Prevalence of anti-toxoplasma gondii antibodies in young Iranians: The Caspian III study

Background: Toxoplasmosis is a worldwide neglected tropical and sub-tropical infection caused by Toxoplasma gondii (T. gondii). Most of the previous studies on the seroprevalence of T. gondii in Iran have been done at provincial level and on specific populations, including pregnant females. Socioeconomic parameters are associated with the prevalence of this disease. In this study, the authors evaluated the presence of anti-T. gondii antibodies and the related risk factors in Iranian adolescents. Methods: This was a cross-sectional study on serum samples from the third Iranian national school-based survey (the CASPIAN III study), which included 10- to 18-year-old students. Participants were selected by multistage sampling from 27 Iranian provinces. In this study, serum samples of 882 adolescents from 16 provinces were randomly selected and examined for IgG and IgM antibodies against T. gondiiby theEnzymeLinked Fluorescent Assay (ELFA).Demographicandsocioeconomic factors related to T. gondii infection were gathered using the global school-based health survey (GSHS) questionnaire. Results: The overall T. gondii IgGandIgMseropositivitywas56.3 (95 CI: 53.4 to 59.2)and3.7 (95CI: 2.7 to 4.9), respectively. In multivariate logistic regression model, family size was statistically associated with seroprevalence of anti T. gondii IgG. Living in crowded households (households with more than 4 people vs. households with less than 4 people) increased the risk of seropositivity of T. gondii (OR: 1.40, 95 CI: 1.10 to 1.99). Conclusions: The results of this study indicate that about 40 of Iranian adolescents have not had contact with the T. gondii, thus the risk of congenital toxoplasmosis might be high in young females. Also, household size was the main factor associated with T. gondii infection. Preventive strategies and health education in Iranian adolescents are recommended. © 2017, Pediartric Infections Research Center

Corrosion behavior of friction stir welded lap joints of AA6061-T6 aluminum alloy

In this work, the corrosion behaviors of friction-stir lap welding of 6061-T6 Al-alloy are studied. The friction-stir lap welding was performed under different welding conditions (rotation speed and welding speed). The corrosion behavior of the parent alloy, the weld nugget zone (WNZ), and the heat affected zone (HAZ) of each welded sample working as an electrode, were investigated by the Tafel polarization test in 3.5 wt. (%) NaCl at ambient temperature. The morphology of the corroded surface of each region was analyzed by scanning electron microscopy together with energy dispersive spectroscopy (SEM-EDS). The results showed that the corrosion resistance of the parent alloy was better than the WNZ and the HAZ in both welding conditions. Localized pit dissolution and intergranular corrosion were the dominant corrosion types observed in the parent alloy, WNZ, and HAZ. The parent alloy, WNZ, and HAZ exhibited similar corrosion potentials (Ecorr) after T6 heat treatment. This treatment had a better effect on the corrosion resistance of the welded regions than the parent alloy

De novo TRIM8 variants impair its protein localization to nuclear bodies and cause developmental delay, epilepsy, and focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is the main pathology underlying steroid-resistant nephrotic syndrome (SRNS) and a leading cause of chronic kidney disease. Monogenic forms of pediatric SRNS are predominantly caused by recessive mutations, while the contribution of de novo variants (DNVs) to this trait is poorly understood. Using exome sequencing (ES) in a proband with FSGS/SRNS, developmental delay, and epilepsy, we discovered a nonsense DNV in TRIM8, which encodes the E3 ubiquitin ligase tripartite motif containing 8. To establish whether TRIM8 variants represent a cause of FSGS, we aggregated exome/genome-sequencing data for 2,501 pediatric FSGS/SRNS-affected individuals and 48,556 control subjects, detecting eight heterozygous TRIM8 truncating variants in affected subjects but none in control subjects (p = 3.28 × 10−11). In all six cases with available parental DNA, we demonstrated de novo inheritance (p = 2.21 × 10−15). Reverse phenotyping revealed neurodevelopmental disease in all eight families. We next analyzed ES from 9,067 individuals with epilepsy, yielding three additional families with truncating TRIM8 variants. Clinical review revealed FSGS in all. All TRIM8 variants cause protein truncation clustering within the last exon between residues 390 and 487 of the 551 amino acid protein, indicating a correlation between this syndrome and loss of the TRIM8 C-terminal region. Wild-type TRIM8 overexpressed in immortalized human podocytes and neuronal cells localized to nuclear bodies, while constructs harboring patient-specific variants mislocalized diffusely to the nucleoplasm. Co-localization studies demonstrated that Gemini and Cajal bodies frequently abut a TRIM8 nuclear body. Truncating TRIM8 DNVs cause a neuro-renal syndrome via aberrant TRIM8 localization, implicating nuclear bodies in FSGS and developmental brain disease

Strong protective effect of the APOL1 p.N264K variant against G2-associated focal segmental glomerulosclerosis and kidney disease

African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers. Here, we show that the presence of the APOL1 p.N264K missense variant, when co-inherited with the G2 APOL1 risk allele, substantially reduces the penetrance of the G1G2 and G2G2 high-risk genotypes by rendering these genotypes low-risk. These results align with prior functional evidence showing that the p.N264K variant reduces the toxicity of the APOL1 high-risk alleles. These findings have important implications for our understanding of the mechanisms of APOL1-associated nephropathy, as well as for the clinical management of individuals with high-risk genotypes that include the G2 allele

Study of penculture of the common carp (Cyprinus carpio L.) fingerlings at the Gorgan Bay to the maturity stage (broodstock management)

