Stepwise activation of the immunoglobulin mu heavy chain gene locus.

The immunoglobulin heavy chain (IgH) gene locus spans several megabases. We show that IgH activation during B-cell differentiation, as measured by histone acetylation, occurs in discrete, independently regulated domains. Initially, a 120 kb domain of germline DNA is hyperacetylated, that extends from D(FL16.1), the 5'-most D(H) gene segment, to the intergenic region between Cmu and Cdelta. Germline V(H) genes were not hyperacetylated at this stage, which accounts for D(H) to J(H) recombination occurring first during B-cell development. Subsequent activation of the V(H) locus happens in at least three differentially regulated domains: an interleukin-7-regulated domain consisting of the 5' J558 family, an intermediate domain and the 3' V(H) genes, which are hyperacetylated in response to DJ(H) recombination. These observations lead to mechanisms for two well-documented phenomena in B-cell ontogeny: the sequential rearrangement of D(H) followed by V(H) gene segments, and the preferential recombination of D(H)-proximal V(H) genes in pro-B cells. We suggest that stepwise activation may be a general mechanism by which large segments of the genome are prepared for expression.     

Association of Endogenous Testosterone with Lipid and Blood Glucose Profiles in Elderly Men with Angiographically Proven Cardiovascular Disease of Nadia and Murshidabad District,West Bengal

Testosterone is commonly known for its role in the regulation of reproductive physiology in men. Epidemiologic studies suggest that endogenous testosterone levels may be implicated in cardiovascular diseases (CVDs). Our study aimed to investigate the relationship between serum total testosterone (TT) levels and lipid profile as well as fasting blood glucose (FBG) levels in male patients ranging from 40 to 70 years old with angiographically proven CVDs from Nadia and Murshidabad district of West Bengal, India. These data were compared with the normal men with no CVD history. We observed a significantly low serum TT levels in CVD patient group compared to the normal group. Among CVD patients, a significant (p < 0.05) negative association was found between serum TT and total cholesterol, triglyceride, low density lipoprotein and very low density lipoprotein, whereas a significant positive correlation (p < 0.05) was found between serum TT and high density lipoprotein. We also observed a highly significant negative correlation between TT and FBG levels in CVD patient group. Thus, in these two densely populated district of West Bengal with poor socio-economic condition, low levels of serum TT in elderly men is associated with CVD that appear together with an atherogenic lipid milieu that may be involved in the pathogenesis of CVD. Results further indicate that low serum TT might have a role in the development of hyperglycemia as evidenced from high FBG level in elderly men.     

Effect of estrogen on biochemical composition of the rat seminiferous tubules

This study concerns the effect of graded doses of estrogen, alone or in combinations with progesterone, on the biochemical composition of the rat seminiferous tubules. Data on the accessory genital organs and pituitary gonadotrophic activity are added. Adult male albino rats received estradiol dipropionate (.1, 1 and 5 mcg/rat) injected intramuscularly, in .1 ml olive oil, daily for 30 days. Animals given the 5 mcg dose were given a 30 day rest period to determine reversibility of effects. In another group estrogen (5 mcg/rat) and progesterone (1 mg/rat) were given concurrently but at different sites for 30 days. Controls received vehicle only. Animals were sacrificed 24 hours after the last injection or rest period and genital organs and the pituitary were removed for study. A progessive reduction in testis weight with dosage was found after estrogen or the combination (p is less that .01). The low dose (.1mcg) had an inconsistent effect on spermatogenesis and endocrine function of the testis. Diameter of the tubules was reduced. Spermatogenesis was arrested in 25% of the tubules at the spermatid of secondary spermatocyte stage. Some normal spermatozoa were seen. Tunica propria was thickened. Some Leydig cells showed atrophy. Vascularity was increased. The median dose (1 mcg) caused spermatogenic arrest at the spermatid or secondary spermatocyte stage but the Sertoli cells were prominent. Only a few spermatozoa were seen. There was some desquamation of seminiferous epithilium. Tubular diameter was still further reduced and the tunica propria thickened. Leydig cells were atrophied. Few spermatozoa were found although 25-30% showed some spermatogenesis. The high dose (5 mcg) caused marked reduction in the diameter of the tubules. Spermatogenesis was arrested at the primary spermatocyte or spermatogonial stage. The tunica popria was much thickened. There was much desquamation and tubular lumeus were filled with debris. The Sertoli cells were hypertrophied. The Leydig cells were atrophied. The tunica albuginea was thickened. There were no spermatozoa. In the recovery group estrogen effects had disappeared, but the tubular diameter remained reduced. Tunica propria was normal. Spermatogenesis progressed to the spermatid stage and in 50% of the tubules many spermatozoa were present. The Leydig cells appeared normal. However spermatozoa were not found in the vas defereus. The histological appearance of the teatis in the estrogen and progesterone group was of the high dose estrogen type but with arrest of spermatogenesis at the spermatid, spermatocye or spermatogonial stage. The Sertoli cells remained hypertrophied. Leydig cells were atrophic. The large blood vessels were engorged. Weight of organs returned almost to normal. Estrogen .1 and 1 mcg had no effect on pituitary weight or gonadotrophin content. The high dose (5 mcg) alone or with progesterone caused a significant increase in pituitary weight (p is less than .0). Estrogen alone (5 mcg) caused a significant decline in pituitary gonadotrophin content (p is less than .0) but the combined therapy had no effect. None of the biochemical constituents of the seminiferous tubules showed any change after injection of .1 mcg of estrogen but 1 mcg dose caused an increase in protein nitrogen, alkaline phosphatase activity and total lipids. The high dose (5 mcg) provoked higher levels.     

