Continuous dechlorination of tetrachloroethene in an upflow anaerobic sludge blanket reactor

Influences of hydraulic retention time (HRT) on dechlorination of tetrachloroethene (PCE) were investigated in an upflow anaerobic sludge blanket (UASB) reactor inoculated with anaerobic granular sludge non-pre-exposed to chlorinated compounds. PCE was introduced into the reactor at a loading rate of 3 mg/l d. PCE removal increased from 51 +/- 5% to 87 +/- 3% when HRT increased from 1 to 4 d, corresponding to an increase in the PCE biotransformation rate from 10.5 +/- 2.3 to 21.3 +/- 3.7 mumol/d. A higher ethene production rate, 0.9 +/- 0.2 mumol/d, was attained without accumulation of dichloroethenes at the HRT of 4 d. Dehalococcoides-like species were detected in sludge granules by fluorescence in situ hybridization, with signal strength in proportion to the extent of PCE dechlorination.     

Dopa-responsive dystonia induced by a recessive GTP cyclohydrolase I mutation

GTP cyclohydrolase I (GTPCH) catalyzes the rate-limiting step of tetrahydrobiopterin (BH4) biosynthesis. GTPCH has been associated with two clinically distinct human diseases: the recessive hyperphenylalaninemia (HPA) and the dominant dopa-responsive dystonia (DRD). We found a recessive GTPCH mutation (R249S, 747C-->G in a dystonia patient. Her PHA-stimulated mononuclear blood cells had a normal amount of GTPCH mRNA, but low GTPCH activity. Arginine 249 is located at the C-terminus of GTPCH, outside the catalytic site. E. coli expressed recombinant R249S mutant protein possessed normal enzyme activity and kinetics. However, in transfected eukaryotic cells, R249S mutant protein expression level was lower than the wild-type protein. Therefore, this is suspected to be a destabilizing mutation. Our data suggest that DRD could be either dominantly or recessively inherited, and the inheritance might be determined by the mechanism of mutation.     

Enthalpy and enzyme activity of modified histidine residues of adenosine deaminase and diethyl pyrocarbonate complexes

Kinetic and thermodynamic studies have been made on the effect of diethyl pyrocarbonate as a histidine modifier on the active site of adenosine deaminase in 50 mM sodium phosphate buffer pH 6.8, at 27 degrees C using UV spectrophotometry and isothermal titration calorimetry (ITC). Inactivation of adenosine deaminase by diethyl pyrocarbonate is correlated with modification of histidyl residues. The number of modified histidine residues complexed to active site of adenosine deaminase are equivalent to 4. The number and energy of histidine binding sets are determined by enthalpy curve, which represents triple stages. These stages are composed of 3,1 and 1 sites of histidyl modified residues at diethyl pyrocarbonate concentrations, 0.63, 1.8, 3.3 mM. The heat contents corresponding to the first, second and third sets are found to be 18000, 22000 and 21900 kJ mol(-1) respectively.     

Effect of reversing dark-light cycles on normal diurnal variation and related metabolic disturbance in rats

Diurnal variation of glucose tolerance and insulin action was studied in male Sprague-Dawley rats with a normal or reversed light-dark cycle. A series of experiments conducted was at 12 AM and 12 PM in the two groups. All measurements were separated by a recovery period of at least 3 days and preceded by a 16-hour fast. Glucose tolerance and insulin action were measured by both an oral glucose tolerance test and intraperitoneal insulin tolerance test. Normal light-dark cycle rats had significantly (P < 0.05) greater insulin sensitivity at 12 PM than at 12 AM, whereas reversed light-dark cycle rats had the opposite results (P < 0.05). Rats in the normal light-dark cycle group had a significantly higher growth hormone concentration at 12 AM than at 12 PM, whereas rats in the reversed group had the opposite results. Measurement of insulin-stimulated glucose uptake of isolated adipocytes preincubated with or without 100 ng/ml growth hormone at 37 degrees C for 5 hours revealed that approximately 30% of insulin-stimulated glucose uptake was suppressed when adipocytes were treated with growth hormone. These results indicate that male rats exhibit significant diurnal variation of glucose tolerance and insulin sensitivity, and suggest that the concomitant diurnal variation of growth hormone may have a superimposed and amplifying effects on this variation.     

Prenatal diagnosis and genetic counseling of mucopolysaccharidosis type II (Hunter syndrome)

We present prenatal diagnosis of mucopolysaccharidosis type II (MPS II) (Hunter syndrome) and demonstrate marked mucopolysaccharide deposition in multiple vital organs in a 22-gestational-week affected fetus. Level II ultrasound showed cardiomegaly and hepatomegaly. Histological examinations of the fetal vital organs manifested marked mucopolysaccharide deposition. We suggest that any therapeutic approach and counseling for prenatally diagnosed MPS II should consider the early signs of in utero marked mucopolysaccharide storage.     

Novel arylhydrazone-conjugated gold nanoparticles with DNA-cleaving ability: the first DNA-nicking nanomaterial

Arylhydrazones were linked onto gold nanoparticles through the poly(ethylene glycol) spacer to produce a new type of photoinduced DNA-cleaving nanomaterials with great potency.     

