The evaluation of time series: their scientific value and contribution to policy needs. Occasional Publication of the Marine Biological Association 22

In 2000 a Review of Current Marine Observations in relation to present and future needs was undertaken by the Inter-Agency Committee for Marine Science and Technology (IACMST). The Marine Environmental Change Network (MECN) was initiated in 2002 as a direct response to the recommendations of the report. A key part of the current phase of the MECN is to ensure that information from the network is provided to policy makers and other end-users to enable them to produce more accurate assessments of ecosystem state and gain a clearer understanding of factors influencing change in marine ecosystems. The MECN holds workshops on an annual basis, bringing together partners maintaining time-series and long-term datasets as well as end-users interested in outputs from the network. It was decided that the first workshop of the MECN continuation phase should consist of an evaluation of the time series and data sets maintained by partners in the MECN with regard to their ‘fit for purpose’ for answering key science questions and informing policy development. This report is based on the outcomes of the workshop. Section one of the report contains a brief introduction to monitoring, time series and long-term datasets. The various terms are defined and the need for MECN type data to complement compliance monitoring programmes is discussed. Outlines are also given of initiatives such as the United Kingdom Marine Monitoring and Assessment Strategy (UKMMAS) and Oceans 2025. Section two contains detailed information for each of the MECN time series / long-term datasets including information on scientific outputs and current objectives. This information is mainly based on the presentations given at the workshop and therefore follows a format whereby the following headings are addressed: Origin of time series including original objectives; current objectives; policy relevance; products (advice, publications, science and society). Section three consists of comments made by the review panel concerning all the time series and the network. Needs or issues highlighted by the panel with regard to the future of long-term datasets and time-series in the UK are shown along with advice and potential solutions where offered. The recommendations are divided into 4 categories; ‘The MECN and end-user requirements’; ‘Procedures & protocols’; ‘Securing data series’ and ‘Future developments’. Ever since marine environmental protection issues really came to the fore in the 1960s, it has been recognised that there is a requirement for a suitable evidence base on environmental change in order to support policy and management for UK waters. Section four gives a brief summary of the development of marine policy in the UK along with comments on the availability and necessity of long-term marine observations for the implementation of this policy. Policy relating to three main areas is discussed; Marine Conservation (protecting biodiversity and marine ecosystems); Marine Pollution and Fisheries. The conclusion of this section is that there has always been a specific requirement for information on long-term change in marine ecosystems around the UK in order to address concerns over pollution, fishing and general conservation. It is now imperative that this need is addressed in order for the UK to be able to fulfil its policy commitments and manage marine ecosystems in the light of climate change and other factors.

Apparent Specific Dynamic Action In Mytilus-Edulis L

The results of experiments recorded by Bayne & Scullard (1977) confirmed earlier studies (Bayne, 1973) in describing a decline in the rate of oxygen uptake (Vo2) by Mytilus edulis during starvation, eventually reaching a steady-state value, called the standard rate of oxygen consumption. Earlier experiments had also shown that if such starved mussels were fed, oxygen uptake increased rapidly to a high level called the active rate of oxygen consumption (Thompson & Bayne, 1972; Bayne, Thompson & Widdows, 1973). Some of this increase in metabolic rate is undoubtedly due to an increased filtration rate that is stimulated by the presence of food (the ‘mechanical cost of feeding’ discussed by Bayne et al. 1976), and part is due to the ‘physiological costs of feeding’, which includes energy utilized in digestion and assimilation of the food, and energy that is lost during deamination and other catabolic processes that accompany digestion (Warren & Davis, 1967). Increases in metabolic rate associated with feeding have been called the specific dynamic action (SDA) of the ration (see Harper, 1971, for a discussion) or the apparent SDA (Beamish, 1974)5 and they have been related to aspects of protein metabolism (Krebs, 1964). This paper describes the results of some experiments designed to examine the relationships between SDA and ammonia excretion in Mytilus edulis L.

Isoform-specific inhibition of TRPC4 channel by phosphatidylinositol 4,5-bisphosphate.

