Distribution of C3 phenotypes in North India: A pilot study

Summary A patient with partial trisomy 22 (PT22) is presented. Inheritance is presumed to be due to secondary nondisjunction in her mother, who has a balanced translocation t(11;22)(q25;q13). The problem of the phenotypic heterogeneity observed with this chromosome change is discussed.     

Reproductive biology of two species of Canavalia DC. (Fabaceae)—A non-conventional wild legume

The reproductive biology of two important species of Canavalia, i.e. Canavalia gladiata and Canavalia virosa, was investigated in detail by studying floral phenology, floral biology including fruit and seed set, breeding system and pollinator's activity. Both the species flower and set their seed primarily from August to December. The study of pollen–-pistil interaction indicated the existence of morphological protandry in both species, and pollen germination occurred only after rupture of the stigmatic surface. This suggests that some form of self-incompatibility operates in these species. Ants were the common vectors tripping the stigma and transporting some foreign pollen. Campylomma verbasci (large black ants) were only seen on the flowers of C. virosa, while Monomorium minimum (small black ants) were restricted to the flowers of C. gladiata. Inadequacy of reliable pollinators and high rate of bud/flower drop may be the main factors for low fruit and seed set in both the species.     

Synaptotagmin VII is targeted to secretory organelles in PC12 cells, where it functions as a high-affinity calcium sensor

Synaptotagmin (syt) I is thought to act as a Ca2+ sensor that regulates neuronal exocytosis. Fifteen additional isoforms of syt have been identified, but their functions are less well understood. Here, we used PC12 cells to test the idea that different isoforms of syt impart cells with distinct metal (i.e., Ca2+, Ba2+, and Sr2+) requirements for secretion. These cells express syt's I and IX (syt IX sometimes referred to as syt V), which have low apparent metal affinities, at much higher levels than syt VII, which we show has a relatively high apparent affinity for metals. We found that syt I and VII partially colocalize on large dense core vesicles and that upregulation of syt VII produces a concomitant increase in the divalent cation sensitivity of catecholamine release from PC12 cells. Furthermore, RNA interference-mediated knockdown of endogenous syt VII reduced the metal sensitivity of release. These data support the hypothesis that the complement of syt's expressed by a cell, in conjunction with their metal affinity, determines the divalent cation sensitivity of exocytosis.     

Lack of response of (Ca2+ + Mg2+) ATPase to atrial natriuretic peptide in basolateral membranes from kidney cortex of chronic diabetic rats

Incubation of basolateral membranes obtained from control rat kidney cortex in the presence of atrial natriuretic peptide (ANP) increased (Ca2+ + Mg2+) ATPase activity in a dose-dependent manner. Such response was absent in membranes obtained from animals made diabetic by streptozotocin injection (65 mg/kg, iv). The differential responses in the ATPase activity were not due to changes in the affinity for Ca2+ and insulin treatment in the diabetic animals completely reversed the situation. Our data suggest that ANP may mediate its cellular effects in part by changes in cellular Ca2+ homeostasis in kidney cortex and the lack of response of (Ca2+ + Mg2+) ATPase to ANP in chronic diabetes may contribute to the development of intracellular Ca2+ overload and nephropathy.     

Osteogenic activity of constituents from Butea monosperma

Phytochemical investigation from the stem bark of Butea monosperma, led to the isolation and identification of three new compounds named buteaspermin A (1), buteaspermin B (2) and buteaspermanol (3), along with 19 known compounds. The structure of compounds 1–22 were established on the basis of their spectroscopic data. The isolated compounds 2–17 were evaluated using neonatal (1–3 day old) rat calvaria derived primary osteoblast cultures. Five of these compounds 7, 10–13 showed promising osteogenic activity, attributed to increased osteoblast proliferation, differentiation and mineralization as evidenced by marked increase in expression of alkaline phosphatase, an early phase differentiation marker, and alizarin Red S staining of osteoblasts cultured for 48 h and von Kossa silver staining of nodules formed 15 days after culture with these compounds. Quantification of mineralization by optical density measurement of Alizarin Red S extracted from stained osteoblasts cultured for 7 days in presence of these compounds showed significant (P < 0.05, vs corresponding vehicle control group) increase in mineralization. On the basis of biological results, structure–activity relationships are discussed.     

