bluuebunny/crossref_metadata_2025_split huggingface dataset:
The HSFA1a is stabilized by the co-chaperone HSP70-HSP90 organizing protein HOP in Arabidopsis
Authors: Toribio René , Navarro Aurora , Castellano M. Mar 
Published: January 2024

ABSTRACTLiving organisms have the capacity to sense and respond to environmental stimuli, including warm conditions. Upon the increase of temperature, eukaryotic cells promote the onset of a universal transcriptional response called the heat stress response (HSR). HSR is triggered by the activation of the heat shock factor 1 (HSF1), whose activity is highly regulated in all eukaryotes. A common process of HSFA1 regulation involves its binding to HSP70 and HSP90 chaperones. However, the effect of this binding differs among eukaryotes and is not fully elucidated in plants. Moreover, the role of chaperone auxiliary proteins, such as HOP, in HSF1 regulation remains unknown. Here, we show that HOP is involved in the folding and stabilization of the HSFA1a and is required for the onset of the HSR during thermomorphogenesis in Arabidopsis. Our results demonstrate that the members of the AtHOP family bind in vivo to the HSFA1a and that the expression of multiple genes involved in the HSR, including numerous HSFA1a-responsive genes, is altered in thehop1 hop2 hop3mutant under warm temperature. HOP is not involved in the subcellular localization of the AtHSFA1a. Instead, HSFA1a is accumulated at lower levels in thehop1 hop2 hop3mutant while control levels are recovered in the presence of the proteasome inhibitor MG132 or the synthetic chaperone TUDCA. This uncovers the HSFA1a as a new client of HOP in plants and reveals the participation of HOP in HSFA1a stability, expanding the notorious function of the co-chaperone HOP in thermomorphogenesis.
ThePrimula edelbergii S-locus is an example of a jumping supergene
Authors: Potente Giacomo , Yousefi Narjes , Keller Barbara , Mora-Carrera Emiliano , Szövényi Péter , Conti Elena 
Published: January 2024

AbstractResearch on supergenes, non-recombining genomic regions housing tightly linked genes that control complex phenotypes, has gained prominence in genomics, with supergenes having been described in most eukaryotic lineages. Heterostyly, a floral heteromorphism promoting outcrossing in several angiosperm families, is controlled by theS-locus supergene. Historically, theS-locus has been studied primarily in closely relatedPrimulaspecies and, more recently, in other groups that independently evolved heterostyly. However, it remains unknown whether genetic architecture and composition of theS-locus are maintained among species that share a common origin of heterostyly and subsequently diverged across larger time scales. To address this research gap, we present a chromosome-scale genome assembly ofPrimula edelbergii, a species that shares the same origin of heterostyly withPrimula veris(whoseS-locus has been characterized) but diverged from it ca. 18 million years ago. Comparative genomic analyses betweenP. edelbergiiandP. verisallowed us to show, for the first time, that theS-locus can ‘jump’ (i.e. translocate) between chromosomes. Additionally, we found that fourS-locus genes were maintained across time but were reshuffled within the supergene, seemingly without affecting their expression. Furthermore, we confirmed thatS-locus hemizygosity counteracts genetic degeneration, otherwise expected in supergenes. Finally, we investigatedP. edelbergiievolutionary history within Ericales in terms of whole genome duplications and transposable element accumulation. In summary, our work provides a valuable resource for comparative analyses aimed at investigating the genetics of heterostyly and the pivotal role of supergenes in shaping the evolution of complex phenotypes.
Uniquome: Construction and Decoding of a Novel Proteomic Atlas that Contains New Peptide Entities
Authors: Kontopodis Evangelos , Pierros Vasileios , Vorgias Constantinos E. , Papassideri Issidora S. , Stravopodis Dimitrios J. , Tsangaris George Th. 
Published: January 2024

