bluuebunny/crossref_metadata_2025 huggingface dataset:
Mex3cregulates insulin-like growth factor 1 (IGF1) expression and promotes postnatal growth
Authors: Jiao Yan , Bishop Colin E. , Lu Baisong
Published: February 2012

Insulin-like growth factor 1 (IGF1) mediates the growth-promoting activities of growth hormone. How Igf1 expression is regulated posttranscriptionally is unclear. Caenorhabditis elegans muscle excess 3 (MEX-3) is involved in cell fate specification during early embryonic development through regulating mRNAs involved in specifying cell fate. The function of its mammalian homologue, MEX3C, is unknown. Here we show that MEX3C deficiency in Mex3c homozygous mutant mice causes postnatal growth retardation and background-dependent perinatal lethality. Hypertrophy of chondrocytes in growth plates is significantly impaired. Circulating and bone local production of IGF1 are both decreased in mutant mice. Mex3c mRNA is strongly expressed in the testis and the brain, and highly expressed in resting and proliferating chondrocytes of the growth plates. MEX3C is able to enrich multiple mRNA species from tissue lysates, including Igf1. Igf1 expression in bone is decreased at the protein level but not at the mRNA level, indicating translational/posttranslational regulation. We propose that MEX3C protein plays an important role in enhancing the translation of Igf1 mRNA, which explains the perinatal lethality and growth retardation observed in MEX3C-deficient mice.
Centrosome misorientation mediates slowing of the cell cycle under limited nutrient conditions inDrosophilamale germline stem cells
Authors: Roth Therese M. , Chiang C.-Y. Ason , Inaba Mayu , Yuan Hebao , Salzmann Viktoria , Roth Caitlin E. , Yamashita Yukiko M.
Published: February 2012

Drosophila male germline stem cells (GSCs) divide asymmetrically, balancing self-renewal and differentiation. Although asymmetric stem cell division balances between self-renewal and differentiation, it does not dictate how frequently differentiating cells must be produced. In male GSCs, asymmetric GSC division is achieved by stereotyped positioning of the centrosome with respect to the stem cell niche. Recently we showed that the centrosome orientation checkpoint monitors the correct centrosome orientation to ensure an asymmetric outcome of the GSC division. When GSC centrosomes are not correctly oriented with respect to the niche, GSC cell cycle is arrested/delayed until the correct centrosome orientation is reacquired. Here we show that induction of centrosome misorientation upon culture in poor nutrient conditions mediates slowing of GSC cell proliferation via activation of the centrosome orientation checkpoint. Consistently, inactivation of the centrosome orientation checkpoint leads to lack of cell cycle slowdown even under poor nutrient conditions. We propose that centrosome misorientation serves as a mediator that transduces nutrient information into stem cell proliferation, providing a previously unappreciated mechanism of stem cell regulation in response to nutrient conditions.
ATR cooperates with CTC1 and STN1 to maintain telomeres and genome integrity inArabidopsis
Authors: Boltz Kara A. , Leehy Katherine , Song Xiangyu , Nelson Andrew D. , Shippen Dorothy E.
Published: February 2012

The CTC1/STN1/TEN1 (CST) complex is an essential constituent of plant and vertebrate telomeres. Here we show that CST and ATR (ataxia telangiectasia mutated [ATM] and Rad3-related) act synergistically to maintain telomere length and genome stability in Arabidopsis. Inactivation of ATR, but not ATM, temporarily rescued severe morphological phenotypes associated with ctc1 or stn1. Unexpectedly, telomere shortening accelerated in plants lacking CST and ATR. In first-generation (G1) ctc1 atr mutants, enhanced telomere attrition was modest, but in G2 ctc1 atr, telomeres shortened precipitously, and this loss coincided with a dramatic decrease in telomerase activity in G2 atr mutants. Zeocin treatment also triggered a reduction in telomerase activity, suggesting that the prolonged absence of ATR leads to a hitherto-unrecognized DNA damage response (DDR). Finally, our data indicate that ATR modulates DDR in CST mutants by limiting chromosome fusions and transcription of DNA repair genes and also by promoting programmed cell death in stem cells. We conclude that the absence of CST in Arabidopsis triggers a multifaceted ATR-dependent response to facilitate maintenance of critically shortened telomeres and eliminate cells with severe telomere dysfunction.
α‐Defensins and outcome in patients with chronic heart failure
Authors: Christensen Heidi M. , Frystyk Jan , Faber Jens , Schou Morten , Flyvbjerg Allan , Hildebrandt Per , Raymond Ilan , Klausen Tobias W. , Kistorp Caroline
Published: February 2012

