Critical role of the plasma membrane for expression of mammalian mitochondrial side chain cleavage activity in yeast.

Engineered yeast cells efficiently convert ergosta-5-eneol to pregnenolone and progesterone provided that endogenous pregnenolone acetylase activity is disrupted and that heterologous sterol delta7-reductase, cytochrome P450 side chain cleavage (CYP11A1) and 3beta hydroxysteroid dehydrogenase/isomerase (3beta-HSD) activities are present. CYP11A1 activity requires the expression of the mammalian NADPH-adrenodoxin reductase (Adrp) and adrenodoxin (Adxp) proteins as electron carriers. Several parameters modulate this artificial metabolic pathway: the effects of steroid products; the availability and delivery of the ergosta-5-eneol substrate to cytochrome P450; electron flux and protein localization. CYP11A1, Adxp and Adrp are usually located in contact with inner mitochondrial membranes and are directed to the outside of the mitochondria by the removal of their respective mitochondrial targeting sequences. CYP11A1 then localizes to the plasma membrane but Adrp and Adxp are detected in the endoplasmic reticulum and cytosol as expected. The electron transfer chain that involves several subcellular compartments may control side chain cleavage activity in yeast. Interestingly, Tgl1p, a potential ester hydrolase, was found to enhance steroid productivity, probably through both the availability and/or the trafficking of the CYP11A1 substrate. Thus, the observation that the highest cellular levels of free ergosta-5-eneol are found in the plasma membrane suggests that the substrate is freely available for pregnenolone synthesis.     

Geographic range structure in North American landbrids: variation with migratory strategy, trophic level, and breeding habitat

We investigated the relationship between abundance and geographic range structure of 258 North American landbirds. For this purpose we used six measures of range structure based upon fractal geometry and geostatistics, and three ecological characteristics that can influence avian distribution. Permanent residents (PRs) that were abundant showed little fragmentation of their abundance surface at the periphery of their breeding range. Conversely, common Neotropical migrants (NTMs) exhibited low fragmentation of their central populations the abundance surface was smoother for PRs than NTMs or short-distance migrants (SDMs). indicating that changes in abundance occurred more gradually across space for this group. The areas of high abundance for grassland species had little demographic fragmentation, but other populations showed little spatial autocorrelation in abundance. Species that bred in late-successional forests were relatively rare compared to species breeding in other habitat types. Among carnivores. PRs had a higher average abundance than either NTMs or SDMs. Although carnivores had more distributional gaps within their ranges than other trophic groups, the number of gaps did not differ between rare and abundant species, indicating that increased abundance did not change their presence. absence distribution maps. Knowledge of patterns and variations of geographic range structure among species may provide insights into processes that shape and maintain the biodiversity of a continent.     

Essential Role for the Lymphostromal Plasma Membrane Ly-6 Superfamily Molecule Thymic Shared Antigen 1 in Development of the Embryonic Adrenal Gland

Thymic shared antigen 1 (TSA-1) is a plasma membrane protein of the Ly-6 superfamily expressed on thymocytes, thymic stromal cells, and other cells of the hematopoietic system. TSA-1 is also expressed in other nonhematopoietic tissues, in particular, embryonic and adult adrenal glands. To address the function of TSA-1, we generated mutant mice in which TSA-1 expression was inactivated by gene targeting. Here we show that deletion of both TSA-1 alleles results in abnormal adrenal gland development and midgestational lethality due to cardiac abnormalities. We also report that TSA-1-deficient adrenal glands have significantly reduced levels of the catecholamines noradrenaline and adrenaline. We conclude that TSA-1 is required for normal embryonic development but that deletion of its expression does not obviously impair lymphoid development.     

MicroRNAs in hereditary and sporadic premature aging syndromes and other laminopathies

Hereditary and sporadic laminopathies are caused by mutations in genes encoding lamins, their partners, or the metalloprotease ZMPSTE24/FACE1. Depending on the clinical phenotype, they are classified as tissue‐specific or systemic diseases. The latter mostly manifest with several accelerated aging features, as in Hutchinson–Gilford progeria syndrome (HGPS) and other progeroid syndromes. MicroRNAs are small noncoding RNAs described as powerful regulators of gene expression, mainly by degrading target mRNAs or by inhibiting their translation. In recent years, the role of these small RNAs has become an object of study in laminopathies using in vitro or in vivo murine models as well as cells/tissues of patients. To date, few miRNAs have been reported to exert protective effects in laminopathies, including miR‐9, which prevents progerin accumulation in HGPS neurons. The recent literature has described the potential implication of several other miRNAs in the pathophysiology of laminopathies, mostly by exerting deleterious effects. This review provides an overview of the current knowledge of the functional relevance and molecular insights of miRNAs in laminopathies. Furthermore, we discuss how these discoveries could help to better understand these diseases at the molecular level and could pave the way toward identifying new potential therapeutic targets and strategies based on miRNA modulation.     

NF-κB-Chromatin Interactions Drive Diverse Phenotypes by Modulating Transcriptional Noise

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Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma gondii-Mediated Inflammation

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Palaeobiogeographic implications of the first report of the eocrinoid genus Ascocystites Barrande (Echinodermata,Blastozoa) in the Upper Ordovician of the Ougarta Range (Western Algeria)

Several specimens of the genus Ascocystites (Blastozoa, Eocrinoidea) are described for the first time in Late Ordovician deposits (Bou M’Haoud Formation) from the Ougarta Range, Algeria. This genus was previously known in Darriwilian–Sandbian deposits of four other areas of the Mediterranean Province (Czech Republic, France, Morocco and Portugal). The Algerian material completes its palaeobiogeographic distribution in the peri-Gondwanan area, restricted in shallow water settings.