The human homologue of the yeast mitochondrial AAA metalloprotease Yme1p complements a yeast yme1 disruptant

AbstractIn yeast, three AAA superfamily metalloproteases (Yme1p, Afg3p and Rca1p) are localized to the mitochondrial inner membrane where they perform roles in the assembly and turnover of the respiratory chain complexes. We have investigated the function of the proposed human orthologue of yeast Yme1p, encoded by the YME1L gene on chromosome 10p. Transfection of both HEK-293EBNA and yeast cells with a green fluorescent protein-tagged YME1L cDNA confirmed mitochondrial targeting. When expressed in a yme1 disruptant yeast strain, YME1L restored growth on glycerol at 37°C. We propose that YME1L plays a phylogenetically conserved role in mitochondrial protein metabolism and could be involved in mitochondrial pathologies

SWOT analysis of risk factors associated with introduction of African Swine Fever through vehicles returning after export of pigs

Denmark is a major pig exporter and applies a high level of biosecurity, with washing and disinfecting stations for returning livestock vehicles. The introduction of African Swine Fever (ASF) would have significant economic consequences related to loss of export of live pigs and products thereof. In this study, we focused on the role of empty livestock vehicles returning after exports of pigs for the introduction of ASF. Initially, the current components and measures related to export of livestock were described. Next, analyses of strengths, weaknesses, opportunities, and threats (SWOT) were conducted, covering the components and measures identified. Then, export of pigs was described either through assembly centers or directly from farms. Washing and disinfection, as required and undertaken at the designated stations, constitutes the most important among all risk-reducing measures identified. Recommendations are to: (1) ensure the quality of washing and disinfection through staff training; (2) find new, safe, and more efficient disinfectants; (3) ensure the required temperature, and therefore effect, of the disinfectant and water. It was impossible to assess, the influence of export through assembly centers compared to direct transport. However, through SWOT analyses we identified the strengths and weaknesses of the two pathways. Moreover, components/measures with risks of unknown sizes are also discussed, such as vehicles undertaking cabotage and the current vehicle quarantine periods

Risk of developing adenomas and carcinomas in the ileal pouch in patients with familial adenomatous polyposis.

Contains fulltext : 71124.pdf (publisher's version ) (Closed access)BACKGROUND & AIMS: At present, more than half of patients with familial adenomatous polyposis (FAP) are treated with a proctocolectomy and an ileal pouch-anal anastomosis (IPAA). Originally it was thought that this procedure would eliminate the risk of developing rectal cancer. However, an increasing number of studies reported development of adenoma and carcinoma in the pouch. The aim of this study was to evaluate the long-term risk of developing adenomas and carcinomas in the pouch in a large cohort of Dutch FAP patients. METHODS: A total of 254 patients with FAP who underwent an IPAA were selected from the Dutch Polyposis Registry. The results of the surveillance examinations and the pathology reports were analyzed. Surveillance with chromoendoscopy was offered to a subgroup of patients. RESULTS: Full information on follow-up was available in 212 (84%) patients. These patients (56% male) underwent a total of 761 endoscopies. The mean follow-up was 7.9 years (range, 0.4-20.3 years). The cumulative risk of developing an adenoma in the pouch at 10-year follow-up was 45%. Twenty-five patients (11.8%) developed an adenoma with advanced pathology, and 4 (1.9%) developed a carcinoma. The cumulative risk of developing a pouch carcinoma at 10-year follow-up was 1%. A very high prevalence (75.7%) of adenomas was found in a subgroup of patients who were examined with chromoendoscopy. CONCLUSIONS: This study demonstrated that although the risk of developing adenomas in the pouch after an IPAA is high, the risk of malignant degeneration appears to be low. The use of chromoendoscopy improves the detection of small adenomas

Non-invasive prenatal testing for aneuploidy and beyond: challenges of responsible innovation in prenatal screening

This paper contains a joint ESHG/ASHG position document with recommendations regarding responsible innovation in prenatal screening with non-invasive prenatal testing (NIPT). By virtue of its greater accuracy and safety with respect to prenatal screening for common autosomal aneuploidies, NIPT has the potential of helping the practice better achieve its aim of facilitating autonomous reproductive choices, provided that balanced pretest information and non-directive counseling are available as part of the screening offer. Depending on the health-care setting, different scenarios for NIPT-based screening for common autosomal aneuploidies are possible. The trade-offs involved in these scenarios should be assessed in light of the aim of screening, the balance of benefits and burdens for pregnant women and their partners and considerations of cost-effectiveness and justice. With improving screening technologies and decreasing costs of sequencing and analysis, it will become possible in the near future to significantly expand the scope of prenatal screening beyond common autosomal aneuploidies. Commercial providers have already begun expanding their tests to include sex-chromosomal abnormalities and microdeletions. However, multiple false positives may undermine the main achievement of NIPT in the context of prenatal screening: the significant reduction of the invasive testing rate. This document argues for a cautious expansion of the scope of prenatal screening to serious congenital and childhood disorders, only following sound validation studies and a comprehensive evaluation of all relevant aspects. A further core message of this document is that in countries where prenatal screening is offered as a public health programme, governments and public health authorities should adopt an active role to ensure the responsible innovation of prenatal screening on the basis of ethical principles. Crucial elements are the quality of the screening process as a whole (including non-laboratory aspects such as information and counseling), education of professionals, systematic evaluation of all aspects of prenatal screening, development of better evaluation tools in the light of the aim of the practice, accountability to all stakeholders including children born from screened pregnancies and persons living with the conditions targeted in prenatal screening and promotion of equity of access

Whole-genome sequencing in health care.

Contains fulltext : 134632.pdf (publisher's version ) (Closed access