AbstractCellular and molecular uniqueness has recently gained eminent importance, due to the large amount of data produced by “-omics” technologies. Herein, we have constructed and decoded the “Uniquome”, by introduction of the new peptide entities: (a) “Core Unique Peptide” (CrUP), defined as the peptide whose sequence is accommodated, specifically and exclusively, only in one protein in a given proteome, and also bears the minimum length of amino acid sequence; (b) “Composite Unique Peptide” (CmUP), defined as the peptide composed by the linear unification of CrUPs, when two or more successive in order CrUPs overlap one another; (c) “Family Unique Peptide” (FUP), defined as the CrUPs that are common between all members of a given family, but unique only for the protein members of the particular family, and (d) “Universal Unique Peptides” (UUPs), which are the common CrUPs in a given protein across organisms, carrying the important ability to securely identify a protein independently of an organism. By these entities as tool-box, we have analyzed the human and model organisms, respective, proteomes. We demonstrate that these novel peptide entities play a crucial role for protein identification, protein-function prediction, cell physiology, tissue pathology, therapeutic oncology and translational medicine. Finally, we suggest that across species the conserved sequences are not DNA nucleotides but CrUPs entities.One-Sentence SummaryWe constructed and decoded the “Uniquome”, by introducing the new peptide entities Core Unique Peptide, Composite Unique Peptide, Family Unique Peptide and Universal Unique Peptide
Single-cell Rapid Capture Hybridization sequencing (scRaCH-seq) to reliably detect isoform usage and coding mutations in targeted genes at a single-cell level
Authors: Peng Hongke , Jabbari Jafar S. , Tian Luyi , Chua Chong Chyn , Anstee Natasha S. , Amin Noorul , Wei Andrew H. , Davidson Nadia M. , Roberts Andrew W. , Huang David C. S. , Ritchie Matthew E. , Thijssen Rachel 
Published: January 2024

AbstractSingle-cell long-read sequencing has transformed our understanding of isoform usage and the mutation heterogeneity between cells. Despite unbiased in-depth analysis, the low sequencing throughput often results in insufficient read coverage thereby limiting our ability to perform mutation calling for specific genes. Here, we developed asingle-cellRapid CaptureHybridizationsequencing (scRaCH-seq) method that demonstrated high specificity and efficiency in capturing targeted transcripts using long-read sequencing, allowing an in-depth analysis of mutation status and transcript usage for genes of interest. The method includes creating a probe panel for transcript capture, using barcoded primers for pooling and efficient sequencing via Oxford Nanopore Technologies platforms. scRaCH-seq is applicable to stored and indexed single-cell cDNA which allows analysis to be combined with existing short-read RNA-seq datasets. In our investigation of BTK and SF3B1 genes in samples from patients with chronic lymphocytic leukaemia (CLL), we detected SF3B1 isoforms and mutations with high sensitivity. Integration with short-read scRNA-seq data revealed significant gene expression differences in SF3B1-mutated CLL cells, though it did not impact the sensitivity of the anti-cancer drug venetoclax. scRaCH-seq’s capability to study long-read transcripts of multiple genes makes it a powerful tool for single-cell genomics.
The structure of the Orm2-containing serine palmitoyltransferase complex reveals distinct inhibitory potentials of yeast Orm proteins
Authors: Körner Carolin , Schäfer Jan-Hannes , Esch Bianca M. , Parey Kristian , Walter Stefan , Teis David , Januliene Dovile , Schmidt Oliver , Moeller Arne , Fröhlich Florian 
Published: January 2024

