bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rosin Soap Exhibits Virucidal Activity
Authors: Bell Stephen H , Fairley Derek J , Kettunen Hannele , Vuorenmaa Juhani , Orte Juha , Bamford Connor G G , McGrath John W 
Published: July 2021

AbstractChemical methods of virus inactivation are used routinely to prevent viral transmission in both a personal hygiene capacity but also in at-risk environments like hospitals. Several ‘virucidal’ products exist, including hand soaps, gels and surface disinfectants. Resin acids, which can be derived from Tall oil produced from trees, have been shown to exhibit anti-bacterial activity. However, whether these products or their derivatives have virucidal activity is unknown. Here, we assessed the capacity of Rosin soap to inactivate a panel of pathogenic mammalian viruses in vitro. We show that Rosin soap can inactivate the human enveloped viruses: influenza A virus (IAV), respiratory syncytial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For IAV, rosin soap could provide a 100,000-fold reduction in infectivity. However, Rosin soap failed to affect the non-enveloped encephalomyocarditis virus (EMCV). The inhibitory effect of Rosin soap against IAV infectivity was dependent on its concentration but not dependent on incubation time nor temperature. Together, we demonstrate a novel chemical inactivation method against enveloped viruses, which could be of use in preventing virus infections in certain settings.ImportanceViruses remain a significant cause of human disease and death, most notably illustrated through the current Covid-19 pandemic. Control of virus infection continues to pose a significant global health challenge to the human population. Viruses can spread through multiple routes, including via environmental and surface contamination where viruses can remain infectious for days. Methods to inactivate viruses on such surfaces may help mitigate infection. Here we present evidence identifying a novel ‘virucidal’ product in Rosin soap, which is produced from Tall oil from coniferous trees. Rosin soap was able to rapidly and potently inactivate influenza virus and other enveloped viruses.
The angiotensin antagonist Losartan modulates social reward motivation and punishment sensitivity via modulating midbrain-striato-frontal circuits
Authors: Zhou Xinqi , Xu Ting , Zeng Yixu , Zhang Ran , Qi Ziyu , Zhao Weihua , Kendrick Keith M , Becker Benjamin 
Published: July 2021

AbstractSocial deficits and dysregulations in dopaminergic midbrain-striato-frontal circuits represent transdiagnostic symptoms across psychiatric disorders. Animal models suggest that interactions between the dopamine and renin-angiotensin system may modulate learning and reward-related processes. The present study therefore examined the behavioral and neural effects of the angiotensin II type 1 receptor (AT1R) antagonist Losartan on social reward and punishment processing in humans. A pre-registered randomized double-blind placebo-controlled between-subject pharmacological design was combined with a social incentive delay fMRI paradigm during which subjects could avoid social punishment or gain social reward. Healthy volunteers received a single-dose of Losartan (50mg, n=43) or placebo (n=44). Reaction times and emotional ratings served as behavioral outcomes, on the neural level activation and connectivity were modelled. Relative to placebo, Losartan modulated the reaction time and arousal differences between social punishment and social reward. On the neural level the Losartan-enhanced motivational salience of social rewards was accompanied by stronger ventral striatum-prefrontal connectivity during reward anticipation. Losartan increased the reward-neutral difference in the ventral tegmental area (VTA) and attenuated VTA associated connectivity with the bilateral insula in response to punishment during the outcome phase. Losartan modulated approach-avoidance motivation and emotional salience during social punishment versus social reward via modulating distinct core nodes of the midbrain-striato-frontal circuits. The findings document a modulatory role of the renin-angiotensin system in these circuits and associated social processes, suggesting a promising treatment target to alleviate social dysregulations.Significance StatementSocial deficits and anhedonia characterize several mental disoders and have been linked to the midbrain-striato-frontal circuits of the brain. Based on initial findings from animal models we here combine the pharmacological blockade of the angiotensin II type 1 receptor (AT1R) via Losartan with functional MRI to demonstrate that AT1R blockade enhances the motivational salience of social rewards and attenuates the negative impact of social punishment via modulating the communication in the midbrain-striato-frontal circuits in humans. The findings demonstrate for the first time an important role of the AT1R in social reward processing in humans and render the AT1R as promising novel treatment target for social and motivational deficits in mental disoders.
CulebrONT: a streamlined long reads multi-assembler pipeline for prokaryotic and eukaryotic genomes
Authors: Orjuela Julie , Comte Aurore , Ravel Sébastien , Charriat Florian , Vi Tram , Sabot François , Cunnac Sébastien 
Published: July 2021

