Cholinergic blockade and the mesenteric artery response to head-up tilt-induced central hypovolaemia

The methylation of phosphatidylethanolamine is an auxiliary pathway for phosphatidylcholine biosynthesis in liver. Two forms of the enzyme, phosphatidylethanolamine N-methyltransferase, which catalyses this reaction, are located on the endoplasmic reticulum and mitochondria-associated membranes. Both forms are encoded by a single murine gene, Pempt, located on chromosome 11. The expression of the gene begins at birth. An inverse relationship exists between the rate of liver growth and the expression of phosphatidylethanolamine N-methyltransferase. However, disruption of the Pempt gene does not alter liver growth in mice or cause any other obvious phenotype.     

A Golgi localization signal identified in the Menkes recombinant protein

Menkes disease arises from a genetic impairment in copper transport. The gene responsible for the phenotype has been identified as a copper transporting ATPase ( ATP7A ). Recently, the protein encoded by the ATP7A gene has been localized to the Golgi complex. In order to investigate the role of the Menkes disease protein in copper transport, recombinant constructs containing both the full-length open reading frame and an alternatively spliced form have been successfully expressed and localized in mammalian cells. Other studies of a patient with occipital horn syndrome, an allelic variant of Menkes disease, have demonstrated that only this alternatively spliced isoform and not the full-length form is expressed in this patient. The milder form of this patient's phenotype suggests that the alternatively spliced isoform has some functional role in copper transport. In the present study the full-length recombinant Menkes protein was shown by immunofluorescence to localize to the Golgi apparatus and the alternatively spliced form, lacking sequences for transmembrane domains 3 and 4 encoded by exon 10, was shown to localize to the endoplasmic reticulum. Using sequences from exon 10 fused to a non-Golgi reporter molecule, a 38 amino acid sequence containing transmembrane domain 3 of the Menkes protein was found to be sufficient for localization to the Golgi complex. Therefore, the protein sequence encoded by exon 10 may be responsible for this differential localization and both isoforms may be required for comprehensive transport of copper within the cell.     

Effects of growth hormone, insulin-like growth factor-I, and cortisol on periparturient antibody response profiles of dairy cattle

The objectives of this study were to determine hormone and antibody response profiles from the prepartum period to peak lactation, and evaluate potential immunomodulatory effects of the classic endocrine hormones, growth hormone (GH), insulin-like growth factor-I (IGF-I) and cortisol. Specifically, 33 Holstein cows were immunized with ovalbumin (OVA) and Escherichia coli J5 at weeks -8 and -3 prior to parturition. At parturition (week 0), cows received an additional immunization of OVA. Blood was collected at weeks -8, -3, 0, 3 and 6 relative to parturition and various samples were used to determine plasma hormone concentration, serum immunoglobulin (Ig), and specific antibody response to OVA and E. coli. Colostrum and milk samples were also collected post-parturition to monitor local immunoglobulin and antibody responses. Results indicated that not all periparturient cows exhibited depressed immune response, and that antibody response to OVA could be used to partition cows into 3 groups recognizing animals with sustained measurable antibody response before and after parturition (Group 1), animals which responded poorly to immunization at parturition (Group 2), and animals which did not respond to immunizations at week -3 or parturition (Group 3). Cows with the highest antibody response to OVA (Group 1) also tended (P < or = 0.10) to have the highest response to E. coli J5 at parturition and had the lowest incidence of disease, particularly mastitis. Antibody response to OVA measured in milk tended to be higher in Group 1 cows, particularly at week 0 (P < or = 0.06) compared to cows of Group 3. IGF-I was higher (P < or = 0.05) in cows of Group 1 than Group 3 at peak lactation (week 6).     

