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1.
RNA-Seq techniques generate hundreds of millions of short RNA reads using next-generation sequencing (NGS). These RNA reads can be mapped to reference genomes to investigate changes of gene expression but improved procedures for mining large RNA-Seq datasets to extract valuable biological knowledge are needed. RNAMiner—a multi-level bioinformatics protocol and pipeline—has been developed for such datasets. It includes five steps: Mapping RNA-Seq reads to a reference genome, calculating gene expression values, identifying differentially expressed genes, predicting gene functions, and constructing gene regulatory networks. To demonstrate its utility, we applied RNAMiner to datasets generated from Human, Mouse, Arabidopsis thaliana, and Drosophila melanogaster cells, and successfully identified differentially expressed genes, clustered them into cohesive functional groups, and constructed novel gene regulatory networks. The RNAMiner web service is available at http://calla.rnet.missouri.edu/rnaminer/index.html.  相似文献   
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BackgroundThe overall prognosis of colorectal cancer (CRC) patients is unsatisfactory due to cancer metastasis after operation. This study aims to investigate the clinical significance of plasma osteopontin (OPN) levels as minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC patients.MethodsThis randomized study design consists of pre-operative and post-operative plasma samples from a total of 79 patients. We determined plasma levels of OPN by ELISA and examined their correlation with the clinicopathological parameters of CRC patients. The effects of endogenous and exogenous OPN on CRC metastasis were investigated by examination of the effect on regulators of epithelial to messenchymal transition and migration assay.ResultsOur findings demonstrated for the first time the clinical correlation of plasma OPN with metastasis of CRC patients. High post-operative plasma OPN level (>153.02 ng/ml) associated with development of metastasis after curative resection (p<0.001). Moreover, post-operative plasma OPN level correlated with disease-free survival of CRC patients (p=0.009) and was an independent factor for predicting development of metastasis in CRC patients after curative resection (p=0.036). Our in vitro model showed that OPN ectopic expression induced DLD1 cell migration through Snail and Twist1 overexpression and E-cadherin repression, and secretory OPN level enhanced cell migration.ConclusionsThe results of the current study suggest that post-operative plasma OPN correlated with post-operative metastasis, suggesting that it is a potential non-invasive biomarker for the development of future metastasis in CRC patients. In addition, OPN was shown to be involved in the metastatic process and thus inhibition of OPN is a potential therapeutic approach to treat CRC patients.  相似文献   
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Inflammatory bowel disease is a chronic gastrointestinal inflammatory disorder associated with changes in neuropeptide expression and function, including vasoactive intestinal peptide (VIP). VIP regulates intestinal vasomotor and secretomotor function and motility; however, VIP’s role in development and maintenance of colonic epithelial barrier homeostasis is unclear. Using VIP deficient (VIPKO) mice, we investigated VIP’s role in epithelial barrier homeostasis, and susceptibility to colitis. Colonic crypt morphology and epithelial barrier homeostasis were assessed in wildtype (WT) and VIPKO mice, at baseline. Colitic responses were evaluated following dinitrobenzene sulfonic acid (DNBS) or dextran-sodium sulfate (DSS) exposure. Mice were also treated with exogenous VIP. At baseline, VIPKO mice exhibited distorted colonic crypts, defects in epithelial cell proliferation and migration, increased apoptosis, and altered permeability. VIPKO mice also displayed reduced goblet cell numbers, and reduced expression of secreted goblet cell factors mucin 2 and trefoil factor 3. These changes were associated with reduced expression of caudal type homeobox 2 (Cdx2), a master regulator of intestinal function and homeostasis. DNBS and DSS-induced colitis were more severe in VIPKO than WT mice. VIP treatment rescued the phenotype, protecting VIPKO mice against DSS colitis, with results comparable to WT mice. In conclusion, VIP plays a crucial role in the development and maintenance of colonic epithelial barrier integrity under physiological conditions and promotes epithelial repair and homeostasis during colitis.  相似文献   
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Migratory animals present a unique challenge for understanding the consequences of habitat loss on population dynamics because individuals are typically distributed over a series of interconnected breeding and non‐breeding sites (termed migratory network). Using replicated breeding and non‐breeding populations of Drosophila melanogaster and a mathematical model, we investigated three hypotheses to explain how habitat loss influenced the dynamics of populations in networks with different degrees of connectivity between breeding and non‐breeding seasons. We found that habitat loss increased the degree of connectivity in the network and influenced population size at sites that were not directly connected to the site where habitat loss occurred. However, connected networks only buffered global population declines at high levels of habitat loss. Our results demonstrate why knowledge of the patterns of connectivity across a species range is critical for predicting the effects of environmental change and provide empirical evidence for why connected migratory networks are commonly found in nature.  相似文献   
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It is well known that lipids are heterogeneously distributed throughout the cell. Most lipid species are synthesized in the endoplasmic reticulum (ER) and then distributed to different cellular locations in order to create the distinct membrane compositions observed in eukaryotes. However, the mechanisms by which specific lipid species are trafficked to and maintained in specific areas of the cell are poorly understood and constitute an active area of research. Of particular interest is the distribution of phosphatidylserine (PS), an anionic lipid that is enriched in the cytosolic leaflet of the plasma membrane. PS transport occurs by both vesicular and non‐vesicular routes, with members of the oxysterol‐binding protein family (Osh6 and Osh7) recently implicated in the latter route. In addition, the flippase activity of P4‐ATPases helps build PS membrane asymmetry by preferentially translocating PS to the cytosolic leaflet. This asymmetric PS distribution can be used as a signaling device by the regulated activation of scramblases, which rapidly expose PS on the extracellular leaflet and play important roles in blood clotting and apoptosis. This review will discuss recent advances made in the study of phospholipid flippases, scramblases and PS‐specific lipid transfer proteins, as well as how these proteins contribute to subcellular PS distribution.   相似文献   
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Background

In vitro isolated heart preparations are valuable tools for the study of cardiac anatomy and physiology, as well as for preclinical device testing. Such preparations afford investigators a high level of hemodynamic control, independent of host or systemic interactions. Here we hypothesize that recovered human and swine heart-lung blocs can be reanimated using a clear perfusate and elicit viable cardiodynamic and pulmonic function. Further, this approach will facilitate multimodal imaging, which is particularly valuable for the study of both functional anatomy and device-tissue interactions. Five human and 18 swine heart-lung preparations were procured using techniques analogous to those for cardiac transplant. Specimens were then rewarmed and reperfused using modifications of a closed circuit, isolated, beating and ventilated heart-lung preparation. Positive pressure mechanical ventilation was also employed, and epicardial defibrillation was applied to elicit native cardiac sinus rhythm. Videoscopy, fluoroscopy, ultrasound, and infrared imaging were performed for anatomical and experimental study.

Results

Systolic and diastolic left ventricular pressures observed for human and swine specimens were 68/2?±?11/7 and 74/3?±?17/5 mmHg, respectively, with associated native heart rates of 80?±?7 and 96?±?16 beats per minute. High-resolution imaging within functioning human pulmonary vasculature was obtained among other anatomies of interest. Note that one human specimen elicited poor cardiac performance post defibrillation.

Conclusions

We report the first dynamic videoscopic images of the pulmonary vasculature during viable cardiopulmonary function in isolated reanimated heart-lung blocs. This experimental approach provides unique in vitro opportunities for the study of novel medical therapeutics applied to large mammalian, including human, heart-lung specimens.
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