bluuebunny/crossref_metadata_2025_split huggingface dataset:
Matreex: compact and interactive visualisation for scalable studies of large gene families
Authors: Rossier Victor , Train Clement , Nevers Yannis , Robinson-Rechavi Marc , Dessimoz Christophe 
Published: February 2023

AbstractStudying gene family evolution strongly benefits from insightful visualisations. However, the evergrowing number of sequenced genomes is leading to increasingly larger gene families, which challenges existing gene tree visualisations. Indeed, most of them present users with a dilemma: display complete but intractable gene trees, or collapse subtrees, thereby hiding their children’s information. Here, we introduce Matreex, a new dynamic tool to scale-up the visualisation of gene families. Matreex’s key idea is to use “phylogenetic” profiles, which are dense representations of gene repertoires, to minimise the information loss when collapsing subtrees. We illustrate Matreex usefulness with three biological applications. First, we demonstrate on the MutS family the power of combining gene trees and phylogenetic profiles to delve into precise evolutionary analyses of large multi-copy gene families. Secondly, by displaying 22 intraflagellar transport gene families across 622 species cumulating 5’500 representatives, we show how Matreex can be used to automate large-scale analyses of gene presence-absence. Notably, we report for the first time the complete loss of intraflagellar transport in the myxozoanThelohanellus kitauei. Finally, using the textbook example of visual opsins, we show Matreex’s potential to create easily interpretable figures for teaching and outreach. Matreex is available from the Python Package Index (pip install matreex) with the source code and documentation available athttps://github.com/DessimozLab/matreex.
Bacterial responses to complex mixtures of chemical pollutants
Authors: Smith Thomas P. , Clegg Tom , Ransome Emma , Martin-Lilley Thomas , Rosindell James , Woodward Guy , Pawar Samraat , Bell Thomas 
Published: February 2023

AbstractOur understanding of how microbes respond to pollutants is almost wholly based on single-species responses to individual chemicals. However, in natural environments, microbes experience the effects of multiple pollutants simultaneously, and their responses to these mixtures of chemicals may not be readily predictable based on their responses to each pollutant in isolation. Here we extended the scope and complexity of previous multi-stressor experiments by assaying the growth of model and non-model strains of bacteria in all 255 combinations of 8 chemical stressors. This approach allowed us to identify fitness effects arising from potential high-order interactions among stressor responses. We found that the bacterial strains responded in different ways to stressor mixtures, which could not be predicted simply from their phylogenetic relatedness. Responses to increasingly complex chemical mixtures were more likely to show a significant deviation from a null model based on the responses to each chemical alone. However, these net responses were mainly driven by lower-order interactions among a small number of chemicals, suggesting a limited role for complex high-order interactions. These results simplify the predictability of microbial populations and communities responding to multiple stressors, paving the way for the development of efficient next-generation eco-toxicological assays.
Serotonin modulates social responses to stressed conspecifics via insular 5-HT2Creceptors in rat
Authors: Ng Alexandra J. , Vincelette Lindsay K. , Li Jiayi , Brady Bridget H. , Christianson John P. 
Published: February 2023

ABSTRACTSocial interaction allows for the transfer of affective states among individuals, and the behaviors and expressions associated with pain and fear can evoke anxiety-like states in observers which shape subsequent social interactions. We hypothesized that social reactions to stressed individuals engage the serotonergic dorsal raphe nucleus (DRN) which promotes anxiety-like behavior via postsynaptic action of serotonin at serotonin 2C (5-HT2C) receptors in the forebrain. First, we inhibited the DRN by administering an agonist (8-OH-DPAT, 1µg in 0.5µL) for the inhibitory 5-HT1Aautoreceptors which silences 5-HT neuronal activity via G-protein coupled inward rectifying potassium channels. 8-OH-DPAT prevented the approach and avoidance, respectively, of stressed juvenile (PN30) or stressed adult (PN60) conspecifics in the social affective preference (SAP) test in rats. Similarly, systemic administration of a 5-HT2Creceptor antagonist (SB242084, 1mg/kg, i.p.) prevented approach and avoidance of stressed juvenile or adult conspecifics, respectively. Seeking a locus of 5-HT2Caction, we considered the posterior insular cortex which is critical for social affective behaviors and rich with 5-HT2Creceptors. SB242084 administered directly into the insular cortex (5µM in 0.5µL bilaterally)interfered with the typical approach and avoidance behaviors observed in the SAP test. Finally, using fluorescentin situhybridization, we found that 5-HT2Creceptor mRNA (htr2c)is primarily colocalized with mRNA associated with excitatory glutamatergic neurons (vglut1) in the posterior insula. Importantly, the results of these treatments were the same in male and female rats. These data suggest that interactions with stressed others require the serotonergic DRN and that serotonin modulates social affective decision-making via action at insular 5-HT2Creceptors.
mRNA interactions with disordered regions control protein activity
Authors: Luo Yang , Pratihar Supriya , Horste Ellen H. , Mitschka Sibylle , Mey Antonia S. J. S. , Al-Hashimi Hashim M. , Mayr Christine 
Published: February 2023

