bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo rates and selection of large copy number variation
Authors: Itsara Andy , Wu Hao , Smith Joshua D. , Nickerson Deborah A. , Romieu Isabelle , London Stephanie J. , Eichler Evan E.
Published: September 2010

While copy number variation (CNV) is an active area of research, de novo mutation rates within human populations are not well characterized. By focusing on large (>100 kbp) events, we estimate the rate of de novo CNV formation in humans by analyzing 4394 transmissions from human pedigrees with and without neurocognitive disease. We show that a significant limitation in directly measuring genome-wide CNV mutation is accessing DNA derived from primary tissues as opposed to cell lines. We conservatively estimated the genome-wide CNV mutation rate using single nucleotide polymorphism (SNP) microarrays to analyze whole-blood derived DNA from asthmatic trios, a collection in which we observed no elevation in the prevalence of large CNVs. At a resolution of ∼30 kb, nine de novo CNVs were observed from 772 transmissions, corresponding to a mutation rate of μ = 1.2 × 10−2 CNVs per genome per transmission (μ = 6.5 × 10−3 for CNVs >500 kb). Combined with previous estimates of CNV prevalence and assuming a model of mutation-selection balance, we estimate significant purifying selection for large (>500 kb) events at the genome-wide level to be s = 0.16. Supporting this, we identify de novo CNVs in 717 multiplex autism pedigrees from the AGRE collection and observe a fourfold enrichment (P = 1.4 × 10−3) for de novo CNVs in cases of multiplex autism versus unaffected siblings, suggesting that many de novo CNV mutations contribute a subtle, but significant risk for autism. We observe no parental bias in the origin or transmission of CNVs among any of the cohorts studied.
Functional metagenomics to mine the human gut microbiome for dietary fiber catabolic enzymes
Authors: Tasse Lena , Bercovici Juliette , Pizzut-Serin Sandra , Robe Patrick , Tap Julien , Klopp Christophe , Cantarel Brandi L. , Coutinho Pedro M. , Henrissat Bernard , Leclerc Marion , Doré Joël , Monsan Pierre , Remaud-Simeon Magali , Potocki-Veronese Gabrielle
Published: September 2010

The human gut microbiome is a complex ecosystem composed mainly of uncultured bacteria. It plays an essential role in the catabolism of dietary fibers, the part of plant material in our diet that is not metabolized in the upper digestive tract, because the human genome does not encode adequate carbohydrate active enzymes (CAZymes). We describe a multi-step functionally based approach to guide the in-depth pyrosequencing of specific regions of the human gut metagenome encoding the CAZymes involved in dietary fiber breakdown. High-throughput functional screens were first applied to a library covering 5.4 × 109 bp of metagenomic DNA, allowing the isolation of 310 clones showing beta-glucanase, hemicellulase, galactanase, amylase, or pectinase activities. Based on the results of refined secondary screens, sequencing efforts were reduced to 0.84 Mb of nonredundant metagenomic DNA, corresponding to 26 clones that were particularly efficient for the degradation of raw plant polysaccharides. Seventy-three CAZymes from 35 different families were discovered. This corresponds to a fivefold target-gene enrichment compared to random sequencing of the human gut metagenome. Thirty-three of these CAZy encoding genes are highly homologous to prevalent genes found in the gut microbiome of at least 20 individuals for whose metagenomic data are available. Moreover, 18 multigenic clusters encoding complementary enzyme activities for plant cell wall degradation were also identified. Gene taxonomic assignment is consistent with horizontal gene transfer events in dominant gut species and provides new insights into the human gut functional trophic chain.
Structural Sterols Are Involved in Both the Initiation and Tip Growth of Root Hairs inArabidopsis thaliana
Authors: Ovečka Miroslav , Berson Tobias , Beck Martina , Derksen Jan , Šamaj Jozef , Baluška František , Lichtscheidl Irene K.
Published: September 2010

Structural sterols are abundant in the plasma membrane of root apex cells in Arabidopsis thaliana. They specifically accumulate in trichoblasts during the prebulging and bulge stages and show a polar accumulation in the tip during root hair elongation but are distributed evenly in mature root hairs. Thus, structural sterols may serve as a marker for root hair initiation and growth. In addition, they may predict branching events in mutants with branching root hairs. Structural sterols were detected using the sterol complexing fluorochrome filipin. Application of filipin caused a rapid, concentration-dependent decrease in tip growth. Filipin-complexed sterols accumulated in globular structures that fused to larger FM4-64–positive aggregates in the tip, so-called filipin-induced apical compartments, which were closely associated with the plasma membrane. The plasma membrane appeared malformed and the cytoarchitecture of the tip zone was affected. Trans-Golgi network/early endosomal compartments containing molecular markers, such as small Rab GTPase RabA1d and SNARE Wave line 13 (VTI12), locally accumulated in these filipin-induced apical compartments, while late endosomes, endoplasmic reticulum, mitochondria, plastids, and cytosol were excluded from them. These data suggest that the local distribution and apical accumulation of structural sterols may regulate vesicular trafficking and plasma membrane properties during both initiation and tip growth of root hairs in Arabidopsis.
The dynamic labor force: findings from the 2009 annual meeting of the Southern Management Association
Authors: Lambert Jason R.
Published: September 2010

Purpose

The purpose of this paper is to review the highlights of research on gender and diversity that was presented at the recent 2009 annual meeting of the Southern Management Association in Asheville, North Carolina.

