Neural cell adhesion molecules in rat endocrine tissues and tumor cells: distribution and molecular analysis

The adhesive properties of neural cell adhesion molecules (NCAMs) can be modified by alternative splicing of the primary transcript or posttranslational modifications. In the present study, we describe distinct forms of alternative splicing and posttranslational modification of the extracellular domain of NCAM of various endocrine tissues and derived tumor cells of the rat. Using an antiserum detecting the immunoglobulin-like domains of NCAM as well as a monoclonal antibody recognizing the NCAM-specific polysialic acid (PSA), we observed a similar staining pattern in adrenals, pituitary, and neoplastic endocrine cells. In endocrine tumor cells [pheochromocytoma (PC12), insulinoma (RINA2), and pituitary tumor cells (GH3)], NCAM immunoreactivity was most intense at contact sites between the cells. The immunocytochemical data were substantiated by results of in situ hybridization histochemistry. Specifically, higher levels of NCAM mRNA were detected in the adrenal cortex than in the medulla. In the pituitary, NCAM mRNA was more abundant in the anterior and intermediate lobes than in the neural lobe. The sequence of NCAM mRNAs in endocrine cells was analyzed by polymerase chain reaction and S1 nuclease protection assays. We found that major exons 4-13 of the NCAM mRNA in endocrine tissues and related tumor cell lines were homologous to those in the brain. However, PC12, RINA2, and GH3 tumor cells; normal rat pituitaries; and adrenals contained different amounts of NCAM mRNA with an alternative extra exon, termed VASE (also called pi in mouse) between constitutive exons 7 and 8. In addition, in pituitaries, we detected an alternative exon in splice site a between the constitutive exons 12 and 13, termed a15, with or without an AAG triplett. These sites are thought to be important for the adhesive properties of NCAM. Therefore, these results suggest that modifications of NCAM may be important for adhesive interactions in normal and neoplastic endocrine cells

HIV infection and cardiovascular disease

Aims With the success of antiretroviral therapy (ART), non-human immunodeficiency virus (HIV)-related comorbidities like cardiovascular diseases (CVDs) are of increasing concern. We describe important recent research developments on the epidemiology of CVD in HIV infection, ART-related metabolic changes, and cardioprotective anti-inflammatory mechanisms, and summarize management strategies for CVD risk reduction. Methods and results We systematically identified and analysed systematic reviews and most cited literature published in the last 3 years and supplemented findings with selected evidence based on clinical expertise. Among HIV-infected individuals, the prevalence of CVD risk factors and the risk for CVD is higher compared with HIV negatives. Antiretroviral drugs may induce dyslipidaemia, reduce insulin sensitivity, and promote body fat redistribution that additionally contributes to CVD risk. Some antiretroviral drugs may increase risk for CVD events, but the absolute risk increase is moderate and has to be put into perspective with the massive HIV-related benefits. Sustained HIV suppression reduces systemic inflammatory markers and is associated with a moderate reduction in CVD events. Regular CVD risk assessment and counselling to stop smoking must be regularly done in all HIV-infected individuals. Statins are effective for the treatment of dyslipidaemia in HIV infection, but drug interactions with ART need to be considered. Conclusion Human immunodeficiency virus-infected individuals are at increased risk for CVD. Timely initiation of ART with consequent viral suppression is likely to reduce CVD events and to offset potential side effects from ART-induced metabolic changes. Reduction in smoking in HIV-infected individuals is a public health priorit

Reaction Textures and Metamorphic Evolution of Sapphirine-bearing Granulites from the Gruf Complex, Italian Central Alps

Mineral chemistries and textures are described from a suite of sapphirine-bearing granulites from the Gruf Complex of the Italian Central Alps. The granulites contain combinations of garnet, orthopyroxene, sapphirine, sillimanite, cordierite, biotite, quartz, spinel, corundum, staurolite, plagioclase, K-feldspar, ilmenite and rutile, in assemblages with low (usually negative) variance. They are outstanding in that they preserve a textural and chemical record of a protracted metamorphic evolution. Reaction textures are common and include: (i) pseudomorphs (e.g. of sillimanite after kyanite); (ii) relatively coarse-grained monomineralic reaction rims (e.g. of cordierite between sapphirine and quartz); (iii) fine-grained symplectitic coronas (e.g. of orthopyroxene + sapphirine round garnet); (iv) inclusions, in garnet cores, of minerals (e.g. staurolite) not found elsewhere in the rocks. Detailed microprobe study has revealed large chemical variations within each phase. Different textural types of each phase have different compositions, and strong zoning is preserved in garnet (Mg/(Mg + Fe) from 0.30 to 0.61) and coarse sapphirine. Inclusion populations in garnet correlate with host composition. The textural and chemical features are interpreted in terms of successive equilibrium assemblages and reactions. Metamorphic conditions operative at each stage in the evolution are calculated using published geothermometers and geobarometers as well as thermodynamically calibrated MAS and FASH equilibria. The results are used to construct a P—T-time path for the sapphirine-granulites, which can be summarized as follows: (i) Increasing T at high P (>7 kb). Partial melting. (ii) A maximum T of ∼830 °C attained at ∼10 kb. (iii) Almost isothermal decompression, reaching 750 °C at ∼5 kb, under conditions of low μH2O. (iv) Further cooling, and decompression. Localized hydration. Rocks exposed. The P—T-time path is interpreted as the product of a single metamorphic cycle (the tertiary ‘Lepontine' event) and is extrapolated to the Gruf Complex as a whole. When combined with published geochronological data, the results indicate an average uplift rate in excess of 2 mm/yr for the Gruf Complex between 38 and 30 Ma ago. An in situ partial melting origin for the sapphirine-granulites is favoured. Extraction of an iron-rich granitic liquid from a normal pelitic palaeosome could generate a refractory residue with the required Mg, Al-rich composition. The change in bulk solid composition during partial melting is thought to account for the extraordinarity strong zoning in the garnet

An integrated approach to rotorcraft human factors research

As the potential of civil and military helicopters has increased, more complex and demanding missions in increasingly hostile environments have been required. Users, designers, and manufacturers have an urgent need for information about human behavior and function to create systems that take advantage of human capabilities, without overloading them. Because there is a large gap between what is known about human behavior and the information needed to predict pilot workload and performance in the complex missions projected for pilots of advanced helicopters, Army and NASA scientists are actively engaged in Human Factors Research at Ames. The research ranges from laboratory experiments to computational modeling, simulation evaluation, and inflight testing. Information obtained in highly controlled but simpler environments generates predictions which can be tested in more realistic situations. These results are used, in turn, to refine theoretical models, provide the focus for subsequent research, and ensure operational relevance, while maintaining predictive advantages. The advantages and disadvantages of each type of research are described along with examples of experimental results