Malignant transformation of colonic epithelial cells by a colon-derived long noncoding RNA.

Recent progress has been made in the identification of protein-coding genes and miRNAs that are expressed in and alter the behavior of colonic epithelia. However, the role of long non-coding RNAs (lncRNAs) in colonic homeostasis is just beginning to be explored. By gene expression profiling of post-mitotic, differentiated tops and proliferative, progenitor-compartment bottoms of microdissected adult mouse colonic crypts, we identified several lncRNAs more highly expressed in crypt bottoms. One identified lncRNA, designated non-coding Nras functional RNA (ncNRFR), resides within the Nras locus but appears to be independent of the Nras coding transcript. Stable overexpression of ncNRFR in non-transformed, conditionally immortalized mouse colonocytes results in malignant transformation, as determined by growth in soft agar and formation of highly invasive tumors in nude mice. Moreover, ncNRFR appears to inhibit the function of the tumor suppressor let-7. These results suggest precise regulation of ncNRFR is necessary for proper cell growth in the colonic crypt, and its misregulation results in neoplastic transformation.

Antimutagenic and antioxidant properties of plumbagin and other naphthoquinones.

The structure-function relationships of the naphthoquinone phytochemicals, plumbagin, juglone, and menadione, have been studied with regard to antimutagenic and antioxidant activities. Antimutagenicity of these compounds was assessed by the Ames test and RNA polymerase B (rpoB)-based rifampicin resistance assay. Antioxidant potential was evaluated by radical scavenging assays and reducing power measurement. Protection of cells and DNA against gamma radiation-induced oxidative damage was assayed by survival analysis and gel electrophoresis profiling, respectively. On the 1,4-naphthoquinone nucleus, plumbagin possesses 5-hydroxyl and 2-methyl functional groups, whereas juglone has only the 5-hydroxyl and menadione only the 2-methyl group. Plumbagin showed strong antimutagenic (against ultraviolet and ethyl methanesulfonate) and antioxidant activities, whereas juglone displayed only strong antimutagenic, and menadione only strong antioxidant activities. Thus, these two functional groups (5-OH/2-CH3) play important roles in the differential bioactivity of naphthoquinones. Escherichia coli, microarray analysis showed upregulation of the genes rep (replication/repair), ybaK (tRNA editing), speE (spermidine synthesis), and yjfC (glutathionyl spermidine synthesis) by plumbagin or juglone, and sodC (superoxide dismutase), xthA (oxidative repair), hycB (electron carrier between hydrogenase 3 and fumarate dehydrogenase), and ligA (formation of phosphodiester bond in DNA) by plumbagin or menadione. Studies with E. coli single-gene knockouts showed that ybaK and speE, reported to prevent mistranslation, are likely to be involved in the antimutagenicity displayed by juglone, and sodC to be involved in the antioxidant activity of menadione.

Transcriptomic analyses of Hand2 transgenic embryos.

In this article, we further provide the data generated for the previously published research article "Specification of jaw identity by the Hand2 transcription factor." To better understand the downstream genes of the basic helix-loop-helix transcription factor Hand2, we generated double-transgenic mice (Hand2 (NC) ) by intercrossing CAG-floxed CAT-Hand2 mice with Wnt1-Cre mice for conditional activation of Hand2 expression in the neural crest. Altered expression of Hand2 induces transformation of the upper jaw to the lower jaw in Hand2 (NC) mutant mice. This data article provides Tables detailing the differentially expressed genes between wild-type and Hand2 (NC) mutant embryos. The raw array data of our transcriptomes as generated using Affymetrix microarrays are available on the NCBI Gene Expression Omnibus (GEO) browser (Reference number GSE75805).

Genome-wide analysis of the heat stress response in Zebu (Sahiwal) cattle.

Environmental-induced hyperthermia compromises animal production with drastic economic consequences to global animal agriculture and jeopardizes animal welfare. Heat stress is a major stressor that occurs as a result of an imbalance between heat production within the body and its dissipation and it affects animals at cellular, molecular and ecological levels. The molecular mechanism underlying the physiology of heat stress in the cattle remains undefined. The present study sought to evaluate mRNA expression profiles in the cattle blood in response to heat stress. In this study we report the genes that were differentially expressed in response to heat stress using global scale genome expression technology (Microarray). Four Sahiwal heifers were exposed to 42°C with 90% humidity for 4h followed by normothermia. Gene expression changes include activation of heat shock transcription factor 1 (HSF1), increased expression of heat shock proteins (HSP) and decreased expression and synthesis of other proteins, immune system activation via extracellular secretion of HSP. A cDNA microarray analysis found 140 transcripts to be up-regulated and 77 down-regulated in the cattle blood after heat treatment (P<0.05). But still a comprehensive explanation for the direction of fold change and the specific genes involved in response to acute heat stress still remains to be explored. These findings may provide insights into the underlying mechanism of physiology of heat stress in cattle. Understanding the biology and mechanisms of heat stress is critical to developing approaches to ameliorate current production issues for improving animal performance and agriculture economics.