bluuebunny/crossref_metadata_2025_split huggingface dataset:
Formation of an Enduring Ensemble of Accumbens Neurons Leads to Prepotent Seeking for Cocaine Over Natural Reward Cues
Authors: Chalhoub Reda M , Testen Anze , Hopkins Jordan , Carthy Camille , Kalivas Peter W 
Published: August 2024

SUMMARYNeuronal activity in the nucleus accumbens core (NAcore) is necessary for reward-seeking behaviors. We hypothesized that the differential encoding of natural and drug rewards in the NAcore contributes to substance use disorder. We leveraged single-cell calcium imaging of dopamine D1- and D2-receptor-expressing medium spiny neurons (MSNs) in the NAcore of mice to examine differences between sucrose and cocaine rewarded (self-administration) and unrewarded (abstinent and cue-induced) seeking. Activity was time-locked to nose-poking for reward, clustered, and compared between sucrose and cocaine. Only in cocaine-trained mice were excited D1-MSNs securely stable, capable of decoding nose-poking in all rewarded and unrewarded sessions and correlated with the intensity of nose-poking for unrewarded seeking. Furthermore, D1-MSNs formed a stable ensemble predictive of seeking behavior after extended cocaine, but not sucrose abstinence. The excited D1-MSN ensemble uniquely drives cue-induced cocaine seeking and may contribute to why drug seeking is prepotent over natural reward seeking in cocaine use disorder.
Zinc and Metformin Co-Functionalized Polyetheretherketone: A Novel Dental Implant Material Tailored for the Elderly
Authors: Liu Zhengwei , Zhao Enze , Huang Hanwei , Wu Yuxun , He Yicong , Bai Shuting , Wang Suwen , Fan Shirou , Cao Shuaishuai , Tang Bin , Wang Yansong 
Published: August 2024

AbstractThis study focuses on addressing the challenges of dental implants in the geriatric population by enhancing the bioactivity of polyetheretherketone (PEEK) through surface modification. PEEK, with its elastic modulus close to alveolar bone, mitigates stress shielding but faces limitations in osseointegration due to low bioactivity. We introduced zinc (Zn) and metformin (MF) onto PEEK surfaces via a dopamine-assisted physical adhesion method, creating a functionalized derivative called ZnMF@PEEK. This combination targets diminished osteogenic potential, persistent inflammation, and cell senescence, which are common issues in elderly patients. Comprehensive physicochemical characterizations confirmed the successful preparation of ZnMF@PEEK, and invitroand invivoexperiments systematically evaluated its biocompatibility and bioactivity. The results indicate that ZnMF@PEEK holds promise as a dental implant material tailored to the specific needs of the elderly, addressing multifaceted challenges in osseointegration.
CryoEM structure of an MHC-I/TAPBPR peptide bound intermediate reveals the mechanism of antigen proofreading
Authors: Sun Yi , Pumroy Ruth Anne , Mallik Leena , Chaudhuri Apala , Wang Chloe , Hwang Daniel , Danon Julia N. , Goli Kimia Dasteh , Moiseenkova-Bell Vera , Sgourakis Nikolaos G. 
Published: August 2024

AbstractClass I major histocompatibility complex (MHC-I) proteins play a pivotal role in adaptive immunity by displaying epitopic peptides to CD8+ T cells. The chaperones tapasin and TAPBPR promote the selection of immunogenic antigens from a large pool of intracellular peptides. Interactions of chaperoned MHC-I molecules with incoming peptides are transient in nature, and as a result, the precise antigen proofreading mechanism remains elusive. Here, we leverage a high-fidelity TAPBPR variant and conformationally stabilized MHC-I, to determine the solution structure of the human antigen editing complex bound to a peptide decoy by cryogenic electron microscopy (cryo-EM) at an average resolution of 3.0 Å. Antigen proofreading is mediated by transient interactions formed between the nascent peptide binding groove with the P2/P3 peptide anchors, where conserved MHC-I residues stabilize incoming peptides through backbone-focused contacts. Finally, using our high-fidelity chaperone, we demonstrate robust peptide exchange on the cell surface across multiple clinically relevant human MHC-I allomorphs. Our work has important ramifications for understanding the selection of immunogenic epitopes for T cell screening and vaccine design applications.
Assessing the effects of female protections on size structure and spawning potential in two clawed lobster fisheries subject to varying exploitation levels
Authors: Theberge Kaitlyn , Sørdalen Tonje K. , Pugh Tracy L. , Kindsvater Holly K. 
Published: August 2024

