Concentration of atomic hydrogen diffused into silicon in the temperature range 900–1300 °C

Boron-doped Czochralski silicon samples with [B]~1017 cm−3 have been heated at various temperatures in the range 800–1300 °C in an atmosphere of hydrogen and then quenched. The concentration of [H-B] pairs was measured by infrared localized vibrational mode spectroscopy. It was concluded that the solubility of atomic hydrogen is greater than [Hs] = 5.6 × 1018 exp( − 0.95 eV/kT)cm−3 at the temperatures investigated

Post-treatment follow-up study of abdominal cystic echinococcosis in Tibetan communities of northwest Sichuan Province, China

Background: Human cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, with the liver as the most frequently affected organ, is known to be highly endemic in Tibetan communities of northwest Sichuan Province. Antiparasitic treatment with albendazole remains the primary choice for the great majority of patients in this resource-poor remote area, though surgery is the most common approach for CE therapy that has the potential to remove cysts and lead to complete cure. The current prospective study aimed to assess the effectiveness of community based use of cyclic albendazole treatment in Tibetan CE cases, and concurrently monitor the changes of serum specific antibody levels during treatment. Methodology/Principal Findings: Ultrasonography was applied for diagnosis and follow-up of CE cases after cyclic albendazole treatment in Tibetan communities of Sichuan Province during 2006 to 2008, and serum specific IgG antibody levels against Echinococcus granulosus recombinant antigen B in ELISA was concurrently monitored in these cases. A total of 196 CE cases were identified by ultrasound, of which 37 (18.9%) showed evidence of spontaneous healing/involution of hepatic cyst(s) with CE4 or CE5 presentations. Of 49 enrolled CE cases for treatment follow-up, 32.7% (16) were considered to be cured based on B-ultrasound after 6 months to 30 months regular albendazole treatment, 49.0% (24) were improved, 14.3% (7) remained unchanged, and 4.1% (2) became aggravated. In general, patients with CE2 type cysts (daughter cysts present) needed a longer treatment course for cure (26.4 months), compared to cases with CE1 (univesicular cysts) (20.4 months) or CE3 type (detached cyst membrane or partial degeneration of daughter cysts) (9 months). In addition, the curative duration was longer in patients with large (.10 cm) cysts (22.3 months), compared to cases with medium (5– 10 cm) cysts (17.3 months) or patients with small (,5 cm) cysts (6 months). At diagnosis, seven (53.8%) of 13 cases with CE1 type cysts without any previous intervention showed negative specific IgG antibody response to E. granulosus recombinant antigen B (rAgB). However, following 3 months to 18 months albendazole therapy, six of these 7 initially seronegative CE1 cases sero-converted to be specific IgG antibody positive, and concurrently ultrasound scan showed that cysts changed to CE3a from CE1 type in all the six CE cases. Two major profiles of serum specific IgG antibody dynamics during albendazole treatment were apparent in CE cases: (i) presenting as initial elevation followed by subsequent decline, or (ii) a persistent decline. Despite a decline, however, specific antibody levels remained positive in most improved or cured CE cases. Conclusions: This was the first attempt to follow up community-screened cystic echinococcosis patients after albendazole therapy using ultrasonography and serology in an endemic Tibetan region. Cyclic albendazole treatment proved to be effective in the great majority of CE cases in this resource-poor area, but periodic abdominal ultrasound examination was necessary to guide appropriate treatment. Oral albendazole for over 18 months was more likely to result in CE cure. Poor drug compliance resulted in less good outcomes. Serology with recombinant antigen B could provide additional limited information about the effectiveness of albendazole in CE cases. Post-treatment positive specific IgG antibody seroconversion, in initially seronegative, CE1 patients was considered a good indication for positive therapeutic efficacy of albendazole

Therapeutic effects of the mitochondrial ROS-redox modulator KH176 in a mammalian model of Leigh Disease

