bluuebunny/crossref_metadata_2025_split huggingface dataset:
Organization of an Ascending Circuit that Conveys Flight Motor State
Authors: Cheong Han S. J. , Boone Kaitlyn N. , Bennett Marryn M. , Salman Farzaan , Ralston Jacob D. , Hatch Kaleb , Allen Raven F. , Phelps Alec M. , Cook Andrew P. , Phelps Jasper S. , Erginkaya Mert , Lee Wei-Chung A. , Card Gwyneth M. , Daly Kevin C. , Dacks Andrew M. 
Published: June 2023

SummaryNatural behaviors are a coordinated symphony of motor acts which drive self-induced or reafferent sensory activation. Single sensors only signal presence and magnitude of a sensory cue; they cannot disambiguate exafferent (externally-induced) from reafferent sources. Nevertheless, animals readily differentiate between these sources of sensory signals to make appropriate decisions and initiate adaptive behavioral outcomes. This is mediated by predictive motor signaling mechanisms, which emanate from motor control pathways to sensory processing pathways, but how predictive motor signaling circuits function at the cellular and synaptic level is poorly understood. We use a variety of techniques, including connectomics from both male and female electron microscopy volumes, transcriptomics, neuroanatomical, physiological and behavioral approaches to resolve the network architecture of two pairs of ascending histaminergic neurons (AHNs), which putatively provide predictive motor signals to several sensory and motor neuropil. Both AHN pairs receive input primarily from an overlapping population of descending neurons, many of which drive wing motor output. The two AHN pairs target almost exclusively non-overlapping downstream neural networks including those that process visual, auditory and mechanosensory information as well as networks coordinating wing, haltere, and leg motor output. These results support the conclusion that the AHN pairs multi-task, integrating a large amount of common input, then tile their output in the brain, providing predictive motor signals to non-overlapping sensory networks affecting motor control both directly and indirectly.
Protein-Protein Interaction Prediction is Achievable with Large Language Models
Authors: Hallee Logan , Gleghorn Jason P. 
Published: June 2023

AbstractPredicting protein-protein interactions (PPIs) is vital for elucidating fundamental biology, designing peptide therapeutics, and for high-throughput protein annotation. This is particularly relevant in the current biotechnology landscape characterized by the proliferation of protein generative models, which necessitate a high-throughput and generalized PPI predictor for proteins regardless of conventional motifs or known biological functions. Our work addresses this need and provides strong evidence of the utility and reliability of protein language models (pLMs) in learning the PPI objective. We demonstrated that with the use of a sizable balanced dataset, pLMs achieve state-of-the-art performance metrics in PPI prediction on diverse proteins. To generate a dataset that allows for the approximation of these conditions, we implemented a novel synthetic data generation scheme to augment BIOGRID and Negatome datasets. The enhancement of these datasets was then used to fine-tune ProtBERT for PPI prediction to develop a model that we call SYNTERACT (SYNThetic data-driven protein-protein intERACtion Transformer). Our results are compelling, demonstrating 92% accuracy on validated positive and negative interacting pairs derived from 50 different organisms, all of which were excluded from the training phase. In addition to the high metrics, secondary analysis revealed that our synthetic negative data was able to successfully mimic actual negative samples, further reinforcing the integrity of synthetic data additions to PPI datasets. Another notable discovery was the ease in which previously existing PPI datasets could be predicted with simplistic features, calling into question if they can actually inform PPI prediction. We find that the subcellular compartment bias inherent to the compilation of these datasets is learnable with deep learning methods and demonstrate that our approach is not burdened by this disadvantage.
Fundamental role for the creatine kinase pathway in protection from murine colitis
Authors: Hall Caroline HT , Lanis Jordi M , Dowdell Alexander S , Murphy Emily M , Colgan Sean P 
Published: June 2023

