bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rice WRKY13 TF protein binds to motifs in the promoter region to regulate downstream disease resistance-related genes
Authors: Jimmy John Lilly , Karn Rohit , Kumari Sweta , Sruthilaxmi Chitathoor Balasubramane , Pooja Singh , Babu Subramanian 
Published: January 2023

AbstractIn plants, pathogen resistance is brought about due to the binding of certain transcription factors (TF) proteins to the cis-elements of certain target genes. These cis-elements are present up-stream in the motif of the promoters of each gene. This ensures the binding of a specific transcription factor to a specific promoter, therefore regulating the expression of that gene. Therefore, the study of each promoter sequence of all the rice genes would help identify the target genes of a specific transcription factor. Rice 1kb upstream promoter sequences of 55,986 annotated genes were analyzed using the Perl program algorithm to detect WRKY13 binding motifs (bm). The resulting genes were grouped using gene ontology and gene set enrichment analysis. Gene with more than 4 TFbm in their promoter was selected. Nine genes reported to have a role in rice disease resistance were selected for further analysis.Cis-acting regulatory element analysis was carried out to find the cis-elements and to confirm the presence of the corresponding motifs in the promoter sequences of these genes. The 3D structure of WRKY13 TF and the corresponding nine genes were built and the interacting residues were determined. The binding capacity of WRKY13 to the promoter of these selected genes was analyzed using docking studies.WRKY13 was also considered for docking analysis based on the prior reports of autoregulation. Molecular dynamic simulations provided more details regarding the interactions. Expression data revealed the expression of the genes that helped to provide the mechanism of interaction. Further co-expression network helped to characterize the interaction of these selected diseases resistance-related genes with WRKY13 TF protein. This study suggests the target downstream genes that are regulated by WRKY13 TF. The molecular mechanism involving the gene network regulated by WRKY13 TF in disease resistance against rice fungal pathogens is explored.
Morphology as indicator of adaptive changes of model tissues in osmotically and chemically changing environments
Authors: Höllring Kevin , Vurnek Damir , Gehrer Simone , Dudziak Diana , Hubert Maxime , Smith Ana-Sunčana 
Published: January 2023

AbstractWe investigate the formation and maintenance of the homeostatic state in the case of 2D epithelial tissues following an induction of hyperosmotic conditions, using media enriched with 80 to 320 mOsm of mannitol, NaCl, and urea. We characterise the changes in the tissue immediately after the osmotic shock, and follow it until the new homeostatic state is formed. We characterise changes in cooperative motility and proliferation pressure in the tissue upon treatment with the help of a theoretical model based on the delayed Fisher-Kolmogorov formalism, where the delay in density evolution is induced by the the finite time of the cell division. Finally we explore the adaptation of the homeostatic tissue to highly elevated osmotic conditions by evaluating the morphology and topology of cells after 20 days in incubation. We find that hyperosmotic environments together with changes in the extracellular matrix induce different mechanical states in viable tissues, where only some remain functional. The perspective is a relation between tissue topology and function, which could be explored beyond the scope of this manuscript.Experimental investigation of morphological effect of change of osmotic conditions on long-term tissue morphology and topologyEffect of osmotic changes on transient tissue growth behaviourAnalysis of recovery process of tissues post-osmotic-shockToxicity limits of osmolytes in mid- to long-term tissue evolutionTissue adaptation to physiological changes in environmentLong-term tissue stabilisation under altered osmotic conditions.Abstract Figure
Glycoproteome remodelling and granule-specificN-glycosylation accompany neutrophil granulopoiesis
Authors: Kawahara Rebeca , Ugonotti Julian , Chatterjee Sayantani , Tjondro Harry C. , Loke Ian , Parker Benjamin L. , Venkatakrishnan Vignesh , Dieckmann Regis , Sumer-Bayraktar Zeynep , Karlsson-Bengtsson Anna , Bylund Johan , Thaysen-Andersen Morten 
Published: January 2023

