Cognitive function in adolescence and the risk for premature diabetes and cardiovascular mortality in adulthood

Background

Epidemiological studies have demonstrated a relationship between cognitive function in youth and the future risk of death. Less is known regarding the relationship with diabetes related death. This study assessed the relationship between cognitive function in late adolescence and the risk for diabetes, cardiovascular- (CVD) and all-cause mortality in adulthood.

Methods

This retrospective study linked data from 2,277,188 16–19 year olds who had general intelligence tests (GIT) conducted during pre-military recruitment assessment with cause of death as coded by the Israel Central Bureau of Statistics. The associations between cognitive function and cause-specific mortality were assessed using Cox models.

Results

There were 31,268 deaths that were recorded during 41,916,603 person-years of follow-up, with a median follow-up of 19.2 (IQR 10.7, 29.5) years. 3068, 1443, 514 and 457 deaths were attributed to CVD, CHD, stroke, and diabetes, respectively. Individuals in the lowest GIT vs. highest GIT quintiles in unadjusted models had the highest risk for all-cause mortality (HR 1.84, 95% CI 1.78, 1.91), total CVD (HR 3.32, 95% CI 2.93, 3.75), CHD (HR 3.49 95% CI 2.92, 4.18), stroke (HR 3.96 95% CI 2.85, 5.5) and diabetes-related (HR 6.96 95% CI 4.68, 10.36) mortality. These HRs were attenuated following adjustment for age, sex, birth year, body-mass index, residential socioeconomic status, education and country of origin for all-cause (HR 1.23, 95% CI 1.17, 1.28), CVD (HR 1.76, 95% CI 1.52, 2.04), CHD (HR 1.7 95% CI 1.37, 2.11), stroke (HR 2.03, 95% CI 1.39, 2.98) and diabetes-related (HR 3.14 95% CI 2.00, 4.94) mortality. Results persisted in a sensitivity analyses limited to participants with unimpaired health at baseline and that accounted competing risk.

Conclusions

This analysis of over 2 million demonstrates a strong relationship between cognitive function at youth and the risk for diabetes, all-cause and CVD-related mortality independent of adolescent obesity.

     

CoQ10 supplementation rescues nephrotic syndrome through normalization of H2S oxidation pathway

Nephrotic syndrome (NS), a frequent chronic kidney disease in children and young adults, is the most common phenotype associated with primary coenzyme Q₁₀ (CoQ₁₀) deficiency and is very responsive to CoQ₁₀ supplementation, although the pathomechanism is not clear. Here, using a mouse model of CoQ deficiency-associated NS, we show that long-term oral CoQ₁₀ supplementation prevents kidney failure by rescuing defects of sulfides oxidation and ameliorating oxidative stress, despite only incomplete normalization of kidney CoQ levels and lack of rescue of CoQ-dependent respiratory enzymes activities. Liver and kidney lipidomics, and urine metabolomics analyses, did not show CoQ metabolites. To further demonstrate that sulfides metabolism defects cause oxidative stress in CoQ deficiency, we show that silencing of sulfide quinone oxido-reductase (SQOR) in wild-type HeLa cells leads to similar increases of reactive oxygen species (ROS) observed in HeLa cells depleted of the CoQ biosynthesis regulatory protein COQ8A. While CoQ₁₀ supplementation of COQ8A depleted cells decreases ROS and increases SQOR protein levels, knock-down of SQOR prevents CoQ₁₀ antioxidant effects. We conclude that kidney failure in CoQ deficiency-associated NS is caused by oxidative stress mediated by impaired sulfides oxidation and propose that CoQ supplementation does not significantly increase the kidney pool of CoQ bound to the respiratory supercomplexes, but rather enhances the free pool of CoQ, which stabilizes SQOR protein levels rescuing oxidative stress.     

Trypanosomatid parasites rescue heme from endocytosed hemoglobin through lysosomal HRG transporters

Pathogenic trypanosomatid parasites are auxotrophic for heme and they must scavenge it from their human host. Trypanosoma brucei (responsible for sleeping sickness) and Leishmania (leishmaniasis) can fulfill heme requirement by receptor‐mediated endocytosis of host hemoglobin. However, the mechanism used to transfer hemoglobin‐derived heme from the lysosome to the cytosol remains unknown. Here we provide strong evidence that HRG transporters mediate this essential step. In bloodstream T. brucei, TbHRG localizes to the endolysosomal compartment where endocytosed hemoglobin is known to be trafficked. TbHRG overexpression increases cytosolic heme levels whereas its downregulation is lethal for the parasites unless they express the Leishmania orthologue LmHR1. LmHR1, known to be an essential plasma membrane protein responsible for the uptake of free heme in Leishmania, is also present in its acidic compartments which colocalize with endocytosed hemoglobin. Moreover, LmHR1 levels modulated by its overexpression or the abrogation of an LmHR1 allele correlate with the mitochondrial bioavailability of heme from lysosomal hemoglobin. In addition, using heme auxotrophic yeasts we show that TbHRG and LmHR1 transport hemoglobin‐derived heme from the digestive vacuole to the cytosol. Collectively, these results show that trypanosomatid parasites rescue heme from endocytosed hemoglobin through endolysosomal HRG transporters, which could constitute novel drug targets.     

