High prevalence of chitotriosidase deficiency in Peruvian Amerindians exposed to chitin-bearing food and enteroparasites

The human genome encodes a gene for an enzymatically active chitinase (CHIT1) located in a single copy on Chromosome 1, which is highly expressed by activated macrophages and in other cells of the innate immune response. Several dysfunctional mutations are known in CHIT1, including a 24-bp duplication in Exon 10 causing catalytic deficiency. This duplication is a common variant conserved in many human populations, except in West and South Africans. Thus it has been proposed that human migration out of Africa and the consequent reduction of exposure to chitin from environmental factors may have enabled the conservation of dysfunctional mutations in human chitinases. Our data obtained from 85 indigenous Amerindians from Peru, representative of populations characterized by high prevalence of chitin-bearing enteroparasites and intense entomophagy, reveal a very high frequency of the 24-bp duplication (47.06%), and of other single nucleotide polymorphisms which are known to partially affect enzymatic activity (G102S: 42.7% and A442G/V: 25.5%). Our finding is in line with a founder effect, but appears to confute our previous hypothesis of a protective role against parasite infection and sustains the discussion on the redundancy of chitinolytic function

The epidemiology and factors associated with nocturnal enuresis among boarding and daytime school children in southeast of Turkey: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Nocturnal enuresis is an important problem among young children living in Turkey. The purpose of this study was to determine the possible differences in the prevalence of enuresis between children in boarding school and daytime school and the association of enuresis with sociodemographic factors.</p> <p>Methods</p> <p>This was a cross-sectional survey. A total of 562 self-administered questionnaires were distrubuted to parents from two different types of schools. One of them was a day-time school and the other was a boarding school. To describe enuresis the ICD-10 definition of at least one wet night per month for three consecutive months was used. Chi-square test and a logistic regression model was used to identify significant predictive factors for enuresis.</p> <p>Results</p> <p>The overall prevalence of nocturnal enuresis was 14.9%. The prevalence of nocturnal enuresis declined with age. Of the 6 year old children 33.3% still wetted their beds, while the ratio was 2.6% for 15 years-olds. There was no significant difference in prevalence of nocturnal enuresis between boys and girls (14.3% versus 16. 8%). Enuresis was reported as 18.5% among children attending day time school and among those 11.5% attending boarding school (p < 0.05). Prevalence of enuresis was increased in children living in villages, with low income and with positive family history (p < 0.05). After multivariate analysis, history of urinary tract infection (OR = 2.02), age (OR = 1.28), low monthly income (OR = 2.86) and family history of enuresis (OR = 3.64) were factors associated with enuresis. 46.4% of parents and 57.1% of enuretic children were significantly concerned about the impact of enuresis.</p> <p>Conclusion</p> <p>Enuresis was more frequent among children attending daytime school when compared to boarding school. Our findings suggest that nocturnal enuresis is a common problem among school children, especially with low income, smaller age, family history of enuresis and history of urinary tract infection. Enuresis is a pediatric public health problem and efforts at all levels should be made such as preventive, etiological and curative.</p

Disruption of Growth Hormone Receptor Prevents Calorie Restriction from Improving Insulin Action and Longevity

Most mutations that delay aging and prolong lifespan in the mouse are related to somatotropic and/or insulin signaling. Calorie restriction (CR) is the only intervention that reliably increases mouse longevity. There is considerable phenotypic overlap between long-lived mutant mice and normal mice on chronic CR. Therefore, we investigated the interactive effects of CR and targeted disruption or knock out of the growth hormone receptor (GHRKO) in mice on longevity and the insulin signaling cascade. Every other day feeding corresponds to a mild (i.e. 15%) CR which increased median lifespan in normal mice but not in GHRKO mice corroborating our previous findings on the effects of moderate (30%) CR on the longevity of these animals. To determine why insulin sensitivity improves in normal but not GHRKO mice in response to 30% CR, we conducted insulin stimulation experiments after one year of CR. In normal mice, CR increased the insulin stimulated activation of the insulin signaling cascade (IR/IRS/PI3K/AKT) in liver and muscle. Livers of GHRKO mice responded to insulin by increased activation of the early steps of insulin signaling, which was dissipated by altered PI3K subunit abundance which putatively inhibited AKT activation. In the muscle of GHRKO mice, there was elevated downstream activation of the insulin signaling cascade (IRS/PI3K/AKT) in the absence of elevated IR activation. Further, we found a major reduction of inhibitory Ser phosphorylation of IRS-1 seen exclusively in GHRKO muscle which may underpin their elevated insulin sensitivity. Chronic CR failed to further modify the alterations in insulin signaling in GHRKO mice as compared to normal mice, likely explaining or contributing to the absence of CR effects on insulin sensitivity and longevity in these long-lived mice