AbstractInflammatory diseases of the digestive tract, including inflammatory bowel disease (IBD), cause metabolic stress within mucosal tissue. Creatine is a key energetic regulator. We previously reported a loss of creatine kinases (CKs) and the creatine transporter expression in IBD patient intestinal biopsy samples and that creatine supplementation was protective in a dextran sulfate sodium (DSS) colitis mouse model. In the present studies, we evaluated the role of CK loss in active inflammation using the DSS colitis model. Mice lacking expression of CKB/CKMit (CKdKO) showed increased susceptibility to DSS colitis (weight loss, disease activity, permeability, colon length and histology). In a broad cytokine profiling, CKdKO mice expressed near absent IFN-γ levels. We identified losses in IFN-γ production from CD4+and CD8+T cells isolated from CKdKO mice. Addback of IFN-γ during DSS treatment resulted in partial protection for CKdKO mice. We identified basal stabilization of the transcription factor hypoxia-inducible factor (HIF) in CKdKO splenocytes and pharmacological stabilization of HIF resulted in reduced IFN-γ production by control splenocytes. Thus, the loss of IFN-γ production by CD4+and CD8+T cells in CKdKO mice resulted in increased colitis susceptibility and indicates that CK is protective in active mucosal inflammation.
The genomic landscape of wildSaccharomyces cerevisiaeis shaped by complex patterns of admixture, aneuploidy and recombination
Authors: Ward Chris M. , Onetto Cristobal A. , Van Den Heuvel Steven , Cuijvers Kathleen M. , Hale Laura J. , Borneman Anthony R. 
Published: June 2023

AbstractCultural exchange of fermentation techniques has driven the spread ofSaccharomyces cerevisiaeacross the globe, establishing wild populations in many countries. Despite this, most modern commercial fermentations are inoculated using monocultures, rather than relying on natural populations, potentially impacting wild population diversity. Here we investigate the genomic landscape of 411 wildS. cerevisiaeisolated from spontaneous grape fermentations in Australia across multiple locations, years, and grape cultivars. Spontaneous fermentations contained highly recombined mosaic strains that commonly exhibited aneuploidy of chromosomes 1, 3, 6 and 9. Assigning wild genomic windows to putative ancestral origin revealed that few closely related commercial lineages have come to dominate the genetic landscape, contributing most of the genetic variation. Fine-scale phylogenetic analysis of loci not observed in strains of commercial wine origin identified widespread admixture with the Beer2 clade along with three independent admixture events from potentially endemic Oceanic lineages that last shared an ancestor with modern East AsianS. cerevisiaepopulations. Our results illustrate how commercial use of microbes can affect local microorganism genetic diversity and demonstrates the presence of non-domesticated, non-European derived lineages ofS. cerevisiaein Australian ecological niches that are actively admixing.
Sex specific role of RNA-binding protein, AUF1, on prolonged hypersensitivity after repetitive ischemia with reperfusion injury
Authors: Quijas Meranda M. , Queme Luis F. , Weyler Alex A. , Butterfield Ally , Joshi Diya P. , Mitxelena-Balerdi Irati , Jankowski Michael P. 
Published: June 2023

AbstractRepetitive ischemia with reperfusion (I/R) injury is a common cause of myalgia. I/R injuries occur in many conditions that differentially affect males and females including complex regional pain syndrome and fibromyalgia. Our preclinical studies have indicated that primary afferent sensitization and behavioral hypersensitivity due to I/R may be due to sex specific gene expression in the DRGs and distinct upregulation of growth factors and cytokines in the affected muscles. In order to determine how these unique gene expression programs may be established in a sex dependent manner in a model that more closely mimics clinical scenarios, we utilized a newly developed prolonged ischemic myalgia model in mice whereby animals experience repeated I/R injuries to the forelimb and compared behavioral results to unbiased and targeted screening strategies in male and female DRGs. Several distinct proteins were found to be differentially expressed in male and female DRGs, including AU-rich element RNA binding protein (AUF1), which is known to regulate gene expression. Nerve specific siRNA-mediated knockdown of AUF1 inhibited prolonged hypersensitivity in females only, while overexpression of AUF1 in male DRG neurons increased some pain-like responses. Further, AUF1 knockdown was able to specifically inhibit repeated I/R induced gene expression in females but not males. Data suggests that RNA binding proteins like AUF1 may underlie the sex specific effects on DRG gene expression that modulate behavioral hypersensitivity after repeated I/R injury. This study may aid in finding distinct receptor differences related to the evolution of acute to chronic ischemic muscle pain development between sexes.
Brain network dynamics in transitions of consciousness reorganize according to task engagement
Authors: Kumar Samika S. , Arzi Anat , Bareham Corinne , Gonzalez-Castillo Javier , Fernandez Isabel , Tagliazucchi Enzo , Mediano Pedro A.M. , Bandettini Peter A. , Bekinschtein Tristan A. 
Published: June 2023

