bluuebunny/crossref_metadata_2025_split huggingface dataset:
Euchromatin factors HULC and Set1C affect heterochromatin organization for mating-type switching in fission yeastSchizosaccharomyces pombe
Authors: Esquivel-Chávez Alfredo , Maki Takahisa , Tsubouchi Hideo , Handa Testuya , Kimura Hiroshi , Haber James E. , Thon Genevieve , Iwasaki Hiroshi 
Published: March 2021

AbstractMating-type (P or M) of fission yeastSchizosaccharomyces pombeis determined by the transcriptionally activemat1cassette and is switched by gene conversion using a donor, eithermat2ormat3, located in an adjacent heterochromatin region (mating-type switching; MTS). In the process, heterochromatic donors of genetic information are selected based on the P or M cell type and on the action of two recombination enhancers,SRE2promoting the use ofmat2-PandSRE3promoting the use ofmat3-M, leading to replacement of the content of the expressedmat1cassette. Recently, we found that the histone H3K4 methyltransferase complex Set1C participates in donor selection, raising the question of how a complex best known for its effects in euchromatin controls recombination in heterochromatin. Here, we report that the histone H2BK119 ubiquitin ligase complex HULC functions with Set1C in MTS, as mutants in theshf1, brl1, brl2andrad6genes showed defects similar to Set1C mutants and belonged to the same epistasis group asset1Δ. Moreover, using H3K4R and H2BK119R histone mutants and a Set1-Y897A catalytic mutant indicated that ubiquitylation of histone H2BK119 by HULC and methylation of histone H3K4 by Set1C are functionally coupled in MTS. Cell-type biases in MTS in these mutants suggested that HULC and Set1C inhibit the use of theSRE3recombination enhancer in M cells, thus favoringSRE2andmat2-P. Consistently, imbalanced switching in the mutants was traced to compromised association of the directionality factor Swi6 with the recombination enhancers in M cells. Based on their known effects at other chromosomal locations, we speculate that HULC and Set1C might control nucleosome mobility and strand invasion near theSREelements. In addition, we uncovered distinct effects of HULC and Set1C on histone H3K9 methylation and gene silencing, consistent with additional functions in the heterochromatic domain.
Mild CF Lung Disease is Associated with Bacterial Community Stability
Authors: Hampton Thomas H. , Thomas Devin , van der Gast Christopher , O’Toole George A. , Stanton Bruce A. 
Published: March 2021

AbstractMicrobial communities in the airways of persons with CF (pwCF) are variable, may include genera that are not typically associated with CF, and their composition can be difficult to correlate with long-term disease outcomes. Leveraging two large datasets characterizing sputum communities of 167 pwCF and associated metadata, we identify five bacterial community types. These communities explain 24% of the variability in lung function in this cohort, far more than single factors like Simpson diversity, which explains only 4%. Subjects withPseudomonas-dominated communities tended to be older and have reduced percent predicted FEV1(ppFEV1) than subjects withStreptococcus-dominated communities, consistent with previous findings. To assess the predictive power of these five communities in a longitudinal setting, we used random forests to classify 346 additional samples from 24 subjects observed 8 years on average in a range of clinical states. Subjects with mild disease were more likely to be observed at baseline, that is, not in the context of a pulmonary exacerbation, and community structure in these subjects was more self-similar over time, as measured by Bray-Curtis distance. Interestingly, we found that subjects with mild disease were more likely to remain in a mixedPseudomonascommunity, providing some support for the climax-attack model of the CF airway. In contrast, patients with worse outcomes were more likely to show shifts among community types. Our results suggest that bacterial community instability may be a risk factor for lung function decline and indicates the need to better understand factors that drive shifts in community composition.
gen3sis: the general engine for eco-evolutionary simulations on the origins of biodiversity
Authors: Hagen Oskar , Flück Benjamin , Fopp Fabian , Cabral Juliano S. , Hartig Florian , Pontarp Mikael , Rangel Thiago F. , Pellissier Loïc 
Published: March 2021