Aim

α‐Defensins are part of the innate immune system. Low‐grade inflammation seems to play a crucial role in development and progression of chronic heart failure (CHF). The aims of the present study were to compare plasma levels of α‐defensins in CHF patients and healthy controls and to examine the predictive ability of α‐defensins, alone and combined with N‐terminal pro brain natriuretic peptide (NT‐proBNP), with respect to all‐cause mortality.

Methods and results

In a prospective observational study lasting 2.6 years we examined the prognostic value of plasma α‐defensins with respect to mortality in 194 CHF patients, and compared plasma levels with those of 98 age‐matched healthy controls. α‐Defensin levels were twice as high among CHF patients in New York Heart Association (NYHA) functional class III–IV than in patients in NYHA class I–II and healthy controls (P = 0.001). The absolute increase in risk of mortality for patients with α‐defensin levels in the upper tertile vs. the lowest tertile was 30% (P = 0.002). After adjusting for potential confounders including NT‐proBNP, plasma α‐defensins remained independently associated with an increased risk of all‐cause mortality (hazard ratio 1.65, 95% confidence interval 1.19–2.28, P = 0.002) per 1 standard deviation increment in Ln (natural logarithm)‐transformed α‐defensin values. The combination of high α‐defensins and NT‐proBNP levels provided incremental prognostic information independent of well‐known prognostic biomarkers in heart failure.

Conclusion

Plasma α‐defensins appear to have prognostic information regarding mortality among patients with CHF and seem to provide incremental information to established clinical risk markers.
Ethanol‐Production Performance of Ozone‐Treated Tannin Grain Sorghum Flour
Authors: Yan Shuping , Wu Xiaorong , Faubion Jon , Bean Scott R. , Cai Liming , Shi Yong‐Cheng , Sun Xiuzhi S. , Wang Donghai
Published: February 2012

Ozone has been reported as being able to degrade macromolecules such as cellulose, starch, lignins, and tannins in the textile, pulping, and water‐treatment industries. Thus, we hypothesized that ozone treatment may also inactivate tannin activity and increase fermentation efficiency of tannin sorghum lines. The objective of this research was to study the physicochemical properties of ozone‐treated whole tannin grain sorghum flour and its fermentation performance in ethanol production. Results showed that the ethanol yields from ozone‐treated tannin grain sorghums were significantly higher than yields from the untreated flour. The fermentation efficiency of ozone‐treated tannin grain sorghum was approximately 90%, which was 8–14% higher than that of untreated samples at the 36th hr of fermentation. At the end of 72 hr of fermentation, the efficiencies of ozone‐treated sorghum flour were 2–5% higher than those of untreated samples. Measured tannin levels of ozone‐treated samples decreased significantly from 3.8 to 2.7%. Gel‐permeation chromatographic results indicated that both degradation and polymerization processes might have happened to starch molecules during ozone treatment. Rapid Visco Analyzer data showed that the setback of viscosity of ozone‐treated flour was lower than that of untreated flours. Distillers dried grains with solubles made from ozone‐treated sorghum were low in residual starch (<1%) and high in crude protein (≈35%). Therefore, ozonation could be a novel and useful method to improve ethanol yield and fermentation efficiency of tannin grain sorghum.
Mapping of functional region conferring nuclear localization and karyopherin α-binding activity of the C2 protein of bhendi yellow vein mosaic virus
Authors: Chandran Sam A. , Levy Yael , Mett Anahit , Belausov Eduard , Ramakrishnan Usha , Gafni Yedidya
Published: February 2012

