bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the ACMG/AMP guidelines-based seven-category variant classification system
Authors: Chen Jian-Min , Masson Emmanuelle , Zou Wen-Bin , Liao Zhuan , Génin Emmanuelle , Cooper David N. , Férec Claude 
Published: January 2023

AbstractBackgroundOne shortcoming of employing the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP)-recommended five-category variant classification scheme (“pathogenic”, “likely pathogenic”, “uncertain significance”, “likely benign” and “benign”) in medical genetics lies in the scheme’s inherent inability to deal properly with variants that fall midway between “pathogenic” and “benign”. Employing chronic pancreatitis as a disease model, and focusing on the four most studied chronic pancreatitis-related genes, we recently expanded the five-category ACMG/AMP scheme into a seven-category variant classification system. With the addition of two new classificatory categories, “predisposing” and “likely predisposing”, our seven-category system promises to provide improved classification for the entire spectrum of variants in any disease-causing gene. The applicability and practical utility of our seven-category variant classification system however remains to be demonstrated in other disease/gene contexts, and this has been the aim of the current analysis.ResultsWe have sought to demonstrate the potential universality of pathological variants that could be ascribed the new variant terminology (‘predisposing’) by trialing it across three Mendelian disease contexts (i.e., autosomal dominant, autosomal recessive and X-linked). To this end, we firstly employed illustrative genes/variants characteristic of these three contexts. On the basis of our own knowledge and expertise, we identified a series of variants that fitted well with our “predisposing” category, including “hypomorphic” variants in thePKD1gene and “variants of varying clinical consequence” in theCFTRgene. These examples, followed by reasonable extrapolations, enabled us to infer the widespread occurrence of “predisposing” variants in disease-causing genes. Such “predisposing” variants are likely to contribute significantly to the complexity of human genetic disease and may account not only for a considerable proportion of the unexplained cases of monogenic and oligogenic disease but also for much of the “missing heritability” characteristic of complex disease.ConclusionEmploying an evidence-based approach together with reasonable extrapolations, we demonstrate both the applicability and utility of our seven-category variant classification system for disease-causing genes. The recognition of the new “predisposing” category not only has immediate implications for variant detection and interpretation but should also have important consequences for reproductive genetic counseling.
NGS-enriched activated sludge modelling of industrial wastewater treatment plant
Authors: Prawira Negara M A , Keesman K J , Euverink G J W , Jayawardhana B 
Published: January 2023

ABSTRACTMetagenomics advances with the Next Generation Sequencing (NGS) technology offer detailed insights into the microbial communities and their activities in a Wastewater Treatment Plant (WWTP). Since it has been shown recently that the microbial communities can be related to process data through machine learning, we investigate in this paper the enrichment of Activated Sludge Model 1 (ASM1) using time-series NGS data. We first present a modified ASM1 (mod-ASM1) to describe the industrial wastewater treatment at North Water’s WWTP facility in Delfzijl, the Netherlands. Subsequently, we identify the parameters for the ten weeks (weeks 40-50, 2014) of process data from North Water WWTP with prior parameters from the recommended ones from IWA. We further established a subset of parameters that are correlated to NGS data. Based on this relationship, a parameter-varying mod-ASM1 is obtained where the parameter variation is directly linked to the NGS data. We validate the NGS-enriched mod-ASM1 in the prediction of process data in the subsequent three weeks (weeks 50-53, 2014). While the enriched mod-ASM1 gives a good estimation of the COD effluent data, it cannot capture the production of nitrogen, which is often missed when the static model is deployed.
Robust and fast multicolor Single Molecule Localization Microscopy using spectral separation and demixing
Authors: Friedl Karoline , Mau Adrien , Caorsi Valentina , Bourg Nicolas , Lévêque-Fort Sandrine , Leterrier Christophe 
Published: January 2023

