Allelic and genotypic frequencies in polymorphic Booroola fecundity gene and their association with multiple birth and postnatal growth in Chhotanagpuri sheep.

AIM: Chhotanagpuri breed of sheep reared for mutton in Jharkhand, India, having problem of low litter size and body weight. The response of genetic improvement for traits with low heritability through traditional selection method is time-consuming. Therefore, marker-assisted selection based on a polymorphism study of suitable candidate gene can response quickly. Thus, this study was aimed at identification of different allelic and genotypic frequencies of Booroola fecundity (FecB) gene and its association with multiple birth and postnatal growth in Chhotanagpuri sheep. MATERIALS AND METHODS: DNA isolation and gene-specific amplification of FecB gene was performed from blood samples of from 92 Chhotanagpuri lambs maintained under similar feeding and management conditions. Custom nucleotide sequencing and single-strand conformational polymorphism analysis were performed to identify different genotypes with respect to the target gene. Statistical analysis was performed for determination of allelic and genotypic frequencies of FecB gene polymorphisms and its association with multiple birth and postnatal growth of lambs from birth to 52 weeks age. RESULTS: "AA," "AB," and "BB" genotypes were found at locus-1 as it is polymorphic for FecB gene while locus-2 was found to be monomorphic for FecB gene. Higher frequency of "A" allele at locus-1 was found in single born lambs, whereas "B" allele was predominant among multiple born lambs. The lambs having "BB" genotype weighed significantly (p≤0.01) heavier than those of "AB" and "AA" genotype at 52 weeks of age. CONCLUSION: "BB" genotype has emerged as favored genotype for multiple births and better growth indicator. Therefore, homozygous lambs for "B" allele should be selected and utilized in breeding program for better growth rate.

Mir143 expression inversely correlates with nuclear ERK5 immunoreactivity in clinical prostate cancer.

BACKGROUND: Aberrant mitogen/extracellular signal-regulated kinase 5 (MEK5)-extracellular signal-regulated protein kinase 5 (ERK5)-mediated signalling has been implicated in a number of tumour types including prostate cancer (CaP). The mechanism for ERK5 activation in CaP remains to be fully elucidated. Studies have recently implicated the role of microRNA (miRNA) mir143 expression in the regulation of ERK5 expression. METHODS: We utilised a tissue microarray (TMA) of 530 CaP cores from 168 individual patients and stained for both mir143 and ERK5. These TMAs were scored by a combination of observer and automated methods. RESULTS: We observed a strong inverse relation between ERK5 and mir143, which manifested itself most strongly in the subgroup of 417 cores with non-zero mir143 and ERK5 immunoreactivity, or with only one of mir143 or ERK5 being zero (cc=0.2558 and P<0.0001). Mir143 neither correlate with Gleason scores or prostate-specific antigen levels, nor was it a predictor of disease-specific survival on univariate analysis. CONCLUSION: Although the mechanism for ERK5 activation in CaP remains to be fully elucidated, we have further validated the potential role of mir143 in regulating ERK5 levels in the clinical context. In addition, we demonstrate that the automated counting method for nuclear ERK5 is a clinically useful alterative to observer counting method in patient stratification in the context of ERK5 targeting therapy.

Estimation of proximate composition, micronutrients and phytochemical compounds in traditional vegetables from Andaman and Nicobar Islands.

In present study, 10 preferred traditional vegetables from Andaman and Nicobar Islands, India, were analysed for nutritional profiles. Moisture content in their edible parts ranged from 83.43 to 94.78%. Maximum ash content was recorded in Portulaca oleracea, crude protein in Colocasia esculenta, crude fibre in Eryngium foetidum and fat in E. foetidum. Phosphorus was maximum in Ipomea aquatica, potassium in C. esculenta, zinc, calcium and manganese in Centella asiatica, copper in Sauropus androgynous, sodium and iron in P. oleracea, magnesium in Amaranthus viridi and cobalt in C. esculenta. Maximum polyphenol was recorded in Hibiscus sabdariffa, carotenoids in A. viridi, ascorbic acid in Saursops androgynus, anthocyanin in C. esculenta and chlorophyll in S. androgynus. Antioxidant activity was maximum in P. oleracea. Positive correlation was observed between polyphenol and tannin content and also between antioxidant activity and photochemicals. The developed nutritional profiles is being used in health and nutrition related schemes in Islands.

Ras mutation cooperates with ß-catenin activation to drive bladder tumourigenesis.

