs resistance of αSyn aggregates-bearing ITNs in the secondary motor cortex (M2) are increased, along with a noticeable shrinkage of cell bodies and loss of dendritic spines. Last, neither the intrinsic excitability of CSNs nor their thalamocortical input was altered by a partial striatal dopamine depletion associated with αSyn pathology. Our results documented motor cortical neuronal hyperexcitability associated with αSyn aggregation and provided a novel mechanistic understanding of cortical circuit dysfunction in PD.
“Comparative Analysis of Glycoproteomic Software Using a Tailored Glycan Database”
Authors: Hogan Reuben A. , Pepi Lauren E. , Riley Nicholas M. , Chalkley Robert J. 
Published: July 2024

AbstractGlycoproteomics is a rapidly developing field, and data analysis has been stimulated by several technological innovations. As a result, there are many software tools from which to choose; and each comes with unique features that can be difficult to compare. This work presents a head-to-head comparison of five modern analytical software: Byonic, Protein Prospector, MSFraggerGlyco, pGlyco3, and GlycoDecipher. To enable a meaningful comparison, parameter variables were minimized. One potential confounding variable is the glycan database that informs glycoproteomic searches. We performed glycomic profiling of the samples and used the output to construct matched glycan databases for each software. Up to 19,000 glycopeptide spectra were identified across three replicates of wild-type SH-SY5Y cells. There was substantial overlap among most software for glycoproteins identified, locations of glycosites, and glycans, although Byonic reported a suspiciously large number of glycoproteins and glycosites of questionable reliability. We show that Protein Prospector identified the most glycopeptide spectrum matches with high agreement to known glycosites in UniProt. Overall, our results indicate that glycoproteomic searches should involve more than one software to generate confidence. It may be useful to consider software with peptide-first approaches and with glycan-first approaches.
Differential Reactivation of Task-Demand-Associated Firing Patterns in Subicular and CA1 Place Cells during a Hippocampal Memory Task
Authors: Seol Jae-Min , Lee Su-Min , Lee Inah 
Published: July 2024

AbstractReactivation of place cells during sharp-wave ripples (SWRs) in the hippocampus is pivotal for memory consolidation, yet differences in SWR dynamics between the hippocampus and its neighboring subiculum remain underexplored. We examined the differential reactivations of task-demand-associated representations during SWR events in the subiculum and CA1 during a visual scene memory task in rats. In the task, the spiking activity of place cell ensembles was reactivated during a SWR event according to task demands. These reactivations were more frequent and were associated with more heterogeneous task-demand types in the subiculum compared with the CA1. Neural manifold analysis showed that the neural states of the reactivated ensemble were more clearly clustered into distinct states during subicular SWRs according to the task-demand-associated variables. These subicular characteristics were driven by multiple subfields of the subicular place field, parcellated by the theta phase precession cycle. In contrast, CA1 exhibited a higher incidence of spatial replay than the subiculum. These findings indicate that the subiculum plays a key role in transmitting task-specific variables from the hippocampus to other brain regions.
Control of tongue movements by the Purkinje cells of the cerebellum
Authors: Hage Paul , Fakharian Mohammad Amin , Shoup Alden M. , Pi Jay S. , Sedaghat-Nejad Ehsan , Orozco Simon P. , Jang In Kyu , Looi Vivian , Elseweifi Hisham Y. , Mohammadrezaei Nazanin , Vasserman Alexander N. , Arginteanu Toren , Shadmehr Reza 
Published: July 2024

AbstractWe use our tongue much like our hands: to interact with objects and transport them. For example, we use our hands to sense properties of objects and transport them in the nearby space, and we use our tongue to sense properties of food morsels and transport them through the oral cavity. But what does the cerebellum contribute to control of tongue movements? Here, we trained head-fixed marmosets to make skillful tongue movements to harvest food from small tubes that were placed at sharp angles to their mouth. We identified the lingual regions of the cerebellar vermis and then measured the contribution of each Purkinje cell (P-cell) to control of the tongue by relying on the brief but complete suppression that they experienced following an input from the inferior olive. When a P-cell was suppressed during protraction, the tongue’s trajectory became hypermetric, and when the suppression took place during retraction, the tongue’s return to the mouth was slowed. Both effects were amplified when two P-cells were simultaneously suppressed. Therefore, suppression of P-cells in the lingual vermis disrupted the forces that would normally decelerate the tongue as it approached the target. Notably, the population simple spike activity peaked near deceleration onset when the movement required precision (aiming for a tube), but not when the movement was for the purpose of grooming. Thus, the P-cells appeared to signal when to stop protrusion as the tongue approached its target.
No evidence of musical training influencing the cortical contribution to the speech-FFR and its modulation through selective attention
Authors: Riegel Jasmin , Schüller Alina , Reichenbach Tobias 
Published: July 2024

