bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genomics of five Valsa species gives insights on their pathogenicity evolution
Authors: Sun Guangchao , Xie Shichang , Tang Lin , Zhao Chao , Zhang Mian , Huang Lili 
Published: December 2022

Abstract
Valsa is a genus of ascomycetes within the Valsaceae family. This family includes many wood destructive pathogens such as the well known Valsa mali and Valsa pyri which cause canker diseases in fruit trees and threaten the global fruit production. Lack of genomic information of this family is impeding our understandings about their evolution and genetic basis of their pathogenicity divergence. Here, we report genome assemblies of Valsa malicola, Valsa persoonii, and Valsa sordida which represent close relatives of Valsa mali and Valsa pyri with different host preferences. Comparative genomics analysis revealed that segmental rearrangements, inversions, and translocations frequently occurred among Valsa spp. genomes. Gene families that exhibited gene copy expansions tended to be associated with secondary metabolism, transmembrane transport, and pyrophosphatase activities. Orthologous genes in regions lost synteny exhibited significantly higher rate of synonymous substitution (KS) than those in regions retained synteny. Moreover, among these genes, membrane transporter families associated with antidrug (MFS, DHA) activities and nutrient transportation (SP and APCs) activities were significantly over-represented. Lineage specific synonymous substitution (KS) and nonsynonymous substitution (KA) analysis based on the phylogeny constructed from 11 fungal species identified a set of genes with selection signatures in Valsa clade and these genes were significantly enriched in functions associated with fatty acid beta-oxidation, DNA helicase activity, and ATPase activity. Furthermore, unique genes that possessed or retained by each of the five Valsa species are more likely part of the secondary metabolic (SM) gene clusters. SM gene clusters conserved across five Valsa species showed various degrees of diversification in both identity and completeness. All 11 syntenically conserved SM clusters showed differential expression during the infection of apple branch with Valsa mali suggesting involvements of secondary metabolism in the pathogenicity of Valsa species.
Envirome-wide associations enhance multi-year genome-based prediction of historical wheat breeding data
Authors: Costa-Neto Germano , Crespo-Herrera Leonardo , Fradgley Nick , Gardner Keith , Bentley Alison R , Dreisigacker Susanne , Fritsche-Neto Roberto , Montesinos-López Osval A , Crossa Jose 
Published: December 2022

Abstract
Linking high-throughput environmental data (enviromics) to genomic prediction (GP) is a cost-effective strategy for increasing selection intensity under genotype-by-environment interactions (G × E). This study developed a data-driven approach based on Environment–Phenotype Association (EPA) aimed at recycling important G × E information from historical breeding data. EPA was developed in two applications: (1) scanning a secondary source of genetic variation, weighted from the shared reaction-norms of past-evaluated genotypes and (2) pinpointing weights of the similarity among trial-sites (locations), given the historical impact of each envirotyping data variable for a given site. These results were then used as a dimensionality reduction strategy, integrating historical data to feed multi-environment GP models, which led to the development of four new G × E kernels considering genomics, enviromics, and EPA outcomes. The wheat trial data used included 36 locations, 8 years, and three target populations of environments (TPEs) in India. Four prediction scenarios and six kernel models within/across TPEs were tested. Our results suggest that the conventional GBLUP, without enviromic data or when omitting EPA, is inefficient in predicting the performance of wheat lines in future years. Nevertheless, when EPA was introduced as an intermediary learning step to reduce the dimensionality of the G × E kernels while connecting phenotypic and environmental-wide variation, a significant enhancement of G × E prediction accuracy was evident. EPA revealed that the effect of seasonality makes strategies such as “covariable selection” unfeasible because G × E is year-germplasm specific. We propose that the EPA effectively serves as a “reinforcement learner” algorithm capable of uncovering the effect of seasonality over the reaction-norms, with the benefits of better forecasting the similarities between past and future trialing sites. EPA combines the benefits of dimensionality reduction while reducing the uncertainty of genotype-by-year predictions and increasing the resolution of GP for the genotype-specific level.
A pilot study to evaluate tissue- and plasma-based DNA driver mutations in a cohort of patients with pancreatic intraductal papillary mucinous neoplasms
Authors: Park Margaret A , Zaw Thinzar , Yoder Sean J , Gomez Maria , Genilo-Delgado Maria , Basinski Toni , Katende Esther , Dam Aamir , Mok Shaffer R S , Monteiro Alvaro , Mohammadi Amir , Jeong Daniel K , Jiang Kun , Centeno Barbara A , Hodul Pamela , Malafa Mokenge , Fleming Jason , Chen Dung-Tsa , Mo Qianxing , Teer Jamie K , Permuth Jennifer B 
Published: December 2022

