Continuous-flow laboratory simulation of stream water quality changes downstream of an untreated wastewater discharge.

In regions of the world with poor provision of wastewater treatment, raw sewage is often discharged directly into surface waters. This paper describes an experimental evaluation of the fate of two organic chemicals under these conditions using an artificial channel cascade fed with a mix of settled sewage and river water at its upstream end and operated under continuous steady-state conditions. The experiments underpin an environmental risk assessment methodology based on the idea of an “impact zone” (IZ) – the zone downstream of wastewater emission in which water quality is severely impaired by high concentrations of unionised ammonia, nitrite and biochemical oxygen demand (BOD). Radiolabelled dodecane-6-benzene sulphonate (DOBS) and aniline hydrochloride were used as the model chemical and reference compound respectively. Rapid changes in 14C counts were observed with flow-time for both these materials. These changes were most likely to be due to complete mineralisation. A dissipation half-life of approximately 7.1 h was observed for the 14C label with DOBS. The end of the IZ was defined as the point at which the concentration of both unionised ammonia and nitrite fell below their respective predicted no-effect concentrations for salmonids. At these points in the cascade, approximately 83 and 90% of the initial concentration of 14C had been removed from the water column, respectively. A simple model of mineral nitrogen transformations based on Michaelis–Menten kinetics was fitted to observed concentrations of NH4, NO2 and NO3. The cascade is intended to provide a confirmatory methodology for assessing the ecological risks of chemicals under direct discharge co

Characterization of the Roco Protein Family in Dictyostelium discoideum

The Roco family consists of multidomain Ras-GTPases that include LRRK2, a protein mutated in familial Parkinson's disease. The genome of the cellular slime mold Dictyostelium discoideum encodes 11 Roco proteins. To study the functions of these proteins, we systematically knocked out the roco genes. Previously described functions for GbpC, Pats1, and QkgA (Roco1 to Roco3) were confirmed, while novel developmental defects were identified in roco4- and roco11-null cells. Cells lacking Roco11 form larger fruiting bodies than wild-type cells, while roco4-null cells show strong developmental defects during the transition from mound to fruiting body; prestalk cells produce reduced levels of cellulose, leading to unstable stalks that are unable to properly lift the spore head. Detailed phylogenetic analysis of four slime mold species reveals that QkgA and Roco11 evolved relatively late by duplication of an ancestor roco4 gene (later than ∼300 million years ago), contrary to the situation with other roco genes, which were already present before the split of the common ancestor of D. discoideum and Polysphondylium pallidum (before ∼600 million years ago). Together, our data show that the Dictyostelium Roco proteins serve a surprisingly diverse set of functions and highlight Roco4 as a key protein for proper stalk cell formation

The Roco protein family:a functional perspective

In this review, we discuss the evolutionary, biochemical, and functional data available for members of the Roco protein family. They are characterized by having a conserved supradomain that contains a Ras-like GTPase domain, called Roc, and a characteristic COR (C-terminal of Roc) domain. A kinase domain and diverse regulatory and protein protein interaction domains are also often found in Roco proteins. First detected in the slime mold Dictyostelium discoideum, they have a broad phylogenetic range, being present in both prokaryotes and eukaryotes. The functions of these proteins are diverse. The best understood are Dictyostelium Rocos, which are involved in cell division, chemotaxis, and development. However, this family has received extensive attention because mutations in one of the human Roco genes (LRRK2) cause familial Parkinson disease. Other human Rocos are involved in epilepsy and cancer. Biochemical data suggest that Roc domains are capable of activating kinase domains intramolecularly. Interestingly, some of the dominant, disease-causing mutations in both the GTPase and kinase domains of LRRK2 increase kinase activity. Thus, Roco proteins may act as stand-alone transduction units, performing roles that were thought so far to require multiple proteins, as occur in the Ras transduction pathway

