Template unwinding during DNA replication initiation requires the loading of the MCM helicase activator Cdc45 at replication origins. We show that Cdc45 interacts with the DNA unwinding element (DUE) binding protein DUE-B, and that these proteins localize to the DUEs of active replication origins. DUE-B and Cdc45 are not bound at the inactive c-myc replicator in the absence of a functional DUE, or at the recently identified ataxin 10 (ATX10) origin which is silent before disease-related (ATTCT)n repeat length expansion of its DUE sequence, despite the presence of ORC and MCM proteins at these origins. Addition of a heterologous DUE to the ectopic c-myc origin, or expansion of the ATX10 DUE, leads to origin activation, DUE-B binding, and Cdc45 binding. DUE-B, Cdc45 and topoisomerase IIbeta binding protein 1 (TopBP1) form complexes in cell extracts and when expressed from baculovirus vectors. During replication in Xenopus egg extracts, DUE-B and Cdc45 bind to chromatin with similar kinetics, and DUE-B immunodepletion blocks replication and the loading of Cdc45 and a fraction of TopBP1. The coordinated binding of DUE-B and Cdc45 to origins, and the physical interactions of DUE-B, Cdc45 and TopBP1 suggest that complexes of these proteins are necessary for replication initiation.

Calpain system is generally known to be comprised of three molecules: two Ca(2+)-dependent proteases: mu- and m-calpains, and their endogenous inhibitor, calpastatin. While calpains have previously been considered as the cytoplasmic enzymes, research in the recent past demonstrated that mu-calpain, m-calpain and calpain 10 are present in mitochondria, which play important roles in a variety of pathophysiological conditions including necrotic and apoptotic cell death phenomena. Although a number of original research articles on mitochondrial calpain system are available, yet to the best of our knowledge, a precise review article on mitochondrial calpain system has, however, not been available. This review outlines the key features of the mitochondrial calpain system, and its roles in several cellular and biochemical events under normal and some pathophysiological conditions.

INTRODUCTION: Significant proportions of liver cirrhotic patients develop hepatocellular carcinoma and have to undergo hepatic resection. The compromised cirrhotic liver cannot withstand further removal of hepatic tissue, thus, leading to postoperative complication and death. METHODS: In this study, we enrolled 20 patients having liver cirrhosis with hepatocellular carcinoma and randomly assigned them into two groups to receive autologous stem cells or placebo. RESULTS: After 3 weeks, all participants underwent liver resection and were followed for 12 weeks postoperative. We observed that the group receiving preoperative stem cell therapy had shown a significant improvement in all parameters of liver function and had no postoperative complications compared to the group treated with placebo, which showed no improvement in liver parameters and had postoperative complications. DISCUSSION: In conclusion, autologous stem cell therapy can improve the surgical outcome in cirrhotic livers and should be considered as an adjuvant treatment in such patients undergoing hepatic resection.

Myosin II disassembly in Dictyostelium is regulated by three structurally-related myosin heavy chain kinases (MHCK-A,-B, and -C). We show that the WD-repeat domain of MHCK-C is unique in that it mediates both substrate targeting and subcellular localization, revealing a target for regulation that is distinct from the other MHCKs.

Enterotoxigenic Escherichia coli (ETEC) are the most common bacterial cause of childhood diarrhea in Bangladesh. Among the virulence factors of ETEC, toxins and colonization factors (CFs) play a major role in pathogenesis. Unlike Vibrio cholerae the relationship between ETEC and ETEC specific phages has been poorly understood and so far the possible role of ETEC phages on the evolution of ETEC strains in the environment is yet to be established. This study was designed specifically to isolate phages which are specific for ETEC virulence factor. Among the forty nine phages isolated from twelve different surface water samples thirteen were tested against 211 ETEC strains collected from clinical and environmental sources. One phage designated as IMM-001 showed a significant specificity towards CS7 colonization factor as it attacked all the CS7 expressing ETEC. Electron microscopic analyses showed that the isolated phage possessed an isomeric hexagonal head and long filamentous tail. Both antibody blocking method and phage neutralization assay confirmed CS7 pilus is required for the phage infection process and signifies the role of CS7 fimbrial protein as a potential receptor for IMM-001. In summary the study shows the presence of a lytic phage in the environmental water which is specific for the CS7 colonization factor of ETEC.