AbstractMusicians can have better abilities to understand speech in adverse conditions such as background noise than non-musicians. However, the neural mechanisms behind such enhanced behavioral performances remain largely unclear. Studies have found that the subcortical frequency-following response to the fundamental frequency of speech and its higher harmonics (speech-FFR) may be involved since it is larger in people with musical training than in those without. Recent research has shown that the speech-FFR consists of a cortical contribution in addition to the subcortical sources. Both the subcortical and the cortical contribution are modulated by selective attention to one of two competing speakers. However, it is unknown whether the strength of the cortical contribution to the speech-FFR, or its attention modulation, is influenced by musical training. Here we investigate these issues through magnetoencephalographic (MEG) recordings of 52 subjects (18 musicians, 25 non-musicians, and 9 neutral participants) listening to two competing male speakers while selectively attending one of them. The speech-in-noise comprehension abilities of the participants were not assessed. We find that musicians and non-musicians display comparable cortical speech-FFRs and additionally exhibit similar subject-to-subject variability in the response. Furthermore, we also do not observe a difference in the modulation of the neural response through selective attention between musicians and non-musicians. Moreover, when assessing whether the cortical speech-FFRs are influenced by particular aspects of musical training, no significant effects emerged. Taken together, we did not find any effect of musical training on the cortical speech-FFR.Significance statementIn previous research musicians have been found to exhibit larger subcortical responses to the pitch of a speaker than non-musicians. These larger responses may reflect enhanced pitch processing due to musical training and may explain why musicians tend to understand speech better in noisy environments than people without musical training. However, higher-level cortical responses to the pitch of a voice exist as well and are influenced by attention. We show here that, unlike the subcortical responses, the cortical activities do not differ between musicians and non-musicians. The attentional effects are not influenced by musical training. Our results suggest that, unlike the subcortical response, the cortical response to pitch is not shaped by musical training.
Enhancing Statistical Power While Maintaining Small Sample Sizes in Behavioral Neuroscience Experiments Evaluating Success Rates
Authors: Desachy Theo , Thevenet Marc , Garcia Samuel , Lightning Anistasha , Didier Anne , Mandairon Nathalie , Kuczewski Nicola 
Published: July 2024

AbstractStudies with low statistical power reduce the probability of detecting true effects and often lead to overestimated effect sizes, undermining the reproducibility of scientific results. While several free statistical software tools are available for calculating statistical power, they often do not account for the specialized aspects of experimental designs in behavioral studies that evaluate success rates. To address this gap, we developed “SuccessRatePower” a free and user-friendly power calculator based on Monte Carlo simulations that takes into account the particular parameters of these experimental designs. Using “SuccessRatePower”, we demonstrated that statistical power can be increased by modifying the experimental protocol in three ways: 1) reducing the probability of succeeding by chance (chance level), 2) increasing the number of trials used to calculate subject success rates, and 3) employing statistical analyses suited for discrete values. These adjustments enable even studies with small sample sizes to achieve high statistical power. Finally, we performed an associative behavioral task in mice, confirming the simulated statistical advantages of reducing chance levels and increasing the number of trials in such studies
Non-invasive Ultrasound Deep Neuromodulation of the Human Nucleus Accumbens Increases Win-Stay Behaviour
Authors: Yaakub Siti N. , Bault Nadège , Lojkiewiez Mathilde , Bellec Elouan , Roberts Jamie , Philip Noah S. , Rushworth Matthew F.S. , Fouragnan Elsa F. 
Published: July 2024

AbstractCurrent methods for directly modulating activity in deep human brain structures are limited and invasive. Here, we demonstrate modulation of activity in human deep brain structures using non-invasive transcranial ultrasound stimulation (TUS) and show it exerts selective effects on learning and decision making. 26 healthy adults participated in a within-subject repeated TUS– functional magnetic resonance imaging (fMRI) experiment with three sonication conditions. Participants performed a probabilistic learning task while undergoing fMRI scanning after counterbalanced 80 s 5 Hz repetitive TUS of the nucleus accumbens (NAcc), dorsal anterior cingulate cortex (dACC), or Sham. TUS-NAcc altered parametric BOLD response to reward expectation in NAcc and adjacent areas. Moreover, it induced changes specific to reward-related behaviours including in the use of win–stay strategy, learning rate following rewards, learning curve for choices of the rewarding option, and rate of repetition for rewarded choices. The results demonstrate TUS’s utility for human non-invasive deep-brain neuromodulation and the causal role of the human NAcc in learning from positive outcomes.SummaryPrecisely neuromodulating deep brain regions in humans could bring transformative advancements in both cognitive neuroscience and brain disorder treatment. In a within subject experiment, twenty-six healthy adults underwent a series of transcranial ultrasound stimulation procedures, including stimulation of the nucleus accumbens, the dorsal anterior cingulate cortex, or no sonication. Results revealed that ultrasound stimulation of the nucleus accumbens (NAcc) induced changes in reward-related behaviours, including in the tendency to stick with winning choices, the rate of learning specifically from positive feedback, and the rate of repeating rewarded choices. Functional brain scans showed corresponding neural changes in response to reward expectations in targeted and interconnected brain areas. These findings demonstrate the causal role of the human NAcc in learning from positive feedback, as well as the feasibility of using non-invasive neuromodulation deep in the human brain to modulate learning and decision making both as a research tool and as a potential component of future treatments for disorders involving reward sensitivity.
The plasmid-bornehipBAoperon ofKlebsiella michiganensisencodes a potent plasmid stabilization system
Authors: Shutt-McCabe J , Shaik KB , Hoyles L , McVicker G 
Published: July 2024

