bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of cell-type-specific risk-CpG sites in epigenome-wide association studies
Authors: Luo Xiangyu , Yang Can , Wei Yingying 
Published: July 2019

AbstractIn epigenome-wide association studies, the measured signals for each sample are a mixture of methylation profiles from different cell types. Current approaches to the association detection claim whether a cytosine-phosphate-guanine (CpG) site is associated with the phenotype or not at aggregate level and can suffer from low statistical power. Here, we propose a statistical method, HIgh REsolution (HIRE), which not only improves the power of association detection at aggregate level as compared to the existing methods but also enables the detection of risk-CpG sites for individual cell types.
Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma
Authors: Mourikis Thanos P. , Benedetti Lorena , Foxall Elizabeth , Temelkovski Damjan , Nulsen Joel , Perner Juliane , Cereda Matteo , Lagergren Jesper , Howell Michael , Yau Christopher , Fitzgerald Rebecca C. , Scaffidi Paola ,   The Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) Consortium, Noorani Ayesha , Edwards Paul A. W. , Elliott Rachael Fels , Grehan Nicola , Nutzinger Barbara , Hughes Caitriona , Fidziukiewicz Elwira , Bornschein Jan , MacRae Shona , Crawte Jason , Northrop Alex , Contino Gianmarco , Li Xiaodun , de la Rue Rachel , Katz-Summercorn Annalise , Abbas Sujath , Loureda Daniel , O’Donovan Maria , Miremadi Ahmad , Malhotra Shalini , Tripathi Monika , Tavaré Simon , Lynch Andy G. , Eldridge Matthew , Secrier Maria , Bower Lawrence , Devonshire Ginny , Jammula Sriganesh , Davies Jim , Crichton Charles , Carroll Nick , Safranek Peter , Hindmarsh Andrew , Sujendran Vijayendran , Hayes Stephen J. , Ang Yeng , Sharrocks Andrew , Preston Shaun R. , Oakes Sarah , Bagwan Izhar , Save Vicki , Skipworth Richard J. E. , Hupp Ted R. , Robert O’Neill J. , Tucker Olga , Beggs Andrew , Taniere Philippe , Puig Sonia , Underwood Timothy J. , Walker Robert C. , Grace Ben L. , Barr Hugh , Shepherd Neil , Old Oliver , Gossage James , Davies Andrew , Chang Fuju , Zylstra Janine , Mahadeva Ula , Goh Vicky , Sanders Grant , Berrisford Richard , Harden Catherine , Lewis Mike , Cheong Ed , Kumar Bhaskar , Parsons Simon L. , Soomro Irshad , Kaye Philip , Saunders John , Lovat Laurence , Haidry Rehan , Igali Laszlo , Scott Michael , Sothi Sharmila , Suortamo Sari , Lishman Suzy , Hanna George B. , Peters Christopher J. , Moorthy Krishna , Grabowska Anna , Turkington Richard , McManus Damian , Khoo David , Fickling Will , Ciccarelli Francesca D. 
Published: July 2019

AbstractThe identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy.
Optogenetic control of Bacillus subtilis gene expression
Authors: Castillo-Hair Sebastian M. , Baerman Elliot A. , Fujita Masaya , Igoshin Oleg A. , Tabor Jeffrey J. 
Published: July 2019

AbstractThe Gram-positive bacteriumBacillus subtilisexhibits complex spatial and temporal gene expression signals. Although optogenetic tools are ideal for studying such processes, none has been engineered for this organism. Here, we port a cyanobacterial light sensor pathway comprising the green/red photoreversible two-component system CcaSR, two metabolic enzymes for production of the chromophore phycocyanobilin (PCB), and an output promoter to control transcription of a gene of interest intoB. subtilis. Following an initial non-functional design, we optimize expression of pathway genes, enhance PCB production via a translational fusion of the biosynthetic enzymes, engineer a strong chimeric output promoter, and increase dynamic range with a miniaturized photosensor kinase. Our final design exhibits over 70-fold activation and rapid response dynamics, making it well-suited to studying a wide range of gene regulatory processes. In addition, the synthetic biology methods we develop to port this pathway should makeB. subtilis easier to engineer in the future.
Landscape of transcriptomic interactions between breast cancer and its microenvironment
Authors: Fox Natalie S. , Haider Syed , Harris Adrian L. , Boutros Paul C. 
Published: July 2019

