Raising automotive fuel efficiency

The Obama administration recently moved up the schedule for achieving the fuel efficiency standards set forth by Congress in the 2007 Energy Independence and Security Act. The deadline for meeting these standards is now vehicle model year 2016 instead of 2020.Fuel ; Energy industries

Internalisation of membrane progesterone receptor-α after treatment with progesterone: Potential involvement of a clathrin-dependent pathway

This article has been made available through the Brunel Open Access Publishing Fund.Internalisation and recycling of seven trans-membrane domain receptors is a critical regulatory event for their signalling. The mechanism(s) by which membrane progesterone receptor-α (mPRα) number is regulated on the cell surface is unclear. In this study, we investigated the cellular distribution of mPRα and mechanisms of mPRα trafficking using a cell line derived from a primary culture of human myometrial cells (M11) as an experimental model. RT-PCR and immunofluorescent analysis demonstrated expression of mPRα in M11 cells with mPRα primarily distributed on the cell surface under basal conditions. For the first time, plasma membrane localisation of mPRα was confirmed using immuno-gold transmission electron microscopy. Stimulation of M11 cells with progesterone (P4, 100 nM) resulted in internalisation of mPRα from the plasma membrane to the cytoplasm (10 min) and subsequent partial translocation back to the cell surface (20 min). We investigated potential endocytotic pathways involved in trafficking of mPRα after its internalisation. Partial co-localisation of clathrin with mPRα was obvious after 10 min of P4 treatment. Of note, chlorpromazine (inhibitor of clathrin-mediated pathway) inhibited the endocytosis of mPRα, whereas treatment with nystatin (inhibitor of caveolae-mediated pathway) did not affect internalisation. Collectively, these data suggest that mPRα is expressed on the cell surface of M11 cells and undergoes endocytosis after P4 stimulation primarily via a clathrin-mediated pathway.This article is available through the Brunel Open Access Publishing Fun

Expression of membrane and nuclear progesterone receptors in two human placental choriocarcinoma cell lines (JEG-3 and BeWo): Effects of syncytialization

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2011 Spandidos Publications Ltd.A vital function of the human placenta is to produce steroid hormones such as progesterone, which are essential for the maintenance of pregnancy and the onset of parturition. Although choriocarcinoma cell lines are valuable placental models for investigations of steroid hormone actions, little is known about the expression of progesterone receptors (PRs) in these cell lines. Therefore, in this study, the expression of membrane and nuclear PRs was investigated in cultures of fusigenic (BeWo) and non-fusigenic (JEG-3) human choriocarcinoma cell lines. In addition, the effects of an inducer of syncytialization (forskolin) on the PR expression in BeWo cells were assessed. Quantitative RT-PCR revealed that in fully syncytialized BeWo cells (treated with 50 mu M forskolin for 72 h) there was a significant down-regulation of mPR alpha and up-regulation of mPR beta and of the progesterone membrane component-1 (PGRMC1) when compared with non-syncytialized BeWo cells. Expression of all the mPR and PGRMC1 mRNAs was significantly lower in JEG-3 cells compared to non-syncytialized BeWo cells. Interestingly, expression of PR-B was unaltered between the two BeWo states but was significantly higher in JEG-3 cells. Immunofluorescence analysis revealed that mPR proteins are differentially expressed in these choriocarcinoma cell lines as well as in the human placenta. The data demonstrate that human choriocarcinoma cell lines have a complex system of progesterone signalling involving multiple classes of PRs. The finding that syncytialization is accompanied by changes in the expression of these receptors may suggest that this process influences progesterone signalling

Tourniquet Test for Dengue Diagnosis: Systematic Review and Meta-analysis of Diagnostic Test Accuracy.

BACKGROUND: Dengue fever is a ubiquitous arboviral infection in tropical and sub-tropical regions, whose incidence has increased over recent decades. In the absence of a rapid point of care test, the clinical diagnosis of dengue is complex. The World Health Organisation has outlined diagnostic criteria for making the diagnosis of dengue infection, which includes the use of the tourniquet test (TT). PURPOSE: To assess the quality of the evidence supporting the use of the TT and perform a diagnostic accuracy meta-analysis comparing the TT to antibody response measured by ELISA. DATA SOURCES: A comprehensive literature search was conducted in the following databases to April, 2016: MEDLINE (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, BIOSIS, Web of Science, SCOPUS. STUDY SELECTION: Studies comparing the diagnostic accuracy of the tourniquet test with ELISA for the diagnosis of dengue were included. DATA EXTRACTION: Two independent authors extracted data using a standardized form. DATA SYNTHESIS: A total of 16 studies with 28,739 participants were included in the meta-analysis. Pooled sensitivity for dengue diagnosis by TT was 58% (95% Confidence Interval (CI), 43%-71%) and the specificity was 71% (95% CI, 60%-80%). In the subgroup analysis sensitivity for non-severe dengue diagnosis was 55% (95% CI, 52%-59%) and the specificity was 63% (95% CI, 60%-66%), whilst sensitivity for dengue hemorrhagic fever diagnosis was 62% (95% CI, 53%-71%) and the specificity was 60% (95% CI, 48%-70%). Receiver-operator characteristics demonstrated a test accuracy (AUC) of 0.70 (95% CI, 0.66-0.74). CONCLUSION: The tourniquet test is widely used in resource poor settings despite currently available evidence demonstrating only a marginal benefit in making a diagnosis of dengue infection alone. REGISTRATION: The protocol for this systematic review was registered at PROSPERO: CRD42015020323