Leigh Disease is a progressive neurometabolic disorder for which a clinical effective treatment is currently still lacking. Here, we report on the therapeutic efficacy of KH176, a new chemical entity derivative of Trolox, in Ndufs4 (-/-) mice, a mammalian model for Leigh Disease. Using in vivo brain diffusion tensor imaging, we show a loss of brain microstructural coherence in Ndufs4 (-/-) mice in the cerebral cortex, external capsule and cerebral peduncle. These findings are in line with the white matter diffusivity changes described in mitochondrial disease patients. Long-term KH176 treatment retained brain microstructural coherence in the external capsule in Ndufs4 (-/-) mice and normalized the increased lipid peroxidation in this area and the cerebral cortex. Furthermore, KH176 treatment was able to significantly improve rotarod and gait performance and reduced the degeneration of retinal ganglion cells in Ndufs4 (-/-) mice. These in vivo findings show that further development of KH176 as a potential treatment for mitochondrial disorders is worthwhile to pursue. Clinical trial studies to explore the potency, safety and efficacy of KH176 are ongoing

Heterogeneity in drinking practices in England and Wales and its association with violent behaviour: a latent class analysis

Background: Crude single-item consumption metrics, such as ‘binge drinking’ measures, mask the complexity and heterogeneity in young people’s drinking; thus limiting our understanding of young people’s drinking patterns as well as how alcohol drinking is associated with violent outcomes. Objectives: The current study employed a range of consumption and contextual indicators to explore heterogeneity in young people’s (16-29 years) drinking practices, giving due consideration to their social nature. It also assessed to what extent heterogeneity in drinking practices was associated with violent outcomes. Methods: Employing data from the 2006 Offending Crime and Justice Survey, three measures of alcohol consumption and nine drinking context indicators were utilised within latent class analysis to create typologies of drinking practices amongst current drinkers in England and Wales (n=2,711) and examine their association with violent outcomes. The validity of the typologies was also assessed on age, sex and socio-economic status. Results: Three discernible drinking profiles were identified: ‘regular social drinkers’ (48%), ‘regular pub binge drinkers’ (32%), and ‘moderate drinkers’ (20%). The ‘regular pub binge drinkers’ were found to be more than twice as likely to commit an assault offence (odds ratio = 2.8 95% CI [1.3, 6.2]) when compared to ‘moderate drinkers’. Interaction analyses demonstrated a stronger risk of violence among ‘regular social drinkers’ of low socio-economic status. Conclusions: Interventions aimed at reducing alcohol-related violence ought to give due consideration to the social context of drinking, the levels of consumption, as well as the socio-economic characteristics of the drinker

An Easy and Efficient Method for Native and Immunoreactive Echinococcus granulosus Antigen 5 Enrichment from Hydatid Cyst Fluid

Background: Currently, the serodiagnosis of cystic echinococcosis relies mostly on crude Echinococcus granulosus hydatid cyst fluid as the antigen. Consequently, available immunodiagnostic tests lack standardization of the target antigen and, in turn, this is reflected on poor sensitivity and specificity of the serological diagnosis. Methodology/Principal Findings: Here, a chromatographic method enabling the generation of highly enriched Antigen 5 (Ag5) is described. The procedure is very easy, efficient and reproducible, since different hydatid cyst fluid (HCF) sources produced very similar chromatograms, notwithstanding the clearly evident and extreme heterogeneity of the starting material. In addition, the performance of the antigen preparation in immunological assays was preliminarily assessed by western immunoblotting and ELISA on a limited panel of cystic echinococcosis patients and healthy controls. Following western immunoblotting and ELISA experiments, a high reactivity of patient sera was seen, with unambiguous and highly specific results. Conclusions/Significance: The methods and results reported open interesting perspectives for the development of sensitive diagnostic tools to enable the timely and unambiguous detection of cystic echinococcosis antibodies in patient sera.This work was supported by Regione Autonoma della Sardegna (http://www.regione.sardegna.it/)Pubblicat

Production of transmitochondrial cybrids containing naturally occurring pathogenic mtDNA variants