Genetic algorithm-based medium optimization for enhanced production of fluorescent pseudomonad R81 and siderophore

Fluorescent pseudomonad R81, a root-colonizing bacterium, is a potential bio-inoculant due to its plant growth promoting characteristics. It produces hydroxamate-type siderophore which is involved in disease suppression in plants. Genetic algorithm (GA) methodology was applied for the optimization of siderophore and cell mass production simultaneously in shake flask experiments. A total of 10 medium components were optimized within 80 experiments. A high siderophore concentration of 1.9 g/L and cell mass concentration of 2.8 g/L was achieved in the optimized medium. The application of GA was well suited for determination of optimum concentration levels of the medium constituents for a bi-objective function. GA was able to increase the siderophore concentration by 2.8-fold when compared to RSM-based optimization. Further, the batch fermentation of the GA-optimized medium in 14 L bioreactor without pH control produced 2.2 g/L siderophore in 36 h, the highest reported so far. GA was also successfully used to estimate the kinetic parameters of the mathematical models of the batch fermentation.     

Different modes of DNA cleavage activity of dihydroxo-bridged dicopper(II) complexes having phenanthroline bases

Dihydroxo-bridged dicopper(II) complexes [(Cu(phen))(2)(mu-OH)(2)](ClO(4))(2) (1), [(Cu(dpq))(2)(mu-OH)(2)](ClO(4))(2) (2) and [(Cu(dppz)(DMF))(2)(mu-OH)(2)](PF(6))(2) (3), where phen, dpq and dppz are 1,10-phenanthroline, dipyridoquinoxaline and dipyridophenazine, respectively, are prepared and their DNA binding and cleavage properties studied. Complex 3 has been structurally characterized by X-ray crystallography. The complexes have a (Cu(2)(mu-OH)(2))(2+) core with an essentially planar arrangement of two CuN(2)O(2) basal planes. The complexes are avid binder to calf thymus DNA (K(app) value of 4.8 x 10(6) and 5.9 x 10(6) M(-1) for 2 and 3, respectively, from ethidium displacement assay) and exhibits significant cleavage of supercoiled (SC) pUC19 DNA in dark in presence of mercaptopropionic acid. Besides, the dpq and dppz complexes display photo-induced DNA cleavage on UV (312 nm) and red light (632.8 nm) irradiations in absence of any additives. Mechanistic investigations reveal minor groove binding for the phen and dpq complexes, and major groove preference for the dppz species. The oxidative DNA cleavage reactions in presence of mercaptopropionic acid as a reducing agent involve hydroxyl radicals. The photo-cleavage reactions at UV light involve singlet oxygen as the reactive species, while similar reactions on red light irradiation (632.8 nm) proceed through the formation of hydroxyl radical. The complexes show significant DNA hydrolase activity in absence of any additives under dark reaction conditions.     

Melanoma invasion - current knowledge and future directions

The acquisition of invasive behaviour is the key transition in the progression of benign melanocyte hyperplasia to life threatening melanoma. Understanding this transition and the mechanisms of invasion are the key to understanding why malignant melanoma is such a devastating disease and will aid treatment strategies. Underlying the invasive behaviour is increased cell motility caused by changes in cytoskeletal organization and altered contacts with the extra-cellular matrix (ECM). In addition, changes in the interactions of melanoma cells with keratinocytes and fibroblasts enable them to survive and proliferate outside their normal epidermal location. Proteomic and genomic initiatives are greatly increasing our knowledge of which gene products are deregulated in invasive and metastatic melanoma; however, the next challenge is to understand how these genes promote the invasion of melanoma cells. In recent years new models have been developed that more closely recapitulate the conditions of melanoma invasion in vivo. It is hoped that these models will give us a better understanding of how the genes implicated in melanoma progression affect the motility of melanoma cells and their interactions with the ECM, stromal cells and blood vessels. This review will summarise our current understanding of melanoma invasion and focus on the new model systems that can be used to study melanoma.