Design/methodology/approach

The papers covering topics relevant to gender and diversity are summarized. The papers vary in terms of research design and methodology. There was a mix of conceptual papers and empirical studies using both quantitative and qualitative analysis.

Findings

Overall, the emerging trend of an increase in minority and women employees is becoming greater. Owing to this trend it is necessary for organizations to prepare themselves in order to accommodate and properly manage this workforce. Minority and women employees should also prepare themselves with strategies to combat discrimination at work in order to benefit fully from this emerging trend. Gender impacts the perceptions of both men and women employees, and associated outcomes may vary based on the type of job or position held by the employee. Religion is becoming more important to employees and their religious beliefs and level of spirituality may be linked to both individual performance and interdependent work outcomes.

Originality/value

The papers presented contribute to the body of research knowledge and better the understanding of the role that diversity plays in organizations. Ideas for future research and practical implications are also presented.
Market liberalization and crop planting decision: a case of China
Authors: Pan Suwen , Malaga Jaime , He Xiurong
Published: September 2010

Purpose

The paper aims to measure the effects of market liberalization on Chinese farmers' crop planting decisions.

Design/methodology/approach

The effects are measured using a censored, two‐stage, least‐square regression.

Findings

The results show that the effects of market liberalization on planting decisions are more significant in the case of crops with minimum support price (rice, wheat, and corn) than in the case of crops where planting decision is determined by market prices (cotton and soybean). The effects appear to be different across regions and time zones and more significant in 1993 than in 2005.

Originality/value

The result suggests that market liberalization along the past ten years achieved significant effects in Chinese farmers planting decision. This outcome should be taken into consideration when evaluating and implementing future Chinese agricultural policy income‐based interventions as a means to meet domestic food security goals and increase farmers' income level.
Prescribing and sale of ophthalmic chloramphenicol following reclassification to over-the-counter availability
Authors: Walker Roger , Hinchliffe Anne
Published: September 2010

Objectives

The impact of over-the-counter (OTC) availability of chloramphenicol eye drops and eye ointment was investigated on the prescribing and overall supply of ophthalmic chloramphenicol in primary care.

Methods

Primary care prescription data for ophthalmic chloramphenicol and ophthalmic antibacterials in England and Wales were analysed from December 2003 (month 1) to September 2008 (month 58). OTC data were analysed from June 2005 when the first OTC product was launched (months 19 to 58).

Key findings

In the 40 months following reclassification more than 2.9 million packs (53.9 per 1000 population) of chloramphenicol were sold in England and 152 024 (51.7 per 1000 population) in Wales. In the 12 months to September 2008 sales of the drops and ointment were 67 and 40% of their respective prescription volumes in England. In Wales sales of drops were 52% and ointment 26% of their respective prescription volumes. The number of chloramphenicol packs sold was 2.2 times greater than the calculated reduction in ophthalmic antibacterial prescription items in England and 2.9 times greater than the reduction seen in Wales.

Conclusion

Following the reclassification of chloramphenicol there have been significant increases in the supply of the ophthalmic antibacterials in both England and Wales.
Spawning frequency of brood dams and sires in a marine fish stock‐enhancement hatchery
Authors: Gold J. R. , Renshaw M. A. , Saillant E. , Vega R. R.
Published: September 2010

Parentage analysis, employing five hypervariable microsatellite markers, was used to follow spawning patterns of red drum Sciaenops ocellatus broodfish in two spawning tanks through most of a calendar year in a marine fish hatchery dedicated to stock enhancement. Five of six dams and all four sires spawned at least once during the year. Variation in dam and sire spawning incidence and in number of progeny produced per dam and per sire translated into reduced genetic effective size (Ne) per spawn by 40·6% in one tank and 50·8% in the other.
Who Controls US?
Authors: Gadhoum Yoser , Lang Larry H. P. , Young Leslie
Published: September 2010

Berle and Means asserted that US corporations typically have dispersed shareholders; their evidence did not support this conclusion. Today, 59.74% of US corporations have ‘controlling shareholders’ who hold at least 10% of the shares; 24.57% are controlled and managed by a family; 16.33% are controlled by a widely‐held financial institution; 13.55% are controlled through family trusts. In all size ranges, the USA has more corporations controlled by families than by financial institutions. In almost all size ranges, it has a higher percentage of family‐controlled corporations than any of next four largest economies.
Peer smoking and the nicotinic receptor genes: an examination of genetic and environmental risks for nicotine dependence
Authors: Johnson Eric O. , Chen Li‐Shiun , Breslau Naomi , Hatsukami Dorothy , Robbins Tania , Saccone Nancy L. , Grucza Richard A. , Bierut Laura J.
Published: September 2010

Background  Peer smoking provides a socially reinforcing context of friends' encouragement and approval that contributes to smoking behavior. Twin studies show correlations and interactions between peer substance use and genetic liability for substance use. However, none examined specific genes. Here we test the hypothesis that the nicotinic receptor genes CHRNA5 (rs16969968), CHRNA3 (rs578776), CHRNB3 (rs13277254) and CHRND (rs12466358) modify the risk for nicotine dependence associated with peer smoking.

Methods  Cases of current nicotine dependence [Fagerström Test for Nicotine Dependence (FTND) ≥ 4] and smoking‐exposed (smoked 100+ cigarettes life‐time), but non‐dependent controls (life‐time FTND = 0) came from the Collaborative Genetic Study of Nicotine Dependence (n = 2038). Peer smoking was assessed retrospectively for grades 9–12.