The human mitochondrial genome (mtDNA) encodes polypeptides that are critical for coupling oxidative phosphorylation. Our detailed understanding of the molecular processes that mediate mitochondrial gene expression and the structure–function relationships of the OXPHOS components could be greatly improved if we were able to transfect mitochondria and manipulate mtDNA in vivo. Increasing our knowledge of this process is not merely of fundamental importance, as mutations of the mitochondrial genome are known to cause a spectrum of clinical disorders and have been implicated in more common neurodegenerative disease and the ageing process. In organellar or in vitro reconstitution studies have identified many factors central to the mechanisms of mitochondrial gene expression, but being able to investigate the molecular aetiology of a limited number of cell lines from patients harbouring mutated mtDNA has been enormously beneficial. In the absence of a mechanism for manipulating mtDNA, a much larger pool of pathogenic mtDNA mutations would increase our knowledge of mitochondrial gene expression. Colonic crypts from ageing individuals harbour mutated mtDNA. Here we show that by generating cytoplasts from colonocytes, standard fusion techniques can be used to transfer mtDNA into rapidly dividing immortalized cells and, thereby, respiratory-deficient transmitochondrial cybrids can be isolated. A simple screen identified clones that carried putative pathogenic mutations in MTRNR1, MTRNR2, MTCOI and MTND2, MTND4 and MTND6. This method can therefore be exploited to produce a library of cell lines carrying pathogenic human mtDNA for further study

Pig-farming systems and porcine cysticercosis in the north of Cameroon

A survey was conducted in 150 households owning 1756 pigs in the rural areas of Mayo-Danay division in the north of Cameroon. A questionnaire survey was carried out to collect information on the pig-farming system and to identify potential risk factors for Taenia solium cysticercosis infection in pigs. Blood samples were collected from 398 pigs with the aim of estimating the seroprevalence of T. solium cysticercosis. The results showed that 90.7% of the pigs are free roaming during the dry season and that 42.7% of households keeping pigs in the rural areas have no latrine facility. Seventy-six per cent of the interviewed pig owners confirmed that members of the household used open-field defecation. Enzyme-linked immunosorbent assay (ELISA) for antigen and antibody detection showed an apparent prevalence of cysticercosis of 24.6% and 32.2%, respectively. A Bayesian approach, using the conditional dependence between the two diagnostic tests, indicated that the true seroprevalence of cysticercosis in Mayo-Danay was 26.6%. Binary logistic regression analysis indicated that a lack of knowledge of the taeniasis–cysticercosis complex and the absence of a pig pen in the household were associated with pig cysticercosis

Promoter analysis by saturation mutagenesis

Gene expression and regulation are mediated by DNA sequences, in most instances, directly upstream to the coding sequences by recruiting transcription factors, regulators, and a RNA polymerase in a spatially defined fashion. Few nucleotides within a promoter make contact with the bound proteins. The minimal set of nucleotides that can recruit a protein factor is called a cis-acting element. This article addresses a powerful mutagenesis strategy that can be employed to define cis-acting elements at a molecular level. Technical details including primer design, saturation mutagenesis, construction of promoter libraries, phenotypic analysis, data analysis, and interpretation are discussed

The Pseudouridine Synthase RPUSD4 Is an Essential Component of Mitochondrial RNA Granules

Mitochondrial gene expression is a fundamental process that is largely dependent on nuclear-encoded proteins. Several steps of mitochondrial RNA processing and maturation, including RNA post-transcriptional modification, appear to be spatially organized into distinct foci, which we have previously termed mitochondrial RNA granules (MRGs). Although an increasing number of proteins have been localized to MRGs, a comprehensive analysis of the proteome of these structures is still lacking. Here, we have applied a microscopy-based approach that has allowed us to identify novel components of the MRG proteome. Among these, we have focused our attention on RPUSD4, an uncharacterized mitochondrial putative pseudouridine synthase. We show that RPUSD4 depletion leads to a severe reduction of the steady-state level of the 16S mitochondrial (mt) rRNA with defects in the biogenesis of the mitoribosome large subunit and consequently in mitochondrial translation. We report that RPUSD4 binds 16S mt-rRNA, mt-tRNA(Met), and mt-tRNA(Phe), and we demonstrate that it is responsible for pseudouridylation of the latter. These data provide new insights into the relevance of RNA pseudouridylation in mitochondrial gene expression.This work was supported by the Swiss National Science Foundation Grant SNF310030B_160257/1, Wellcome Trust Grant 096919/Z/11/Z, and core funding of Medical Research Council, UK