Effect of Pedoclimatic Conditions on the Chemical Composition of the Sigoise Olive Cultivar

The present work focused on the quality and the chemical composition of monovarietal virgin olive oil from the Sigoise variety grown in two different locations in Tunisia, viz., a sub‐humid zone (Béjaoua, Tunis) and an arid zone (Boughrara, Sfax). In addition to the quality characteristics (acidity, peroxide value, and the spectrophotometric indices K232 and K270) and the chemical composition (content of fatty acids, antioxidants, and volatile compounds) of the oil, the fruit characteristics of the olives were studied. Except for the content of the majority of the fatty acids, there were significant differences observed in the oil composition of olives that were cultivated in different locations. The content of total phenols and lipoxygenase (LOX) oxidation products was higher for olives grown at the higher altitude, whereas that of α‐tocopherol, carotenes, and chlorophylls was higher for olives from the Boughrara region (lower altitude). Moreover, olives produced at the higher altitude showed a higher ripeness index and oil content than those cultivated at the lower altitude.     

A putative Alzheimer's disease risk allele in PCK1 influences brain atrophy in multiple sclerosis

Background

Brain atrophy and cognitive dysfunction are neurodegenerative features of Multiple Sclerosis (MS). We used a candidate gene approach to address whether genetic variants implicated in susceptibility to late onset Alzheimer''s Disease (AD) influence brain volume and cognition in MS patients.

Methods/Principal Findings

MS subjects were genotyped for five single nucleotide polymorphisms (SNPs) associated with susceptibility to AD: PICALM, CR1, CLU, PCK1, and ZNF224. We assessed brain volume using Brain Parenchymal Fraction (BPF) measurements obtained from Magnetic Resonance Imaging (MRI) data and cognitive function using the Symbol Digit Modalities Test (SDMT). Genotypes were correlated with cross-sectional BPF and SDMT scores using linear regression after adjusting for sex, age at symptom onset, and disease duration. 722 MS patients with a mean (±SD) age at enrollment of 41 (±10) years were followed for 44 (±28) months. The AD risk-associated allele of a non-synonymous SNP in the PCK1 locus (rs8192708^G) is associated with a smaller average brain volume (P = 0.0047) at the baseline MRI, but it does not impact our baseline estimate of cognition. PCK1 is additionally associated with higher baseline T2-hyperintense lesion volume (P = 0.0088). Finally, we provide technical validation of our observation in a subset of 641 subjects that have more than one MRI study, demonstrating the same association between PCK1 and smaller average brain volume (P = 0.0089) at the last MRI visit.

Conclusion/Significance

Our study provides suggestive evidence for greater brain atrophy in MS patients bearing the PCK1 allele associated with AD-susceptibility, yielding new insights into potentially shared neurodegenerative process between MS and late onset AD.     

Universal influenza vaccination: the time to act is now

Annual influenza epidemics create a significant public health burden each year in the United States. That influenza continues to pose a public health threat despite being largely preventable through vaccination is indicative of continuing weaknesses in the U.S.'s public health system. Moreover, the burden of annual influenza epidemics and the fragility and instability of the capacity to respond to them underscore the U.S.'s ongoing vulnerability to pandemic influenza and highlights gaps in bioterrorism preparedness and response efforts. This article examines the burden of annual influenza epidemics in the U.S., efforts to combat that burden with vaccination, shortcomings of influenza vaccination efforts, and how those shortcomings exemplify weaknesses in pandemic influenza and bioterrorism preparedness efforts. We make the case for establishing an annual universal influenza vaccination program to assure access to influenza vaccination to anyone who can safely receive vaccination and desires it. Such a program could greatly reduce the annual burden of influenza while advancing and maintaining U.S. pandemic influenza and bioterrorism preparedness and response efforts.     

TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes

CD3-specific antibodies have the unique capacity to restore self-tolerance in established autoimmunity. They induce long-term remission of overt diabetes in nonobese diabetic (NOD) mice and in human type I diabetes. The underlying mechanisms had been unclear until now. Here we report that treatment with CD3epsilon-specific antibodies induces transferable T-cell-mediated tolerance involving CD4+CD25+ cells. However, these CD4+CD25+ T cells are distinct from naturally occurring regulatory T cells that control physiological autoreactivity. CD3-specific antibody treatment induced remission in NOD Cd28-/- mice that were devoid of such regulatory cells. Remission of diabetes was abrogated by coadministration of a neutralizing transforming growth factor (TGF)-beta-specific antibody. The central role of TGF-beta was further suggested by its increased, long-lasting production by CD4+ T cells from tolerant mice. These data explain the intriguing tolerogenic effect of CD3-specific antibodies and position them as the first clinically applicable pharmacological stimulant of TGF-beta-producing regulatory CD4+ T cells.     