Mutations in the Ras family of proteins (predominantly in H-Ras) occur in approximately 40% of urothelial cell carcinoma (UCC). However, relatively little is known about subsequent mutations/pathway alterations that allow tumour progression. Indeed, expressing mutant H-Ras within the mouse bladder does not lead to tumour formation, unless this is expressed at high levels. The Wnt signalling pathway is deregulated in approximately 25% of UCC, so we examined if this correlated with the activation of MAPK signalling in human UCC and found a significant correlation. To test the functional significance of this association we examined the impact of combining Ras mutation (H-Ras(Q61L) or K-Ras(G12D)) with an activating ß-catenin mutation within the mouse bladder using Cre-LoxP technology. Although alone, neither Ras mutation nor ß-catenin activation led to UCC (within 12 months), mice carrying both mutations rapidly developed UCC. Mechanistically this was associated with reduced levels of p21 with dependence on the MAPK signalling pathway. Moreover, tumours from these mice were sensitive to MEK inhibition. Importantly, in human UCC there was a negative correlation between levels of p-ERK and p21 suggesting that p21 accumulation may block tumour progression following Ras mutation. Taken together these data definitively show Ras pathway activation strongly cooperates with Wnt signalling to drive UCC in vivo.

ß-Catenin activation synergizes with PTEN loss to cause bladder cancer formation.

Although deregulation of the Wnt signalling pathway has been implicated in urothelial cell carcinoma (UCC), the functional significance is unknown. To test its importance, we have targeted expression of an activated form of ß-catenin to the urothelium of transgenic mice using Cre-Lox technology (UroIICRE(+) ß-catenin(exon3/+)). Expression of this activated form of ß-catenin led to the formation of localized hyperproliferative lesions by 3 months, which did not progress to malignancy. These lesions were characterized by a marked increase of the phosphatase and tensin homologue (PTEN) tumour suppressor protein. This appears to be a direct consequence of activating Wnt signalling in the bladder as conditional deletion of the adenomatous polyposis coli (Apc) gene within the adult bladder led rapidly to coincident ß-catenin and PTEN expression. This PTEN expression blocked proliferation. Next, we combined PTEN deficiency with ß-catenin activation and found that this caused papillary UCC. These tumours had increased pAKT signalling and were dependent on mammalian target of rapamycin (mTOR). Importantly, in human UCC, there was a significant correlation between high levels of ß-catenin and pAKT (and low levels of PTEN). Taken together these data show that deregulated Wnt signalling has a critical role in promoting UCC, and suggests that human UCC that have high levels of Wnt and PI3 kinase signalling may be responsive to mTOR inhibition.

Injections for health-related reasons amongst injecting drug users in New Delhi and Imphal, India.

OBJECTIVES: In many parts of the world where unsafe injection practices in health settings are common, the prevalence of blood-borne viruses (BBVs) is high amongst injecting drug users (IDUs). If IDUs in these settings are receiving injections for health-related reasons, the possibility of amplification of BBV transmission via medical injections exists. The aim of this study is to describe the nature and extent of injections received for health-related reasons amongst IDUs in two Indian cities, New Delhi and Imphal. METHODS: A cross-sectional survey of 200 IDUs was conducted in late 2004. Trained peer outreach workers asked participants about health problems experienced, consultations with healthcare providers and health-related injections received in the preceding 4 weeks. RESULTS: Most participants (99.5%) were male, the average age was 29 years, and the average time since first injection of illicit drugs was 6 years. A total of 133 injections were received for health-related reasons during the preceding 4 weeks by 15% of the participants. The average number of injections was 8.6/participant/year. CONCLUSION: Injections for health-related reasons were commonplace amongst these IDUs. Therefore, amplification of BBV transmission within communities due to unsafe injections is possible and warrants further investigation.

Experimental studies on sodhana of aconite.

Sodhana, a preliminary treatment is known to reduce toxicity, enhance therapeutic merits of drugs and even impart additional pharmacodynamic properties. The present study - Sodhana Aconite, conducted to establish the effect in toxicity chemical changes and comparative pharmacological activity, show definite reduction in the intense cardiotoxic effect in crude Aconite.

Urolithiasis in Manipur (north eastern region of India). Incidence and chemical composition of stones.

The incidence of urolithiasis in Manipur is very high. From hospital records for a period of 7 years and 3 months, it was observed to be 11.6% of all general surgery cases in the General Hospital, Imphal. This is alarmingly high. The social, eating, drinking, and living habits are different among the three major populations in this state. The prevalence was minimal among Tribals. Compared to them the prevalence was about one and one half times higher among Muslims (also called Pangals) and seven times higher among Hindus. Surprisingly, the incidence of renal calcalus was higher in females. One hundred ninety-six stones were studied by wet chemical analysis. Calcium and oxalate were present in all stones. Phosphate was present in 194 stones and uric acid (including urate) was present in 146 stones.