bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extraction and selection of high-molecular-weight DNA for long-read sequencing from Chlamydomonas reinhardtii
Authors: Chaux-Jukic Frédéric , Agier Nicolas , Eberhard Stephan , Xu Zhou 
Published: August 2022

AbstractRecent advances in long-read sequencing technologies have enabled the complete assembly of eukaryotic genomes from telomere to telomere by allowing repeated regions to be fully sequenced and assembled, thus filling the gaps left by previous short-read sequencing methods. Furthermore, long-read sequencing can also help characterizing structural variants, with applications in the fields of genome evolution or cancer genomics. For many organisms, the main bottleneck to sequence long reads remains the lack of robust methods to obtain high-molecular-weight (HMW) DNA. For this purpose, we developed an optimized protocol to extract DNA suitable for long-read sequencing from the unicellular green alga Chlamydomonas reinhardtii, based on CTAB/phenol extraction followed by a size selection step for long DNA molecules. We provide validation results for the extraction protocol, as well as statistics obtained with Oxford Nanopore Technologies sequencing.
Characterization of an Eye Field-like State during Optic Vesicle Organoid Development
Authors: Owen Liusaidh J. , Rainger Jacqueline , Bengani Hemant , Kilanowski Fiona , FitzPatrick David R. , Papanastasiou Andrew S. 
Published: August 2022

ABSTRACTSpecification of the eye field (EF) within the neural plate marks the earliest detectable stage of eye development. Experimental evidence, primarily from non-mammalian model systems, indicates that the stable formation of this group of cells requires the activation of a set of key transcription factors (TFs). This critical event is challenging to probe in mammals and, quantitatively, little is known regarding the regulation of the transition of cells to this ocular fate. Using optic vesicle organoids to model the onset of the EF, we generate timecourse transcriptomic data allowing us to identify dynamic gene-expression programs that characterise this cellular-state transition. Integrating this with chromatin accessibility data suggests a direct role of canonical EFTFs in regulating these gene-expression changes, and high-lights candidate cis-regulatory elements through which these TFs act. Finally, we begin to test a subset of these candidate enhancer elements, within the organoid system, by perturbing the underlying DNA sequence and measuring transcriptomic changes during EF activation.
Separate and shared low-dimensional neural architectures for error-based and reinforcement motor learning
Authors: Areshenkoff Corson N. , de Brouwer Anouk , Gale Daniel J. , Nashed Joseph Y. , Gallivan Jason P. 
Published: August 2022

AbstractMotor learning is supported by multiple systems adapted to processing different forms of sensory information (e.g., reward versus error feedback), and by higher-order systems supporting strategic processes. Yet, the extent to which these systems recruit shared versus separate neural pathways is poorly understood. To elucidate these pathways, we separately studied error-based (EL) and reinforcement-based (RL) motor learning in two functional MRI experiments in the same human subjects. We find that EL and RL occupy opposite ends of neural axis broadly separating cerebellar and striatal connectivity, respectively, with somatomotor cortex, and that alignment of this axis to each task is related to performance. Further, we identify a separate neural axis that is associated with strategy use during EL, and show that the expression of this same axis during RL predicts better performance. Together, these results offer a macroscale view of the common versus distinct neural architectures supporting different learning systems.
Nudibranch predation boosts sponge silicon cycling
Authors: López-Acosta María , Potel Clémence , Gallinari Morgane , Pérez Fiz F. , Leynaert Aude 
Published: August 2022

AbstractSponges are singular players in the marine silicon cycle. They accumulate vast stocks of biogenic silica within their bodies and in the sediments beneath them over long periods. These silica stocks are recycled at slow rates, much slower than that of other silicon users such as diatoms. The observation of an abrupt change in sponge biomass in a temperate coastal ecosystem led us to study the effect of nudibranch (Doris verrucosa) predation on the silicon budget of a sponge (Hymeniacidon perlevis) population on an annual scale. Predation rates and the associated sponge silicon fluxes were determined. After 5 months of predation, the abundance of sponge individuals did not change but their biomass decreased by 95%, of which 48% can be explained by nudibranch predation. About 97% of sponge spicules ingested by nudibranchs while feeding was excreted, most of them unbroken, implying a high rate of sponge silica deposition in the surrounding sediments. After predation, sponges partially recovered their biomass stocks within 7 months. This involved a rapid growth rate and large consumption of dissolved silicon, with the highest rates ever recorded unexpectedly occurring when the dissolved silicon concentration was minimal in seawater (< 1.5 μM). These findings reveal that the annual sponge predation-recovery cycle triggers unprecedented intra-annual changes in sponge silicon stocks and boosts nutrient cycling. They also highlight the need for intra-annual data collection to understand the dynamics and resilience of sponge ecosystem functioning.
Automatic and accurate ligand structure determination guided by cryo-electron microscopy maps
Authors: Muenks Andrew , Zepeda Samantha , Zhou Guangfeng , Veesler David , DiMaio Frank 
Published: August 2022