Choristoneura fumiferana Granulovirus p74 protein, a highly conserved baculoviral envelope protein

A gene that encodes a homologue to baculoviral p74, an envelope-associated viral structural protein, has been identified and sequenced on the genome of Choristoneura fumiferana granulovirus (ChfuGV). A part of the ChfuGV p74 gene was located on an 8.9 kb BamHI subgenomic fragment using different sets of degenerated primers. These were designed using the results of the protein sequencing of a major 74 kDa structural protein that is associated with the occlusion-derived virus (ODV). The gene has a 1992 nucleotide (nt) open-reading frame (ORF) that encodes a protein with 663 amino acids with a predicted molecular mass of 74,812 Da. Comparative studies revealed the presence of two major conserved regions in the ChfuGV p74 protein. This study also shows that all of the p74 proteins contain two putative transmembrane domains at their C-terminal segments. At the nucleotide sequence level, two late promoter motifs (TAAG and GTAAG) were located upstream of the first ATG of the p74 gene. The gene contained a canonical poly(A) signal, AATAAA, at its 3 non-translated region. A phylogenetic tree for baculoviral p74 was constructed using a maximum parsimony analysis. The phylogenetic estimation demonstrated that ChfuGV p74 is related the closest to those of Cydia pomonella granulovirus (CpGV) and Phthorimaea operculella granulovirus (PhopGV).     

Evaluation of various serum and animal protein free media for the production of a veterinary rabies vaccine in BHK-21 cells

We have carried out the adaptation of BHK-21 cells to two serum free (Ex Cell 520 and HyQ PF CHO) and three animal protein free media: Ex Cell 302, HyQ PF CHO MPS and Rencyte BHK. After a direct switch or a gradual adaptation, we have achieved BHK-21 cells growth in the following media: HyQ PF CHO, HyQ PF CHO MPS, Rencyte BHK and Ex Cell 302. The most suitable media for BHK-21 cells growth, with respect to cell density and specific growth rate, were HyQ PF CHO and HyQ PF CHO MPS. Hence we have selected these media to study cell growth and the production of rabies virus. Kinetic studies of cell growth in spinner flasks using the selected media have shown that a maximal cell density of 2x10(6) cells x ml(-1) was reached in both media. For rabies virus production, the viral titer obtained was 1.7x10(6) FFU x ml(-1) in HyQ PF CHO as well as in HyQ PF CHO MPS medium. The optimization of rabies virus production by BHK-21 cells grown in a 2 l bioreactor using the selected media, pointed to the following parameters: culture mode, perfusion rate and multiplicity of infection (MOI), as being the critical factors for achieving a good virus yield. When tested in mice, the activity of the experimental vaccines prepared on HyQ PF CHO MPS medium has shown a protective activity that meets WHO requirements.     

Early events in the activation of Fc gamma RIIA in human neutrophils: stimulated insolubilization, translocation to detergent-resistant domains, and degradation of Fc gamma RIIA

The signal transduction mechanisms associated with the ligation of FcgammaRIIA in human neutrophils are as yet only incompletely characterized. In the present study, we have investigated the distribution and fate of FcgammaRIIA following its cross-linking. The results obtained indicate that cross-linking of FcgammaRIIA led, within a few seconds, to its translocation into a nonionic detergent-insoluble fraction. This was followed, within a couple of minutes, by a substantial loss of immunoreactive FcgammaRIIA in the cells. The stimulated degradation of FcgammaRIIA was blocked by the Src kinase inhibitor PP1 but not by wortmannin, ST-638, piceatannol, or cytochalasin B. Cross-linked FcgammaRIIA could be solubilized by saponin (in the presence of Nonidet P-40) and by beta-octylglucoside. Sucrose gradient analysis of the distribution of FcgammaRIIA revealed that its cross-linking led to its translocation into the pellets and not the light buoyant density fractions classically associated with lipid rafts. Disruption of cholesterol-containing membrane microdomains with filipin prevented the degradation of FcgammaRIIA but did not inhibit the stimulation of the pattern of tyrosine phosphorylation or the mobilization of calcium that followed FcgammaRIIA cross-linking. These data suggest that both cholesterol-rich domains and Src kinases are required for the degradation of the activated FcgammaRIIA and provide new insights into the early events following FcgammaRIIA cross-linking.     

Effect of hyperthermia on blood constituents in the domestic rabbit (Lepus cuniculus)

1. 1. Effects of exposing rabbits to temperatures 37–50°C on body-core temperature and some blood constituents were investigated.

2. 2. Heat stroke death occurred at or above a critical core-temperature of 43.0°C.

3. 3. Plasma osmolality and levels of glucose, urea and lactate were significantly elevated in hyperthermia.

4. 4. Widespread tissue damage was indicated by increases in plasma activities of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and creatinine phosphokinase (CPK).

5. 5. The most sensitive indicators of impending heat stroke in heat stressed rabbits were plasma levels or urea, lactate and CPK.

Heterogeneity of mutations in the uroporphyrinogen III synthase gene in congenital erythropoietic porphyria

Summary Congenital erythropoietic porphyria (CEP) or Günther's disease is an inborn error of heme biosynthesis transmitted as an autosomal recessive trait and characterized by a profound deficiency of uroporphyrinogen III synthase (UROIIIS) activity. We have previously described two missense mutations in the UROIIIS gene, confirming that the primary defect responsible for CEP is a structural alteration of this gene. We have extended our work to 5 additional unrelated families. Two new point mutations, a deletion and an insertion have been found in the messenger RNA. Our study shows that a molecular heterogeneity of the mutations exists in Günther's disease. One mutation (C73R), however, appears to be more frequent than the others. Finally, the different normal and mutated proteins have been expressed in Escherichia coli to determine the consequence of the mutations on the enzyme activity.