Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides

Recent molecular-dynamics simulations have suggested that the arginine-rich HIV Tat peptides translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, Arg residues play a fundamental role not only in the binding of the peptide to the surface of the membrane, but also in the destabilization and nucleation of transient pores across the bilayer. Here we present a molecular-dynamics simulation of a peptide composed of nine Args (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test experimentally the hypothesis that transient pores open by measuring ionic currents across phospholipid bilayers and cell membranes through the pores induced by Arg-9 peptides. We find that Arg-9 peptides, in the presence of an electrostatic potential gradient, induce ionic currents across planar phospholipid bilayers, as well as in cultured osteosarcoma cells and human smooth muscle cells. Our results suggest that the mechanism of action of Arg-9 peptides involves the creation of transient pores in lipid bilayers and cell membranes.Facultad de Ciencias Exacta

Group versus Individualised Minimum Velocity Thresholds in the Prediction of Maximal Strength in Trained Female Athletes

This study examined the accuracy of di erent velocity-based methods in the prediction of bench press and squat one-repetition maximum (1RM) in female athletes. Seventeen trained females (age 17.8 1.3 years) performed an incremental loading test to 1RM on bench press and squat with the mean velocity being recorded. The 1RM was estimated from the load–velocity relationship using the multiple- (8 loads) and two-point (2 loads) methods and group and individual minimum velocity thresholds (MVT). No significant e ect of method, MVT or interaction was observed for the two exercises (p > 0.05). For bench press and squat, all prediction methods demonstrated very large to nearly perfect correlations with respect to the actual 1RM (r range = 0.76 to 0.97). The absolute error (range = 2.1 to 3.8 kg) for bench press demonstrated low errors that were independent of the method and MVT used. For squat, the favorable group MVT errors for the multiple- and two-point methods (absolute error = 7.8 and 9.7 kg, respectively) were greater than the individual MVT errors (absolute error = 4.9 and 6.3 kg, respectively). The 1RM can be accurately predicted from the load–velocity relationship in trained females, with the two-point method o ering a quick and less fatiguing alternative to the multiple-point method

Oscillator Strengths and Damping Constants for Atomic Lines in the J and H Bands

We have built a line list in the near-infrared J and H bands (1.00-1.34, 1.49-1.80 um) by gathering a series of laboratory and computed line lists. Oscillator strengths and damping constants were computed or obtained by fitting the solar spectrum. The line list presented in this paper is, to our knowledge, the most complete one now available, and supersedes previous lists.Comment: Accepted, Astrophysical Journal Supplement, tentatively scheduled for the Sep. 1999 Vol. 124 #1 issue. Text and tables also available at http://www.iagusp.usp.br/~jorge

Altered liver gene expression in CCl4-cirrhotic rats is partially normalized by insulin-like growth factor-I

We have previously shown that the administration of low doses of insulin-like growth factor-I (IGF-I) to CCl4-cirrhotic rats improves liver function and reduces fibrosis. To better understand the mechanisms behind the hepatoprotective effects of IGF-I, and to identify those genes whose expression is affected in cirrhosis and after IGF-1 treatment, we have performed differential display of mRNA analysis by means of polymerase chain reaction (PCR) in livers from control and CCl4-cirrhotic rats treated or not with IGF-I. We have identified 16 genes that were up- or down-regulated in the cirrhotic liver. IGF-I treatment partially normalized the expression of eight of these genes, including serine proteinase inhibitors such as serpin-2 and alpha-1-antichymotripsin, alpha-1-acid glycoprotein, and alpha-2u-globulin. Additionally, we show that IGF-I enhanced the regenerative activity in the cirrhotic liver, as determined by the increased expression of the proliferating cell nuclear antigen (PCNA). Finally, IGF-I treatment partially restored the expression of growth hormone receptor (GHR) and the levels of global genomic DNA methylation, which are reduced in human and experimental cirrhosis. Taken together, our observations confirm the hepatoprotective effects of IGF-I, and suggest that this action can be exerted in part through the normalization of liver gene expression, growth hormone (GH) responsiveness and global genomic DNA methylation

