Vascular cell-adhesion molecule 1 (VCAM-1) regulates JunB-mediated IL-8/CXCL1 expression and pathological neovascularization.

Vascular adhesion molecules play an important role in various immunological disorders, particularly in cancers. However, little is known regarding the role of these adhesion molecules in proliferative retinopathies. We observed that IL-33 regulates VCAM-1 expression in human retinal endothelial cells and that genetic deletion of IL-33 reduces hypoxia-induced VCAM-1 expression and retinal neovascularization in C57BL/6 mice. We found that VCAM-1 via JunB regulates IL-8 promoter activity and expression in human retinal endothelial cells. In addition, our study outlines the regulatory role of VCAM-1-JunB-IL-8 signaling on retinal endothelial cell sprouting and angiogenesis. Our RNA sequencing results show an induced expression of CXCL1 (a murine functional homolog of IL-8) in the hypoxic retina, and intravitreal injection of VCAM-1 siRNA not only decreases hypoxia-induced VCAM-1-JunB-CXCL1 signaling but also reduces OIR-induced sprouting and retinal neovascularization. These findings suggest that VCAM-1-JunB-IL-8 signaling plays a crucial role in retinal neovascularization, and its antagonism might provide an advanced treatment option for proliferative retinopathies.

A comprehensive review of genomic perspectives of canine diseases as a model to study human disorders.

The domestic dog has been given considerable attention as a system for investigating the genetics of human diseases. Population diversity and breed structure are unique features that make dogs particularly amenable to genetic studies. Dogs show distinguished features of breed-specific homogeneity, which is associated with striking interbreed heterogeneity. This review discusses the significance of studying the genetic maps, genome-wide association studies (GWAS), and usefulness of this species as an animal model. Most canine genetic disorders are similar to those of humans, including inherited, psychiatric, and genetic disorders. In addition to revealing new candidate genes, canine models allow access to experimental resources, such as cells, tissues, and even live animals, for research and intervention purposes.

Le chien domestique a reçu une attention considérable en tant que système d'investigation de la génétique des maladies humaines. La diversité de la population et la structure de la race sont des caractéristiques uniques qui rendent les chiens particulièrement propices aux études génétiques. Les chiens présentent des caractéristiques distinctes d'homogénéité spécifique à la race, qui est associée à une hétérogénéité interraciale frappante. Cette revue traite de l'importance de l'étude des cartes génétiques, des études d'association à l'échelle du génome (GWAS) et de l'utilité de cette espèce en tant que modèle animal. La plupart des troubles génétiques canins sont similaires à ceux des humains, y compris les troubles héréditaires, psychiatriques et génétiques. En plus de révéler de nouveaux gènes candidats, les modèles canins permettent d'accéder à des ressources expérimentales, telles que des cellules, des tissus et même des animaux vivants, à des fins de recherche et d'intervention.(Traduit par Docteur Serge Messier).

Sero-epidemiology of porcine parvovirus, circovirus, and classical swine fever virus infections in India.

Reproductive problems in swine caused by porcine viruses pose a serious threat to the pig industry in developing countries like India. For evaluating the true extent of porcine infections, a total of 1308 representative sera samples were collected from 92 different pig farms covering 8 North-Eastern states and Punjab state of Northern India during a period of 2 years (2011-2013). Sera samples were tested for the presence of antibodies against porcine parvovirus (PPV), porcine circovirus-2 (PCV-2), and classical swine fever virus (CSFV) using commercial enzyme-linked immunosorbent assay (ELISA) kits. In the North-Eastern states, the seroprevalence of CSFV in non-vaccinated animals was 6.30% and that of PCV2 and PPV was 6.28% and 1.24%, respectively. In Punjab, the seroprevalence of CSFV in non-vaccinated animals was 44.44% and seroprevalence of PCV-2 and PPV was 34.07% and 39.10%, respectively. Detection of antibodies against more than one virus revealed that 4.66% animals had co-infection with PCV-2 and PPV, 1.75% with CSF and PPV, 1.98% with CSF and PCV-2, and 1.75% with all the three viruses. The receiver operator characteristics (ROC) curve analysis depicted that piglet mortality, parvovirus, and CSFV were the most important parameters with an AUC value of 0.997, 0.897, and 0.973, respectively. Incidence of single or co-infection with different viruses showed that the occurrence of single infection was significantly more prevalent than co-infection. This study provides useful information to set up future epidemiologic, flock management, and public animal health policies for the prevention and control of PCV-2, PPV, and CSF in India.

