Ovarian hormones after postnatal day 20 reduce neuron number in the rat primary visual cortex

Previous work from our lab has documented a sex difference in neuron number in the binocular region of the adult rat primary visual cortex (Oc1B), with males having 19% more neurons than females. In the present study, the role of developmental steroid hormones in the formation of this difference was explored. Male and female rats underwent neonatal hormone manipulation (female + testosterone or dihydrotestosterone; male + flutamide) followed by gonadectomy on postnatal day 20. Animals that did not undergo hormone manipulation were either gonadectomized or sham operated at day 20. Neuron number was quantified in the monocular (Oc1M) and binocular (Oc1B) subfields of the adult rat primary visual cortex using the optical disector technique. As adults, day 20 gonadectomized females, as well as females + testosterone and females + dihydrotestosterone, had significantly more neurons than intact females. There was no difference in neuron number between postnatal day 20 gonadectomized males, males + flutamide, and intact males. Also, intact males had significantly more neurons than intact females in both in Oc1M and Oc1B. It appears that ovarian steroids after day 20 are the primary cause of the lower number of neurons in the primary visual cortex of the female rat.     

Factors affecting the distribution of vascular plants, springtails, butterflies and birds on small tropical islands

Aim

The primary objective of our study was to examine the factors affecting the distribution of vascular plants, springtails, butterflies and birds on small tropical islands to understand how different groups of organisms with distinct biological traits respond to biogeographical variables, such as island area.

Location

The Republic of Singapore (103°50′E, 1°20′N) located at the southern tip of Peninsular Malaysia.

Methods

Seventeen islands were surveyed for vascular plants, springtails, butterflies and birds. Correlation analysis, simple linear and multiple regression analyses and the nestedness index were used to test the hypotheses that (1) area is the best predictor of species/genus richness at both the community and specific/generic levels; (2) there is no correlation between population density and island area; and (3) species/genera are distributed as nested subsets.

Results

Area was the most significant factor in determining the island distribution of springtails, butterflies and birds at both the community and specific/generic levels, although there were disparate responses to the biogeographical variables between the three taxonomic groups, as well as between common species within each group. Individual species displayed disparate responses to biogeographical variables, suggesting that patterns of distribution at the community level may not be a good indicator of the population dynamics of individual species/genera. Plant species richness did not show any correlation with any of the tested variables. Population densities of springtails, butterflies and birds were positively correlated with area, contradicting the assumption of the equilibrium theory of island biogeography that population density of island species is independent of area. Population densities of plants showed no correlation with any of the tested biogeographical variables. Vascular plant, springtail, butterfly and bird communities on the islands showed significant patterns of nestedness, indicating there may be species/genus‐specific responses to biogeographical variables.

Main conclusions

We conclude that although area was the most important factor affecting the island distribution of springtails, butterflies and birds, conservation planning must take into consideration how target taxonomic groups respond to biogeographical variables, instead of relying on general principles (e.g. those derived from the equilibrium theory). On a local scale, in order to preserve the island biodiversity of Singapore, the highest priority should be given to preserving the larger islands (e.g. Pulau Ubin) which not only have higher numbers of species, but also species that are absent on smaller islands.

     

Protective effect of N-acetylcysteine in isoniazid induced hepatic injury in growing rats

Status of oxidative/antioxidative profile was the mechanistic approach to inumerate the nature of protection by N-acetylcysteine (NAC) in isoniazid (INH) exposed experimental animals. Analysis of lipid peroxidation, thiol levels, cytochrome P450, superoxide dismutase (SOD), catalase, glutathione peroxidase, reductase and transferase were estimated in liver along with the body and liver weight of animals and histological observations. Isoniazid exposure to animals resulted in no change in body and liver weights. Thiols, lipid peroxidation, catalase, SOD glutathione peroxidase, reductase, transferase and cytochrome P450 levels were altered with INH exposure. Supplementation of NAC with INH protected the animals against hepatotoxic reactions by minimizing the free radical induced tissue injury and overall maintenance of the endogenous scavengers of free radicals.     

