bluuebunny/crossref_metadata_2025_split huggingface dataset:
The requirement of GW182 in miRNA-mediated gene silencing inDrosophilalarval development
Authors: Matsuura-Suzuki Eriko , Kiyokawa Kaori , Iwasaki Shintaro , Tomari Yukihide 
Published: June 2022

AbstractmicroRNAs (miRNAs) regulate a wide variety of biological processes by silencing their target genes. Argonaute (AGO) proteins load miRNAs to form RNA-induced silencing complex (RISC), which mediates translational repression and/or mRNA decay of the targets. A scaffold protein called GW182 directly binds AGO and the CCR4-NOT deadenylase complex, initiating the mRNA decay reaction. Although previous studies have demonstrated the critical role of GW182 in cultured cells as well as in cell-free systems, its biological significance in living organisms remains poorly explored, especially inDrosophila melanogaster. Here, we generatedgw182-null flies using the CRISPR/Cas9 system and found that, unexpectedly, they can survive until an early second instar larval stage. Moreover, in vivo miRNA reporters can be effectively repressed ingw182-null first instar larvae. Nevertheless,gw182-null flies have defects in the expression of chitin-related genes and the formation of the larval trachea system, preventing them to complete the larval development. Our results highlight the importance of both GW182-dependent and -independent silencing mechanisms in vivo.
Effective Representation Learning via The Integrated Self-Supervised Pre-training models of StyleGAN2-ADA and DINO for Colonoscopy Images
Authors: Kim Jong-Yeup , Tangriberganov Gayrat , Jung Woochul , Kim Dae Sung , Koo Hoon Sup , Lee Suehyun , Kim Sun Moon 
Published: June 2022

AbstractIn order to reach better performance in visual representation learning from image or video dataset, huge amount of annotated data are on demand. However, collecting and annotating large-scale datasets are costly and time-consuming tasks. Especially, in a domain like medical, it is hard to access patient images because of the privacy concerns and also not knowing what exactly to annotate without expert effort. One of the solutions to obviate the hassle is to use Self-Supervised learning methods (SSL) and Generative Adversarial Networks (GANs) together. SSL and GANs are quickly advancing fields. GANs have unique capability to create unlabeled data sources containing photo-realistic images while SSL methods are able to learn general image and video features from large-scale data without using any human-annotated labels. In this work, we explore leveraging the power of recently introduced StyleGAN2-ada and Self-Supervised Pre-Training of Dino together for the pretext task. Our underlying insight is also that leveraging the current approaches with Transfer Learning (TF) together brings benefit on doing pretext task in medical domain. By the strategy of unifying these two approaches, we propose the integrated version and use it derive representation learning on polyp dataset.
CeGAL: revisiting a widespread fungal-specific TF family using an in silico error-aware approach to identify missing zinc cluster domains
Authors: Mayer Claudine , Vogt Arthur , Uslu Tuba , Scalzitti Nicolas , Poch Olivier , Thompson Julie D. 
Published: June 2022

ABSTRACTTranscription factors (TF) regulate gene activity in eukaryotic cells by binding specific regions of genomic DNA. In fungi, the most abundant TF class contains a fungal-specific ‘GAL4-like’ Zn2C6 DNA binding domain (DBD), while the second class contains another fungal-specific domain, known as ‘fungal_trans’ or Middle Homology Domain (MHD), whose function remains largely uncharacterized. Remarkably, almost a third of MHD-containing TF in public sequence databases apparently lack DNA binding activity, since they are not predicted to contain a DBD. Here, we reassess the domain organization of these ‘MHD-only’ proteins using an in silico error-aware approach. Our large-scale analysis of ~17000 MHD-only TF sequences showed that the vast majority (>90%) result from gene annotation errors, thus contradicting previous findings that the MHD-only TF are widespread in fungi. We show that they are in fact exceptional cases, and that the Zn2C6-MHD domain pair represents the canonical domain signature defining a new TF family composed of two fungal-specific domains. We call this family CeGAL, after the most characterized members: Cep3, whose 3D structure has been determined and GAL4, an archetypal eukaryotic TF. This definition should improve the classification of the Zn2C6 TF and provide critical insights into fungal gene regulatory networks.IMPORTANCEIn fungi, extensive efforts focus on genome-wide characterization of potential Transcription Factors (TFs) and their targets genes to provide a better understanding of fungal processes and a rational for transcriptional manipulation. The second most abundant families of fungal-specific TFs, characterized by a Middle Homology Domain, are major regulators of primary and secondary metabolisms, multidrug resistance and virulence. Remarkably, one third of these TFs do not have a DNA Binding Domain (DBD-orphan) and thus are excluded from genome-wide studies. This particularity has been the subject of debate for many years. By computationally inspecting the close genomic environment of about 20,000 DBD-orphan TFs from a wide range of fungal species, we reveal that more than 90% contained sequences encoding a zinc-finger DBD. This analysis implies that the arrays of DBD containing TFs and their control DNA-sequences in target genes need to be reconsidered and expands the combinatorial regulation degree of the crucial fungal processes controlled by this TF family.
A single-nucleus transcriptomics study of alcohol use disorder in the nucleus accumbens
Authors: van den Oord Edwin J.C.G. , Xie Lin Y , Zhao Min , Aberg Karolina A. , Clark Shaunna L. 
Published: June 2022