AbstractUsing long reads provides higher contiguity and better genome assemblies. However, producing such high quality sequences from raw reads requires to chain a growing set of tools, and determining the best workflow is a complex task.To tackle this challenge, we developed CulebrONT, an open-source, scalable, modular and traceable Snakemake pipeline for assembling long reads data. CulebrONT enables to perform tests on multiple samples and multiple long reads assemblers in parallel, and can optionally perform, downstream circularization and polishing. It further provides a range of assembly quality metrics summarized in a final user-friendly report.CulebrONT alleviates the difficulties of assembly pipelines development, and allow users to identify the best assembly options.
Mitochondrial Respiratory Chain Protein Co-Regulation in the Human Brain
Authors: Trumpff Caroline , Owusu-Ansah Edward , Klein Hans-Ulrich , Lee Annie , Petyuk Vladislav , Wingo Thomas S. , Wingo Aliza P. , Thambisetty Madhav , Ferrucci Luigi , Seyfried Nicholas T. , Bennett David A. , De Jager Philip L. , Picard Martin 
Published: July 2021

SummaryMitochondrial respiratory chain (RC) function requires the stoichiometric interaction among dozens of proteins but their co-regulation has not been defined in the human brain. Here, using quantitative proteomics across three independent cohorts we systematically characterized the co-regulation patterns of mitochondrial RC proteins in the human dorsolateral prefrontal cortex (DLPFC). Whereas the abundance of RC protein subunits that physically assemble into stable complexes were correlated, indicating their co-regulation, RC assembly factors exhibited modest co-regulation. Within complex I, nuclear DNA-encoded subunits exhibited >2.5-times higher co-regulation than mitochondrial (mt)DNA-encoded subunits. Moreover, mtDNA copy number was unrelated to mtDNA-encoded subunits abundance, suggesting that mtDNA content is not limiting. Alzheimer’s disease (AD) brains exhibited reduced abundance of complex I RC subunits, an effect largely driven by a 2-4% overall lower mitochondrial protein content. These findings provide foundational knowledge to identify molecular mechanisms contributing to age- and disease-related erosion of mitochondrial function in the human brain.
Network expansion of genetic associations defines a pleiotropy map of human cell biology
Authors: Barrio-Hernandez Inigo , Schwartzentruber Jeremy , Shrivastava Anjali , del-Toro Noemi , Zhang Qian , Bradley Glyn , Hermjakob Henning , Orchard Sandra , Dunham Ian , Anderson Carl A. , Porras Pablo , Beltrao Pedro 
Published: July 2021

AbstractProteins that interact within molecular networks tend to have similar functions and when perturbed influence the same organismal traits. Interaction networks can be used to expand the list of likely trait associated genes from genome-wide association studies (GWAS). Here, we used improvements in SNP-to-gene mapping to perform network based expansion of trait associated genes for 1,002 human traits showing that this recovers known disease genes or drug targets. The similarity of network expansion scores identifies groups of traits likely to share a common genetic basis as well as the biological processes underlying this. We identified 73 pleiotropic gene modules linked to multiple traits that are enriched in genes involved in processes such as protein ubiquitination and RNA processing. We show examples of modules linked to human diseases enriched in genes with pathogenic variants found in patients or relevant mouse knock-out phenotypes and can be used to map targets of approved drugs for repurposing opportunities. Finally, we illustrate the use of the network expansion scores to study genes at inflammatory bowel disease (IBD) GWAS loci, and implicate IBD-relevant genes with strong functional and genetic support.
The zebra finch auditory cortex reconstructs occluded syllables in conspecific song
Authors: Le Bao , Bjoring Margot C , Meliza C Daniel 
Published: July 2021

