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51.
Rahul C Deo Gabriel Musso Murat Tasan Paul Tang Annie Poon Christiana Yuan Janine F Felix Ramachandran S Vasan Rameen Beroukhim Teresa De Marco Pui-Yan Kwok Calum A MacRae Frederick P Roth 《Genome biology》2014,15(12)
Background
Cardiovascular disease (CVD) is the leading cause of death in the developed world. Human genetic studies, including genome-wide sequencing and SNP-array approaches, promise to reveal disease genes and mechanisms representing new therapeutic targets. In practice, however, identification of the actual genes contributing to disease pathogenesis has lagged behind identification of associated loci, thus limiting the clinical benefits.Results
To aid in localizing causal genes, we develop a machine learning approach, Objective Prioritization for Enhanced Novelty (OPEN), which quantitatively prioritizes gene-disease associations based on a diverse group of genomic features. This approach uses only unbiased predictive features and thus is not hampered by a preference towards previously well-characterized genes. We demonstrate success in identifying genetic determinants for CVD-related traits, including cholesterol levels, blood pressure, and conduction system and cardiomyopathy phenotypes. Using OPEN, we prioritize genes, including FLNC, for association with increased left ventricular diameter, which is a defining feature of a prevalent cardiovascular disorder, dilated cardiomyopathy or DCM. Using a zebrafish model, we experimentally validate FLNC and identify a novel FLNC splice-site mutation in a patient with severe DCM.Conclusion
Our approach stands to assist interpretation of large-scale genetic studies without compromising their fundamentally unbiased nature.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0534-8) contains supplementary material, which is available to authorized users. 相似文献52.
53.
Pellicle or temporary cysts of Pyrodinium bahamense var. compressum (Böhm) Steidinger, Tester & F.J.R. Taylor and their role in bloom dynamics have not yet been adequately characterized and understood. We investigated the role of temperature- and nutrient-mediated stress as factors that could induce pellicle formation in batch cultures. Cellular features and their implications for temporary cyst viability were examined using confocal laser scanning microscopy (CLSM). Our data suggest that temperature change is one of the key factors influencing pellicle formation, preserving viability at low temperature (i.e. 13°C). Hypnocysts (resting cysts) were not observed. During pellicle formation, motile cells generally undergo ecdysis, extrusion of cytoplasmic materials and bacteria, compaction of the nucleus and non-motility. The outermost covering of the temporary cysts shows red autofluorescence and it contains lower concentrations of chlorophyll (chl) a and no detectable chl c. The nuclear region is surrounded by transitional red bodies and other unidentified cellular structures. Temporary cysts can immediately revert back to the motile state upon exposure to optimum conditions. This is accompanied by the expansion of the nuclear region, regeneration of the chloroplasts and enlargement of the cell. Developmental changes during reversal of temporary cysts to motile forms were also observed to cause breaks in the cell covering that could serve as sites for bacterial entry. Though observed in vitro, such behaviour may also be occurring in nature especially as a response to drastic short-lived environmental changes. This is the first detailed report on the characteristics of temporary cysts of P. bahamense var. compressum. 相似文献
54.
Enhancing factor (EF), a 14 kDa protein, isolated from mouse small intestines, has been reported from this laboratory. Based on our earlier studies EF has been implicated in cell proliferation. Preliminary immunohistochemical studies have shown EF to be localized in the Paneth cells of small intestines. In this paper we report the tissue distribution of EF using conditions optimized for immunohistochemical staining. In addition, the data are supported by northern blot analysis using a nick translated cDNA probe specific for EF. The results indicate that EF gene is actively transcribed mainly in the intestines. The chief source of synthesis of EF appears to be the Paneth cells located at the base of the crypts of Lieberkühn. 相似文献
55.
Barley plants (Hordeum vulgare L.) received foliar applications of 10?4 M gibberellic acid (GA3) and Kinetin (KN) individually and in combination at one or more of three growth stages: flag leaf appearance (I), ear emergence (II), and the first stage of senescence initiation in the flag leaf (III). Both plant growth regulators (PGR) hastened onset of senescence when sprayed at Stage I and/or Stage II. Treatment at Stage III, either alone or in combination with treatments at the other stages, tended to postpone senescence. Yield components also showed stage-dependent response: Stage I treatment increased the formation of total and bearing tillers, and Stage III treatment improved grain number and weight. However, while GA3 proved more effective than KN, the two together acted antagonistically. 相似文献
56.