AbstractSingle Molecule Localization Microscopy (SMLM) is a straightforward approach to reach sub-50 nm resolution using techniques such as Stochastic Optical Reconstruction Microscopy (STORM) or DNA-Point Accumulation for Imaging in Nanoscale Topography (PAINT), and to resolve the arrangement of cellular components in their native environment. However, SMLM acquisitions are slow, particularly for multicolor experiments where channels are usually acquired in sequence. In this work, we evaluate two approaches to speed-up multicolor SMLM using a module splitting the fluorescence emission toward two cameras: simultaneous 2-color PAINT (S2C-PAINT) that images spectrally-separated red and far-red imager strands on each camera, and spectral demixing STORM (SD-STORM) that uses spectrally-close far-red fluorophores imaged on both cameras before assigning each localization to a channel by demixing. For each approach, we carefully evaluate the crosstalk between channels using three types of samples: DNA origami nanorulers of different sizes, single-target labeled cells, or cells labeled for multiple targets. We then devise experiments to assess how crosstalk can potentially affect the detection of biologically-relevant subdiffraction patterns. Finally, we show how these approaches can be combined with astigmatism to obtain three-dimensional data, and how SD-STORM can be extended three-color imaging, making spectral separation and demixing attractive options for robust and versatile multicolor SMLM investigations.
Exploring the genetic diversity of the Japanese Population: Insights from a Large-Scale Whole Genome Sequencing Analysis
Authors: Kawai Yosuke , Watanabe Yusuke , Omae Yosuke , Miyahara Reiko , Khor Seik-Soon , Noiri Eisei , Kitajima Koji , Shimanuki Hideyuki , Gatanaga Hiroyuki , Hata Kenichiro , Hattori Kotaro , Iida Aritoshi , Ishibashi-Ueda Hatsue , Kaname Tadashi , Kanto Tatsuya , Matsumura Ryo , Miyo Kengo , Noguchi Michio , Ozaki Kouichi , Sugiyama Masaya , Takahashi Ayako , Tokuda Haruhiko , Tomita Tsutomu , Umezawa Akihiro , Watanabe Hiroshi , Yoshida Sumiko , Goto Yu-ichi , Maruoka Yutaka , Matsubara Yoichi , Niida Shumpei , Mizokami Masashi , Tokunaga Katsushi 
Published: January 2023

AbstractThe Japanese archipelago is a terminal location for human migration, and the contemporary Japanese people represent a unique population whose genomic diversity has been shaped by multiple migrations from Eurasia. Through high-coverage whole-genome sequencing (WGS) analysis of 9,850 samples from the National Center Biobank Network, we analyzed the genomic characteristics that define the genetic makeup of the modern Japanese population from a population genetics perspective. The dataset comprised populations from the Ryukyu Islands and other parts of the Japanese archipelago (Hondo). Low frequency detrimental or pathogenic variants were found in these populations. The Hondo population underwent two episodes of population decline during the Jomon period, corresponding to the Late Neolithic, and the Edo period, corresponding to the Early Modern era, while the Ryukyu population experienced a population decline during the shell midden period of the Late Neolithic in this region. Genes related to alcohol and lipid metabolism were affected by positive natural selection. Two genes related to alcohol metabolism were found to be 12,500 years out of phase with the time when they began to be affected by positive natural selection; this finding indicates that the genomic diversity of Japanese people has been shaped by events closely related to agriculture and food production.Author summaryThe human population in the Japanese archipelago exhibits significant genetic diversity, with the Ryukyu Islands and other parts of the archipelago (Hondo) having undergone distinct evolutionary paths that have contributed to the genetic divergence of the populations in each region. In this study, whole genome sequencing of healthy individuals from national research hospital biobanks was utilized to investigate the genetic diversity of the Japanese population. Haplotypes were inferred from the genomic data, and a thorough population genetic analysis was conducted. The results indicated not only genetic differentiation between Hondo and the Ryukyu Islands, but also marked differences in past population size. In addition, gene genealogies were inferred from the haplotypes, and the patterns were scrutinized for evidence of natural selection. This analysis revealed unique traces of natural selection in East Asian populations, many of which were believed to be linked to dietary changes brought about by agriculture and food production.
The spectral slope as a marker of excitation/inhibition ratio and cognitive functioning in multiple sclerosis
Authors: Akbarian Fahimeh , Rossi Chiara , Costers Lars , D’hooghe Marie B , D’haeseleer Miguel , Nagels Guy , Schependom Jeroen Van 
Published: January 2023