Melamine in sojaschilfers, oorzaak van verschillen tussen laboratoria

In november 2008 is door het bedrijfsleven in een tweetal partijen diervoedergrondstoffen (sojaschilfers/-meel) melamine aangetroffen op niveaus tussen 40 en 800 mg/kg. Naar aanleiding hiervan heeft de VWA aan RIKILT verzocht om deze monsters (genomen door het bedrijfsleven) te analyseren op melamine en daarnaast, ten behoeve van de risicobeoordeling, op de hydrolyseproducten ammeline, ammelide en cyanuurzuu

Diagnostic approach to paediatric movement disorders:a clinical practice guide

Paediatric movement disorders (PMDs) comprise a large group of disorders (tics, myoclonus, tremor, dystonia, chorea, Parkinsonism, ataxia), often with mixed phenotypes. Determination of the underlying aetiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This can make the diagnostic process time-consuming and difficult. In this overview, we present a diagnostic approach for PMDs, with emphasis on genetic causes. This approach can serve as a framework to lead the clinician through the diagnostic process in eight consecutive steps, including recognition of the different movement disorders, identification of a clinical syndrome, consideration of acquired causes, genetic testing including next-generation sequencing, post-sequencing phenotyping, and interpretation of test results. The aim of this approach is to increase the recognition and diagnostic yield in PMDs.</p

Trendanalyse dierlijke eiwitten in diervoeder(grondstoffen)

In dit rapport worden, in opdracht van de VWA, historische gegevens gebruikt om inzicht te krijgen in het voorkomen van dierlijke eiwitten (bestanddelen) in diervoeders en diervoedergrondstoffen. Dierlijke eiwitten in diervoeders spelen een belangrijke rol in het verspreiden van BSE (gekke koeien ziekte). Daarom zijn er maatregelen genomen om blootstelling van runderen aan dierlijk eiwit via het diervoeder te voorkomen. Er zijn diverse verboden en regels door de Europese overheid opgelegd en door de Nederlandse overheid (VWA) wordt toezicht gehouden op de naleving van deze regelgevin

Информационное обеспечение в процессно-ориентированной модели управления предприятиями

Приведено описание информационного обеспечения как составной части менеджмента производственного предприятия в его современном, процессном представлении. Информационное обеспечение предприятий связано с качеством функционирования, которое с точки зрения процессно-ориентированных стандартов характеризуется результативностью и эффективностью.It has been accomplished the description of data-ware as a component of manufacturing enterprise management in its modern process presentation. The data-ware of enterprise is connected with quality of functioning, which is defined by effectiveness and efficiency of the according process-oriented standards

Challenges in Clinicogenetic Correlations:One Phenotype – Many Genes

Background: In the field of movement disorders, what you see (phenotype) is seldom what you get (genotype). Whereas 1 phenotype was previously associated to 1 gene, the advent of next-generation sequencing (NGS) has facilitated an exponential increase in disease-causing genes and genotype-phenotype correlations, and the "one-phenotype-many-genes" paradigm has become prominent.Objectives: To highlight the "one-phenotype-many-genes" paradigm by discussing the main challenges, perspectives on how to address them, and future directions.Methods: We performed a scoping review of the various aspects involved in identifying the underlying molecular cause of a movement disorder phenotype.Results: The notable challenges are (1) the lack of gold standards, overlap in clinical spectrum of different movement disorders, and variability in the interpretation of classification systems; (2) selecting which patients benefit from genetic tests and the choice of genetic testing; (3) problems in the variant interpretation guidelines; (4) the filtering of variants associated with disease; and (5) the lack of standardized, complete, and up-to-date gene lists. Perspectives to address these include (1) deep phenotyping and genotype-phenotype integration, (2) adherence to phenotype-specific diagnostic algorithms, (3) implementation of current and complementary bioinformatic tools, (4) a clinical-molecular diagnosis through close collaboration between clinicians and genetic laboratories, and (5) ongoing curation of gene lists and periodic reanalysis of genetic sequencing data.Conclusions: Despite the rapidly emerging possibilities of NGS, there are still many steps to take to improve the genetic diagnostic yield. Future directions, including post-NGS phenotyping and cohort analyses enriched by genotype-phenotype integration and gene networks, ought to be pursued to accelerate identification of disease-causing genes and further improve our understanding of disease biology