SUMMARYSubstantial changes in behavior, physiology, and brain function occur when alertness decreases1– 5. These changes in brain function involve increased synchronization between cortical areas6,7as well as alterations in sensory processing pathways and networks connecting the thalamus and cortex5,8–11. Cognitive tasks engage overlapping functional networks with sensory pathways facilitating information processing12,13, and thalamocortical and corticocortical networks supporting task performance14,15. Frontoparietal circuits play a crucial role in cognitive tasks16and states of decreased consciousness17. To develop an integrated framework of consciousness and cognition, it is important to understand how fluctuations in alertness and cognitive processing interact in these shared circuits18. Our hypothesis is that during periods of low alertness, individuals who actively maintain task engagement would recruit additional frontoparietal and sensory processing networks, while thalamocortical dynamics that typically change during sleep onset would remain unaffected. Our findings demonstrated that as alertness decreased, passively listening to auditory tones led to increased synchronization in the parietal lobe, whereas actively performing an auditory task resulted in increased long-range frontoparietal synchronization. During decreasing alertness, passive listening (but not active task engagement) was associated with widespread increased synchronization between the thalamus and cortex. In contrast, active task engagement (but not passive listening) led to increased synchronization between the auditory cortex and the rest of the brain. These results reveal the functional mechanisms of the brain’s flexible reorganization during transitions of consciousness when individuals are actively engaged in cognitive processes.
Genome analysis ofLegionella pneumophilaST901 an Italian endemic strain
Authors: Ricci Maria Luisa , Fillo Silvia , Giordani Francesco , Ciammaruconi Andrea , Girolamo Antonietta , Anselmo Anna , Monte Anella , Cusimano Valerio , Caporali Maria Grazia , Rota Maria Cristina , Petzol Markus , Afshar Baharak , Lista Florigio , Luck Christian , Scaturro Maria 
Published: June 2023

AbstractLegionella pneumophilatyping, based on SBT analysis, has been allowing to identify sequence types (ST) responsible for many Legionnaires’ disease cases. ST901 has so far been identified only in a town of the northern Italy, where it caused numerous travel-associated Legionnaires’ disease cases over a 32-year period. In this study, ST901 were analyzed by whole genome sequencing in looking for both differences and similarities inside this ST and with other unrelatedLegionellastrains. To this aim core genome multi locus sequence type, single nucleotide polymorphisms and pangenome analyses were performed. ST901 resulted highly similar each other, characterized by I-C CRISPR-cas system, located on the chromosome and by a putative plasmid, highly similar to that found in Lp strain Lens, which contains I-F CRISPR-cas system. Accessory genomic islands, either already described or specifically found in ST901, were also shown.In conclusion ST901 has been quite preserved over the time. The co-occurrence of two phage resistance systems and genomic islands of virulence could have made the ST901 enough virulent to cause such a high number of cases.Summary blurbST901 appears as endemic of the Northern Italy, with virulence traits similar to those in Alcoy and Corby, and with two CRISPR-cas systems which probably preserved them in their environmental niche.
Tonic Meningeal Interleukin-10 Upregulates Delta Opioid Receptor to Prevent Relapse to Pain
Authors: Inyang Kufreobong E. , Sim Jaewon , Clark Kimberly B. , Matan Geron , Monahan Karli , Evans Christine , Beng Po , Ma Jiacheng “Vicky” , Heijnen Cobi J. , Dantzer Robert , Scherrer Gregory , Kavelaars Annemieke , Bernard Matthew , Aldhamen Yasser , Folger Joseph K. , Laumet Geoffroy 
Published: June 2023

