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.     

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.     

A novel putative auxin carrier family regulates intracellular auxin homeostasis in plants

The phytohormone auxin acts as a prominent signal, providing, by its local accumulation or depletion in selected cells, a spatial and temporal reference for changes in the developmental program. The distribution of auxin depends on both auxin metabolism (biosynthesis, conjugation and degradation) and cellular auxin transport. We identified in silico a novel putative auxin transport facilitator family, called PIN-LIKES (PILS). Here we illustrate that PILS proteins are required for auxin-dependent regulation of plant growth by determining the cellular sensitivity to auxin. PILS proteins regulate intracellular auxin accumulation at the endoplasmic reticulum and thus auxin availability for nuclear auxin signalling. PILS activity affects the level of endogenous auxin indole-3-acetic acid (IAA), presumably via intracellular accumulation and metabolism. Our findings reveal that the transport machinery to compartmentalize auxin within the cell is of an unexpected molecular complexity and demonstrate this compartmentalization to be functionally important for a number of developmental processes.     

TUSC3: functional duality of a cancer gene

Two decades ago, following a systematic screening of LOH regions on chromosome 8p22, TUSC3 has been identified as a candidate tumor suppressor gene in ovarian, prostate and pancreatic cancers. Since then, a growing body of evidence documented its clinical importance in various other types of cancers, and first initial insights into its molecular function and phenotypic effects have been gained, though the precise role of TUSC3 in different cancers remains unclear. As a part of the oligosaccharyltransferase complex, TUSC3 localizes to the endoplasmic reticulum and functions in final steps of N-glycosylation of proteins, while its loss evokes the unfolded protein response. We are still trying to figure out how this mechanistic function is reconcilable with its varied effects on cancer promotion. In this review, we focus on cancer-related effects of TUSC3 and envisage a possible role of TUSC3 beyond endoplasmic reticulum.     

The practical use of a systems approach in large-scale designing

This paper describes in short a new approach to the solution of a practical design problem. The procedures for the approach are based on the use of a systems methodology. The main topics present the development of a project from the external assignment through detailed algorithms of systems modeling to the identification of the solution system.     

Apolipoprotein-mediated pathways of lipid antigen presentation

Peptide antigens are presented to T cells by major histocompatibility complex (MHC) molecules, with endogenous peptides presented by MHC class I and exogenous peptides presented by MHC class II. In contrast to the MHC system, CD1 molecules bind lipid antigens that are presented at the antigen-presenting cell (APC) surface to lipid antigen-reactive T cells. Because CD1 molecules survey endocytic compartments, it is self-evident that they encounter antigens from extracellular sources. However, the mechanisms of exogenous lipid antigen delivery to CD1-antigen-loading compartments are not known. Serum apolipoproteins are mediators of extracellular lipid transport for metabolic needs. Here we define the pathways mediating markedly efficient exogenous lipid antigen delivery by apolipoproteins to achieve T-cell activation. Apolipoprotein E binds lipid antigens and delivers them by receptor-mediated uptake into endosomal compartments containing CD1 in APCs. Apolipoprotein E mediates the presentation of serum-borne lipid antigens and can be secreted by APCs as a mechanism to survey the local environment to capture antigens or to transfer microbial lipids from infected cells to bystander APCs. Thus, the immune system has co-opted a component of lipid metabolism to develop immunological responses to lipid antigens.