ABSTRACTAdvances in cryo-electron microscopy (cryoEM) and deep-learning guided protein structure prediction have expedited structural studies of protein complexes. However, methods for accurately determining ligand conformations are lacking. In this manuscript, we develop a tool for automatically determining ligand structures guided by medium-resolution cryoEM density. We show this method is robust at predicting ligands in maps as low as 6Å resolution, and is able to correct receptor sidechain errors. Combining this with a measure of placement confidence, and running on all protein/ligand structures in EMDB, we show that 58% of ligands replicate the deposited model, 16% confidently find alternate conformations, 22% have ambiguous density where multiple conformations might be present, and 4% are incorrectly placed. For five cases where our approach finds an alternate conformation with high confidence, high-resolution crystal structures validate our placement. This tool and the resulting analysis should prove critical in using cryoEM to investigate protein-ligand complexes.
Examining Reproducibility of EEG Schizophrenia Biomarkers Across Explainable Machine Learning Models
Authors: Ellis Charles A. , Sattiraju Abhinav , Miller Robyn , Calhoun Vince 
Published: August 2022

AbstractSchizophrenia (SZ) is a neuropsychiatric disorder that adversely effects millions of individuals globally. Current diagnostic efforts are symptom based and hampered due to the variability in symptom presentation across individuals and overlap of symptoms with other neuropsychiatric disorders. This spawns the need for (1) biomarkers to aid with empirical SZ diagnosis and (2) the development of automated diagnostic approaches that will eventually serve in a clinical decision support role. In this study, we train random forest (RF) and support vector machine (SVM) models to differentiate between individuals with schizophrenia and healthy controls using spectral features extracted from resting state EEG data. We then perform two explainability analyses to gain insight into key frequency bands and channels. In our explainability analyses, we examine the reproducibility of SZ biomarkers across models with the goal of identifying those that have potential clinical implications. Our model performance results are well above chance level indicating the broader utility of spectral information for SZ diagnosis. Additionally, we find that the RF prioritizes the upper γ-band and is robust to loss of information from individual electrodes, while the SVM prioritizes the α and θ-bands and P4 and T8 electrodes. It is our hope that our findings will inform future efforts towards the empirical diagnosis of SZ and towards the development of clinical decision support systems for SZ diagnosis.
Mitochondrial-encoded complex I impairment induces a targetable dependency on aerobic fermentation in Hürthle cell carcinoma of the thyroid
Authors: Frank Anderson R , Li Vicky , Shelton Spencer D , Kim Jiwoong , Stott Gordon M , Neckers Leonard , Xie Yang , Williams Noelle S , Mishra Prashant , McFadden David G 
Published: August 2022

SUMMARYA metabolic hallmark of cancer identified by Warburg is the increased consumption of glucose and secretion of lactate, even in the presence of oxygen. Although many tumors exhibit increased glycolytic activity, most forms of cancer rely on mitochondrial respiration for tumor growth. We report here that Hürthle cell carcinoma of the thyroid (HTC) models harboring mitochondrial DNA-encoded defects in complex I of the mitochondrial electron transport chain exhibit impaired respiration and alterations in glucose metabolism. CRISPR/Cas9 pooled screening identified glycolytic enzymes as selectively essential in complex I-mutant HTC cells. We demonstrate in cultured cells and a PDX model that small molecule inhibitors of lactate dehydrogenase selectively induce an ATP crisis and cell death in HTC. This work demonstrates that complex I loss exposes fermentation as a therapeutic target in HTC and has implications for other tumors bearing mutations that irreversibly damage mitochondrial respiration.
Host Age Structure Defines Interactions with Pathogens: Grandparent Effect under Collaboration and Virulent Mutualism under Competition
Authors: Portner Carsten O.S. , Rong Edward G. , Ramirez Jared A. , Wolf Yuri I , Bosse Angelique P. , Koonin Eugene V. , Rochman Nash D. 
Published: August 2022