AbstractChronic pain often alternates between transient remission and relapse of severe pain. While most research on chronic pain has focused on mechanisms maintaining pain, there is a critical unmet need to understand what prevents pain from re-emerging in those who recover from acute pain. We found that interleukin (IL)-10, a pain resolving cytokine, is persistently produced by resident macrophages in the spinal meninges during remission from pain. IL-10 upregulated expression and analgesic activity of δ-opioid receptor (δOR) in the dorsal root ganglion. Genetic or pharmacological inhibition of IL-10 signaling or δOR triggered relapse to pain in both sexes. These data challenge the widespread assumption that remission of pain is simply a return to the naïve state before pain was induced. Instead, our findings strongly suggest a novel concept that: remission is a state of lasting pain vulnerability that results from a long-lasting neuroimmune interactions in the nociceptive system.
Co-evolutionary dynamics of mammalian brain and body size
Authors: Venditti Chris , Baker Joanna , Barton Robert A. 
Published: June 2023

SummaryDespite decades of comparative studies, fundamental questions remain about how brain and body size co-evolved. Divergent explanations exist concurrently in the literature for phenomena such as variation in brain relative to body size, variability in the scaling relationship across taxonomic levels and between taxonomic groups, and purported evolutionary trends. Here we resolve these issues using a comprehensive dataset of brain and body masses across the mammal radiation, and a method enabling us to study brain relative to body mass evolution while estimating their evolutionary rates along the branches of a phylogeny. Contrary to the rarely questioned assumption of a log-linear relationship, we find that a curvilinear model best describes the evolutionary relationship between log brain mass and log body mass. This model greatly simplifies our understanding of mammalian brain-body co-evolution: it can simultaneously explain both the much-discussed taxon-level effect and variation in slopes and intercepts previously attributed to complex scaling patterns. We also document substantial variation in rates of relative brain mass evolution, with bursts of change scattered through the tree. General trends for increasing relative brain size over time are found in only three mammalian orders, with the most extreme case being primates, setting the stage for the uniquely rapid directional increase that ultimately produced the computational powers of the human brain.
Brain Representations of Affective Valence and Intensity in Sustained Pleasure and Pain
Authors: Lee Soo Ahn , Lee Jae-Joong , Han Jisoo , Choi Myunghwan , Wager Tor D. , Woo Choong-Wan 
Published: June 2023

ABSTRACTPleasure and pain are two opposites that compete and influence each other, implying the existence of brain systems that integrate them to generate modality-general affective experiences. Here, we examined the brain’s general affective codes (i.e., affective valence and intensity) across sustained pleasure and pain through an fMRI experiment (n= 58). We found that the distinct sub-populations of voxels within the ventromedial and lateral prefrontal cortices, the orbitofrontal cortex, the anterior insula, and the amygdala were involved in decoding affective valence versus intensity, which was replicated in an independent test dataset (n= 62). The affective valence and intensity models were connected to distinct large-scale brain networks—the intensity model to the ventral attention network and the valence model to the limbic and default mode networks. Overall, this study identified the brain representations of affective valence and intensity across pleasure and pain, promoting the systems-level understanding of human affective experiences.
Not everything, not everywhere, not all at once: a study of brain-wide encoding of movement
Authors: Wang Ziyue Aiden , Chen Susu , Liu Yi , Liu Dave , Svoboda Karel , Li Nuo , Druckmann Shaul 
Published: June 2023

AbstractActivity related to movement is found throughout sensory and motor regions of the brain. However, it remains unclear how movement-related activity is distributed across the brain and whether systematic differences exist between brain areas. Here, we analyzed movement related activity in brain-wide recordings containing more than 50,000 neurons in mice performing a decision-making task. Using multiple techniques, from markers to deep neural networks, we find that movement-related signals were pervasive across the brain, but systematically differed across areas. Movement-related activity was stronger in areas closer to the motor or sensory periphery. Delineating activity in terms of sensory- and motor-related components revealed finer scale structures of their encodings within brain areas. We further identified activity modulation that correlates with decision-making and uninstructed movement. Our work charts out a largescale map of movement encoding and provides a roadmap for dissecting different forms of movement and decision-making related encoding across multi-regional neural circuits.
Proactive Versus Reactive Control Strategies Differentially Mediate Alcohol Drinking in Wistar and P rats
Authors: Morningstar M.D. , Timme N.M. , Ma B. , Cornwell E. , Galbari T. , Lapish C.C. 
Published: June 2023