Results  Peer smoking and the four single nucleotide polymorphisms (SNPs) were associated with nicotine dependence. A statistically significant interaction was found between peer smoking and rs16969968 (P = 0.0077). Overall risk of nicotine dependence was highest for the rs16969968 AA genotype. However, variance in nicotine dependence attributable to peer smoking was substantially lower among those with the AA genotype at rs16969968 than the lower‐risk genotypes: AA = 2.5%, GA/AG = 11.2%, GG = 14.2%; P ≤ 0.004.

Conclusions  Peer smoking had a substantially lower effect on nicotine dependence among those with the high‐risk AA genotype at the functional SNP rs16969968 (CHRNA5) than among those with lower‐risk genotypes. Such results highlight the possibility that given drug exposure those with specific genetic risks may be less affected by social contexts and intervention strategies focused upon social factors could have less influence on those at highest genetic risk.
Impulsivity and socio‐economic status interact to increase the risk of gambling onset among youth
Authors: Auger Nathalie , Lo Ernest , Cantinotti Michael , O'Loughlin Jennifer
Published: September 2010

Aims  To determine if impulsivity and socio‐economic status (SES) interact to influence gambling onset in youth.

Design  Longitudinal study of grade 7 students followed for 8 years.

Setting  Montréal, Canada.

Participants  A total of 628 adult students aged 12.6 years on average at cohort inception.

Measurements  Impulsivity and SES (parent education, area deprivation) were collected during secondary school. Age of gambling onset was collected retrospectively when participants were aged 20.3 years. Cox proportional hazards regression was used to model the association between time to first report of gambling and interaction terms for each of impulsivity and parent education, and impulsivity and area deprivation accounting for sex and ethnicity.

Findings  Median (interquartile range) age of gambling onset was 17.0 (4.0) years. Impulsivity independently increased the risk of gambling onset among participants with no university‐educated parent [hazard ratio (HR) 1.3; 95% confidence interval 1.1–1.5] and those living in highly deprived areas (HR 1.7; 1.5–2.0). Impulsivity was not associated with gambling onset among high SES youth. Among participants with high impulsivity, risks were elevated for those with no university‐educated parent relative to one or more university‐educated parent (HR 1.7; 1.1–2.7), and for participants living in deprived relative to advantaged areas (HR 5.0; 2.6–9.6). SES was not associated with gambling onset among participants with low impulsivity.

Conclusions  Impulsivity is a risk factor for gambling onset among low but not high SES youth, and low SES influences gambling onset primarily among impulsive youth. Gambling prevention programmes may need to consider potential interaction between impulsivity and SES.
Self‐reported side effects in buprenorphine and methadone patients receiving antiretroviral therapy: results from the MANIF 2000 cohort study
Authors: Carrieri M. Patrizia , Roux Perrine , Cohen Julien , Ravaux Isabelle , Dellamonica Pierre , Protopopescu Camelia , Spire Bruno , Rosenblum Andrew
Published: September 2010

Aims  The aim of the study was to investigate the relationship between methadone and buprenorphine treatment and self‐reported symptoms in HIV‐infected opioid dependent individuals receiving antiretroviral therapy (ART).

Design  Longitudinal study.

Setting  The French MANIF2000 cohort was used to compare self‐reported symptoms in buprenorphine and methadone patients also receiving ART.

Participants  We selected individuals receiving ART and OAT (342 visits among 106 patients).

Measurements  Symptoms were self‐reported using a list of 14 symptoms (e.g. nausea, fatigue, fever) perceived during the previous 4 weeks, including three painful symptoms (abdominal or muscular pain, headaches). A two‐step Heckman approach enabled us to account for the non‐random assignment of OAT: a probit model identified predictors of starting either buprenorphine or methadone. A Poisson regression based on generalized estimating equations (GEE) was then used to identify predictors of the number of symptoms while adjusting for the non‐random assignment of OAT.

Findings  The median (interquartile range) number of symptoms was 4 (1–6) and 2 (1–6) among buprenorphine and methadone patients, respectively. After adjustment for non‐random assignment of OAT type, depressive and opioid withdrawal symptoms, anxiolytics consumption and daily cannabis use, methadone patients were more likely to report a lower number of symptoms than those receiving buprenorphine.

Conclusions  Methadone patients on ART report fewer symptoms than buprenorphine patients on ART under current treatment conditions in France. Further experimental research is still needed to identify an OAT–ART strategy which would minimize the burden of self‐reported symptoms and potential interactions, while assuring sustainability and response to both treatments.
Depressive mood, suicide ideation and anxiety in smokers who do and smokers who do not manage to stop smoking after a target quit day
Authors: Berlin Ivan , Chen Henian , Covey Lirio S.
Published: September 2010

Aims  The effect of successful and unsuccessful smoking cessation on depressive mood, anxiety‐ and suicide‐related outcomes is unclear. The aim of this secondary analysis was to explore the relationship between abstinence status and these outcomes.

Design  Cohort of adult smokers attempting to stop smoking. Smoking status was assessed by a daily diary; depressed mood, anxiety and suicidal tendencies by the Hamilton Depression Rating Scale (HDRS). The association of complete and point‐prevalence abstinence with the HDRS variables was assessed using multi‐level linear regression models.

Setting  Randomized trial of sertraline versus placebo for smoking cessation with weekly behavioural support provided in a clinic.

Participants  A total of 133 adult smokers with past major depression.

