bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empirical evidence for epigenetic inheritance driving evolutionary adaptation
Authors: Stajic Dragan , Jansen Lars E. T. 
Published: April 2021

The cellular machinery that regulates gene expression can be self-propagated across cell division cycles and even generations. This renders gene expression states and their associated phenotypes heritable, independently of genetic changes. These phenotypic states, in turn, can be subject to selection and may influence evolutionary adaptation. In this review, we will discuss the molecular basis of epigenetic inheritance, the extent of its transmission and mechanisms of evolutionary adaptation. The current work shows that heritable gene expression can facilitate the process of adaptation through the increase of survival in a novel environment and by enlarging the size of beneficial mutational targets. Moreover, epigenetic control of gene expression enables stochastic switching between different phenotypes in populations that can potentially facilitate adaptation in rapidly fluctuating environments. Ecological studies of the variation of epigenetic markers (e.g. DNA methylation patterns) in wild populations show a potential contribution of this mode of inheritance to local adaptation in nature. However, the extent of the adaptive contribution of the naturally occurring variation in epi-alleles compared to genetic variation remains unclear.
This article is part of the theme issue ‘How does epigenetics influence the course of evolution?’
Evolution of epigenetic transmission when selection acts on fecundity versus viability
Authors: Kuijper Bram , Johnstone Rufus A. 
Published: April 2021

Existing theory on the evolution of parental effects and the inheritance of non-genetic factors has mostly focused on the role of environmental change. By contrast, how differences in population demography and life history affect parental effects is poorly understood. To fill this gap, we develop an analytical model to explore how parental effects evolve when selection acts on fecundity versus viability in spatio-temporally fluctuating environments. We find that regimes of viability selection, but not fecundity selection, are most likely to favour parental effects. In the case of viability selection, locally adapted phenotypes have a higher survival than maladapted phenotypes and hence become enriched in the local environment. Hence, simply by being alive, a parental phenotype becomes correlated to its environment (and hence informative to offspring) during its lifetime, favouring the evolution of parental effects. By contrast, in regimes of fecundity selection, correlations between phenotype and environment develop more slowly: this is because locally adapted and maladapted parents survive at equal rates (no survival selection), so that parental phenotypes, by themselves, are uninformative about the local environment. However, because locally adapted parents are more fecund, they contribute more offspring to the local patch than maladapted parents. In case these offspring are also likely to inherit the adapted parents’ phenotypes (requiring pre-existing inheritance), locally adapted offspring become enriched in the local environment, resulting in a correlation between phenotype and environment, but only in the offspring’s generation. Because of this slower build-up of a correlation between phenotype and environment essential to parental effects, fecundity selection is more sensitive to any distortions owing to environmental change than viability selection. Hence, we conclude that viability selection is most conducive to the evolution of parental effects.This article is part of the theme issue ‘How does epigenetics influence the course of evolution?’
Uncovering divergence in gene expression regulation in the adaptation of yeast to nitrogen scarcity
Authors: Villarroel Carlos A. , Bastías Macarena , Canessa Paulo , Cubillos Francisco A. 
Published: April 2021

AbstractSaccharomyces cerevisiaerewires its transcriptional output to survive stressful environments, such as nitrogen scarcity under fermentative conditions. Although divergence in nitrogen metabolism has been described among natural yeast populations, the impact of regulatory genetic variants modulating gene expression and nitrogen consumption remains to be investigated. Here, we employed an F1 hybrid from two contrastingS. cerevisiaestrains, providing a controlled genetic environment to mapcisfactors involved in the divergence of gene expression regulation in response to nitrogen scarcity. We used a dual approach to obtain genome-wide allele-specific profiles of chromatin accessibility, transcription factor binding, and gene expression through ATAC-seq and RNA-seq. We observed large variability in allele-specific expression and accessibility between the two genetic backgrounds, with a third of these differences specific to a deficient nitrogen environment. Furthermore, we discovered events of allelic bias in gene expression correlating with allelic bias in transcription factor binding solely under nitrogen scarcity, where the majority of these transcription factors orchestrates the Nitrogen Catabolite Repression regulatory pathway and demonstrates acisx environment-specific response. Our approach allowed us to findcisvariants modulating gene expression, chromatin accessibility and allelic differences in transcription factor binding in response to low nitrogen culture conditions.ImportanceHistorically, coding variants were prioritized when searching for causal mechanisms driving adaptation of natural populations to stressful environments. However, the recent focus on non-coding variants demonstrated their ubiquitous role in adaptation. Here we performed genome-wide regulatory variation profiles between two divergent yeast strains when facing nitrogen nutritional stress. The open chromatin availability of several regulatory regions changes in response to nitrogen scarcity. Importantly we describe regulatory events that deviate between strains. Our results demonstrate a widespread variation in gene expression regulation between naturally occurring populations in response to stressful environments.
A content-based representational scaffold for naturalistic event memories
Authors: Reagh Zachariah M. , Ranganath Charan 
Published: April 2021