AbstractAimsKlebsiella michiganensisis a medically-important bacterium that has been subject to relatively little attention in the literature. Interrogation of sequence data fromK. michiganensisstrains in our collection has revealed the presence of multiple large plasmids encoding type II toxin-antitoxin (TA) systems. Such TA systems are responsible for mediating a range of phenotypes including plasmid stability (“addiction”) and antibiotic persistence. In this work, we characterize thehipBATA locus found within theKlebsiella oxytocaspecies complex (KoSC).Methods and ResultsThe HipBA TA system is encoded on a plasmid carried byK. michiganensisPS_Koxy4, isolated from an infection outbreak. Employing viability and plasmid stability assays, we demonstrate that PS_Koxy4 HipA is a potent antibacterial toxin and that HipBA is a functional TA module contributing substantially to plasmid maintenance. Further, we providein silicodata comparing HipBA modules across the entire KoSC.ConclusionsWe provide the first evidence of the role of a plasmid-encoded HipBA system in stability of mobile genetic elements and analyze the presence of HipBA across the KoSC. These results expand our knowledge of both a common enterobacterial TA system and a highly medically-relevant group of bacteria.Impact StatementThe HipBA TA system is typically encoded on bacterial chromosomes where it contributes to antimicrobial tolerance by interfering with translation during cellular stress. Here, we show that plasmid-encoded HipBA from a disease isolate ofKlebsiella michiganensisis responsible for highly effective plasmid addiction; the first such evidence of a HipBA module contributing to plasmid stability. This has important implications for enteric pathogen evolution and horizontal gene transfer in the era of multidrug resistance.
Molecular dissection of the chromosome partitioning protein RocS and regulation by phosphorylation
Authors: Demuysere Margaux , Ducret Adrien , Grangeasse Christophe 
Published: July 2024

ABSTRACTChromosome segregation in bacteria is a critical process ensuring that each daughter cell receives an accurate copy of the genetic material during cell division. Active segregation factors such as the ParABS system or SMC complexes, are usually essential for this process but are surprisingly dispensable inStreptococcus pneumoniae. Rather, chromosome segregation inS. pneumoniaerelies on the protein RocS, although the molecular mechanisms involved remain elusive. By combining genetics,in vivoimaging and biochemical approaches, we dissected the molecular features of RocS involved in chromosome segregation. Specifically, we investigated the respective function of the three RocS domains, specifically the C-terminal amphipathic helix (AH), the N-terminal DNA-binding domain (DBD) and the coiled-coil domain (CCD) separating the AH and the DBD. Notably, we found that a single AH is not sufficient for membrane binding and that RocS requires prior oligomerization to interact with the membrane. We further demonstrated that this self-interaction was driven by the N-terminal part of the CCD. On the other hand, we revealed that the C-terminal part of the CCD corresponds to a domain of unknown function (DUF 536) defined by three conserved glutamines which play a crucial role in RocS-mediated chromosome segregation. Finally, we showed that the DBD is phosphorylated by the unique serine-threonine kinase ofS. pneumoniaeStkP, and that mimicking this phosphorylation abrogated RocS binding to DNA. Overall, this study offers new insights into chromosome segregation in Streptococci and paves the way for a deeper understanding of RocS-like proteins in other bacteria.IMPORTANCEBacteria have evolved a variety of mechanisms to properly segregate their genetic material during cell division. In this study, we performed a molecular dissection of the chromosome partitioning protein RocS, a pillar element of chromosome segregation inS. pneumoniaethat is also generally conserved in theStreptococcaceaefamily. Our systematic investigation shed light on the molecular features required for successful pneumococcal chromosome segregation and the regulation of RocS by phosphorylation. In addition, our study also revealed that RocS shares functional domains with the Par protein, involved in an atypical plasmid segregation system. Therefore, we expect that our findings may serve to extend our understanding of RocS and RocS-like proteins, while broadening the repertoire of partitioning systems used in bacteria.