Hepatic VLDL secretion : DGAT1 determines particle size but not particle number, which can be supported entirely by DGAT2

We investigated whether, in view of its activity being expressed on both aspects of the endoplasmic reticulum (ER; dual membrane topology), diacylglycerol acyltransferase 1 (DGAT1) plays a distinctive role in determining the triglyceride (TAG) content of VLDL particles secreted by the liver. Mice in which the DGAT1 gene was specifically ablated in hepatocytes (DGAT1-LKO mice) had the same number of VLDL particles (apoB concentration) in the plasma 1 h after Triton 1339 treatment, but these particles were approximately half the size of VLDL particles secreted by control mice and had a proportionately decreased content of TAG, with normal cholesterol and cholesteryl ester contents. Analyses of purified microsomal fractions prepared from 16 h fasted control and DAGT1-LKO mice showed that the TAG/protein ratio in the ER was significantly lower in the latter. Electron micrographs of these livers showed that those from DGAT1-LKO mice did not show the increased lipid content of the smooth ER shown by control livers. The effects of DGAT1- and DGAT2-specific inhibitors on apoB secretion by HepG2 cells showed that DGAT1 is not indispensable for apoB secretion and demonstrated redundancy in the ability of the two enzymes to support apoB secretion. Therefore, our findings show that DGAT1 is essential for the complete lipidation and maturation of VLDL particles within the lumen of the ER, consistent with its dual topology within the ER membrane. In the mouse, DGAT2 can support apoB secretion (particle number) even when TAG availability for full VLDL lipidation is restricted in the absence of DGAT1

Agricultural Waste Biomass Energy Potential In Pakistan

Pakistan has a major electricity supply problem with urban areas having a very intermittent supply of electricity. The supply gap at periods of high demand is 6 GW. Pakistan has a large agricultural economic sector and produces a substantial amount of waste material that has little current economic use. This work shows that these agricultural wastes are a significant energy resource that could be used to generate electricity using relatively small biomass generator sets that could take all the waste biomass from the surrounding agricultural area. Pakistan currently imports most of the oil used for electricity generation. The cost of this result in high cost electricity and it is shown that bio-electricity could be generated competitively in Pakistan. It was estimated, based on 30% thermal efficiency of electric power generation, that the annual production of crop residues have the potential to generate 76% of the annual electricity requirements of Pakistan. For this to come from agricultural wastes in farmland, transport costs would have to be minimised. It is proposed that a series of about 10MWe plants should be established (which are commercially available) with all farms in about a 10km radius delivering their agricultural solid waste to the plant at the farmers cost with direct payment by the power generator

EPIDEMIOLOGICAL INVESTIGATIONS OF A PESTE DES PETITS RUMINANTS (PPR) OUTBREAK IN AFGHAN SHEEP IN PAKISTAN

Epidemiological and virological investigations were carried out during an outbreak of Peste des petits ruminants (PPR) in Afghan (Bulkhi) sheep in Pakistan. The overall morbidity, mortality and case fatality rates were 41.0, 1.2 and 3.0%, respectively. The epidemic curve was plotted and the values for basic reproductive number (R0) and herd immunity threshold (HIT) for the affected flock were estimated to be 6.85 and 85.4%, respectively. The morbid material analysis by immuno-capture ELISA (Ic-ELISA) and haemagglutination assay (HA) revealed the presence of PPR virus. The PPR virus was isolated and identified through cytopathic effects, Ic-ELISA and transmission electron microscopy (TEM)

Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers

Poly (ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapies have been found to be particularly effective in tumors that harbor deleterious germline or somatic mutations in the BRCA1 or BRCA2 genes, the products of which contribute to the conservative homologous recombination repair of DNA double-strand breaks. Nonetheless, several setbacks in clinical trial settings have highlighted some of the issues surrounding the investigation of PARP inhibitors, especially the identification of patients who stand to benefit from such drugs. One potential approach to finding this patient subpopulation is to examine the tumor DNA for evidence of a homologous recombination defect. However, although the genomes of many breast and ovarian cancers are replete with aberrations, the presence of numerous factors able to shape the genomic landscape means that only some of the observed DNA abnormalities are the outcome of a cancer cell’s inability to faithfully repair DNA double-strand breaks. Consequently, recently developed methods for comprehensively capturing the diverse ways in which homologous recombination deficiencies may arise beyond BRCA1/2 mutation have used DNA microarray and sequencing data to account for potentially confounding features in the genome. Scores capturing telomeric allelic imbalance, loss of heterozygosity (LOH) and large scale transition score, as well as the total number of coding mutations are measures that summarize the total burden of certain forms of genomic abnormality. By contrast, other studies have comprehensively catalogued different types of mutational pattern and their relative contributions to a given tumor sample. Although at least one study to explore the use of the LOH scar in a prospective clinical trial of a PARP inhibitor in ovarian cancer is under way, limitations that result in a relatively low positive predictive value for these biomarkers remain. Tumors whose genome has undergone one or more events that restore high-fidelity homologous recombination are likely to be misclassified as double-strand break repair-deficient and thereby sensitive to PARP inhibitors and DNA damaging chemotherapies as a result of prior repair deficiency and its genomic scarring. Therefore, we propose that integration of a genomic scar-based biomarker with a marker of resistance in a high genomic scarring burden context may improve the performance of any companion diagnostic for PARP inhibitors

L-arginine: A unique amino acid for improving depressed wound immune function following hemorrhage

Objective: To determine whether L-arginine has any salutary effects on wound immune cell function following trauma-hemorrhage. Background. Depressed wound immune function contributes to an increased incidence of wound infections following hemorrhage. Although administration of L-arginine has been shown to restore depressed cell-mediated immune responses following hemorrhage potentially by maintaining organ blood flow, it remains unknown whether Larginine has any salutary effects on the depressed local immune response at the wound site. Methods: Male mice were subjected to a midline laparotomy and polyvinyl sponges were implanted subcutaneously in the abdominal wound prior to hemorrhage (35 +/- 5 mm Hg for 90 min and resuscitation) or sham operation. During resuscitation mice received 300 mg/kg body weight L-arginine or saline (vehicle). Sponges were harvested 24 h thereafter, wound fluid collected and wound immune cells cultured for 24 h in the presence of LPS. Pro- (IL-1beta, IL-6) and anti-inflammatory (IL-10) cytokines were determined in the supernatants and the wound fluid. In addition, wounds were stained for IL-6 immunohistochemically. In a separate set of animals, skin and muscle blood flow was determined by microspheres. Results: The capacity of wound immune cells to release IL-1beta and IL-6 in vitro was significantly depressed in hemorrhaged mice receiving vehicle. Administration of L-arginine, however, improved wound immune cell function. In contrast, in vivo the increased IL-6 release at the wound site was decreased in L-arginine-treated mice following hemorrhage. Moreover, IL-10 levels were significantly increased in the wound fluid in hemorrhaged animals receiving L-arginine compared to vehicle-treated mice. In addition, the depressed skin and muscle blood flow after hemorrhage was restored by L-arginine. Conclusions: Thus, L-arginine might improve local wound cell function by decreasing the inflammatory response at the wound site. Since L-arginine protected wound immune cell function this amino acid might represent a novel and useful adjunct to fluid resuscitation for decreasing wound complications following hemorrhage. Copyright beta 2002 S. Karger AG, Basel

From soil to plant, the journey of P through trophic relationships and ectomycorrhizal association

Phosphorus (P) is essential for plant growth and productivity. It is one of the most limiting macronutrients in soil because it is mainly present as unavailable, bound P whereas plants can only use unbound, inorganic phosphate (Pi), which is found in very low concentrations in soil solution. Some ectomycorrhizal fungi are able to release organic compounds (organic anions or phosphatases) to mobilize unavailable P. Recent studies suggest that bacteria play a major role in the mineralization of nutrients such as P through trophic relationships as they can produce specific phosphatases such as phytases to degrade phytate, the main form of soil organic P. Bacteria are also more effective than other microorganisms or plants at immobilizing free Pi. Therefore, bacterial grazing by grazers, such as nematodes, could release Pi locked in bacterial biomass. Free Pi may be taken up by ectomycorrhizal fungus by specific phosphate transporters and transferred to the plant by mechanisms that have not yet been identified. This mini-review aims to follow the phosphate pathway to understand the ecological and molecular mechanisms responsible for transfer of phosphate from the soil to the plant, to improve plant P nutrition