AbstractBackgroundSymbiotic relationships are ubiquitous in the biosphere. Inter-species symbiosis is impacted by intra-specific distinctions, in particular, those defined by the age structure of a population. Older individuals compete with younger individuals for resources despite being less likely to reproduce, diminishing the fitness of the population. Conversely, however, older individuals can support the reproduction of younger individuals, increasing the population fitness. Parasitic relationships are commonly age structured, typically, more adversely affecting older hosts.ResultsWe employ mathematical modeling to explore the differential effects of collaborative or competitive host age structures on host-parasite relationships. A classical epidemiological compartment model is constructed with three disease states: susceptible, infected, and recovered. Each of these three states is partitioned into two compartments representing young, potentially reproductive, and old, post-reproductive, hosts, yielding 6 compartments in total. In order to describe competition and collaboration between old and young compartments, we model the reproductive success to depend on the fraction of young individuals in the population. Collaborative populations with relatively greater numbers of post-reproductive hosts enjoy greater reproductive success whereas in purely competitive populations, increase of the post-reproductive subpopulation reduces reproductive success. However, in competitive populations, virulent pathogens preferentially targeting old individuals can increase the population fitness.ConclusionsWe demonstrate that, in collaborative host populations, pathogens strictly impacting older, post-reproductive individuals can reduce population fitness even more than pathogens that directly impact younger, potentially reproductive individuals. In purely competitive populations, the reverse is observed, and we demonstrate that endemic, virulent pathogens can oxymoronically form a mutualistic relationship with the host, increasing the fitness of the host population. Applications to endangered species conservation and invasive species containment are discussed.
Dodecaploid Xenopus longipes provides insight into the emergence of size scaling relationships during development
Authors: Miller Kelly , Cadart Clotilde , Heald Rebecca 
Published: August 2022

SUMMARYGenome and cell size are strongly correlated across species1–6 and influence physiological traits like developmental rate7–12. Although size scaling features such as the nuclear-cytoplasmic (N/C) ratio are precisely maintained in adult tissues13, it is unclear when during embryonic development size scaling relationships are established. Frogs of the genus Xenopus provide a model to investigate this question, since 29 extant Xenopus species vary in ploidy from 2 to 12 copies (n) of the genome, ranging from 20 to 108 chromosomes14,15. The most widely studied species, X. laevis (4n=36) and X. tropicalis (2n=20), scale at all levels from body size to cellular and subcellular16. Paradoxically, the rare, critically endangered dodecaploid (2n=108) X. longipes is a small frog15,17. We observed that despite some morphological differences, X. longipes and X. laevis embryogenesis occurred with similar timing, with genome to cell size scaling emerging at the swimming tadpole stage. Across the three species, cell size was determined primarily by egg size, while nuclear size correlated with genome size during embryogenesis, resulting in different nuclear-cytoplasmic ratios at the mid-blastula transition. At the subcellular level, nuclear size correlated more strongly with genome size, whereas mitotic spindle size scaled with cell size. Our cross-species study indicates that scaling of cell size to ploidy is not due to abrupt changes in cell division timing, that different size scaling regimes occur during embryogenesis, and that the developmental program of Xenopus is remarkably consistent across a wide range of genome and egg sizes.ONE SENTENCE SUMMARYComparison of size metrics in embryos from different ploidy Xenopus species, including the dodecaploid X. longipes, reveals distinct size scaling regimes during development.
The genome of a vestimentiferan tubeworm (Ridgeia piscesae) provides insights into its adaptation to a deep-sea environment
Authors: Wang Muhua , Ruan Lingwei , Liu Meng , Liu Zixuan , He Jian , Zhang Long , Wang Yuanyuan , Shi Hong , Chen Mingliang , Yang Feng , Zeng Runying , He Jianguo , Guo Changjun , Chen Jianming 
Published: August 2022