Abstract
Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions to pancreatic ductal adenocarcinoma that are challenging to manage due to limited imaging, cytologic, and molecular markers that accurately classify lesions, grade of dysplasia, or focus of invasion preoperatively. The objective of this pilot study was to determine the frequency and type of DNA mutations in a cohort of surgically resected, pathologically confirmed IPMN, and to determine if concordant mutations are detectable in paired pretreatment plasma samples. Formalin-fixed paraffin-embedded (FFPE) tissue from 46 surgically resected IPMNs (31 low-grade, 15 high-grade) and paired plasma from a subset of 15 IPMN cases (10 low-grade, 5 high-grade) were subjected to targeted mutation analysis using a QIAseq Targeted DNA Custom Panel. Common driver mutations were detected in FFPE from 44 of 46 (95.6%) IPMN cases spanning all grades; the most common DNA mutations included: KRAS (80%), RNF43 (24%), and GNAS (43%). Of note, we observed a significant increase in the frequency of RNF43 mutations from low-grade to high-grade IPMNs associated or concomitant with invasive carcinoma (trend test, P = 0.01). Among the subset of cases with paired plasma, driver mutations identified in the IPMNs were not detected in circulation. Overall, our results indicate that mutational burden for IPMNs is a common occurrence, even in low-grade IPMNs. Furthermore, although blood-based biopsies are an attractive, noninvasive method for detecting somatic DNA mutations, the QIAseq panel was not sensitive enough to detect driver mutations that existed in IPMN tissue using paired plasma in the volume we were able to retrieve for this retrospective study.
Identification of candidate genes responsible for innate fear behavior in the chicken
Authors: Ochiai Takayuki , Sakaguchi Marina , Kawakami Shin-Ichi , Ishikawa Akira 
Published: December 2022

Abstract
Identifying the genes responsible for quantitative traits remains a major challenge. We previously found a major QTL on chromosome 4 affecting several innate fear behavioral traits obtained by an open-field test in an F2 population between White Leghorn and Nagoya breeds of chickens (Gallus gallus). Here, an integrated approach of transcriptome, haplotype frequency, and association analyses was used to identify candidate genes for the QTL in phenotypically extreme individuals selected from the same segregating F2 population as that used in the initial QTL analysis. QTL mapping for the first principal component, which summarizes the variances of all affected behavioral traits in the F2 population, revealed the behavioral QTL located at 14–35 Mb on chromosome 4 with 333 genes. After RNA-seq analysis using two pooled RNAs from extreme F2 individuals, real-time qPCR analysis in the two parental breeds and their F1 individuals greatly reduced the number of candidate genes in the QTL interval from 333 to 16 genes. Haplotype frequency analysis in the two extreme F2 groups further reduced the number of candidate genes from 16 to 11. After comparing gene expression in the two extreme groups, a conditional correlation analysis of diplotypes between gene expression and phenotype of extreme individuals revealed that NPY5R and LOC101749214 genes were strong candidate genes for innate fear behavior. This study illustrates how the integrated approach can identify candidate genes more rapidly than fine mapping of the initial QTL interval and provides new information for studying the genetic basis of innate fear behavior in chickens.
Myxoid pleomorphic liposarcoma of the falciform ligament: a rare case report
Authors: AlObaid Bashayer , Alzahrani Nayef A , Shokor Nada , Alshammari Kanan 
Published: December 2022

Abstract
Liposarcomas are a group of malignancies that mainly affect adults. Myxoid pleomorphic liposarcoma (MPL) is a newly added subtype of liposarcomas [1]. It is extremely rare and mostly affects infants and children, and it has a predilection for the mediastinum. We report a case of a 58-years-old female with MPL originating from the falciform ligament who presented initially with vague abdominal pain. MPLs have an aggressive pathology and high metastasis and recurrence potential.
A multi-omic landscape of steatosis-to-NASH progression
Authors: Xiang Liping , Li Xiaoyan , Luo Yunchen , Zhou Bing , Liu Yuejun , Li Yao , Wu Duojiao , Jia Lijing , Zhu Pei-Wu , Zheng Ming-Hua , Wang Hua , Lu Yan 
Published: December 2022

