Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis

Mitochondrial cytochrome c release and inositol (1,4,5) trisphosphate receptor (InsP(3)R)-mediated calcium release from the endoplasmic reticulum mediate apoptosis in response to specific stimuli. Here we show that cytochrome c binds to the InsP(3)R during apoptosis. Addition of 1 nM cytochrome c blocks calcium-dependent inhibition of InsP(3)R function. Early in apoptosis, cytochrome c translocates to the endoplasmic reticulum where it selectively binds InsP(3)R, resulting in sustained, oscillatory cytosolic calcium increases. These calcium events are linked to the coordinate release of cytochrome c from all mitochondria. Our findings identify a feed-forward mechanism whereby early cytochrome c release increases InsP(3)R function, resulting in augmented cytochrome c release that amplifies the apoptotic signal.     

Shape based virtual screening and molecular docking towards designing novel pancreatic lipase inhibitors

Increase in obesity rates and obesity associated health issues became one of the greatest health concerns in the present world population. With alarming increase in obese percentage there is a need to design new drugs related to the obesity targets. Among the various targets linked to obesity, pancreatic lipase was one of the promising targets for obesity treatment. Using the in silico methods like structure based virtual screening, QikProp, docking studies and binding energy calculations three molecules namely zinc85531017, zinc95919096 and zinc33963788 from the natural database were reported as the potential inhibitors for the pancreatic lipase. Among them zinc95919096 presented all the interactions matching to both standard and crystal ligand and hence it can be further proceeded to drug discovery process.     

Gametophytes,embryogeny and pericarp ofMicrostylis wallichii lindl. (Orchidaceae)

The anther wall is 4-layered thick. Its development is of the Monocotyledonous type. Simultaneous cytokinesis results in decussate, isobilateral, linear and tetrahedral tetrads. At anthesis, the microspores are 2-celled. The mature ovules are anatropous, bitegmic and tenuinucellate. Both the integuments are dermal in origin and 2-layered. The inner integument alone forms the micropyle. Development of the female gametophyte is of the Monosporic type. Double fertilization occurs but the primary endosperm nucleus degenerates without any division. Development of embryo corresponds to the variation of the Onagrad type. The mature embryo lacks differentiation. The seeds are minute and non-endospermic. The seed coat is formed entirely by the outer layer of outer integument. There are three sterile and three fertile valves in the ovary. In the prefertilization stages valves consist of parenchymatous cells. After fertilization, the sterile valves become sclerenchymatous whereas the fertile valves remain parenchymatous.     

Constancy of wheat histones during development

Summary Histones were extracted from leaves of winter- and spring-wheat seedlings, flowering shoots of spring wheat, shoots of vernalized and control winter wheat, and roots and shoots of winter wheat, and were compared by polyacrylamide-gel electrophoresis. No differences were found either in the electrophoretic mobility or relative quantity of the various fractions. Wheat histones contained fractions of the exact electrophoretic mobility as F2a1 and F3 of calf thymus and pea histones. Other major fractions of the wheat histones had electrophoretic mobilities similar to those of F1, F2b and F2a2 of peas.     

Protection conferred by Bcl-2 expression involves reduced oxidative stress and increased glutathione production during hypothermia-induced apoptosis in AK-5 tumor cells

Hypothermia is known to retard mammalian cell growth, however, BC-8 cells, which have originated from AK-5 tumor after single cell cloning, were triggered into apoptotic pathway when grown at 30 degrees C. Cell death process showed typical apoptotic features like DNA fragmentation, cytochrome c release, etc. Introduction of Bcl-2 gene in BC-8 cells inhibited hypothermia-induced apoptotic process, which is ascribed to reduced ROS generation and higher glutathione production. Thus, Bcl-2 seems to control the apoptotic induction process at the level of redox regulation, in addition to its known effects at the mitochondrial dysregulation. These observations suggest that tumors, which are low in Bcl-2 expression, are sensitive to hypothermic shock and make hypothermia an interesting inducer of apoptosis in tumor cells.     

