bluuebunny/crossref_metadata_2025_split huggingface dataset:
A meta-analysis of the effect of protein synthesis inhibitors on rodent fear conditioning
Authors: Carneiro Clarissa F. D. , Amorim Felippe E. , Amaral Olavo B. 
Published: October 2022

AbstractSystematic reviews and meta-analyses have been increasingly recognized for their potential value in pre-clinical research, but their applications have not been extensively explored in behavioral neuroscience. In this work, we studied protein synthesis inhibition, a classic intervention used to disrupt fear learning, reconsolidation, and extinction in rodents, to explore how meta-analyses can identify potential moderators of its effect. We initially performed separate meta-analyses for different injection sites and target sessions to evaluate the effect of the intervention in various scenarios. Heterogeneity was further investigated by multilevel meta-regression models aggregating various sites, with article or research group as additional levels. We detected robust effects of protein synthesis inhibitors on training and reconsolidation, but not on extinction, possibly due to the lower number of studies on the latter. Our analyses identified some well-established moderators, such as intervention timing and reexposure duration. However, other factors proposed as boundary conditions for reconsolidation, such as memory age and training strength, were not associated with effect size. While our results point to the value of meta-analyses in consolidating findings from the literature, we believe that associations suggested by data synthesis should ideally be verified by well-powered, rigorous confirmatory experiments.
What is hidden in the darkness? Characterization of AlphaFold structural space
Authors: Durairaj Janani , Pereira Joana , Akdel Mehmet , Schwede Torsten 
Published: October 2022

AbstractThe recent public release of the latest version of the AlphaFold database has given us access to over 200 million predicted protein structures. We use a “shape-mer” approach, a structural fragmentation method analogous to sequencek-mers, to describe these structures and look for novelties - both in terms of proteins with rare or novel structural composition and possible functional annotation of under-studied proteins. Data and code will be made available athttps://github.com/TurtleTools/afdb-shapemer-darkness
Recurrent impairments in visual perception and place avoidance across autism models are causally linked in the haploinsufficiency model of intellectual disabilitySetd5
Authors: Burnett Laura E. , Koppensteiner Peter , Symonova Olga , Masson Tomás , Vega-Zuniga Tomas , Contreras Ximena , Rülicke Thomas , Shigemoto Ryuichi , Novarino Gaia , Jösch Maximilian 
Published: October 2022

AbstractDespite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in three independent models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments - a non-perceptual trait. Focusing on a common cause of ASDs, theSetd5gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1) mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment, and define a non-developmental source of such deficits in ASD.
Functional annotation of the animal genomes: an integrated annotation resource for the horse
Authors: Peng Sichong , Dahlgren Anna R. , Donnelly Callum G. , Hales Erin N. , Petersen Jessica L. , Bellone Rebecca R. , Kalbfleisch Ted , Finno Carrie J. 
Published: October 2022

AbstractThe genomic sequence of the horse has been available since 2009, providing critical resources for discovering important genomic variants regarding both animal health and population structures. However, to fully understand the functional implications of these variants, detailed annotation of the horse genome is required. Currently, the horse genome is annotated using limited available RNA-seq data, as well as through comparative genomics by translating human and mouse genome annotation. While this approach has served the equine researchers well and led to various discoveries that would improve care and management of horses, many important questions remain unanswered. The limitation of the current annotation is two pronged. First, the heavy reliance on short-read sequencing-based RNA-seq data meant that alternate isoforms could not be accurately resolved. Second, epigenomic regulatory elements are crucial to detailed understanding of gene expression network but are yet to be systemically identified in the horse. Many of these regulatory elements, including enhancers, promoters, and insulators, are either not transcribed or transcribed at a very low level, necessitating alternate approaches to identify them. To solve above problems, the Functional Annotation of the Animal Genomes (FAANG) project proposed a systemic approach to tissue collection, phenotyping, and data generation, adopting the blueprint laid out by the Encyclopedia of DNA Elements (ENCODE) project. Here we detail the first comprehensive overview of gene expression and regulation in the horse, providing the equine research community an expanded set of genomics resources for studies of complex traits in the horse.Author SummaryFunctional annotation of a reference genome provides critical information that pertains the tissue-specific gene expression and regulation. Non-model organisms often rely on existing annotations of human and mouse genomes and the conservation between species for their genome annotation. This approach has limited power in annotating transcripts and regulatory elements that are less evolutionarily conserved. Such are the cases of alternatively spliced isoforms and enhancer elements. In a large-scale collaborated effort, Functional Annotation of Animal Genome (FAANG) aims to generate species-specific and tissue-aware functional annotation for farm animals. In this study, we present the overall annotation efforts and findings from the equine FAANG group. This integrated annotation for the horse genome provides, for the first time, a comprehensive overview of gene expression and regulation landscape in nine major equine tissues, as well as an analytical framework for further inclusion of other important tissues.
Pangenome-based dynamic trajectories of intracellular gene transfers in Poaceae unveil a high rate of unceasing integration and selective retention in Triticeae
Authors: Chen Yongming , Guo Yiwen , Xie Xiaoming , Wang Zihao , Miao Lingfeng , Yang Zhengzhao , Jiao Yuannian , Xie Chaojie , Liu Jie , Hu Zhaorong , Xin Mingming , Yao Yingyin , Ni Zhongfu , Sun Qixin , Peng Huiru , Guo Weilong 
Published: October 2022

