Solvent-Free CO2 Capture Using Membrane Capacitive Deionization.

Capture of CO2, originating from both fossil fuels, such as coal combustion, and from renewables, such as biogas, appears to be one of the greatest technological challenges of this century. In this study, we show that membrane capacitive deionization (MCDI) can be used to capture CO2 as bicarbonate and carbonate ions produced from the reaction of CO2 with water. This novel approach allows capturing CO2 at room temperature and atmospheric pressure without the use of chemicals. In this process, the adsorption and desorption of bicarbonate ions from the deionized water solution drive the CO2(g) absorption-desorption from the gas phase. In this work, the effects of the current density and the CO2 partial pressure were studied. We found that between 55 and 75% of the electrical charge of the capacitive electrodes can be directly used to absorb CO2 gas. The energy requirement of such a system was found to be ≈40 kJ mol-1 at 15% CO2 and could be further improved by reducing the ohmic and non-ohmic energy losses of the MCDI cell.

The influence of variations in the DNA repair (XRCC1) gene on HIV-1/AIDS among Indian population.

Genetic polymorphisms in DNA repair genes may influence individual variations in the DNA repair capacity. Polymorphisms in the XRCC1 gene that cause amino acid substitutions may impair the interaction of its proteins (XRCC1) with the other enzymatic proteins and consequently alter DNA repair function, which may be associated with the risk of HIV-1/AIDS disease. In this study, we aimed to determine the frequency of polymorphisms in XRCC1 codon 399 in a sample of Indian population with HIV-1/AIDS to evaluate its association with the disease. Polymerase chain reaction and restriction fragment length polymorphism were used to analyse XRCC1 Arg399Gln polymorphisms in 300 positively diagnosed cases with HIV-1/AIDS and an equal number of negatively diagnosed controls of the matched age. The XRCC1 homozygous variant genotype Gln399Gln was associated with an increased risk of HIV-1/AIDS disease (OR = 1.8, 95% CI 1.10-2.94), while no association was found with the Arg399Gln genotype. Polymorphisms in the XRCC1 homozygous variant genotype for the 399Gln allele were associated with the risk of HIV-1/AIDS disease in a sample of North Indian population.

Progressive mitochondrial disease resulting from a novel missense mutation in the mitochondrial DNA ND3 gene.

We describe a 42-year-old man who presented with a progressive history of epilepsy, stroke-like episodes, bilateral optic atrophy, and cognitive decline. Investigation of his muscle biopsy revealed a specific defect in complex I activity. Subsequent analysis of the mitochondrial genome identified a novel heteroplasmic T10191C mutation in the ND3 gene. The mutation was present at lower levels in blood from the patient and unaffected maternal relatives and is the first pathogenic mitochondrial DNA mutation in the ND3 gene to be described.

The mitochondrial ND6 gene is a hot spot for mutations that cause Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a common cause of bilateral optic nerve disease. The majority of LHON patients harbour one of three point mutations of the mitochondrial DNA (mtDNA) complex I, or NADH:ubiquinone oxidoreductase (ND) genes (G11778A in ND4, G3460A in ND1, T14484C in ND6). As a consequence, screening for these mutations has become part of the routine clinical investigation of young adults who present with bilateral optic neuropathy, and the absence of these mutations is interpreted as indicating there is a low likelihood that an optic neuropathy is LHON. However, there are many individuals who develop the clinical features of LHON but who do not harbour one of these primary LHON mutations. We describe two LHON pedigrees that harbour the same novel point mutation within the mtDNA ND6 gene (A14495G). This mutation was heteroplasmic in both families, and sequencing of the mitochondrial genome confirmed that the mutation arose on two independent occasions. This is the seventh mutation in the ND6 gene that causes optic neuropathy, indicating that this gene is a hot spot for LHON mutations. Protein modelling studies indicate that all of these pathogenic mutations lie within close proximity to one another in a hydrophobic cleft or pocket. This is the first evidence for a relationship between a specific disease phenotype and a specific structural domain within a mitochondrial respiratory chain subunit. These findings suggest that the mtDNA ND6 gene should be sequenced in all patients with LHON who do not harbour one of the three common LHON mutations.

The epidemiology of pathogenic mitochondrial DNA mutations.

