bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing the Effect of Vascular Structure on Laser Speckle Contrast Imagining
Authors: Jafari Chakameh Z. , Sullender Colin T. , Miller David R. , Mihelic Samuel A. , Dunn Andrew K. 
Published: June 2020

AbstractLaser Speckle Contrast Imaging (LSCI) is a powerful tool for non-invasive, real-time imaging of blood flow in tissue. However, the effect of tissue geometry on the form of the electric field autocorrelation function and speckle contrast values is yet to be investigated. In this paper, we present an ultrafast forward model for simulating a speckle contrast image with the ability to rapidly update the image for a desired illumination pattern and flow perturbation. We demonstrate the first simulated speckle contrast image and compare it against experimental results. We simulate three mouse-specific cerebral cortex decorrelation time images and implement three different schemes for analyzing the effects of homogenization of vascular structure on correlation decay times. Our results indicate that dissolving structure and assuming homogeneous geometry creates up to ∼ 10x shift in the correlation function decay times and alters its form compared with the case for which the exact geometry is simulated. These effects are more pronounced for point illumination and detection imaging schemes. Further analysis indicates that correlated multiple scattering events, on average, account for 50% of all dynamic scattering events for a detector over a vessel region and 31% that of a detector over parenchyma region, highlighting the significance of accurate modeling of the three-dimensional vascular geometry for accurate blood flow estimates.
Aneuploid cells activate NF-κB to promote their immune clearance by NK cells
Authors: Wang Ruoxi W. , Viganò Sonia , Ben-David Uri , Amon Angelika , Santaguida Stefano 
Published: June 2020

SummaryThe immune system plays a major role in the protection against cancer. Identifying and characterizing the pathways mediating this immune surveillance is thus critical for understanding how cancer cells are recognized and eliminated. We previously found that untransformed cells that had undergone senescence due to highly abnormal karyotypes are eliminated by Natural Killer (NK) cellsin vitro. Here we show that this is also true for aneuploid untransformed cells that had not lost their ability to proliferate. Their elimination by NK cells, like that of aneuploid senescent cells, is predominantly mediated by non-cell autonomous mechanisms. Our data further indicate that NF-κB signaling in aneuploid cells is central to eliciting this immune response. Inactivating NF-κB abolishes NK-cell mediated clearance in aneuploid cellsin vitro. In cancer cell lines, NF-κB signaling correlates with degree of aneuploidy, raising the possibility that aneuploidy-induced immune recognition is partially retained in cancer.
Scalable learning of interpretable rules for the dynamic microbiome domain
Authors: Maringanti Venkata Suhas , Bucci Vanni , Gerber Georg K. 
Published: June 2020

AbstractThe microbiome, which is inherently dynamic, plays essential roles in human physiology and its disruption has been implicated in numerous human diseases. Linking dynamic changes in the microbiome to the status of the human host is an important problem, which is complicated by limitations and complexities of the data. Model interpretability is key in the microbiome field, as practitioners seek to derive testable biological hypotheses from data or develop diagnostic tests that can be understood by clinicians. Interpretable structure must take into account domainspecific information key to biologists and clinicians including evolutionary relationships (phylogeny) and dynamic behavior of the microbiome. A Bayesian model was previously developed in the field, which uses Markov Chain Monte Carlo inference to learn human interpretable rules for classifying the status of the human host based on microbiome time-series data, but that approach is not scalable to increasingly large microbiome datasets being produced. We present a new fully-differentiable model that also learns human-interpretable rules for the same classification task, but in an end-to-end gradient-descent based framework. We validate the performance of our model on human microbiome data sets and demonstrate our approach has similar predictive performance to the fully Bayesian method, while running orders-of-magnitude faster and moreover learning a larger set of rules, thus providing additional biological insight into the effects of diet and environment on the microbiome.
POMC-specific knockdown of Tril reduces body adiposity and increases hypothalamic leptin responsiveness
Authors: Moura-Assis Alexandre , Nogueira Pedro A. , de-Lima-Junior Jose C. , Simabuco Fernando M. , Gaspar Joana M. , Donato Jose , Velloso Licio A. 
Published: June 2020