Bhendi yellow vein mosaic disease is caused by a complex consisting of a monopartite begomovirus associated with a β-satellite. The C2 protein of bhendi yellow vein mosaic virus (BYVMV) is a suppressor of post-transcriptional gene silencing and also functions as a transcriptional activator. To explore the molecular mechanisms of its nuclear trafficking and self-interaction, fusion proteins of fluorescent proteins with wild-type or mutated constructs of BYVMV C2 were expressed in tobacco protoplasts. Analyses revealed that the BYVMV C2 nuclear localization signal (NLS) was located in the N terminus of the protein, comprising aa 17–31 of C2. NLSs are recognized by a class of soluble transport receptors termed karyopherins α and β. The BYVMV C2 NLS was found to be necessary for this protein’s interaction with its nuclear import mediator, karyopherin α, ensuring its nuclear localization. Nevertheless, when deleted, C2 was found in both the cytoplasm and the nucleus, suggesting NLS-independent nuclear import of this protein. Homotypic interaction of BYVMV C2 was also found, which correlates with the nuclear localization needed for efficient activation of transcription.
The tale of xenotropic murine leukemia virus-related virus
Authors: Groom Harriet C. T. , Bishop Kate N.
Published: February 2012

In 2006, a new retrovirus was isolated from prostate cancer patient tissue. Named xenotropic murine leukemia virus-related virus (XMRV), this was potentially the third class of retrovirus to be pathogenic in humans. XMRV made a more dramatic impact on the wider scientific community, and indeed the media, in 2009 when it was reported to be present in a remarkably high proportion of patients with chronic fatigue syndrome as well as a significant, albeit smaller, proportion of healthy controls. The apparent strong link to disease and the fear of a previously unknown retrovirus circulating in the general population lead to a surge in XMRV research. Subsequent studies failed to find an association of XMRV with disease and, in most cases, failed to find the virus in human samples. In 2011, the case against XMRV and human disease strengthened, ending with several decisive publications revealing the origin of the virus and demonstrating contamination of samples. In this review, we outline the passage of research on XMRV and its potential association with disease from its isolation to the present day, where we find ourselves at the end of a turbulent story.
Global profiling of DNA methylation erasure in mouse primordial germ cells
Authors: Guibert Sylvain , Forné Thierry , Weber Michael
Published: February 2012

Epigenetic reprogramming, characterized by loss of cytosine methylation and histone modifications, occurs during mammalian development in primordial germ cells (PGCs), yet the targets and kinetics of this process are poorly characterized. Here we provide a map of cytosine methylation on a large portion of the genome in developing male and female PGCs isolated from mouse embryos. We show that DNA methylation erasure is global and affects genes of various biological functions. We also reveal complex kinetics of demethylation that are initiated at most genes in early PGC precursors around embryonic day 8.0–9.0. In addition, besides intracisternal A-particles (IAPs), we identify rare LTR-ERV1 retroelements and single-copy sequences that resist global methylation erasure in PGCs as well as in preimplantation embryos. Our data provide important insights into the targets and dynamics of DNA methylation reprogramming in mammalian germ cells.
Nimustine hydrochloride: the first crystal structure determination of a 2-chloroethyl-N-nitrosourea hydrochloride derivative by X-ray powder diffraction and solid-state NMR
Authors: Bekö Sándor L. , Urmann David , Lakatos Andrea , Glaubitz Clemens , Schmidt Martin U.
Published: February 2012

Nimustine hydrochloride [systematic name: 4-amino-5-({[N-(2-chloroethyl)-N-nitrosocarbamoyl]amino}methyl)-2-methylpyrimidin-1-ium chloride], C9H14ClN6O2+·Cl−, is a prodrug of CENU (chloroethylnitrosourea) and is used as a cytostatic agent in cancer therapy. Its crystal structure was determined from laboratory X-ray powder diffraction data. The protonation at an N atom of the pyrimidine ring was established by solid-state NMR spectroscopy.
The effect of adrenaline on the temperature dependency of cardiac action potentials in pink salmon Oncorhynchus gorbuscha
Authors: Ballesta S. , Hanson L. M. , Farrell A. P.
Published: February 2012