AbstractNeutrophils store microbicidal glycoproteins in cytosolic granules to fight intruding pathogens, but their granule distribution and formation mechanism(s) during granulopoiesis remain unmapped. Herein, we perform comprehensive spatiotemporalN-glycoproteome profiling of isolated granule populations from blood-derived neutrophils and during their maturation from bone marrow-derived progenitors using glycomics-assisted glycoproteomics. Interestingly, the granules of resting neutrophils exhibited distinctive glycophenotypes including, most strikingly, peculiar highly truncatedN-glycosylation in the azurophilic granules. Excitingly, proteomics and transcriptomics data from discrete myeloid progenitor stages revealed that profound glycoproteome remodelling underpins the promyelocytic-to-metamyelocyte transition and that remodelling is driven primarily by changes in protein expression and less by the glycosylation machinery. Notable exceptions were the oligosaccharyltransferase subunits responsible for initiation ofN-glycoprotein biosynthesis that were strongly expressed in early myeloid progenitors correlating with high glycosylation efficiencies of the azurophilic granule proteins. Our study provides spatiotemporal insights into the complex neutrophilN-glycoproteome featuring an intriguing granule-specificN-glycosylation formed by dynamic remodelling during myeloid progenitor-to-neutrophil maturation.Key pointsSystems glycobiology reveals that profoundN-glycoproteome remodelling accompanies early neutrophil granulopoiesisPrecision glycoproteomics produces detailed cartography of neutrophils that exhibit site-, protein- and granule-specific N-glycosylation
Combined CRISPRi and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression ofRUVBL1and prostate cancer progression
Authors: Tian Yijun , Dong Dandan , Wang Zixian , Wu Lang , Park Jong Y , Wei Gong-Hong , Wang Liang ,   PRACTICAL/ELLIPSE consortium
Published: January 2023

SummaryGenome-wide association studies along with expression quantitative trait loci (eQTL) mapping have identified hundreds of single nucleotide polymorphisms (SNPs) and their target genes in prostate cancer (PCa), yet functional characterization of these risk loci remains challenging. To screen for potential regulatory SNPs, we designed a CRISPRi library containing 9133 guide RNAs (gRNAs) to target 2,166 candidate SNP sites implicated in PCa and identified 117 SNPs that could regulate 90 genes for PCa cell growth advantage. Among these, rs60464856 was covered by multiple gRNAs significantly depleted in the screening (FDR<0.05). Pooled SNP association analysis in the PRACTICAL and FinnGen cohorts showed significantly higher PCa risk for the rs60464856 G allele (pvalue=1.2E-16 and 3.2E-7). Subsequent eQTL analysis revealed that the G allele is associated with increasedRUVBL1expression in multiple datasets. Further CRISPRi and xCas9 base editing proved the rs60464856 G allele leading to an elevatedRUVBL1expression. Furthermore, SILAC-based proteomic analysis demonstrated allelic binding of cohesin subunits at the rs60464856 region, where HiC dataset showed consistent chromatin interactions in prostate cell lines.RUVBL1depletion inhibited PCa cell proliferation and tumor growth in xenograft mouse model. Gene set enrichment analysis suggested an association ofRUVBL1expression with cell-cycle-related pathways. An increased expression ofRUVBL1and activations of cell-cycle pathways were correlated with poor PCa survival in TCGA datasets. Together, our CRISPRi screening prioritized about one hundred regulatory SNPs essential for prostate cell proliferation. In combination with proteomics and functional studies, we characterized the mechanistic role of rs60464856 andRUVBL1in PCa progression.
Variation in temperature of peak trait performance constrains adaptation of arthropod populations to climatic warming
Authors: Pawar Samraat , Huxley Paul J. , Smallwood Thomas R. C. , Nesbit Miles L. , Chan Alex H. H. , Shocket Marta S. , Johnson Leah R. , Kontopoulos Dimitrios - Georgios , Cator Lauren 
Published: January 2023

AbstractThe capacity of arthropod populations to adapt to long-term climatic warming is uncertain. Here, we combine theory and extensive data on diverse arthropod taxa to show that their rate of thermal adaptation to climatic warming will be constrained in two fundamental ways. First, the rate of thermal adaptation is predicted to be limited by the rate of shift in the temperature of peak performance of four life-history traits in a specific order: juvenile development, adult fecundity, juvenile mortality, and adult mortality. Second, thermal adaptation will be constrained due to differences in the temperature of peak performance among these four traits, which are expected to persist because of trade-offs. By compiling a new global dataset of 61 diverse arthropod species, we find strong evidence that contemporary populations have indeed evolved under these constraints. Our results provide a basis for using relatively feasible trait measurements to predict the adaptive capacity of diverse arthropod populations to climatic warming.
Amplitude modulation pattern of rat distress vocalisations during fear conditioning
Authors: Gonzalez-Palomares Eugenia , Boulanger-Bertolus Julie , Dupin Maryne , Mouly Anne-Marie , Hechavarria Julio C. 
Published: January 2023