Evaluation of genetic differentiation in Bos indicus cattle breeds from Marathwada region of India using microsatellite polymorphism

Elucidation of genetic variability and genetic relationship among breeds has direct relevance with the issues of sustainable use of domestic animal genetic resources. In the present study, genetic polymorphism was evaluated using 22 microsatellite loci in unrelated samples of Red Kandhari and Deoni cattle breeds inhabiting the same geographical area of Marathwada region in Maharashtra state (western India). This work was mainly aimed at assessing the current genetic diversity to understand whether the two zebu populations in question are genetically differentiated. A total of 164 alleles were detected with an average of 5.82 and 5.86 alleles per locus (MNA) in Red Kandhari and Deoni breeds, respectively. The estimated mean observed (Ho) and expected (He) heterozygosity were 0.47 and 0.64 in Red Kandhari vs. 0.57 and 0.69 in Deoni cattle, respectively, demonstrating considerable level of genetic variation in both the populations. Mean estimates of F statistics were: F (FIT) = 0.315 +/- 0.035, f(FIS) = 0.231 +/- 0.031, theta(FST) = 0.110 +/- 0.022, with both the breeds exhibiting significant deficit of heterozygotes (FIS = 0.179 in Deoni; 0.278 in Red Kandhari). The multilocus FST values implied that 11.0% of the total genetic variation corresponds to breed and were statistically greater than zero for the two populations, suggesting population division. The evaluation of exact test also indicated that allele frequencies across all the loci differed significantly (P < 0.001) between two zebu breeds, further supporting population differentiation. Different genetic distance measures showed considerable levels of distances between the two cattle breeds (0.318 = Nei's standard DS; 0.250 = Nei's DA; 0.416 = Cavalli-Sforza and Edwards's Dc; 0.164 = Reynold's, and 2.64 = Delta mu square (dmicro)2. Bayesian statistical approach to assign each individual to the population also supported considerable differentiation between the two cattle breeds, possibly reflecting the limited gene flow between the two Marthwada cattle populations. The existence of cohesive breeding structure of both the breeds was further substantiated by allele-sharing distance measures (DAS) among individual animals. The results of this study thus revealed that the two Bos indicus breeds sharing the common breeding tracts are genetically differentiated enough as separate breeds.     

Rac1 function is required for Src-induced transformation. Evidence of a role for Tiam1 and Vav2 in Rac activation by Src

The proto-oncogene c-Src has been implicated in the development and progression of a number of human cancers including those of colon and breast. Accumulating evidence indicates that activated alleles of Src may induce cell transformation through Ras-ERK-dependent and -independent pathways. Here we show that Rac1 activity is strongly elevated in Src-transformed cells and that this small G protein is a critical component of the pathway connecting oncogenic Src with cell transformation. We further show that Vav2 and the ubiquitously expressed Rac1 guanine nucleotide exchange factor Tiam1 are phosphorylated in tyrosine residues in cells transfected with active and oncogenic Src. Moreover, phosphorylation of Tiam1 in cells treated with pervanadate, a potent inhibitor of tyrosine phosphatases, was partially inhibited by the Src inhibitor SU6656. Using truncated mutants of Tiam1, we demonstrate that multiple sites can be tyrosine-phosphorylated by Src. Furthermore, Tiam1 cooperated with Src to induce activation of Rac1 in vivo and the formation of membrane ruffles. Similarly, activation of JNK and the c-jun promoter by Src were also potently increased by Tiam1. Together, these results suggest that Vav2 and Tiam1 may act as downstream effectors of Src, thereby regulating Rac1-dependent pathways that participate in Src-induced cell transformation.     

Studies on organomercury(II) complexes of isoniazid

A number of organomercury(II) complexes involving isoniazid (I), of the type RHgCl(L)(II) [R = phenyl(C6H5), o-hydroxyphenyl (o-HOC6H4), p-hydroxyphenyl (p-HOC6H4), p-acetoxyphenyl (p-AcOC6H4), 2-furyl (2-C4H3O); L = isoniazid] have been synthesized and characterized. Conductance measurements indicate that the complexes are nonelectrolytes. From IR and UV studies, it is concluded that isoniazid acts as a bidentate ligand, coordinating through hydrazinic nitrogen and carbonyl oxygen. 1H and 13C NMR support the stoichiometry of the complexes. From fluoroscence studies a number of photochemical parameters have been elucidated. For the C6H5HgCl(L), p-HOC6H4HgCl(L), and p-AcOC6H4HgCl(L) complexes, thermogravimetric studies have been carried out and relevant kinetic and thermodynamic parameters for thermal degradation have been enumerated. In addition, the fragmentation pattern of the complexes has been analyzed on the basis of mass spectra. The C6H5HgCl(L) and p-HOC6H4HgCl(L) complexes have been screened for tuberculosis activity.     

