High affinity human IgE receptor (Fc epsilon RI). Analysis of functional domains of the alpha-subunit with monoclonal antibodies.

The binding of IgE to the high affinity Fc epsilon receptor (Fc epsilon RI) on mast cells and basophils is mediated by the alpha-subunit of the tetrameric receptor complex. Based on sequence homologies, the 50-kDa alpha-subunit is a member of the immunoglobulin superfamily of proteins and has two predicted disulfide-bonded loops. Monoclonal antibodies specific for the human alpha-subunit have been identified and separated into two major classes: inhibitory and noninhibitory antibodies. Inhibitory antibodies (i.e. 15A5) block 125I-IgE binding to a recombinant chimeric alpha-subunit (ch-alpha-protein) expressed on Chinese hamster ovary cells and immunoprecipitate 125I-labeled purified ch-alpha-protein. Noninhibitory antibodies (i.e. 22E7) immunoprecipitate both 125I-labeled ch-alpha-protein and the soluble complex of 125I-IgE cross-linked to ch-alpha-protein but do not block 125I-IgE binding to the ch-alpha-protein expressed on Chinese hamster ovary cells. Both classes of antibodies bind to natural Fc epsilon RI present on human basophils and induce histamine release from these cells. Inhibitory antibody 15A5 specifically binds to a peptide corresponding to amino acids 125-140 of the putative second domain of the alpha-subunit sequence. All the inhibitory antibodies compete with 125I-15A5 for binding to the ch-alpha-protein, indicating that these antibodies recognize inhibitory epitopes that are either identical or sterically overlapping. Noninhibitory antibodies (i.e. 22E7) do not block 125I-15A5 binding to the ch-alpha-protein. These data suggest that antibodies binding to the predicted second domain of the alpha-subunit can inhibit IgE binding to the alpha-subunit, while antibodies binding at a distance from this site do not inhibit IgE binding. These inhibitory antibodies may block IgE binding to the ch-alpha-protein by direct overlap, steric inhibition, or induced conformational changes of the receptor contact points for IgE.     

Programmed cell death 4: A novel player in the pathogenesis of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a pathological condition recognized by menstrual cycle irregularities, androgen excess, and polycystic ovarian morphology, affecting a significant proportion of women of childbearing age and accounting for the most prevalent cause of anovulatory sterility. In addition, PCOS is frequently accompanied by metabolic and endocrine disturbances such as obesity, dyslipidemia, insulin resistance, and hyperinsulinemia, indicating the multiplicity of mechanisms implicated in the progression of PCOS. However, the exact pathogenesis of PCOS is yet to be elucidated. Programmed cell death 4 (PDCD4) is a ubiquitously expressed protein that contributes to the regulation of various cellular processes, including gene expression, cell cycle progression, proliferation, and apoptosis. Despite some disparities concerning its exact cellular effects, PDCD4 is generally characterized as a protein that inhibits cell cycle progression and proliferation and instead drives the cell into apoptosis. The apoptosis of granulosa cells (GCs) is speculated to take a major part in the occurrence and progression of PCOS by ceasing antral follicle development and compromising oocyte competence. Given the possible involvement of GC apoptosis in the progression of PCOS, as well as the contribution of PDCD4 to the regulation of cell apoptosis and the development of metabolic diseases, the current review aimed to discuss whether or how PDCD4 can play a role in the pathogenesis of PCOS by affecting GC apoptosis.     

Severe hepatic fibrosis in Schistosoma mansoni infection is controlled by a major locus that is closely linked to the interferon-gamma receptor gene.

Lethal disease due to hepatic periportal fibrosis occurs in 2%-10% of subjects infected by Schistosoma mansoni in endemic regions such as Sudan. It is unknown why few infected individuals present with severe disease, and inherited factors may play a role in fibrosis development. Schistosoma mansoni infection levels have been shown to be controlled by a locus that maps to chromosome 5q31-q33. To investigate the genetic control of severe hepatic fibrosis (assessed by ultrasound examination) causing portal hypertension, a segregation analysis was performed in 65 Sudanese pedigrees from the same village. Results provide evidence for a codominant major gene, with.16 as the estimated allele A frequency predisposing to advanced periportal fibrosis. For AA males, AA females, and Aa males a 50% penetrance is reached after, respectively, 9, 14, and 19 years of residency in the area, whereas for other subjects the penetrance remains <.02 after 20 years of exposure. Linkage analysis performed in four candidate regions shows that this major locus maps to chromosome 6q22-q23 and that it is closely linked (multipoint LOD score 3.12) to the IFN-gammaR1 gene encoding the receptor of the strongly antifibrogenic cytokine interferon-gamma. These results show that infection levels and advanced hepatic fibrosis in human schistosomiasis are controlled by distinct loci; they suggest that polymorphisms within the IFN-gammaR1 gene could determine severe hepatic disease due to S. mansoni infection and that the IFN-gammaR1 gene is a strong candidate for the control of abnormal fibrosis observed in other diseases.     