During the past decade, there have been many descriptions of patients with neurological disorders due to mitochondrial DNA (mtDNA) mutations, but the extent and spectrum of mtDNA disease in the general population have not yet been defined. Adults with suspected mtDNA disease in the North East of England were referred to a single neurology center for investigation over the 10-year period from 1990 to 1999 inclusive. We defined the genetic defect in these individuals. For the midyear period of 1997, we calculated the minimum point prevalence of mtDNA disease in the adults of working age (> 16-<60 years old for female subjects and <65 years old for male subjects) and the minimum prevalence of adults and children (<60 years for female subjects, <65 years for male subjects) at risk of developing mtDNA disease. mtDNA defects caused disease in 6.57 per 100,000 individuals in the adult population of working age, and 7.59 per 100,000 unaffected adults and children were at risk of developing mtDNA disease. Overall, 12.48 per 100,000 individuals in the adult and child population either had mtDNA disease or were at risk of developing mtDNA disease. These results reflect the minimum prevalence of mtDNA disease and pathogenic mtDNA mutations and demonstrate that pathogenic mtDNA mutations are a common cause of chronic morbidity. These findings have resource implications, particularly for supportive care and genetic counseling.

Choromosome instabililty and sister chromatid exchange (SCE) studies in patients with carcinoma of cervix uteri.

Cytogenetic studies have been carried out using the G-banding technique in peripheral blood lymphocytes of 14 patients with carcinoma of the cervix uteri. Simultaneously, sister chromatid exchange (SCE) was also analyzed in the peripheral blood lymphocytes of these patients, along with those of 20 age-matched control subjects. The frequency of aberrant metaphases is significantly higher in patients with carcinoma of the cervix uteri (7.85%) than in the age-matched controls (3.35%). A large number of chromosome aberrations in lymphocytes of these patients have also been detected. Sister chromatid exchange (SCE) was also analyzed in lymphocytes of 14 patients with carcinoma of the cervix uteri and 20 age-matched control subjects. The mean SCE frequencies were 9.44 +/- 0.34 (n = 637) and 6.09 +/- 0.24 (n = 900) per metaphase in patients and controls, respectively. The increase of SCE frequency in cancer patients was statistically significant (p < 0.001), but not seen in controls. Our results suggest that patients with carcinoma of the cervix uteri show a degree of chromosomal instability that might be related to a predisposition to neoplasia.

In vitro and in vivo genotoxicity of hormonal drugs. VI. Fluoxymesterone.

Genotoxic evaluation of a commonly used synthetic steroidal androgen, fluoxymesterone, was undertaken using a combination of in vitro and in vivo assays. The clastogenic potential of fluoxymesterone was evident from the chromosome aberrations and sister chromatid exchanges induced by it in the cultured human lymphocytes and also from the increased frequencies of micronuclei and sister chromatid exchanges in bone marrow cells of mice. However, in Ames Salmonella assay both with and without S9 mix and in host-mediated assay using bacterial strains of S. typhimurium as indicator organism, fluoxymesterone did not cause any significant increase/decrease in His+ revertants.

Sister chromatid exchange (SCE) studies in breast cancer patients: a follow-up study.

Sister chromatid exchanges (SCEs) were studied in 20 patients with breast cancer (stage II) before surgery, one month after surgery, and after three years as a follow-up study. Data from 50 age-matched, normal healthy females, preferably from the affected families, served as controls. In each patient, 50 well-spread metaphases were scored for SCEs. The mean values of SCEs per metaphase were 5.80, 4.69, and 5.98 in breast cancer patients before surgery, one month after surgery, and after a gap of three years as a follow-up, respectively. The one-way analysis of variance was applied and it was found that there was a highly significant difference in the frequency of sister chromatid exchanges in these patients before surgery, one month after surgical removal of cancerous tissue, and after three years as a follow-up study. The elevated level of SCEs three years after surgical removal of cancerous tissue predict the chances of development of another type of cancer.

In vitro and in vivo genotoxicity evaluation of hormonal drugs v. mestranol.

Genotoxicity of a widely used estrogen, Mestranol, was undertaken using in vitro, in vivo and host-mediated assay with bacteria as indicator organism. Analyses of chromosome aberrations and sister chromatid exchanges (SCEs) in human lymphocytes and chromosome aberrations, micronuclei and sister chromatid exchanges (SCEs) in bone-marrow cells of mice showed the drug to be capable of attacking the genetic material. However, both Ames Salmonella/S9 assay with and without S9 mix and host-mediated assay using same tester strains of Salmonella, did not show any significant increase/decrease in the His+ revertants.

Intramitochondrial control of the oxidation of hexadecanoate in skeletal muscle. A study of the acyl-CoA esters which accumulate during rat skeletal-muscle mitochondrial beta-oxidation of [U-14C]hexadecanoate and [U-14C]hexadecanoyl-carnitine.