AbstractIn the perceptual illusion known as phonemic (or auditory) restoration, listeners hear sounds occluded by short bursts of noise. The neural mechanisms that create this illusion by generating predictions of the missing information remain poorly understood. Zebra finches (Taeniopygia guttata) use song, a sequence of complex vocal elements, to communicate in noisy social environments. Here, we found that in anesthetized finches, populations of single units in the homolog of auditory cortex respond to occluded songs as if the missing elements were present. This occurs even for songs birds have never heard, but not if the context is masked or lacks species-typical syntax. These results suggest that local neural dynamics pre-attentively instantiate a general model of conspecific song that biases auditory responses to restore missing information.
A high-throughput assay for directly monitoring nucleolar rRNA biogenesis
Authors: Bryant Carson J. , McCool Mason A. , Abriola Laura , Surovtseva Yulia V. , Baserga Susan J. 
Published: July 2021

AbstractStudies of the regulation of nucleolar function are critical for ascertaining clearer insights into the basic biological underpinnings of ribosome biogenesis, and for future development of therapeutics to treat cancer and ribosomopathies. A number of high-throughput primary assays based on morphological alterations of the nucleolus can indirectly identify hits affecting ribosome biogenesis. However, there is a need for a more direct high-throughput assay for nucleolar function to further evaluate hits. Previous reports have monitored nucleolar RNA biogenesis using 5-ethynyl uridine (5-EU) in low-throughput. We report a miniaturized, high-throughput 5-EU assay for nucleolar function which enables specific calculation of nucleolar rRNA biogenesis inhibition, based on co-staining of the nucleolar protein fibrillarin (FBL). The assay utilizes two siRNA controls, a negative non-targeting siRNA control (siNT) and a positive siRNA control targetingPOLR1A(siPOLR1A), and specifically quantifies median 5-EU signal within nucleoli. Maximum nuclear 5-EU signal can also be used to monitor the effects of putative small molecule inhibitors of RNAP1, like BMH-21, or other treatment conditions that cause FBL dissociation. We validate the 5-EU assay on 68 predominately nucleolar hits from a high-throughput primary screen, showing that 58/68 hits significantly inhibit nucleolar rRNA biogenesis. Our new method establishes direct quantification of nucleolar function in high-throughput, facilitating closer study of ribosome biogenesis in health and disease.
A natural single nucleotide mutation in the small regulatory RNA ArcZ ofDickeya solaniswitches off the antimicrobial activities against yeast and bacteria
Authors: Brual T , Effantin G , Baltenneck J , Attaiech L , Grosbois C , Royer M , Cigna J , Faure D , Hugouvieux-Cotte-Pattat N , Gueguen E 
Published: July 2021

ABSTRACTThe necrotrophic plant pathogenic bacteriumDickeya solaniemerged in the potato agrosystem in Europe. All isolated strains ofD. solanicontain several large polyketide synthase/non-ribosomal peptide synthetase gene clusters. Analogy with genes described in other bacteria suggests that the clustersoocandzmsare involved in the production of secondary metabolites of the oocydin and zeamine families, respectively. A third cluster that we namedssmforsolanisecondarymetabolite had an unknown function. In this study, we constructed mutants impaired in each of the three secondary metabolite clustersssm, ooc, andzmsto compare first the phenotype of theD. solaniwild-type strain D s0432-1 with its associated mutants. We demonstrated the antimicrobial functions of these three PKS/NRPS clusters against bacteria, yeasts or fungi. The secondary metabolite clusterssm, conserved in several otherDickeyaspecies, produces a secondary metabolite inhibiting yeasts. Phenotyping and comparative genomics of differentD. solaniwild-type isolates revealed that the small regulatory RNA ArcZ plays a major role in the control of the clustersssmandzms. A single-point mutation, conserved in someDickeyawild-type strains, including the type strain IPO 2222, impairs the ArcZ function by affecting its processing into an active form.AUTHOR SUMMARYThe development of new antibacterial molecules is critical in tackling the emergence of new pathogens or bacterial strains resistant to already available antibiotics. Bacterial phytopathogens can potentially synthesize novel compounds capable of targeting a specific type of microorganism.Dickeya solaniis the only of the twelve describedDickeyaspecies that has the three secondary metabolic pathwaysssm, oocandzms. An investigation of the functions of these three clusters allowed us to identify the anti-yeast activity of thessmcluster, a potential new molecule of clinical importance. By comparing the antimicrobial activity of severalDickeya solanistrains, we identified the small RNA regulator ArcZ as a critical regulator in the activation of thessmandzmsclusters. Our study showed that single-nucleotide polymorphisms of sRNA encoding genes can have huge impacts on bacterial phenotypes. It is thus critical to pay attention to the allele diversity of sRNA genes.
TGF-β-dependent Lymphoid Tissue Residency of Stem-like T cells Limits the Response to Tumor Vaccine
Authors: Li Guo , Wang Liwen , Ma Chaoyu , Liao Wei , Liu Yong , Mishra Shruti , Zhang Xin , Qiu Yuanzheng , Lu Qianjin , Zhang Nu 
Published: July 2021