AbstractIn a public dataset of transcripts differentially expressed in selected neuronal subpopulations of the arcuate nucleus, we identified TLR4-interactor with leucine-rich repeats (Tril) as a potential candidate for mediating the harmful effects of a high-fat diet in proopiomelanocortin (POMC) neurons. The non-cell-specific inhibition of Tril in the arcuate nucleus resulted in reduced hypothalamic inflammation, protection against diet-induced obesity associated with increased whole-body energy expenditure and increased systemic glucose tolerance. The inhibition of Tril, specifically in POMC neurons, resulted in a trend for protection against diet-induced obesity, increased energy expenditure and increased hypothalamic sensitivity to leptin. Thus, Tril emerges as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental diet-induced obesity.
Accessible, Reproducible, and Scalable Machine Learning for Biomedicine
Authors: Gu Qiang , Kumar Anup , Bray Simon , Creason Allison , Khanteymoori Alireza , Jalili Vahid , Grüning Björn , Goecks Jeremy 
Published: June 2020

AbstractSupervised machine learning, where the goal is to predict labels of new instances by training on labeled data, has become an essential tool in biomedical data analysis. To make supervised machine learning more accessible to biomedical scientists, we have developed Galaxy-ML, a platform that enables scientists to perform end-to-end reproducible machine learning analyses at large scale using only a web browser. Galaxy-ML extends Galaxy, a biomedical computational workbench used by tens of thousands of scientists across the world, with a machine learning tool suite that supports end-to-end analysis.
Deep ancestral introgression shapes evolutionary history of dragonflies and damselflies
Authors: Suvorov Anton , Scornavacca Celine , Fujimoto M. Stanley , Bodily Paul , Clement Mark , Crandall Keith A. , Whiting Michael F. , Schrider Daniel R. , Bybee Seth M. 
Published: June 2020

SUMMARYIntrogression is arguably one of the most important biological processes in the evolution of groups of related species, affecting at least 10% of the extant species in the animal kingdom. Introgression reduces genetic divergence between species, and in some cases can be highly beneficial, facilitating rapid adaptation to ever-changing environmental pressures. Introgression also significantly impacts inference of phylogenetic species relationships where a strictly binary tree model cannot adequately explain reticulate net-like species relationships. Here we use phylogenomic approaches to understand patterns of introgression along the evolutionary history of a unique, non-model insect system: dragonflies and damselflies (Odonata). We demonstrate that introgression is a pervasive evolutionary force across various taxonomic levels within Odonata. In particular, we show that the morphologically “intermediate” species of Anisozygoptera (one of the three primary suborders within Odonata besides Zygoptera and Anisoptera), which retain phenotypic characteristics of the other two suborders, experienced high levels of introgression likely coming from zygopteran genomes. Additionally, we found evidence for multiple cases of deep inter-superfamilial ancestral introgression.
Anα-cyanostilbene derivative for the enhanced detection and imaging of amyloid fibril aggregates
Authors: Marzano Nicholas. R , Wray Kelly M , Johnston Caitlin L , Paudel Bishnu P , Hong Yuning , van Oijen Antoine , Ecroyd Heath 
Published: June 2020

AbstractThe aggregation of proteins into amyloid fibrils has been implicated in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Benzothiazole dyes such as Thioflavin T (ThT) are well characterised and widely used fluorescent probes for monitoring amyloid fibril formation. However, existing dyes lack sensitivity and specificity to oligomeric intermediates formed during fibril formation. In this work we describe the use of an α-cyanostilbene derivative with aggregation-induced emission properties (called ASCP) as a fluorescent probe for the detection of amyloid fibrils. Similar to ThT, ASCP is fluorogenic in the presence of amyloid fibrils and upon binding and excitation at 460 nm produces a red-shifted emission with a large Stokes shift of 145 nm. ASCP has a higher binding affinity to fibrillar α-synuclein than ThT and likely shares the same binding sites to amyloid fibrils. Importantly, ASCP was found to also be fluorogenic in the presence of amorphous aggregates and can detect oligomeric species formed early during aggregation. Moreover, ASCP can be used to visualise fibrils via Total Internal Reflection Fluorescence (TIRF) microscopy and, due to its large Stokes shift, simultaneously monitor the fluorescence emission of other labelled proteins following excitation with the same laser used to excite ASCP. Consequently, ASCP possesses enhanced and unique spectral characteristics compared to ThT that make it a promising alternative for thein vitrostudy of amyloid fibrils and the mechanisms by which they form.
Problem drinking before and during the COVID-19 crisis in US and UK adults: Evidence from two population-based longitudinal studies
Authors: Daly Michael , Robinson Eric 
Published: June 2020