ABSTRACTIntracellular gene transfers (IGTs) between the nucleus and organelles, including plastids and mitochondria, constantly reshapes the nuclear genome during evolution. Despite the substantial contribution of IGTs to genome variation, the dynamic trajectories of IGTs at the pangenomic level remain elusive. Here, we propose a novel approach, IGTminer, to map the evolutionary trajectories of IGTs by collinearity and gene reannotation across multiple genome assemblies. IGTminer was applied to create a nuclear organelle gene (NOG) map across 67 genomes covering 15 Poaceae species, including important crops, revealing the polymorphisms and trajectory dynamics of NOGs. The NOGs produced were verified by experimental evidence and resequencing datasets. We found that most of the NOGs were recently transferred and lineage specific, and that Triticeae species tended to have more NOGs than other Poaceae species. Wheat had a higher retention rate of NOGs than maize and rice, and the retained NOGs were likely involved in the photosynthesis and translation pathways. Large numbers of NOG clusters were aggregated in hexaploid wheat during two rounds of polyploidization and contributed to the genetic diversities among modern wheat varieties. Finally, we proposed a radiocarbon-like model illustrating the transfer and elimination dynamics of NOGs, highlighting the unceasing integration and selective retention of NOGs over evolutionary time. In addition, we implemented an interactive webserver for NOG exploration in Poaceae. In summary, this study provides new resources and clues for the roles of IGTs in shaping inter- and intraspecies genome variation and driving plant genome evolution.
Decoding brain basis of laughter and crying in natural scenes
Authors: Nummenmaa Lauri , Malèn Tuulia , Nazari-Farsani Sanaz , Seppälä Kerttu , Sun Lihua , Karlsson Henry K. , Hudson Matthew , Hirvonen Jussi , Sams Mikko , Scott Sophie , Putkinen Vesa 
Published: October 2022

AbstractLaughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 minutes of a full-length feature film, and iii) listened to 15 minutes of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated by independent observes, and the resulting time series were used to predict hemodynamic activity to laughter and crying episodes. Multivariate pattern analysis (MVPA) was used to test for regional selectivity in laughter and crying evoked activations. Laughter induced widespread activity in ventral visual cortex and superior and middle temporal and motor cortices. Crying activated thalamus, cingulate cortex along the anterior-posterior axis, insula and orbitofrontal cortex. Both laughter and crying could be decoded accurately (66-77% depending on the experiment) from the BOLD signal, and the voxels contributing most significantly to classification were in superior temporal cortex. These results suggest that perceiving laughter and crying engage distinct neural networks, whose activity suppresses each other to manage appropriate behavioral responses to others’ bonding and distress signals.Significance statementLaughter and crying are universal signals of prosociality and distress, respectively. They occur in complex, dynamic social settings with variable and dynamically evolving time courses. Here we used functional magnetic resonance imaging experiments and statistical pattern recognition for disentangling the neural systems that encode laughter and crying signals from dynamic and highly naturalistic scenes. These results show that separable neural circuits are engaged in processing distinct types of social attachment cues, and that pattern recognition during dynamic scene perception allows reliable separation of laughter and crying evoked activation patterns. Coordinated activity of these networks allows managing appropriate behavioral responses to others’ bonding and distress signals.
Investigating the oral microbiome in retrospective and prospective cases of prostate, colon, and breast cancer
Authors: Nearing Jacob T. , DeClercq Vanessa , Langille Morgan G.I. 
Published: October 2022

