A sperm-specific proteome-scale metabolic network model identifies non-glycolytic genes for energy deficiency in asthenozoospermia

About 15% of couples experience difficulty in conceiving a child, of which half of the cases are thought to be male-related. Asthenozoospermia, or low sperm motility, is one of the frequent types of male infertility. Although energy metabolism is suggested to be central to the etiology of asthenozoospermia, very few attempts have been made to identify its underlying metabolic pathways. Here, we reconstructed SpermNet, the first proteome-scale model of the sperm cell by using whole-proteome data and the mCADRE algorithm. The reconstructed model was then analyzed using the COBRA toolbox. Genes were knocked-out in the model to investigate their effect on ATP production. A total of 78 genes elevated ATP production rate considerably of which most encode components of oxidative phosphorylation, fatty acid oxidation, the Krebs cycle, and members of the solute carrier 25 family. Among them, we identified 11 novel genes which have previously not been associated with sperm cell energy metabolism and may thus be implicated in asthenozoospermia. We further examined the reconstructed model by in silico knock out of currently known asthenozoospermia implicated-genes that were not predicted by our model. The pathways affected by knocking out these genes were also related to energy metabolism, confirming previous findings. Therefore, our model not only predicts the known pathways, it also identifies several non-glycolytic genes for deficient energy metabolism in asthenozoospermia. Finally, this model supports the notion that metabolic pathways besides glycolysis such as oxidative phosphorylation and fatty acid oxidation are essential for sperm energy metabolism and if validated, may form a basis for fertility recovery.

Abbreviations: mCADRE: metabolic context-specificity assessed by deterministic reaction evaluation; ATP: adenosine triphosphate; RNA: ribonucleic acid; FBA: flux balance analysis; FVA: flux variability analysis; DAVID: database for annotation, visualization and integrated discovery; OXPHOS: oxidative phosphorylation; ETC: electron transfer chain; SLC: solute carrier; DLD: dihydrolypoamide dehydrogenase; DLST: dihydrolypoamide S-succinyl transferase; OGDH: oxoglutarate dehydrogenase; CS: citrate synthase; FH: fumarate hydratase; IDH: isocitrate dehydrogenase; SUCLG1: succinate-CoA ligase; SD: succinate dehydrogenase; HADHA: hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, subunit A; HADHB: hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, subunit B; PPA2: pyrophosphatase (inorganic) 2; PP_i: inorganic phosphate; GALT: galactose-1-phosphate uridylyltransferase     

Isolation and characterization of a novel γ‐radiation‐resistant bacterium from hot spring in Iran

30 pure colonies with various colors and shapes were isolated from the samples of water and mud which were collected from the Abe‐Siah hot springs in Ramsar, a city in north of Iran, with high‐level of radiation (up to 4 Gy). Colonies were irradiated by 22 KGy radiations and only one of them survived. The survived bacterium with an optimum growth of 30 to 37 °C, pH 6 to 7, and at minimum of 5% NaCl concentration showed promising characteristics. This strain is aerobic, mesophilic, white colony, with catalase‐positive, oxidase‐negative, non motile, spore forming, rod‐shape and finally Gram positive. Strain Bacillus sp. WHO represented a strain of genus Bacillus megaterium according to a phylogenetic analysis of the 16S rDNA and biochemical features. Its radio‐resistancy was compared with E. coli and B. megaterium which were inactivated in 2 KGy and 5.9 KGy respectively. In order to reveal the mechanisms of this extreme radio‐resistancy and WHO DNA repair system we examined its proteomic map, following γ‐irradiation, using two‐dimensional polyacrylamide gel electrophoresis and silver‐staining. The expression levels of majority number of protein spots showed significant changes under radiation stress. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Do dietary amino acid ratios predict risk of incident hypertension among adults?

In the current study, we investigated the association between dietary amino acid ratios and the 3-year incidence of hypertension, conducted in the framework of the Tehran Lipid and Glucose Study with 4287 adults(41.9% men), aged 20–70?y. Dietary intakes of amino acids were assessed using a valid and reliable food frequency questionnaire and reported as percentage of protein. Then amino acid ratios including Leu.Ser/Thr.Trp, Leu/Trp, Leu/Thr, and Ser/Thr were calculated. We identified 429(10%) cases of hypertension during 3.1?y of follow up. The adjusted OR of the highest quartile of dietary Leu.Ser/Thr.Trp intake was 1.48 (95%CI:1.04–2.09, P for trend:0.02) compared with the lowest one. Furthermore, the OR of hypertension in the highest, compared with the lowest quartile of the leu/Thr ratio(2.19 vs 2.02) was 1.46(1.01–2.12), P for trend?=?0.07. Our findings suggest that high dietary intakes of Leu.Ser/Thr.Trp ratio were associated with higher risk of incident hypertension and BP levels.     

Formation of ultrafine deferasirox particles via rapid expansion of supercritical solution (RESS process) using Taguchi approach

The poor water solubility of many drugs is a challenge in pharmaceutical research. Recently, there have been great interests in finding environmentally friendly methods producing fine particles of pharmaceutical products for applications in pharmaceutical engineering. A promising method to improve the bioavailability of pharmaceutical agents is the rapid expansion of supercritical solutions. Deferasirox (DFS), a tridentate chelator, requires two molecules for iron (III) coordination. The bioavailability (the percentage of the drug absorbed compared to its initial dosage) is limited by this insolubility. The effect of four different RESS parameters including, extraction temperature (308-318K), extraction pressure (140-200 bar), effective nozzle diameter (500-1200 μm), with and without cosolvents were investigated on the size and morphology of the precipitated particles of deferasirox based on Taguchi design. The results show great reduction in the size of the precipitated particles of deferasirox (50 nm-5 μm) via RESS process compared with the original particles of deferasirox (5-500 μm).     