AbstractBackgroundThe impact of the COVID-19 crisis on potentially harmful alcohol consumption is unclear.AimsTo test whether the prevalence of problem drinking has changed from before to during the COVID-19 crisis in the US and UK.Design/SettingWe examined nationally representative longitudinal data on how problem drinking has changed from pre-pandemic levels among adults in the US (N=7,327; Understanding America Study) and UK (N=12,594; UK Household Longitudinal Study).MethodsIn the US, we examined rates of consuming alcohol ≥ 4 times in the past week at baseline (March, 2020) and across four waves of follow-up (April-May, 2020). In the UK we assessed the prevalence of consuming alcohol ≥ 4 times per week and weekly heavy episodic drinking using the AUDIT-C at baseline (2017-2019) and during the COVID-19 lockdown (April, 2020). We also tested whether there were specific groups at greater risk of increased problem drinking during the pandemic.ResultsAmong US adults, there was a statistically significant increase in the percentage of participants reporting drinking alcohol ≥ 4 times a week which rose significantly from 11.7% to 17.9% (53% increase, p < .001) as the COVID-19 crisis developed in the US. Among UK adults, the percentage of participants reporting drinking ≥ 4 times a week increased significantly from 14.2% to 23% (62% increase, p < .001) and heavy episodic drinking at least weekly increased significantly from 9.7% to 16.6% (71% increase, p < .001) when compared to pre-COVID-19 lockdown levels. Trends were similar across population demographics, although those aged under 50 years and higher income groups displayed the largest increases.ConclusionsThe COVID-19 crisis has been associated with substantial increases in problematic drinking in both US and UK adults.
Teach, and teach and teach: does the average citizen use masks correctly during daily activities? Results from an observational study with more than 12,000 participants
Authors: Stanislau Affonso de Araújo Evaldo , Henriques Amaral Fatima Maria Bernardes , Park Dongmin , Ceraldi Cameira Ana Paola , da Cunha Murilo Augustinho Muniz , Karl Evelyn Gutierrez , Henderson Sheila J. 
Published: June 2020

AbstractCOVID-19 is a new disease with no treatment and no vaccine so far. The pandemic is still growing in many areas. Among the core measures to prevent disease spread is the use of face masks. We observed 12,588 people in five Brazilian cities within the Baixada Santista metropolitan area. Even though this is densely populated region and heavily impacted by COVID-19 with a high risk population, only 45.1% of the observed population wore in face masks in a correct way, and another 15.5% simply did not use masks at all. The remainder used masks incorrectly, which is evidence of the worst scenario of people believing that they are protected when they are not. This is among the first studies, to the best of our knowledge, that measures real life compliance with face masks during this COVID-19 pandemic. It is our conclusion that it is paramount to first control the virus before allowing people back in the streets. We should not assume that people will wear masks properly. Equally important is to instruct and sensitize people on how to use face masks and why it is important.
Immunochemical analysis of the integrin expression in retinal pigment epithelial cells
Authors: Heller Janosch P , Heintz Tristan G , Kwok Jessica CF , Martin Keith R , Fawcett James W 
Published: June 2020

AbstractRetinal pigment epithelial (RPE) cells have been used in disease modelling and transplantation studies in retinal diseases. Several types of RPE cells have been trialed, ranging from primary cells and immortalized cell lines to stem cell-derived RPE cells. During aging and in disease, the extracellular environment of the RPE cells changes, interfering with RPE cell adhesion. We hypothesize that this could be a key problem in transplantation studies that have reported lack of adhesion and survival of the transplanted RPE cells. Integrins are essential for the proper function of the RPE, mediating adhesion to Bruch’s membrane, and the binding and subsequent phagocytosis of photoreceptor outer segments. Variability that has been found in clinical trials might be due to the variability of cell types used and their expression profiles of surface molecules. Here, we set out to analyze integrin expression in primary rat RPE cells and in the human cell line ARPE-19 using immunochemistry. We found that both cell types express integrins to varying degrees. After long-term culturing, ARPE-19 cells resemble mature RPE cells, and increase integrin expression. We hence argue that it is important to test the properties of these cells prior to transplantation to avoid failure of adhesion and to facilitate correct function.
IKBIP is a novel EMT-related biomarker and predicts poor survival in glioma
Authors: Yang Ying , Wang Jin , Xu Shihai , Lv Wen , Shi Fei , Shan Aijun 
Published: June 2020

