Human Umbilical Cord Blood-Derived CD34+ Cells Reverse Osteoporosis in NOD/SCID Mice by Altering Osteoblastic and Osteoclastic Activities

Osteoporosis is a bone disorder associated with loss of bone mineral density and micro architecture. A balance of osteoblasts and osteoclasts activities maintains bone homeostasis. Increased bone loss due to increased osteoclast and decreased osteoblast activities is considered as an underlying cause of osteoporosis.The cures for osteoporosis are limited, consequently the potential of CD34+ cell therapies is currently being considered. We developed a nanofiber-based expansion technology to obtain adequate numbers of CD34(+) cells isolated from human umbilical cord blood, for therapeutic applications. Herein, we show that CD34(+) cells could be differentiated into osteoblastic lineage, in vitro. Systemically delivered CD34(+) cells home to the bone marrow and significantly improve bone deposition, bone mineral density and bone micro-architecture in osteoporotic mice. The elevated levels of osteocalcin, IL-10, GM-CSF, and decreased levels of MCP-1 in serum parallel the improvements in bone micro-architecture. Furthermore, CD34(+) cells improved osteoblast activity and concurrently impaired osteoclast differentiation, maturation and functionality.These findings demonstrate a novel approach utilizing nanofiber-expanded CD34(+) cells as a therapeutic application for the treatment of osteoporosis

The Arabidopsis thaliana F-box gene HAWAIIAN SKIRT is a new player in the microRNA pathway

In Arabidopsis, the F-box HAWAIIAN SKIRT (HWS) protein is important for organ growth. Loss of function of HWS exhibits pleiotropic phenotypes including sepal fusion. To dissect the HWS role, we EMS-mutagenized hws-1 seeds and screened for mutations that suppress hws-1 associated phenotypes. We identified shs-2 and shs-3 (suppressor of hws-2 and 3) mutants in which the sepal fusion phenotype of hws-1 was suppressed. shs-2 and shs-3 (renamed hst-23/hws-1 and hst-24/hws-1) carry transition mutations that result in premature terminations in the plant homolog of Exportin-5 HASTY (HST), known to be important in miRNA biogenesis, function and transport. Genetic crosses between hws-1 and mutant lines for genes in the miRNA pathway, also suppress the phenotypes associated with HWS loss of function, corroborating epistatic relations between the miRNA pathway genes and HWS. In agreement with these data, accumulation of miRNA is modified in HWS loss or gain of function mutants. Our data propose HWS as a new player in the miRNA pathway, important for plant growth

Global Analysis of the Evolution and Mechanism of Echinocandin Resistance in Candida glabrata

The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia. Whole genome sequencing identified a mutation in the drug target, FKS2, accompanying a major resistance increase, and 8 additional non-synonymous mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance, and associated with a fitness cost that was mitigated with further evolution, observed in vitro and in a murine model of systemic candidemia. A CDC6-A511G(K171E) mutation acquired before FKS2-T1987C(S663P), conferred a small resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S) mutation after FKS2-T1987C(S663P), ameliorated fitness. To discover strategies to abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90 or calcineurin function reduced basal tolerance and resistance. Hsp90 and calcineurin were required for caspofungin-dependent FKS2 induction, providing a mechanism governing echinocandin resistance. A mitochondrial respiration-defective petite mutant in the series revealed that the petite phenotype does not confer echinocandin resistance, but renders strains refractory to synergy between echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected with the petite mutant were sterile, while those infected with the HSP90-repressible strain had reduced fungal burden. We provide the first global view of mutations accompanying the evolution of fungal drug resistance in a human host, implicate the premier compensatory mutation mitigating the cost of echinocandin resistance, and suggest a new mechanism of echinocandin resistance with broad therapeutic potential

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Not AvailableThe aim of the present study is to understand the people’s dependency on Hilsa fishery as their livelihood and to suggest the appropriate measures for its conservation and economic sustainability. The anadromous Hilsa enjoys the highest attraction due to its unique taste, flavour, and culinary properties. About 15-20 per cent of global Hilsa catch is reported by India. Though, a report revealing the decline of Hilsa yield, bountiful harvest of samewas reported in Brahmaputra river of Dhubri district. The primary data of 30 Hilsa fishers have been selected randomly to study the economic status, constraints faced by them, exploitation level. About 40% of respondents involved in both fishing and agriculture and 30% are only engaged in fishing. About 63.33% of fishers owned motorised boats and the gear used for Hilsa fishing is monofilament Gill net with mesh size 7cm to 12 cm. About 63.66% of respondents are found to be perennial fishers. The average Hilsa landing is 6.25 tonnes in one landing centre during the Hilsa season. The economic analysis shows that motorised boat owners have highest B:C ratio (1.7) against traditional fishers (1.4) during Hilsa season. Overcrowding of fishers during Hilsa season, Price fluctuations, lack of weighing system, Small and unhygienic auctioning centre, etc. are some of the constraint faced by the Hilsa fishers. Implementation of Licence system onnumber of boats to be operated, measures for habitat restoration, check on mess size regulationshave to be given focus to make the Hilsa fishery economical and sustainable.Not Availabl

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Not AvailableCharacteristics and freezability of Assam Hill goat semen.Not Availabl

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Not AvailableAssam Hill goat (AHG) is an important goat germplasm found in Assam and its adjoining areas of India. The study was designed with an objective to study the semen characteristics and freezability of AHG buck semen using Tris -Egg yolkCitrate-Fructose diluent. The mean values of fresh semen characteristics in AHG bucks viz., ejaculate volume (ml), initial sperm motility (%), sperm concentration (x106/ml), live sperm (%), sperm abnormality (%), HOST-reacted sperm (%) andintact acrosome (%) recorded were 0.39 ± 0.01, 77.97 ± 0.73, 3201.00 ± 143.78, 83.02 ± 0.65, 7.66 ± 0.73, 66.95 ± 0.74 and 93.34 ± 0.51, respectively. Mean values for post-thaw semen characteristics i.e., sperm motility (%), live sperm (%),HOST-reacted sperm (%) and intact acrosome (%) were 55.39 ± 0.97, 71.01 ± 0.78, 54.77 ± 0.55 and 82.16 ± 0.43, respectively. It can be concluded that AHG bucks donate acceptable quality of semen which can be frozen successfully in Tris-Egg yolk-Citrate-Fructose diluents for using in Artificial Insemination.Not Availabl

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Not AvailableAn experiment was carried out to study the electrophoretic profile of sperm membrane proteins in Assam Hill goat (AHG) bucks and their correlation with fresh semen characteristics. Ejaculates (64) consisting of 8 each from 8 bucks were collected by artificial vagina method. Each ejaculate was split into 2 equal parts. First part was used for fresh semen evaluation and the other part for protein study. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated 20 different protein bands with molecular weight ranging from 10 kDa to 75 kDa. Among the 20 proteins, only 6 proteins bands were consistently present in all 8 bucks (100%). Protein bands with molecular weight 10, 14, 22, 28, 55, 57 and 60 kDa showed significant positive correlation with certain parameters of the fresh semen, while 47 kDa protein band presented negative correlation with fresh semen characteristics in AHG bucks. In conclusion, the proteins showing significant positive correlation with fresh semen characteristics might serve to screen semen of AHG bucks for breeding programmes.Not Availabl