AbstractSolid tumours comprise mixtures of tumour cells (TCs) and tumour-adjacent cells (TACs), and the intricate interconnections between these diverse populations shape the tumour’s microenvironment. Despite this complexity, clinical genomic profiling is typically performed from bulk samples, without distinguishing TCs from TACs. To better understand TC–TAC interactions, we computationally distinguish their transcriptomes in 1780 primary breast tumours. We show that TC and TAC mRNA abundances are divergently associated with clinical phenotypes, including tumour subtypes and patient survival. These differences reflect distinct responses of TCs and TACs to specific somatic driver mutations, particularly TP53. These data further elucidate how the molecular interplay between breast tumours and their microenvironment drives aggressive tumour phenotypes.
Laser-sculptured ultrathin transition metal carbide layers for energy storage and energy harvesting applications
Authors: Zang Xining , Jian Cuiying , Zhu Taishan , Fan Zheng , Wang Wanlin , Wei Minsong , Li Buxuan , Follmar Diaz Mateo , Ashby Paul , Lu Zhengmao , Chu Yao , Wang Zizhao , Ding Xinrui , Xie Yingxi , Chen Juhong , Hohman J. Nathan , Sanghadasa Mohan , Grossman Jeffrey C. , Lin Liwei 
Published: July 2019

AbstractUltrathin transition metal carbides with high capacity, high surface area, and high conductivity are a promising family of materials for applications from energy storage to catalysis. However, large-scale, cost-effective, and precursor-free methods to prepare ultrathin carbides are lacking. Here, we demonstrate a direct pattern method to manufacture ultrathin carbides (MoCx, WCx, and CoCx) on versatile substrates using a CO2 laser. The laser-sculptured polycrystalline carbides (macroporous, ~10–20 nm wall thickness, ~10 nm crystallinity) show high energy storage capability, hierarchical porous structure, and higher thermal resilience than MXenes and other laser-ablated carbon materials. A flexible supercapacitor made of MoCx demonstrates a wide temperature range (−50 to 300 °C). Furthermore, the sculptured microstructures endow the carbide network with enhanced visible light absorption, providing high solar energy harvesting efficiency (~72 %) for steam generation. The laser-based, scalable, resilient, and low-cost manufacturing process presents an approach for construction of carbides and their subsequent applications.
Weakly supervised classification of aortic valve malformations using unlabeled cardiac MRI sequences
Authors: Fries Jason A. , Varma Paroma , Chen Vincent S. , Xiao Ke , Tejeda Heliodoro , Saha Priyanka , Dunnmon Jared , Chubb Henry , Maskatia Shiraz , Fiterau Madalina , Delp Scott , Ashley Euan , Ré Christopher , Priest James R. 
Published: July 2019

AbstractBiomedical repositories such as the UK Biobank provide increasing access to prospectively collected cardiac imaging, however these data are unlabeled, which creates barriers to their use in supervised machine learning. We develop a weakly supervised deep learning model for classification of aortic valve malformations using up to 4,000 unlabeled cardiac MRI sequences. Instead of requiring highly curated training data, weak supervision relies on noisy heuristics defined by domain experts to programmatically generate large-scale, imperfect training labels. For aortic valve classification, models trained with imperfect labels substantially outperform a supervised model trained on hand-labeled MRIs. In an orthogonal validation experiment using health outcomes data, our model identifies individuals with a 1.8-fold increase in risk of a major adverse cardiac event. This work formalizes a deep learning baseline for aortic valve classification and outlines a general strategy for using weak supervision to train machine learning models using unlabeled medical images at scale.
Fourier ring correlation simplifies image restoration in fluorescence microscopy
Authors: Koho Sami , Tortarolo Giorgio , Castello Marco , Deguchi Takahiro , Diaspro Alberto , Vicidomini Giuseppe 
Published: July 2019

