Potential of Deshi Cattle of India for Dairy Production

There were 1,405 lactation records of 336 cows at the Central Livestock Research- cum-Breeding Station, Haringhata, India from 1958 to 1968 used to estimate the potential dairy merit of Deshi cattle. This breed is native to northeast India and one of the smallest breeds in India (mature females 200 kg and males 250 kg). Averages and standard deviations for milk yield (exclusive of that suckled), age of first calving, calving interval, lactation length, days open, and days dry were 412 ± 178 kg, 44.5 ± 6.8 months, 419 ± 90 days, 264 ± 81 days, 135 ± 86 days, and 139 ± 80 days. Mortality, culling, and retention rates for females from birth to first calving were 24, 27, and 49%. Lactation number, season of calving, and death of calf early in lactation had significant effects on milk yield. Repeatabilities of milk yield, lactation length, calving interval, dry period, and days open were .42, .19, .21, .03, and .23 with corresponding heritabilities .64, .19, .09, .19, and .27. Heritability for age of first calving was .84. Confounding by some environmental effects probably biased heritability estimates upward. Potential genetic improvement of milk yield by mass selection was estimated at .8% per year. Contemporary Jersey X Deshi crosses exceeded Deshi for milk yield, age of first calving, lactation length, calving interval, and days open by +923 kg, -15 months, +41, -84, and -96 days. At least one generation of crossing with European breeds is recommended over mass selection of Deshi

Design aspects and laboratory simulation study of a floating marine fish cage prototype with mooring system

In India, open sea cage culture has been successfully demonstrated and several experimental offshore cages for mariculture were installed along the coast for on-farm demonstration by the Central Marine Fisheries Research Institute, Cochin. In the present study, a model cage was fabricated and tested in a towing tank under different waves and current load conditions. The tension on the mooring chain was measured during the experimental study, besides the towing speed and wave parameters. Based on the experimental data, drag coefficient for the cage net twine was estimated. The tensions in the mooring chain and the cage net twine of the prototype cage were predicted based on the model data. The maximum tension on a single twine of the outer and inner fish net were estimated as 0.15 N and 0.028 N respectively. The force on the net was more than 1.7 times the force on the floating collar and sinker pipe. The tension in the mooring line is mainly due to the force on the net. Further it was observed that the force on the net due to current was 10 times higher than that due to wave. This information will be useful in future while deciding the diameter of the cage, the type of net to be used for cage according to the site where the cage is to be installed

Three dimensional rotational angiography imaging of double aortic arch vascular ring

Three dimensional (3D) rotational angiography is a technique used increasingly for imaging in congenital heart disease. Here the use of this technique for imaging of double aortic arch vascular ring is described and the advantages of this modality. are discussed. 3D rotational angiography is an excellent tool for imaging of various vascular anomalies. It provides high quality accurate images through a quick and safe procedure.peer-reviewe

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

Discovery and validation of small-molecule heat-shock protein 90 inhibitors through multimodality molecular imaging in living subjects

Up-regulation of the folding machinery of the heat-shock protein 90 (Hsp90) chaperone protein is crucial for cancer progression. The two Hsp90 isoforms (α and β) play different roles in response to chemotherapy. To identify isoform-selective inhibitors of Hsp90(α/β)/cochaperone p23 interactions, we developed a dual-luciferase (Renilla and Firefly) reporter system for high-throughput screening (HTS) and monitoring the efficacy of Hsp90 inhibitors in cell culture and live mice. HTS of a 30,176 small-molecule chemical library in cell culture identified a compound, N-(5-methylisoxazol-3-yl)-2-[4-(thiophen-2-yl)-6-(trifluoromethyl)pyrimidin-2-ylthio]acetamide (CP9), that binds to Hsp90(α/β) and displays characteristics of Hsp90 inhibitors, i.e., degradation of Hsp90 client proteins and inhibition of cell proliferation, glucose metabolism, and thymidine kinase activity, in multiple cancer cell lines. The efficacy of CP9 in disrupting Hsp90(α/β)/p23 interactions and cell proliferation in tumor xenografts was evaluated by non-invasive, repetitive Renilla luciferase and Firefly luciferase imaging, respectively. At 38 h posttreatment (80 mg/kg × 3, i.p.), CP9 led to selective disruption of Hsp90α/p23 as compared with Hsp90β/p23 interactions. Small-animal PET/CT in the same cohort of mice showed that CP9 treatment (43 h) led to a 40% decrease in 18F-fluorodeoxyglucose uptake in tumors relative to carrier control-treated mice. However, CP9 did not lead to significant degradation of Hsp90 client proteins in tumors. We performed a structural activity relationship study with 62 analogs of CP9 and identified A17 as the lead compound that outperformed CP9 in inhibiting Hsp90(α/β)/p23 interactions in cell culture. Our efforts demonstrated the power of coupling of HTS with multimodality molecular imaging and led to identification of Hsp90 inhibitors

Resistance to HSP90 inhibition involving loss of MCL1 addiction

YesInhibition of the chaperone heat-shock protein 90 (HSP90) induces apoptosis, and it is a promising anti-cancer strategy. The mechanisms underpinning apoptosis activation following HSP90 inhibition and how they are modified during acquired drug resistance are unknown. We show for the first time that, to induce apoptosis, HSP90 inhibition requires the cooperation of multi BH3-only proteins (BID, BIK, PUMA) and the reciprocal suppression of the pro-survival BCL-2 family member MCL1, which occurs via inhibition of STAT5A. A subset of tumour cell lines exhibit dependence on MCL1 expression for survival and this dependence is also associated with tumour response to HSP90 inhibition. In the acquired resistance setting, MCL1 suppression in response to HSP90 inhibitors is maintained; however, a switch in MCL1 dependence occurs. This can be exploited by the BH3 peptidomimetic ABT737, through non-BCL-2-dependent synthetic lethality