Abstract
Nonalcoholic steatohepatitis (NASH) has emerged as a major cause of liver failure and hepatocellular carcinoma. Investigation into the molecular mechanisms that underlie steatosis-to-NASH progression is key to understanding the development of NASH pathophysiology. Here, we present comprehensive multi-omic profiles of preclinical animal models to identify genes, non-coding RNAs, proteins, and plasma metabolites involved in this progression. In particular, by transcriptomics analysis, we identified Growth Differentiation Factor 3 (GDF3) as a candidate noninvasive biomarker in NASH. Plasma GDF3 levels are associated with hepatic pathological features in patients with NASH, and differences in these levels provide a high diagnostic accuracy of NASH diagnosis (AUROC = 0.90; 95% confidence interval: 0.85−0.95) with a good sensitivity (90.7%) and specificity (86.4%). In addition, by developing integrated proteomic-metabolomic datasets and performing a subsequent pharmacological intervention in a mouse model of NASH, we show that ferroptosis may be a potential target to treat NASH. Moreover, by using competing endogenous RNAs network analysis, we found that several miRNAs, including miR-582-5p and miR-292a-3p, and lncRNAs, including XLOC-085738 and XLOC-041531, are associated with steatosis-to-NASH progression. Collectively, our data provide a valuable resource into the molecular characterization of NASH progression, leading to the novel insight that GDF3 may be a potential noninvasive diagnostic biomarker for NASH while further showing that ferroptosis is a therapeutic target for the disease.
GeneFriends: gene co-expression databases and tools for humans and model organisms
Authors: Raina Priyanka , Guinea Rodrigo , Chatsirisupachai Kasit , Lopes Inês , Farooq Zoya , Guinea Cristina , Solyom Csaba-Attila , de Magalhães João Pedro 
Published: December 2022

Abstract
Gene co-expression analysis has emerged as a powerful method to provide insights into gene function and regulation. The rapid growth of publicly available RNA-sequencing (RNA-seq) data has created opportunities for researchers to employ this abundant data to help decipher the complexity and biology of genomes. Co-expression networks have proven effective for inferring the relationship between the genes, for gene prioritization and for assigning function to poorly annotated genes based on their co-expressed partners. To facilitate such analyses we created previously an online co-expression tool for humans and mice entitled GeneFriends. To continue providing a valuable tool to the scientific community, we have now updated the GeneFriends database and website. Here, we present the new version of GeneFriends, which includes gene and transcript co-expression networks based on RNA-seq data from 46 475 human and 34 322 mouse samples. The new database also encompasses tissue-specific gene co-expression networks for 20 human and 21 mouse tissues, dataset-specific gene co-expression maps based on TCGA and GTEx projects and gene co-expression networks for additional seven model organisms (fruit fly, zebrafish, worm, rat, yeast, cow and chicken). GeneFriends is freely available at http://www.genefriends.org/.
SUMO conjugation regulates the activity of the Integrator complex
Authors: Bragado Laureano , Magalnik Melina , Mammi Pablo , Romero Agustín , Gaioli Nicolás , Pozzi Berta , Srebrow Anabella 
Published: December 2022

Abstract
RNA polymerase II (RNAPII) transcribes small nuclear RNA (snRNA) genes in close proximity to Cajal bodies, subnuclear compartments that depend on the SUMO isopeptidase USPL1 for their assembly. We show here that overexpression of USPL1 as well as of another nuclear SUMO isopeptidase, SENP6, alters snRNA 3′-end cleavage, a process carried out by the Integrator complex. Beyond its role in snRNA biogenesis, this complex is responsible for regulating the expression of different RNAPII transcripts. While several subunits of the complex are SUMO conjugation substrates, we found that the SUMOylation of the INTS11 subunit is regulated by USPL1 and SENP6. We defined Lys381, Lys462 and Lys475 as bona fide SUMO attachment sites on INTS11 and observed that SUMOylation of this protein modulates its subcellular localization and is required for Integrator activity. Moreover, while an INTS11 SUMOylation-deficient mutant is still capable of interacting with INTS4 and INTS9, its interaction with other subunits of the complex is affected. These findings point to a regulatory role for SUMO conjugation on Integrator activity and suggest the involvement of INTS11 SUMOylation in the assembly of the complex. Furthermore, this work adds Integrator-dependent RNA processing to the growing list of cellular processes regulated by SUMO conjugation.
Human DNA polymerase α has a strong mutagenic potential at the initial steps of DNA synthesis
Authors: Lisova Alisa E , Baranovskiy Andrey G , Morstadt Lucia M , Babayeva Nigar D , Tahirov Tahir H 
Published: December 2022