AbstractAlthough every life event is unique, there are considerable commonalities across events. However, little is known about whether or how the brain flexibly represents information about different event components at encoding and during remembering. Here, we show that different cortico-hippocampal networks systematically represent specific components of events depicted in videos, both during viewing and during episodic memory retrieval. Regions of an Anterior Temporal Network represented information about people, generalizing across contexts, whereas regions of a Posterior Medial Network represented context information, generalizing across people. Medial prefrontal cortex generalized across videos depicting the same schema, whereas the hippocampus maintained event-specific representations. Similar effects were seen in real-time and recall, suggesting reuse of event components across overlapping episodic memories. These findings reveal a computationally optimal strategy in cortico-hippocampal networks for encoding different high-level event components, supporting efficient reuse for event comprehension, imagination, and recollection.
Nucleosome patterns in four plant pathogenic fungi with contrasted genome structures
Authors: Colin Clairet , Nicolas Lapalu , Adeline Simon , Soyer Jessica L. , Muriel Viaud , Enric Zehraoui , Berengère Dalmais , Isabelle Fudal , Nadia Ponts 
Published: April 2021

AbstractFungal pathogens represent a serious threat towards agriculture, health, and environment. Control of fungal diseases on crops necessitates a global understanding of fungal pathogenicity determinants and their expression during infection. Genomes of phytopathogenic fungi are often compartmentalized: the core genome contains housekeeping genes whereas the fast-evolving genome mainly contains transposable elements and species-specific genes. In this study, we analysed nucleosome landscapes of four phytopathogenic fungi with contrasted genome organizations to describe and compare nucleosome repartition patterns in relation with genome structure and gene expression level. We combined MNase-seq and RNA-seq analyses to concomitantly map nucleosome-rich and transcriptionally active regions during fungal growth in axenic culture; we developed the MNase-seq Tool Suite (MSTS) to analyse and visualise data obtained from MNase-seq experiments in combination with other genomic data and notably RNA-seq expression data. We observed different characteristics of nucleosome profiles between species, as well as between genomic regions within the same species. We further linked nucleosome repartition and gene expression. Our findings support that nucleosome positioning and occupancies are subjected to evolution, in relation with underlying genome sequence modifications. Understanding genomic organization and its role in expression regulation is the next gear to understand complex cellular mechanisms and their evolution.
Telomere-to-telomere gapless chromosomes of banana using nanopore sequencing
Authors: Belser Caroline , Baurens Franc-Christophe , Noel Benjamin , Martin Guillaume , Cruaud Corinne , Istace Benjamin , Yahiaoui Nabila , Labadie Karine , Hřibová Eva , Doležel Jaroslav , Lemainque Arnaud , Wincker Patrick , D’Hont Angélique , Aury Jean-Marc 
Published: April 2021

AbstractLong-read technologies hold the promise to obtain more complete genome assemblies and to make them easier. Coupled with long-range technologies, they can reveal the architecture of complex regions, like centromeres or rDNA clusters. These technologies also make it possible to know the complete organization of chromosomes, which remained complicated before even when using genetic maps. However, generating a gapless and telomere-to-telomere assembly is still not trivial, and requires a combination of several technologies and the choice of suitable software. Here, we report a chromosome-scale assembly of a banana genome (Musa acuminata) generated using Oxford Nanopore long-reads. We generated a genome coverage of 177X from a single PromethION flowcell with near 17X with reads longer than 75Kb. From the 11 chromosomes, 5 were entirely reconstructed in a single contig from telomere to telomere, revealing for the first time the content of complex regions like centromeres or clusters of paralogous genes.
Age-dependent decrease of hepatic geranylgeranoic acid and its oral supplementation prevents spontaneous hepatoma in C3H/HeN mice
Authors: Tabata Yuki , Omori Masahide , Shidoji Yoshihiro 
Published: April 2021

