bluuebunny/crossref_metadata_2025 huggingface dataset:
Human skin pigmentation as an adaptation to UV radiation
Authors: Jablonski Nina G. , Chaplin George
Published: May 2010

Human skin pigmentation is the product of two clines produced by natural selection to adjust levels of constitutive pigmentation to levels of UV radiation (UVR). One cline was generated by high UVR near the equator and led to the evolution of dark, photoprotective, eumelanin-rich pigmentation. The other was produced by the requirement for UVB photons to sustain cutaneous photosynthesis of vitamin D
3
in low-UVB environments, and resulted in the evolution of depigmented skin. As hominins dispersed outside of the tropics, they experienced different intensities and seasonal mixtures of UVA and UVB. Extreme UVA throughout the year and two equinoctial peaks of UVB prevail within the tropics. Under these conditions, the primary selective pressure was to protect folate by maintaining dark pigmentation. Photolysis of folate and its main serum form of 5-methylhydrofolate is caused by UVR and by reactive oxygen species generated by UVA. Competition for folate between the needs for cell division, DNA repair, and melanogenesis is severe under stressful, high-UVR conditions and is exacerbated by dietary insufficiency. Outside of tropical latitudes, UVB levels are generally low and peak only once during the year. The populations exhibiting maximally depigmented skin are those inhabiting environments with the lowest annual and summer peak levels of UVB. Development of facultative pigmentation (tanning) was important to populations settling between roughly 23° and 46° , where levels of UVB varied strongly according to season. Depigmented and tannable skin evolved numerous times in hominin evolution via independent genetic pathways under positive selection.
Altered redox state of monocytes from cryopyrin-associated periodic syndromes causes accelerated IL-1β secretion
Authors: Tassi Sara , Carta Sonia , Delfino Laura , Caorsi Roberta , Martini Alberto , Gattorno Marco , Rubartelli Anna
Published: May 2010

In healthy monocytes, Toll-like receptor (TLR) engagement induces production of reactive oxygen species (ROS), followed by an antioxidant response involved in IL-1β processing and secretion. Markers of the antioxidant response include intracellular thioredoxin and extracellular release of reduced cysteine. Cryopyrin-associated periodic syndromes (CAPS) are autoinflammatory diseases in which Nod-like receptor family pyrin domain–containing 3 (
NLRP3)
gene mutations lead to increased IL-1β secretion. We show in a large cohort of patients that IL-1β secretion by CAPS monocytes is much faster than that by healthy monocytes. This accelerated kinetics is caused by alterations in the basal redox state, as well as in the redox response to TLR triggering displayed by CAPS monocytes. Indeed, unstimulated CAPS monocytes are under a mild oxidative stress, with elevated levels of both ROS and antioxidants. The redox response to LPS is quickened, with early generation of the reducing conditions favoring IL-1β processing and secretion, and then rapidly exhausted. Therefore, secretion of IL-1β is accelerated, but reaches a plateau much earlier than in healthy controls. Pharmacologic inhibition of the redox response hinders IL-1β release, confirming the functional link between redox impairment and altered kinetics of secretion. Monocytes from patients with juvenile idiopathic arthritis display normal kinetics of redox response and IL-1β secretion, excluding a role of chronic inflammation in the alterations observed in CAPS. We conclude that preexisting redox alterations distinct from CAPS monocytes anticipate the pathogen-associated molecular pattern molecule–induced generation of the reducing environment favorable to inflammasome activation and IL-1β secretion.
Work stressors, Chinese coping strategies, and job performance in Greater China
Authors: Lu Luo , Kao Shu‐Fang , Siu Oi‐Ling , Lu Chang‐Qin
Published: May 2010

Theaim of this research was to jointly test effects of work stressors and coping strategies on job performance among employees in the Greater China region. A self‐administered survey was conducted to collect data from three major cities in the region, namely Beijing, Hong Kong, and Taipei (N = 380). Four important work stressors were assessed: heavy workload, organizational constraints, lack of work autonomy, and interpersonal conflict. We used a four‐factor model of Chinese coping strategies composed of hobbies/relaxation, active action, seeking social support, and passive adaptation. Job performance was indicated by both task performance (quantity of work, quality of work, job knowledge) and contextual performance (attendance, getting along with others). We found that: (1) work stressors were related to job performance. Specifically, workload had a positive relation with quantity of work, whereas organizational constraints had negative relations with quantity of work and attendance. In addition, interpersonal conflict had a negative relation with getting along with others. (2) Chinese positive coping strategies were positively related to job performance. Specifically, seeking social support had positive relations with quantity of work and getting along with others, whereas active action had positive relations with attendance and job knowledge. (3) Chinese passive adaptation coping behaviors were negatively related to job performance. Specifically, passive adaptation had negative relations with quantity of work, quality of work, and getting along with others. The present study thus found joint effects of work stressors and coping behaviors among Chinese employees in the Greater China region, encompassing three sub‐societies of mainland China, Hong Kong, and Taiwan. Differential effects of Chinese positive and passive coping strategies were also noted. Most importantly, all these effects were demonstrated on multiple indicators of job performance, a rarely studied but important strain variable from the organizational point of view.
Mitochondrial Fragmentation Leads to Intracellular Acidification inCaenorhabditis elegansand Mammalian Cells
Authors: Johnson David , Nehrke Keith
Published: May 2010