AbstractFourier ring correlation (FRC) has recently gained popularity among fluorescence microscopists as a straightforward and objective method to measure the effective image resolution. While the knowledge of the numeric resolution value is helpful in e.g., interpreting imaging results, much more practical use can be made of FRC analysis—in this article we propose blind image restoration methods enabled by it. We apply FRC to perform image de-noising by frequency domain filtering. We propose novel blind linear and non-linear image deconvolution methods that use FRC to estimate the effective point-spread-function, directly from the images. We show how FRC can be used as a powerful metric to observe the progress of iterative deconvolution. We also address two important limitations in FRC that may be of more general interest: how to make FRC work with single images (within certain practical limits) and with three-dimensional images with highly anisotropic resolution.
Sticky collisions of ultracold RbCs molecules
Authors: Gregory Philip D. , Frye Matthew D. , Blackmore Jacob A. , Bridge Elizabeth M. , Sawant Rahul , Hutson Jeremy M. , Cornish Simon L. 
Published: July 2019

AbstractUnderstanding and controlling collisions is crucial to the burgeoning field of ultracold molecules. All experiments so far have observed fast loss of molecules from the trap. However, the dominant mechanism for collisional loss is not well understood when there are no allowed 2-body loss processes. Here we experimentally investigate collisional losses of nonreactive ultracold 87Rb133Cs molecules, and compare our findings with the sticky collision hypothesis that pairs of molecules form long-lived collision complexes. We demonstrate that loss of molecules occupying their rotational and hyperfine ground state is best described by second-order rate equations, consistent with the expectation for complex-mediated collisions, but that the rate is lower than the limit of universal loss. The loss is insensitive to magnetic field but increases for excited rotational states. We demonstrate that dipolar effects lead to significantly faster loss for an incoherent mixture of rotational states.
SHB1 and CCA1 interaction desensitizes light responses and enhances thermomorphogenesis
Authors: Sun Qingbin , Wang Shulei , Xu Gang , Kang Xiaojun , Zhang Min , Ni Min 
Published: July 2019

AbstractLight and temperature are two important environmental signals to plants. After dawn, photo-activated phytochromes translocate into the nucleus and interact with a family of negative basic helix-loop-helix PIF regulators. Subsequent phosphorylation and degradation of PIFs triggers a series of photomorphogenic responses. However, excess light can damage the photosynthetic apparatus and leads to photoinhibition. Plants acclimate to a balanced state of photomorphogenesis to avoid photodamage. Here, we show that upregulation of PIF4 expression by SHB1 and CCA1 under red light represents a desensitization step. After dawn, the highly expressed circadian clock protein CCA1 brings circadian signals to the regulatory region of the PIF4 signaling hub. Recruitment of SHB1 by CCA1 modulates red light-specific induction of PIF4 expression thus integrating circadian and light signals. As noon approaches and light intensity and ambient temperature tend to increase, the SHB1–CCA1 interaction sustains PIF4 expression to trigger thermomorphogenic responses to changing light and temperature conditions.
Rapid fabrication of reinforced and cell-laden vascular grafts structurally inspired by human coronary arteries
Authors: Akentjew Tamara L. , Terraza Claudia , Suazo Cristian , Maksimcuka Jekaterina , Wilkens Camila A. , Vargas Francisco , Zavala Gabriela , Ocaña Macarena , Enrione Javier , García-Herrera Claudio M. , Valenzuela Loreto M. , Blaker Jonny J. , Khoury Maroun , Acevedo Juan Pablo 
Published: July 2019

AbstractDesign strategies for small diameter vascular grafts are converging toward native-inspired tissue engineered grafts. A new automated technology is presented that combines a dip-spinning methodology for depositioning concentric cell-laden hydrogel layers, with an adapted solution blow spinning (SBS) device for intercalated placement of aligned reinforcement nanofibres. This additive manufacture approach allows the assembly of bio-inspired structural configurations of concentric cell patterns with fibres at specific angles and wavy arrangements. The middle and outer layers were tuned to structurally mimic the media and adventitia layers of native arteries, enabling the fabrication of small bore grafts that exhibit the J-shape mechanical response and compliance of human coronary arteries. This scalable automated system can fabricate cellularized multilayer grafts within 30 min. Grafts were evaluated by hemocompatibility studies and a preliminary in vivo carotid rabbit model. The dip-spinning-SBS technology generates constructs with native mechanical properties and cell-derived biological activities, critical for clinical bypass applications.
Reward signaling in a recurrent circuit of dopaminergic neurons and peptidergic Kenyon cells
Authors: Lyutova Radostina , Selcho Mareike , Pfeuffer Maximilian , Segebarth Dennis , Habenstein Jens , Rohwedder Astrid , Frantzmann Felix , Wegener Christian , Thum Andreas S. , Pauls Dennis 
Published: July 2019