AbstractUnderstanding the origins of biodiversity has been an aspiration since the days of early naturalists. The immense complexity of ecological, evolutionary and spatial processes, however, has made this goal elusive to this day. Computer models serve progress in many scientific fields, but in the fields of macroecology and macroevolution, eco-evolutionary models are comparatively less developed. We present a general, spatially-explicit, eco-evolutionary engine with a modular implementation that enables the modelling of multiple macroecological and macroevolutionary processes and feedbacks across representative spatio-temporally dynamic landscapes. Modelled processes can include environmental filtering, biotic interactions, dispersal, speciation and evolution of ecological traits. Commonly observed biodiversity patterns, such as α, β and γ diversity, species ranges, ecological traits and phylogenies, emerge as simulations proceed. As a case study, we examined alternative hypotheses expected to have shaped the latitudinal diversity gradient (LDG) during the Earth’s Cenozoic era. We found that a carrying capacity linked with energy was the only model variant that could simultaneously produce a realistic LDG, species range size frequencies, and phylogenetic tree balance. The model engine is open source and available as an R-package, enabling future exploration of various landscapes and biological processes, while outputs can be linked with a variety of empirical biodiversity patterns. This work represents a step towards a numeric and mechanistic understanding of the physical and biological processes that shape Earth’s biodiversity.
Loss of Nuclear DNA Ligase III Reverts PARP Inhibitor Resistance in BRCA1/53BP1 Double-deficient Cells by Exposing ssDNA Gaps
Authors: Dias Mariana Paes , Tripathi Vivek , van der Heijden Ingrid , Cong Ke , Manolika Eleni-Maria , Bhin Jinhyuk , Gogola Ewa , Galanos Panagiotis , Annunziato Stefano , Lieftink Cor , Andújar-Sánchez Miguel , Chakrabarty Sanjiban , Smith Graeme C. M. , van de Ven Marieke , Beijersbergen Roderick L. , Bartkova Jirina , Rottenberg Sven , Cantor Sharon , Bartek Jiri , Chaudhuri Arnab Ray , Jonkers Jos 
Published: March 2021

SUMMARYInhibitors of poly(ADP-ribose) (PAR) polymerase (PARPi) have entered the clinic for the treatment of homologous recombination (HR)-deficient cancers. Despite the success of this approach, preclinical and clinical research with PARPi has revealed multiple resistance mechanisms, highlighting the need for identification of novel functional biomarkers and combination treatment strategies. Functional genetic screens performed in cells and organoids that acquired resistance to PARPi by loss of 53BP1 identified loss of LIG3 as an enhancer of PARPi toxicity in BRCA1-deficient cells. Enhancement of PARPi toxicity by LIG3 depletion is dependent on BRCA1 deficiency but independent of the loss of 53BP1 pathway. Mechanistically, we show that LIG3 loss promotes formation of MRE11-mediated post-replicative ssDNA gaps in BRCA1-deficient and BRCA1/53BP1 double-deficient cells exposed to PARPi, leading to an accumulation of chromosomal abnormalities. LIG3 depletion also enhances efficacy of PARPi against BRCA1-deficient mammary tumors in mice, suggesting LIG3 as a potential therapeutic target.
Uncharted biosynthetic potential of the ocean microbiome
Authors: Paoli Lucas , Ruscheweyh Hans-Joachim , Forneris Clarissa C. , Kautsar Satria , Clayssen Quentin , Salazar Guillem , Milanese Alessio , Gehrig Daniel , Larralde Martin , Carroll Laura M. , Sánchez Pablo , Zayed Ahmed A. , Cronin Dylan R. , Acinas Silvia G. , Bork Peer , Bowler Chris , Delmont Tom O. , Sullivan Matthew B. , Wincker Patrick , Zeller Georg , Robinson Serina L. , Piel Jörn , Sunagawa Shinichi 
Published: March 2021

SummaryMicrobes are phylogenetically and metabolically diverse. Yet capturing this diversity, assigning functions to host organisms and exploring the biosynthetic potential in natural environments remains challenging. We reconstructed >25,000 draft genomes, including from >2,500 uncharacterized species, from globally-distributed ocean microbial communities, and combined them with ∼10,000 genomes from cultivated and single cells. Mining this resource revealed ∼40,000 putative biosynthetic gene clusters (BGCs), many from unknown phylogenetic groups. Among these, we discoveredCandidatusEudoremicrobiaceae as one of the most biosynthetically diverse microbes detected to date. Discrete transcriptional states structuring natural populations were associated with a potentially niche-partitioning role for BGC products. Together with the characterization of the first Eudoremicrobiaceae natural product, this study demonstrates how microbiomics enables prospecting for candidate bioactive compounds in underexplored microbes and environments.
Herpesviral induction of germline transcription factor DUX4 is critical for viral gene expression
Authors: Walter Stephanie , Franke Vedran , Drayman Nir , Wyler Emanuel , Tay Savaş , Landthaler Markus , Akalin Altuna , Ensser Armin , Full Florian 
Published: March 2021