Findings  Pre‐quit mood scores did not predict smoking status post‐quit day. Both continuous and point‐prevalence abstainers had significantly lower total HDRS, suicide and anxiety scores, adjusted for all potential confounders, during the period following quit day than did non‐abstainers who experienced a significant mood deterioration. There was a significant effect of sertraline on post‐quit HDRS scores but not on abstinence.

Conclusions  Contrary to expectation, smoking abstinence among smokers with a history of major depression did not lead to increase in depression, anxiety or suicide ideation; however, failed quit attempts did. Persisting with a quit attempt while unable to achieve abstinence may be associated with mood deterioration.
Current approaches to measuring human islet-antigen specific T cell function in type 1 diabetes
Authors: Mannering S I , Wong F S , Durinovic-Belló I , Brooks-Worrell B , Tree T I , Cilio C M , Schloot N C , Mallone R ,   on behalf of the Immunology of Diabetes Society T-Cell Workshop Committee
Published: September 2010

Type 1 diabetes (T1D) is an autoimmune disease caused by the T cell-mediated destruction of the pancreatic insulin-producing beta cells. Currently there are no widely accepted and standardized assays available to analyse the function of autoreactive T cells involved in T1D. The development of such an assay would greatly aid efforts to understand the pathogenesis of T1D and is also urgently required to guide the development of antigen-based therapies intended to prevent, or cure, T1D. Here we describe some of the assays used currently to detect autoreactive T cells in human blood and review critically their strengths and weaknesses. The challenges and future prospects for the T cell assays are discussed.
Moderate exercise improves leucocyte function and decreases inflammation in diabetes
Authors: Belotto M F , Magdalon J , Rodrigues H G , Vinolo M A R , Curi R , Pithon-Curi T C , Hatanaka E
Published: September 2010

The genesis and progression of diabetes occur due in part to an uncontrolled inflammation profile with insulin resistance, increased serum levels of free fatty acids (FFA), proinflammatory cytokines and leucocyte dysfunction. In this study, an investigation was made of the effect of a 3-week moderate exercise regimen on a treadmill (60% of VO2max, 30 min/day, 6 days a week) on inflammatory markers and leucocyte functions in diabetic rats. The exercise decreased serum levels of tumour necrosis factor (TNF)-α (6%), cytokine-induced neutrophil chemotactic factor 2 alpha/beta (CINC-2α/β) (9%), interleukin (IL)-1β (34%), IL-6 (86%), C-reactive protein (CRP) (41%) and FFA (40%) in diabetic rats when compared with sedentary diabetic animals. Exercise also attenuated the increased responsiveness of leucocytes from diabetics when compared to controls, diminishing the reactive oxygen species (ROS) release by neutrophils (21%) and macrophages (28%). Exercise did not change neutrophil migration and the proportion of neutrophils and macrophages in necrosis (loss of plasma membrane integrity) and apoptosis (DNA fragmentation). Serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH) were not modified in the conditions studied. Therefore, physical training did not alter the integrity of muscle cells. We conclude that moderate physical exercise has marked anti-inflammatory effects on diabetic rats. This may be an efficient strategy to protect diabetics against microorganism infection, insulin resistance and vascular complications.
Department of Medicine, University of Innsbruck, Austria
Authors: Sandhofer F. , Bolzano K. , Sailer S. , Braansteiner H.
Published: September 2010

Abstract. In 5 patients with chronic liver disease (chronic persistent hepatitis, chronic aggressive hepatitis, posthepatitic cirrhosis, alcoholic cirrhosis and primary biliary cirrhosis) various parameters of cholesterol turnover were estimated from the specific activity time curve of plasma cholesterol after an intravenous injection of labelled cholesterol. The mean size of the more rapidly exchangeable pool A (which essentially includes cholesterol of plasma, erythrocytes, bile, liver, intestine and some cholesterol of other organs such as spleen, kidney, and lung) was significantly increased as compared with that of 16 healthy individuals. The mean production rate of cholesterol (synthesis plus absorption), the mean rate constant for cholesterol turnover in pool A (kAA), and the mean fraction of cholesterol of pool A which leaves the system per unit of time (kA) were significantly decreased as compared with the corresponding values of the control group. The mean transfer rates between pool A and the more slowly exchangeable pool B (which includes exchangeable cholesterol in tissues other than pool A) and the mean size of pool B were not significantly altered in the patients with chronic liver disease. SVom these findings and from the interrelationships between the various parameters of cholesterol turnover it is suggested that the increased size of pool A may be the result of the decreased removal of cholesterol from this pool. The plasma cholesterol pool is not related to the size of pool A. In chronic liver disease without cholestasis, the decreased production rate of cholesterol is associated with a low plasma cholesterol concentration.
The Response to TRH, LH‐RH, Metyrapone and Vasopressin in Patients with Hypothalamo‐Pituitary Disorders
Authors: Lundberg P. O. , Wide L.
Published: September 2010