Early embryonic mortality in strain crossed gilts

Digitized 2007 AES.Includes bibliographical references (page [36])

Lupus autoantibodies interact directly with distinct glomerular and vascular cell surface antigens

Lupus autoantibodies interact directly with distinct glomerular and vascular cell surface antigens. We have identified monoclonal anti-DNA antibodies derived from lupus prone MRL-lpr/lpr mice that produce glomerular immune deposits and nephritis after passive transfer to normal mice. Particularly noteworthy is that the location of immune deposition varied among nephritogenic Ig, and this was associated with distinctive histologies and clinical disease profiles. Although their autoantigen binding properties differed, they were highly cross-reactive, in a manner similar to Ig deposited in glomeruli of lupus mice. This antigen binding profile was also typical of other previously described nephritogenic autoantibodies that bound directly to glomerular antigens to initiate immune deposit formation. In this study, we questioned whether ligation of different glomerular antigens by individual autoantibodies could contribute to the observed differences in the location of immune deposits. To examine this possibility, monoclonal anti-DNA antibodies (IgG2a) that produced glomerular immune deposits in different locations were evaluated. H221 produced mesangial, intracapillary (that is, intraluminal or within the capillary lumen) and subendothelial deposits associated with heavy proteinuria, whereas H147 produced mesangial, subendothelial and linear basement membrane deposits associated with proliferative glomerulonephritis. Initially, the capacity of H221 and H147 to bind directly to glomerular and vascular cell surfaces was evaluated. As demonstrated by FACS, H221 bound preferentially to mesangial cells whereas H147 bound preferentially to endothelial cells. To identify possible target cell surface antigens, Western blots, immunoprecipitation of surface labeled cells, and 2D gel electrophoresis were employed. H221 reacted with a 108kDa protein on mesangial cells not identified by H147, whereas H147 reacted with a 45kDa protein on endothelial cells not identified by H221. These results support the hypothesis that some nephritogenic lupus autoantibodies initiate immune deposit formation through direct interaction with glomerular antigens. Furthermore, they suggest that the site of immune deposition is determined by both antigen binding properties of the relevant antibody and the location of its target ligand within the glomerulus. In a given individual, therefore, the predominant autoantibody-glomerular antigen interaction may influence the morphologic and clinical phenotype expressed. Variation in the predominant interaction may also contribute to variations in disease expression among individuals with lupus nephritis

Illumination devices for photodynamic therapy of the oral cavity

Three compact and efficient designs are proposed to deliver an average irradiance of 50 mW/cm2 with spatial uniformity well above 90% over a 25 mm2 target area for photodynamic therapy of the oral cavity. The main goal is to produce uniform illumination on the target while limiting irradiation of healthy tissue, thus overcoming the need of shielding the whole oral cavity and greatly simplifying the treatment protocol. The first design proposed consists of a cylindrical diffusing fiber placed in a tailored reflector derived from the edge-ray theorem with dimensions 5.5 × 7.2 × 10 mm3; the second device combines a fiber illuminator and a lightpipe with dimensions 6.8 × 6.8 × 50 mm3; the third design, inspired by the tailored reflector, is based on a cylindrical diffusing fiber and a cylinder reflector with dimensions 5 × 10 × 11 mm3. A prototype for the cylinder reflector was built that provided the required illumination for photodynamic therapy of the oral cavity, producing a spatial uniformity on the target above 94% and an average irradiance of 51 mW/cm2 for an input power of 70 mW

Analysis of inhibitor of apoptosis protein family expression during mammary gland development

<p>Abstract</p> <p>Background</p> <p>Inhibitors-of-Apoptosis-Proteins (IAPs) are an evolutionarily conserved family of proteins capable of regulating several facets of apoptosis. IAPs are frequently dysregulated in cancer, but their role in the regulation of apoptosis during developmental processes is not fully understood. Here we examined the expression of IAPs during the post-natal development of the mouse mammary gland, which is a tissue that exhibits a profound induction of apoptosis during involution.</p> <p>Results</p> <p>Six out of eight mammalian IAP family members are expressed in the mammary gland. Notably, quantitative PCR and immunoblotting revealed that XIAP, c-IAP1 and c-IAP2 are down-regulated in pregnancy and lactation, and prior to the onset of involution. In cultured mammary epithelial cells (MECs), XIAP levels decreased in response to inhibition of growth factor signalling. Maintaining XIAP levels in MECs by expressing exogenous XIAP protected them from all apoptotic stimuli tested.</p> <p>Conclusions</p> <p>These data suggest that the developmental regulation of IAP expression <it>in vivo </it>contributes to naturally occurring programmes of cell death.</p