AbstractAimGeranylgeranoic acid (GGA) has been developed as a preventive agent against second primary hepatoma. Recently, GGA was reported to induce cell death in human hepatoma cells via TLR4-mediated pyroptosis. We have reported that GGA is enzymatically biosynthesized from mevalonic acid in human hepatoma-derived cells and that endogenous GGA is found in most organs of rats. In addition, we found that upregulation of endogenous GGA levels by zaragozic acid A (ZAA) induced cell death in human hepatoma-derived cells. Therefore, we investigated the age-related changes of hepatic GGA and the possibility of suppressing hepatocarcinogenesis by GGA supplementation using male C3H/HeN mice that spontaneously develop hepatoma.MethodsWe measured endogenous GGA and mRNA of MAOB, a key enzyme of GGA biosynthesis, in the liver of male C3H/HeN mice aged 6–93 weeks. We also tried suppressing spontaneous hepatocarcinogenesis by a single administration of GGA to C3H/HeN mice.ResultsHepatic GGA content andMaobmRNA expression level age-dependently decreased in male C3H/HeN mice, some of which produced spontaneous hepatoma in 2 years. A single oral administration of GGA at 11 months of age significantly prevented hepatoma in terms of the number and weight of tumors per mouse at 23 months. Oral supplementation with GGA or geranylgeraniol significantly increased endogenous hepatic GGA contents dose-dependently, and ZAA dramatically upregulated hepatic GGA.ConclusionIn this study, we found an age-dependent decrease in hepatic endogenous GGA in male C3H/HeN mice and efficient prevention of spontaneous hepatoma by a single administration of GGA at 11 months of age.
The Alzheimer’s disease risk factor APOE4 drives pro-inflammation in human astrocytesviaHDAC-dependent repression of TAGLN3
Authors: Arnaud Laurie , Benech Philippe , Greetham Louise , Stephan Delphine , Jimenez Angélique , Jullien Nicolas , García-González Laura , Tsvetkov Philipp O. , Devred François , Sancho-Martinez Ignacio , Belmonte Juan-Carlos Izpisua , Baranger Kevin , Rivera Santiago , Nivet Emmanuel 
Published: April 2021

ABSTRACTThe Apolipoprotein E4 (APOE4) is the major allelic risk factor for late-onset Alzheimer’s disease (AD). APOE4 associates with a pro-inflammatory phenotype increasingly considered as critical in AD initiation and progression. Yet, the mechanisms driving an APOE4-dependent neuroinflammation remain unelucidated. Leveraging patient specific human induced Pluripotent Stem Cells (iPSCs) we demonstrate inflammatory chronicity and hyperactivated responses upon cytokines in human APOE4 astrocytesviaa novel mechanism. We uncovered that APOE4 represses Transgelin 3 (TAGLN3), a new interacting partner of IκBα, thus increasing the NF-kB activity. The transcriptional repression of TAGLN3 was shown to result from an APOE4-dependent histone deacetylase (HDAC) activity. The functional relevance of TAGLN3 was demonstrated by the attenuation of APOE4-driven neuroinflammation after TAGLN3 supplementation. Importantly, TAGLN3 downregulation was confirmed in the brain of AD patients. Our findings highlight the APOE4-TAGLN3 axis as a new pathogenic pathway that paves the way for the development of therapeutics to prevent maladaptive inflammatory responses inAPOE4carriers, while placing TAGLN3 downregulation as a potential biomarker of AD.GRAPHICAL ABSTRACT
Isolation of the side population from adult neurogenic niches enriches for endothelial cells
Authors: Kalinina Alena , Gnyra Catherine , Xue Yingben , Lagace Diane 
Published: April 2021

