Chronic hypobaric hypoxia diminishes the expression of base excision repair OGG1 enzymes in spermatozoa.

Hypobaric hypoxia induces DNA damage in rat testicular cells, the production of defective spermatozoids and decreased sperm count, associated with an increase in oxidative stress. 8-Oxoguanine glycosylase (OGG1) enzymes are main members of the base excision repair (BER) system, a DNA repair mechanism. We determined the expression levels of mitochondrial and nuclear OGG1 isoforms in spermatozoa collected from cauda epididymis in rats exposed to chronic hypobaric hypoxia (CHH) for 5, 15 and 30 days. CHH attenuates OGG1 expression in a time-dependent fashion, with a greater reduction in the mitochondrial isoform OGG1-2a (p < .05). Attenuation of the BER system may contribute to DNA damage under hypoxia exposure.

Effect of UV radiation on habitat selection by Girella laevifrons and Graus nigra (Kyphosidae).

The effect of UV radiation on habitat use of two species of intertidal fishes that inhabit the same pools but exhibit different activity levels and diets was measured: the highly active omnivorous Girella laevifrons and the cryptic carnivorous Graus nigra. Individuals of each species were acclimated to a tank divided in three sections with different illumination; no light (NL), ultraviolet light (UV) and white light (WL), and the time spent and number of visits to each section were recorded. Although both species preferred the NL section, G. laevifrons spent more time in UV and less time in WL compared with G. nigra; G. laevifrons also displayed higher number of visits to UV, suggesting a different tendency in space use in response to UV exposure in intertidal fishes.

Can upwelling signals be detected in intertidal fishes of different trophic levels?

For intertidal fishes belonging to three species, the herbivore Scartichthys viridis (Blenniidae), the omnivore Girella laevifrons (Kyphosidae) and the carnivore Graus nigra (Kyphosidae), mass and body size relationships were higher in individuals from an upwelling zone compared with those from a non-upwelling zone. RNA:DNA were higher in the herbivores and omnivores from the upwelling zone. Higher biomass and RNA:DNA in the upwelling intertidal fishes may be a consequence of an increased exposure to higher nutrient availability, suggesting that increased physiological conditioning in vertebrates from upwelling areas can be detected and measured using intertidal fishes of different trophic levels.

[Roux-en-Y gastric bypass for treatment of patients with DM type 2 and BMI of 30 to 35 Kg/m²]. / Bypass gástrico en Y de Roux para el tratamiento de pacientes con diabetes mellitus tipo II con IMC de 30 a 35 kg/m²

BACKGROUND: The incidence of obesity and its most feared comorbidity, diabetes mellitus type 2, is increasing and there would not seem to be any medical treatment to help control these pandemics. However, there is a bariatric surgery technique, the Roux-en-Y Gastric Bypass (RYGB), which is safe and not only helps control excess weight, but produces encouraging results in the control and remission of diabetes. METHODS: We present 15 selected patients with a BMI between 30 and 35 kg/mt² and diabetes type 2 who underwent a laparoscopic RYGB with of one-year follow-up. RESULTS: A total of 14 women and one man were operated with the following average values: age: 37 years, weight: 88.3 kg, BMI: 32.8 kg/mt², blood glucose: 120 ± 38.8 mg%, HbA1c: 7.6 ± 0.73. Forty percent (40%) suffered from high blood pressure and 33.3% were dyslipidemic. Average surgical time was 75 minutes, hospital length of stay was two days, and there was a low rate of complications and no mortality. Diabetes remission was achieved in 93% of cases with significant drops in blood glucose and HbA1c (p ≤ 0.05 and p ≤ 0.001 respectively), dyslipidemia was 100% controlled and hypertension was 83.3% controlled. CONCLUSIONS: RYGB in selected patients with obesity type 1 and diabetes mellitus type 2 is a safe and effective technique for metabolic control and obesity control.