AbstractDopaminergic neurons in the brain of the Drosophila larva play a key role in mediating reward information to the mushroom bodies during appetitive olfactory learning and memory. Using optogenetic activation of Kenyon cells we provide evidence that recurrent signaling exists between Kenyon cells and dopaminergic neurons of the primary protocerebral anterior (pPAM) cluster. Optogenetic activation of Kenyon cells paired with odor stimulation is sufficient to induce appetitive memory. Simultaneous impairment of the dopaminergic pPAM neurons abolishes appetitive memory expression. Thus, we argue that dopaminergic pPAM neurons mediate reward information to the Kenyon cells, and in turn receive feedback from Kenyon cells. We further show that this feedback signaling is dependent on short neuropeptide F, but not on acetylcholine known to be important for odor-shock memories in adult flies. Our data suggest that recurrent signaling routes within the larval mushroom body circuitry may represent a mechanism subserving memory stabilization.
Natural course of fatty liver in 36,195 South Korean adults
Authors: Sung Ki-Chul , Lee Mi-Yeon , Lee Jong-Young , Lee Sung-Ho , Kim Yong-Bum , Song Won-Jun , Huh Ji-Hye , Park Jin-Sun , Shin Jeong-Hun , Seo Mi Hae , Kim Seong-Hwan , Kim Sun H. 
Published: July 2019

AbstractNonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease, and yet the natural course remains unclear. Study population included 36,195 individuals who participated in a health-screening program and diagnosed with fatty liver by abdominal ultrasound. Participants were provided written information regarding fatty liver and advised to make lifestyle changes. Ultrasound was repeated after at least 6 months. After a mean follow up of 4.9 years (±3.4), 19.6% resolved their fatty liver. Individuals who resolved were more likely female (22.9% vs. 12.3%), thinner (body mass index [BMI], 25.2 ± 2.7 vs. 26 ± 2.7), and with lower HOMA-IR (1.4 vs. 1.7) (P .70.001). Decrease in BMI predicted resolution of fatty liver with 42% of those in the top quartile of BMI decline resolving compared with 5.7% in the lowest quartile (odds ratio [OR] (95% confidence interval [CI]) 15.65 (14.13–17.34), P < 0.001)). Baseline HOMA-IR also predicted resolution with those in the top quartile (most insulin resistant) being least likely to resolve (12%) vs. those in the lowest quartile (25%) (OR 0.36 [0.31–0.42], P < 0.001). Fatty liver disease is persistent. Individuals with higher degree of insulin resistance are also the most likely to have persistent steatosis at follow up.
Environmentally-Controlled Near Infrared Spectroscopic Imaging of Bone Water
Authors: Ailavajhala Ramyasri , Oswald Jack , Rajapakse Chamith S. , Pleshko Nancy 
Published: July 2019

AbstractWe have designed an environmentally-controlled chamber for near infrared spectroscopic imaging (NIRSI) to monitor changes in cortical bone water content, an emerging biomarker related to bone quality assessment. The chamber is required to ensure repeatable spectroscopic measurements of tissues without the influence of atmospheric moisture. A calibration curve to predict gravimetric water content from human cadaveric cortical bone was created using NIRSI data obtained at six different lyophilization time points. Partial least squares (PLS) models successfully predicted bone water content that ranged from 0–10% (R = 0.96, p < 0.05, root mean square error of prediction (RMSEP) = 7.39%), as well as in the physiologic range of 4–10% of wet tissue weight (R = 0.87, p < 0.05, RMSEP = 14.5%). Similar results were obtained with univariate and bivariate regression models for prediction of water in the 0–10% range. Further, we identified two new NIR bone absorbances, at 6560 cm−1 and 6688 cm−1, associated with water and collagen respectively. Such data will be useful in pre-clinical studies that investigate changes in bone quality with disease, aging and with therapeutic use.
SDHC epi-mutation testing in gastrointestinal stromal tumours and related tumours in clinical practice
Authors: Casey Ruth T. , ten Hoopen Rogier , Ochoa Eguzkine , Challis Benjamin G. , Whitworth James , Smith Philip S. , Martin Jose Ezequiel , Clark Graeme R. , Rodger Fay , Maranian Mel , Allinson Kieren , Madhu Basetti , Roberts Thomas , Campos Luis , Anstee Joanne , Park Soo-Mi , Marker Alison , Watts Colin , Bulusu Venkata R. , Giger Olivier T. , Maher Eamonn R. 
Published: July 2019