Abstract
DNA polymerase α (Polα) is essential for DNA replication initiation and makes a notable contribution to genome mutagenesis. The activity and fidelity of Polα during the early steps of DNA replication have not been well studied. Here we show that at the beginning of DNA synthesis, when extending the RNA primer received from primase, Polα is more mutagenic than during the later DNA elongation steps. Kinetic and binding studies revealed substantially higher activity and affinity to the template:primer when Polα interacts with ribonucleotides of a chimeric RNA–DNA primer. Polα activity greatly varies during first six steps of DNA synthesis, and the bias in the rates of correct and incorrect dNTP incorporation leads to impaired fidelity, especially upon the second step of RNA primer extension. Furthermore, increased activity and stability of Polα/template:primer complexes containing RNA–DNA primers result in higher efficiency of mismatch extension.
Pushing the limits of HiFi assemblies reveals centromere diversity between two Arabidopsis thaliana genomes
Authors: Rabanal Fernando A , Gräff Maike , Lanz Christa , Fritschi Katrin , Llaca Victor , Lang Michelle , Carbonell-Bejerano Pablo , Henderson Ian , Weigel Detlef 
Published: December 2022

Abstract
Although long-read sequencing can often enable chromosome-level reconstruction of genomes, it is still unclear how one can routinely obtain gapless assemblies. In the model plant Arabidopsis thaliana, other than the reference accession Col-0, all other accessions de novo assembled with long-reads until now have used PacBio continuous long reads (CLR). Although these assemblies sometimes achieved chromosome-arm level contigs, they inevitably broke near the centromeres, excluding megabases of DNA from analysis in pan-genome projects. Since PacBio high-fidelity (HiFi) reads circumvent the high error rate of CLR technologies, albeit at the expense of read length, we compared a CLR assembly of accession Eyach15-2 to HiFi assemblies of the same sample. The use of five different assemblers starting from subsampled data allowed us to evaluate the impact of coverage and read length. We found that centromeres and rDNA clusters are responsible for 71% of contig breaks in the CLR scaffolds, while relatively short stretches of GA/TC repeats are at the core of &gt;85% of the unfilled gaps in our best HiFi assemblies. Since the HiFi technology consistently enabled us to reconstruct gapless centromeres and 5S rDNA clusters, we demonstrate the value of the approach by comparing these previously inaccessible regions of the genome between the Eyach15-2 accession and the reference accession Col-0.
Comparison of functional classification systems
Authors: Zeller Monika , Huson Daniel H 
Published: December 2022

Abstract
In microbiome analysis, functional profiling is based on assigning reads or contigs to terms or nodes in a functional classification system. There are a number of large, general-purpose functional classifications that are in use, such as eggNOG, KEGG, InterPro and SEED. Smaller, special-purpose classifications include CARD, EC, MetaCyc and VFDB. Here, we compare the different classifications in terms of their overlap, redundancy, structure and assignment rates. We also provide mappings between main concepts in different classifications. For the large classifications, we find that eggNOG performs the best with respect to sequence redundancy and structure, SEED has the cleanest hierarchy, whereas KEGG and InterPro:BP might be more informative for medical applications. We illustrate the practical assignment rates for different classifications using a number of metagenomic samples.
Strategies for knowledge exchange for action to address place-based determinants of health inequalities: an umbrella review
Authors: Halliday E , Tompson A , McGill E , Egan M , Popay J 
Published: December 2022

AbstractBackgroundPlace-based health inequalities persist despite decades of academics and other stakeholders generating ideas and evidence on how to reduce them. This may in part reflect a failure in effective knowledge exchange (KE). We aim to understand what KE strategies are effective in supporting actions on place-based determinants and the barriers and facilitators to this KE.MethodsAn umbrella review was undertaken to identify relevant KE strategies. Systematic reviews were identified by searching academic databases (Medline, Embase, Scopus, Web of Science) and handsearching. Synthesis involved charting and thematic analysis.ResultsFourteen systematic reviews were included comprising 105 unique, relevant studies. Four approaches to KE were identified: improving access to knowledge, collaborative approaches, participatory models and KE as part of advocacy. While barriers and facilitators were reported, KE approaches were rarely evaluated for their effectiveness.ConclusionsBased on these four approaches, our review produced a framework, which may support planning of future KE strategies. The findings also suggest the importance of attending to political context, including the ways in which this may impede a more upstream place-based focus in favour of behavioural interventions and the extent that researchers are willing to engage with politicized agendas.
Large-Scale Thalamocortical Triple Network Dysconnectivities in Patients With First-Episode Psychosis and Individuals at Risk for Psychosis
Authors: Kim Minah , Kim Taekwan , Ha Minji , Oh Harin , Moon Sun-Young , Kwon Jun Soo 
Published: December 2022

