Evaluation of candidate International Standards for meningococcal capsular polysaccharide groups W and Y.

Two candidate International Standards for meningococcal capsular group W and Y (MenW and MenY, respectively) polysaccharides were assessed for their suitability as quantitative standards in various physicochemical assays. The study was designed to evaluate the intended purpose of these standards, namely, to standardize the quantification of the respective polysaccharide content in meningococcal polysaccharide and conjugate vaccines and their intermediate components. Twelve laboratories from eleven different countries participated in the collaborative study of candidate preparations for International Standards for MenW and MenY polysaccharide (coded 16/152 and 16/206, respectively).

Endocrine Disruption Is Reduced but Still Widespread in Wild Roach () Living in English Rivers.

Endocrine disruption of wild fish, primarily resulting in the feminization of males, has been reported in English river sites for several decades. Estrogenic activity emanating from wastewater treatment works (WwTW) has been conclusively demonstrated to be the main driver of these feminized phenotypes. Here, we revisit 10 English river sites previously surveyed in the late 1990s and early 2000s to assess how the frequency and severity of feminization now compare with the historical surveys.

Feminizing effects of ethinylestradiol in roach (Rutilus rutilus) populations with different estrogenic pollution exposure histories.

Experimental exposures aimed at assessing the risks posed by estrogens in waste-water treatment work (WwTW) effluents to fish populations have rarely considered whether populations differ in their sensitivity to estrogenic compounds. This is despite evidence that selection at genes involved in the estrogen response has occurred in wild populations, and evidence that genotype can influence estrogen-response. In this study we compare the effects of a two-year exposure to a low measured concentration (1.

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use.

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.

Saccharide dosage content of meningococcal polysaccharide conjugate vaccines determined using WHO International Standards for serogroup A, C, W, Y and X polysaccharides.

Potency of meningococcal polysaccharide-protein conjugate vaccines relies on the polysaccharide content to prevent meningitis. NIBSC, as the official national control laboratory in UK, analysed ten different mono- and multi-meningococcal conjugate vaccines, using established International Standards for meningococcal serogroups A, C, W, Y and X, by resorcinol or HPAEC-PAD assay. Most saccharide contents were within ±20% of their claimed content for licensure with taking different O-acetylation levels into consideration, with only MenC content in two vaccines below (by 60% and 54%) the labelled value, however, previous study showed different dosage was not necessarily correlated to the immunogenicity of those vaccines.

Validation of Arxula Yeast Estrogen Screen assay for detection of estrogenic activity in water samples: Results of an international interlaboratory study.

Endocrine-active substances can adversely impact the aquatic ecosystems. A special emphasis is laid, among others, on the effects of estrogens and estrogen mimicking compounds. Effect-based screening methods like in vitro bioassays are suitable tools to detect and quantify endocrine activities of known and unknown mixtures.

Quality, immunogenicity and stability of meningococcal serogroup ACWY-CRM, DT and TT glycoconjugate vaccines.

A physicochemical and immunological study of the stability of three different meningococcal (Men) ACWY conjugate vaccines was performed to evaluate any patterns of serogroup oligo- or polysaccharide-specific or carrier protein-specific stability that would affect immunogenicity. Critical quality and stability-indicating characteristics were measured, with the study supporting the suitability of both HPLC-SEC and HPAEC-PAD methods to detect changes following inappropriate vaccine storage. All three final products, ACWY-CRM, -DT and -TT conjugate vaccines had expected quality indicator values and similar immunogenicity in a mouse model (anti-PS IgG and rSBA) when stored at +2-8°C.

Evaluation of candidate international standards for meningococcal serogroups A and X polysaccharide.

Polysaccharide (PS) based meningococcal vaccines are primarily evaluated by physicochemical methods to ensure batches are consistently manufactured. As PS content is determined by different methods across numerous laboratories, there is a need for International Standards (IS) to calibrate the assays. Following the successful introduction of the WHO Meningococcal group C (MenC) IS in 2011, NIBSC initiated projects to prepare similar standards for groups A, W, Y and X (MenA/W/Y/X) to standardise all meningococcal- PS based vaccines.

Use of a Battery of Chemical and Ecotoxicological Methods for the Assessment of the Efficacy of Wastewater Treatment Processes to Remove Estrogenic Potency.

Endocrine Disrupting Compounds pose a substantial risk to the aquatic environment. Ethinylestradiol (EE2) and estrone (E1) have recently been included in a watch list of environmental pollutants under the European Water Framework Directive. Municipal wastewater treatment plants are major contributors to the estrogenic potency of surface waters.

No evidence of exposure to environmental estrogens in two feral fish species sampled from the Yarra River, Australia: A comparison with Northern Hemisphere studies.

Environmental estrogens originate from a variety of sources including sewage treatment plant (STP) effluents and adverse physiological effects (endocrine disruption) have been observed in several fish species sampled downstream of STP discharges. In this study we examined common carp (Cyprinus carpio) and roach (Rutilis rutilis) for signs of exposure to environmental estrogens in the iconic Yarra River, Melbourne, Australia. The Yarra River flows through the city of Melbourne and more than 2 million people live within the catchment.

From single chemicals to mixtures--reproductive effects of levonorgestrel and ethinylestradiol on the fathead minnow.

The aquatic environment is polluted with thousands of chemicals. It is currently unclear which of these pose a significant threat to aquatic biota. The typical exposure scenario is now represented by a widespread blanket of contamination composed of myriads of individual pollutants-each typically present at a low concentration.

Removal of ecotoxicity of 17α-ethinylestradiol using TAML/peroxide water treatment.

