PGC-1α senses the CBC of pre-mRNA to dictate the fate of promoter-proximally paused RNAPII

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The mast cells of the mammalian central nervous system V. The effect of compound 48|80 on the neurolipomastocytoid cells and related areas of the CNS: Early changes

Summary The response of the neurolipomastocytoid cells (NLMs) and elements in their vicinity within the central nervous system of various animal species was studied following injection of the animals with the specific mast cell (MC)-discharger compound 48/80. The observed alterations were grouped into those occurring early (0–21 days) and later (up to 18 months). In the present report, only the acute changes are described, light and electron microscopically.Most experimental animals developed prostration, scratching, acral-type reaction, signs of respiratory distress and salivation, and, in the monkey, uncontrollable somnolence. Within about 2 weeks after the injection some animals (especially guinea pigs) manifested various degrees of limb paralysis. The NLMs, like MCs outside the CNS, responded to injection by various degrees of degranulation, vacuolation, marked variation in granule size, apparent cell loss and sometimes an increase in number. Electron microscopically, particulate breakdown products of the granules of the NLMs appeared in the cytoplasm; occasionally there was suggestive evidence that they had passed inward across the vessel wall to reach the lumen, and also outward through the outermost basal lamina. Perivascular astrocytic feet showed swelling and vacuolation shortly after the injection, which was followed by evidence of gliosis and later scarring; occasionally, alterations in the mitochondria were observed. In the spinal cord of the guinea pig, capillary neoformation was observed with endothelial cells and adjacent NLMs taking up tritiated thymidine.The discussion centers on the partial similarity of response to compound 48/80 of the NLMs to that of MCs outside the CNS, and the probable involvement of NLM-damage in the parenchymal changes.The preliminary portion of this work was done with T. Wiedman at Ames Research Center, Moffett Field, California; a short communication has been published (Ibrahim 1970), and part of the study was presented at the Annual Meeting of the American Association of Anatomists (Ibrahim et al. 1976)Supported by a grant from the Incentive Plan of the Medical School, American University of Beirut, Lebanon, by Biomedical Research support Grant RR 05373 from the Biomedical Research Support Branch, Division of Research Facilities and Resources, National Institutes of Health, and by Research Grant No. MA 004 from the College of Graduate Studies, University of Kuwait     

Enhanced gene replacements in Ku80 disruption mutants of the dermatophyte, Trichophyton mentagrophytes

The frequency of targeted gene disruption via homologous recombination is low in the clinically important dermatophyte, Trichophyton mentagrophytes . The Ku genes, Ku70 and Ku80 , encode key components of the nonhomologous end-joining pathway involved in DNA double-strand break repair. Their deletion increases the homologous recombination frequency, facilitating targeted gene disruption. To improve the homologous recombination frequency in T. mentagrophytes , the Ku80 ortholog was inactivated. The nucleotide sequence of the Ku80 locus containing a 2788-bp ORF encoding a predicted product of 728 amino acids was identified, and designated as TmKu80 . The predicted TmKu80 product showed a high degree of amino acid sequence similarity to known fungal Ku80 proteins. Ku80 disruption mutant strains of T. mentagrophytes were constructed by Agrobacterium tumefaciens -mediated genetic transformation. The average homologous recombination frequency was 73.3 ± 25.2% for the areA/nit-2 -like nitrogen regulatory gene ( tnr ) in Ku80⁻ mutants, about 33-fold higher than that in wild-type controls. A high frequency ( c . 67%) was also obtained for the Tri m4 gene encoding a putative serine protease. Ku80 ⁻ mutant strains will be useful for large-scale reverse genetics studies of dermatophytes, including T. mentagrophytes , providing valuable information on the basic mechanisms of host invasion.     

Developmental and housekeeping transcriptional programs in Drosophila require distinct chromatin remodelers

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A hexasome is the preferred substrate for the INO80 chromatin remodeling complex,allowing versatility of function

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Plant-species richness and extinction on isolated dunes along the rocky coast of northwestern Spain

Abstract. Data on distribution and abundance of rare plant species on isolated coastal dunes along the rocky coast of northwestern Spain were compared with the local floristic literature in order to reconstruct past distribution and local extinction of species. Species extinction was not confined to species with a narrow distribution but also included widely distributed ones. Moreover, there was no evidence of colonization. Species number was related to beach and dune area, but species differed in the minimum area required for occurrence. The largest dune reserve possible would probably be insufficient to avoid further extinctions, so also small areas containing particular species should be preserved. There was no significant relationship between abundance of species in the local dune communities and their total distribution, and there were few satellite species. The former might be attributed to low fertility and habitat diversity.     

Increases in permeability of Escherichia coli outer membrane induced by polycations

The action of polycations (such as polylysine and compound 48/80) on Escherichia coli was studied with use of Ca2+, K+ and TPP+ ion-selective electrodes. Rapid efflux of Ca2+ was observed when a polycation was added in cell suspension. The polycation treatment promoted a drug-inducing K+ release from the cytoplasmic membrane. TPP+ uptake was also increased by addition of a polycation. Without the polycation treatment, the uptake of TPP+ was largely suppressed due to a permeability barrier of the outer membrane. The results show that a polycation disrupted the permeability barrier of the outer membrane.     

The Role of 80K/MARCKS,a Specific Substrate of Protein Kinase C,in Cell Growth and Tumour Progression

Since its discovery more than a decade ago [Wu et al., 1982; Rozengurt et al., 1983], the 80-87 kDa myristoylated a lanine-rich C-kinase substrate (80K/MARCKS) protein has attracted a great deal of attention from researchers interested in cell growth and tumour progression. However, despite its ubiquitous distribution, a definitive functional role for 80K/MARCKS has not been found. The purpose of this review is to describe the properties, distribution and regulation of 80K/MARCKS and to discuss some of the most recent findings, both from our laboratory and from others, that have suggested a functional role for this protein in modulating cell growth and tumour progression. Furthermore, I will present data from our laboratory that implicates 80K/MARCKS as a novel tumour suppressor in cells of melanocyte origin.