AbstractIn stem cell research, DNA-binding dyes offer the ability to purify live stem cells using flow cytometry as they form a low-fluorescence side population due to the activity of ABC transporters. Adult neural stem cells exist within the lateral ventricle and dentate gyrus of the adult brain yet the ability of DNA-binding dyes to identify these adult stem cells as side populations remain untested. The following experiments utilize the efflux of a DNA-binding dye, Vyrbant DyeCycle Violet (DCV), to isolatebona fideside populations in the adult mouse dentate gyrus and SVZ and test their sensitivity to ABC transporter inhibitors. A distinct side population was found in both the adult lateral ventricle and dentate gyrus using DCV fluorescence and forward scatter instead of the conventional dual fluorescence approach. These side populations responded strongly to inhibition with the ABC transporter antagonists, verapamil and fumitremorgin C. The cells in the side population were identified as cerebrovascular endothelial cells characterized by their expression of CD31. These findings, therefore, suggest that the side population analysis provides an efficient method to purify endothelial cells, but not adult neural stem cells.
Statistical learning of frequent distractor locations in visual search involves regional signal suppression in early visual cortex
Authors: Zhang Bei , Weidner Ralph , Allenmark Fredrik , Bertleff Sabine , Fink Gereon R. , Shi Zhuanghua , Müller Hermann J. 
Published: April 2021

AbstractObservers can learn the locations where salient distractors appear frequently to reduce potential interference – an effect attributed to better suppression of distractors at frequent locations. But how distractor suppression is implemented in the visual cortex and frontoparietal attention networks remains unclear. We used fMRI and a regional distractor-location learning paradigm (Sauter et al. 2018, 2020) with two types of distractors defined in either the same (orientation) or a different (colour) dimension to the target to investigate this issue. fMRI results showed that BOLD signals in early visual cortex were significantly reduced for distractors (as well as targets) occurring at the frequent versus rare locations, mirroring behavioural patterns. This reduction was more robust with same-dimension distractors. Crucially, behavioural interference was correlated with distractor-evoked visual activity only for same- (but not different-) dimension distractors. Moreover, with different- (but not same-) dimension distractors, a colour-processing area within the fusiform gyrus was activated more when a colour distractor was present versus absent and with a distractor occurring at a rare versus frequent location. These results support statistical learning of frequent distractor locations involving regional suppression in the early visual cortex and point to differential neural mechanisms of distractor handling with different-versus same-dimension distractors.
Oxford Nanopore and Bionano Genomics technologies evaluation for plant structural variation detection
Authors: Canaguier Aurélie , Guilbaud Romane , Denis Erwan , Magdelenat Ghislaine , Belser Caroline , Istace Benjamin , Cruaud Corinne , Wincker Patrick , Le Paslier Marie-Christine , Faivre-Rampant Patricia , Barbe Valérie 
Published: April 2021

AbstractBackgroundStructural Variations (SVs) are very diverse genomic rearrangements. In the past, their detection was restricted to cytological approaches, then to NGS read size and partitionned assemblies. Due to the current capabilities of technologies such as long read sequencing and optical mapping, larger SVs detection are becoming more and more accessible.This study proposes a comparison in SVs detection and characterization from long-read sequencing obtained with the MinION device developed by Oxford Nanopore Technologies and from optical mapping produced by the Saphyr device commercialized by Bionano Genomics. The genomes of the twoArabidopsis thalianaecotypes Columbia-0 (Col-0) and Landsbergerecta1 (Ler-1) were chosen to guide the use of one or the other technology.ResultsWe described the SVs detected from the alignment of the best ONT assembly and DLE-1 optical maps ofA. thalianaLer-1 on the public reference Col-0 TAIR10.1. After filtering, 1 184 and 591 Ler-1 SVs were retained from ONT and BioNano technologies respectively. A total of 948 Ler-1 ONT SVs (80.1%) corresponded to 563 Bionano SVs (95.3%) leading to 563 common locations in both technologies. The specific locations were scrutinized to assess improvement in SV detection by either technology. The ONT SVs were mostly detected near TE and gene features, and resistance genes seemed particularly impacted.ConclusionsStructural variations linked to ONT sequencing error were removed and false positives limited, with high quality Bionano SVs being conserved. When compared with the Col-0 TAIR10.1 reference, most of detected SVs were found in same locations. ONT assembly sequence leads to more specific SVs than Bionano one, the later being more efficient to characterize large SVs. Even if both technologies are obvious complementary approaches, ONT data appears to be more adapted to large scale populations study, while Bionano performs better in improving assembly and describing specificity of a genome compared to a reference.
Adaptive subsets limit the anti-tumoral NK-cell activity in Hepatocellular Carcinoma
Authors: Rennert Charlotte , Tauber Catrin , Fehrenbach Pia , Heim Kathrin , Bettinger Dominik , Sogukpinar Oezlem , Schuch Anita , Zecher Britta Franziska , Bengsch Bertram , Lang Sven A. , Bronsert Peter , Björkström Niklas K. , Fichtner-Feigl Stefan , Schultheiss Michael , Thimme Robert , Hofmann Maike 
Published: April 2021