AbstractThe human microbiome has been proposed as a useful biomarker for several different human diseases including various cancers. To answer this question, we examined salivary samples from two Canadian population cohorts, the Atlantic Partnership for Tomorrow’s Health project (PATH) and Alberta’s Tomorrow Project (ATP). Sample selection was then divided into both a retrospective and prospective case control design examining individuals with prostate, breast, or colon cancer. In total 89 retrospective and 260 prospective cancer cases were matched to non-cancer controls and saliva samples were sequenced using 16S rRNA gene sequencing to compare bacterial diversity, and taxonomic composition. We found no significant differences in alpha or beta diversity across any of the three cancer types and two study designs. Although retrospective colon cancer samples did show evidence on visual clustering in weighted beta diversity metrics. Differential abundance analysis of individual taxon showed several taxa that were associated with previous cancer diagnosis in all three groupings within the retrospective study design. However, only one genus (Ruminococcaceae UCG-014) in breast cancer and one ASV (Fusobacterium periodonticum) in colon cancer was identified by more than one differential abundance (DA) tool. In prospective cases of disease three ASVs were associated with colon cancer, one ASV with breast cancer, and one ASV with prostate cancer. None overlapped between the two different study cohorts. Attempting to identify microbial signals using Random Forest classification showed relatively low levels of signal in both prospective and retrospective cases of breast and prostate cancer (AUC range: 0.394-0.665). Contrastingly, colon cancer did show signal in our retrospective analysis (AUC: 0.745) and in one of two prospective cohorts (AUC: 0.717). Overall, our results indicate that it is unlikely that reliable oral microbial biomarkers of disease exist in the context of both breast and prostate cancer. However, they do suggest that further research into the relationship between the oral microbiome and colon cancer could be fruitful. Particularly in the context of early disease progression and risk of cancer development.
Development of SARS-CoV-2 replicons for the ancestral virus and variant of concern Delta for antiviral screening
Authors: Erdmann Maximilian , Williamson Maia Kavanagh , Jearanaiwitayakul Tuksin , Bazire James , Matthews David A. , Davidson Andrew D. 
Published: October 2022

AbstractSARS-CoV-2 is the aetiologic agent of COVID-19 and the associated ongoing pandemic. As the pandemic has progressed, Variants of Concern (VOC) have emerged with lineage defining mutations. Using a SARS-CoV-2 reverse genetic system, based on transformation associated recombination in yeast, a series of replicons were produced for the ancestral Wuhan virus and the SARS-CoV-2 VOC Delta in which different combinations of the Spike, membrane, ORF6 and ORF7a coding sequences were replaced with sequences encoding the selectable marker puromycin N-acetyl transferase and reporter proteins (Renillaluciferase, mNeonGreen and mScarlet). Replicon RNAs were replication competent in African green monkey kidney (Vero E6) derived cells and a range of human cell lines, with a Vero E6 cell line expressing ACE2 and TMPRSS2 showing much higher transfection efficiency and overall levels ofRenillaluciferase activity. The replicons could be used for transient gene expression studies, but cell populations that stably maintained the replicons could not be propagated. Replication of the transiently expressed replicon RNA genomes was sensitive to remedesivir, providing a system to dissect the mechanism of action of antiviral compounds.
Maternal body condition and season influence RNA deposition in the oocytes of alfalfa leafcutting bees (Megachile rotundata)
Authors: Hagadorn Mallory A. , Hunter Frances K. , DeLory Tim , Johnson Makenna M. , Pitts-Singer Theresa L. , Kapheim Karen M. 
Published: October 2022

AbstractMaternal effects are an important source of phenotypic variance, whereby females influence offspring developmental trajectory beyond direct genetic contributions, often in response to changing environmental conditions. However, relatively little is known about the mechanisms by which maternal experience is translated into molecular signals that shape offspring development. One such signal may be maternal RNA transcripts (mRNAs and miRNAs) deposited into maturing oocytes. These regulate the earliest stages of development of all animals, but are understudied in most insects. Here we investigated the effects of female internal (body condition) and external (time of season) environmental conditions on maternal RNA in the maturing oocytes and 24 hr old eggs of alfalfa leafcutting bees. Using gene expression and WGCNA analysis, we found that females adjust the quantity of mRNAs related to protein phosphorylation, transcriptional regulation, and nuclease activity deposited into maturing oocytes in response to both poor body condition and shorter day lengths that accompany the late season. However, the magnitude of these changes was higher for time of season. Females also adjusted miRNA deposition in response to seasonal changes, but not body condition. We did not observe significant changes in maternal RNAs in response to either body condition or time of season in 24-hr-old eggs, which were past the maternal-to-zygotic transition. Our results suggest that females adjust the RNA transcripts they provide for offspring to regulate development in response to both internal and external environmental cues. Variation in maternal RNAs may, therefore, be important for regulating offspring phenotype in response to environmental change.
The unifying catalytic mechanism of the RING-between-RING E3 ligase family
Authors: Wang Xiangyi S. , Cotton Thomas R. , Trevelyan Sarah J. , Richardson Lachlan W. , Lee Wei Ting , Silke John , Lechtenberg Bernhard C. 
Published: October 2022