Functional interrelationship between TFII‐I and E2F transcription factors at specific cell cycle gene loci 下载免费PDF全文
57.
Zhao-Jun Liu Pirouz Daftarian Letícia Kovalski Bo Wang Runxia Tian Diego M. Castilla Emre Dikici Victor L. Perez Sapna Deo Sylvia Daunert Omaida C. Velazquez 《PloS one》2016,11(4)
Stem cell therapy has emerged as a promising approach for treatment of a number of diseases, including delayed and non-healing wounds. However, targeted systemic delivery of therapeutic cells to the dysfunctional tissues remains one formidable challenge. Herein, we present a targeted nanocarrier-mediated cell delivery method by coating the surface of the cell to be delivered with dendrimer nanocarriers modified with adhesion molecules. Infused nanocarrier-coated cells reach to destination via recognition and association with the counterpart adhesion molecules highly or selectively expressed on the activated endothelium in diseased tissues. Once anchored on the activated endothelium, nanocarriers-coated transporting cells undergo transendothelial migration, extravasation and homing to the targeted tissues to execute their therapeutic role. We now demonstrate feasibility, efficacy and safety of our targeted nanocarrier for delivery of bone marrow cells (BMC) to cutaneous wound tissues and grafted corneas and its advantages over conventional BMC transplantation in mouse models for wound healing and neovascularization. This versatile platform is suited for targeted systemic delivery of virtually any type of therapeutic cell. 相似文献
58.
59.
Arora Shiyana Venugopalan Aishwarya Dharavath Ravinder Naik Bishnoi Mahendra Kondepudi Kanthi Kiran Chopra Kanwaljit 《Neurochemical research》2021,46(5):1177-1187
Neurochemical Research - Growing experimental evidences have suggested the reciprocal correlation between sleep deprivation and pain. Inflammation and oxidative stress are among the key pathways... 相似文献
60.
Epidemiological evidence demonstrates positive correlation between environmental and occupational arsenic or fluoride exposure
and risk to various cardio-respiratory disorders. Arsenic-exposure has been associated with atherosclerosis, hypertension,
cerebrovascular diseases, ischemic heart disease, and peripheral vascular disorders, whereas Fluoride-exposure manifests cardiac
irregularities and low blood pressure (BP). Present study aims to study the combined effects of these toxicants on various
cardio-respiratory variables in male rats. Single intravenous (i.v.) dose of arsenic (1, 5, 10 mg/kg) or fluoride (5, 10,
20, 36.5 mg/kg) either alone or in combination were administered. Individual exposure to arsenic or fluoride led to a significant
depletion of mean arterial pressure, heart rate (HR), respiration rate and neuromuscular (NM) transmission in a dose-dependent
manner. These changes were accompanied by increased levels of blood reactive oxygen species (ROS) and decreased glutathione
(GSH) concentrations. An increase in the blood acetyl cholinesterase (AChE) activity was observed in both arsenic or fluoride
exposed rats. These changes were significantly more pronounced in arsenic-exposed animals than in fluoride. During combined
exposure to arsenic (5 mg/kg) + fluoride (20 mg/kg) or arsenic (10 mg/kg) + fluoride (36.5 mg/kg) the toxic effects were more
pronounced compared to individual toxicities of arsenic or fluoride alone. However, combined exposure to arsenic (5 mg/kg) + fluoride
(36.5 mg/kg) resulted in antagonistic effects on variables suggestive of altered cardio-respiratory function and oxidative
stress. The results from the present study suggest that arsenic or fluoride individually demonstrate cardio-respiratory failure
at all doses whereas during combination exposure these toxins show variable toxicities; both synergistic and antagonistic
effects depending upon the dose. Moreover, it may be concluded that arsenic and/or fluoride cardio-respiratory toxicity may
be mediated via oxidative stress. However, these results are new in the discipline thus requires further exploration. 相似文献