A genome‐wide quantitative trait loci scan of neurocognitive performances in families with schizophrenia

Patients with schizophrenia frequently display neurocognitive dysfunction, and genetic studies suggest it to be an endophenotype for schizophrenia. Genetic studies of such traits may thus help elucidate the biological pathways underlying genetic susceptibility to schizophrenia. This study aimed to identify loci influencing neurocognitive performance in schizophrenia. The sample comprised of 1207 affected individuals and 1035 unaffected individuals of Han Chinese ethnicity from 557 sib‐pair families co‐affected with DSM‐IV (Diagnostic and Statistical Manual, Fourth Edition) schizophrenia. Subjects completed a face‐to‐face semi‐structured interview, the continuous performance test (CPT) and the Wisconsin card sorting test (WCST), and were genotyped with 386 microsatellite markers across the genome. A series of autosomal genome‐wide multipoint nonparametric quantitative trait loci (QTL) linkage analysis were performed in affected individuals only. Determination of genome‐wide empirical significance was performed using 1000 simulated genome scans. One linkage peak attaining genome‐wide significance was identified: 12q24.32 for undegraded CPT hit rate [nonparametric linkage z (NPL‐Z) scores = 3.32, genome‐wide empirical P = 0.03]. This result was higher than the peak linkage signal obtained in the previous genome‐wide scan using a dichotomous diagnosis of schizophrenia. The identification of 12q24.32 as a QTL has not been consistently implicated in previous linkage studies on schizophrenia, which suggests that the analysis of endophenotypes provides additional information from what is seen in analyses that rely on diagnoses. This region with linkage to a particular neurocognitive feature may inform functional hypotheses for further genetic studies for schizophrenia.     

Genome-wide gene expression analysis implicates the immune response and lymphangiogenesis in the pathogenesis of fetal chylothorax

Fetal chylothorax (FC) is a rare condition characterized by lymphocyte-rich pleural effusion. Although its pathogenesis remains elusive, it may involve inflammation, since there are increased concentrations of proinflammatory mediators in pleural fluids. Only a few hereditary lymphedema-associated gene loci, e.g. VEGFR3, ITGA9 and PTPN11, were detected in human fetuses with this condition; these cases had a poorer prognosis, due to defective lymphangiogenesis. In the present study, genome-wide gene expression analysis was conducted, comparing pleural and ascitic fluids in three hydropic fetuses, one with and two without the ITGA9 mutation. One fetus (the index case), from a dizygotic pregnancy (the cotwin was unaffected), received antenatal OK-432 pleurodesis and survived beyond the neonatal stage, despite having the ITGA9 mutation. Genes and pathways involved in the immune response were universally up-regulated in fetal pleural fluids compared to those in ascitic fluids. Furthermore, genes involved in the lymphangiogenesis pathway were down-regulated in fetal pleural fluids (compared to ascitic fluid), but following OK-432 pleurodesis, they were up-regulated. Expression of ITGA9 was concordant with overall trends of lymphangiogenesis. In conclusion, we inferred that both the immune response and lymphangiogenesis were implicated in the pathogenesis of fetal chylothorax. Furthermore, genome-wide gene expression microarray analysis may facilitate personalized medicine by selecting the most appropriate treatment, according to the specific circumstances of the patient, for this rare, but heterogeneous disease.     

Location of DNA sequences complementary to small nuclear repeat RNA (fr 3-RNA) in relation to DNA sequences coding for albumin and alpha-fetoprotein in rat liver cells

Rat liver nuclei contain a 29-nucleotides-long RNA (fr 3-RNA) which is transcribed from middle repetitive DNA sequences. By Southern analysis of restriction fragments of rat albumin and alpha-fetoprotein genomic clones, DNA sequences complementary to this RNA were detected on a 4.6 kbp Eco RI fragment located 600 bp downstream from the termination exon of the albumin gene and on a 2 kbp Eco RI-HindIII fragment located 10 kbp downstream from the restriction fragment containing the alpha-fetoprotein site. No sequence complementary to this RNA was found either in the introns of exons of both genes or in the regions extending 7 kbp upstream from the first albumin exon and 10 kbp upstream of the first alpha-fetoprotein exon. We concluded that sequences complementary to fr 3-RNA are present at the 3'-end flanking regions of the rat albumin and alpha-fetoprotein gene complexes.     

Thermophilic high-rate anaerobic treatment of wastewater containing long-chain fatty acids: impact of reactor hydrodynamics

The liquid superficial up_ow velocity (V_up) and hydraulic retention time (HRT) on the thermophilic treatment of oleate in expanded granular sludge bed (EGSB) reactors were investigated. The highest methane conversion rate of oleate, 93 mg CH₄-COD/g VSS.d, was attained in a reactor operating at a V_up of 1 m/h and an HRT of 24 h. The typical EGSB reactor hydrodynamics (V_up > 4 m/h and HRT < 10 h) inhibited the treatment performance, mainly due to biomass washout in particulate form. This revised version was published online in November 2006 with corrections to the Cover Date.