Nanometer-scale ablation with a table-top soft x-ray laser

Includes bibliographical references (page 3617).Ablation of holes with diameters as small as 82 nm and very clean walls was obtained in poly(methyl methacrylate) focusing pulses from a Ne-like Ar 46.9 nm compact capillary-discharge laser with a freestanding Fresnel zone plate diffracting into third order. These results demonstrate the feasibility of using focused soft x-ray laser beams for the direct nanoscale patterning of materials and the development of new nanoprobes

Comprehensive identification of essential Staphylococcus aureus genes using Transposon-Mediated Differential Hybridisation (TMDH).

BACKGROUND: In recent years there has been an increasing problem with Staphylococcus aureus strains that are resistant to treatment with existing antibiotics. An important starting point for the development of new antimicrobial drugs is the identification of "essential" genes that are important for bacterial survival and growth. RESULTS: We have developed a robust microarray and PCR-based method, Transposon-Mediated Differential Hybridisation (TMDH), that uses novel bioinformatics to identify transposon inserts in genome-wide libraries. Following a microarray-based screen, genes lacking transposon inserts are re-tested using a PCR and sequencing-based approach. We carried out a TMDH analysis of the S. aureus genome using a large random mariner transposon library of around a million mutants, and identified a total of 351 S. aureus genes important for survival and growth in culture. A comparison with the essential gene list experimentally derived for Bacillus subtilis highlighted interesting differences in both pathways and individual genes. CONCLUSION: We have determined the first comprehensive list of S. aureus essential genes. This should act as a useful starting point for the identification of potential targets for novel antimicrobial compounds. The TMDH methodology we have developed is generic and could be applied to identify essential genes in other bacterial pathogens.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Tratamiento de la cirrosis biliar primaria con ácido ursodesoxicólico. Resultados a corto y medio plazo y relación con el estudio de la enfermedad

We present the results of the treatment with ursodeoxycholic acid (UDCA, 7-9 mg/kg body weight daily) of 17 patients with primary biliary cirrhosis (8 in stages I-II; 9 in stages III-IV). At two months the mean values of alkaline phosphatase, gammaglutamiltranspeptidase, alanine and aspartate aminotransferase were reduced (p less than 0.001, p less than 0.001, p less than 0.01 and p less than 0.01 respectively). This improvement persisted without increase during the first year. At two months the total bilirubin value was reduced (p less than 0.01) associated with a reduction in the conjugated fraction (p less than 0.05). Cholesterol and gammaglobulin mean values also decreased at two months (p less than 0.05). We found no changes in IgM levels and antimitochondrial antibody titers. The improvement was similar in both groups (early I-II and advanced III-IV stages) and the treatment showed no undesirable effects either in early or advanced stages. Almost all the patients with pruritus (6 out of 7) improved with the treatment and the use of cholestyramine was reduced in al

Mutations in TRAPPC11 are associated with a congenital disorder of glycosylation.

Congenital disorders of glycosylation (CDG) are a heterogeneous and rapidly growing group of diseases caused by abnormal glycosylation of proteins and/or lipids. Mutations in genes involved in the homeostasis of the endoplasmic reticulum (ER), the Golgi apparatus (GA), and the vesicular trafficking from the ER to the ER-Golgi intermediate compartment (ERGIC) have been found to be associated with CDG. Here, we report a patient with defects in both N- and O-glycosylation combined with a delayed vesicular transport in the GA due to mutations in TRAPPC11, a subunit of the TRAPPIII complex. TRAPPIII is implicated in the anterograde transport from the ER to the ERGIC as well as in the vesicle export from the GA. This report expands the spectrum of genetic alterations associated with CDG, providing new insights for the diagnosis and the understanding of the physiopathological mechanisms underlying glycosylation disorders