Methomyl, S-methyl (EZ)-N-(methylcarbamoyloxy)thioacetimidate, is a systemic insecticide chosen for the management of shoot and fruit borer, Leucinodes orbonalis G. Codex Alimentarious Commission has proposed a maximum residue limit (MRL) of 0.2 mg kg(- 1) of methomyl, and there is a need to validate this value on eggplant. First + first-order model can explain the nonlinear dissipation pattern of methomyl conveniently in comparison to first-order kinetics. The preharvest intervals (PHI) of 27.3 and 35.3 days as obtained from first + first-order model for single and double doses would bring down the methomyl residue below MRL in actual practice. The respective half-lives were 6.6 and 7.8 days. On the other hand, first-order model suggests methomyl dissipated with a half-life value around 5 days and proposed PHIs of 6.57 and 8.57 days for single and double doses, which was far from reality. Hence, five different decontamination agents were chosen for the decontamination of methomyl from eggplant. Safety factors such as theoretical maximum daily intake and maximum permissible intake were used to evaluate risk assessment to human health. A 3-day waiting period for the both doses, following conventional agricultural practice and processing factor could not ensure sufficient margin of safety. Subjecting the data to a processing factor of 60% could not bring the residues below the proposed MRL by Codex. Methomyl is not found appropriate and effective for application in eggplant. Either the proposed MRL needs to be revised or good agricultural practice involving methomyl for plant protection in eggplant cultivation is questioned.

A total of 75 animals between 1.5 and 8 years old were randomly selected for the study. Of these, 57.8% were cross-bred animals and the rest were non-descript. Moreover, 61.8% of the animals under study were brought for slaughter from local sources and the rest from farm houses. Samples collected from five districts revealed contamination with traces of organochlorine pesticides (0.01-0.22 mug g(- 1)) and organophosphorus pesticides (0.111-0.098 mug g(- 1)). In general, all the raw meat samples possessed dichlorodiphenyltrichloroethane at the highest level. Contamination was highest in cow meat samples and lowest in chicken samples. No particular district-wise trend was obtained for the pesticides selected for analysis. Subsequent decontamination study revealed that cooking is the best option in reducing pesticide load in raw meat samples. Cooked chicken is the safest foodstuff for consumption.

The determination of the condensed-phase preignition chemistry of hypergolic bipropellant pairs has been considerably challenging due to toxicity and reactivity of the used materials. In this work, we describe a new experimental technique for characterizing preignition behavior of hypergolic materials. Small quantities of the bipropellant pair are brought in contact under isothermal conditions, and spectral transmission measurements on the evolved products are performed using Fourier transform infrared spectroscopy. The gaseous products are subsequently quantified to yield species concentration profiles at various temperatures, hence facilitating the elucidation of the detailed condensed-phase chemical kinetics responsible for the ignition in the gas phase.

We describe the medicinal chemistry programme that led to the identification of the EP(1) receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP(1) antagonists such as GW848687X and was found to display excellent activity in preclinical models of inflammatory pain. However, upon cross species pharmacokinetic profiling, GSK269984A was predicted to have suboptimal human pharmacokinetic and was thus progressed to a human microdose study.

Quinalphos 20 AF was applied at the rate of 500 and 1,000 g a.i. ha(- 1) in cabbage for two consecutive seasons and the samples harvested at intervals of 0 (3 h after application), 2, 4, 6, 8, and 10 days interval after application. The calculated half-life values were 1.27-1.38 days and 1.12-1.24 days for cabbage heads and cropped soil, respectively. The calculated safe waiting period based on field dissipation study was 5.28-6.7 days, which indicated its persistence nature. Thus, to reduce the safe waiting period, efforts were made to decontaminate the Quinalphos residue from cabbage head by various household preparations (viz. washing, cooking, washing plus cooking, salt water dipping, dipping in boiled salt water, dipping in detergent solution, and dipping in boiled detergent solution). Statistical analysis of the data using Duncan's multiple range test revealed that various household processing substantially reduced the residue of Quinalphos in cabbage heads in the range of 27.72-75.01% irrespective of any dose and seasons, but none were able to satisfactorily bring down the residue below the tolerance level of 0.05 mg kg(- 1).