Abstract. The effects of slow intravenous infusion of synthetic TRH on serum TSH and of synthetic LH‐RH on serum LH measured by radioimmunoassay were studied in healthy persons and in 36 cases with sellar tumours and other hypo‐thalamo‐pituitary disorders. The results were also compared with the responses to oral metyrapone and intravenous infusion of lysine‐8‐vasopressin, as tests for the hypothalamo‐pituitary‐adrenal regulation. 200 μg of TRH was found to give a mean increase of serum TSH of +10.4 μ/ml in eight males and of +15.7 μ/ml in nine females. LH‐RH infusion was found to give a mean increase of serum LH of ‐f‐1.78 ng/ml in six young males. The TRH test gave a pathologically low response in one out of nine patients with an intrasellar tumour. On the other hand in patients with a craniopharyngioma, which usually causes more pronounced pituitary destruction, the response was pathologically low in five out of six cases. A normal response to TRH was obtained in seven out of nine patients with disorders mainly affecting the hypothalamus. When twelve patients with pituitary adenomas were tested post‐surgery six patients gave a pathologically low TRH response. The response to LH‐RH was pathologically low in five out of eight cases with a pathologically low TRH response and normal in six out of six cases with a normal TRH response. However, there was a poor correlation between the results of these two tests and the vasopressin and metyrapone administration. This difference may be explained by the direct effect of the releasing hormones on the pituitary and the need for a certain hypothalamic function to obtain a response to the vasopressin and metyrapone tests.
Treatment of congestive heart failure – current status of use of digitoxin
Authors: Belz G. G. , Breithaupt‐Grögler K. , Osowski U.
Published: September 2010

Digitalis glycosides exert a positive inotropic effect, i.e. an increase in myocardial contractility associated with a prolongation of relaxation period, and glycosides lower the heart rate (negative chronotropic), impede stimulus conduction (negative dromotropic) and promote myocardial excitability (positive bathmotropic). They seem to influence the activities of both the vagal and the sympathetic systems. Digitalis glycosides that belong to different substance classes are closely comparable concerning pharmacodynamics but differ substantially in regard to pharmacokinetics. Digoxin and its derivatives are less lipophilic, show lower protein binding and shorter half‐life, are mainly eliminated via the kidney and accumulate rather rapidly in cases of insufficient kidney function. Digitoxin is highly lipophilic and extensively bound to plasma proteins, has a longer half‐life, is mainly eliminated in the metabolized state via urine and faeces and does not accumulate in kidney dysfunction. As a result of a more stable pharmacokinetic profile, the incidence of toxic side effects seems to be lower with digitoxin than with digoxin. Since the beginning of the 1990s, the antagonists of the RAAS qualified as the standard treatment for congestive heart failure, often in combination with diuretics, vasodilators or β‐antagonists. However, the important role of digitalis glycosides as therapeutic comedication or alternative was never denied, especially in atrial fibrillation with tachycardia. The PROVED and RADIANCE trials proved a detrimental effect of the withdrawal of digoxin therapy on exercise capacity, left‐ventricular ejection fraction and clinical symptoms. The DIG trial revealed that digoxin comedication in sinus rhythm patients with congestive heart failure was associated with a lower morbidity (as taken from death or hospitalization because of worsening heart failure) and an unchanged overall mortality – being a unique feature among the available inotropic drugs. Comparable studies for digitoxin have not yet been performed but, because of its higher pharmacological stability, it might well be associated with even more advantages in this regard than digoxin.
Local and systemic effects of Na+/K+ATPase inhibition
Authors: Joubert P. H. , Grossmann M.
Published: September 2010

The positive inotropic and electrophysiological effects of cardiac glycosides on cardiac muscle are mediated through inhibition of Na+/K+ATPase by binding to a specific extracytoplasmic site of the a‐subunit of this enzyme. The inhibition of Na+/K+ATPase affects ionic flux and produces direct local effects on cardiac contractility, electrical excitability and conduction, but also profound systemic effects mainly as a result of haemodynamic changes. These effects are responsible for beneficial therapeutic as well as toxic effects.

Inhibition of Na+/K+ATPase results in potentiation of K+loss from cells and Na+entry into cells, so consequently affects action potential generation and propagation. This also underlines the potentiation of certain effects of cardiac glycosides by hypokalemia and hypomagnesaemia, and the effects of changes in calcium homeostasis on the cardiac glycoside pharmacodynamics. Furthermore, inhibition of Na+/Ca++exchange enhances Ca++mobilization and promotes contractility. These effects (locally and systemically) differ greatly, depending on the haemodynamic status and myocardial oxygen supply.

Cardiac glycosides have less affinity for Na+/K+ATPases at other sites (e.g. skeletal muscle), but some extracardiac effects (vascular effects, effects on colour vision, CNS and autonomic effects, renal effects) may be related to Na+/K+ATPase inhibition.
Genetic influence in antithrombotic actions of atorvastatin in hypercholesterolaemia
Authors: Puccetti L. , Bruni F. , Pasqui A. L. , Pastorelli M. , Ciani F. , Palazzuoli A. , Acampa M. , Auteri A.
Published: September 2010

Background  Recent data indicate that statins could offer coronary artery disease (CAD) benefit even by mechanisms beyond lipid lowering. Genetic influence has been shown for some antithrombotic actions of statins via oxidized‐low‐density lipoprotein cholesterol (ox‐LDL) receptors and nitric oxide synthase (NOS) activity modulation. The present study was designed to evaluate the influence of ox‐LDL lectin‐like receptor‐1 (LOX‐1) and NOS polymorphisms in the incidence of cardiovascular events in pure hypercholesterolaemic subjects during statin treatment.

