Relevance of gamma interferon, tumor necrosis factor alpha, and interleukin-10 gene polymorphisms to susceptibility to Mediterranean spotted fever.

The acute phase of Mediterranean spotted fever (MSF) is characterized by dramatic changes in cytokine production patterns, clearly indicating their role in the immunomodulation of the response against the microorganism, and the differences in cytokine production seem to influence the extent and severity of the disease. In this study, the single nucleotide polymorphisms (SNPs) of tumor necrosis factor alpha (TNF-α) -308G/A (rs1800629) and interleukin-10 (IL-10) -1087G/A (rs1800896), -824C/T (rs1800871), and -597C/A (rs1800872) and the gamma interferon (IFN-γ) T/A SNP at position +874 (rs2430561) were typed in 80 Sicilian patients affected by MSF and in 288 control subjects matched for age, gender, and geographic origin. No significant differences in TNF-α -308G/A genotype frequencies were observed. The +874TT genotype, associated with an increased production of IFN-γ, was found to be significantly less frequent in MSF patients than in the control group (odds ratio [OR], 0.18; 95% confidence interval [95% CI], 0.06 to 0.51; P corrected for the number of genotypes [Pc], 0.0021). In addition, when evaluating the IFN-γ and IL-10 genotype interaction, a significant increase of +874AA/-597CA (OR, 5.31; 95% CI, 2.37 to 11.88; Pc, 0.0027) combined genotypes was observed. In conclusion, our data strongly suggest that finely genetically tuned cytokine production may play a crucial role in the regulation of the immune response against rickettsial infection, therefore influencing the disease outcomes, ranging from nonapparent or subclinical condition to overt or fatal disease

Role of prothrombotic polymorphisms in successful or unsuccessful aging

The study of the genetic profile of centenarians aims to identify the genes and allelic variants which may influence a greater life expectancy and that can be considered as predisposing factors associated to the aging diseases, such as Alzheimer. Centenarians, that represent a cohort of selected survivors, show an hypercoagulability state characterised by striking signs of high coagulation enzyme activity, as directly assessed by the tested higher plasma level of some important factors involved in the haemostasis balance. Anyway, these individuals seem to have a reduced susceptibility to dementia, as well as to cardiovascular events. In this study we analyze the frequencies of Leiden Factor V polymorphism (G1691A), and G20210A of prothrombin (FII) in three cohorts of subjects: patients with Alzheimer\u2019s disease (unsuccessful aging), nonagenarians (successful aging) and young healthy controls, to assess whether allelic variants associated to the modification of haemostatic system function, may play a role in the protection or susceptibility to Alzheimer disease, as well as to reach a successful aging. No significant differences were observed in the frequencies of the three groups studied. These results indicate that the presence or absence of the gene variants examined did not influence the achievement of advanced age and are not risk factors for Alzheimer\u2019s disease. The state of hypercoagulability and the possession of these risk alleles appear to be compatible with the achievement of longevity and are not implied as risk factors in Alzheimer disease development

Analysis of the Regional Ionosphere at Low Latitudes in Support of the Biomass ESA Mission

Biomass is a spaceborn polarimetric P-band (435 MHz) synthetic aperture radar (SAR) in a dawn-dusk low Earth orbit. Its principal objective is to measure biomass content and change in all the Earth’s forests. The ionosphere introduces Faraday rotation on every pulse emitted by low-frequency SAR and scintillations when the pulse traverses a region of plasma irregularities, consequently impacting the quality of the imaging. Some of these effects are due to Total Electron Content (TEC) and its gradients along the propagation path. Therefore, an accurate assessment of the ionospheric morphology and dynamics is necessary to properly understand the impact on image quality, especially in the equatorial and tropical regions. To this scope, we have conducted an in-depth investigation of the significant noise budget introduced by the two crests of the Equatorial Ionospheric Anomaly (EIA) over Brazil and South-East Asia. The work is characterized by a novel approach to conceive a SAR-oriented ionospheric assessment, aimed at detecting and identifying spatial and temporal TEC gradients, including scintillation effects and Traveling Ionospheric Disturbances, by means of Global Navigation Satellite Systems (GNSS) ground-based monitoring stations. The novelty of this approach resides in the customization of the information about the impact of the ionosphere on SAR imaging as derived by local dense networks of ground instruments operating during the passes of Biomass spacecraft. The results identify the EIA crests as the regions hosting the bulk of irregularities potentially causing degradation on SAR imaging. Interesting insights about the local characteristics of low-latitudes ionosphere are also highlighted