Mitochondrial structural dynamics are regulated through the opposing processes of membrane fission and fusion, which are conserved from yeast to man. The chronic inhibition of mitochondrial fusion as a result of genetic mutation is the cause of human autosomal dominant optic atrophy (ADOA) and Charcot-Marie-Tooth syndrome type 2A (CMT-2A). Here, we demonstrate that genetic fragmentation of the mitochondrial network in Caenorhabditis elegans induces cellular acidification in a broad range of tissues from the intestine, to body wall muscles, and neurons. Genetic epistasis analyses demonstrate that fragmentation itself, and not the loss of a particular protein, leads to acidosis, and the worm's fitness matches the extent of acidification. We suggest that fragmentation may cause acidification through two distinct processes: oxidative signaling after the loss of the ability of the mitochondrial inner membrane to undergo fusion and lactic acidosis after the loss of outer membrane fusion. Finally, experiments in cultured mammalian cells demonstrate a conserved link between mitochondrial morphology and cell pH homeostasis. Taken together these data reveal a potential role for acidosis in the differing etiology of diseases associated with mitochondrial morphology defects such as ADOA and CMT-2A.
The Smc5/6 Complex and Esc2 Influence Multiple Replication-associated Recombination Processes inSaccharomyces cerevisiae
Authors: Choi Koyi , Szakal Barnabas , Chen Yu-Hung , Branzei Dana , Zhao Xiaolan
Published: May 2010

Replication-associated recombinational repair is important for genome duplication and cell survival under DNA damage conditions. Several nonclassical recombination factors have been implicated in this process, but their functional relationships are not clear. Here, we show that three of these factors, Mph1, Mms2, and the Shu complex, can act independently to promote the formation of recombination intermediates during impaired replication. However, their functions become detrimental when cells lack the Smc5/6 complex or Esc2. We show that mph1Δ, mms2Δ, and shu1Δ suppress the sensitivity to the replication-blocking agent methylmethane sulfonate (MMS) in smc6 mutants, with double deletions conferring stronger suppression. These deletion mutations also rescue the MMS sensitivity of esc2Δ cells. In addition, two-dimensional gel analysis demonstrates that mph1Δ, mms2Δ, and shu1Δ each reduce the level of recombination intermediates in an smc6 mutant when cells replicate in the presence of MMS, and that double deletions lead to a greater reduction. Our work thus suggests that Mph1, Mms2, and the Shu complex can function in distinct pathways in replication-associated recombinational repair and that the Smc5/6 complex and Esc2 prevent the accumulation of toxic recombination intermediates generated in these processes.
The Polarized Distribution of Na+,K+-ATPase: Role of the Interaction between β Subunits
Authors: Padilla-Benavides Teresita , Roldán María L. , Larre Isabel , Flores-Benitez David , Villegas-Sepúlveda Nicolas , Contreras Ruben G. , Cereijido Marcelino , Shoshani Liora
Published: May 2010

The very existence of higher metazoans depends on the vectorial transport of substances across epithelia. A crucial element of this transport is the membrane enzyme Na+,K+-ATPase. Not only is this enzyme distributed in a polarized manner in a restricted domain of the plasma membrane but also it creates the ionic gradients that drive the net movement of glucose, amino acids, and ions across the entire epithelium. In a previous work, we have shown that Na+,K+-ATPase polarity depends on interactions between the β subunits of Na+,K+-ATPases located on neighboring cells and that these interactions anchor the entire enzyme at the borders of the intercellular space. In the present study, we used fluorescence resonance energy transfer and coprecipitation methods to demonstrate that these β subunits have sufficient proximity and affinity to permit a direct interaction, without requiring any additional extracellular molecules to span the distance.
Experimentalist Meets Theoretician: A Tale of Two Scientific Cultures
Authors: Drubin David G. , Oster George
Published: May 2010

This is the story of how a small team of experimentalists and theoreticians collaborated to develop a theoretical model for vesicle formation during endocytosis. In telling our story, we hope to distil some general conclusions about the purpose and value of theoretical models and how best to navigate collaborations between experimentalists and theoreticians. We encountered challenges in building and publishing our model, but through our experiences we gained insight into how such collaborations can be profitably conducted. We also developed opinions about how theoretical models should be evaluated by peer reviewers and editors. During the evolution of our theoretical model, we educated each other, organized our thoughts and our data, developed a conceptual framework for understanding the mechanochemistry of endocytosis, and generated testable hypotheses that stimulated new experiments.
Farm Animal Welfare, Consumer Willingness to Pay, and Trust: Results of a Cross‐National Survey
Authors: Nocella Giuseppe , Hubbard Lionel , Scarpa Riccardo
Published: May 2010

Higher animal welfare standards increase costs along the supply chain of certified animal‐friendly products (AFP). Since the market outcome of certified AFP depends on consumer confidence toward supply chain operators complying with these standards, the role of trust in consumer willingness‐to‐pay (WTP) for AFP is paramount. Results from a contingent valuation survey administered in five European Union countries show that WTP estimates were sensitive to robust measures of consumer trust for certified AFP. Deriving the WTP effect of a single food category on total food expenditure is difficult for survey respondents; hence, a budget approach was employed to facilitate this process.
An Investigation of Factors that Influence the Survival of Contracts in the DOCa Rioja Wine Industry
Authors: Fernández Olmos Marta
Published: May 2010