17α-ethinylestradiol (EE2), a synthetic oestrogen in oral contraceptives, is one of many pharmaceuticals found in inland waterways worldwide as a result of human consumption and excretion into wastewater treatment systems. At low parts per trillion (ppt), EE2 induces feminisation of male fish, diminishing reproductive success and causing fish population collapse. Intended water quality standards for EE2 set a much needed global precedent.

Several synthetic progestins with different potencies adversely affect reproduction of fish.

Synthetic progestins are widely used as a component in both contraceptives and in hormone replacement therapy (HRT), both on their own and in combination with EE2. Their presence in the environment is now established in wastewater effluent and river water and this has led to concerns regarding their potential effects on aquatic organisms living in these waters. We carried out in vivo experiments to determine the potencies of four different synthetic progestins on the reproductive capabilities of the fathead minnow (Pimephales promelas).

Additional treatment of wastewater reduces endocrine disruption in wild fish--a comparative study of tertiary and advanced treatments.

Steroid estrogens are thought to be the major cause of feminization (intersex) in wild fish. Widely used wastewater treatment technologies are not effective at removing these contaminants to concentrations thought to be required to protect aquatic wildlife. A number of advanced treatment processes have been proposed to reduce the concentrations of estrogens entering the environment.

UvrD2 is essential in Mycobacterium tuberculosis, but its helicase activity is not required.

UvrD is an SF1 family helicase involved in DNA repair that is widely conserved in bacteria. Mycobacterium tuberculosis has two annotated UvrD homologues; here we investigate the role of UvrD2. The uvrD2 gene at its native locus could be knocked out only in the presence of a second copy of the gene, demonstrating that uvrD2 is essential.

Phylogenetic and genetic linkage between novel atypical dual-specificity phosphatases from non-metazoan organisms.

Dual-specificity phosphatases (DSPs) constitute a large protein tyrosine phosphatase (PTP) family, with examples in distant evolutive phyla. PFA-DSPs (Plant and Fungi Atypical DSPs) are a group of atypical DSPs present in plants, fungi, kinetoplastids, and slime molds, the members of which share structural similarity with atypical- and lipid phosphatase DSPs from mammals. The analysis of the PFA-DSPs from the plant Arabidopsis thaliana (AtPFA-DSPs) showed differential tissue mRNA expression, substrate specificity, and catalytic activity for these proteins, suggesting different functional roles among plant PFA-DSPs.

Estrogenic activity of tropical fish food can alter baseline vitellogenin concentrations in male fathead minnow (Pimephales promelas).

Vitellogenin (VTG) is a precursor of egg-yolk protein and is therefore present at high concentrations in the plasma of female fish. In male fish, VTG concentrations are usually undetectable or low but can be induced upon exposure to estrogenic substances either via the water or the diet. This work was performed to determine the reason for the apparently elevated VTG concentrations in unexposed stock male fathead minnow maintained in our laboratory.

A new family of phosphoinositide phosphatases in microorganisms: identification and biochemical analysis.

Background: Phosphoinositide metabolism is essential to membrane dynamics and impinges on many cellular processes, including phagocytosis. Modulation of phosphoinositide metabolism is important for pathogenicity and virulence of many human pathogens, allowing them to survive and replicate in the host cells. Phosphoinositide phosphatases from bacterial pathogens are therefore key players in this modulation and constitute attractive targets for chemotherapy.

Hypoxia does not influence the response of fish to a mixture of estrogenic chemicals.

Chemical risk assessment procedures assign a major role to standardized toxicity tests, in which the response of a particular organism to a single test substance is determined under otherwise constant and favorable conditions in the laboratory. This approach fails to consider the potential for chemical interactions, as well as failing to consider how the toxicological response varies, depending on the conditions of exposure. As yet, the issue of confounding factors on chemically mediated effects in wildlife has received little attention, despite the fact that a range of physicochemical parameters, including temperature, water quality, and pH, are known to modify chemical toxicity.

MptpB, a virulence factor from Mycobacterium tuberculosis, exhibits triple-specificity phosphatase activity.

Bacterial pathogens have developed sophisticated mechanisms of evading the immune system to survive in infected host cells. Central to the pathogenesis of Mycobacterium tuberculosis is the arrest of phagosome maturation, partly through interference with PtdIns signalling. The protein phosphatase MptpB is an essential secreted virulence factor in M.

Novel estrogen receptor-related Transcripts in Marisa cornuarietis; a freshwater snail with reported sensitivity to estrogenic chemicals.

We have isolated novel molluskan steroid receptor transcripts orthologous to vertebrate estrogen receptors (ERs) and estrogen receptor-related receptors (ERRs) from the freshwater snail Marisa cornuarietis. Radiolabeled ligand binding analyses showed that neither recombinant receptor protein specifically bound 17beta-estradiol over the range applied (0.3-9.

Characterization of an HMG-CoA reductase from Listeria monocytogenes that exhibits dual coenzyme specificity.

HMG-CoA reductase (HMGR) is an enzyme critical for cellular cholesterol synthesis in mammals and isoprenoid synthesis in certain eubacteria, catalyzing the NAD(P)H-dependent reduction of HMG-CoA to mevalonate. We have isolated the gene encoding HMG-CoA reductase from Listeria monocytogenes and expressed the recombinant 6x-His-tagged form in Escherichia coli. Using NAD(P)(H), the enzyme catalyzes HMG-CoA reduction approximately 200-fold more efficiently than mevalonate oxidation in vitro.

COMPRENDO: Focus and approach.

Tens of thousands of man-made chemicals are in regular use and discharged into the environment. Many of them are known to interfere with the hormonal systems in humans and wildlife. Given the complexity of endocrine systems, there are many ways in which endocrine-disrupting chemicals (EDCs) can affect the body's signaling system, and this makes unraveling the mechanisms of action of these chemicals difficult.