AbstractThe cytoplasm is compartmentalized into different translation environments. mRNAs use their 3′UTRs to localize to distinct cytoplasmic compartments, including TIS granules (TGs). Many transcription factors, including MYC, are translated in TGs. It was shown that translation of proteins in TGs enables the formation of protein complexes that cannot be established when these proteins are translated in the cytosol, but the mechanism is poorly understood. Here we show that MYC protein complexes that involve binding to the intrinsically disordered region (IDR) of MYC are only formed when MYC is translated in TGs. TG-dependent protein complexes require TG-enriched mRNAs for assembly. These mRNAs bind to a new and widespread RNA-binding domain in neutral or negatively charged IDRs in several transcription factors, including MYC. RNA-IDR interaction changes the conformational ensemble of the IDR, enabling the formation of MYC protein complexes that act in the nucleus and control functions that cannot be accomplished by cytosolically-translated MYC. We propose that certain mRNAs have IDR chaperone activity as they control IDR conformations. In addition to post-translational modifications, we found a novel mode of protein activity regulation. Since RNA-IDR interactions are prevalent, we suggest that mRNA-dependent control of protein functional states is widespread.
LRG1 is a novel HER3 ligand to promote growth in colorectal cancer
Authors: Rathore Moeez , Wright Michel’le , Martin Daniel , Huang Wei , Taylor Derek , Miyagi Masaru , Feng Hao , Li Yamu , Wang Zhenghe , Elis Lee M , Winter Jordan , Moss Stephen , Greenwood John , Wang Rui 
Published: February 2023

SummaryTherapy failure for patients with metastatic colorectal cancer (mCRC) remains an overarching challenge in the clinic. We find that liver endothelial cells secrete soluble factor(s) to promote mCRC growth in vitro and in vivo. We identify LRG1 in ECs secretome, which promotes growth in tumor cells through binding and activation of HER3. Pharmacological blocking of the LRG1/HER3 axis using LRG1 antibody 15C4 completely attenuated LRG1-induced HER3 activation and in vitro and in vivo growth of the tumor. Moreover, LRG1-/- mice with CRC allografts in the liver had 2 times longer overall survival than tumor-bearing LRG1+/+ mice. Lastly, unbiased -omics analysis and target-specific inhibitors identified eIF4-protein synthesis is significantly activated by the LRG1/HER3/RSK1/2 axis. This work reveals a paracrine mechanism of mCRC growth in liver microenvironment and highlighted the potential of blocking LRG1-HER3 and involved downstream pathways for treating patients with mCRC.Abstract Figure
A quantitative PCR assay for detection of the mycotoxigenic plant pathogen and food spoiling moldPaecilomyces niveusin fruit, food, and soil
Authors: Wang Tristan W. , Strickland David A. , Haredy Yasmin , Cox Kerik D. , Hodge Kathie T. 
Published: February 2023