AbstractVestimentifera (Polychaeta, Siboglinidae) is a taxon of deep-sea worm-like animals living in the deep-sea hydrothermal vent and cold seep areas. The morphology and lifespan of Ridgeia piscesae, which is the only vestimentiferan tubeworm species found in the hydrothermal vents on the Juan de Fuca Ridge, vary greatly according to the endemic environments. Recent analyses have revealed the genomic basis of adaptation in three vent- and seep-dwelling vestimentiferan tubeworms. However, the evolutionary history and mechanism of adaptation in R. piscesae, a unique species in the family Siboglinidae, is remained to be investigated. Here we report a high-quality genome of R. piscesae collected at Cathedral vent of the Juan de Fuca Ridge. Comparative genomic analysis revealed that that the high growth rates of vent-dwelling tubeworms might derive from small genome size. The small genome sizes of these tubeworms are attributed to the repeat content but not the number of genes and intron sizes. Additionally, four genes involved in cell proliferation were subject to positive selection in the genome of R. piscesae, suggesting that, besides apoptosis, cell proliferation is important for regulating growth rate in this species.
DeepDetect: deep learning of peptide detectability enhanced by peptide digestibility
Authors: Yang Jinghan , Gong Fuzhou , Fu Yan 
Published: August 2022

ABSTRACTIn tandem mass spectrometry-based proteomics, proteins are digested by specific protease(s) into peptides, but generally only a fraction of theoretical peptides can be detected. To explore the characteristics of proteotypic peptides, we have developed a series of methods for peptide digestibility and detectability prediction, and this is the latest one of them. Specifically, we propose here a bidirectional long short-term memory (BiLSTM)-based algorithm, named DeepDetect, for the prediction of peptide detectability enhanced by peptide digestibility. Compared with existing algorithms, DeepDetect is featured by its improved accuracy of prediction and wide applicability to commonly used proteases covering Trypsin, ArgC, Chymotrypsin, GluC, LysC, AspN, LysN, and LysargiNase. On eleven independent test data sets, DeepDetect achieved AUCs of 0.858~0.957, superior to the state-of-the-art algorithms, AP3 and PepFormer, which either used conventional machine learning methods or disregarded the digestibility feature. As an application, the predicted peptide detectability was utilized to re-rank and validate the peptide-spectrum matches, and showed the potential to promote the sensitivity of peptide identification.
Modulation of Capsid Dynamics in Bromoviruses by the Host and Heterologous Viral Replicase
Authors: Chakravarty Antara , Rao A. L. N. 
Published: August 2022

ABSTRACTThe tripartite genome of Cowpea chlorotic mottle virus is packaged into three morphologically indistinguishable icosahedral virions with T=3 symmetry. The two virion types, C1V and C2V, package genomic RNAs 1 (C1) and 2 (C2), respectively. The third virion type, C3+4V, co-packages genomic RNA3 and its sub-genomic RNA (RNA4). In this study, each virion type was separately assembled in planta using a previously established agroinfiltration approach. The three virion types are indistinguishable under the EM and by electrophoretic mobility. However, the stability and the capsid dynamics evaluated respectively by the differential scanning fluorimetry and MALDI-TOF analysis following trypsin digestion distinguished the three virions type. Proteolytic analysis revealed that, while retaining the structural integrity, C1V and C2V virions released peptide regions encompassing the N-terminal arginine-rich RNA binding motif. In contrast, a minor population of the C3+4V virion type was sensitive to trypsin-releasing peptides encompassing the entire capsid protein region. In addition, we also evaluated the effect of the two host organisms on the capsid dynamics. The wild-type CCMV virions purified from cowpea are highly susceptible to trypsin digestion, while those from N. benthamiana remained resistant. Finally, the MALDI-TOF evaluated the relative dynamics of C3+4V and B3+4V virions assembled under the control of the homologous vs. heterologous replicase. The significance of the viral replicase in modulating the capsid dynamics was evident by the differential sensitivity to protease exhibited by B3+4V and C3+4V virions assembled under the homologous vs. heterologous replicase. The significance of these results in relation to viral biology is discussed.IMPORTANCEInfectious virus particles or virions are considered static structures and undergo various conformational transitions to replicate and infect many eukaryotic cells. Although viral capsid fluctuations, referred to as dynamics or breathing, have been well studied in RNA viruses pathogenic to animals, such information is limited among plant viruses. Cowpea chlorotic mottle virus (CCMV) and Brome mosaic virus (BMV), RNA viruses pathogenic to plants, contain a segmented genome distributed among three physically and structurally homogenous icosahedral virion types. This study examines the role of the host organism and the heterologous viral replicase in modulating the thermal stability and capsid dynamics in CCMV and BMV. The results accentuate that alteration of the capsid dynamics by the host type and heterologous replicase are likely to affect the biology of the virus.
Fasting-sensitive SUMO-switch on Prox1 controls hepatic cholesterol metabolism
Authors: Alfaro Nunez Ana Jimena , Dittner Claudia , Becker Janina , Loft Anne , Mhamane Amit , Maida Adriano , Georgiadi Anastasia , Tsokanos Phivos , Klepac Katarina , Molocea Eveline , Merahbi Rabih , Motzler Karsten , Geppert Julia , Karikari Rhoda Anane , Szendrödi Julia , Feuchtinger Annette , Hofmann Susanna , Melchior Frauke , Herzig Stephan 
Published: August 2022