The efficiency of 1M NH4Cl and 2 M NaCl for the isolation of pathogenic Nocardia from soil

The present paper reports an improvement to the classical method of the paraffin bait, by the usage of 1 M NH₄Cl or 2 M NaCl to eliminate contaminant microflora of soil.The purpose is to introduce a change in the paraffin bait method in order to reduce time required to isolate pathogenic strains of Nocardia from their natural sources.For this study three main criteria were used: a) Determination of the inhibitory effect of different concentrations of salts on soil microflora; b) The tolerance of Nocardia brasiliensis, Nocardia asteroides and Nocardia caviae (Nocardia otitidis caviarum) strains to these chemical inhibitors; c) Determination of the efficiency of salts in the isolation of Nocardia from soil when strains are grown on paraffin baits.     

Differential effect of αdifluoromethyl-ornithine on the proliferation of balb 3T3 and chemically transformed 3T3 cells

In order to study the effect of polyamine depletion on growth and proliferation of untransformed and chemically transformed cells, α-difluoromethyl-ornithine (DFMO) was added to cultures of 3T3 cells and their benzo[a]pyrene derivative BP-3T3. Both types of cells stopped their proliferation after 72 hr of treatment with the inhibitor. When DFMO was removed and cells were cultivated afterwards in fresh medium without the drug, untransformed cells resumed growth after a lag period, whereas transformed cells were unable to proliferate unless exogenous polyamine was added. These alterations showed a strict correlation with intracellular polyamine pools, since after removal of DFMO from the culture medium, polyamine concentrations increased to almost normal values in 3T3 cells, but remained at low levels or decreased even more in the transformed cells BP-3T3. The analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of labeled proteins of both cell extracts has indicated that the described control of cell proliferation by intracellular polyamine levels might be related to the synthesis of at least two proteins with molecular weights of about 36,000 and 55,000 daltons.     

Amino acid pools and protein synthesis in germinating maize embryos

Amino acid pools were analyzed in maize (Zea mays L.) axes germinated for 0, 6 and 24 h. Proteins synthesized at early (0–6 h) and late (18–24 h) stages were characterized by gel electrophoresis and fluorography after either ¹⁴C-leucine or ¹⁴C-lysine pulses. An increase of amino acid incorporation after 18–24 h was observed, as well as changes in the protein patterns of the corresponding fluorographs. Analysis of the endogenous amino acid pools showed major changes in contents of proline, alanine, isoleucine, valine, leucine and lysine. A selective increase of lysine incorporation into proteins during the late stage was detected.Under the Academic Colaboration Program between the Universidad Nacional Autónoma de México and the Colegio de Postgraduados, Chapingo, México.     

Color inheritance and pigment characterization of red (wild-type), greenish-brown, and green strains of Gracilaria birdiae (Gracilariales, Rhodophyta)

Species of Gracilaria are some of the most useful algae in the world for the production of agar. As a consequence of its economic importance, the genus has been the subject of many studies worldwide. Color variants of Gracilaria birdiae have been found in the natural population on the Brazilian coast, and they have also been isolated from plants cultivated in laboratory. These findings raised new questions regarding intraspecific variation and the prospects of cultivating such variants for their agar production. Therefore, this work aimed to determine the mode of color inheritance for two G. birdiae strains: a greenish-brown strain (gb) found in a natural population and a green strain (gr) which had arisen as a spontaneous mutation in a red plant cultured in the laboratory. The pigment contents of these strains, as well as the red wild-type (rd), were also characterized. Crosses between female and male plants of the same color (rd, gr, or gb) and between different colors were performed. Crosses between plants of the same color showed tetrasporophytic and gametophytic descendents of the parental color. Recessive nuclear inheritance was found in the greenish-brown strain, and cytoplasmic maternal inheritance was found in the green strain; both had lower phycoerythrin and higher concentrations of allophycocyanin and phycocyanin than the wild-type. Chlorophyll a contents were similar among all strains. Taken together, our results contribute to knowledge about the variability of this important red algae. In addition, since greenish-brown and green strains showed stability of color, both could be selected and tested in experimental sea cultivation to evaluate if mutants have advantageous performance when compared with red strain.