AbstractThe postharvest fruit pathogenPaecilomyces niveusproduces ascospores that can survive some pasteurization temperatures, spoil fruit products, and contaminate them with patulin, an FDA-regulated mycotoxin. PreventingP. niveusfrom entering food systems requires a robust detection method to effectively determine sources ofP. niveusspoilage and disease inoculum. We designed a new robust and culture-independent detection method using species-specific primers (PnPATf/r) based on the patK gene, encoding a 6-methylsalicylic acid synthase, inP. niveus, for use in a rapid qPCR assay. Primer specificity was validated using 24 differentP. niveusisolates and 16 other important food spoilage and fruit pathogenic fungi. The threshold for detection of qPCR was 18 genome equivalents. To further validate our new detection method, we demonstrate its use in detectingP. niveusin infected fruits, infested soils and ciders, and in fruit arising from apple blossoms sprayed with aP. niveusspore suspension. Results from this study may help fruit producers address spoilage and patulin contamination by this food spoiling fungus.HighlightsNew primers specific toPaecilomyces niveus(PnPATf/r) were developed based on the patK geneA qPCR assay to detectP. niveuswas validated, and shown to be able to detect quantities ofP. niveusDNA as low as 18 genome equivalentsThe new qPCR assay was used to investigate the ability ofP. niveusascospores to infect strawberry fruits and enter apple fruits through apple blossom infestation
Is resting state fMRI better than individual characteristics at predicting cognition?
Authors: Omidvarnia Amir , Sasse Leonard , Larabi Daouia I. , Raimondo Federico , Hoffstaedter Felix , Kasper Jan , Dukart Juergen , Petersen Marvin , Cheng Bastian , Thomalla Götz , Eickhoff Simon B. , Patil Kaustubh R. 
Published: February 2023

AbstractChanges in spontaneous brain activity at rest provide rich information about behavior and cognition. The mathematical properties of resting-state functional magnetic resonance imaging (rsfMRI) are a depiction of brain function and are frequently used to predict cognitive phenotypes. Individual characteristics such as age, gender, and total intracranial volume (TIV) play an important role in predictive modeling of rsfMRI (for example, as “confounders” in many cases). It is unclear, however, to what extent rsfMRI carries independent information from the individual characteristics that is able to predict cognitive phenotypes. Here, we used predictive modeling to thoroughly examine the predictability of four cognitive phenotypes in 20,000 healthy UK Biobank subjects. We extracted common rsfMRI features of functional brain connectivity (FC) and temporal complexity (TC). We assessed the ability of these features to predict outcomes in the presence and absence of age, gender, and TIV. Additionally, we assessed the predictiveness of age, gender, and TIV only. We find TC and FC features to perform comparably with regard to predicting cognitive phenotypes. As compared to rsfMRI features, individual characteristics provide systematically better predictions with smaller sample sizes and, to some extent, in larger cohorts. It is also consistent across different levels of inherent temporal noise in rsfMRI. Our results suggest that when the objective is to perform cognitive predictions as opposed to understanding the relationship between brain and behavior, individual characteristics are more applicable than rsfMRI features.
Cortical activity emerges in region-specific patterns during early brain development
Authors: Suárez Rodrigo , Bluett Tobias , McCullough Michael H. , Avitan Lilach , Black Dylan A. , Paolino Annalisa , Fenlon Laura R. , Goodhill Geoffrey J. , Richards Linda J. 
Published: February 2023