ABSTRACTCurrent fishery management practices in both the U.S. Gulf of Maine and Norwegian clawed lobster fisheries primarily focus on conserving mature females to maximize egg production. While abundance of adult American lobsters (Homarus americanus) in the Gulf of Maine remains high, declines appear to be on the horizon. Similarly, the European lobster (Homarus gammarus), is facing its lowest recorded population size in southern Norway. Understanding how management strategies and fishing practices impact lobster size structure and spawning potential could inform management to improve resiliency to climate-induced changes. In the Gulf of Maine fishery, egg-bearing (ovigerous) female lobsters are not only protected from harvest, but also v-notched which offers additional protection up to several years. Norway, however, protects egg-bearing females without v-notching. Comparing these fisheries allows us to test the effect of the different management practices and how they interact with key vital rates, including growth and natural mortality rates. We used deterministic size- and age-structured models and empirically estimated growth and molt functions to simulate relative changes in abundance, size structure, egg production, and sex ratios in response tothesetwo female protection strategies. Our findings suggest that in all scenarios, controlling total fishing effort to low or moderate levels - relative to theF> 1 that has been estimated for American lobster - is most important for the effectiveness of size-based restrictions on harvest of larger individuals. Both forms of female protection enhance overall egg production in both species across levels of fishing intensity, but also result in a skewed sex ratio in favor of females and a more pronounced size disparity between female and male lobsters. Moreover, our results suggest that American and European lobster populations exhibit differential responses to the management strategies, likely due to variations in estimates of natural mortality rates and growth rates. Our results highlight the sensitivity of management effectiveness to assumptions regarding the underlying biology, but also provide a clear message that current intense fishing practices have likely depleted the ability of both species to compensate for fishing mortality in the long term.
Trophic transfer and bioaccumulation of nanoplastics inCoryphaena hippurus(Mahi-mahi) and effect of depuration
Authors: Dey Preyojon , Bradley Terence M. , Boymelgreen Alicia 
Published: August 2024

AbstractOcean plastic pollution is a global concern, exacerbated by the distinctive physiochemical characteristics of nanoplastics (NPs), making it crucial to study the impacts on marine animals. While most studies focus on the impacts of waterborne NP exposure, trophic transfer is another key transport mechanism that may also provide insight into the potential transfer of NPs to humans through the food chain. This study investigates polystyrene NP transfer toCoryphaena hippurus(mahi-mahi) larvae, a widely consumed fish and significant marine predator, during the early life stage. Using a two-step food chain,Brachionus plicatilis(rotifers) were exposed to NPs, and subsequently fed toC. hippuruslarvae, with exposure durations ranging from 24 to 96 h. Significant NP transfer was observed via the food chain, varying with exposure duration. A depuration study over 72 h, simulating environmental intermittent NP exposure, revealed substantial NP excretion but also notable retention in the larvae. Biodistribution analysis indicated that most NPs accumulated in the gut, with a significant portion remaining post-depuration and some translocating to other body parts. Despite no significant effects on body length and eye diameter during this short study period, histopathological analysis revealed intestinal tissue damage in the larvae.Graphical abstract
Ethanol exposure model in zebrafish causes phenotypic, behavioral and gene expression changes that mimic Fetal Alcohol Spectrum Disorders in human birth cohorts
Authors: Yilmaz Elanur , Nelson Nastasia , Tosto Giuseppe , Carter R. Colin , Kizil Caghan 
Published: August 2024

