bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review of Interventions for Balance Dysfunction in Patients With Vestibular Schwannoma
Authors: Ojha Shilpa , Clamp Philip J. 
Published: December 2019

Objective:
Dizziness is a major contributing factor to poor quality of life for patients with vestibular schwannoma (acoustic neuroma). We wished to review the literature on interventions for balance dysfunction in these patients.

Data Sources:
A systematic literature review was performed identifying studies that measured balance function before and after treatment for vestibular schwannoma. Data sources include Medline (1950–present), EMBASE (1974–present), Cochrane Library (issue 3, 2008), NHS Centre of reviews and dissemination, Clinical Evidence, Cochrane central register of controlled trial, and CINAHL.

Study Selection:
A minimum follow-up of 6 months was required, to estimate long-term balance function. Eight articles were identified, including five studies with surgical intervention, two studies with stereotactic radiotherapy, and one comparing the two. Study design was generally poor with a high risk of bias. These studies all utilized the Dizziness Handicap Inventory (DHI) as a measure of pre- and postintervention balance function.

Data Extraction:
Results showed that overall DHI scores are not statistically affected by intervention irrespective of modality (surgery or stereotactic radiotherapy). Patients selected with severe dizziness, who undergo surgery, improved postoperatively. No other studies for severe dizziness were noted for comparison.

Conclusions:
Age, sex, and tumor size have no statistically significant effect on DHI outcomes, and no evidence to suggest which treatment modality has better dizziness related outcomes.
No specific treatment modality was superior in terms of long-term balance function. Patients with severe dizziness may benefit from surgery, although no comparator studies were identified.
ParB spreading on DNA requires cytidine triphosphatein vitro
Authors: Jalal Adam S. B. , Tran Ngat T. , Le Tung B. K. 
Published: December 2019

ABSTRACTIn all living organisms, it is essential to transmit genetic information faithfully to the next generation. The SMC-ParAB-parSsystem is widely employed for chromosome segregation in bacteria. A DNA-binding protein ParB nucleates onparSsites and must associate with neighboring DNA, a process known as spreading, to enable efficient chromosome segregation. Despite its importance, how the initial few ParB molecules nucleating atparSsites recruit hundreds of further ParB to spread is not fully understood. Here, we reconstitute aparS-dependent ParB spreading event using purified proteins fromCaulobacter crescentusand show that CTP is required for spreading. We further show that ParB spreading requires a closed DNA substrate, and a DNA-binding transcriptional regulator can act as a roadblock to attenuate spreading unidirectionallyin vitro. Our biochemical reconstitutions recapitulate many observedin vivoproperties of ParB and opens up avenues to investigate the interactions between ParB-parSwith ParA and SMC.
Bayesian inference associates rareKDRvariants with specific phenotypes in pulmonary arterial hypertension
Authors: Swietlik Emilia M. , Greene Daniel , Zhu Na , Megy Karyn , Cogliano Marcella , Rajaram Smitha , Pandya Divya , Tilly Tobias , Lutz Katie A. , Welch Carrie C. L. , Pauciulo Michael W. , Southgate Laura , Martin Jennifer M. , Treacy Carmen M. , Penkett Christopher J. , Stephens Jonathan C. , Bogaard Harm J. , Church Colin , Coghlan Gerry , Coleman Anna W. , Condliffe Robin , Eyries Mélanie , Gall Henning , Ghio Stefano , Girerd Barbara , Holden Simon , Howard Luke , Humbert Marc , Kiely David G. , Kovacs Gabor , Lordan Jim , Machado Rajiv D. , Ross Robert V. MacKenzie , McCabe Colm , Moledina Shahin , Montani David , Olschewski Horst , Pepke-Zaba Joanna , Price Laura , Rhodes Christopher J. , Seeger Werner , Soubrier Florent , Suntharalingam Jay , Toshner Mark R. , Noordegraaf Anton Vonk , Wharton John , Wild Jim , Wort Stephen John ,   NIHR BioResource for Translational Research - Rare Diseases,   National Cohort Study of Idiopathic and Heritable PAH,   PAH Biobank Enrolling Centers’ Investigators, Lawrie Allan , Wilkins Martin R. , Trembath Richard C. , Shen Yufeng , Chung Wendy K. , Swift Andrew J. , Nichols William C. , Morrell Nicholas W. , Gräf Stefan 
Published: December 2019