AbstractThe development of precise neural circuits in the brain requires spontaneous patterns of neural activity prior to functional maturation. In the rodent cerebral cortex patchwork and wave patterns of activity develop in somatosensory and visual regions, respectively, and are present at birth. However, whether such activity patterns occur in non-eutherian mammals, as well as when and how they arise during development remain open questions relevant to understand brain formation in health and disease. Since the onset of patterned cortical activity is challenging to study prenatally in eutherians, here we offer a new approach in a minimally invasive manner using marsupial dunnarts, whose cortex forms postnatally. We discovered similar patchwork and travelling waves in the dunnart somatosensory and visual cortices at stage 27 (equivalent to newborn mice), and examined progressively earlier stages of development to determine their onset and how they first emerge. We observed that these patterns of activity emerge in a region-specific and sequential manner, becoming evident as early as stage 24 in somatosensory and stage 25 in visual cortices (equivalent to embryonic day 16 and 17, respectively, in mice), as cortical layers establish and thalamic axons innervate the cortex. In addition to sculpting synaptic connections of existing circuits, evolutionarily conserved patterns of neural activity could therefore help regulate early events in cortical development.Significance StatementRegion-specific patterns of neural activity are present at birth in rodents and are thought to refine synaptic connections during critical periods of cerebral cortex development. Marsupials are born much more immature than rodents, allowing the investigation of how these patterns arise in vivo. We discovered that cortical activity patterns are remarkably similar in marsupial dunnarts and rodents, and that they emerge very early, before cortical neurogenesis is complete. Moreover, they arise from the outset in different patterns specific to somatosensory and visual areas (i.e., patchworks and waves) indicating they may also play evolutionarily conserved roles in cortical regionalization during development.
The Relationship between Alcohol- and Sleep-related Traits: Results from Polygenic Risk Score Analyses and Mendelian Randomization Studies
Authors: Chakravorty Subhajit , Kember Rachel L. , Mazzotti Diego R. , Dashti Hassan S. , Toikumo Sylvanus , Gehrman Philip R. , Kranzler Henry R. 
Published: February 2023

AbstractBackgroundEpidemiologic studies have shown an association between sleep abnormalities and alcohol-related traits. Recent genome-wide association studies (GWAS) have identified genetic variants associated with sleep-related traits, including insomnia and sleep duration, and with alcohol-related phenotypes, including alcohol use disorder (AUD) and level of alcohol consumption.ObjectivesWe investigated whether genetic risk for insomnia and sleep duration abnormalities are associated with AUD and alcohol consumption. We also evaluated the causal relationships between sleep- and alcohol-related traits.MethodsIndividual level phenotype and genotype data from the Million Veteran Program was used. Polygenic risk scores (PRS) were computed using summary statistics from two recent discovery GWAS of insomnia (N=453,379 European-ancestry (EA) individuals) and sleep duration (N=446,118 EAs) and tested for association with lifetime AUD diagnosis (cases, N=34,658 EAs) and past-year Alcohol Use Disorders Identification Test-Consumption scale scores (AUDIT-C, N=200,680 EAs). Bi-directional two-sample Mendelian Randomization (MR) analyses assessed causal associations between the two sleep traits and the two alcohol-related traits.ResultsInsomnia PRS was positively associated with AUD at 2/9 PRS thresholds, with p<0.01 being the most significant (OR = 1.02, p = 3.48 × 10−5). Conversely, insomnia PRS was negatively associated with AUDIT-C at 6/9 PRS thresholds (most significant threshold being p=0.001 (β = - 0.02, p = 5.6 × 10−8). Sleep duration PRS was not associated with AUD, but was positively associated with AUDIT-C at 2/9 PRS thresholds, with the most significant threshold being p = 1 × 10−6(β = 0.01, p = 0.0009). MR analyses supported a significant positive causal effect of insomnia on AUD (14 SNPs; beta = 104.14; SE = 16.19; p = 2.22 × 10−5), although with significant heterogeneity. MR analyses also provided nominal evidence of a causal effect of AUD on insomnia (10 SNPs; beta = 0.01; SE = 0.007; p = 0.01). Finally, MR analyses showed that decreased sleep duration had a causal effect on the risk of AUD (27 SNPs; beta = -63.05; SE = 3.54; p = 4.55 × 10−16) and was robust to sensitivity analyses.ConclusionThe genetic risk for insomnia shows pleiotropy with AUD, and sleep continuity abnormalities have a causal influence on the development of AUD.
Tau expression and phosphorylation in enteroendocrine cells
Authors: Chapelet Guillaume , Béguin Nora , Castellano Blandine , Grit Isabelle , Oullier Thibauld , Neunlist Michel , Blottière Hervé , Rolli-Derkinderen Malvyne , Dréan Gwenola Le , Derkinderen Pascal 
Published: February 2023