Materials and methods  A prospective 4‐year study involving 1039 event‐free subjects (643 males, 396 females) treated with atorvastatin (10–40 mg day−1) to reach the appropriate Adult Treatment Panel‐III LDL target of 3·36 mmol L−1. Enrolled subjects were evaluated every 6 months or at a clinical event. LOX‐1 3′UTR/T‐C and NOS G894T polymorphisms were detected by allelic discrimination assays (polymerase chain reaction), lipid profile by enzymatic‐colorimetric method, ox‐LDL by enzyme linked immunosorbent assay, platelet activation by P‐selectin (P‐sel) expression (FACScan), NOS activity (by intracellular citrullin recovery) and homocysteine (high performance liquid chromatography), C‐reactive protein (CRP) by sensitive nephelometric technique.

Results  LOX‐1 3′UTR/T showed the strongest association with events in the whole cohort with respect to each other variable including LDL reduction and NOS G894T (OR 4·90, 95% CI 3·19–6·98, P < 0·00001). Smoking influenced events in LDL‐targeted subjects (P < 0·0001). Ox‐LDL and P‐sel were better indicators than LDL or other variables according to 3′UTR/C genotype regardless of the magnitude of LDL reduction (OR 4·21, 95% CI 2·29–6·70 P < 0·0001).

Conclusions  LOX‐1 polymorphisms could influence statin effectiveness in CAD prevention by induction of sensitivity to antithrombotic mechanisms such as antiplatelet activity.
Cytogenetic patterns in multiple myeloma after a phase of preceding MGUS
Authors: Kaufmann H. , Ackermann J. , Odelga V. , Sagaster V. , Nösslinger T. , Pfeilstöcker M. , Keck A. , Ludwig H. , Gisslinger H. , Drach J.
Published: September 2010

Background  Presenting the same histological diagnosis, multiple myeloma (MM) shows a large genomic variety, resulting in variable times of overall survival.

Materials and methods  To investigate major cytogenetic categories (any 14q‐translocation, t(11;14), t(4;14), 13q‐deletions, 17p‐deletions) and their clinical consequences in MM after a pre‐existing monoclonal gammopathy (MM post‐MGUS), we performed a comparative analysis of 41 patients with MM post‐MGUS and 287 patients with unknown prior history MM (U‐MM).

Results  In MM post‐MGUS, a t(11;14) was found to be more frequent than in U‐MM (24% vs. 14%) and it was associated with significantly shortened survival (24 months vs. 70 months in U‐MM; P = 0·01). MM post‐MGUS was further characterized by a higher frequency of 13q‐deletions only (absence of all other specific abnormalities; 28% vs. 12% in U‐MM; P = 0·02). A 13q‐deletion only was an indicator of long survival in MM post‐MGUS (median not yet reached) as opposed to U‐MM (median survival, 29 months; P = 0·001). 17p‐deletions were infrequent in MM post‐MGUS (3% vs. 16% in U‐MM; P = 0·04). Survival times for patients with t(4;14) and/or 17p‐deletions and other abnormalities were similar in both MM patient cohorts.

Conclusions  Our data suggest that t(11;14) and 13q‐deletions have distinct prognostic implications in the context of MM post‐MGUS.
Role of raloxifene on platelet metabolism and plasma lipids
Authors: Nanetti L. , Camilletti A. , Francucci C. M. , Vignini A. , Raffaelli F. , Mazzanti L. , Boscaro M.
Published: September 2010

Background  This study was performed to understand the metabolic effects of raloxifene, a selective oestrogen receptor modulator, on platelets in healthy non‐obese postmenopausal women. The data were compared to untreated subjects.

Materials and methods  Platelet nitric oxide activity (NO) and peroxynitrite level, platelet inducible and endothelial nitric oxide synthase expression and plasma lipids were evaluated at baseline and after 12 months of raloxifene or placebo treatment.

Results  A significant increase of platelet NO and reduction of platelet peroxynitrite levels, as well as a decrease of inducible nitric oxide synthase expression, was observed 12 months after raloxifene therapy as compared to baseline or placebo treatment. Moreover, raloxifene treatment caused a significant increase in high‐density lipoprotein cholesterol and a decrease of total cholesterol and low‐density lipoprotein cholesterol were observed versus baseline values (P < 0·05). A significant positive correlation was observed between high‐density lipoprotein cholesterol and platelet NO (r = 0·76, P < 0·005) in the raloxifene group.

Conclusion  Our results showed that raloxifene improves platelet metabolism in healthy postmenopausal women through an increase of the bioavailability of platelet NO by a reduction of iNOS and the beneficial effects on lipid metabolism. This mechanism of action of raloxifene on platelet activity may explain some cardiovascular protective effects of this selective oestrogen receptor modulator.
Impaired aortic elastic properties in patients with systemic sarcoidosis
Authors: Moyssakis I. , Gialafos E. , Tentolouris N. , Floudas C. S. , Papaioannou T. G. , Kostopoulos Ch. , Latsi P. , Vaiopoulos G. , Votteas V. , Rapti A.
Published: September 2010

Background  Systemic sarcoidosis (Sar) is a granulomatous disorder involving multiple organs. Widespread vascular involvement and microangiopathy are common in patients with Sar. In addition, subclinical cardiac involvement is increasingly recognized in patients with Sar. However, data on the effect of Sar on the elastic properties of the arteries and myocardial performance are limited. In this study we looked for differences in aortic distensibility (AoD) which is an index of aortic elasticity, and myocardial performance of the ventricles, between patients with Sar and healthy subjects. In addition, we examined potential associations between AoD and clinical, respiratory and echocardiographic findings in patients with Sar.