AbstractBackgroundApproximately 25% of patients with pulmonary arterial hypertension (PAH) have been found to harbor rare mutations in disease-causing genes. To identify missing heritability in PAH we integrated deep phenotyping with whole-genome sequencing data using Bayesian statistics.MethodsWe analyzed 13,037 participants enrolled in the NIHR BioResource - Rare Diseases (NBR) study, of which 1,148 were recruited to the PAH domain. To test for genetic associations between genes and selected phenotypes of pulmonary hypertension (PH), we used the Bayesian rare-variant association method BeviMed.ResultsHeterozygous, high impact, likely loss-of-function variants in the Kinase Insert Domain Receptor (KDR) gene were strongly associated with significantly reduced transfer coefficient for carbon monoxide (KCO, posterior probability (PP)=0.989) and older age at diagnosis (PP=0.912). We also provide evidence for familial segregation of a rare nonsenseKDRvariant with these phenotypes. On computed tomographic imaging of the lungs, a range of parenchymal abnormalities were observed in the five patients harboring these predicted deleterious variants inKDR. Four additional PAH cases with rare likely loss-of-function variants inKDRwere independently identified in the US PAH Biobank cohort with similar phenotypic characteristics.ConclusionsThe Bayesian inference approach allowed us to independently validateKDR, which encodes for the Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), as a novel PAH candidate gene. Furthermore, this approach specifically associated high impact likely loss-of-function variants in the genetically constrained gene with distinct phenotypes. These findings provide evidence forKDRbeing a clinically actionable PAH gene and further support the central role of the vascular endothelium in the pathobiology of PAH.
Chr21 protein-protein interactions: enrichment in products involved in intellectual disabilities, autism and Late Onset Alzheimer Disease
Authors: Viard Julia , Loe-Mie Yann , Daudin Rachel , Khelfaoui Malik , Plancon Christine , Boland Anne , Tejedor Francisco , Huganir Richard L. , Kim Eunjoon , Kinoshita Makoto , Liu Guofa , Haucke Volker , Moncion Thomas , Yu Eugene , Hindie Valérie , Bléhaut Henri , Mircher Clotilde , Herault Yann , Deleuze Jean-François , Rain Jean-Christophe , Simonneau Michel , Lepagnol-Bestel Aude-Marie 
Published: December 2019

ABSTRACTIntellectual disability (ID) found in Down syndrome (DS), which is characterized by an extra copy of 234 genes on Chr21 is poorly understood. We first used two DS mouse models that either display an extra copy of theDyrk1Agene or of the mouse Chr16 syntenic region. Exome sequencing of transcripts deregulated in embryonic hippocampus uncovers enrichment in genes involved in chromatin and synapse respectively. Using large-scale yeast two-hybrid screen (154 distinct screens) of human brain library containing at least 107independent fragments, we identified 3,636 novel protein-protein interactions with an enrichment of direct interactors of both Chromosome 21(Hsa21) baits and rebounds in ID-related genes. Using proximity ligation assays, we identified that Hsa21-encoded proteins are located at the dendritic spine postsynaptic density in a protein network located at the dendritic spine post synapse. We located Hsa21 DYRK1A and DSCAM that confers a ∼ 20-fold increase in Autism Spectrum Disorders (ASDs), in this postsynaptic network. We found that a DSCAM intracellular domain binds either DYRK1A or DLGs that are multimeric scaffolds for the clustering of receptors, ion channels, and associated signaling proteins. The DYRK1A-DSCAM interaction is conserved from drosophila to humans. The identified postsynaptic.network is enriched in ARC-related synaptic plasticity, ASDs and Late-Onset Alzheimer Disease. Altogether, these results emphasize links between DS and brain diseases with complex genetics.
Bromodomain inhibition reveals FGF15/19 as a target of epigenetic regulation and metabolic control
Authors: Kozuka Chisayo , Sales Vicencia , Osataphan Soravis , Yuchi Yixing , Chimene-Weiss Jeremy , Mulla Christopher , Isganaitis Elvira , Desmond Jessica , Sanechika Suzuka , Kusuyama Joji , Goodyear Laurie , Shi Xu , Gerszten Robert E. , Wu Lei , Qi Jun , Patti Mary-Elizabeth 
Published: December 2019