This study applied a multi‐theoretical perspective to explore factors that determine the duration of continuing supply relationships between grape processors and growers. Our empirical study employed hazard rate models with time‐varying covariates, using data from supply contracts between wineries and growers in the DOCa Rioja wine industry. We found evidence that rates of contract termination: (1) decrease with the level of site‐specificity in the processor‐grower relationship; (2) increase with the existence of market uncertainty; (3) decrease with the existence of monitoring; and (4) increase (rather than decrease) over time.
LCE: a link-based cluster ensemble method for improved gene expression data analysis
Authors: Iam-on Natthakan , Boongoen Tossapon , Garrett Simon
Published: May 2010

Motivation: It is far from trivial to select the most effective clustering method and its parameterization, for a particular set of gene expression data, because there are a very large number of possibilities. Although many researchers still prefer to use hierarchical clustering in one form or another, this is often sub-optimal. Cluster ensemble research solves this problem by automatically combining multiple data partitions from different clusterings to improve both the robustness and quality of the clustering result. However, many existing ensemble techniques use an association matrix to summarize sample-cluster co-occurrence statistics, and relations within an ensemble are encapsulated only at coarse level, while those existing among clusters are completely neglected. Discovering these missing associations may greatly extend the capability of the ensemble methodology for microarray data clustering.

Results: The link-based cluster ensemble (LCE) method, presented here, implements these ideas and demonstrates outstanding performance. Experiment results on real gene expression and synthetic datasets indicate that LCE: (i) usually outperforms the existing cluster ensemble algorithms in individual tests and, overall, is clearly class-leading; (ii) generates excellent, robust performance across different types of data, especially with the presence of noise and imbalanced data clusters; (iii) provides a high-level data matrix that is applicable to many numerical clustering techniques; and (iv) is computationally efficient for large datasets and gene clustering.

Availability: Online supplementary and implementation are available at: http://users.aber.ac.uk/nii07/bioinformatics2010

Contact:  nii07@aber.ac.uk; natthakan@mfu.ac.th

Supplementary information:  Supplementary data are available at Bioinformatics online.
Herbal Medicine and Hepatocellular Carcinoma: Applications and Challenges
Authors: Li Yan , Martin Robert C. G.
Published: May 2010

Use of herbal medicine in the treatment of liver cancer has a long tradition. The compounds derived from the herb and herbal composites are of considerable interest among oncologists. In the past, certain herbal compounds and herbal composite formulas have been studied through in vitro and in vivo as an anti‐hepatocellular carcinoma (HCC) agent, enhancing our knowledge about their biologic functions and targets. However there is a significant distinction between the herbal medicine and the herbal production even though both are the plant‐based remedies used in the practice. In this article, for the sake of clarity, the effective herbal compounds and herbal composite formulas against HCC are discussed, with emphasizing the basic conceptions of herbal medicine in order to have a better understanding of the prevention and treatment of HCC by herbal active compounds and herbal composite formulas.
Body-size distributions and size-spectra: universal indicators of ecological status?
Authors: Petchey Owen L. , Belgrano Andrea
Published: May 2010

The sizes of individual organisms, rather than their taxonomy, are used to inform management and conservation in some aquatic ecosystems. The European Science Foundation Research Network, SIZEMIC, facilitates integration of such approaches with the more taxonomic approaches used in terrestrial ecology. During its 4-year tenure, the Network is bringing together researchers from disciplines including theorists, empiricists, government employees, and practitioners, via a series of meetings, working groups and research visits. The research conducted suggests that organismal size, with a generous helping of taxonomy, provides the most probable route to universal indicators of ecological status.
Buckling of sheared and compressed microfibrils
Authors: Nadermann Nichole , Kumar Ajeet , Goyal Sachin , Hui Chung-Yuen
Published: May 2010

In this paper, we study the stability of an initially straight elastic fibril clamped at one end, while the other end is subjected to a constant normal compressive force and a prescribed shear displacement. We found the buckling load of a sheared fibril to be always less than the Euler buckling load. Furthermore, if the end of the fibril loses adhesion, then the buckling load can be considerably less. Our result suggests that the static friction of microfibre arrays can decrease with increasing normal compressive load and, in some cases, friction force can actually become negative.
Host–symbiont recombination versus natural selection in the response of coral–dinoflagellate symbioses to environmental disturbance
Authors: LaJeunesse Todd C. , Smith Robin , Walther Mariana , Pinzón Jorge , Pettay Daniel T. , McGinley Michael , Aschaffenburg Matthew , Medina-Rosas Pedro , Cupul-Magaña Amilcar L. , Pérez Andrés López , Reyes-Bonilla Hector , Warner Mark E.
Published: May 2010

Mutualisms between reef-building corals and endosymbiotic dinoflagellates are particularly sensitive to environmental stress, yet the ecosystems they construct have endured major oscillations in global climate. During the winter of 2008, an extreme cold-water event occurred in the Gulf of California that bleached corals in the genus
Pocillopora
harbouring a thermally ‘sensitive’ symbiont, designated
Symbiodinium C1b-c
, while colonies possessing
Symbiodinium D1
were mostly unaffected. Certain bleached colonies recovered quickly while others suffered partial or complete mortality. In most colonies, no appreciable change was observed in the identity of the original symbiont, indicating that these partnerships are stable. During the initial phases of recovery, a third species of symbiont
B1