Full-length transient receptor potential (TRP) cation channel TRPC4alpha and shorter TRPC4beta lacking 84 amino acids in the cytosolic C terminus are expressed in smooth muscle and endothelial cells where they regulate membrane potential and Ca(2+) influx. In common with other "classical" TRPCs, TRPC4 is activated by G(q)/phospholipase C-coupled receptors, but the underlying mechanism remains elusive. Little is also known about any isoform-specific channel regulation. Here we show that TRPC4alpha but not TRPC4beta was strongly inhibited by intracellularly applied phosphatidylinositol 4,5-bisphosphate (PIP(2)). In contrast, several other phosphoinositides (PI), including PI(3,4)P(2), PI(3,5)P(2), and PI(3,4,5)P(3), had no effect or even potentiated TRPC4alpha indicating that PIP(2) inhibits TRPC4alpha in a highly selective manner. We show that PIP(2) binds to the C terminus of TRPC4alpha but not that of TRPC4beta in vitro. Its inhibitory action was dependent on the association of TRPC4alpha with actin cytoskeleton as it was prevented by cytochalasin D treatment or by the deletion of the C-terminal PDZ-binding motif (Thr-Thr-Arg-Leu) that links TRPC4 to F-actin through the sodium-hydrogen exchanger regulatory factor and ezrin. PIP(2) breakdown appears to be a required step in TRPC4alpha channel activation as PIP(2) depletion alone was insufficient for channel opening, which additionally required Ca(2+) and pertussis toxin-sensitive G(i/o) proteins. Thus, TRPC4 channels integrate a variety of G-protein-dependent stimuli, including a PIP(2)/cytoskeleton dependence reminiscent of the TRPC4-like muscarinic agonist-activated cation channels in ileal myocytes.

The Association Between Childhood Trauma and Memory Functioning in Schizophrenia

Objective: Both neurocognitive impairments and a history of childhood abuse are highly prevalent in patients with schizophrenia. Childhood trauma has been associated with memory impairment as well as hippocampal volume reduction in adult survivors. The aim of the following study was to examine the contribution of childhood adversity to verbal memory functioning in people with schizophrenia. Methods: Eighty-five outpatients with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnosis of chronic schizophrenia were separated into 2 groups on the basis of self-reports of childhood trauma. Performance on measures of episodic narrative memory, list learning, and working memory was then compared using multivariate analysis of covariance. Results: Thirty-eight (45%) participants reported moderate to severe levels of childhood adversity, while 47 (55%) reported no or low levels of childhood adversity. After controlling for premorbid IQ and current depressive symptoms, the childhood trauma group had significantly poorer working memory and episodic narrative memory. However, list learning was similar between groups. Conclusion: Childhood trauma is an important variable that can contribute to specific ongoing memory impairments in schizophrenia.

No or only population-specific effect of PON1 on human longevity: A comprehensive meta-analysis

Paraoxonase 1 (PON1) has been suggested as a plausible candidate gene for human longevity due to its modulation of cardiovascular disease risk, by preventing oxidation of atherogenic low-density lipoprotein. The role of the PON1 192 Q/R polymorphism has been analyzed for association with survival at old age in several populations, albeit with controversial results. To reconcile the conflicting evidence, we performed a large association study with two samples of 2357 Germans and 1025 French, respectively. We combined our results with those from seven previous studies in the largest and most comprehensive meta-analysis on PON1 192 Q/R and longevity to-date, to include a total of 9580 individuals. No significant association of PON1 192 Q/R with longevity was observed, for either R allele or carriership. This finding relied on very large sample sizes, is supported by different analysis methods and is therefore considered very robust. Moreover, we have investigated a potential interaction of PON1 192 Q/R with APOE epsilon4 using data from four populations. Whereas a significant result was found in the German sample, this could not be confirmed in the other examined groups. Our large-scale meta-analysis provided no evidence that the PON1 192 Q/R polymorphism is associated with longevity, but this does not exclude the possibility of population-specific effects due to the influence of, and interaction between, different genetic and/or environmental factors (e.g. diet).