AbstractPurposeI kappa B-interacting protein (IKBIP) in cancer has rarely been reported. This study aimed at investigating its expression pattern and biological function in brain glioma at transcriptional level.MethodsWe selected 301 glioma patients with microarray data from CGGA database and 697 glioma patients with RNAseq data from TCGA database. Transcriptome data and clinical data of 998 samples were analyzed. Statistical analysis and figure generating were performed with R language.ResultsWe found that IKBIP expression showed positive correlation with WHO grade of glioma. IKBIP was increased in IDH wildtype and mesenchymal molecular subtype of glioma. Gene ontology analysis demonstrated that IKBIP was profoundly associated with extracellular matrix organization, cell-substrate adhesion and response to wounding in both pan-glioma and glioblastoma. Subsequent GSEA analysis revealed that IKBIP was particularly correlated with epithelial-to-mesenchymal transition (EMT). To further elucidate the relationship between IKBIP and EMT, we performed GSVA analysis to screen the EMT-related signaling pathways, and found that IKBIP expression was significantly associated with PI3K/AKT, hypoxia and TGF-β pathway. Moreover, IKBIP expression was found to be synergistic with key biomarkers of EMT, especially with N-cadherin, vimentin, snail, slug and TWIST1. Finally, higher IKBIP indicated significantly shorter survival for glioma patients.ConclusionsIKBIP was associated with more aggressive phenotypes of gliomas.Furthermore, IKBIP was significantly involved in EMT and could serve as an independent prognosticator in glioma.
Atlas and developmental dynamics of mouse DNase I hypersensitive sites
Authors: Breeze Charles E. , Lazar John , Mercer Tim , Halow Jessica , Washington Ida , Lee Kristen , Ibarrientos Sean , Castillo Andres , Neri Fidencio , Haugen Eric , Rynes Eric , Reynolds Alex , Bates Daniel , Diegel Morgan , Dunn Douglas , Kaul Rajinder , Sandstrom Richard , Meuleman Wouter , Bender M.A. , Groudine Mark , Stamatoyannopoulos John A. 
Published: June 2020

AbstractEarly mammalian development is orchestrated by genome-encoded regulatory elements populated by a changing complement of regulatory factors, creating a dynamic chromatin landscape. To define the spatiotemporal organization of regulatory DNA landscapes during mouse development and maturation, we generated nucleotide-resolution DNA accessibility maps from 15 tissues sampled at 9 intervals spanning post-conception day 9.5 through early adult, and integrated these with 41 adult-stage DNase-seq profiles to create a global atlas of mouse regulatory DNA. Collectively, we delineated >1.8 million DNase I hypersensitive sites (DHSs), with the vast majority displaying temporal and tissue-selective patterning. Here we show that tissue regulatory DNA compartments show sharp embryonic-to-fetal transitions characterized by wholesale turnover of DHSs and progressive domination by a diminishing number of transcription factors. We show further that aligning mouse and human fetal development on a regulatory axis exposes disease-associated variation enriched in early intervals lacking human samples. Our results provide an expansive new resource for decoding mammalian developmental regulatory programs.
3-Dimensional Magnetic Resonance Imaging of the Freely Moving Human Eye
Authors: Franceschiello Benedetta , Di Sopra Lorenzo , Minier Astrid , Ionta Silvio , Zeugin David , Notter Michael P. , Bastiaansen Jessica A.M. , Jorge João , Yerly Jérôme , Stuber Matthias , Murray Micah M. 
Published: June 2020