ABSTRACTFetal Alcohol Spectrum Disorders (FASD) represent a significant global health challenge, characterized by physical and neurodevelopmental abnormalities in offspring resulting from prenatal alcohol exposure. This study aims to utilize the zebrafish to examine the phenotypic, behavioral, and molecular changes associated with embryonic ethanol exposure, providing a model for human FASD conditions. Our study exposed zebrafish embryos to 0.5% ethanol during a critical developmental window (2-24 hours post-fertilization) and documented significant craniofacial and cardiac deformities, which recapitulate what has been observed in human FASD in humans. Notably, exposed zebrafish exhibited reduced skull and eye sizes, thickened jaw size, and enlarged heart chambers. We found reduced burst swim distance following a touch stimulus, a novel behavioral assessment of potential deficits in sensory processing such as processing speed and/or stress/startle response, both of which are affected in human FASD. Whole-organism gene expression was found to be altered by ethanol for orthologs of four of five inflammation-related genes for which placental expression was previously found to be altered in response to alcohol in human placentas (SERPINE1, CRHB, BCL2L1, PSMB4, PTGS2A). We conclude that the zebrafish model effectively mimics several FASD phenotypes observed in humans, confirming gene expression changes we have previously documented in a human observational study and providing a valuable platform for exploring the underlying mechanisms of alcohol-induced embryonic alterations and for developing diagnostic markers and therapeutic targets for early intervention.
Evolution ofsex hormone-binding globulingene expression in the primate testis
Authors: Meyers Warren M. , Hammond Geoffrey L. 
Published: August 2024

AbstractIn lower mammals testicular sex hormone-binding globulin (SHBG), also known as androgen binding protein, is well known to be a product of the Sertoli cells. However in humans, testicular SHBG is a product of the germ cells, is expressed from an upstream promoter and contains an alternative first exon 1A. Examination of testicularSHBGtranscripts from members across primate suborders revealed that transcripts containing exon 1A are unique to Hominoids and Old World Monkeys. In contrast testicularSHBGtranscripts in gray mouse lemur contained the proximal exon 1, while no evidence forSHBGexpression could be detected in marmoset monkey testes. In general, the exonic identity of primate testicularSHBGtranscripts could be predicted based on the structure of their gene’s 5’ regulatory region and we show that they change through the primate clade. This work provides insights into how molecular evolution of higher primateSHBGgenes has resulted in distinct changes in how it is expressed in their testes.
Taking on colonial institutions: making room for an Indigenous Research Paradigm in prospective biomedical research in tertiary hospitals
Authors: O’Brien Jessica , Gutman Sarah J , Wade Vicki , Walker Toni , Taylor Andrew J , Adams Karen 
Published: August 2024

AbstractBackgroundA paradigmatic clash exists between biomedical and Indigenous research frameworks. Problematically, when ill-fit biomedical research frameworks are applied Indigenous peoples can experience exclusion from biomedical studies and consequent potential health benefits. To overcome these issues, community based participatory research methodologies are often recommended. However, these can prove difficult to apply in tertiary healthcare research where prospective Indigenous peoples and families participating in research will come from unforeseen and numerous Indigenous communities. Adding further complexity, there appears a dearth of information for achieving incorporation of decolonising and Indigenous research frameworks into this type of prospective research.MethodsWe sought to reflect on and describe inclusion of an Indigenous Research Paradigm into the establishment of a prospective multi-site tertiary healthcare study on improving diagnosis and treatment of acute rheumatic fever. To generate reflection, the First Nations’ Yarning method was employed allowing qualitative findings to be generated via Indigenous epistemology and ontology.FindingsFour main areas were identified as requiring significant change to align with an Indigenous Research Paradigm: stakeholder engagement, project design, consent processes, and multi-site approach. Multi-layered Indigenous leadership was recognised as a crucial component of the transformation and of the project’s success more broadly.InterpretationWith extensive local First Nations involvement and a First Nations-led research team, a multi-site institution-based biomedical research project can be successfully adapted to be more in keeping with an Indigenous Research Paradigm.
Incidence of TB-IRIS Among HIV+ve Patients in North India: A Prospective Study
Authors: Gupta Priyanka , Tripathi Anil Kumar , Singh Kaleshwar Prasad , Gupta Abhishek 
Published: August 2024