Materials and methods  A total of 83 consecutive patients (26 male/57 female, mean age 51·1 ± 13·3 years) with Sar, without cardiac symptoms, were included. All patients underwent echocardiographic and respiratory evaluation including lung function tests. Additionally, 83 age‐ and sex‐matched healthy subjects served as controls. AoD was determined non‐invasively by ultrasonography.

Results  AoD was lower in the Sar compared to the control group (2·29 ± 0·26 vs. 2·45 ± 0·20 ·10−6 cm2· dyn−1, P < 0·01), while left ventricular mass (LVM) was higher in the Sar group (221·3 ± 50·2 vs. 195·6 ± 31·3 g, P = 0·007). Furthermore, myocardial performance of both ventricles was impaired in the Sar group. Multivariate linear regression analysis in the total sample population demonstrated a significant and independent inverse relationship between AoD and the presence of Sar (P < 0·001). The same analysis in the Sar patients showed that AoD was associated significantly and independently with the stage of Sar, age, systolic blood pressure, LVM and myocardial performance of both ventricles. No significant relationship was found between AoD and disease duration, pulmonary artery pressure or lung function tests.

Conclusions  Presence and severity of Sar are associated with reduced aortic distensibility, irrespective of the disease duration, pulmonary artery pressure and lung function. In addition, patients with Sar have increased LVM and impaired myocardial performance.
Angiogenesis in inflammatory bowel disease
Authors: Pousa I. D. , Maté J. , Gisbert J. P.
Published: September 2010

Both ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel diseases, are recognized, at the moment, as perplexing and challenging clinical entities, in which several molecules and cell types are implicated. Recent molecular evidence proposes the intestinal microvascular remodelling or angiogenesis, as a phenomenon implicated in the pathogenesis of these chronic inflammatory disorders, together with other proposed theories involved in the pathogenesis of inflammatory bowel diseases, such as genetic, microbacterial and immune factors.

Intestinal damage is followed by a physiological angiogenesis, but the abnormal expression of pro‐ and anti‐angiogenic molecules and the changes of vascular cell types could reflect a pathological vascular remodelling. Thus, the inflammation may be favoured and maintained by a pathological angiogenesis.

A better understanding of the angiogenic process may facilitate the design of more effective therapies for chronic intestinal inflammation.
Expression of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas
Authors: Rau S. , Autschbach F. , Riedel H. D. , Konig J. , Kulaksiz H. , Stiehl A. , Riemann J. F. , Rost D.
Published: September 2010

Background  Cholangiocellular carcinomas and gallbladder carcinomas are highly aggressive tumours with a poor prognosis and are generally regarded as chemoresistant tumours. Overexpression of ATP‐binding cassette transporters of the multidrug resistance protein (MDR) and multidrug resistance‐related protein (MRP) family in cancer cells is a major cause for the multidrug resistance phenotype in vitro and in vivo. To further define the role of MRP family members in biliary tract cancer, we studied the expression and localization of MRP2 and MRP3 in cholangiocellular carcinomas and gallbladder carcinomas.

Materials and methods  The expression and cellular localization of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas and gallbladder carcinomas were analysed by immunohistochemistry using isoform‐specific antibodies. Expression of MRP isoforms was studied in vitro in Mz‐ChA‐1 cells derived from gallbladder adenocarcinoma by reverse transcription–polymerase chain reaction (RT‐PCR), immunoblotting and immunofluorescence microscopy.

Results  Mz‐ChA‐1 cells constitutively expressed MDR P‐glycoproteins, MRP1, MRP2 and MRP3 by RT‐PCR, immunoblotting and immunofluorescence microscopy. MRP2 and MRP3 are expressed in the respective apical and basolateral membrane domains. MRP3 was the predominant MRP isoform in gallbladder carcinomas (93%) and cholangiocellular carcinomas (57%), whereas MRP2 expression was detected in only 29% of gallbladder carcinomas and was undetectable in cholangiocellular carcinomas.

Conclusions  Our findings suggest that the intrinsic multidrug resistance of cholangiocellular and gallbladder carcinomas seems to be independent of MRP2 expression while the expression of MRP3 may contribute to the MDR phenotype.
A new coding region polymorphism of human IgLC2
Authors: Naud J.‐F. , Gibson D. M.
Published: September 2010

A new allelic form of the human IgLC2 gene is described. The marker involves a T to C substitution in the Cλ2 constant region gene, a silent substitution at amino acid coding position 178 (YAASSYLSL) and two substitutions in the 3′‐flanking region. Analysis of IgLC2 alleles in a total of 60 individuals has indicated a frequency of 0.32 for the new allele, which has been designated IgLC2*B2. The *B1 and *B2 alleles encode T and C, respectively, at nucleotide position 212 in the IgLC2 coding region. Both the *B1 and *B2 alleles are found in individuals homozygous for the single‐copy RFLP allele of IgLC2/IgLC3 (8 kb EcoRI). Knowledge of alleles of this marker will be important for studies on the expression of the IgLC2 and IgLC3 isotypes in normal and autoimmune lymphocyte populations, as the coding regions of the two isotypes differ only at this position. The marker will also be useful in further studies of linkage with other IgLV and IgLC markers and to establish possible correlations with susceptibility to autoimmune disorders.
Development of an accumulation‐based system for cost‐effective chamber measurements of inert trace gas fluxes
Authors: Ambus P. , Skiba U. , Drewer J. , Jones S. K. , Carter M. S. , Albert K. R. , Sutton M. A.
Published: September 2010