SummaryEpigenetic regulation is an important factor in glucose metabolism, but underlying mechanisms remain largely unknown. Here we demonstrated that bromodomain-containing proteins (Brds), transcriptional regulators binding to acetylated histone, are potent modulators of glucose metabolism via the gut-liver farnesoid X receptor (FXR)-fibroblast growth factor 15/19 (FGF15/19) pathway. In vivo inhibition of Brd4 by the inhibitor JQ1 in mice strongly inhibited ileal expression of FGF15, resulting in decreased FGFR4-related signaling, increased glucose production in the liver and hyperglycemia. Adverse metabolic effects of BRD4 inhibition were reversed by overexpression of FGF19, with improvement in hyperglycemia. At a cellular level, we demonstrate that BRD4 binds to the promoter region of FGF19 in human intestinal cells; BRD inhibition by JQ1 reduces binding to the FGF19 promoter and downregulates FGF19 expression. Thus, we identify Brd4 as a novel transcriptional regulator of intestinal FGF15/19 in ileum, and a contributor to hepatic and systemic glucose metabolism.
SingleCellSignalR: Inference of intercellular networks from single-cell transcriptomics
Authors: Cabello-Aguilar Simon , Tack Fabien Kon Sun , Alame Mélissa , Fau Caroline , Lacroix Matthieu , Colinge Jacques 
Published: December 2019

ABSTRACTSingle-cell transcriptomics offers unprecedented opportunities to infer the ligand-receptor interactions underlying cellular networks. We introduce a new, curated ligand-receptor database and a novel regularized score to perform such inferences. For the first time, we try to assess the confidence in predicted ligand-receptor interactions and show that our regularized score outperforms other scoring schemes while controlling false positives. SingleCellSignalR is implemented as an open-access R package accessible to entry-level users and available fromhttps://github.com/SCA-IRCM. Analysis results come in a variety of tabular and graphical formats. For instance, we provide a unique network view integrating all the intercellular interactions, and a function relating receptors to expressed intracellular pathways. A detailed comparison with related tools is conducted. Among various examples, we demonstrate SingleCellSignalR on mouse epidermis data and discover an oriented communication structure from external to basal layers.
Early life glucocorticoid exposure modulates immune function in zebrafish (Danio rerio) larvae
Authors: van den Bos Ruud , Cromwijk Suzanne , Tschigg Katharina , Althuizen Joep , Zethof Jan , Whelan Robert , Flik Gert , Schaaf Marcel 
Published: December 2019

AbstractIn this study we have assessed the effects of increased cortisol levels during early embryonic development on immune function in zebrafish (Danio rerio) larvae. Fertilized eggs were exposed to either a cortisol-containing, a dexamethasone-containing (to stimulate the glucocorticoid receptor selectively) or a control medium for 6 hours post-fertilisation (0-6 hpf). First, we measured baseline expression of a number of immune-related genes (socs3a,mpeg1.1,mpeg1.2andirg1l) 5 days post-fertilisation (dpf) in larvae of the AB and TL strain to assess the effectiveness of our exposure procedure and potential strain differences. Cortisol and dexamethasone strongly up-regulated baseline expression of these genes independent of strain. The next series of experiments were therefore carried out in larvae of the AB strain only. We measured neutrophil/macrophage recruitment following tail fin amputation (performed at 3 dpf) and phenotypical changes as well as survival following LPS-induced sepsis (150 μg/ml; 4-5 dpf). Dexamethasone, but not cortisol, exposure at 0-6 hpf enhanced neutrophil recruitment 4 hours post tail fin amputation. Cortisol and dexamethasone exposure at 0-6 hpf led to a milder phenotype (e.g. less tail fin damage) and enhanced survival following LPS challenge compared to control exposure. Gene-expression analysis showed accompanying differences in transcript abundance oftlr4bb, cxcr4a, myd88,il1β and il10. These data show that early-life exposure to cortisol, which may be considered to be a model or proxy of maternal stress, induces an adaptive response to immune challenges, which seems mediated via the glucocorticoid receptor.
Element content and distribution has limited, tolerance metric dependent, impact on salinity tolerance in cultivated sunflower (Helianthus annuus)
Authors: Temme A.A. , Burns V.A. , Donovan L.A. 
Published: December 2019