SummaryThe levels of sphingolipids are crucial determinants of neurodegenerative disorders. Therefore, sphingolipid levels have to be tightly regulated. The Orm protein family and ceramides act as inhibitors in the rate-limiting step of sphingolipid biosynthesis – the condensation of L-serine and palmitoyl-CoA. The two yeast isoforms Orm1 and Orm2 form a complex with the serine palmitoyltransferase (SPT). While the sequences of the Orm proteins are highly similar, however, Orm1 and Orm2 are differentially regulated in yeast cells. The mechanistic details of the differential regulation remain elusive. To elucidate the regulatory mechanism, we determined the cryo-electron microscopy structure of the SPT complex containing Orm2. Throughin vitroactivity assays and a newly developed plasmid coverage assay combined with targeted lipidomics, we demonstrate that the SPT complex with Orm2 exhibits lower activity in comparison to the complex containing Orm1. This collectively suggests a higher inhibitory potential of Orm2, despite the remarkably similar structures of the Orm1- and Orm2 containing complexes. The high conservation of the SPT from yeast to man implies that the three human ORMDL isoforms could also have different regulatory capacities, which might be essential to understanding their role in sphingolipid-mediated neurodegenerative disorders.HighlightsCryo-EM structures of serine palmitoyltransferase with Orm2 fromS. cerevisiaeCeramide-mediated inhibition on SPT activity is conserved amongst SPTsThe two yeast Orm isoforms have different regulatory capacity
The limits of predicting maladaptation to future environments with genomic data
Authors: Lind Brandon M. , Lotterhos Katie E. 
Published: January 2024

AbstractAnthropogenically driven changes in land use and climate patterns pose unprecedented challenges to species persistence. To understand the extent of these impacts, genomic offset methods have been used to forecast maladaptation of natural populations to future environmental change. However, while their use has become increasingly common, little is known regarding their predictive performance across a wide array of realistic and challenging scenarios. Here, we evaluate four offset methods (Gradient Forests, the Risk-Of-Non-Adaptedness, redundancy analysis, and LFMM2) using an extensive set of simulated datasets that vary demography, adaptive architecture, and the number and spatial patterns of adaptive environments. For each dataset, we train models using eitherall, adaptive, orneutralmarker sets and evaluate performance usingin silicocommon gardens by correlating known fitness with projected offset. Using over 4,850,000 of such evaluations, we find that 1) method performance is largely due to the degree of local adaptation across the metapopulation (LAΔSA), 2)adaptivemarker sets provide minimal performance advantages, 3) within-landscape performance is variable across gardens and declines when offset models are trained using additional non-adaptive environments, and 4) despite (1), performance declines more rapidly in novel climates for metapopulations with higherLAΔSAthan lowerLAΔSA. We discuss the implications of these results for management, assisted gene flow, and assisted migration.
Examining motor evidence for the pause-then-cancel model of action-stopping: Insights from motor system physiology
Authors: Tatz Joshua R. , Carlson Madeline O. , Lovig Carson , Wessel Jan R. 
Published: January 2024

AbstractStopping initiated actions is fundamental to adaptive behavior. Longstanding, single-process accounts of action-stopping have been challenged by recent, two-process, ‘pause-then-cancel’ models. These models propose that action-stopping involves two inhibitory processes: 1) a fast Pause process, which broadly suppresses the motor system as the result of detecting any salient event, and 2) a slower Cancel process, which involves motor suppression specific to the cancelled action. A purported signature of the Pause process is global suppression, or the reduced corticospinal excitability (CSE) of task-unrelated effectors early on in action-stopping. However, unlike the Pause process, few (if any) motor system signatures of a Cancel process have been identified. Here, we used single- and paired-pulse TMS methods to comprehensively measure the local physiological excitation and inhibition of both responding and task-unrelated motor effector systems during action-stopping. Specifically, we measured CSE, short-interval intracortical inhibition (SICI), and the duration of the cortical silent period (CSP). Consistent with key predictions from the pause-then-cancel model, CSE measurements at the responding effector indicated that additional suppression was necessary to counteract Go-related increases in CSE during-action-stopping, particularly at later timepoints. Increases in SICI on Stop-signal trials did not differ across responding and non-responding effectors, or across timepoints. This suggests SICI as a potential source of global suppression. Increases in CSP duration on Stop- signal trials were more prominent at later timepoints. SICI and CSP duration therefore appeared most consistent with the Pause and Cancel processes, respectively. Our study provides further evidence from motor system physiology that multiple inhibitory processes influence action-stopping.
Cortical multi-area model with joint excitatory-inhibitory clusters accounts for spiking statistics, inter-area propagation, and variability dynamics
Authors: Pronold Jari , Morales-Gregorio Aitor , Rostami Vahid , van Albada Sacha J. 
Published: January 2024