AbstractBackground and HypothesisAberrant thalamocortical connectivity and large-scale network interactions among the default mode network (DMN), salience network (SN), and executive control network (ECN) (ie, triple networks) have been regarded as critical in schizophrenia pathophysiology. Despite the importance of network properties and the role of the thalamus as an integrative hub, large-scale thalamocortical triple network functional connectivities (FCs) in different stages of the psychotic disorder have not yet been reported.Study DesignThirty-nine first-episode psychosis (FEP) patients, 75 individuals at clinical high risk (CHR) for psychosis, 46 unaffected relatives (URs) of schizophrenia patients with high genetic loading, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI). Modular community detection was used to identify cortical and thalamic resting-state networks, and thalamocortical network interactions were compared across the groups.Study ResultsThalamic triple networks included higher-order thalamic nuclei. Thalamic SN–cortical ECN FC was greater in the FEP group than in the CHR, UR, and HC groups. Thalamic DMN–cortical DMN and thalamic SN–cortical DMN FCs were greater in FEP and CHR participants. Thalamic ECN–cortical DMN and thalamic ECN–cortical SN FCs were greater in FEP patients and URs.ConclusionsThese results highlight critical modulatory functions of thalamic triple networks and the shared and distinct patterns of thalamocortical triple network dysconnectivities across different stages of psychotic disorders. The current study findings suggest that large-scale thalamocortical triple network dysconnectivities may be used as an integrative biomarker for extending our understanding of the psychosis pathophysiology and for targeting network-based neuromodulation therapeutics.
Substance Use and Sleep Problems in Patients With Psychotic Disorders
Authors: Cederlöf Erik , Holm Minna , Ahti Johan , Lähteenvuo Markku , Hietala Jarmo , Häkkinen Katja , Isometsä Erkki , Kampman Olli , Lahdensuo Kaisla , Lönnqvist Jouko , Suvisaari Jaana , Tiihonen Jari , Wegelius Asko , Veijola Juha , Palotie Aarno , Kieseppä Tuula , Niemelä Solja , Paunio Tiina 
Published: December 2022

Abstract

Background
Substance use and sleep problems are common in patients with psychotic disorders, but their associations in these patients have not been evaluated. We aimed to investigate associations between substance use and sleep problems in a large nationwide cohort of patients with a psychotic disorder.

Study Design
This study is part of the Finnish SUPER study, which belongs to the Stanley Global Neuropsychiatric Genomics Initiative. In this cross-sectional, multicenter study, participants (N = 8616) were recruited from primary and specialized healthcare. Patients with schizophrenia, schizoaffective disorder, bipolar disorder, and psychotic depression were included. Information on current alcohol (Alcohol Use Disorders Identification Test-Concise) and cigarette use as well as on lifetime illicit drug use, including cannabis, benzodiazepines, amphetamines, and opioids, was collected using questionnaires. The sleep outcomes in our logistic regression analysis were short (≤6 h) and long sleep (≥10 h) duration, difficulties initiating asleep, early morning awakenings, fatigue, and poor sleep quality (SQ).

Results
Self-reported substance use was associated with a higher prevalence of sleep problems. After adjustments with age, gender, diagnostic group, and living status, hazardous alcohol use (eg, poor SQ odds ratio [OR] = 1.80, 95% CI: 1.49 to 2.16, P &lt; .001), current smoking (short sleep duration OR = 1.28, 95% CI: 1.08 to 1.52, P = .005), and lifetime benzodiazepine misuse (difficulties initiating sleep OR = 2.00, 95% CI: 1.55 to 2.48, P &lt; .001) were associated with sleep problems.

Conclusions
Substance use was associated with sleep problems. Our findings underline the potential benefits of screening substance use when treating sleep problems in patients with psychotic disorders.