AbstractDisruption of ion homeostasis is a major component of salinity stress’s effect on crop yield. In cultivated sunflower prior work revealed a trade-off between vigor and salinity tolerance. Here we determined the association of elemental content/distribution traits with salinity tolerance, both with and without taking this trade-off into account. We grew seedlings of twelve Helianthus annuus genotypes in two treatments (0/100 mM NaCl). Plants were measured for biomass (+allocation), and element content (Na, P, K, Ca, Mg, S, Fe, B, Mn, Cu, Zn) in leaves (young and mature), stem, and roots. Genotype tolerance was determined by the proportional decline in biomass and as the deviation from the expected vigor/tolerance trade-off. Genotype rankings on these metrics were not the same. Elemental content and allocation/distribution were highly correlated both at the plant and organ level. Suggestive associations between tolerance and elemental traits were fewer and weaker than expected and differed by tolerance metric. Given the highly correlated nature of elemental content, it remains difficult to pinpoint specific traits underpinning tolerance. Results do show that taking vigor related trade-offs into account is important in determining traits related to tolerance and that the multivariate nature of associated traits should be considered.
A Registration and Deep Learning Approach to Automated Landmark Detection for Geometric Morphometrics
Authors: Devine Jay , Aponte Jose D. , Katz David C. , Liu Wei , Lo Vercio Lucas D. , Forkert Nils D. , Percival Christopher J. , Hallgrímsson Benedikt 
Published: December 2019

ABSTRACTGeometric morphometrics is the statistical analysis of landmark-based shape variation and its covariation with other variables. Over the past two decades, the gold standard of landmark data acquisition has been manual detection by a single observer. This approach has proven accurate and reliable in small-scale investigations. However, big data initiatives are increasingly common in biology and morphometrics. This requires fast, automated, and standardized data collection. Image registration, or the spatial alignment of images, is a fundamental technique in automatic image analysis that is well-poised for such purposes. Yet, in the few studies that have explored the utility of registration-based landmarks for geometric morphometrics, relatively high or catastrophic labelling errors around anatomical extrema are common. Such errors can result in misleading representations of the mean shape, an underestimation of biological signal, and altered variance-covariance patterns.We combine image registration with a deep and domain-specific neural network to automate and optimize anatomical landmark detection for geometric morphometrics. Using micro-computed tomography images of genetically and morphologically variable mouse skulls, we test our landmarking approach under a variety of registration conditions, including different non-linear deformation frameworks (small vs. large) and atlas strategies (single vs. multi).Compared to landmarks derived from conventional image registration workflows, our optimized landmark data show significant reductions in error at problematic locations (up to 0.63 mm), a 36.4% reduction in average landmark coordinate error, and up to a 45.1% reduction in total landmark distribution error. We achieve significant improvements in estimates of the sample mean shape and variance-covariance structure.For biological imaging datasets and morphometric research questions, our method can eliminate the time and subjectivity of manual landmark detection whilst retaining the biological integrity of these expert annotations.
A receptor-like kinase mediated phosphorylation of Gα protein affects signaling during nodulation
Authors: Choudhury Swarup Roy , Pandey Sona 
Published: December 2019

SUMMARYHeterotrimeric G-proteins, comprised of Gα, Gβ and Gγ subunits regulate signaling in eukaryotes. In metazoans, G-proteins are activated by GPCR-mediated GDP to GTP exchange on Gα; however, the role of receptors in regulating plant G-protein signaling remains equivocal. Mounting evidence points to the involvement of receptor-like kinases (RLKs) in regulating plant G-protein signaling pathways, but their mechanistic details remain limited. We have previously shown that during soybean nodulation, the nod factor receptor 1 (NFR1) interacts with G-protein components and indirectly controls signaling.We explored the direct regulation of G-protein signaling by RLKs using protein-protein interactions, receptor-mediated phosphorylation and the effects of such phosphorylations on soybean nodule formation.Results presented in this study demonstrate a direct, phosphorylation-based regulation of Gα by symbiosis receptor kinase (SymRK). SymRKs interact with and phosphorylate Gα at multiple residues, including two in its active site, which abolishes GTP binding. In addition, phospho-mimetic Gα fails to interact with Gβγ, potentially allowing for constitutive signaling by the freed Gβγ.These results uncover a novel mechanism of G-protein cycle regulation in plants where receptor-mediated phosphorylation of Gα not only affects its activity, but also influences the availability of its signaling partners, thereby exerting a two-pronged control on signaling.
The importance of Indigenous Peoples’ lands for the conservation of terrestrial vertebrates
Authors: O’Bryan Christopher J. , Garnett Stephen T. , Fa John E. , Leiper Ian , Rehbein Jose , Fernández-Llamazares Álvaro , Jackson Micha V. , Jonas Harry D. , Brondizio Eduardo S. , Burgess Neil D. , Robinson Catherine J. , Zander Kerstin K. , Venter Oscar , Watson James E.M. 
Published: December 2019