1. We describe the acyl-CoA and acyl-carnitine esters which arise from the incubation of well-coupled State 3 rat skeletal-muscle mitochondrial fractions with [U-14C]hexadecanoate and [U-14C]hexadecanoyl-carnitine. 2. Acyl-CoA ester intermediates of chain length 16, 14, 12, 10 and 8 carbons were detected. 3. Although incubations were in steady state in respect of oxygen consumption, 14CO2 production and generation of acid-soluble radioactivity, quantitative analysis of acyl-CoA esters showed that steady state was not achieved in respect of all intermediates. 4. 3-Hydroxyacyl- and 2-enoyl-CoA and -carnitine esters were found under normoxic conditions. 5. Direct measurement of NAD+ and NADH shows that under identical incubation conditions our observations cannot be explained by gross perturbation of the [NAD+]/[NADH] ratio. 6. We hypothesize that there is a small pool of rapidly recycling NAD+ channelled between complex I of the respiratory chain and the newly described mitochondrial-inner-membrane-associated beta-oxidation trifunctional enzyme [Uchida, Izai, Orii and Hashimoto (1992) J. Biol. Chem. 267, 1034-1041].

Combined enzyme defect of mitochondrial fatty acid oxidation.

A young girl presented with recurrent episodes of muscle weakness culminating in a severe attack of generalized muscle weakness. In the muscle mitochondria from the patient there was an abnormal pattern of intermediates of beta-oxidation with an accumulation of 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters, and 3-oxoacylcarnitines. There was low activity of long-chain 3-hydroxyacyl-CoA dehydrogenase in mitochondria from all tissues. The activity of long-chain 2-enoyl-CoA hydratase was low in muscle mitochondria and 3-oxoacyl-CoA thiolase activity measured with 3-oxohexadecanoyl-CoA as substrate was low in fibroblast, muscle, and cardiac mitochondria but only partial deficiency was present when the activity was measured with 3-oxooctanoyl-CoA. The activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-oxoacyl-CoA thiolase in fibroblasts from the patient's parents was intermediate between those of controls and the patient. The patient has a combined defect of the long-chain 3-hydroxyacyl-CoA dehydrogenase, long-chain 3-oxoacyl-CoA thiolase, and long-chain 2-enoyl-CoA hydratase which appears to be inherited in an autosomal recessive manner. This suggests there is a multifunctional enzyme catalyzing these activities in human mitochondria and that this enzyme is deficient in our patient.

The measurement of mitochondrial beta-oxidation by release of 3H2O from [9,10-3H]hexadecanoate: application to skeletal muscle and the use of inhibitors as models of metabolic disease.

We describe the use of a simple assay for beta-oxidation which depends on the release of 3H2O from [9,10-3H]hexadecanoate. This was compared with the use of [1-14C]hexadecanoate which gave comparable results when all the products of beta-oxidation were measured. The prediction that 75% of the tritium is released as 3H2O and 25% as [2-3H]acetyl units was confirmed. The assay was used successfully to demonstrate impaired beta-oxidation in tissue preparations from rats treated with etomoxir and methylenecyclopropylpyruvate which are known inhibitors of beta-oxidation. Abnormalities of beta-oxidation were also detected in skeletal muscle from patients with defects of mitochondrial oxidation.

Quantitation of acyl-CoA and acylcarnitine esters accumulated during abnormal mitochondrial fatty acid oxidation.

We have used radio-high pressure liquid chromatography to study the acyl-CoA ester intermediates and the acylcarnitines formed during mitochondrial fatty acid oxidation. During oxidation of [U-14C]hexadecanoate by normal human fibroblast mitochondria, only the saturated acyl-CoA and acylcarnitine esters can be detected, supporting the concept that the acyl-CoA dehydrogenase step is rate-limiting in mitochondrial beta-oxidation. Incubations of fibroblast mitochondria from patients with defects of beta-oxidation show an entirely different profile of intermediates. Mitochondria from patients with defects in electron transfer flavoprotein and electron transfer flavoprotein:ubiquinone oxido-reductase are associated with slow flux through beta-oxidation and accumulation of long chain acyl-CoA and acylcarnitine esters. Increased amounts of saturated medium chain acyl-CoA and acylcarnitine esters are detected in the incubations of mitochondria with medium chain acyl-CoA dehydrogenase deficiency, whereas long chain 3-hydroxyacyl-CoA dehydrogenase deficiency is associated with accumulation of long chain 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters. These studies show that the control strength at the site of the defective enzyme has increased. Radio-high pressure liquid chromatography analysis of intermediates of mitochondrial fatty acid oxidation is an important new technique to study the control, organization and defects of the enzymes of beta-oxidation.

Deficiency of the pyruvate dehydrogenase complex and of mitochondrial fatty acid oxidation.

Defects of the pyruvate dehydrogenase complex and of mitochondrial fatty acid oxidation are important causes of disease. Defects of pyruvate dehydrogenase may present in early childhood with severe CNS changes or, as lactic acidosis or later with ataxia. Defects of fatty acid oxidation may present with hypoglycaemic coma, myopathy, liver disease with encephalopathy, cardiomyopathy or sudden infant death. The investigation of both these groups of disorders is difficult and depends upon a combination of biochemical and molecular biology techniques.