AbstractThe enzyme succinate dehydrogenase (SDH) functions in the citric acid cycle and loss of function predisposes to the development of phaeochromocytoma/paraganglioma (PPGL), wild type gastrointestinal stromal tumour (wtGIST) and renal cell carcinoma. SDH-deficient tumours are most commonly associated with a germline SDH subunit gene (SDHA/B/C/D) mutation but can also be associated with epigenetic silencing of the SDHC gene. However, clinical diagnostic testing for an SDHC epimutation is not widely available. The objective of this study was to investigate the indications for and the optimum diagnostic pathways for the detection of SDHC epimutations in clinical practice. SDHC promoter methylation analysis of 32 paraffin embedded tumours (including 15 GIST and 17 PPGL) was performed using a pyrosequencing technique and correlated with SDHC gene expression. SDHC promoter methylation was identified in 6 (18.7%) tumours. All 6 SDHC epimutation cases presented with SDH deficient wtGIST and 3/6 cases had multiple primary tumours. No case of constitutional SDHC promoter hypermethylation was detected. Whole genome sequencing of germline DNA from three wtGIST cases with an SDHC epimutation, did not reveal any causative sequence anomalies. Herein, we recommend a diagnostic workflow for the detection of an SDHC epimutation in a service setting.
Sperm transfer through hyper-elongated beetle penises – morphology and theoretical approaches
Authors: Matsumura Yoko , Michels Jan , Rajabi Hamed , Shimozawa Tateo , Gorb Stanislav N. 
Published: July 2019

AbstractMany insects possess a hyper-elongated intromittent organ with a diameter of only a few micrometers. Using morphological and theoretical approaches, we investigated the biomechanics of sperm transfer through such organs by calculating (1) how far and how fast sperm could fill in the penis by capillary action, (2) how much capillary pressure is generated in the penis, and (3) how much pressure is needed to pump sperm out of the penis. The results enabled us to propose the following hypotheses: (1) penile filling basically occurs by capillary action, and (2) sperm transport to females occurs by contracting the sperm pump muscles or by active propulsion of spermatozoa. Potential experimental approaches to test these hypotheses are discussed.
Anti-inflammatory nutrition with high protein attenuates cardiac and skeletal muscle alterations in a pulmonary arterial hypertension model
Authors: Vinke Paulien , Bowen T. Scott , Boekschoten Mark. V. , Witkamp Renger F. , Adams Volker , van Norren Klaske 
Published: July 2019

AbstractPulmonary arterial hypertension (PAH) is characterized by remodelling of the pulmonary arteries and right ventricle (RV), which leads to functional decline of cardiac and skeletal muscle. This study investigated the effects of a multi-targeted nutritional intervention with extra protein, leucine, fish oil and oligosaccharides on cardiac and skeletal muscle in PAH. PAH was induced in female C57BL/6 mice by weekly injections of monocrotaline (MCT) for 8 weeks. Control diet (sham and MCT group) and isocaloric nutritional intervention (MCT + NI) were administered. Compared to sham, MCT mice increased heart weight by 7%, RV thickness by 13% and fibrosis by 60% (all p < 0.05) and these were attenuated in MCT + NI mice. Microarray and qRT-PCR analysis of RV confirmed effects on fibrotic pathways. Skeletal muscle fiber atrophy was induced (P < 0.05) by 22% in MCT compared to sham mice, but prevented in MCT + NI group. Our findings show that a multi-targeted nutritional intervention attenuated detrimental alterations to both cardiac and skeletal muscle in a mouse model of PAH, which provides directions for future therapeutic strategies targeting functional decline of both tissues.