AbstractThe primate brain uses billions of interacting neurons to produce macroscopic dynamics and behavior, but current methods only allow neuroscientists to investigate a subset of the neural activity. Computational modeling offers an alternative testbed for scientific hypotheses, by allowing full control of the system. Here, we test the hypothesis that local cortical circuits are organized into joint clusters of excitatory and inhibitory neurons by investigating the influence of this organizational principle on cortical resting-state spiking activity, inter-area propagation, and variability dynamics. The model represents all vision-related areas in one hemisphere of the macaque cortex with biologically realistic neuron densities and connectivities, expanding on a previous unclustered model of this system. Each area is represented by a square millimeter microcircuit including the full density of neurons and synapses, avoiding downscaling artifacts and testing cortical dynamics at the natural scale. We find that joint excitatory-inhibitory clustering normalizes spiking activity statistics in terms of firing rate distributions and inter-spike interval variability. A comparison with data from cortical areas V1, V4, FEF, 7a, and DP shows that the clustering enables the resting-state activity of especially higher cortical areas to be better captured. In addition, we find that the clustering supports signal propagation across all areas in both feedforward and feedback directions with reasonable latencies. Finally, we also show that localized stimulation of the clustered model quenches the variability of neural activity, in agreement with experimental observations. We conclude that joint clustering of excitatory and inhibitory neurons is a likely organizational principle of local cortical circuits, supporting resting-state spiking activity statistics, inter-area propagation, and variability dynamics.
Acute sleep deprivation reduces fear memories in male and female mice
Authors: Foilb Allison R. , Taylor-Yeremeeva Elisa M. , Schmidt Brett D. , Ressler Kerry J. , Carlezon William A. 
Published: January 2024

ABSTRACTSleep problems are a prominent feature of mental health conditions including post-traumatic stress disorder (PTSD). Despite its potential importance, the role of sleep in the development of and/or recovery from trauma-related illnesses is not understood. Interestingly, there are reports that sleep deprivation immediately after a traumatic experience can reduce fear memories, an effect that could be utilized therapeutically in humans. While the mechanisms of this effect are not completely understood, one possible explanation for these findings is that immediate sleep deprivation interferes with consolidation of fear memories, rendering them weaker and more sensitive to intervention. Here, we allowed fear-conditioned mice to sleep immediately after fear conditioning during a time frame (18 hr) that includes and extends beyond periods typically associated with memory consolidation before subjecting them to 6 hr of sleep deprivation. Mice deprived of sleep with this delayed regimen showed dramatic reductions in fear during tests conducted immediately after sleep deprivation, as well as 24 hr later. This sleep deprivation regimen also increased levels of mRNA encoding brain-derived neurotrophic factor (BDNF), a molecule implicated in neuroplasticity, in the basolateral amygdala (BLA), a brain area implicated in fear and its extinction. These findings raise the possibility that the effects of our delayed sleep deprivation regimen are not due to disruption of memory consolidation, but instead are caused by BDNF-mediated neuroadaptations within the BLA that actively suppress expression of fear. Treatments that safely reduce expression of fear memories would have considerable therapeutic potential in the treatment of conditions triggered by trauma.
Bold zebrafish (danio rerio) learn faster in an associative learning task
Authors: Corcoran Jamie , Storks Levi , Wong Ryan Y. 
Published: January 2024

AbstractAnimals differ in their ability to learn. One potential factor contributing to learning differences is personality types. We investigated the relationship between learning and the bold-shy continuum by comparing performance of bold and shy zebrafish in conditioned place preference (CPP) and 2 choice tasks. Bold fish learned significantly faster than the shy fish but there were no differences in their final performance. When tested in the 2 choice task, we found no clear evidence of learning, however bold fish made more initial choices than shy fish. Overall,our study suggests that bold fish tend to be faster learners when compared to shy fish. The lack of differences in the final change in behavior suggests that the learning difference is due to neophobic tendencies and resulting initial interactions with the learning stimulus.
DE Novo emerged gene SEarch in Eukaryotes with DENSE
Authors: Roginski Paul , Grandchamp Anna , Quignot Chloé , Lopes Anne 
Published: January 2024