ABSTRACTAlcohol use disorder (AUD) is a significant public health problem. Gene expression studies offer promising opportunities to better understand the underlying pathogenic processes. As cell-types differ in their function, gene expression profiles will typically vary across cell-types. When studying bulk tissue, failure to account for this cellular diversity has a detrimental impact on the ability to detect disease associations. We therefore assayed the transcriptomes of 32,531 individual nuclei extracted from the nucleus accumbens (NAc) of 9 donors with AUD and 9 controls. Our study identified 17 clearly delineated cell-types. We detected 26 transcriptome-wide significant association signals (q-value<0.1) that mainly involved medium spiny neurons with both D1-type and D2-type dopamine receptors, microglia and oligodendrocytes. A significantly higher number of findings than expected by chance replicated in an existing single nucleus gene expression study of alcohol dependence in the pre-frontal cortex (enrichment ratio 1.91, P value 0.019). The alcohol related genes and pathways detected for each cell-type were consistent with the functions of those cell-types reported in the literature. Thus, for the neurons we observed alcohol related neurodegeneration, disruption of circadian rhythms, alterations in glucose metabolism, and changes in synaptic plasticity. For microglia we found neuroinflammation and immune-related processes and for oligodendrocytes disruptions in myelination. This identification of the specific cell-types from which the association signals originate is key for designing proper follow-up experiments and, eventually, for developing new and targeted clinical interventions.
COVID-19 redux: clinical, virologic, and immunologic evaluation of clinical rebound after nirmatrelvir/ritonavir
Authors: Epling Brian P. , Rocco Joseph M. , Boswell Kristin L. , Laidlaw Elizabeth , Galindo Frances , Kellogg Anela , Das Sanchita , Roder Allison , Ghedin Elodie , Kreitman Allie , Dewar Robin L. , Kelly Sophie E. M. , Kalish Heather , Rehman Tauseef , Highbarger Jeroen , Rupert Adam , Kocher Gregory , Holbrook Michael R. , Lisco Andrea , Manion Maura , Koup Richard A. , Sereti Irini 
Published: June 2022

AbstractClinical rebound of COVID-19 after nirmatrelvir/ritonavir treatment has been reported. We performed clinical, virologic, and immune measurements in seven patients with symptomatic rebound, six after nirmatrelvir/ritonavir treatment and one without previous treatment. There was no evidence of severe disease or impaired antibody and T-cell responses in people with rebound symptoms.
DORA-compliant measures to assess research quality and impact in biomedical institutions: review of published research, international best practice and Delphi survey
Authors: Gagliardi Anna R , Chen Rob HC , Boury Himani , Albert Mathieu , Chow James , DaCosta Ralph S , Hoffman Michael , Keshavarz Behrang , Kontos Pia , Liu Jenny , McAndrews Mary Pat , Protze Stephanie 
Published: June 2022