AbstractProblematic alcohol consumption is associated with deficits in decision-making, and alterations in prefrontal cortex neural activity likely contributes. We hypothesized that differences in cognitive control would be evident between male Wistar rats and a model for genetic risk for alcohol use disorder (alcohol-preferring P rats). Cognitive control can be split into proactive and reactive components. Proactive control maintains goal-directed behavior independent of a stimulus whereas reactive control elicits goal-directed behavior at the time of a stimulus. We hypothesized that Wistars would show proactive control over alcohol-seeking whereas P rats would show reactive control over alcohol-seeking. Neural ensembles were recorded from prefrontal cortex during an alcohol seeking task that utilized two session types. On congruent sessions the CS+ was on the same side as alcohol access. Incongruent sessions presented alcohol opposite the CS+. Wistars, but not P rats, exhibited an increase in incorrect approaches during incongruent sessions, suggesting that Wistars utilized the previously learned task-rule. This motivated the hypothesis that ensemble activity reflecting proactive control would be observable in Wistars but not P rats. While P rats showed differences in neural activity at times relevant for alcohol delivery, Wistars showed differences prior to approaching the sipper. These results support our hypothesis that Wistars are more likely to engage proactive cognitive-control strategies whereas P rats are more likely to engage reactive cognitive control strategies. Although P rats were bred to prefer alcohol, differences in cognitive control may reflect a sequela of behaviors that mirror those in humans at risk for an AUD.Significance StatementCognitive control refers to the set of executive functions necessary for goal-directed behavior. It is a major mediator of addictive behaviors and can be subdivided into proactive and reactive cognitive control. We observed behavioral and electrophysiological differences between outbred Wistar rats and the selectively bred Indiana alcohol-preferring P rat while they sought and consumed alcohol. These differences are best explained by reactive cognitive control in P rats and proactive in Wistar rats.
Low-dose exposure to malathion and radiation culminates in the dysregulation of multiple neuronal processes instigating neurotoxicity and activation of neurodegeneration pathways in mice hippocampus
Authors: Rekha K N , Venkidesh B S , Nayak Sangeetha , Reghunathan Dinesh , Mallya Sandeep , Sharan Krishna , Satish Rao B S , Mumbrekar Kamalesh Dattaram 
Published: June 2023

AbstractNeurodegenerative disorders are a debilitating and persistent threat to the global elderly population carrying grim outcomes. Their genesis is often multifactorial, with a history of early exposure to xenobiotics like pesticides or diagnostic exposure to ionizing radiation. A holistic molecular insight into their mechanistic induction is still unclear upon single or combinatorial exposure to different toxicants. In the present study, one-month-old C57/BL-6J male mice were treated orally with malathion (MAL) (50mg/kg body wt. for 14 days) and/or a single whole-body radiation (IR) (0.5 Gy) on the 8thday. Post-treatment, behavioral assays were conducted to assess exploratory behavior, memory, and learning. Following sacrifice, brains were collected for histology, biochemical assays, and transcriptomic analysis. Differential expression analysis, Gene ontology, and pathway enrichment revealed several common and uniquely altered genes, biological processes, and pathways related to neurodegeneration, synaptic transmission and plasticity, neuronal survival, proliferation, and regulation of neuronal death. Increased astrogliosis was observed in the IR and co-exposure groups, with significant neuronal cell death and reduction in the expression of NeuN in all three groups. Sholl analysis and dendritic arborization/ spine density study revealed decreased total apical neuronal path length and dendritic spine density in all three groups. Decreased levels of antioxidant enzymes GST and GSH and acetylcholinesterase enzyme activity were also detected. However, there were no changes in exploratory behavior or learning and memory. Thus, explicating the molecular mechanisms behind MAL and IR can provide novel insights into the genesis of environmental factor-driven neurodegenerative pathogenesis.