Aiptasia

, genetically identical to that harboured by the invasive anemone,
Aiptasia
sp., grew opportunistically and was visible as light-yellow patches on the branch tips of several colonies. However, this symbiont did not persist and was displaced in all cases by
C1b-c
several months later. Colonies with
D1
were abundant at inshore habitats along the continental eastern Pacific, where seasonal turbidity is high relative to offshore islands. Environmental conditions of the central and southern coasts of Mexico were not sufficient to explain the exclusivity of
D1 Pocillopora
in these regions. It is possible that mass mortalities associated with major thermal disturbances during the 1997–1998 El Niño Southern Oscillation eliminated
C1b-c
holobionts from these locations. The differential loss of
Pocillopora
holobionts in response to thermal stress suggests that natural selection on existing variation can cause rapid and significant shifts in the frequency of particular coral–algal partnerships. However, coral populations may take decades to recover following episodes of severe selection, thereby raising considerable uncertainty about the long-term viability of these communities.
Paternal effects inArabidopsisindicate that offspring can influence their own size
Authors: House Clarissa , Roth Charlotte , Hunt John , Kover Paula X.
Published: May 2010

The existence of genetic variation in offspring size in plants and animals is puzzling because offspring size is often strongly associated with fitness and expected to be under stabilizing selection. An explanation for variation in seed size is conflict between parents and between parents and offspring. However, for this hypothesis to be true, it must be shown that the offspring genotype can affect its own size. The existence of paternal effects would support this hypothesis, but these have rarely been shown. Using a diallel cross among four natural accessions ofArabidopsis thalianawe show that maternal, paternal and positional effects jointly influence seed size, number and the frequency of seed abortion. We found that seed abortion (%) depends on the combination of maternal and paternal genotypes, suggesting the existence of mate choice or epistatic incompatibility among accessions ofA. thaliana. In addition, since paternal genotype explains approximately 10 per cent of the variation in seed size, we propose thatA. thaliana'soffspring must influence the amount of resources allocated to themselves. Identification of paternal effects inArabidopsisshould facilitate dissection of the genetic mechanisms involved in paternal effects.
Lack of association between the presence and persistence of betapapillomavirus DNA in eyebrow hairs and betapapillomavirus L1 antibodies in serum
Authors: Plasmeijer Elsemieke I. , Neale Rachel E. , O'Rourke Peter , Mallitt Kylie-Ann , de Koning Maurits N. C. , Quint Wim , Buettner Petra G. , Pawlita Michael , Waterboer Tim , Green Adele C. , Feltkamp Mariet C. W.
Published: May 2010

Betapapillomavirus (βPV) DNA and seroresponses are highly prevalent in the general population and both are frequently used as infection markers in epidemiological studies to elucidate an association with cutaneous squamous cell carcinoma (SCC). Little is known about the natural history ofβPV infection and the aspects of infection that drive antibody responses. To investigate the relationship between these markers, this study assessed whether the presence or persistence ofβPV DNA in eyebrow hairs and L1 antibodies of the sameβPV type co-occurred more frequently than would be expected by chance in both a cross-sectional assessment and a longitudinal study.βPV DNA in plucked eyebrow hairs and L1 antibodies in serum were measured in 416 participants of the Australian community-based Nambour Skin Cancer Study in 1996. Similar data were available for a subset of 148 participants in 2003. Observed co-occurrence ofβPV DNA and antibodies was compared with expected values based on prevalence. A case-wise concordance index was used to calculate the overall concordance ofβPV DNA and antibodies of the same type. No significant associations were found between the presence or persistence ofβPV DNA and antibody responses. The age and sex of the host did not influence the association, and nor did SCC status or a history of sunburns. It was concluded thatβPV antibody responses in adults are not primarily driven byβPV infection as measured in eyebrow hairs. Other factors, such as viral load, may play a more pivotal role in the induction of detectable seroresponses.
Salmonid‐egg floating boxes as bioindication for riverine water quality and stocking success
Authors: Pander J. , Geist J.
Published: May 2010

The salmonid‐egg floating box provides an easy bioindication tool for an assessment of water quality, as demonstrated here for the reintroduction of Europe's largest salmonid species, the huchen Hucho hucho.
The effect of elevated hydrostatic pressure upon selected biomarkers in juvenile blackspot seabream Pagellus bogaraveo in a 14 day‐long experiment
Authors: Kopecka‐Pilarczyk J. , Coimbra J.
Published: May 2010

Hydrostatic pressure elevated to 500 kPa for 14 days was found to affect hepatic 7‐ethoxyresorufin‐O‐deethylase (EROD), oxidized protein (POx), protein yield and branchial Na+–K+‐ATPase. No effect on glutathione‐S‐transferase (GST), superoxidase dismutase (SOD), catalase (CAT), lipid peroxidation (LP), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), condition factor (K) and hepato‐somatic index (IH) was encountered.
Mentoring Siblings of Gang Members: A Template for Reaching Families of Gang Members?
Authors: Medina Juanjo , Ralphs Robert , Aldridge Judith
Published: May 2010

