The molecular basis of cytochrome oxidase deficiency in childhood

The mitochondrial respiratory chain and oxidative phosphorylation system (complexes I-V) produce ATP by aerobic metabolism. Complex IV or cytochrome c oxidase (COX) catalyses transfer of electrons from reduced cytochrome c to molecular oxygen, coupled with proton pumping across the inner mitochondrial membrane. Human COX has 13 polypeptide subunits. Three subunits (I, II and III) constitute the enzyme's catalytic core and are encoded on the mitochondrial genome. The remaining subunits are nuclear-encoded. COX deficiency, either total or partial, is the most commonly recognised respiratory chain defect in childhood. This may be an isolated defect, or combined with deficiencies of other respiratory chain components. Clinical presentations are heterogeneous but most patients with COX deficiency remain uncharacterised at the molecular level. COX subunit expression patterns were analysed in 5 patients with known mitochondrial DNA (mtDNA) mutations and 36 uncharacterised patients. A specific pattern of COX subunit loss was identified in COX deficiency secondary to mtDNA mutations. This suggested that immunohistochemistry using monoclonal antibodies may distinguish between mtDNA defects and nuclear defects in COX deficiency. Subsequent sequence analysis, targeted by immunohistochemistry findings, led to identification of a missense mutation of COX subunit II that causes defective assembly and myopathy. Characterisation of this mutation provided information about assembly of the metal centres of COX. Thus identification of naturally occurring COX mutations allows insight into structure-function relationships within the enzyme. The majority of children with COX deficiency did not have selective loss of mtDNA- encoded subunits, suggesting that nuclear gene defects account for many cases of childhood-onset COX deficiency. One nuclear gene SURF1 is responsible for COX assembly or maintenance. Four patients had homozygous SURF1 mutations, associated with reduced expression of both mtDNA- and nuclear-encoded COX subunits. Studying patterns of subunit expression in COX-deficient patients is fundamental to understanding the pathogenesis of respiratory chain enzyme deficiencies

Anti-Ulcer Effects of Piper Betel, Solanum Nigrum and Zingibercassumunar on Ulceration Induced by Selected Ulcerogens Inrats

Piper betel, Solanum nigrum and Zingiber cassumunar have been used among Malay community in traditional medicine for curing many diseases. These plants are believed to protect the mucosal lining of the stomach from ulcerogens. This study was conducted to investigate the antiulcerogenic properties of ethanol extracts of these plants. One hundred and forty four Sprague Dawley rats were used in this study. The rats were divided into two major groups, the control and treatment group. There were 6 groups of control rats (normal saline (Al); ethanol (Bl); aspirin (Cl); acetic acid (Dl); indomethacin (El); and cimetidine (Fl)). All control groups received distilled water ad libitum 7 days and fasted 24 hours prior forced fed either with normal saline, ethanol, aspirin, acetic acid, indomethacin and cimetidine accordingly. Treated groups were given 2mg / lOOg body weight per day of Piper betel, Solanum nigrum and Zingiber cassumunar extract for 7 days, fasted 24 hours prior force fed with either normal saline (Group A2, A3, A4); ethanol (Group B2, B3, B4); aspirin (Group C2, C3, C4); acetic acid (Group D2, D3, D4); indomethacin (Group E2, E3, E4) or cimetidine (Group F2, F3, F4) accordingly. They were 18 groups all together. They were then fasted again for 24 hours before sacrificed. Macroscopically, the stomachs of rats treated with all plant extracts of all ulcerogen groups (B2, B3, B4; C2, C3, C4; D2, D3, D4; E2, E3, E4; F2, F3, F4) showed a reduced ulcers with significant different (p < 0.05) when compared to B1, C1, Dl and El control groups. Even though treated groups showed some edema and small ulcers, they gave less lesion score when compared to B1, Cl, Dl and El control group. Histological findings showed reduced damage and inflammation score without erosion of mucosal layer in groups treated with Piper betel, Solanum nigrum and Zingiber cassumunar when compared to B1, C1, Dl and El groups. Even though there was slight epithelial disruptions, minimal inflammatory reactions and presence of red blood cells, the damage and inflammation score were less and significantly reduced (p < 0.05) when compared to control groups. This present study suggests that Piper betel, Solanum nigrum and Zingiber cassumunar have some beneficial properties implying that they may have some protective mechanisms to protect stomach from ulcerogens

Duration of Breastfeeding and Its Correlates in Bangladesh

The purpose of this study was to assess the duration of breastfeeding and the sociodemographic factors affecting it. Data for the study were drawn from the Bangladesh Demographic and Health Survey 2004. In total 5,364 mothers were included in the study. The life table and Cox's proportional hazards model were employed for the analysis of breastfeeding-related data, which showed that the average duration of breastfeeding was 31.9 months. Cox regression analysis revealed that the duration of breastfeeding was positively associated with maternal age, contraceptive-use, work status, and religion and was negatively associated with age at marriage, parity, delivery status, region, and maternal education. Younger mothers, having higher education, higher maternal parity, caesarean-section birth, being a Muslim, and mothers who have not used any contraceptive were associated with lower duration of breastfeeding. The findings suggest that health institutions can play a significant role in promoting breastfeeding in Bangladesh. Educational campaigns that stress the benefits of lactation are important strategies for encouraging mothers to breastfeed longer