AbstractThe discovery of de novo emerged genes, originating from previously noncoding DNA regions, challenges traditional views of species evolution. Indeed, the hypothesis of neutrally evolving sequences giving rise to functional proteins is highly unlikely. This conundrum has sparked numerous studies to quantify and characterize these genes, aiming to understand their functional roles and contributions to genome evolution. Yet, no fully automated pipeline for their identification is available. Therefore, we introduce DENSE (DE Novo emerged gene Search), an automated Nextflow pipeline based on two distinct steps: detection of Taxonomically Restricted Genes (TRGs) through phylostratigraphy, and filtering of TRGs for de novo emerged genes via genome comparisons and synteny search. DENSE is available as a user-friendly command-line tool, while the second step is accessible through a web server upon providing a list of TRGs. Highly flexible, DENSE provides various strategy and parameter combinations, enabling users to adapt to specific configurations or define their own strategy through a rational framework, facilitating protocol communication, and study interoperability. We apply DENSE to seven model organisms, exploring the impact of its strategies and parameters on de novo gene predictions. This thorough analysis across species with different evolutionary rates reveals useful metrics for users to define input datasets, identify favorable/unfavorable conditions for de novo gene detection, and control potential biases in genome annotations. Additionally, predictions made for the seven model organisms are compiled into a requestable database, that we hope will serve as a reference for de novo emerged gene lists generated with specific criteria combinations.Significance StatementThe identification and classification of de novo genes, which originate from noncoding regions of DNA, remain an ongoing challenge in genomics research. While various approaches have been employed for their identification, the lack of a standardized protocol has resulted in varying lists of de novo genes across studies. This study introduces a novel tool: DENSE, that formalizes the common practices used in the field into a comprehensive and automated pipeline. DENSE streamlines the identification of taxonomically restricted genes, homology searches, and synteny analysis. This standardized methodology aims to enhance the accuracy and reliability of de novo gene identification, fostering a deeper understanding of the evolutionary mechanisms that drive gene birth and shape the genetic diversity of organisms.
A spinal cord injury time and severity consensus transcriptomic reference suite in rat reveals translationally-relevant biomarker genes
Authors: Grillo-Risco Rubén , Hidalgo Marta R. , Rojas Beatriz Martínez , Moreno-Manzano Victoria , García-García Francisco 
Published: January 2024

AbstractSpinal cord injury (SCI) is a devastating condition that leads to motor, sensory, and autonomic dysfunction. Current therapeutic options remain limited, emphasizing the need for a comprehensive understanding of the underlying SCI-associated molecular mechanisms. This study characterized distinct SCI phases and severities at the gene and functional levels, focusing on biomarker gene identification. Our approach involved a systematic review, individual transcriptomic analysis, gene meta-analysis, and functional characterization. We compiled a total of fourteen studies with 273 samples, leading to the identification of severity-specific biomarker genes for injury prognosis (e.g., Srpx2, Hoxb8, Acap1, Snai1, and Aadat) and phase-specific genes for the precise classification of the injury profile (e.g., Il6, Fosl1, Cfp, C1qc, Cp). We investigated the potential transferability of severity-associated biomarkers and identified a twelve-gene signature that predicted injury prognosis from human blood samples. We also report the development of MetaSCI-app - an interactive web application designed for researchers - that allows the exploration and visualization of all generated results (https://metasci-cbl.shinyapps.io/metaSCI). Overall, we present a transcriptomic reference and provide a comprehensive framework for assessing SCI considering severity and time perspectives.TeaserA transcriptomic meta-analysis of spinal cord injury provides a consensus reference and biomarker genes for injury phase/severity.