AbstractStem-like CD8+T cells represent the key subset responding to multiple tumor immunotherapies, including tumor vaccination. However, the signals that control the differentiation of stem-like T cells are not entirely known. Most previous investigations on stem-like T cells are focused on tumor infiltrating T cells (TIL). The behavior of stem-like T cells in other tissues remains to be elucidated. Tissue-resident memory T cells (TRM) are often defined as a non-circulating T cell population residing in non-lymphoid tissues. TILs carrying TRMfeatures are associated with better tumor control. Here, we found that stem-like CD8+T cells differentiated into TRMs in a TGF-β and tumor antigen dependent manner almost exclusively in tumor draining lymph node (TDLN). TDLN-resident stemlike T cells were negatively associated with the response to tumor vaccine. In other words, after tumor vaccine, TDLN stem-like T cells transiently lost TRMfeatures, differentiated into migratory effectors and exerted tumor control.
Bayesian optimisation for yield in high-dimensional trait-space identifies crop ideotypes in Oil Seed Rape
Authors: Calderwood Alexander , Siles Laura , Eastmond Peter J. , Kurup Smita , Morris Richard J. 
Published: July 2021

AbstractThe improvement of crop yield has long been a major breeding target and is increasingly becoming a goal in many areas of plant research. Yield has been shown to be a complex trait, depending on multiple genes, plant architecture and plant-environment interactions. This complexity is frequently reduced by focussing on contributing factors to yield (yield traits). However, a quantitative understanding of the interplay between yield traits, and the effect of these relationships on yield is largely unexplored. Consequently, the extent to which crop varieties achieve their optimal morphology in a given environment and how this impacts on seed yield is unknown.Here we use causal inference to model the hierarchically structured effects of 27 macro and micro yield traits on each other over the course of plant development, and on seed yield in Spring and Winter oilseed rape plants. We perform Bayesian optimisation on the modelled yield potential, identifying the morphology of ideotype plants which are expected to be higher yielding than the existing varieties in the studied panels. We find that existing Spring varieties occupy the optimal regions of trait-space, but that potentially high yielding strategies are unexplored in extant Winter varieties.In addition to concrete recommendations for varietal improvement in oilseed rape, this work provides a novel, general methodological framework for the study of crop breeding as an optimisation problem.
The ASC Speck and NLRP3 Inflammasome Function Are Spatially and Temporally Distinct
Authors: Nagar Abhinit , Rahman Tabassum , Harton Jonathan A. 
Published: July 2021

ABSTRACTAlthough considered the ternary inflammasome structure, whether the singular, perinuclear NLRP3:ASC speck is synonymous with the NLRP3 inflammasome is unclear. Herein we report that the NLRP3:ASC speck is not required for nigericin-induced inflammasome activation, but facilitates and maximizes IL-1β processing. Further, the NLRP3 agonists H2O2 and MSU elicited IL-1β maturation without inducing specks. Notably, caspase-1 activity is spatially distinct from the speck, occurring at multiple cytoplasmic sites. Additionally, caspase-1 activity negatively regulates speck frequency and speck size while speck numbers and IL-1β processing are negatively correlated, cyclical, and can be uncoupled by NLRP3 mutations or inhibiting microtubule polymerization. Finally, when specks are present, caspase-1 is likely activated after leaving the speck structure. Thus, the speck is not the NLRP3 inflammasome itself, but is instead a dynamic structure which may amplify the NLRP3 response to weak stimuli by facilitating the formation and release of small NLRP3:ASC complexes which in turn activate caspase-1.
Energetics but not development is impacted in coral embryos exposed to ocean acidification
Authors: Chille EE , Strand EL , Scucchia F , Neder M , Schmidt V , Sherman MO , Mass T , Putnam HM 
Published: July 2021