Mentoring has become a popular model of intervention to reduce the risk of offending, and has been proposed as an effective tool to tackle the risk of gang membership. This paper reviews the existing literature on mentoring and reports on a qualitative evaluation of a mentoring programme targeted at young people ‘at risk’ of gang membership in an English city. The study highlights important issues around these interventions. Although we found it a useful way to engage otherwise hard‐to‐reach families, important limitations remain: their potential labelling impact and their limited impact in isolation from other more ambitious measures.
If you try to stop smoking, should we pay for it? The cost–utility of reimbursing smoking cessation support in the Netherlands
Authors: Vemer Pepijn , Rutten‐van Mölken Maureen P. M. H. , Kaper Janneke , Hoogenveen Rudolf T. , Van Schayck C. P. , Feenstra Talitha L.
Published: May 2010

Background Smoking cessation can be encouraged by reimbursing the costs of smoking cessation support (SCS). The short‐term efficiency of reimbursement has been evaluated previously. However, a thorough estimate of the long‐term cost–utility is lacking.

Objectives To evaluate long‐term effects of reimbursement of SCS.

Methods Results from a randomized controlled trial were extrapolated to long‐term outcomes in terms of health care costs and (quality adjusted) life years (QALY) gained, using the Chronic Disease Model. Our first scenario was no reimbursement. In a second scenario, the short‐term cessation rates from the trial were extrapolated directly. Sensitivity analyses were based on the trial's confidence intervals. In the third scenario the additional use of SCS as found in the trial was combined with cessation rates from international meta‐analyses.

Results Intervention costs per QALY gained compared to the reference scenario were approximately €1200 extrapolating the trial effects directly, and €4200 when combining the trial's use of SCS with the cessation rates from the literature. Taking all health care effects into account, even costs in life years gained, resulted in an estimated incremental cost–utility of €4500 and €7400, respectively. In both scenarios costs per QALY remained below €16 000 in sensitivity analyses using a life‐time horizon.

Conclusions Extrapolating the higher use of SCS due to reimbursement led to more successful quitters and a gain in life years and QALYs. Accounting for overheads, administration costs and the costs of SCS, these health gains could be obtained at relatively low cost, even when including costs in life years gained. Hence, reimbursement of SCS seems to be cost‐effective from a health care perspective.
The value of pulse pressure and stroke volume variation as predictors of fluid responsiveness during open chest surgery
Authors: Wyffels P. A. H. , Sergeant P. , Wouters P. F.
Published: May 2010

We investigated the ability of pulse pressure variation and stroke volume variation to predict fluid responsiveness during mechanical ventilation in patients undergoing open chest surgery by comparing their respective correlations with cardiac output changes induced by leg elevation. Serial leg elevation manoeuvres were performed before and after sternotomy in 15 patients scheduled for elective off‐pump coronary bypass surgery. Under closed chest conditions, both pulse pressure variation and stroke volume variation correlated well with the induced cardiac output changes (r = 0.856, p = 0.002 and r = 0.897, p = 0.0012, respectively). These correlations were lost for both parameters following sternotomy. Our data show that pulse pressure variation and stroke volume variation are valid predictors of fluid responsiveness under closed chest conditions but that this property no longer holds when the chest is open.
Melanism in guinea fowl (Numida meleagris) is associated with a deletion of Phenylalanine‐256 in the MC1R gene
Authors: Vidal O. , Araguas R. M. , Fernández R. , Heras S. , Sanz N. , Pla C.
Published: May 2010

We have characterized a deletion in the MC1R gene causing the loss of one amino acid (p.Phe256del), which is perfectly associated with melanism in guinea fowl (Numida meleagris). Co‐segregation of the p.Phe256del with melanism was confirmed in 25 offspring born from a cross of two heterozygote birds; therefore we suggest that this mutation is responsible for the black phenotype. Interestingly, this is the first case of recessive melanism linked to MC1R.
A genetic linkage map of red drum, Sciaenops ocellatus
Authors: Portnoy D. S. , Renshaw M. A. , Hollenbeck C. M. , Gold J. R.
Published: May 2010

Second‐generation, sex‐specific genetic linkage maps were generated for the economically important estuarine‐dependent marine fish Sciaenops ocellatus (red drum). The maps were based on F1 progeny from each of two single‐pair mating families. A total of 237 nuclear‐encoded microsatellite markers were mapped to 25 linkage groups. The female map contained 226 markers, with a total length of 1270.9 centiMorgans (cM) and an average inter‐marker interval of 6.53 cM; the male map contained 201 markers, with a total length of 1122.9 cM and an average inter‐marker interval of 6.03 cM. The overall recombination rate was approximately equal in the two sexes (♀:♂ = 1.03:1). Recombination rates in a number of linkage intervals, however, differed significantly between the same sex in both families and between sexes within families. The former occurred in 2.4% of mapped intervals, while the latter occurred in 51.2% of mapped intervals. Sex‐specific recombination rates varied within chromosomes, with regions of both female‐biased and male‐biased recombination. Original clones from which the microsatellite markers were generated were compared with genome sequence data for the spotted green puffer, Tetraodon nigroviridis; a total of 43 matches were located in 17 of 21 chromosomes of T. nigroviridis, while seven matches were in unknown portions of the T. nigroviridis genome. The map for red drum provides a new, useful tool for aquaculture, population genetics, and comparative genomics of this economically important marine species.
Mosapride as an adjunct to lansoprazole for symptom relief of reflux oesophagitis
Authors: Hsu Yao‐Chun , Yang Tzeng‐Huey , Hsu Wei‐Lun , Wu Huei‐Tang , Cheng Yang‐Chih , Chiang Ming‐Feng , Wang Chaur‐Shine , Lin Hwai‐Jeng
Published: May 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Reflux oesophagitis is a common clinical disorder associated with significant morbidity. Proton pump inhibitors are the current pharmacotherapy of choice, but not all treated patients achieve symptom relief. Little is known about the efficacy of mosapride, a prokinetic agent which decreases episodes of gastro‐oesophageal reflux, as an adjunct to proton pump inhibitors in improving the symptoms of reflux oesophagitis.