Composting of waste from palm oil mill: a sustainable waste management practice

Malaysia is blessed with abundant natural resources and bears a favorable climate for commercial cultivation of crops such as oil palm. In Malaysia the total plantation area of oil palm was 4,487,957 ha in 2008. It has been reported that in 2005 there was a total of 423 palm oil mills having production capacity of approximately 89 million tonnes of fresh fruit bunch (FFB) per year. Waste from the oil palm mill process include palm oil mill effluent (POME), generated mainly from oil extraction, washing and cleaning up processes. POME contains cellulosic material, fat, oil, and grease. Discharging untreated effluent into water streams may cause considerable environmental problems. The solid wastes generated are mainly decanter cake, empty fruit bunches, seed shells and fibre from the mesocarp. POME as well as the solid wastes may rapidly deteriorate the surrounding environment if not dealt with properly. Hence there is an urgent need for a sustainable waste management system to tackle these wastes. As these wastes are organic in origin, they are rich in plant nutrients. Composting of waste generated from palm oil mills can be good practice as it will be helpful in recycling useful plant nutrients. This review deals with various aspects of waste management practices in palm oil mills and the possibility of composting the wastes.     

Ultrastructure of insect and spider cocoon silks

Despite much interest in the extraordinary mechanical properties of silks, the structure of native silk fibers is still not fully understood. In the present study, the morphology, topography, and organization of insect and spider cocoon silks were investigated using a range of imaging methods. Field emission scanning electron microscopy was used to observe transverse and longitude structures in silk fibers subjected to tensile fracturing, freeze fracturing, or polishing. In addition, ultrathin sections of silk brins embedded in resin were examined using transmission electron microscopy. Finally, dry silk brins were examined by confocal microscopy. The results confirmed the existence of well-oriented bundles of nanofibrils in all the silks examined and gave an indication of a hierarchical construction of the brin. Observed separation of the microfibrils in fractured brins suggests that the multifibrillar structure of the silk fiber contributes to toughness by allowing dissipation of energy in the controlled propagation of cracks.     

Born to run; the story of the PEPCK-Cmus mouse

In order to study the role of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK-C) in skeletal muscle, PEPCK-Cmus mice were created by introducing the cDNA for the enzyme, linked to the human alpha-skeletal actin gene promoter, into their germ line. Two founder lines generated by this procedure were bred together, creating a line of mice that have 9.0 units/g skeletal muscle of PEPCK-C, as compared to 0.080 units/g in muscle from control animals. The mice were more active than controls in their cages and could run for up to 5 km, at a speed of 20 m/min without stopping (control mice run for 0.2 km at the same speed). Male PEPCK-Cmus mice are extremely aggressive, as well as hyperactive. During strenuous exercise, they use fatty acids as a fuel more efficiently than do controls and produce far less lactate than do control animals, perhaps due to the greatly increased number of mitochondria in their skeletal muscle. PEPCK-Cmus mice also store up to five-times more triglyceride in their skeletal muscle, but have only marginal amounts of triglyceride in their adipose tissue depots, despite eating 60% more than controls. The concentration of leptin and insulin the blood of 8-12 months of PEPCK-Cmus mice is far lower than noted in the blood of control animals of the same age. These mice live longer than controls and the females remain reproductively active for as long as 35 months. The possible reasons for the profound alteration in activity and longevity caused the introduction of a simple metabolic enzyme into the skeletal muscle of the mice will be discussed.     

Environmental and economic issues arising from the pooling of SMEs’ supply chains: case study of the food industry in western France

Supply chains pooling is an emergent strategy for improving logistical performance. The pooling concept consists in transferring the effort of coordination for consolidating independent operators’ flows towards an ad hoc pooled system. This organisation results from a design of a pooled logistics network by merging different supply chains to share transport and logistics resources in order to improve logistics performance. In this case study, the pooling concept is applied to a collection of small and medium-sized western France food suppliers serving the same retail chain. In order to demonstrate the efficiency of the pooling, the existing transport organisation was compared to various pooling scenarios. The methodology consisted in accessing a current situation through a survey of the flow of goods at one of the main distribution centre of the studied supply network, then comparing this situation with three other pooling scenarios. Using supply network optimisation models, these scenarios were assessed considering cost and CO₂ emission levels. This study demonstrates the interest of transport pooling in the case independent shipping networks of Small and Medium Enterprises compared to the partially know existing strategies adopted by logistics service providers for less than truckload shipments. Moreover, it suggests that there is no dominant supply organisation and that transport pooling is a new stimulus for network design. These results also bring new research perspectives for generalisation of pooling and gain sharing within large coalitions.     

A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology

Atherosclerosis is a chronic inflammatory disease of the vasculature. There are various methods to study the inflammatory compound in atherosclerotic lesions. Mouse models are an important tool to investigate inflammatory processes in atherogenesis, but these models suffer from the phenotypic and functional differences between the murine and human immune system. In vitro cell experiments are used to specifically evaluate cell type-dependent changes caused by a substance of interest, but culture-dependent variations and the inability to analyze the influence of specific molecules in the context of the inflammatory compound in atherosclerotic lesions limit the impact of the results. In addition, measuring levels of a molecule of interest in human blood helps to further investigate its clinical relevance, but this represents systemic and not local inflammation. Therefore, we here describe a plaque culture model to study human atherosclerotic lesion biology ex vivo. In short, fresh plaques are obtained from patients undergoing endarterectomy or coronary artery bypass grafting and stored in RPMI medium on ice until usage. The specimens are cut into small pieces followed by random distribution into a 48-well plate, containing RPMI medium in addition to a substance of interest such as cytokines or chemokines alone or in combination for defined periods of time. After incubation, the plaque pieces can be shock frozen for mRNA isolation, embedded in Paraffin or OCT for immunohistochemistry staining or smashed and lysed for western blotting. Furthermore, cells may be isolated from the plaque for flow cytometry analysis. In addition, supernatants can be collected for protein measurement by ELISA. In conclusion, the presented ex vivo model opens the possibility to further study inflammatory lesional biology, which may result in identification of novel disease mechanisms and therapeutic targets.