A comprehensive molecular characterization of beta thalassemia in a highly heterogeneous population

In Iran, the prevalence of beta-thalassemia trait is approximately 4-8% in most areas, and in Mazandaran province 10% of the population are carriers. Twenty four beta-globin gene mutations were identified in 1635 persons with beta-thalassemia trait using reverse dot blot and restriction fragment length polymorphism analysis. The predominant mutations included IVSII-1 (G-A) (61%), codon 30 (G-C) (7.5%), codon 22 (-7bp) (6.2%), codon 8 (-AA) (5.4%) and IVSI-5 (G-C) (3.6%). These mutations were in different haplotypes, with IVSII-1 being the most heterogeneous. Other less frequent mutations included IVS-II-745 (C-G), codon 44 (-C), codon 39 (C-T), codon 5 (-CT), IVS I-110 (G-A), IVSI-130 (G-C), Fr8/9 (+G), IVSI-1 (G-A), and IVSI (-25bp). All rare mutations except IVSI-130 were encountered in a unique haplotype. The diversity of these mutations reflects the historical admixture of genes in the region. The high prevalence of IVSII-1 (G-A) compared to other parts of the country and the world suggests a founder effect. Our data provide a basis for genetic counseling and prenatal diagnosis.     

Astrocyte ablation induced by La-aminoadipate (L-AAA) potentiates remyelination in a cuprizone demyelinating mouse model

Metabolic Brain Disease - Chronic demyelination in the central nervous system (CNS) is accompanied by an increase in the number of reactive astrocytes and astrogliosis. There are controversial...     

Psychometric properties of the Female Sexual Distress Scale-Revised among a sample of non-clinical Iranian women

Objective. The present study aimed to investigate the psychometric properties of a Persian version of the Female Sexual Distress Scale-Revised (P-FSDS-R) among a sample of healthy Iranian women. Methods. A total of 562 healthy Iranian women completed a battery of questionnaires, including the P-FSDS-R, Depression Anxiety Stress Scales (DASS), Positive and Negative Affect Scales (PANAS) and Locke-Wallace-Marital Adjustment Test (LWMAT). The factor structure and the convergent and divergent validity of the P-FSDS-R were examined, using exploratory and confirmatory factor analysis and Pearson product-moment correlations, respectively. To examine the discriminant validity of the P-FSDS-R, data collected from 562 healthy participants were compared with data from 108 women with sexual problems who completed the P-FSDS-R measure. Results. The results of exploratory and confirmatory factor analyses indicate that the P-FSDS-R is conceptualized within a one - factor model. The results also indicate that the P-FSDS-R has good internal consistency and test-retest reliability. Significant correlations in the predicted directions between the P-FSDS-R scores and the scores of DASS, PANAS and LWMAT support both the convergent and divergent validity of the FSDS-R. The results also indicate that the scores of the P-FSDS-R tests significantly differentiated women with and without sexual problems. Conclusions. In general, these findings support the reliability and the validity of the P-FSDS-R among Iranian women.     

Treating patients differently: Comparison of medical-staff behaviour and attitudes towards cases of self-immolation and unintentional burns

Discrimination in service delivery can interfere with follow-up care, service receipt, and return to normal quality of life. This study was conducted to assess and compare patients’ perception of caregivers’ behaviour and attitudes in two groups; self-immolation and cases of unintentional burn.This study was conducted at the burn unit of Taleqani Hospital in Ilam in 2008. All patients admitted to the burn unit over a 6-month period from September 2008 to March 2009 were enrolled. In the total of 116 patients, 57 cases of self-immolation and 59 cases of unintentional burns were studied. Data were generated through interviews and questionnaires.Among the hospitalised cases, 49.1% were cases of self-immolation. Medical staff behaviour and attitudes were judged as relatively good or good in 86.5% and 68.4% of unintentional burn and self-immolation patients, respectively (P = 0.011). This inter-group difference was only dependent on the nature of burns (self-immolation vs. unintentional), and other studied variables did not significantly affect results.The stigma of self-immolation should not impair the quality of care or the behaviour and attitudes of caregivers. It is necessary to train and monitor staff in this regard so that cases of self-immolation can receive services without discrimination.     

Portrait de la douleur chronique au Canada: les femmes souffrent-elles plus que les hommes ?

The epidemiology of chronic pain remains limited, even if it is recognized as an important public health problem. This study investigated sex and age difference on Canadian chronic pain prevalence and health perception among men and women living with chronic pain. We used Canadian Community Health Survey (CCHS) — cycle 3.1 (2006). Among 132,221 respondents, 40% reported chronic pain (arthritis or rheumatism, low back pain, fibromyalgia, migraine, irritable bowel syndrome). Chronic pain syndromes were predominantly on women and aged people. Women better evaluated their health comparing to chronic pain men. Chronic pain is a major problem in the Canadian community and aged women are more likely to have chronic pain.