AbstractDUX4 is a transcription factor and a master regulator of embryonic genome activation (EGA). During early embryogenesis, EGA is crucial for maternal to zygotic transition at the 8-cell stage in order to overcome silencing of genes and enable transcription from the zygotic genome. In adult somatic cells, DUX4 expression is largely silenced. Activation is likely pathogenic, and in adult muscle cells causes genetic disorder Facioscapulohumeral Muscular Dystrophy (FSHD).We identified activation of DUX4 expression upon lytic replication of the herpesviruses HSV-1, HCMV, EBV and KSHV, but not of adenoviruses, negative strand RNA viruses or positive strand RNA viruses. We demonstrate by RNA-Seq analysis that DUX4 expression upon herpesviral replication leads to the induction of hundreds of DUX4 target genes including germline-specific retroelements as well as several members of the TRIM, PRAMEF and ZSCAN protein families. Moreover, we show that DUX4 expression is a direct consequence of herpesviral infection. DUX4 can be stimulated by overexpression of HSV-1 immediate early proteins, indicating active induction of EGA genes by herpesviral infection. We further show that DUX4 expression is critical for driving HSV-1 gene expression.Our results show that viruses from alpha-, beta- and gamma-herpesvirus subfamilies induce DUX4 expression and downstream germline-specific genes and retroelements. We hypothesize that herpesviruses induce DUX4 expression in order to induce an early embryonic-like transcriptional program that prevents epigenetic silencing of the viral genome and facilitates herpesviral gene expression.
A species-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for preimplantation development
Authors: Modzelewski Andrew , Shao Wanqing , Chen Jingqi , Lee Angus , Qi Xin , Noon Mackenzie , Tjokro Kristy , Sales Gabriele , Biton Anne , Speed Terence , Xuan Zhenyu , Wang Ting , Risso Davide , He Lin 
Published: March 2021

AbstractRetrotransposons mediate gene regulation in multiple developmental and pathological processes. Here, we characterized the transient retrotransposon induction in preimplantation development of eight mammalian species. While species-specific in sequences, induced retrotransposons exhibit a similar preimplantation profile, conferring gene regulatory activities particularly through LTR retrotransposon promoters. We investigated a mouse-specific MT2B2 retrotransposon promoter, which generates an N-terminally truncated, preimplantation-specific Cdk2ap1ΔN isoform to promote cell proliferation. Cdk2ap1ΔN functionally contrasts to the canonical Cdk2ap1, which represses cell proliferation and peaks in mid-gestation stage. The mouse-specific MT2B2 element is developmentally essential, as its deletion abolishes Cdk2ap1ΔN, reduces cell proliferation and impairs embryo implantation. Intriguingly, Cdk2ap1ΔN is evolutionarily conserved across mammals, driven by species-specific promoters. The distinct preimplantation Cdk2ap1ΔN expression across different mammalian species correlates with their different duration in preimplantation development. Hence, species-specific transposon promoters can yield evolutionarily conserved, alternative protein isoforms, bestowing them with new functions and species-specific expression to govern essential biological divergence.One Sentence SummaryIn mammalian preimplantation embryos, retrotransposon promoters generate conserved gene isoforms, confer species-specific expression, and perform essential developmental functions.
Responses of Oil Palm Pollinator,Elaeidobius kamerunicusto Different Concentrations of Estragoles
Authors: Fahmi-Halil Muhammad , Haris-Hussain Mohamad , Mirad Razali , Idris AB , Jalinas Johari 
Published: March 2021