AbstractEye motion is a major confound for magnetic resonance imaging (MRI) in neuroscience or ophthalmology. Currently, solutions toward eye stabilisation include participants fixating or administration of paralytics/anaesthetics. We developed a novel MRI protocol for acquiring 3-dimensional images while the eye freely moves. Eye motion serves as the basis for image reconstruction, rather than an impediment. We fully reconstruct videos of the moving eye and head. We quantitatively validate data quality with millimetre resolution in two ways for individual participants. First, eye position based on reconstructed images correlated with simultaneous eye-tracking. Second, the reconstructed images preserve anatomical properties; the eye’s axial length measured from MRI images matched that obtained with ocular biometry. The technique operates on a standard clinical setup, without necessitating specialized hardware, facilitating wide deployment. In clinical practice, we anticipate that this may help reduce burden on both patients and infrastructure, by integrating multiple varieties of assessments into a single comprehensive session. More generally, our protocol is a harbinger for removing the necessity of fixation, thereby opening new opportunities for ethologically-valid, naturalistic paradigms, the inclusion of populations typically unable to stably fixate, and increased translational research such as in awake animals whose eye movements constitute an accessible behavioural readout.Author contributionsB.F., L.D.S., M.S., and M.M.M. conceptualised the problem. B.F. and L.D.S. developed, implemented, and tested the protocol. A.M. provided optometry assessments and assisted with eye movement analysis. S.I., D.Z., and M.P.N. assisted with installation of the eye-tracking system within the MRI scanner. J.A.M.B., J.J. and J.Y. contributed with the MRI sequences and compressed sensing framework. B.F., L.D.S. and M.M.M. drafted the manuscript, and all authors contributed to internal review.Competing interestsB.F., L.D.S., J.A.M.B., J.Y., M.S., and M.M.M. declare the following competing financial interest: a patent application for the protocol described in this manuscript has been filed (patent application: EP19160832). A.M., S.I., D.Z., M.P.N. and J.J. declare no competing financial interests.
Revisiting the intrageneric structure of the genusPseudomonaswith complete whole genome sequence information: Insights into Diversity and Host-related Genetic Determinants
Authors: Yi Buqing , Dalpke Alexander H. 
Published: June 2020

AbstractPseudomonasspp. exhibit considerable differences in host specificity and virulence. MostPseudomonasspecies were isolated exclusively from environmental sources, ranging from soil to plants, but somePseudomonasspecies have been detected from versatile sources, including both human host and environmental sources. Understanding genome variations that generate the tremendous diversity inPseudomonasbiology is important in controlling the incidence of infections. With a data set of 704Pseudomonascomplete whole genome sequences representing 186 species,Pseudomonasintrageneric structure was investigated by hierarchical clustering based on average nucleotide identity, and by phylogeny analysis based on concatenated core-gene alignment. Further comparative functional analyses indicated thatPseudomonasspecies only living in natural habitats lack multiple functions that are important in the regulation of bacterial pathogenesis, indicating the possession of these functions might be characteristic ofPseudomonashuman pathogens. Moreover, we have performed pangenome based homogeneity analyses, and detected genes with conserved structures but diversified functions across thePseudomonasgenomes, suggesting these genes play a role in driving diversity. In summary, this study provided insights into the dynamics of genome diversity and host-related genetic determinants inPseudomonas, which might help the development of more targeted antibiotics for the treatment ofPseudomonasinfections.
Prions induce minor genome-wide translational changes in neurons compared to glia
Authors: Scheckel Claudia , Imeri Marigona , Schwarz Petra , Aguzzi Adriano 
Published: June 2020

AbstractPrion diseases are caused by PrPSc, a self-replicating pathologically misfolded protein that exerts toxicity predominantly in the brain. The administration of PrPSccauses a robust, reproducible and specific disease manifestation. Here we have applied a combination of translating ribosome affinity purification and ribosome profiling to identify biologically relevant prion-induced changes during disease progression in a cell-type specific and genome-wide manner. Terminally diseased mice with severe neurological symptoms showed extensive alterations in astrocytes and microglia. Surprisingly, we detected only minor changes in the translational profiles of neurons. Prion-induced alterations in glia overlapped with those identified in other neurodegenerative diseases, suggesting that similar events occur in a broad spectrum of pathologies. Our results suggest that aberrant translation within glia may suffice to cause severe neurological symptoms and may even be the primary driver of prion disease.