MicroRNA expression profiling in PBMCs of Indian water Buffalo (Bubalus bubalis) infected with Brucella and Johne's disease.

BACKGROUND: MicroRNAs play key roles in host-pathogen-interactions and disease pathogenesis. Our aim was to characterize the differentially expressed miRNAs in the blood cells of diseased (Brucellosis-positive, Johne's disease-positive) and healthy- water buffaloes. The pooled small-RNA samples of each group were sequenced on Ion Torrent Personal Genome Machine (PGM) sequencer and the data were analyzed for differential expression. RESULTS: Here we identified 274 known miRNAs with bovine homologs and 36 novel mature-star miRNAs from the sequnces of small RNA libraries. Overall 195 miRNAs were common to all the three groups. Certain miRNAs such as bta-miR-21-5p, -26a, -29a/b, -30d - 103, - 140, - 150, - 191, - 374, - 1434-5p,-1260b, - 2484 and let-7 members were abundantly expressed in diseased groups. Bta-miR-1434-5p, - 188, -200c were up-regulated (> 1.5 folds) while bta-miR-27a-5p, -34b and -2285x were down-regulated (> 100 folds) in Brucellosis group. In Johne's Disease group, only 3 miRNAs (bta-miR-1434-5p, - 2340 and - 2484) were up-regulated (> 1.5 folds). The functional classification of miRNA target genes into gene ontology (GO) terms indicated their involvement in innate immunity and cellular process of disease pathogenesis. Expression profile of four differentially expressed miRNAs (bta-miR-9-5p, - 677, - 331-3p and - 2440) and eight predicted target-genes were validated through reverse transcriptase qPCR. CONCLUSION: This study provides a valuable frame of reference for elucidation of regulatory roles of miRNAs associated with disease pathogenesis in water buffaloes as well as identification of miRNA biomarkers for disease diagnosis and treatment.

Long-term exposures to ethion and endotoxin cause lung inflammation and induce genotoxicity in mice.

Ethion, an organophosphorus pesticide, is used worldwide and has potential for toxicity and inflammation. There are very limited data on the pulmonary and genotoxic effects of ethion especially when the exposure is combined with lipopolysaccharide. Therefore, we used a mouse model to test the hypothesis that prolonged exposure to ethion alone or in conjunction with lipopolysaccharide (LPS) will cause lung inflammation and genotoxicity in a mouse model. Swiss albino (n = 30) were divided into a control (n = 10) and two treatment groups (n = 10; each group). The treatment groups were orally administered ethion (4 or 2 mg/kg/animal/day; n = 10 each) dissolved in corn oil for 90 days. After 90 days of exposure, five animals from each of the groups were challenged with 80 µg Escherichia coli lipopolysaccharide (LPS) intranasally and the remaining five animals with normal saline solution via the same route. Ethion at both dosages induced lung inflammation as indicated by increased (p < 0.05) perivascular and peribronchial accumulation of inflammatory cells along with thickening of the alveolar septal wall. Ethion at 4 mg/kg altered (p < 0.05) the mRNA and protein expression of TLR-9 and IL-1ß in the lungs and induced genotoxicity in blood cells as determined by single cell gel electrophoresis (Comet assay). Further, both dosages of ethion in combination with E. coli LPS caused genotoxicity and increased (p < 0.05) pulmonary expression of TLR-4, TLR-9 and IL-1ß. The data taken together suggest ethion induces lung inflammation and interaction between ethion and LPS increases genotoxicity in blood cells.