ABSTRACTIntroductionTB-IRIS is an important cause of morbidity and mortality in patients with HIV disease who are initiated on ART. This prospective study investigates the incidence and associated risk factors of TB-IRIS among HIV+ve patients initiating ART in North India.MethodsThe study included 400 ART-naive HIV+ve patients with or without pre-existing TB. Participants underwent clinical evaluation, laboratory tests, and imaging at baseline, followed by monthly follow-ups to monitor the development of TB-IRIS over a year.ResultsThe study identified a TB-IRIS incidence of 9.5% among the cohort. The mean duration for TB-IRIS onset was 2.87 months, with a higher prevalence noted in patients within the first two months of ART initiation. Key baseline factors associated with TB-IRIS included low CD4 count, Hb levels, high total leukocyte count, serum creatinine, and TC levels. Notably, the CD4 count, and inflammatory markers such as CRP and ESR significantly increased from baseline to the development of TB-IRIS. The study also highlighted a significantly higher mortality rate among TB-IRIS patients compared to those without IRIS.ConclusionThe findings underscore the necessity for vigilant monitoring and early detection of TB-IRIS in HIV+ve patients undergoing ART in TB-endemic regions to mitigate morbidity and mortality.
Repetitive sensory stimulation potentiates and recruits sensory-evoked cortical population activity
Authors: Williams Leena Eve , Küffer Laura , Bawa Tanika , Husi Elodie , Pagès Stéphane , Holtmaat Anthony 
Published: August 2024

ABSTRACTSensory experience and learning are thought to be associated with plasticity of neocortical circuits. Repetitive sensory stimulation can induce long-term potentiation (LTP) of cortical excitatory synapses in anesthetized mice; however, it is unclear if these phenomena are associated with sustained changes in activity during wakefulness. Here we used time-lapse, calcium imaging of layer (L) 2/3 neurons in the primary somatosensory cortex (S1), in awake male mice, to assess the effects of a bout of rhythmic whisker stimulation (RWS) at a frequency by which rodents sample objects. We found that RWS induced a 1h-increase in whisker-evoked L2/3 neuronal activity. This was not observed for whiskers functionally connected to distant cortical columns. We also found that RWS altered whether individual neurons encoded subsequent stimulus representation by either being recruited or suppressed. Vasoactive intestinal-peptide-expressing (VIP) interneurons, which promote plasticity through disinhibition of pyramidal neurons, were found to exclusively elevate activity during RWS. These findings indicate that cortical neurons’ representation of sensory input can be modulated over hours through repetitive sensory stimulation, which may be gated by activation of disinhibitory circuits.SIGNIFICANCE STATEMENTSensory experience and learning are thought to be associated with the plasticity of cortical synaptic circuits. Here, we tested how repeated sensory stimulation changes subsequent sensory-evoked responses, using the mouse somatosensory cortex as a model. This cortical area processes, among others, sensory information from the whiskers. We found that rhythmic whisker stimulation potentiated excitatory neuronal activity for an hour, and identified a disinhibitory interneuron-mediated mechanism that could gate this plasticity. This work increases our understanding of sensory learning and experience-dependent plasticity processes by demonstrating that cortical representations of sensory input are dynamic and are effectively modulated by repeated sensory stimulation.
Magnetoelectric Microrobots for Spinal Cord Injury Regeneration
Authors: Ye Hao , Zang Jingjing , Zhu Jiawei , Arx Denis von , Pustovalov Vitaly , Mao Minmin , Tang Qiao , Veciana Andrea , Torlakcik Harun , Zhang Elric , Sevim Semih , Sanchis-Gual Roger , Chen Xiang-Zhong , Ahmed Daniel , Sanchez-Vives Maria V. , Puigmartí-Luis Josep , Nelson Bradley J. , Neuhauss Stephan C. F. , Pané Salvador 
Published: August 2024

