Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension

To identify renally expressed genes that influence risk for hypertension, we integrated expression quantitative trait locus (QTL) analysis of the kidney with genome-wide correlation analysis of renal expression profiles and blood pressure in recombinant inbred strains derived from the spontaneously hypertensive rat (SHR). This strategy, together with renal transplantation studies in SHR progenitor, transgenic and congenic strains, identified deficient renal expression of Cd36 encoding fatty acid translocase as a genetically determined risk factor for spontaneous hypertension.     

Regulated degradation of a class V myosin receptor directs movement of the yeast vacuole

Normal cellular function requires that organelles be positioned in specific locations. The direction in which molecular motors move organelles is based in part on the polarity of microtubules and actin filaments. However, this alone does not determine the intracellular destination of organelles. For example, the yeast class V myosin, Myo2p, moves several organelles to distinct locations during the cell cycle. Thus the movement of each type of Myo2p cargo must be regulated uniquely. Here we report a regulatory mechanism that specifically provides directionality to vacuole movement. The vacuole-specific Myo2p receptor, Vac17p, has a key function in this process. Vac17p binds simultaneously to Myo2p and to Vac8p, a vacuolar membrane protein. The transport complex, Myo2p-Vac17p-Vac8p, moves the vacuole to the bud, and is then disrupted through the degradation of Vac17p. The vacuole is ultimately deposited near the centre of the bud. Removal of a PEST sequence (a potential signal for rapid protein degradation) within Vac17p causes its stabilization and the subsequent 'backward' movement of vacuoles, which mis-targets them to the neck between the mother cell and the bud. Thus the regulated disruption of this transport complex places the vacuole in its proper location. This may be a general mechanism whereby organelles are deposited at their terminal destination.     

Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6

Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous disease involving abnormalities of melanosomes, platelet dense granules and lysosomes. Here we have used positional candidate and transgenic rescue approaches to identify the genes mutated in ruby-eye 2 and ruby-eye mice (ru2 and ru, respectively), two 'mimic' mouse models of HPS. We also show that these genes are orthologs of the genes mutated in individuals with HPS types 5 and 6, respectively, and that their protein products directly interact. Both genes are previously unknown and are found only in higher eukaryotes, and together represent a new class of genes that have evolved in higher organisms to govern the synthesis of highly specialized lysosome-related organelles.     

Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA nephropathy and breast adenocarcinoma

Glycosylation abnormalities have been observed in autoimmune diseases and cancer. Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune disease, IgA nephropathy. The pathways of aberrant O-glycosylation, although different for MUC1 and IgA1, include dysregulation in glycosyltransferase expression, stability, and/or intracellular localization. Moreover, these aberrant glycoproteins are recognized by antibodies, although with different consequences. In breast cancer, elevated levels of antibodies recognizing aberrant MUC1 are associated with better outcome, whereas in IgA nephropathy, the antibodies recognizing aberrant IgA1 are part of the pathogenetic process.     

The oak processionary caterpillar (Thaumetopoea processionea L.) an urticating caterpillar related to the pine processionary caterpillar (Thaumetopoea pityocampa Schiff.) (Lepidoptera,Thaumetopoeidae)

Summary The hairs ofThaumetopoea processionea caterpillars (Lepidoptera) provoke a cutaneous reaction in man and animals. The urticating apparatus, the urticating gland which produces hairs, and the urticating hairs, are similar to those of theT. pityocampa caterpillar. The irritant fraction extracted from hairs contains soluble proteins; one of these shows immunological identity with thaumetopoein, the urticating protein of theTh. pityocampa caterpillar. This thaumetopoein-like protein is currently undergoing isolation and will be subjected to dermatological tests.     

Lipogenesis in rats adapted to intermittent starvation or continuous underfeeding

Zusammenfassung Albinoratten, bei denen zwischen die Fütterungstage 1–2tägige Hungerperioden eingesetzt wurden, zeigten nach 3 Wochen eine wesentlich erhöhte Inkorporation von 1-C¹⁴-Acetat in die Fettsäuren der Leberschnitte. Selbst bei Herabsetzung der Kalorienzufuhr um ca. 50% stieg hier, im Gegensatz zu kontinuierlich unterernährten Tieren, der prozentuale Körperfettgehalt. Die Resultate sprechen für eine Steigerung der Lipogenese.     

Cytochrome oxidase activity in skeletal muscle and the diaphragm of intermittently starving rats

Zusammenfassung Es wurde die Aktivität der Cytochromoxydase von Skelettmuskulatur und Zwerchfell intermittierend hungernder Ratten und bei chronisch durch verminderte Tagesrationen unterernährten Ratten untersucht. Bei den an intermittierendes Hungern adaptierten Ratten war die auf den Gewebestickstoff bezogene Aktivität dieses Enzyms um 80–100% erhöht im Vergleich zu denad libitum gefütterten Kontrolltieren. Bei den einer gewöhnlichen kalorischen Unterernährung ausgesetzten Tieren war die Cytochromoxydaseaktivität praktisch dieselbe wie die der Kontrolltiere.