Long non-coding RNA: its evolutionary relics and biological implications in mammals: a review.

The central dogma of gene expression propounds that DNA is transcribed to mRNA and finally gets translated into protein. Only 2-3% of the genomic DNA is transcribed to protein-coding mRNA. Interestingly, only a further minuscule part of genomic DNA encodes for long non-coding RNAs (lncRNAs) which are characteristically more than 200 nucleotides long and can be transcribed from both protein-coding (e.g. H19 and TUG1) as well as non-coding DNA by RNA polymerase II. The lncRNAs do not have open reading frames (with some exceptions), 3`-untranslated regions (3'-UTRs) and necessarily these RNAs lack any translation-termination regions, however, these can be spliced, capped and polyadenylated as mRNA molecules. The flexibility of lncRNAs confers them specific 3D-conformations that eventually enable the lncRNAs to interact with proteins, DNA or other RNA molecules via base pairing or by forming networks. The lncRNAs play a major role in gene regulation, cell differentiation, cancer cell invasion and metastasis and chromatin remodeling. Deregulation of lncRNA is also responsible for numerous diseases in mammals. Various studies have revealed their significance as biomarkers for prognosis and diagnosis of cancer. The aim of this review is to overview the salient features, evolution, biogenesis and biological importance of these molecules in the mammalian system.

Y-chromosomal genes affecting male fertility: A review.

The mammalian sex-chromosomes (X and Y) have evolved from autosomes and are involved in sex determination and reproductive traits. The Y-chromosome is the smallest chromosome that consists of 2-3% of the haploid genome and may contain between 70 and 200 genes. The Y-chromosome plays major role in male fertility and is suitable to study the evolutionary relics, speciation, and male infertility and/or subfertility due to its unique features such as long non-recombining region, abundance of repetitive sequences, and holandric inheritance pattern. During evolution, many holandric genes were deleted. The current review discusses the mammalian holandric genes and their functions. The commonly encountered infertility and/or subfertility problems due to point or gross mutation (deletion) of the Y-chromosomal genes have also been discussed. For example, loss or microdeletion of sex-determining region, Y-linked gene results in XY males that exhibit female characteristics, deletion of RNA binding motif, Y-encoded in azoospermic factor b region results in the arrest of spermatogenesis at meiosis. The holandric genes have been covered for associating the mutations with male factor infertility.

Biocomputational characterization and evolutionary analysis of bubaline dicer1 enzyme.

Dicer, an ribonuclease type III type endonuclease, is the key enzyme involved in biogenesis of microRNAs (miRNAs) and small interfering RNAs (siRNAs), and thus plays a critical role in RNA interference through post transcriptional regulation of gene expression. This enzyme has not been well studied in the Indian water buffalo, an important species known for disease resistance and high milk production. In this study, the primary coding sequence (5,778 bp) of bubaline dicer (GenBank: AB969677.1) was determined and the bubaline Dicer1 biocomputationally characterized to determine the phylogenetic signature among higher eukaryotes. The evolutionary tree revealed that all the transcript variants of Dicer1 belonging to a specific species were within the same node and the sequences belonging to primates, rodents and lagomorphs, avians and reptiles formed independent clusters. The bubaline dicer1 is closely related to that of cattle and other ruminants and significantly divergent from dicer of lower species such as tapeworm, sea urchin and fruit fly. Evolutionary divergence analysis conducted using MEGA6 software indicated that dicer has undergone purifying selection over the time. Seventeen divergent sequences, representing each of the families/taxa were selected to study the specific regions of positive vis-à-vis negative selection using different models like single likelihood ancestor counting, fixed effects likelihood, and random effects likelihood of Datamonkey server. Comparative analysis of the domain structure revealed that Dicer1 is conserved across mammalian species while variation both in terms of length of Dicer enzyme and presence or absence of domain is evident in the lower organisms.