AbstractIn humans, screams have strong amplitude modulations (AM) at 30 to 150 Hz. These AM correspond to the acoustic correlate of perceptual roughness. In bats, distress calls can carry AMs, which elicit heart rate increases in playback experiments. Whether amplitude modulation occurs in fearful vocalisations of other animal species beyond humans and bats remains unknown. Here we analysed the AM pattern of rats’ 22-kHz ultrasonic vocalisations emitted in a fear conditioning task. We found that the number of vocalisations decreases during the presentation of conditioned stimuli. We also observed that AMs do occur in rat 22-kHz vocalisations. AMs are stronger during the presentation of conditioned stimuli, and during escape behaviour compared to freezing. Our results suggest that the presence of AMs in vocalisations emitted could reflect the animal’s internal state of fear related to avoidance behaviour.
A method for predicting linear and conformational B-cell epitopes in an antigen from its primary sequence
Authors: Kumar Nishant , Tripathi Sadhana , Sharma Neelam , Patiyal Sumeet , Devi Naorem Leimarembi , Raghava Gajendra P. S. 
Published: January 2023

AbstractB-cell is an essential component of the immune system that plays a vital role in providing the immune response against any pathogenic infection by producing antibodies. Existing methods either predict linear or conformational B-cell epitopes in an antigen. In this study, a single method was developed for predicting both types (linear/conformational) of B-cell epitopes. The dataset used in this study contains 3875 B-cell epitopes and 3996 non-B-cell epitopes, where B-cell epitopes consist of both linear and conformational B-cell epitopes. Our primary analysis indicates that certain residues (like Asp, Glu, Lys, Asn) are more prominent in B-cell epitopes. We developed machine-learning based methods using different types of sequence composition and achieved the highest AUC of 0.80 using dipeptide composition. In addition, models were developed on selected features, but no further improvement was observed. Our similarity-based method implemented using BLAST shows a high probability of correct prediction with poor sensitivity. Finally, we came up with a hybrid model that combine alignment free (dipeptide based random forest model) and alignment-based (BLAST based similarity) model. Our hybrid model attained maximum AUC 0.83 with MCC 0.49 on the independent dataset. Our hybrid model performs better than existing methods on an independent dataset used in this study. All models trained and tested on 80% data using cross-validation technique and final model was evaluated on 20% data called independent or validation dataset. A webserver and standalone package named “CLBTope” has been developed for predicting, designing, and scanning B-cell epitopes in an antigen sequence (https://webs.iiitd.edu.in/raghava/clbtope/).
Catenin signaling controls phrenic motor neuron development and function during a narrow temporal window
Authors: Vagnozzi Alicia N. , Moore Matthew T. , de Boer Raquel López , Agarwal Aambar , Zampieri Niccolò , Landmesser Lynn T. , Philippidou Polyxeni 
Published: January 2023

AbstractPhrenic Motor Column (PMC) neurons are a specialized subset of motor neurons (MNs) that provide the only motor innervation to the diaphragm muscle and are therefore essential for survival. Despite their critical role, the mechanisms that control phrenic MN development and function are not well understood. Here, we show that catenin-mediated cadherin adhesive function is required for multiple aspects of phrenic MN development. Deletion ofβ- andγ-catenin from MN progenitors results in perinatal lethality and a severe reduction in phrenic MN bursting activity. In the absence of catenin signaling, phrenic MN topography is eroded, MN clustering is lost and phrenic axons and dendrites fail to grow appropriately. Despite the essential requirement for catenins in early phrenic MN development, they appear to be dispensable for phrenic MN maintenance, as catenin deletion from postmitotic MNs does not impact phrenic MN topography or function. Our data reveal a fundamental role for catenins in PMC development and suggest that distinct mechanisms are likely to control PMC maintenance.
LRphase: an efficient method for assigning haplotype identity to long reads
Authors: Holmes Monica J. , Mahjour Babak , Castro Christopher P. , Farnum Gregory A. , Diehl Adam G. , Boyle Alan P. 
Published: January 2023