Bypass gástrico en Y de Roux para el tratamiento de pacientes con diabetes mellitus tipo II con IMC de 30 a 35 kg/m2 / Roux-en-Y gastric bypass for treatment of patients with DM type 2 and BMI of 30 to 35 Kg/m2

La incidencia de obesidad y una de sus comorbilidades más temida la diabetes mellitus tipo II está en aumento y no pareciera haber tratamiento médico que ayude a controlar estas pandemias. Existe una técnica quirúrgica bariátrica, el Bypass Gástrico en Y de Roux (BGYR) que es segura y no sólo ayuda a controlar el exceso de peso sino también produce resultados alentadores en el control y remisión de la diabetes. Métodos: Se presentan 15 pacientes con IMC entre 30 y 35 kg/mt2 diabéticos tipo II seleccionados sometidos a BGYR por laparoscopia con seguimiento de un año. Resultados: Se operaron 14 mujeres y un hombre con los siguientes valores promedios: Edad: 37 años, Peso: 88,3 kg, IMC: 32,8 kg/mt2, Glicemia: 120 ± 38,8 mg%, HbA1c: 7,6% ± 0,73. 40% de hipertensión arterial y 33,3% dislipidémicos. El tiempo quirúrgico promedio fue de 75 minutos, dos días de hospitalización bajo índice de complicaciones y sin mortalidad. Se logró una remisión de la diabetes en el 93%, de los casos, con descensos de la glicemia y HbA1c significativos (p ≤ 0,05 y p ≤ 0,001 respectivamente) con un control de la dislipidemia del 100% y 83,3% de la HTA. Conclusiones: El BGYR en obesos tipo I diabéticos seleccionados es una técnica segura y eficaz en el control metabólico y de la obesidad (AU)

Background: The incidence of obesity and its most feared comorbidity, diabetes mellitus type 2, is increasing and there would not seem to be any medical treatment to help control these pandemics. However, there is a bariatric surgery technique, the Roux-en-Y Gastric Bypass (RYGB), which is safe and not only helps control excess weight, but produces encouraging results in the control and remission of diabetes. Methods: We present 15 selected patients with a BMI between 30 and 35 kg/mt2 and diabetes type 2 who underwent a laparoscopic RYGB with of one-year follow-up. Results: A total of 14 women and one man were operated with the following average values: age: 37 years, weight: 88.3 kg, BMI: 32.8 kg/mt2, blood glucose: 120 ± 38.8 mg%, HbA1c: 7.6 ± 0.73. Forty percent (40%) suffered from high blood pressure and 33.3% were dyslipidemic. Average surgical time was 75 minutes, hospital length of stay was two days, and there was a low rate of complications and no mortality. Diabetes remission was achieved in 93% of cases with significant drops in blood glucose and HbA1c (p ≤ 0.05 and p ≤ 0.001 respectively), dyslipidemia was 100% controlled and hypertension was 83.3% controlled. Conclusions: RYGB in selected patients with obesity type 1 and diabetes mellitus type 2 is a safe and effective technique for metabolic control and obesity control (AU)

Fetal and postnatal pulmonary circulation in the Alto Andino.

Lowland mammals at high altitude constrict the pulmonary vessels, augmenting vascular resistance and developing pulmonary arterial hypertension. In contrast, highland mammals, like the llama, do not present pulmonary arterial hypertension. Using wire myography, we studied the sensitivity to norepinephrine (NE) and NO of small pulmonary arteries of fetal llamas and sheep at high altitudes. The sensitivity of the contractile responses to NE was decreased whereas the relaxation sensitivity to NO was augmented in the llama fetus compared to the sheep fetus. Altogether these data show that the fetal llama has a lower sensitivity to a vasoconstrictor (NE) and a higher sensitivity to a vasodilator (NO), than the fetal sheep, consistent with a lower pulmonary arterial pressure found in the neonatal llama in the Andean altiplano. Additionally, we investigated carbon monoxide (CO) in the pulmonary circulation in lowland and highland newborn sheep and llamas. Pulmonary arterial pressure was augmented in neonatal sheep but not in llamas. These sheep had reduced soluble guanylate cyclase and heme oxygenase expression and CO production than at lowland. In contrast, neonatal llamas increased markedly pulmonary CO production and HO expression at high altitude. Thus, enhanced pulmonary CO protects against pulmonary hypertension in the highland neonate. Further, we compared pulmonary vascular responses to acute hypoxia in the adult llama versus the adult sheep. The rise in pulmonary arterial pressure was more marked in the sheep than in the llama. The llama pulmonary dilator strategy may provide insights into new treatments for pulmonary arterial hypertension of the neonate and adult.

Optimal sequences for non-phosphate-directed phosphorylation by protein kinase CK1 (casein kinase-1)--a re-evaluation.