AbstractBackgroundMultiple sclerosis (MS) is a neurodegenerative disease characterized by neuronal and synaptic loss, resulting in an imbalance of excitatory and inhibitory synaptic transmission and potentially cognitive impairment. Current methods for measuring the excitation/inhibition (E/I) ratio are mostly invasive, but recent research combining neurocomputational modeling with measurements of local field potentials has indicated that the slope with which the power spectrum of neuronal activity captured by electro- and/or magnetoencephalography rolls off, is a non-invasive biomarker of the E/I ratio. A steeper roll- off is associated with a stronger inhibition. This novel method can be applied to assess the E/I ratio in people with multiple sclerosis (pwMS), detect the effect of medication such as benzodiazepines, and explore its utility as a biomarker for cognition.MethodsWe recruited 44 healthy control subjects and 95 people with multiple sclerosis (pwMS) who underwent resting-state magnetoencephalographic recordings. The 1/f spectral slope of the neural power spectra was calculated for each subject and for each brain region.ResultsAs expected, the spectral slope was significantly steeper in pwMS treated with benzodiazepines (BZDs) compared to pwMS not receiving BZDs (p = 0.01). In the sub-cohort of pwMS not treated with BZDs, we observed a steeper slope in cognitively impaired pwMS compared to cognitively preserved pwMS (p = 0.01) and healthy subjects (p = 0.02). Furthermore, we observed a significant correlation between 1/f spectral slope and verbal and spatial working memory functioning in the brain regions located in the prefrontal and parietal cortex.ConclusionsIn this study, we highlighted the value of the spectral slope in MS by quantifying the effect of benzodiazepines and by putting it forward as a potential biomarker of cognitive deficits in pwMS.
Topological design principle for the robustness of necroptosis biphasic, emergent, and coexistent (BEC) dynamics
Authors: Xu Fei , Li Xiang , Wu Rui , Qi Hong , Jin Jun , Liu Zhilong , Wu Yuning , Lin Hai , Shen Chuansheng , Shuai Jianwei 
Published: January 2023

AbstractBiphasic dynamics, the variable-dependent ability to enhance or restrain biological function, is prevalent in natural systems. Accompanied by biphasic dynamics, necroptosis signaling dominated by RIP1 also appears emergent and coexistent dynamics. Here, we identify the RIP1-RIP3-C8 incoherent feedforward loop embedded with positive feedback of RIP3 to RIP1 is the core topology, and the scale-free feature of RIP3 peak value dictates necroptosis BEC dynamics. Entropy production is introduced to quantify the uncertainty of coexistent dynamics. RIP3 auto-phosphorylation is further determined as a complementary process for robustly attaining necroptosis BEC dynamics. Through screening all possible two- and three-node circuit topologies, a complete atlas of three-node circuit BEC dynamics is generated and only three minimal circuits emerge as robust solutions, proving incoherent feedforward loop is the core topology. Overall, through highlighting a finite set of circuits, this study yields guiding principles for mapping, modulating, and designing circuits for BEC dynamics in biological systems.
All Quiet on the Western Front? The evolutionary history of monogeneans (Dactylogyridae:Cichlidogyrus, Onchobdella) infecting a West and Central African tribe of cichlid fishes (Chromidotilapiini)
Authors: Moons Tanisha , Kmentová Nikol , Pariselle Antoine , Artois Tom , Bert Wim , Vanhove Maarten P. M. , Cruz-Laufer Armando J. 
Published: January 2023