In silico evolution of functional modules in biochemical networks

Understanding the large reaction networks found in biological systems is a daunting task. One approach is to divide a network into more manageable smaller modules, thus simplifying the problem. This is a common strategy used in engineering. However, the process of identifying biological modules is still in its infancy and very little is understood about the range and capabilities of motif structures found in biological modules. In order to delineate these modules, a library of functional motifs has been generated via in silico evolution techniques. On the basis of their functional forms, networks were evolved from four broad areas: oscillators, bistable switches, homeostatic systems and frequency filters. Some of these motifs were constructed from simple mass action kinetics, others were based on Michaelis-Menten kinetics as found in protein/protein networks and the remainder were based on Hill equations as found in gene/protein interaction networks. The purpose of the study is to explore the capabilities of different network architectures and the rich variety of functional forms that can be generated. Ultimately, the library may be used to delineate functional motifs in real biological networks.     

Plant regeneration from peduncle segments of oil seed Brassica species: Influence of silver nitrate and silver thiosulfate

Cultured peduncle segments of B. juncea, B. campestris, B. napus, B. nigra and B. carinata produced shoot buds on Murashige and Skoog medium supplemented with benzyladenine and 1-naphthalene acetic acid. Supplementation of the media with 30 μm silver nitrate or silver thiosulfate enhanced the frequency of shoot regeneration. The regenerated shoots could be rooted at a frequency of 95% and transferred to soil where 75% survived and set seed. This revised version was published online in June 2006 with corrections to the Cover Date.     

Association of SNPs in EGR3 and ARC with Schizophrenia Supports a Biological Pathway for Schizophrenia Risk

We have previously hypothesized a biological pathway of activity-dependent synaptic plasticity proteins that addresses the dual genetic and environmental contributions to schizophrenia. Accordingly, variations in the immediate early gene EGR3, and its target ARC, should influence schizophrenia susceptibility. We used a pooled Next-Generation Sequencing approach to identify variants across these genes in U.S. populations of European (EU) and African (AA) descent. Three EGR3 and one ARC SNP were selected and genotyped for validation, and three SNPs were tested for association in a replication cohort. In the EU group of 386 schizophrenia cases and 150 controls EGR3 SNP rs1877670 and ARC SNP rs35900184 showed significant associations (p = 0.0078 and p = 0.0275, respectively). In the AA group of 185 cases and 50 controls, only the ARC SNP revealed significant association (p = 0.0448). The ARC SNP did not show association in the Han Chinese (CH) population. However, combining the EU, AA, and CH groups revealed a highly significant association of ARC SNP rs35900184 (p = 2.353 x 10⁻⁷; OR [95% CI] = 1.54 [1.310–1.820]). These findings support previously reported associations between EGR3 and schizophrenia. Moreover, this is the first report associating an ARC SNP with schizophrenia and supports recent large-scale GWAS findings implicating the ARC complex in schizophrenia risk. These results support the need for further investigation of the proposed pathway of environmentally responsive, synaptic plasticity-related, schizophrenia genes.     

Influence of phytohormones,carbohydrates, aminoacids,growth supplements and antibiotics on somatic embryogenesis and plant differentiation in finger millet

Cultured caryopses of finger millet (Eleusine coracana GAERTN) produced callus from shoot apices or mesocotyls depending upon the concentration of picloram and combination of cytokinins in MS basal medium. On subsequent subcultures, numerous somatic embryos differentiated from the callus on MS medium supplemented with picloram and kinetin. The embryos germinated into complete plants on medium devoid of phytohormones. When different carbohydrates were tested, basal medium containing glucose and sucrose produced the highest frequency of germinating somatic embryos. Supplementation of MS basal medium with a variety of aminoacids, osmotic agents and growth supplements had an adverse effect on the germination of embryos. Incorporation of different antibiotics such as carbenicillin, cefotaxime and streptomycin sulfate enhanced plant differentiation from somatic embryos. Cytological analysis of regenerated plants showed normal diploid chromosome number in their root tips.Abbreviations 2,4-D 2,4-dichlorophenoxy acetic acid - BA benzyl adenine - 2,iP 6---dimethylallylamino purine - Kn kinetin - Z zeatin