AbstractMotivationUnderstanding the functional effects of sequence variation is among the primary goals of contemporary genomics. Individual human genomes contain millions of variants which are thought to contribute to phenotypic variability and differential disease risks at the population level. However, because variants rarely act in isolation, we cannot accurately predict functional effects without first considering the potential effects of other interacting variants on the same chromosome. This information can be obtained by phasing the read data from sequencing experiments. However, no standalone tools are available to simply phase reads based on known haplotypes. Here we present LRphase: a user-friendly utility for simple phasing of long sequencing reads.Availability and ImplementationLRphase is implemented in Python, and is freely available athttps://github.com/Boyle-Lab/LRphase, under the MIT license. Version 1.1.0, described in this manuscript, is available through the pip and Bioconda repositories (e.g., “pip install lrphase==1.1.0”).Contactapboyle@umich.eduSupplementary InformationSupplementary methods are available as part of the online version of this publication.
Post-Ischemic Reorganization of Sensory Responses in Cerebral Cortex
Authors: Hayley P , Tuchek C , Dalla S , Borrell J , Murphy MD , Nudo RJ , Guggenmos DJ 
Published: January 2023

AbstractSensorimotor integration is critical for generating skilled, volitional movements. While stroke tends to impact motor function, there are also often associated sensory deficits that contribute to overall behavioral deficits. Because many of the cortico-cortical projections participating in the generation of volitional movement either target or pass-through primary motor cortex (in rats, caudal forelimb area; CFA), any damage to CFA can lead to a subsequent disruption in information flow. As a result, the loss of sensory feedback is thought to contribute to motor dysfunction even when sensory areas are spared from injury. Previous research has suggested that the restoration of sensorimotor integration through reorganization or de novo neuronal connections is important for restoring function. Our goal was to determine if there was crosstalk between sensorimotor cortical areas with recovery from a primary motor cortex injury. First, we investigated if peripheral sensory stimulation would evoke responses in the rostral forelimb area (RFA), a rodent homologue to premotor cortex. We then sought to identify whether intracortical microstimulation-evoked activity in RFA would reciprocally modify the sensory response. We used seven rats with an ischemic lesion of CFA. Four weeks after injury, the rats’ forepaw was mechanically stimulated under anesthesia and neural activity was recorded in the cortex. In a subset of trials, a small intracortical stimulation pulse was delivered in RFA either individually or paired with peripheral sensory stimulation. Our results point to post-ischemic connectivity between premotor and sensory cortex that may be related to functional recovery. Premotor recruitment during the sensory response was seen with a peak in spiking within RFA after the peripheral solenoid stimulation despite the damage to CFA. Furthermore, stimulation evoked activity in RFA modulated and disrupted the sensory response in sensory cortex, providing additional evidence for the transmission of premotor activity to sensory cortex and the sensitivity of sensory cortex to premotor cortex’s influence. The strength of the modulatory effect may be related to the extent of the injury and the subsequent reshaping of cortical connections in response to network disruption.
Defining the cellular complexity of the zebrafish bipotential gonad
Authors: Kossack Michelle E. , Tian Lucy , Bowie Kealyn , Plavicki Jessica S. 
Published: January 2023