AbstractThe liver is the major metabolic hub, ensuring appropriate nutrient supply during fasting and feeding. In obesity, accumulation of excess nutrients hampers proper liver function and is linked to non-alcoholic fatty liver disease. Understanding the signaling mechanisms that enable hepatocytes to quickly adapt to dietary cues, might help to restore balance in liver diseases. Post-translational modification by attachment of the Small Ubiquitin-like Modifier (SUMO), allows for a dynamic regulation of numerous processes including transcriptional reprograming. Here, we demonstrate that the specific SUMOylation of transcription factor Prox1 represents a nutrient-sensitive determinant of hepatic fasting metabolism. Prox1 was highly modified by SUMOylation on lysine 556 in the liver of ad libitum and re-fed mice, while this modification was strongly abolished upon fasting. In a context of diet-induced obesity, Prox1 SUMOylation became insensitive to fasting cues. Hepatocyte-selective knock in of a SUMOylation-deficient Prox1 mutant into mice fed a high fat/high fructose diet led to reduction of systemic cholesterol levels, associated with the induction of bile acid detoxifying pathways in mutant livers during fasting. As appropriate and controlled fasting protocols have been shown to exert beneficial effects on human health, tools to maintain the nutrient-sensitive SUMOylation switch on Prox1 may thus contribute to the development of “fasting-based” approaches for the maintenance of metabolic health.
Do demographic, and clinical characteristics influence meeting NICE quality standards for young people transitioning to adult intellectual disability services?
Authors: Soper Paul , Stewart Alex G. , Nathan Rajan , Nall-Evans Sharleen , Mills Rachel , Michelet Felix , Jaydeokar Sujeet 
Published: August 2022

Purpose
This study aims to evaluate the quality of transition from child and adolescent services to adult intellectual disability services, using the relevant National Institute for Health and Care Excellence (NICE) standard (QS140). In addition, this study also identifies any differences in transition quality between those young people with intellectual disability with and without autism.

Design/methodology/approach
Using routinely collected clinical data, this study identifies demographic and clinical characteristics of, and contextual complexities experienced by, young people in transition between 2017 and 2020. Compliance with the quality standard was assessed by applying dedicated search terms to the records.

Findings
The study highlighted poor recording of data with only 22% of 306 eligible cases having sufficient data recorded to determine compliance with the NICE quality standard. Available data indicated poor compliance with the standard. Child and adolescent mental health services, generally, did not record mental health co-morbidities. Compliance with three out of the five quality statements was higher for autistic young people, but this only reached statistical significance for one of those statements (i.e. having a named worker, p = 0.02).

Research limitations/implications
Missing data included basic clinical characteristics such as the level of intellectual disability and the presence of autism. This required adult services to duplicate assessment procedures that potentially delayed clinical outcomes. This study highlights that poor compliance may reflect inaccurate recording that needs addressing through training and introduction of shared protocols.

Originality/value
To the best of the authors’ knowledge, this is the first study to examine the transition process between children’s and adults’ intellectual disability health services using NICE quality standard 140.