As soil–atmosphere fluxes of greenhouse gases are characterized by high temporal fluctuations, frequent measurements in the range of hours to days need to be deployed, resulting in high analytical costs. We have therefore developed a new low‐cost system that combines high‐frequency automated sampling with low‐frequency chemical analysis. The System for Inert Gas Monitoring by Accumulation (SIGMA) is suited particularly for stand‐alone observations in remote locations. The SIGMA is connected to an automated chamber with headspace sampling several times per day. Air samples are aggregated in sampling bags, which reduces the number of subsequent laboratory analyses and allows calculation of average flux rates over extended sampling periods. The SIGMA was tested under field conditions and compared with a conventional autochamber system, where flux rates were measured several times per day. Sample air fillings of the SIGMA sampling bags varied less than 5% between bags and diverged <1 to 6% of the pre‐set values, justifying the assumption about proportional mixing of chamber headspace samples. When the SIGMA and conventional autochambers were compared simultaneously over the same patch of grassland in Denmark, the estimates agreed within ±12% in the assessment of average N2O fluxes. When deployed to discrete autochambers situated a few metres apart and under various environmental conditions in Denmark and the UK, we found no consistent difference between the two measuring systems. For a N‐fertilized cropland in Denmark the SIGMA N2O and CO2fluxes were 28 and 23% less, respectively than those recorded with the conventional autochamber, while for a N‐fertilized grassland in the UK the SIGMA N2O flux was 47% more than that recorded with the conventional autochamber and 6% less than that recorded with a manual chamber system. Such differences are within the range of natural spatial variability in trace gas fluxes for these ecosystems and indicate the potential for further application of the SIGMA approach as a cost‐effective technique to estimate long‐term trace gas fluxes.
Gross rates of ammonification and nitrification at a nitrogen‐saturated spruce (Picea abies (L.)Karst.) stand in southern Germany
Authors: Rosenkranz P. , Dannenmann M. , Brüggemann N. , Papen H. , Berger U. , Zumbusch E. , Butterbach‐Bahl K.
Published: September 2010

We investigated the magnitudes of temporal and spatial variabilities of gross ammonification and nitrification, in an N‐saturated temperate forest ecosystem. Forest soil gross ammonification, gross nitrification and heterotrophic soil respiration were measured in the forest floor and uppermost mineral layer over a period of 3 years. Total annual gross fluxes for the organic layer and uppermost mineral horizon (0–4 cm) were in the range of 800–980 kg N ha−1 year−1 for gross ammonification and 480–590 kg N ha−1 year−1 for gross nitrification. Annual heterotrophic soil respiration was 8000–8900 kg C ha−1 year−1. Highest soil C and N turnover rates occurred in summer, and a consistent pattern was observed throughout the observation period, with highest values for plots located at a clear‐cut area and lowest values for plots located at an unmanaged, approximately 100‐year‐old, spruce control site. Soil moisture, soil temperature and substrate availability accounted for most of the observed variability of C and N turnover rates. Because gross rates of inorganic N production were more than an order of magnitude larger than ecosystem N losses along hydrological and gaseous pathways, our study underlines the importance of internal microbial N turnover processes for ecosystem N cycling and retention.
The challenge of sustainable use of the Danube Delta Fisheries, Romania
Authors: Navodaru I. , Staras M. , Cernisencu I.
Published: September 2010

The Danube Delta was designated a Biosphere Reserve in 1990. Subsequently the sustainable use of the fish stocks within the reserve became a challenge for management. The fisheries exploit a variety of habitats distributed over about 580 000 ha of wetland. They yield between 5000 and 10 000 t year–1, equivalent in value to 6.3 million US$, making this one of the most important inland fisheries in Europe. Approximately 15 000 inhabitants within the Delta and a further 160 000 from adjacent regions depend fully or partly on the fishery resource. The fisheries are diverse, consisting of lake, river, marine coastal and anadromous fisheries. Fisheries in the Delta operated under an open access system during the transition from a fully controlled state economy to a market economy. New fishing regulations have been established to minimise the risk of the fisheries collapsing as a result of the open access regime. Core regulations including close seasons and closed areas, minimum mesh sizes and fish lengths, output controls (catch quota), and input regulations (limited access to fishery) were introduced.
Review of trends in the development of European inland aquaculture linkages with fisheries
Authors: Váradi L.
Published: September 2010

Aquaculture is a multifaceted, dynamic food production sector in Europe. The average annual growth rate of aquaculture production in Western Europe was 5.5% between 1988 and 1998, while in Eastern Europe production declined by 56% during the same period. The main growth in aquaculture production has taken place in the marine environment, particularly in the expanding salmon, Salmo salar L., industry of Northern Europe. Inland aquaculture only contributed 19% of the total aquaculture production in 1998. Trout in Western Europe, and common carp, Cyprinus carpio L., in Eastern Europe are the dominant species in inland aquaculture. Inland fisheries production has been stagnant in Western Europe and has declined considerably in Eastern Europe. The importance of recreational fisheries is increasing all over Europe, although no reliable data are available on angler catches. The major interactions between aquaculture and fisheries are pollution by untreated effluents from farms and impacts on indigenous fish stocks. The conflict is decreasing as more advanced systems are used in inland aquaculture, including water recirculation and effluent treatment. The positive benefit of aquaculture is that the sector supports extensive stocking programmes in commercial and recreational fisheries all over Europe.