ABSTRACTRegenerative medicine continually seeks effective methods to address spinal cord injuries (SCI), which are known for their limited regenerative potential. Despite advances in neural progenitor cell (NPC) transplants for spinal cord injuries, challenges related to graft survival, reliablein vivodifferentiation, and neural integration significantly hinder real functional recovery and limit clinical outcomes. This study introduces ‘NPCbots’, biohybrid microrobots engineered by integrating human-induced pluripotent stem cell-derived NPCs with magnetoelectric nanoparticles composed of cobalt ferrite-barium titanate. These enable magnetic navigation and neuronal stimulation, enhancing targeted therapeutic interventions. Our lab-on-a-chip system allows for the mass production of NPCbots, ensuring their differentiation and biocompatibility. Remarkably, in a zebrafish model of SCI, NPCbots stimulated by an alternating magnetic field demonstrated rapidin vivodifferentiation and integration into damaged neural pathways, significantly enhancing neural regeneration. Within three days, injured zebrafish treated with NPCbots exhibited almost normal swimming behavior and significantly improved exploratory behavior, showcasing the potential of NPCbots to swiftly repair neural structures and restore the central nervous system’s functionality in spinal cord injury models through non-invasive means. Additionally, precisein vitroandin vivomanipulation of NPCbots indicates their broader application in various neurodegenerative disorders, offering a promising route for effective spinal cord and neurological recovery.
SARM1 orthosteric base exchange inhibitors cause subinhibitory SARM1 activation
Authors: Leahey Rebecca , Weber Martin , Cho Chang Hoon , Hur Seong , Cramer Amber , Manzanares Karla , Babin Brett , Boenig Gladys , Kring Taylor , Liu Liling , Cui Yusi , Ganti Anjani , Evans John P. , Nespi Marika , Ly Justin , Nugent Alicia A. , Green Samantha , Chan Bryan , Hoogenraad Casper C. , Delwig Anton , Hinz Flora I. 
Published: August 2024

ABSTRACTSARM1, an octameric NADase, is a key regulator of axon degeneration and an emerging target in small molecule drug discovery to treat a wide range of neurodegenerative diseases. Recently, a structurally diverse series of adduct-forming, orthosteric SARM1 inhibitors have been discovered. Here, we show that subinhibitory concentrations of these orthosteric inhibitors, under mildly SARM1 activating conditions, cause sustained SARM1 activation. This synergistic adverse effect leads to increased nicotinamide adenine dinucleotide (NAD) consumption, neurodegeneration and release of the biomarker neurofilament-light (NfL) in cultured cortical neurons. In two distinct animal models, we found that low-dose treatment with these orthosteric SARM1 inhibitors results in increased plasma NfL and adverse events when combined with cellular stress or injury conditions. This may present a critical liability for orthosteric SARM1 inhibitors in certain patient populations.
50-year fire legacy regulates soil microbial carbon and nutrient cycling responses to new fire
Authors: Revillini Daniel , Searcy Christopher A. , Afkhami Michelle E. 
Published: August 2024

AbstractFire disturbances are becoming more common, more intense, and further-reaching across the globe, with consequences for ecosystem functioning. Importantly, fire can have strong effects on the soil microbiome, including community and functional changes after fire, but surprisingly little is known regarding the role of soil fire legacy in shaping responses to recent fire. To address this gap, we conducted a manipulative field experiment administering fire across 32 soils with varying fire legacies, including combinations of 1-7 historic fires and 1-33 years since most recent fire. We analyzed soil metatranscriptomes, determining for the first time how fire and fire legacy interactively affect metabolically-active soil taxa, the microbial regulation of important carbon (C), nitrogen (N) and phosphorus (P) cycling, expression of carbohydrate-cycling enzyme pathways, and functional gene co-expression networks. Experimental fire strongly downregulated fungal activity while upregulating many bacterial and archaeal phyla. Further, fire decreased soil capacity for microbial C and N cycling and P transport, and drastically rewired functional gene co-expression. Perhaps most importantly, we highlight a novel role of soil fire legacy in regulation of microbial C, N, and P responses to recent fire. We observed a greater number of functional genes responsive to the interactive effects of fire and fire legacy than those affected solely by recent fire, indicating that many functional genes respond to fire only under certain fire legacy contexts. Therefore, without incorporating fire legacy of soils, studies will miss important ways that fire shapes microbial roles in ecosystem functioning. Finally, we showed that fire caused significant downregulation of carbon metabolism and nutrient cycling genes in microbiomes under abnormal soil fire histories, producing a novel warning for the future: human manipulation of fire legacies, either indirectly through global change-induced fire intensification or directly through fire suppression, can negatively impact soil microbiome functional responses to new fires.