ABSTRACTObjectiveThe San Francisco Declaration on Research Assessment (DORA) advocates for assessing biomedical research quality and impact, yet academic organizations continue to employ traditional measures such as Journal Impact Factor. We aimed to identify and prioritize measures for assessing research quality and impact.MethodsWe conducted a review of published and grey literature to identify measures of research quality and impact, which we included in an online survey. We assembled a panel of researchers and research leaders, and conducted a two-round Delphi survey to prioritize measures rated as high (rated 6 or 7 by ≥ 80% of respondents) or moderate (rated 6 or 7 by ≥ 50% of respondents) importance.ResultsWe identified 50 measures organized in 8 domains: relevance of the research program, challenges to research program, or productivity, team/open science, funding, innovations, publications, other dissemination, and impact. Rating of measures by 44 panelists (60%) in Round One and 24 (55%) in Round Two of a Delphi survey resulted in consensus on the high importance of 5 measures: research advances existing knowledge, research plan is innovative, an independent body of research (or fundamental role) supported by peer-reviewed research funding, research outputs relevant to discipline, and quality of the content of publications. Five measures achieved consensus on moderate importance: challenges to research productivity, potential to improve health or healthcare, team science, collaboration, and recognition by professional societies or academic bodies. There was high congruence between researchers and research leaders across disciplines.ConclusionsOur work contributes to the field by identifying 10 DORA-compliant measures of research quality and impact, a more comprehensive and explicit set of measures than prior efforts. Research is needed to identify strategies to overcome barriers of use of DORA-compliant measures, and to “de-implement” traditional measures that do not uphold DORA principles yet are still in use.
Helicobacter pylori promotes colorectal carcinogenesis by deregulating intestinal immunity and inducing a mucus-degrading microbiota signature
Authors: Ralser Anna , Dietl Alisa , Jarosch Sebastian , Engelsberger Veronika , Wanisch Andreas , Janssen Klaus Peter , Vieth Michael , Quante Michael , Haller Dirk , Busch Dirk H. , Deng Li , Mejías-Luque Raquel , Gerhard Markus 
Published: June 2022

ABSTRACTOBJECTIVEH. pylori infection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show that infected individuals harbor a nearly two-fold increased risk to develop colorectal cancer (CRC). However, a direct causal and functional connection between H. pylori infection and colon cancer is lacking.DESIGNWe infected two Apc-mutant mouse models and C57BL/6 mice with H. pylori and conducted a comprehensive analysis of H. pylori-induced changes in intestinal immune responses and epithelial signatures via flow cytometry, chip cytometry, immunohistochemistry and single cell RNA sequencing. Microbial signatures were characterized and evaluated in germ-free mice and via stool transfer experiments.RESULTSH. pylori infection accelerated tumor development in Apc-mutant mice. We identified a unique H. pylori-driven immune alteration signature characterized by a reduction in regulatory T-cells and proinflammatory T-cells. Furthermore, in the intestinal and colonic epithelium, H. pylori induced pro-carcinogenic STAT3 signaling and a loss of goblet cells, changes that have been shown to contribute - in combination with pro-inflammatory and mucus degrading microbial signatures - to tumor development. Similar immune and epithelial alterations were found in human colon biopsies from H. pylori-infected patients. Housing of Apc-mutant mice under germ-free conditions ameliorated, and early antibiotic eradication of H. pylori infection normalized the tumor incidence to the level of uninfected controls.CONCLUSIONSOur studies provide evidence that H. pylori infection is a strong causal promoter of colorectal carcinogenesis. Therefore, implementation of H. pylori status into preventive measures of CRC should be considered.
RNA polymerase II pausing contributes to maintain chromatin organization in erythrocytes
Authors: Andrés Penagos-Puig , Sherlyn Claudio-Galeana , Aura Stephenson-Gussinye , Karina Jácome-López , Amaury Aguilar-Lomas , Rosario Pérez-Molina , Mayra Furlan-Magaril 
Published: June 2022