Reduced percolation concentration in polypropylene/expanded graphite composites: Effect of viscosity and polypyrrole

With the goal to obtain material combining electrical and thermal conductivity at low filler loadings, composites based on polypropylenes (PP) and expanded graphite (EG) have been prepared. The effects of matrix viscosity and of coating the EG particles with polypyrrole (PPy, EG/PPy = 37.5/62.5 by weight) on the EG dispersibility and formation of percolation structures have been analyzed. When increasing the EG amount from 6 to 8 wt %, the electrical conductivity of PP/EG composites increased by 7–9 orders of magnitude, independent of matrix viscosity. When EG‐PPy is added, percolation was observed between 8 and 12 wt % EG‐PPy (3 and 4.5 wt % EG) in case of PP with higher viscosity and 6 wt % EG (2.25 wt % EG) in case of PP with lower viscosity, exhibiting a strong synergistic effect of EG and PPy in the latter case. In contrast, PPy does not contribute to reduction of thermal percolation concentration. Thermal percolation is observed at 8 wt % EG in PP/EG composites, but no percolation was found in PP/EG‐PPy composites with EG‐PPy contents of up to 20 wt %, corresponding to 7.5 wt % EG. Analyzing the melt rheology it becomes clear that the contribution of PPy to the formation of a filler network is strongly dependent on the matrix viscosity. The comparison of thermal, electrical and rheological percolation reveals that PPy participates in electron transport reducing the electrical percolation but not to heat transport. Overall, we found a good correlation between electrical, thermal, and melt rheological percolation concentrations. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41994.     

Men as caregivers: reciprocal relationships or obligation?

The adult cuticular wing of Drosophila is covered by an array of distally pointing hairs that reveals the planar polarity of the wing. We report here that mutations in dachsous disrupt this regular pattern, and do so by affecting frizzled signaling. dachsous encodes a large membrane protein that contains many cadherin domains and dachsous mutations cause deformed body parts. We found that mutations in dachsous also result in a tissue polarity phenotype that at the cellular level is similar to frizzled, dishevelled and prickle, as many cells form a single hair of abnormal polarity. Although their cellular phenotype is similar to frizzled, dishevelled and prickle, dachsous mutant wings display a unique and distinctive abnormal hair polarity pattern including regions of reversed polarity. The development of this pattern requires the function of frizzled pathway genes suggesting that in a dachsous mutant the frizzled pathway is functioning - but in an abnormal way. Genetic experiments indicated that dachsous was not required for the intracellular transduction of the frizzled signal. However, we found that dachsous clones disrupted the polarity of neighboring wild-type cells suggesting the possibility that dachsous affected the intercellular signaling function of frizzled. Consistent with this hypothesis we found that frizzled clones in a dachsous mutant background displayed enhanced domineering non-autonomy, and that the anatomical direction of this domineering non-autonomy was altered in regions of dachsous wings that have abnormal hair polarity. The direction of this domineering nonautonomy was coincident with the direction of the abnormal hair polarity. We conclude that dachsous causes a tissue polarity phenotype because it alters the direction of frizzled signaling.     

Pathogenic mechanisms in the rheumatoid nodule: comparison of proinflammatory cytokine production and cell adhesion molecule expression in rheumatoid nodules and synovial membranes from the same patient

OBJECTIVE: To investigate the production of proinflammatory cytokines and expression of cell adhesion molecules in the rheumatoid nodule. METHODS: Cytokine content (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], and IL-1 receptor antagonist [IL-1Ra]), at the messenger RNA (mRNA) and protein levels, and cell adhesion molecule expression were studied in 16 rheumatoid nodules and 6 synovial membranes. RESULTS: Macrophages in the rheumatoid nodules contained TNFalpha, IL-1beta, and IL-1Ra mRNA and protein, particularly in perivascular cells of the stroma and in the palisading layer. All cell adhesion molecules studied were expressed in both the rheumatoid nodules and synovial membranes, with increased expression of E-selectin in the rheumatoid nodule compared with the synovial membrane, and with the absence of vascular cell adhesion molecule 1 expression on cells of the palisading layer in the rheumatoid nodule. CONCLUSION: The presence of similar proinflammatory cytokines and cell adhesion molecules in the rheumatoid nodule and synovial membrane suggests that similar pathogenic processes result in the chronic inflammation and tissue destruction in these lesions.