Efficient regeneration of Brassica oleracea hypocotyl protoplasts and high frequency genetic transformation by direct DNA uptake

Summary Efficient regeneration (80%) and high frequency genetic transformation (10–33%) were achieved by culturing protoplasts isolated from hypocotyl tissues of six day old Brassica oleracea seedlings and by subjecting these protoplasts to PEG mediated direct plasmid uptake. Three different plasmid vectors carrying marker genes for resistance to methotrexate (dhfr), hygromycin (hpt) and phosphinotricin (bar) were constructed and used for transformation. Large number of normal, fertile transformants were obtained with vectors carrying hpt and bar genes. No transformants could be regenerated for resistance to methotrexate as it severely suppressed shoot differentiation.Abbreviations bar/PAT bialaphos resistance gene/phosphinotricin acetyltransferase - 2,4-D 2,4-di-chlorophenoxyacetic acid - dhfr/DHPR dihydrofolate reductase gene/enzyme - gus/GUS -glucuronidase gene/enzyme - hpt/HPT hygromycin phosphotransferase gene/enzyme - Kn kinetin - PEG polyethylene glycol - RH relative humidity     

Meta-analysis of sex differences in gene expression in schizophrenia

Schizophrenia is a severe psychiatric disorder which influences around 1 % of the worldwide population. Differences between male and female patients with schizophrenia have been noted. There is an earlier age of onset in males compared with females with this diagnosis, and in addition, there are differences in symptom profiles between the sexes. The underlying molecular mechanism of sex difference remains unclear. Here we present a comprehensive analysis to reveal the sex differences in gene expression in schizophrenia with stringent statistics criteria. We compiled a data set consisting of 89 male controls, 90 male schizophrenia patients, 35 female controls and 32 female schizophrenia patients from six independent studies of the prefrontal cortex (PFC) in postmortem brain. When we tested for a sex by diagnosis interaction on gene expression, 23 genes were up-regulated and 23 genes were down-regulated in the male group (q-value?<?0.05), several genes are related to energy metabolism, while 4 genes are located on sex chromosome. No genes were statistically significant in the female group when multiple testing correction were conducted (q-value <0.05), most likely due to the small sample size. Our protocol and results from the male group provide a starting point for identifying the underlying different mechanism between male and female schizophrenia patients.     

Regulation of nitric oxide production by murine peritoneal macrophages treated in vitro with chemokine monocyte chemoattractant protein 1.

Monocyte chemoattractant protein 1 (MCP-1) is an important mediator of monocyte/macrophage recruitment and activation at the sites of chronic inflammation and neoplasia. In the current study, the role of nitrogen monoxide (NO) in the activation of murine peritoneal macrophages to the tumoricidal state in response to in vitro MCP-1 treatment and the regulatory mechanisms involved therein were investigated. Murine peritoneal macrophages upon activation with MCP-1 showed a dose- and time-dependent production of NO together with increased tumoricidal activity against P815 mastocytoma cells. N-monomethyl-l-arginine (L-NMMA), a specific inhibitor of the l-arginine pathway, inhibited the MCP-1-induced NO secretion and generation of macrophage-mediated tumoricidal activity against P815 (NO-sensitive, TNF-resistant) cells but not the L929 (TNF-sensitive, NO-resistant) cells. These results indicated l-arginine-dependent production of NO to be one of the effector mechanisms contributing to the tumoricidal activity of MCP-1-treated macrophages. Supporting this fact, expression of iNOS mRNA was also detected in the murine peritoneal macrophages upon treatment with MCP-1. Investigating the signal transduction pathway responsible for the NO production by the MCP-1-activated murine peritoneal macrophages, it was observed that the pharmacological inhibitors wortmannin, H-7 (1-(5-isoquinoline sulfonyl)-2-methyl piperazine dihydrochloride), and PD98059 blocked the MCP-1-induced NO production, suggesting the probable involvement of phosphoinositol-3-kinase, protein kinase C, and p42/44 MAPkinases in the above process. Various modulators of calcium and calmodulin (CaM) such as EGTA, nifedipine, TMB-8 (3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester), A23187, and W-7 (N-(6-aminohexyl)-5-chloro-1-napthalenesulfonamide) were also found to modulate the in vitro macrophage NO release in response to MCP-1. This observation indicated the regulatory role of calcium/CaM in the process of MCP-1-induced macrophage NO production. Similarly, the role of serine/threonine and protein tyrosine phosphatases in the above pathway was suggested using the specific inhibitors of these phosphatases, okadaic acid and sodium orthovanadate.