AbstractIn light of the chronic stress and mass mortality reef-building corals face under climate change, it is critical to understand the processes essential to reef persistence and replenishment, including coral reproduction and development. Here we quantify gene expression and size sensitivity to ocean acidification across a set of developmental stages in the rice coral, Montipora capitata. Embryos and swimming larvae were exposed to pH treatments 7.8 (Ambient), 7.6 (Low) and 7.3 (Xlow) from fertilization to 9 days post-fertilization. Embryo and larval volume, and stage-specific gene expression were compared between treatments to determine the effects of acidified seawater on early development. While there was no measurable size differentiation between fertilized eggs and prawn chips exposed to pH 7.8, 7.6, and 7.3, early gastrula and planula raised in reduced pH treatments were significantly smaller than those raised in ambient seawater, suggesting an energetic cost to developing under low pH. However, no differentially expressed genes emerged until 9 days post-fertilization. Notably, gene expression patterns of larvae developing at pH 7.8 and pH 7.3 were more similar than those developing at pH 7.6. Larvae from pH 7.6 showed upregulation of genes involved in cell division, regulation of transcription, lipid metabolism, and oxidative stress in comparison to the other two treatments. While low pH appears to increase energetic demands and trigger oxidative stress, the developmental process is robust to this at a molecular level, with swimming larval stage reached in all pH treatments.Summary statementThis developmental time series tracks the physiological and transcriptomic outcomes of early coral development under ambient pH (pH 7.8), and two low pH conditions (pH 7.6 and 7.3).
Residual dynamics resolves recurrent contributions to neural computation
Authors: Galgali Aniruddh R. , Sahani Maneesh , Mante Valerio 
Published: July 2021

AbstractRelating neural activity to behavior requires an understanding of how neural computations arise from the coordinated dynamics of distributed, recurrently connected neural populations. However, inferring the nature of recurrent dynamics from partial recordings of a neural circuit presents significant challenges. Here, we show that some of these challenges can be overcome by a fine-grained analysis of the dynamics of neural residuals, i.e. trial-by-trial variability around the mean neural population trajectory for a given task condition. Residual dynamics in macaque pre-frontal cortex (PFC) in a saccade-based perceptual decision-making task reveals recurrent dynamics that is time-dependent, but consistently stable, and suggests that pronounced rotational structure in PFC trajectories during saccades is driven by inputs from upstream areas. The properties of residual dynamics restrict the possible contributions of PFC to decision-making and saccade generation, and suggest a path towards fully characterizing distributed neural computations with large-scale neural recordings and targeted causal perturbations.
Tissue-Specific Biochemical Differences Between Chronic Wasting Disease Prions Isolated From Free Ranging, White-Tailed Deer (Odocoileus virginianus)
Authors: Wagner Kaitlyn , Pierce Robyn , Gordon Elizabeth , Ballard Jennifer R. , Moreno Julie A. , Zabel Mark D. 
Published: July 2021

ABSTRACTChronic wasting disease (CWD) is an invariably fatal prion disease affecting cervid species world-wide. Prions can manifest as distinct strains that can influence disease pathology and transmission. CWD is profoundly lymphotropic and most infected cervids likely shed peripheral prions replicated in lymphoid organs. However, CWD is a neurodegenerative disease and most research on prion strains has focused on neurogenic prions. Thus, a knowledge gap exists comparing prions in the brain to prions in the lymph node. In this study we compared prions from the obex and lymph node of naturally exposed white-tailed deer to identify potential biochemical strain differences. Here, we report biochemical evidence of strain differences between the brain and lymph node from these animals. Future work should examine the biological and zoonotic impact of these biochemical differences and examine more cervids from multiple locations to see if these differences are conserved across species and locations.