AbstractChicken erythrocytes are nucleated cells often referred to as transcriptionally inactive, although the epigenetic changes and chromatin remodeling that mediate transcriptional repression and the extent of gene silencing during avian terminal erythroid differentiation are not fully understood. Here we characterized the changes in gene expression, chromatin accessibility, genome organization, and chromatin nuclear disposition during the terminal stages of erythropoiesis in chicken and found a complex chromatin reorganization at different genomic scales. We identified a robust decrease in transcription in erythrocytes. Nevertheless, a set of genes maintains their expression in erythrocytes, including genes involved in RNA pol II promoter-proximal pausing. Erythrocytes exhibit an inverted nuclear architecture and reposition euchromatin towards the nuclear periphery together with the paused RNA polymerase. In erythrocytes, chromatin domains are partially lost genome-wide except at mini domains retained around paused promoters. Our results suggest that promoter-proximal pausing of the RNA pol II participates in the transcriptional regulation of the erythroid genome and highlight the role of RNA polymerase in the maintenance of local chromatin organization.
Systematic microscopical analysis reveals obligate synergy between extracellular matrix components during Bacillus subtilis colony biofilm development
Authors: Porter Michael , Davidson Fordyce A. , MacPhee Cait E. , Stanley-Wall Nicola R. 
Published: June 2022

AbstractSingle-species bacterial colony biofilms often present recurring morphologies that are thought to be of benefit to the population of cells within and known to be dependent on the self-produced extracellular matrix. However, much remains unknown in terms of the developmental process at the single cell level. Here, we design and implement systematic time-lapse imaging and quantitative analyses of the growth of Bacillus subtilis colony biofilms. We follow development from the initial deposition of founding cells through to the formation of large-scale complex structures. Using the model biofilm strain NCIB 3610, we examine the movement dynamics of the growing biomass and compare with those displayed by a suite of otherwise isogenic matrix-mutant strains. Correspondingly, we assess the impact of an incomplete matrix on biofilm morphologies and sessile growth rate. Our results indicate that radial expansion of colony biofilms results from division of bacteria at the biofilm periphery rather than being driven by swelling due to fluid intake. Moreover, we show that lack of exopolysaccharide production has a negative impact on cell division rate, and the extracellular matrix components act synergistically to give the biomass the structural strength to produce aerial protrusions and agar substrate-deforming ability.
Vitrocam: A simple low cost Vitrobot camera for assessing grid quality
Authors: Chua Eugene Y.D. , Serbynovskyi Viacheslav , Gheorghita Robert , Alink Lambertus M. , Podolsky Daniel , Potter Clinton S. , Carragher Bridget 
Published: June 2022

AbstractThe most widely used sample preparation method for single particle cryo-electron microscopy (cryo-EM) today involves the application of 3-4 μl of sample onto a cryo-EM grid, removing most of the liquid by blotting with filter paper, then rapidly plunging into liquid ethane to vitrify the sample. To determine if the grid has appropriate ice thicknesses and sufficient area for cryo-EM imaging, the grid must be inserted into a transmission electron microscope (TEM) and screened. This process to evaluate grid quality is costly and time consuming. Here, we present our initial attempt to image the sample preparation process in one of the most commonly used plunge freezing devices, the Vitrobot. We do this by building the Vitrocam, a Raspberry Pi high-speed camera, that captures images of grids mid-plunge. Images from the Vitrocam can be correlated to TEM atlases and show promise for providing preliminary feedback on grid quality and ice thickness.
Spatial tuning in nociceptive processing is driven by attention
Authors: Adamczyk Wacław M. , Katra Michał , Szikszay Tibor M. , Peugh James , King Christopher D. , Luedtke Kerstin , Coghill Robert C. 
Published: June 2022