AbstractBackground and objectiveThere is mounting evidence to suggest that the gut-brain axis is involved in the development of Parkinson’s disease (PD). In this regard, the enteroendocrine cells (EEC), which faces the gut lumen and are connected with both enteric neurons and glial cells have received growing attention. The recent observation showing that these cells express alpha-synuclein, a presynaptic neuronal protein genetically and neuropathologically linked to PD came to reinforce the assumption that EEC might be a key component of the neural circuit between the gut lumen and the brain for the bottom-up propagation of PD pathology. Besides alpha-synuclein, tau is another key protein involved in neurodegeneration and converging evidences indicate that there is an interplay between these two proteins at both molecular and pathological levels. There are no existing studies on tau in EEC and therefore we set out to examine the isoform profile and phosphorylation state of tau in these cells.MethodsSurgical specimens of human colon from control subjects were analyzed by immunohistochemistry using a panel of anti-tau antibodies together with chromogranin A and Glucagon-like peptide-1 (two EEC markers) antibodies. To investigate tau phosphorylation and expression further, two EEC lines, namely GLUTag and NCI-H716 were analyzed by western blot after dephosphorylation with pan-tau and tau isoform specific antibodies. Eventually, GLUTag were treated with propionate and butyrate, two short chain fatty acids known to sense EEC, and analyzed at different time points by western blot with an antibody specific for tau phosphorylated at Thr205.ResultsWe found that tau is expressed and phosphorylated in EEC in adult human colon and that both EEC lines mainly express two tau isoforms that are phosphorylated under basal condition. Both propionate and butyrate regulated tau phosphorylation state by decreasing its phosphorylation at Thr205.Conclusion and inferenceOur study is the first to characterize tau in human EEC and in EEC lines. As a whole, our findings provide a basis to unravel the functions of tau in EEC and to further investigate the possibility of pathological changes in tauopathies and synucleinopathies.
Reorganization of corticospinal projections after prominent recovery of finger dexterity from partial spinal cord injury in macaque monkeys
Authors: Sawada Masahiro , Yoshino-Saito Kimika , Ninomiya Taihei , Oishi Takao , Yamashita Toshihide , Onoe Hirotaka , Takada Masahiko , Nishimura Yukio , Isa Tadashi 
Published: February 2023

ABSTRACTWe investigated morphological changes in the corticospinal tract (CST) to understand the mechanism underlying recovery of hand function after lesion of the CST at the C4/C5 border in 7 macaque monkeys. All monkeys exhibited complete recovery of precision grip success ratio within a few months. The trajectories and terminals of CST from the contralesional (n = 4) and ipsilesional (n = 3) hand area of primary motor cortex (M1) were investigated at 5-29 months after the injury using an anterograde neural tracer, biotinylated dextran amine (BDA). Reorganization of the CST was assessed by counting the number of BDA-labeled axons and button-like swellings in the gray and white matters. Rostral to the lesion (at C3), the number of axon collaterals of the descending axons from both contralesional and ipsilesional M1 entering the ipsilesional and contralesional gray matter, respectively, were increased. Caudal to the lesion (at C8), axons originating from the contralesional M1, descending in the preserved gray matter around the lesion, and terminating in ipsilesional laminae VI/VII and IX were observed. In addition, axons and terminals from the ipsilesional M1 increased in the ipsilesional laminae VI/VII and IX after recrossing the midline, which were not observed in intact monkeys. Conversely, axons originating from the ipsilesional M1 and directed toward the contralesional laminae VI/VII and IX decreased. These results suggest that multiple reorganizations of the corticospinal projections to spinal segments both rostral and caudal to the lesion originating from bilateral M1 underlie a prominent recovery in long-term after spinal cord injury.SIGNIFICANCE STATEMENTPrevious studies have shown that dexterous finger movements recover prominently after lesion of the corticospinal tract (CST) at the mid-cervical segments through rehabilitative training in macaque monkeys. Here, we show reorganization of the CST including sprouting of axons originating from the contralesional and ipsilesional motor cortex in the gray matter both caudal and rostral to the lesion, including a re-direction of the CST to hand motoneurons in the monkeys 5-29 months after the lesion. Thus, multiple mechanisms of reorganization of CST axons underlie the recovery of impaired cortico-motoneuronal pathways for the long-term recovery of finger dexterity.