WHAT THIS STUDY ADDS

Mosapride was generally not more effective than placebo as an adjunct therapy to a standard dose of lansoprazole in decreasing the symptom burden of patients with reflux oesophagitis. However, in a subgroup with more severe symptoms, combination therapy with lansoprazole and mosapride was possibly superior to monotherapy with lansoprazole.

AIMS

To investigate if mosapride, a prokinetic agent, was an effective adjunct to acid suppression in improving the symptoms of reflux oesophagitis.

METHODS

Patients (n= 96) with reflux oesophagitis were randomly assigned to either mosapride (5 mg three times daily) or placebo for 4 weeks. Symptom severity was assessed by a validated questionnaire at enrolment, 4 and 8 weeks after medication. The primary outcome for the first 4 weeks was decrease in symptom scores. After a 3 day washout period, patients initially allocated to mosapride crossed over to placebo and vice versa for the next 4 weeks. The outcome of the second phase was maintenance of symptom control. All patients received lansoprazole (30 mg once daily) throughout study.

RESULTS

The decreased symptom score after 4 weeks of treatment with lansoprazole and mosapride (n= 50) was 13.42 ± 1.16 (mean ± SEM), similar to that of lansoprazole plus placebo (10.85 ± 1.03, n= 46), with an insignificant difference of 2.57 (95% CI −0.53, 5.67, P= 0.103). However, a sub‐group analysis for patients with pre‐treatment scores of >18 points (n= 48) revealed that lansoprazole plus mosapride achieved a greater reduction of symptom score than lansoprazole plus placebo (18.22 ± 1.91 vs. 12.88 ± 1.65; mean difference of 5.34, 95% CI 0.28, 10.40, P= 0.039). In the second phase, there was no difference between lansoprazole with mosapride or placebo in maintaining symptom control (39/44 or 86.64% vs. 41/50 or 82%, P= 0.401). Subgroup analysis for those with substantial residual symptoms revealed similar results.

CONCLUSION

Compared with placebo, mosapride generally does not provide additional benefit to a standard dose of lansoprazole in patients with reflux oesophagitis, except possibly in the subgroup of severely symptomatic patients.
CYP4F2rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement
Authors: Cen Han‐Jing , Zeng Wu‐Tao , Leng Xiu‐Yu , Huang Min , Chen Xiao , Li Jia‐Li , Huang Zhi‐Ying , Bi Hui‐Chang , Wang Xue‐Ding , He Yan‐Ling , He Fan , Zhou Rui‐Na , Zheng Qi‐Shan , Zhao Li‐Zi
Published: May 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Genetic polymorphisms ofVKORC1andCYP2C9are known to influence warfarin dosage.

• Recent studies among Caucasians showed that polymorphisms ofCYP4F2also play a role in warfarin pharmacogenetics.

• The contribution ofCYP4F2variants to the variability inwarfarin dose requirement in Chinese subjects remains to be investigated.

WHAT THIS STUDY ADDS

• This research was to study the effect ofCYP4F2variants on warfarin requirements in the Han Chinese population.

• This study developed a multiple regression model includingCYP2C9,VKORC13673G>A,CYP4F2genotypes and age, weight, combination use of amiodarone which could explain 56.1% of the individual variability in warfarin doseCYP4F2could explain 4% of the variance in warfarin dose.

• We found that one novel genotypic polymorphism 5417G>T for Asp36Tyr, which was identified as an important marker of warfarin resistance, was absent in the Han Chinese population in our study.

AIMS

The objective of this study was to assess the effect of theCYP4F2on the daily stable warfarin dose requirement in Han Chinese patients with mechanical heart valve replacement (MHVR).

METHODS

From March 2007 to November 2008, 222 Han Chinese MHVR patients were recruited in our study.VKORC13673G>A, 5417G>T,CYP2C9*3 andCYP4F2rs2108622 were genotyped by using the polymerase chain reaction restriction fragment length polymorphism method (PCR‐RFLP). Polymorphisms ofVKORC19041G>A were detected by direct sequencing. Multiple linear regression analysis was used to investigate the contribution ofCYP4F2.

RESULTS

TheCYP4F2rs2108622 CT/TT group took a significantly higher stable warfarin dose (3.2 mg day−1) than the CC group (2.9 mg day−1, 95% CI 0.2, 1.0,P= 0.033). The multiple linear regression model includedVKORC13673G>A,CYP2C9,CYP4F2genotypes and clinical characteristics. The model could explain 56.1% of the variance in stable warfarin dose in Han Chinese patients with MHVR.CYP4F2contributed about 4% to the variance in the warfarin dose. There was no variation in the SNPs ofVKORC15417G>T.