AbstractWhen the source of nociception expands across a body area, the experience of pain increases due to the spatial integration of nociceptive information. This well-established effect is called spatial summation of pain (SSp) and has been the subject of multiple investigations. Here, we used cold-induced SSp to investigate the effect of attention on the spatial tuning of nociceptive processing. Forty pain-free volunteers (N=40, 20 females) participated in this experiment. They took part in an SSp paradigm based on three hand immersions into cold water (5°C): Participants either immersed the ulnar segment (“a”), radial segment (“b”) or both hand segments (“a+b”) and provided overall pain ratings. In some trials based on “a+b” immersions, they were also asked to provide divided (i.e., first pain in “a” then in “b”; or reversed) and directed attention ratings (i.e., pain only in “a” or “b”). Results confirmed a clear SSp effect in which reported pain during immersions of “a” or “b” was less intense than pain during immersions of “a+b” (p<0.001). Data also confirmed that spatial tuning was altered. SSp was fully abolished when participants provided two ratings in a divided fashion (p<0.001). Furthermore, pain was significantly lower when attention was directed only to one segment (“a” OR “b”) during “a+b” immersion (p<0.001). We conclude that spatial tuning is dynamically driven by attention as reflected in abolished SSp. Directed attention was sufficient to focus spatial tuning and abolish SSp. Results support the role of cognitive processes such as attention in spatial tuning.PerspectiveThis article presents experimental investigation of spatial tuning in pain and offers mechanistic insights of contiguous spatial summation of pain in healthy volunteers. Depending on how pain is evaluated in terms of attentional derivative (overall pain, directed, divided attention) the pain is reduced and spatial summation abolished.
Subsistence of sib altruism in different mating systems and Haldane’s arithmetic
Authors: Garay József , Csiszár Villő , Móri Tamás F. 
Published: June 2022

AbstractThe moral rule “Risk your life to save your family members” is, at the same time, a biological phenomenon. The prominent population geneticist, J.B.S. Haldane told his friends that he would risk his life to save two drowning brothers, but not one – so the story goes. In biological terms, Haldane’s arithmetic claims that sib altruism is evolutionarily rational, whenever by “self-sacrifice” an altruistic gene “rescues”, on average, more than one copy of itself in its lineage. Here, we derive conditions for evolutionary stability of sib altruism, using population genetic models for three mating systems (monogamy, promiscuity and polygyny) with linear and non-linear group effect on the siblings’ survival rate.We show that for all considered selection situations, the condition of evolutionary stability is equivalent to Haldane’s arithmetic. The condition for evolutionary stability is formulated in terms of genetic relatedness and the group effect on the survival probability, similarly to the classical Hamilton’s rule. We can set up a “scale of mating systems”, since in pairwise interactions the chance of evolutionary stability of sib altruism decreases in this order: monogamy, polygyny and promiscuity.Practice of marrying and siblings’ solidarity are moral rules in a secular world and in various religious traditions. These moral rules are not evolutionarily independent, in the sense that the subsistence of sib altruism is more likely in a monogamous population.HighlightsHaldane’s arithmetic is introducedConditions for evolutionary stability of sib altruism are givenEvolutionary stability is equivalent to Haldane’s arithmetic in the studied modelGeneralized Hamilton’s rules are formulated
Fitness Functions for RNA Structure Design
Authors: Ward Max , Courtney Eliot , Rivas Elena 
Published: June 2022

AbstractAn RNA design algorithm takes a target RNA structure and finds a sequence that folds into that structure. This is fundamentally important for engineering therapeutics using RNA. Computational RNA design algorithms are guided by fitness functions, but not much research has been done on the merits of these functions. We survey current RNA design approaches with a particular focus on the fitness functions used. We experimentally compare the most widely used fitness functions in RNA design algorithms on both synthetic and natural sequences. It has been almost 20 years since the last comparison was published, and we find similar results with a major new result: maximizing probability outperforms minimizing ensemble defect. The probability is the likelihood of a structure at equilibrium and the ensemble defect is the weighted average number of incorrect positions in the ensemble. Also, we observe that many recently published approaches minimize structure distance to the minimum free energy prediction, which we find to be a poor fitness function.
Reduced PDE4D7 expression in prostate cancer correlates with down-regulation of genomic elements within the up-stream PDE4D coding region on chromosome 5
Authors: Gulliver Chloe , Baillie George S , Hoffmann Ralf 
Published: June 2022

AbstractPDE4D7 expression is diminished during progression of PCa and the phosphodiesterase has been proposed as a prognostic biomarker. RNA sequencing of PCa tissue identified sequences in the PDE4D coding region on Chr5q12 exhibiting similarities in mRNA expression profile to PDE4D7. As previously identified, PART1 had a significantly similar expression pattern to PDE4D7 across samples. However, other genes also matched expression to PDE4D7, including miRNAs and lncRNAs. These novel PDE4D7 associated genes represent putative PCa biomarkers and could have mechanistic roles in PCa progression.