ABSTRACTElaeidobius kamerunicusis the main insect pollinator for oil palm (Elaeis guineensis) worldwide. One of the main reasonE. kamerunicusattracted to oil palm inflorescences is estragole, a volatile organic compound released by the oil palm inflorescences during anthesis stage. However, the amount of estragole released from the oil palm inflorescence is varied due to the influence of abiotic and biotic factors and is seen to have an impact onE. kamerunicuspollination activity on the oil palm. To evaluate the responses ofE. kamerunicus, different types (wild and reared) and sex (male and female) ofE. kamerunicuswere exposed to different concentrations (1, 5, 10, 30, 50, 70, 100, 150 and 200 ppm) of commercial estragole using four-arm olfactometer. Results showed thatE. kamerunicussignificantly preferred 100 ppm of estragole compared to other concentration (F = 139.81; d.f. = 9; P < 0.05). A significant interaction was also recorded between estragole concentrations and sexes ofE. kamerunicus(F = 3.91; d.f. = 9; P < 0.05) where maleE. kamerunicuswas found to be more responsive to 100 ppm of estragole compared femaleE. kamerunicus. TheE. kamerunicusresponses to estragole is in line with the increase of estragole concentration up to 100 ppm. However, the response ofE. kamerunicuswas significantly decreased after the concentration value. The result of this study can be a good platform for future references since the estragole compound plays a significant role in oil palm’s flower pollination byE. kamerunicus. The factor of type and sexes ofE. kamerunicusdid not affect the preferences which indicated thatE. kamerunicusreared in the laboratory have the potential to be released into the oil palm plantation area to overcome the problem of pollination.
Novel cancer subtyping method based on patient-specific gene regulatory network
Authors: Nakazawa Mai Adachi , Tamada Yoshinori , Tanaka Yoshihisa , Ikeguchi Marie , Higashihara Kako , Okuno Yasushi 
Published: March 2021

ABSTRACTThe identification of cancer subtypes is important for the understanding of tumor heterogeneity. In recent years, numerous computational methods have been proposed for this problem based on the multi-omics data of patients. It is widely accepted that different cancer subtypes are induced by different molecular regulatory networks. However, only a few incorporate the differences between their molecular systems into the classification processes. In this study, we present a novel method to classify cancer subtypes based on patient-specific molecular systems. Our method quantifies patient-specific gene networks, which are estimated from their transcriptome data. By clustering their quantified networks, our method allows for cancer subtyping, taking into consideration the differences in the molecular systems of patients. Comprehensive analyses of The Cancer Genome Atlas (TCGA) datasets applied to our method confirmed that they were able to identify more clinically meaningful cancer subtypes than the existing subtypes and found that the identified subtypes comprised different molecular features. Our findings show that the proposed method, based on a simple classification using the patient-specific molecular systems, can identify cancer subtypes even with single omics data, which cannot otherwise be captured by existing methods using multi-omics data.
Whole genome resequencing data enables a targeted SNP panel for conservation and aquaculture ofOreochromiscichlid fishes
Authors: Ciezarek A , Ford AGP , Etherington GJ , Kasozi N , Malinsky M , Mehta T , Penso-Dolfin L , Ngatunga BP , Shechonge A , Tamatamah R , Haerty W , Di Palma F , Genner MJ , Turner GF 
Published: March 2021

AbstractCichlid fish of the genusOreochromisform the basis of the global tilapia aquaculture and fisheries industry. Non-native farmed tilapia populations are known to be widely distributed across Africa and to hybridize with nativeOreochromisspecies. However, many species are difficult to distinguish morphologically, hampering attempts to maintain good quality farmed strains or to identify pure populations of native species. Here, we describe the development of a single nucleotide polymorphism (SNP) genotyping panel from whole-genome resequencing data that enables targeted species identification in Tanzania. We demonstrate that an optimized panel of 96 genome-wide SNPs based on FSToutliers performs comparably to whole genome resequencing in distinguishing species and identifying hybrids. We also show this panel outperforms microsatellite-based and phenotype-based classification methods. Case studies indicate several locations where introduced aquaculture species have become established in the wild, threatening nativeOreochromisspecies. The novel SNP markers identified here represent an important resource for assessing broodstock purity and helping to conserve unique endemic biodiversity, and in addition potentially for assessing broodstock purity in hatcheries.
The natural sequence of events in larval settlement and metamorphosis of Hydroides elegans (Polychaeta; Serpulidae)
Authors: Hadfield Michael G. , Freckelton Marnie L. , Nedved Brian T. 
Published: March 2021