A variety of synthetic peptides derived from either the inhibitor-2 (I-2) phosphoacceptor sites or the optimal sequences selected in an oriented peptide library have been compared for their susceptibility to phosphorylation by protein kinase CK1 (also termed casein kinase-1). The I-2-derived peptides are by far preferred over the library peptides by both rat liver CK1 (and by the alpha/beta, gamma and delta/epsilon isoforms immunoprecipitated from it) and recombinant Xenopus laevis CK1 alpha. The superiority of the I-2-derived peptides over the library ones is reflected by Vmax values one to two orders of magnitude higher while the Km values are comparable. Individual substitutions of any of the aspartic acids with alanine in the I-2-derived peptide RRKHAAIGDDDDAYSITA is detrimental, producing both a fall in Vmax and an increase in Km which are more pronounced at position n -3, but also quite significant at positions n -4, n -5 and, to a lesser extent, n -6. The unfavourable effect of these substitutions is more evident with rat liver CK1 than with recombinant Xenopus laevis CK1 alpha. The chimeric peptide IGDDDDAY-S-IIIFFA, resulting from the combination of the N-terminal acidic sequence of the I-2 (Ser86) site and the C-terminal hydrophobic cluster selected in the library peptides (MAEFDTG-S-IIIFFAKKK and MAYYDAA-S-IIIFFAKKK) is phosphorylated as efficiently as the I-2-derived peptide in terms of both Km and Vmax. These combined data strongly support the conclusion that, at variance with the optimal sequences selected in the library, optimal non-phosphate-directed phosphorylation of peptide substrates by CK1 critically relies on the presence of a cluster of acidic residues (preferably aspartic acid) upstream from position n -2, while the highly hydrophobic region downstream from serine selected in the library appears to be dispensable. The reason for these discrepancies remains unclear. The possibility that the library data are biased by the invariant elements forming its scaffold (MA-x-x-x-x-x-SI-x-x-x-x-AKKK) would be consistent with the observation that the library-selected peptides, despite their low Km values, fail to compete against the phosphorylation of protein and peptide substrates by CK1, suggesting that they bind to elements partially distinct from those responsible for substrate recognition.

The recombinant alpha isoform of protein kinase CK1 from Xenopus laevis can phosphorylate tyrosine in synthetic substrates.

The cDNA coding for protein kinase CK1 alpha has been cloned from a Xenopus laevis cDNA library. The derived amino acid sequence of the protein contains 337 amino acids and has a calculated molecular mass of 38874 Da. The sequence is identical to that of the human CK1 alpha and to the bovine CK1 alpha, except that it is 12 amino acids longer than the latter protein. Southern blotting with a 264-bp probe demonstrates that four or more fragments are obtained upon digestion of genomic DNA with EcoR1 and Hind3, suggesting that X. laevis possesses a family of related CK1 genes. CK1 alpha was expressed in Escherichia coli as a glutathione transferase fusion protein (GT-CK1 alpha) and certain of its characteristics were determined. The recombinant GT-CK1 alpha fusion protein was found to have apparent Km values for ATP (12 microM), casein (1.5 mg/ml) and the specific peptide substrate RRKDLHDDEEDEAMSITA (180 microM) which are similar to those of the rat liver CK1 enzyme. The recombinant CK1 alpha activity is weakly inhibited by heparin, but strongly inhibited by poly(Glu80:Tyr20). This inhibition is competitive and shows an approximate K1 of 5 microM. CK1 alpha can phosphorylate the tyrosine residues of poly(Glu80:Tyr20) and the tyrosine residue in the synthetic peptide RRREEEYEEEE. This kinase preparation also autophosphorylates in serine, threonine and weakly in tyrosine.

Isolation and nucleotide sequence of the Thiobacillus ferrooxidans genes for the small and large subunits of ribulose 1,5-bisphosphate carboxylase/oxygenase.

The genes encoding for the large (rbcL) and small (rbcS) subunits of ribulose-1,5-bisphosphate carboxylase (RuBisCO) were cloned from the obligate autotroph Thiobacillus ferrooxidans, a bacterium involved in the bioleaching of minerals. Nucleotide sequence analysis of the cloned DNA showed that the two coding regions are separated by a 30-bp intergenic region, the smallest described for the RuBisCO genes. The rbcL and rbcS genes encode polypeptides of 473 and 118 amino acids, respectively. Comparison of the nucleotide and amino acid sequences with those of the genes for rbcL and rbcS found in other species demonstrated that the T. ferrooxidans genes have the closest degree of identity with those of Chromatium vinosum and of Alvinoconcha hessleri endosymbiont. Both T. ferrooxidans enzyme subunits contain all the conserved amino acids that are known to participate in the catalytic process or in holoenzyme assembly.