N-terminal acetylation inhibits protein targeting to the endoplasmic reticulum

Amino-terminal acetylation is probably the most common protein modification in eukaryotes with as many as 50%–80% of proteins reportedly altered in this way. Here we report a systematic analysis of the predicted N-terminal processing of cytosolic proteins versus those destined to be sorted to the secretory pathway. While cytosolic proteins were profoundly biased in favour of processing, we found an equal and opposite bias against such modification for secretory proteins. Mutations in secretory signal sequences that led to their acetylation resulted in mis-sorting to the cytosol in a manner that was dependent upon the N-terminal processing machinery. Hence N-terminal acetylation represents an early determining step in the cellular sorting of nascent polypeptides that appears to be conserved across a wide range of species

Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling

AMP-activated kinase (AMPK) and target of rapamycin (TOR) signalling coordinate cell growth, proliferation, metabolism and cell survival with the nutrient environment of cells. The poor vasculature and nutritional stress experienced by cells in solid tumours raises the question: how do they assimilate sufficient nutrients to survive? Here, we show that human and fission yeast cells import ATP and AMP from their external environment to regulate AMPK and TOR signalling. Exposure of fission yeast (Schizosaccharomyces pombe) and human cells to external AMP impeded cell growth; however, in yeast this restraining impact required AMPK. In contrast, external ATP rescued the growth defect of yeast mutants with reduced TORC1 signalling; furthermore, exogenous ATP transiently enhanced TORC1 signalling in both yeast and human cell lines. Addition of the PANX1 channel inhibitor probenecid blocked ATP import into human cell lines suggesting that this channel may be responsible for both ATP release and uptake in mammals. In light of these findings, it is possible that the higher extracellular ATP concentration reported in solid tumours is both scavenged and recognized as an additional energy source beneficial for cell growth

Analysis of the Regional Ionosphere at Low Latitudes in Support of the Biomass ESA Mission

Biomass is a spaceborn polarimetric P-band (435 MHz) synthetic aperture radar (SAR) in a dawn-dusk low Earth orbit. Its principal objective is to measure biomass content and change in all the Earth's forests. The ionosphere introduces the Faraday rotation on every pulse emitted by low-frequency SAR and scintillations when the pulse traverses a region of plasma irregularities, consequently impacting the quality of the imaging. Some of these effects are due to total electron content (TEC) and its gradients along the propagation path. Therefore, an accurate assessment of the ionospheric morphology and dynamics is necessary to properly understand the impact on image quality, especially in the equatorial and tropical regions. To this scope, we have conducted an in-depth investigation of the significant noise budget introduced by the two crests of the equatorial ionospheric anomaly (EIA) over Brazil and Southeast Asia. This paper is characterized by a novel approach to conceive a SAR-oriented ionospheric assessment, aimed at detecting and identifying spatial and temporal TEC gradients, including scintillation effects and traveling ionospheric disturbances, by means of Global Navigation Satellite Systems ground-based monitoring stations. The novelty of this approach resides in the customization of the information about the impact of the ionosphere on SAR imaging as derived by local dense networks of ground instruments operating during the passes of Biomass spacecraft. The results identify the EIA crests as the regions hosting the bulk of irregularities potentially causing degradation on SAR imaging. Interesting insights about the local characteristics of low-latitudes ionosphere are also highlighted.</p

Efficacy and safety of lomitapide in familial chylomicronaemia syndrome

Familial chylomicronaemia syndrome (FCS) is a rare autosomal recessive disorder, resulting in elevated triglycerides (TGs), abdominal pain and pancreatitis. Treatment options are limited. Lomitapide, a microsomal triglyceride transfer protein inhibitor, is approved for the treatment of homozygous familial hypercholesterolaemia. Whether its therapeutic use may be extended to FCS remains unknown. The aim of this study was to evaluate the efficacy and safety of lomitapide in adult patients with FCS