Histone Variants and Their Post-Translational Modifications in Primary Human Fat Cells

Epigenetic changes related to human disease cannot be fully addressed by studies of cells from cultures or from other mammals. We isolated human fat cells from subcutaneous abdominal fat tissue of female subjects and extracted histones from either purified nuclei or intact cells. Direct acid extraction of whole adipocytes was more efficient, yielding about 100 µg of protein with histone content of 60% –70% from 10 mL of fat cells. Differential proteolysis of the protein extracts by trypsin or ArgC-protease followed by nanoLC/MS/MS with alternating CID/ETD peptide sequencing identified 19 histone variants. Four variants were found at the protein level for the first time; particularly HIST2H4B was identified besides the only H4 isoform earlier known to be expressed in humans. Three of the found H2A potentially organize small nucleosomes in transcriptionally active chromatin, while two H2AFY variants inactivate X chromosome in female cells. HIST1H2BA and three of the identified H1 variants had earlier been described only as oocyte or testis specific histones. H2AFX and H2AFY revealed differential and variable N-terminal processing. Out of 78 histone modifications by acetylation/trimethylation, methylation, dimethylation, phosphorylation and ubiquitination, identified from six subjects, 68 were found for the first time. Only 23 of these modifications were detected in two or more subjects, while all the others were individual specific. The direct acid extraction of adipocytes allows for personal epigenetic analyses of human fat tissue, for profiling of histone modifications related to obesity, diabetes and metabolic syndrome, as well as for selection of individual medical treatments

Immunoblotting analysis of somatic components of Dirofilaria immitis

SDS-PAGE analysis of Dirofilaria immitis extracts demonstrated the complexity of somatic protein component of adult male similar to that of adult female worm. Western blot analysis showed six major peptide bands of 85, 66, 42, 20, 16.2 and 14.5 kDa recognized in the sera of infected dogs. Western blotting sera from dogs with Dirofilaria immitis infection suggest that antigenic components in the low molecular weight region may be related to the anti-parasitic mechanism of the host

TSH influences serum leptin levels independent of thyroid hormones in hypothyroid and hyperthyroid patients

WOS: 000229101300009PubMed ID: 15863950Leptin is considered to play a role in maintenance of energy balance and body weight by neuroendocrine mechanisms. The physiological mechanisms for thyroid hormone-induced alteration in serum leptin are not well known. In the present study, the relationship between thyroid hormones and leptin levels was investigated in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Leptin levels were determined by radioimmunoassay and body mass index (BMI) was calculated for each subject. Serum leptin levels of 26 hypothyroid and 22 hyperthyroid patients were compared with those of 20 healthy volunteers who comprised the controls. Serum teptin levels of hypothyroid patients (28.4 &PLUSMN; 4.1 ng/ml) were found to be significantly higher than the controls (19.1 &PLUSMN; 3.2 ng/ml) (p&LT; 0.01), whereas hyperthyroid patients had lower levels (10.7 &PLUSMN; 1.2 ng/ml) (p&LT; 0.01). In hypothyroid patients, serum leptin levels were decreased significantly to 20.6 &PLUSMN; 2.1 ng/ml with thyroxin treatment (p&LT; 0.05). However, in hyperthyroid group, serum leptin levels were increased to 12.4 &PLUSMN; 2.2 ng/ml by treatment (p&GT; 0.05). BMI was not changed with the treatment in either group. The serum leptin levels were correlated with BMI and thyrotropin (TSH) in both hypothyroid and hyperthyroid patients. Serum leptin levels are affected in thyroid disorders and the correlation of leptin with TSH is independent of thyroid hormones