AbstractBackground and AimsHepatocellular carcinoma (HCC) is a global health burden with increasing incidence, poor prognosis and limited therapeutic options. Natural killer (NK) cells exhibit potent anti-tumoral activity and therefore represent potential targets for immunotherapeutic approaches in HCC treatment. However, the human NK-cell repertoire is highly diverse including conventional and adaptive NK cells that differ in phenotype and effector function. Adaptive NK-cell frequencies are increased in association with HCMV (human cytomegalovirus) seropositivity that is also common in HCC patients. In this study, we aimed to gain a better understanding of the NK-cell repertoire and the associated anti-tumoral activity in HCC patients.MethodsIn-depth phenotypic and functional flow-cytometry analyses of the HCMV-associated NK cell-repertoire obtained from 57 HCC patients, 33 liver cirrhosis patients and 36 healthy donors (HD).ResultsFirst, adaptive subsets are present in all three cohorts with conserved characteristics in patients with liver cirrhosis and HCC. Second, adaptive NK cells can be isolated from HCC tissue however lack features of tissue-residency and thus probably represent circulating/infiltrating lymphocytes. Third, the anti-tumoral activity by adaptive NK cells is reduced compared to conventional NK-cell subsets, also in HCC. Lastly, frequencies of adaptive NK cells were increased in patients suffering from Hepatitis B virus-associated HCC providing a link between etiology and the NK-cell repertoire in HCC.ConclusionAdaptive NK cells limit the anti-tumoral activitity of NK cells in HCC, especially in association with HBV infection that is accompanied by an expansion of this NK cell subset.Lay summaryIn patients with liver cancer (HCC), a subset of natural killer cells, so called adaptive NK cells show a diminished anti-tumoral activity compared to other, called conventional NK cells. Adaptive NK cells are expanded in patients with HCC associated to Hepatitis B virus infection. Thus, presence of adaptive NK cells contributes to the immune escape in HCC.
Potential transmission chains of variant B.1.1.7 and co-mutations of SARS-CoV-2
Authors: Zhang Jingsong , Zhang Yang , Kang Junyan , Chen Shuiye , He Yongqun , Han Benhao , Liu Mofang , Lu Lina , Li Li , Yi Zhigang , Chen Luonan 
Published: April 2021

AbstractThe presence of SARS-CoV-2 mutants, including the emerging variant B.1.1.7, has raised great concerns in terms of pathogenesis, transmission, and immune escape. Characterizing SARS-CoV-2 mutations, evolution, and effects on infectivity and pathogenicity is crucial to the design of antibody therapies and surveillance strategies. Here we analyzed 454,443 SARS-CoV-2 spike genes/proteins and 14,427 whole-genome sequences. We demonstrated that the early variant B.1.1.7 may not have evolved spontaneously in the United Kingdom or within human populations. Our extensive analyses suggested that Canidae, Mustelidae or Felidae, especially the Canidae family (for example, dog) could be a possible host of the direct progenitor of variant B.1.1.7. An alternative hypothesis is that the variant was simply yet to be sampled. Notably, the SARS-CoV-2 whole genome represents a large number of potential co-mutations with very strong statistical significances (p value<E– 44). In addition, we used an experimental SARS-CoV-2 reporter replicon system to introduce the dominant co-mutations NSP12_c14408t, 5’UTR_c241t, and NSP3_c3037t into the viral genome, and to monitor the effect of the mutations on viral replication. Our experimental results demonstrated that the co-mutations significantly attenuated the viral replication. The study provides valuable clues for discovering the transmission chains of variant B.1.1.7 and understanding the evolutionary process of SARS-CoV-2.