AbstractIndigenous Peoples’ lands cover over one-quarter of the Earth’s surface, a significant proportion of which is still free from industrial-level human impacts. As a result, Indigenous Peoples’ lands are crucial for the long-term persistence of Earth’s biodiversity and ecosystem services. Yet, information on species composition within Indigenous Peoples’ lands globally remains unknown. Here, we provide the first comprehensive analysis of terrestrial vertebrate composition across mapped Indigenous lands by using distribution range data for 20,328 IUCN-assessed mammal, bird and amphibian species. We estimate that 12,521 species (62%) have ≥10% of their ranges in Indigenous Peoples’ lands, and 3,314 species (16%) have >half of their ranges within these lands. For threatened species assessed, 1,878 (41.5% of all threatened of all threatened mammals, birds and amphibians) occur in Indigenous Peoples’ lands. We also find that 3,989 species (of which 418 are threatened) have ≥10% of their range in Indigenous Peoples’ lands that have low human pressure. Our results are conservative because not all known Indigenous lands are mapped, and this analysis shows how important Indigenous Peoples’ lands are for the successful implementation of international conservation and sustainable development agendas.
Cerebral artery segmentation based on magnetization-prepared two rapid acquisition gradient echo multi-contrast images in 7 Tesla magnetic resonance imaging
Authors: Choi Uk-Su , Kawaguchi Hirokazu , Kida Ikuhiro 
Published: December 2019

AbstractCerebral artery segmentation plays an important role in the direct visualization of the human brain to obtain vascular system information. At ultra-high field magnetic resonance imaging, hyperintensity of the cerebral arteries in T1 weighted (T1w) images could be segmented from brain tissues such as gray and white matter. In this study, we propose an automated method to segment the cerebral arteries using multi-contrast images including T1w images of a magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE) sequence at 7 T. The proposed method employed a seed-based region-growing strategy with the following procedures. (1) Two seed regions were defined by Frangi filtering applied to T1w images and by a simple calculation from multi-contrast images, (2) the two seed regions were combined, (3) the combined seed regions were expanded using a region growing algorithm to acquire the cerebral arteries. Time-of-flight (TOF) images were obtained as a reference to evaluate the proposed method. We successfully performed vessel segmentations from T1w MP2RAGE images, which mostly overlapped with the segmentations from the TOF images. As large arteries can affect the normalization of anatomical images to the standard coordinate space in functional and structural studies, we also investigated the effect of the cerebral arteries on spatial transformation using vessel segmentation by the proposed method. As a result, the T1w image removing the cerebral arteries showed better agreement with the standard atlas compared with the T1w image containing the arteries. Thus, because the proposed method using MP2RAGE images can obtain brain tissue anatomical information as well as cerebral artery information without need for additional acquisitions such as of the TOF sequence, it is useful and time saving for medical diagnosis and functional and structural studies.
Distinct microbial and immune niches of the human colon
Authors: James KR , Gomes T , Elmentaite R , Kumar N , Gulliver EL , King HW , Stares MD , Bareham BR , Ferdinand JR , Petrova VN , Polanski K , Forster SC , Jarvis LB , Suchanek O , Howlett S , James LK , Jones JL , Meyer KB , Clatworthy MR , Saeb-Parsy K , Lawley TD , Teichmann SA 
Published: December 2019

AbstractGastrointestinal microbiota and immune cells interact closely and display regional specificity, but little is known about how these communities differ with location. Here, we simultaneously assess microbiota and single immune cells across the healthy, adult human colon, with paired characterisation of immune cells in the mesenteric lymph nodes, to delineate colonic immune niches at steady-state. We describe distinct T helper cell activation and migration profiles along the colon and characterise the transcriptional adaptation trajectory of T regulatory cells between lymphoid tissue and colon. Finally, we show increasing B cell accumulation, clonal expansion and mutational frequency from caecum to sigmoid colon, and link this to the increasing number of reactive bacterial species.