ABSTRACTThe RING-between-RING (RBR) E3 ubiquitin ligase family in humans comprises 14 members and is defined by a two-step catalytic mechanism in which ubiquitin is first transferred from an E2 to the RBR active site and then to the substrate. To define the core features of this catalytic mechanism, we structurally and biochemically characterise the two RBRs HOIL-1 and RNF216. Crystal structures of both enzymes in their RBR/E2-Ub/Ub transthiolation complexes capturing the first catalytic step, in combination with complementary functional experiments, reveal the defining features of the RBR catalytic mechanism. RBRs catalyse ubiquitination via a conserved transthiolation complex structure that enables efficient E2-to-RBR ubiquitin transfer. Our data also highlight a conserved RBR allosteric mechanism by distinct ubiquitin linkages that suggests that RBRs employ a feed-forward mechanism accelerating their signalling pathways. We finally identify that the HOIL-1 RING2 domain contains an unusual Zn2/Cys6 bivalent zinc cluster that may represent a specific adaptation enabling HOIL-1’s atypical substrate specificity.
Polyphasic circadian neural circuits drive differential activities in multiple downstream rhythmic centers
Authors: Liang Xitong , Holy Timothy E. , Taghert Paul H. 
Published: October 2022

SUMMARYCircadian clocks align various behaviors such as locomotor activity, sleep/wake, feeding, and mating to times of day that are most adaptive. How rhythmic information in pacemaker circuits is translated to neuronal outputs is not well understood. Here we used brain-wide, 24-hrin vivocalcium imaging in theDrosophilabrain and searched for circadian rhythmic activity among identified clusters of dopaminergic (DA) and peptidergic neuroendocrine (PNE) neurons. Such rhythms were widespread and imposed by the PERIOD-dependent clock activity within the ∼150 cell circadian pacemaker network. The rhythms displayed either a Morning, an Evening, or Mid-Day phase. Different sub-groups of circadian pacemakers imposed neural activity rhythms onto different downstream non-clock neurons. Outputs from the canonical M and E pacemakers converged to regulate DA-PPM3 and DA-PAL neurons. E pacemakers regulate the Evening-active DA-PPL1 neurons. In addition to these canonical M and E oscillators, we present evidence for a third dedicated phase occurring at Mid-Day (MD): the l-LNv pacemakers present the MD activity peak and they regulate the MD-active DA-PPM1/2 neurons and three distinct PNE cell types. Thus, theDrosophilacircadian pacemaker network is a polyphasic rhythm generator. It presents dedicated M, E and MD phases that are functionally transduced as neuronal outputs to organize diverse daily activity patterns in downstream circuits.
Renegade Bacterial Genetic Sequences in a Stealth Adapted Virus: Biological and Diagnostic Implications
Authors: Martin W. John 
Published: October 2022

AbstractThere are major differences between viruses, bacteria, and eukaryotic cells in the structuring of their genomes, modes of replication, and capacity to horizontally transfer genetic sequences. DNA sequencing studies on a virus cultured from a patient with chronic fatigue syndrome (CFS) have confirmed a previously underappreciated capacity of certain viruses to capture and transfer bacterial and cellular genetic sequences between eukaryotic cells as part of the infectious process. The virus originated from an African green monkey simian cytomegalovirus (SCMV). It is termed a stealth adapted virus since infection is not accompanied by inflammation. The immune evasion is attributed to the loss and mutation of the genes coding for the relatively few components that are normally targeted by the cellular immune system. This article provides further elucidation of the origins of many of the bacterial-derived genetic sequences present in the virus. There are multiple clones with close but non-identical sequence alignments with different genomic regions of theOchrobactrum quorumnocensA44 species of bacteria. Another set of clones matched most closely to diverse genomic regions ofMycoplasma fermentansbacteria. The sequences of several other clones could only be approximately aligned to those of different types of bacteria. The sequence of clone 3B513 is consistent with genetic contributions from the genomes of several types of bacteria. The term viteria refers to viruses with bacteria-derived genetic sequences. They are the likely primary cause of CFS and autism, and to act as major cofactors in many illnesses, including AIDS. As a more general phenomenon viteria with different types of renegade bacterial sequences can lead to the mistaken diagnoses of bacterial rather than viral diseases. It is important to genetically sequence additional stealth adapted viruses from patients with a wide range of illnesses, including those currently being attributed to Mycoplasma, Borrelia, or Streptococcal infections.