The aim of present project is study on the possibilities of brood stock production from fingerlings in the penculture condition and the effect of density on it .this project was done during three years with two different treatment and three repetitions in the Gorgan Bay. First treatment with two fingerlings per square meter and the 2nd with four fingerlings per square meter in each pen.To carry out the project at first fingerlings were brought from breeding and recruitment centre –Sijeval (Kolmeh) and the stocked at the earthen pound with concentrated food .After that they were adaptated with brakish water between 7-10 days and transferred to Gorgan Bay for cultivation with average weight of 93.78±32.66 grams and 20.53±2.37 cm in length. It should be noted that 6 pens (which surrounded by nets in the water) were fixed using mast with 15-20 cm in diameter and 5.5 meter in length , Net mesh size was 16 mm with string number 33 of kapron.Feeding was done according to the program two times by giving concentrated food at the period of cultivation Physic -o -chemical factors were measured. biometery was done monthly at each pen and other fishes (unwanted) were observed at the same time. results indicate that in the 1st and 2nd treatments average survival rate was 52.3 and 41 percent respectively with average weight of 410±64.98 grams and 390±52.8 and 28.3±1.79 cm and 27.66±1.57in length. SPSS used to analysethe data such as average length and weight of fish in the treatments and in different months with ANOVA method (p≤ 0.05) . results show that there is no significant difference between treatments. Autopsy observation also showed that fishes (female and male) are mature and histological studies showed that most of observed eggs are entirely mature with 800-1200 micron diameter gonad ( male) were mature at the pen in the Gorgan Bay condition .The male and female hormones were evaluated. 17-B- Estradiol and 11-keto testosterone hormones for adult fish (female and male) parents respectively are similar in dense with those adult fish before injection to use at the artificial breeding. Maturation were verified by autopsy, histology and hormone studies

Genetic studies of IgA nephropathy: past, present, and future

Immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide and an important cause of kidney disease in young adults. Highly variable clinical presentation and outcome of IgAN suggest that this diagnosis may encompass multiple subsets of disease that are not distinguishable by currently available clinical tools. Marked differences in disease prevalence between individuals of European, Asian, and African ancestry suggest the existence of susceptibility genes that are present at variable frequencies in these populations. Familial forms of IgAN have also been reported throughout the world but are probably underrecognized because associated urinary abnormalities are often intermittent in affected family members. Of the many pathogenic mechanisms reported, defects in IgA1 glycosylation that lead to formation of immune complexes have been consistently demonstrated. Recent data indicates that these IgA1 glycosylation defects are inherited and constitute a heritable risk factor for IgAN. Because of the complex genetic architecture of IgAN, the efforts to map disease susceptibility genes have been difficult, and no causative mutations have yet been identified. Linkage-based approaches have been hindered by disease heterogeneity and lack of a reliable noninvasive diagnostic test for screening family members at risk of IgAN. Many candidate-gene association studies have been published, but most suffer from small sample size and methodological problems, and none of the results have been convincingly validated. New genomic approaches, including genome-wide association studies currently under way, offer promising tools for elucidating the genetic basis of IgAN

Human Apolipoprotein A-I-Derived Amyloid: Its Association with Atherosclerosis

Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits of nonvariant protein in atherosclerotic arteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this work we investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated with chronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pH promotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring protein deposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the protein give rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it may produce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated to atherogenesis

Genetic drivers of kidney defects in the digeorge syndrome

BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P = 4.5×1014). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-Altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver

The IgA nephropathy Biobank. An important starting point for the genetic dissection of a complex trait

BACKGROUND: IgA nephropathy (IgAN) or Berger's disease, is the most common glomerulonephritis in the world diagnosed in renal biopsied patients. The involvement of genetic factors in the pathogenesis of the IgAN is evidenced by ethnic and geographic variations in prevalence, familial clustering in isolated populations, familial aggregation and by the identification of a genetic linkage to locus IGAN1 mapped on 6q22–23. This study seems to imply a single major locus, but the hypothesis of multiple interacting loci or genetic heterogeneity cannot be ruled out. The organization of a multi-centre Biobank for the collection of biological samples and clinical data from IgAN patients and relatives is an important starting point for the identification of the disease susceptibility genes. DESCRIPTION: The IgAN Consortium organized a Biobank, recruiting IgAN patients and relatives following a common protocol. A website was constructed to allow scientific information to be shared between partners and to divulge obtained data (URL: ). The electronic database, the core of the website includes data concerning the subjects enrolled. A search page gives open access to the database and allows groups of patients to be selected according to their clinical characteristics. DNA samples of IgAN patients and relatives belonging to 72 multiplex extended pedigrees were collected. Moreover, 159 trios (sons/daughters affected and healthy parents), 1068 patients with biopsy-proven IgAN and 1040 healthy subjects were included in the IgAN Consortium Biobank. Some valuable and statistically productive genetic studies have been launched within the 5(th )Framework Programme 1998–2002 of the European project No. QLG1-2000-00464 and preliminary data have been published in "Technology Marketplace" website: . CONCLUSION: The first world IgAN Biobank with a readily accessible database has been constituted. The knowledge gained from the study of Mendelian diseases has shown that the genetic dissection of a complex trait is more powerful when combined linkage-based, association-based, and sequence-based approaches are performed. This Biobank continuously expanded contains a sample size of adequately matched IgAN patients and healthy subjects, extended multiplex pedigrees, parent-child trios, thus permitting the combined genetic approaches with collaborative studies