Systems Biology Approaches Toward Understanding Primary Mitochondrial Diseases

Primary mitochondrial diseases form one of the most common and severe groups of genetic disease, with a birth prevalence of at least 1 in 5000. These disorders are multi-genic and multi-phenotypic (even within the same gene defect) and span the entire age range from prenatal to late adult onset. Mitochondrial disease typically affects one or multiple high-energy demanding organs, and is frequently fatal in early life. Unfortunately, to date there are no known curative therapies, mostly owing to the rarity and heterogeneity of individual mitochondrial diseases, leading to diagnostic odysseys and difficulties in clinical trial design. This review aims to discuss recent advances and challenges of systems approaches for the study of primary mitochondrial diseases. Although there has been an explosion in the generation of omics data, few studies have progressed toward the integration of multiple levels of omics. It is evident that the integration of different types of data to create a more complete representation of biology remains challenging, perhaps due to the scarcity of available integrative tools and the complexity inherent in their use. In addition, “bottom-up” systems approaches have been adopted for use in the iterative cycle of systems biology: from data generation to model prediction and validation. Primary mitochondrial diseases, owing to their complex nature, will most likely benefit from a multidisciplinary approach encompassing clinical, molecular and computational studies integrated together by systems biology to elucidate underlying pathomechanisms for better diagnostics and therapeutic discovery. Just as next generation sequencing has rapidly increased diagnostic rates from approximately 5% up to 60% over two decades, more recent advancing technologies are encouraging; the generation of multi-omics, the integration of multiple types of data, and the ability to predict perturbations will, ultimately, be translated into improved patient care

Influence of the order in which low and high C/N residues on soil nutrient availability and wheat nutrient uptake

It is well-known that the C/N ratio of plant residues can influence soil nutrient availability, but the effect of repeated addition of plant residues with different C/N ratio is less explored. In previous studies, we showed that nutrient availability and soil respiration after the second residue addition is influenced not only by the C/N ratio of that residue, but also by the C/N ratio of the previously added residue. These experiments were carried out without plants and it was unclear how the legacy effect would influence plant growth and nutrient uptake. The aim of this experiment was to assess plant growth, nutrient uptake and soil nutrient availability after the second residue addition with different length of time between the first and second residue addition where the first and second residue had the same or a different C/N ratio. High (H) or low C/N (L) residue was added at the start of the experiment, the second residue with either the same or a different C/N ratio was added on days 7, 14, 21 or 28 with a total residue addition of 20 g kg-1 giving four residue treatments: HH, LL, LH and HL. Wheat was planted immediately after the second residue addition and grown for 28 days. N and P availability were measured on days 7, 14, 21 and 28 and at plant harvest. Soil N and P availability after the second residue addition were in the order HH&lt;LH&lt;HL&lt;LL. Wheat biomass generally did not differ between LL, HL and LH, but wheat in HL and LH had a lower shoot/root ratio than in LL suggesting that in HL and LH the plants were able to compensate the lower nutrient availability by increased root growth. In conclusion, the C/N ratio of the previous residue addition influenced nutrient availability after the second residue addition, but plant growth did not differ between HL, LH and L because plants in the former developed a more extensive root system and could therefore access the nutrients released during decomposition of L even in treatments where both H and L were present in the soil

Genetic variations of CYP2R1 (rs10741657) in Bangladeshi adults with low serum 25(OH)D level—A pilot study

BACKGROUND: Some studies revealed that despite having sufficient sun exposure and dietary supply, the level of serum 25(OH)D in Bangladeshi adults is lower than its normal range. Genetic pattern of an individual is also an essential factor that regulates the level of serum 25(OH)D. However, the genetic variations of CYP2R1 (rs10741657) and their association with low serum 25(OH)D level in Bangladeshi adults are yet to be explored. OBJECTIVE: This study was conducted to determine the frequency of variants of rs10741657 of CYP2R1 gene and its association with low serum 25(OH)D level among Bangladeshi adults. METHOD: This pilot study was conducted among thirty individuals with low serum 25(OH)D level as the study population and ten subjects with sufficient serum 25(OH)D level as controls based on the inclusion and exclusion criteria. Genetic analysis of rs10741657 of CYP2R1 including primer designing, DNA extraction, PCR of target region with purification and Sanger sequencing of the PCR products were done accordingly. For statistical analysis, One-way ANOVA followed by LSD test, Freeman-Halton extension of Fisher’s exact test, Chi-square test (χ(2)) test and unpaired student t-test were performed. RESULTS: In this study, genetic variants of CYP2R1 (rs10741657) among the study population were genotype GG (63.30%), GA (30%) and AA (6.7%). Minor allele frequency of the study population was 0.217. The association between GG and GA genotypes of CYP2R1 (rs10741657) with low serum 25(OH)D level among the study population was found and it was statistically significant. Statistically significant differences were also observed between the genotypes and alleles of the study population and controls. CONCLUSIONS: The presence of ‘GG’ and ‘GA’ genotypes of rs1041657 in CYP2R1 gene is associated with low serum 25(OH)D level among Bangladeshi adults in this pilot study

Duration of Breastfeeding and Its Correlates in Bangladesh

The purpose of this study was to assess the duration of breastfeeding and the sociodemographic factors affecting it. Data for the study were drawn from the Bangladesh Demographic and Health Survey 2004. In total 5,364 mothers were included in the study. The life table and Cox's proportional hazards model were employed for the analysis of breastfeeding-related data, which showed that the average duration of breastfeeding was 31.9 months. Cox regression analysis revealed that the duration of breastfeeding was positively associated with maternal age, contraceptive-use, work status, and religion and was negatively associated with age at marriage, parity, delivery status, region, and maternal education. Younger mothers, having higher education, higher maternal parity, caesarean-section birth, being a Muslim, and mothers who have not used any contraceptive were associated with lower duration of breastfeeding. The findings suggest that health institutions can play a significant role in promoting breastfeeding in Bangladesh. Educational campaigns that stress the benefits of lactation are important strategies for encouraging mothers to breastfeed longer