AbstractOwing to the largely unexplored diversity of metazoan parasites, their speciation mechanisms and the circumstances under which such speciation occurs—in allopatry or sympatry—remain vastly understudied. Cichlids and their monogenean flatworm parasites have previously served as study system for macroevolutionary processes, e.g. for the role of East African host radiations on parasite communities. Here, we investigate the diversity and evolution of the poorly explored monogeneans infecting a West and Central African lineage of cichlid fishes: Chromidotilapiini Greenwood, 1987, which is the most species-rich tribe of cichlids in this region. We screened gills of 149 host specimens (27 species) from natural history collections and measured systematically informative characters of the sclerotised attachment and reproductive organs of the parasites. Ten monogenean species (Dactylogyridae:CichlidogyrusandOnchobdella) were found, eight of which are described and one redescribed herein. The phylogenetic positions of chromidotilapiines-infecting species ofCichlidogyruswere inferred through a parsimony analysis of the morphological characters. Furthermore, we employed machine learning algorithms to detect morphological features associated with the main lineages ofCichlidogyrus. Although the results of these experimental algorithms remain inconclusive, the parsimony analysis indicates that West and Central African lineages ofCichlidogyrusandOnchobdellaare monophyletic, unlike the paraphyletic host lineages. Several instances of host sharing suggest occurrences of intra-host speciation (sympatry) and host switching (allopatry). Some morphological variation was recorded that may also indicate the presence of species complexes. We conclude that collection material can provide important insights on parasite evolution despite the lack of well-preserved DNA material.Data availability statementType material was deposited in the invertebrate collection of the Royal Museum for Central Africa (Tervuren, Belgium) (RMCA) (RMCA_VERMES_XXXXX–XXX), the collection of the Research Group Zoology: Biodiversity and Toxicology of Hasselt University (Diepenbeek, Belgium) (HU XXX–XXX), the Finnish Museum of Natural History (Helsinki, Finland) (MZH XXXXX–XXX), and the Iziko South African Museum (Cape Town, South Africa) (SAMC-XXXXXXX-XXX). The morphological data that support the findings of this study are openly available in MorphoBank atwww.morphobank.org, at https://dx.doi.org/XXXXXXXX. Phylogenetic trees and data matrices for the analysis in TNT are included as additional data in MorphoBank.
The Sin3B chromatin modifier restricts cell cycle progression to dictate hematopoietic stem cell differentiation
Authors: Calderon Alexander , Mestvirishvili Tamara , Boccalatte Francesco , Ruggles Kelly V. , David Gregory 
Published: January 2023

Abstract/SummaryTo maintain blood homeostasis, millions of terminally differentiated effector cells are produced every day. At the apex of this massive and constant blood production lie hematopoietic stem cells (HSCs), a rare cell type harboring unique self-renewal and multipotent properties. A key feature of HSCs is their ability to temporarily exit the cell cycle in a state termed quiescence. Defective control of cell cycle progression can eventually lead to bone marrow failure or malignant transformation. It is thought that HSCs must re-enter the cell cycle in order to commit to terminal differentiation. However, the molecular mechanisms tying cell cycle re-entry to cell fate commitment in HSCs remain elusive. Here, we identify the chromatin-associated Sin3B protein as a molecular link between cell cycle progression and differentiation in HSCs. We demonstrate that Sin3B is necessary for HSCs’ commitment to differentiation, but dispensable for their self-renewal or survival. Single cell transcriptional profiling of hematopoietic stem and progenitor cells (HSPCs) inactivated for Sin3B reveals aberrant cell cycle gene expression, consistent with the observed aberrant progression through the G1phase of the cell cycle. The defective cell cycle control elicited upon Sin3B inactivation correlates with the engagement of discrete signaling programs, including aberrant expression of cell adhesion molecules and essential components of the interferon signaling cascade in LT-HSCs. Additionally, chromatin accessibility profiling in LT-HSCs reveals the Sin3B-dependent accessibility of genomic elements controlling HSC differentiation, suggesting a functional link between cell cycle progression, and priming of hematopoietic stem cells for differentiation. Together, these results point to controlled progression through the G1phase of the cell cycle as a likely regulator of HSC lineage commitment through the modulation of chromatin features.
AGAMOUS mediates timing of guard cell formation during gynoecium development
Authors: Brazel Ailbhe J. , Fattorini Róisín , McCarthy Jesse , Franzen Rainer , Rümpler Florian , Coupland George , Ó’Maoiléidigh Diarmuid S. 
Published: January 2023