Comparison among four triazole fungicides on growth and development of sheath blight of rice pathogen Rhizoctonia solani Kühn AG1-1A

The sheath blight of rice pathogen Rhizoctonia solani Kühn AG1-1A has long been known as a major crisis in global rice production. The present study aimed to compare the efficacy of four triazole fungicides at different doses on the growth and development of R. solani Kühn AG1-1A. Obtained results demonstrated inhibitory effects of all four fungicides on mycelial growth, sclerotia formation and biomass production of R. solani Kühn AG1-1A with significant variation among the treatment doses as well as fungicide molecules (p ≤ 0.05). At the respective EC₅₀ doses all four fungicides inhibited cell wall degrading enzymes viz. invertase, cellulase, polygalacturonase and pectin lyase, of the sheath blight pathogen. The extent of inhibition of the enzymes significantly varied among the fungicides. It is important to note that in spite of having common mode of action, all four triazole fungicides demonstrated significant variation in their fungicidal efficacy on R. solani Kühn AG1-1A.     

Distinct functions of eukaryotic translation initiation factors eIF1A and eIF3 in the formation of the 40 S ribosomal preinitiation complex.

We have used an in vitro translation initiation assay to investigate the requirements for the efficient transfer of Met-tRNAf (as Met-tRNAf.eIF2.GTP ternary complex) to 40 S ribosomal subunits in the absence of mRNA (or an AUG codon) to form the 40 S preinitiation complex. We observed that the 17-kDa initiation factor eIF1A is necessary and sufficient to mediate nearly quantitative transfer of Met-tRNAf to isolated 40 S ribosomal subunits. However, the addition of 60 S ribosomal subunits to the 40 S preinitiation complex formed under these conditions disrupted the 40 S complex resulting in dissociation of Met-tRNAf from the 40 S subunit. When the eIF1A-dependent preinitiation reaction was carried out with 40 S ribosomal subunits that had been preincubated with eIF3, the 40 S preinitiation complex formed included bound eIF3 (40 S.eIF3. Met-tRNAf.eIF2.GTP). In contrast to the complex lacking eIF3, this complex was not disrupted by the addition of 60 S ribosomal subunits. These results suggest that in vivo, both eIF1A and eIF3 are required to form a stable 40 S preinitiation complex, eIF1A catalyzing the transfer of Met-tRNAf.eIF2.GTP to 40 S subunits, and eIF3 stabilizing the resulting complex and preventing its disruption by 60 S ribosomal subunits.     

Matched Case Control Studies with Random Exposure Effects

A method for analysing matched case control data in presence of overdispersion or correlation between observations within matched sets is presented. A generalised linear mixed model approach is adapted to account for overdispersion by allowing random exposure effects. Expressions for the elements of the estimation equation are derived and a strategy for achieving efficiency in computing is discussed. Results from simulation studies and two applications are presented.