Differential expression of steroid 5 alpha-reductase isozymes and association with disease severity and angiogenic genes predict their biological role in prostate cancer

The biological role of steroid 5 alpha-reductase isozymes (encoded by the SRD5A1 and SRD5A2 genes) and angiogenic factors that play important roles in the pathogenesis and vascularization of prostate cancer (PC) is poorly understood. The sub-cellular expression of these isozymes and vascular endothelial growth factor (VEGF) in PC tissue microarrays (n=62) was examined using immunohistochemistry. The effect of SRD5A inhibition on the angiogenesis pathway genes in PC was also examined in prostate cell lines, LNCaP, PC3, and RWPE-1, by treating them with the SRD5A inhibitors finasteride and dutasteride, followed by western blot, quantitative PCR, and ELISA chip array techniques. In PC tissues, nuclear SRD5A1 expression was strongly associated with higher cancer Gleason scores (P=0.02), higher cancer stage (P=0.01), and higher serum prostate specific antigen (PSA) levels (P=0.01), whereas nuclear SRD5A2 expression was correlated with VEGF expression (P=0.01). Prostate tumor cell viability was significantly reduced in dutasteride-treated PC3 and RWPE-1 cells compared with finasteride-treated groups. Expression of the angiogenesis pathway genes transforming growth factor beta 1 (TGFB1), endothelin (EDN1), TGF alpha (TGFA), and VEGFR1 was upregulated in LNCaP cells, and at least 7 out of 21 genes were upregulated in PC3 cells treated with finasteride (25 mu M). Our findings suggest that SRD5A1 expression predominates in advanced PC, and that inhibition of SRD5A1 and SRD5A2 together was more effective in reducing cell numbers than inhibition of SRD5A2 alone. However, these inhibitors did not show any significant difference in prostate cell angiogenic response. Interestingly, some angiogenic genes remained activated after treatment, possibly due to the duration of treatment and tumor resistance to inhibitors. Endocrine-Related Cancer (2010) 17 757-770

Development of an allele-specific real-time PCR assay for discrimination and quantification of p63 R279H mutation in EEC syndrome

The ectrodactyly-ectodermal dysplasiaclefting syndrome is a rare autosomal dominant disorder caused by heterozygous mutations in the p63 gene, a transcription factor belonging to the p53 family. The majority of cases of ectrodactyly-ectodermal dysplasia syndrome are caused by de novo mutations and are therefore sporadic in approximately 60% of patients. The substitution of arginine to histidine (R279H), due to a c.836G>A mutation in exon 7 of the p63 gene, represents 55% of the identified mutations and is considered a mutational hot spot. A quantitative and sensitive real-time PCR was performed to quantify both wild-type and R279H alleles in DNA extracted from peripheral blood and RNA from cultured epithelial cells. Standard curves were constructed for both wild-type and mutant probes. The sensitivity of the assay was determined by generating serial dilutions of the DNA isolated from heterozygous patients (50% of alleles mutated) with wild-type DNA, thus obtaining decreasing percentages of p63 R279H mutant allele (50%, 37.5%, 25%, 12.5%, 10%, 7.5%, 5%, 2.5%, and 0.0%). The assay detected up to 1% of the mutant p63. The high sensitivity of the assay is of particular relevance to prenatal diagnosis and counseling and to detect therapeutic effects of drug treatment or gene therapy aimed at reducing the amount of mutated p63. © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Association of the G4 rotavirus genotype with gastroenteritis in adults

Rotavirus is the most common etiological cause of acute viral gastroenteritis in infants and young children worldwide, yet its role in the adult population is less well understood. We have recently identified rotavirus as the causative agent of severe diarrhea in adults, specifically in two gastroenteritis outbreaks in separate care for the elderly homes. Strain typing has shown the continued presence of P[8]G1, the emergence of P[8]G9, and the reemergence of P[8]G4. A total of 26 community cases and 6 outbreak cases of rotavirus infection, positive via a molecular screening assay, were subsequently amplified using VP4 and VP7 specific primers (Con2/Con3 and 1A/1B primer sets, respectively). The age range of patients investigated was from