AbstractInArabidopsis thaliana, stomata are composed of two guard cells that control the aperture of a central pore to facilitate gas exchange between the plant and its environment, which is particularly important during photosynthesis. Although leaves are the primary photosynthetic organs of higher plants, floral organs are also photosynthetically active. In the Brassicaceae, evidence suggests that silique photosynthesis is important for optimal seed oil content. A group of transcription factors containing MADS DNA binding domains is necessary and sufficient to confer floral organ identity. Elegant models, such as the ABCE model of flower development and the floral quartet model, have been instrumental in describing the molecular mechanisms by which these floral organ identity proteins govern flower development. However, we lack a complete understanding of how the floral organ identity genes interact with the underlying leaf development program. Here, we show that the MADS domain transcription factor AGAMOUS (AG) represses stomatal development on the gynoecial valves, so that maturation of stomatal complexes coincides with fertilization. We present evidence that this regulation by AG is mediated by direct transcriptional repression of the master regulator of the stomatal lineage,MUTE, and that this interaction is conserved among the Brassicaceae. This work extends on our understanding of the mechanisms underlying floral organ formation and provides a framework to decipher the mechanisms that control floral organ photosynthesis.
Utility of long-read sequencing for All of Us
Authors: Mahmoud M. , Huang Y. , Garimella K. , Audano P. A. , Wan W. , Prasad N. , Handsaker R. E. , Hall S. , Pionzio A. , Schatz M. C. , Talkowski M. E. , Eichler E. E. , Levy S. E. , Sedlazeck F. J. 
Published: January 2023

AbstractTheAll of Us(AoU) initiative aims to sequence the genomes of over one million Americans from diverse ethnic backgrounds to improve personalized medical care. In a recent technical pilot, we compared the performance of traditional short-read sequencing with long-read sequencing in a small cohort of samples from the HapMap project and two AoU control samples representing eight datasets. Our analysis revealed substantial differences in the ability of these technologies to accurately sequence complex medically relevant genes, particularly in terms of gene coverage and pathogenic variant identification. We also considered the advantages and challenges of using low coverage sequencing to increase sample numbers in large cohort analysis. Our results show that HiFi reads produced the most accurate results for both small and large variants. Further, we present a cloud-based pipeline to optimize SNV, indel and SV calling at scale for long-reads analysis. These results will lead to widespread improvements across AoU.
Why do some fungi want to be sterile? The role of dysfunctional Pro1 in the rice blast fungus
Authors: Uchida Momotaka , Konishi Takahiro , Fujigasaki Ayaka , Kita Kohtetsu , Arie Tsutomu , Teraoka Tohru , Arazoe Takayuki , Kamakura Takashi 
Published: January 2023

AbstractAlthough sexual reproduction is widespread in eukaryotes, some fungal species can only reproduce asexually. Therefore, loss of sexual reproduction may confer survival advantages under certain conditions in certain species. In the rice blast fungusPyricularia(Magnaporthe)oryzae, several isolates from the region of origin retain mating ability (female fertility), but most isolates are female sterile. Therefore, it is hypothesized that female fertility was lost during its spread from the origin to the rest of the world, andP. oryzaeis an ideal biological model for studying the cause of the evolutionary shift in the reproductive mode. Here, we show that functional mutations of Pro1, a global transcriptional regulator of mating-related genes in filamentous fungi, is one cause of loss of female fertility in this fungus. Employing backcrossing between female-fertile and female-sterile field isolates, we identified the putative genomic region involved in female sterility by comparative genomics between the genomes of F4female-fertile and -sterile progenies. Further genotyping, linkage, and functional analyses revealed that the functional mutation of Pro1 causes the loss of female fertility. RNA sequencing analysis showed that Pro1 regulates global gene expression, including that of several mating-related genes. The dysfunctional Pro1 did not affect the infection processes, such as conidial germination, appressorium formation, and penetration, but conidial release from conidiophores was increased. Furthermore, various types of mutations in Pro1 were detected in geographically distantP. oryzae, including pandemic isolates of wheat blast fungus. These results provide the first evidence that loss of female fertility may be advantageous to the life cycle of some plant pathogenic fungi.SignificanceMany pathogenic and industrial fungi are thought to have abdicated sexual reproduction, but the mechanisms and biological importance have been a long-standing mystery. Discovering why such fungi lost fertility is important to understand their survival strategies. Here, we revealed the genetic basis of how the rice blast fungus lost female fertility in nature and how this affects the life cycle. This has important implications for understanding evolution of blast pathogens and for developing an effective management strategy to control blast disease before a pandemic. Our findings also provide an additional perspective on advantages of asexual reproduction in some eukaryotes.