AbstractThe broadly distributed serpulid worm Hydroides elegans has become a model organism for studies of marine biofouling, development and the processes of larval settlement and metamorphosis induced by surface microbial films. Contrasting descriptions of the initial events of these recruitment processes, whether settlement is induced by (1) natural multi-species biofilms, (2) biofilms composed of single bacterial species known to induce settlement, or (3) a bacterial extract stimulated the research described here. We found that settlement induced by natural biofilms or biofilms formed by the bacterium Pseudoalteromonas luteoviolacea is invariably initiated by attachment and secretion of an adherent and larva-enveloping primary tube, followed by loss of motile cilia and ciliated cells and morphogenesis. The bacterial extract containing complex tailocin arrays derived from an assemblage of phage genes incorporated into the bacterial genome appears to induce settlement events by destruction of larval cilia and ciliated cells, followed by attachment and primary-tube formation. Similar destruction occurred when precompetent larvae and larvae of a nudibranch gastropod were exposed to the extract, neither of which metamorphosed. We further argue that larvae that lose their cilia before attachment would be swept away from the sites that stimulated settlement by the turbulent flow characteristic of most marine habitats.
Sequence and phylogenetic analysis revealed structurally conserved domains and motifs in lincRNA-p21
Authors: Maulik Aditi , Bandopadhyay Devleena , Singh Mahavir 
Published: March 2021

AbstractLong Intergenic Non-coding RNAs (lincRNAs) are the largest class of long non-coding RNAs in the eukaryotes, which originate from the intergenic regions of the genome. A ~4kb long lincRNA-p21 is derived from a transcription unit next to the p21/Cdkn1a gene locus. LincRNA-p21 plays key regulatory roles in p53 dependent transcriptional repression and translational repression through its physical association with proteins such as hnRNP-K and HuR.It is also involved in the aberrant gene expression in different cancers. However, detailed information on its structure, recognition, and trans-regulation by proteins is not well known. In this study, we have carried out a complete gene analysis and annotation of lincRNA-p21. This analysis showed that lincRNA-p21 is highly conserved in primates, and its conservation drops significantly in lower organisms. Furthermore, our analysis has revealed two structurally conserved domains in the 5’ and 3’ terminal regions of lincRNA-p21. Phylogenetic analysis has revealed discrete evolutionary dynamics in these conserved domains for orthologous sequences of lincRNA-p21, which have evolved slowly across primates compared to other mammals. Using Infernal based covariance analysis, we have computed the secondary structures of these domains. The secondary structures were further validated by energy minimization criteria for individual orthologous sequences as well as the full-length human lincRNA-p21. In summary, this analysis has led to the identification of sequence and structural motifs in the conserved fragments, indicating the functional importance for these regions.
Characterization of regulatory transcriptional mechanisms in hepatocyte lipotoxicity
Authors: Pérez-Schindler Joaquín , Vargas-Fernández Elyzabeth , Karrer-Cardel Bettina , Ritz Danilo , Schmidt Alexander , Handschin Christoph 
Published: March 2021

AbstractNon-alcoholic fatty liver disease is a continuum of disorders among which non-alcoholic steatohepatitis (NASH) is particularly associated with a negative prognosis. Hepatocyte lipotoxicity is one of the main pathogenic factors of liver fibrosis and NASH. However, the molecular mechanisms regulating this process are poorly understood. The main aim of this study was to dissect transcriptional mechanisms regulated by lipotoxicity in hepatocytes. We achieved this aim by combining transcriptomic, proteomic and chromatin accessibility analyses from human liver and mouse hepatocytes. This integrative approach revealed several transcription factor networks deregulated by NASH and lipotoxicity. To validate these predictions, genetic deletion of the transcription factors MAFK and TCF4 was performed, resulting in hepatocytes that were better protected against saturated fatty acid oversupply. MAFK- and TCF4-regulated gene expression profiles suggest a mitigating effect against cell stress, while promoting cell survival and growth. Moreover, in the context of lipotoxicity, some MAFK and TCF4 target genes were to the corresponding differentially regulated transcripts in human liver fibrosis. Collectively, our findings comprehensively profile the transcriptional response to lipotoxicity in hepatocytes, revealing new molecular insights and providing a valuable resource for future endeavours to tackle the molecular mechanisms of NASH.