CONCLUSION

CYP4F2is a minor significant factor of individual variability in the stable warfarin dose in Han Chinese patients with MHVR. The effect ofCYP2C9andVKORC1genotypes on variability in the stable warfarin dose had also been confirmed.
All‐cause mortality of elderly Australian veterans using COX‐2 selective or non‐selective NSAIDs: a longitudinal study
Authors: Kerr Stephen J. , Rowett Debra S. , Sayer Geoffrey P. , Whicker Susan D. , Saltman Deborah C. , Mant Andrea
Published: May 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Previous studies have found varying impact of exposure to COX‐2 selective and non‐selective NSAIDs.

WHAT THIS STUDY ADDS

• Individuals receiving a COX‐2 selective NSAID had an increased risk of all‐cause mortality after correction for age, sex and cardiovascular risk as measured by co‐prescription.

• Despite differences in the pharmacokinetic properties of the COX‐2 selective inhibitor drugs, our study lends no support to clinicians preferring any one COX‐2 selective inhibitor drug, or substituting one for another on the grounds of mortality risk alone.

• The Australian Department of Veterans' Affairs data sets make it possible to conduct timely record linkage studies of all‐cause mortality from use of medicines in a large and clinically relevant population.

AIM To determine hazard ratios for all‐cause mortality in elderly Australian veterans taking COX‐2 selective and non‐selective NSAIDs.

METHODS Patient cohorts were constructed from claims databases (1997 to 2007) for veterans and dependants with full treatment entitlement irrespective of military service. Patients were grouped by initial exposure: celecoxib, rofecoxib, meloxicam, diclofenac, non‐selective NSAID. A reference group was constructed of patients receiving glaucoma/hypothyroid medications and none of the study medications. Univariate and multivariate analyses were performed using Cox proportional hazards regression models. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for each exposure group against each of the reference group. The final model was adjusted for age, gender and co‐prescription as a surrogate for cardiovascular risk. Patients were censored if the gap in supply of study prescription exceeded 30 days or if another study medication was initiated. The outcome measure in all analyses was death.

RESULTS Hazard ratios and 95% CIs, adjusted for age, gender and cardiovascular risk, for each group relative to the reference group were: celecoxib 1.39 (1.25, 1.55), diclofenac 1.44 (1.28, 1.62), meloxicam 1.49 (1.25, 1.78), rofecoxib 1.58 (1.39, 1.79), non‐selective NSAIDs 1.76 (1.59, 1.94).

CONCLUSIONS In this large cohort of Australian veterans exposed to COX‐2 selective and non‐selective NSAIDs, there was a significant increased mortality risk for those exposed to either COX‐2‐selective or non‐selective NSAIDs relative to those exposed to unrelated (glaucoma/hypothyroid) medications.
Skin manifestations of drug allergy
Authors: Ardern‐Jones Michael R. , Friedmann Peter S.
Published: May 2010

Cutaneous adverse drug reactions range from mild to severe and from those localized only to skin to those associated with systemic disease. It is important to distinguish features of cutaneous drug reactions which help classify the underlying mechanism and likely prognosis as both of these influence management decisions, some of which necessarily have to be taken rapidly. Severe cutaneous reactions are generally T cell‐mediated, yet this immunological process is frequently poorly understood and principles for identification of the culprit drug are different to those of IgE mediated allergic reactions. Furthermore, intervention in severe skin manifestations of drug allergy is frequently necessary. However, a substantial literature reports on success or otherwise of glucocorticoids, cyclophsphamide, ciclosporin, intravenous immunoglobulin and anti‐tumour necrosis factor therapy for the treatment of toxic epidermal necrolysis without clear consensus. As well as reviewing the recommended supportive measures and evidence base for interventions, this review aims to provide a mechanistic overview relating to a proposed clinical classification to assist the assessment and management of these complex patients.
Towards understanding of carbon stocks and stabilization in volcanic ash soils in natural Andean ecosystems of northern Ecuador
Authors: Tonneijck F. H. , Jansen B. , Nierop K. G. J. , Verstraten J. M. , Sevink J. , De Lange L.
Published: May 2010

Volcanic ash soils contain very large stocks of soil organic matter (SOM) per unit area. Consequently, they constitute potential sources or sinks for the greenhouse gas carbon dioxide. Whether soils become a net carbon source or sink with climate and/or land‐use change depends on the stability of SOM against decomposition, which is influenced by stabilization mechanisms in the soil. To quantify organic carbon stocks and to clarify the importance of chemical and physical soil characteristics for carbon stabilization in volcanic ash soils, we applied selective extraction techniques, performed X‐ray diffraction analysis of the clay fraction and estimated pore‐size distribution of soils under natural upper montane forest and grassland (páramo) in the Ecuadorian Andes. Our results show that organic carbon stocks under both vegetation types are roughly twice as large as previously reported global averages for volcanic ash soils. SOM stabilization is suggested to be dominantly influenced by the following chemical and physical soil characteristics: (i) direct stabilization of SOM in organo‐metallic (Al‐humus) complexes, explaining at most 40% of carbon accumulation, (ii) indirect protection of SOM (notably aliphatic compounds) through low soil pH and toxic levels of Al, and probably also (iii) physical protection of SOM caused by a very large micro‐porosity. Moreover, in the case of the forest soils, inherent recalcitrance of OM itself was responsible for substantial accumulation in ectorganic horizons. Both vegetation types contributed to soil acidification, thus increasing SOM accumulation.
Interferon‐alpha regulates the dynamic balance between human activated regulatory and effector T cells: implications for antiviral and autoimmune responses
Authors: Golding Amit , Rosen Antony , Petri Michelle , Akhter Ehtisham , Andrade Felipe
Published: May 2010