AbstractZebrafish are routinely used to model reproductive development, function, and disease, yet we still lack a clear understanding of the fundamental steps that occur during early bipotential gonad development, including when endothelial cells, pericytes, and macrophage cells arrive at the bipotential gonad to support gonad growth and differentiation. Here, we use a combination of transgenic reporters and single-cell sequencing analyses to define the arrival of different critical cell types to the larval zebrafish gonad. We determined that blood initially reaches the gonad via a vessel formed from the swim bladder artery, which we have termed the gonadal artery. We find that vascular and lymphatic development occurs concurrently in the bipotential zebrafish gonad and our data suggest that similar to what has been observed in developing zebrafish embryos, lymphatic endothelial cells in the gonad may be derived from vascular endothelial cells. We mined preexisting sequencing data sets to determine whether ovarian pericytes had unique gene expression signatures. We identified 215 genes that were uniquely expressed in ovarian pericytes that were not expressed in larval pericytes. Similar to what has been shown in the mouse ovary, our data suggest thatpdgfrb+ pericytes may support the migration of endothelial tip cells during ovarian angiogenesis. Using a macrophage-driven photoconvertible protein, we found that macrophage established a nascent resident population as early as 12 dpf and can be observed removing cellular material during gonadal differentiation. This foundational information demonstrates that the early bipotential gonad contains complex cellular interactions, which likely shape the health and function of the mature, differentiated gonad.Summary SentenceDelineating the complex cellular interactions between vascular and lymphatic endothelial cells, pericytes, and macrophage in the bipotential gonad is essential for understanding the differentiation and functioning of the mature gonad.Graphical Abstract
Determinants of renin cell differentiation: a single cell epi-transcriptomics approach
Authors: Martini Alexandre G , Smith Jason P. , Medrano Silvia , Sheffield Nathan C. , Sequeira-Lopez Maria Luisa S. , Gomez R. Ariel 
Published: January 2023

RationaleRenin cells are essential for survival. They control the morphogenesis of the kidney arterioles, and the composition and volume of our extracellular fluid, arterial blood pressure, tissue perfusion, and oxygen delivery. It is known that renin cells and associated arteriolar cells descend fromFoxD1+ progenitor cells, yet renin cells remain challenging to study due in no small part to their rarity within the kidney. As such, the molecular mechanisms underlying the differentiation and maintenance of these cells remain insufficiently understood.ObjectiveWe sought to comprehensively evaluate the chromatin states and transcription factors (TFs) that drive the differentiation ofFoxD1+ progenitor cells into those that compose the kidney vasculature with a focus on renin cells.Methods and ResultsWe isolated single nuclei ofFoxD1+ progenitor cells and their descendants fromFoxD1cre/+;R26R-mTmGmice at embryonic day 12 (E12) (ncells=1234), embryonic day 18 (E18) (ncells=3696), postnatal day 5 (P5) (ncells=1986), and postnatal day 30 (P30) (ncells=1196). Using integrated scRNA-seq and scATAC-seq we established the developmental trajectory that leads to the mosaic of cells that compose the kidney arterioles, and specifically identified the factors that determine the elusive, myo-endocrine adult renin-secreting juxtaglomerular (JG) cell. We confirm the role ofNfixin JG cell development and renin expression, and identified the myocyte enhancer factor-2 (MEF2) family of TFs as putative drivers of JG cell differentiation.ConclusionsWe provide the first developmental trajectory of renin cell differentiation as they become JG cells in a single-cell atlas of kidney vascular open chromatin and highlighted novel factors important for their stage-specific differentiation. This improved understanding of the regulatory landscape of renin expressing JG cells is necessary to better learn the control and function of this rare cell population as overactivation or aberrant activity of the RAS is a key factor in cardiovascular and kidney pathologies.
Analysis of convolutional neural networks reveals the computational properties essential for subcortical processing of facial expression
Authors: Lim Chanseok , Inagaki Mikio , Shinozaki Takashi , Fujita Ichiro 
Published: January 2023

AbstractPerception of facial expression is crucial in the social life of primates. This visual information is processed along the ventral cortical pathway and the subcortical pathway. Processing of face information in the subcortical pathway is inaccurate, but the architectural and physiological properties that are responsible remain unclear. We analyzed the performance of convolutional neural networks incorporating three prominent properties of this pathway: a shallow layer architecture, concentric receptive fields at the first processing stage, and a greater degree of spatial pooling. The neural networks designed in this way could be trained to classify seven facial expressions with a correct rate of 51% (chance level, 14%). This modest performance was gradually improved by replacing the three properties, one-by-one, two at a time, or all three simultaneously, with the corresponding features in the cortical pathway. Some processing units in the final layer were sensitive to spatial frequencies (SFs) in the retina-based coordinate, whereas others were sensitive to object-based SFs, similar to neurons in the amygdala. Replacement of any one of these properties affected the SF coordinate of units. All three properties constrain the accuracy of facial expression information in the subcortical pathway, and are essential for determining the coordinate of SF representation.