An adequate effector response against pathogens and its subsequent inactivation after pathogen clearance are critical for the maintenance of immune homeostasis. This process involves an initial phase of T‐cell effector (Teff) activation followed by the expansion of regulatory T cells (Tregs), a unique cell population that limits Teff functions. However, significant questions remain unanswered about the mechanisms that regulate the balance between these cell populations. Using an in vitro system to mimic T‐cell activation in human peripheral blood mononuclear cells (PBMC), we analysed the patterns of Treg and Teff activation, with special attention to the role of type I interferon (IFN‐I). Interestingly, we found that IFN‐α, either exogenously added or endogenously induced, suppressed the generation of CD4+ FoxP3HI IFN‐γNeg activated Tregs (aTregs) while simultaneously promoting propagation of CD4+ FoxP3Low/Neg IFN‐γPos activated Teffs (aTeffs). We also showed that IFN‐α‐mediated inhibition of interleukin (IL)‐2 production may play an essential role in IFN‐α‐induced suppression of aTregs. In order to test our findings in a disease state with chronically elevated IFN‐α, we investigated systemic lupus erythematosus (SLE). Plasma from patients with SLE was found to contain IFN‐I activity that suppressed aTreg generation. Furthermore, anti‐CD3 activated SLE PBMCs exhibited preferential expansion of aTeffs with a very limited increase in aTreg numbers. Together, these observations support a model whereby a transient production of IFN‐α (such as is seen in an early antiviral response) may promote CD4 effector functions by delaying aTreg generation, but a chronic elevation of IFN‐α may tip the aTeff:aTreg balance towards aTeffs and autoimmunity.
Risk factors for visceral leishmaniasis in India: further evidence on the role of domestic animals
Authors: Singh S. P. , Hasker E. , Picado A. , Gidwani K. , Malaviya P. , Singh R. P. , Boelaert M. , Sundar S.
Published: May 2010

Objective  Studies investigating risk factors for visceral leishmaniasis (VL) on the Indian Subcontinent have shown contradictory results related to the role of domestic animals. In some studies having animals in or around the house was a risk factor, in others it was protective. We investigated the specific hypothesis that keeping domestic animals inside the house at night is a risk factor for VL.

Methods  Individually matched case–control study. All patients with VL diagnosed in the study area in Bihar, India between March 1st, 2007 and December 1st, 2008 were eligible. For each case, we selected two random controls, with no history of previous VL; matched on sex, age group and neighbourhood. Patients and controls were subjected to a structured interview on the main exposure of interest and potential confounders; a conditional logistic regression model was used to analyse the data.

Results  We enrolled 141 patients and 282 controls. We found no significant associations between VL and keeping domestic animals inside the house (OR of 0.88 for bovines and 1.00 for ‘any animal’) or ownership of domestic animals (OR of 0.97 for bovines and 1.02 for ‘any animal’). VL was associated with housing conditions. Living in a thatched house (OR 2.60, 95% CI 1.50–4.48) or in a house with damp floors (OR 2.60, 95% CI 1.25–5.41) were risk factors, independently from socio economic status.

Conclusion  Keeping animals inside the house is not a risk factor for VL in Bihar, India. Improving housing conditions for the poor has the potential to reduce VL incidence.
Household cost‐of‐illness of visceral leishmaniasis in Bihar, India
Authors: Sundar Shyam , Arora Rakesh , Singh S. P. , Boelaert Marleen , Varghese Beena
Published: May 2010

Objective  To determine the cost of kala‐azar (KA) to patients in Bihar, India.

Method  A semi‐structured questionnaire was used to collect costs of illness – direct (medical; non‐medical) and indirect costs (work days lost). After screening the community known to be endemic for visceral leishmaniasis (VL), households (HHs) with VL were recruited which reported a case of KA who received treatment between September 2005 and September 2006. The total costs were calculated as a summation of individual costs category. Medians were estimated for the total and for each of the cost categories.

Result  Data from 171 HHs and 183 patients revealed that median age of patients with KA was 18; 59% were men; 33% were employed; household size was 7; household median monthly income was $38. The median total costs per patient were $127, equal to >3 months of income, of which medical care comprised $83 (provider fees $13, medicines $50, diagnostics $9, hospital stay $30); and food and transport comprised $33. Patients also lost almost 2 weeks of work time during illness and even after recovery.

Conclusion  Despite provision of free/subsidized medicines, diagnostics, and hospital stay at public and Non‐Governmental Organization facilities, the impoverished HHs of Bihar with a case of KA incur high expenditures. Easier access to, and more use of free public health services, plus innovative health financing schemes, are urgently required.