Using sharp electrode impalement, action potentials recorded from atrial and ventricular tissue of pink salmon Oncorhynchus gorbuscha generally decreased in duration with increasing test temperature (6, 10, 16 and 20° C). Stimulation of the tissue using 500 nM adrenaline had no significant effect on the duration of the atrial action potential at any test temperature but lengthened the ventricular action potential by ∼17%.
A new species of Triplophysa (Nemacheilidae: Cypriniformes), from Guangxi, southern China
Authors: Zheng L. P. , Yang J. X. , Chen X. Y.
Published: February 2012

A new species, Triplophysa huapingensis, is described from the Hongshuihe River, Guangxi, China. The new species is distinguished from other species of Triplophysa by the following combination of characters: body covered with scales, lateral line complete, eyes not degenerate, dorsal fin truncate, caudal fin forked, tip of pelvic fin not reaching anus, eight branched rays of dorsal fin, six branched rays of pelvic fin, 16 branched rays of caudal fin, grey and black diffused blotches on dorsal and lateral head and body. A key to all recorded species of Triplophysa in the Xijiang River system is provided.
Increase in circulating endothelial progenitor cells predicts response in patients with advanced non‐small‐cell lung cancer
Authors: Sakamori Yuichi , Masago Katsuhiro , Ohmori Katsuyuki , Togashi Yosuke , Nagai Hiroki , Okuda Chiyuki , Kim Young Hak , Ichiyama Satoshi , Mishima Michiaki
Published: February 2012

Previous reports have shown that circulating endothelial progenitor cells (CEPs) are released in response to cytotoxic chemotherapy. We investigate the relationship between the kinetics of CEPs during one cycle of chemotherapy and the response to cytotoxic chemotherapy and prognostic impacts. Previously untreated patients (n = 38) receiving cytotoxic chemotherapy for non‐small‐cell lung cancer were included. Blood sampling was carried out on day 1, day 8, and just before the second cycle of chemotherapy. The mononuclear cell fraction was analyzed for CEPs by FACS analysis. We evaluated the relationship between the kinetics of CEPs, each independent clinicopathological variable, the response to chemotherapy, and the risk factors associated with prognosis. On the eighth day after chemotherapy, a significant decrease in CEPs was observed. In contrast, CEP counts before the second cycle of chemotherapy were significantly increased. The high percentage change in CEPs between day 1 and before the second cycle of chemotherapy is an independent predictive factor for response to chemotherapy. However, the change in CEP levels did not predict progression‐free survival. These findings indicate that the late release of CEPs is a common phenomenon after chemotherapeutic treatment. The correlation with clinical response to chemotherapy provides further support for the biologic relevance of these cells in patients' prognosis and highlights the potential use of CEPs as therapeutic targets. (Cancer Sci 2012; 103: 1065–1070)
Impact of the 2005 smoke‐free policy in Italy on prevalence, cessation and intensity of smoking in the overall population and by educational group
Authors: Federico Bruno , Mackenbach Johan P. , Eikemo Terje A. , Kunst Anton E.
Published: February 2012

Aims  To estimate the immediate as well as the longer‐term impact of the 2005 smoke‐free law on smoking prevalence, cessation and intensity both in the overall population and separately by educational level.

Design  Interrupted time–series analyses of 11 cross‐sectional nationally representative surveys.

Setting  Italy, 1999–2010.

Participants  Adults aged 20–64 years.

Measurements  For each year we computed the prevalence of current smoking, the quit ratio and the mean number of cigarettes smoked per day. All measures were standardized by age. Segmented linear regression analyses were performed for each smoking variable separately by sex.

Findings  Among males, smoking prevalence decreased by 2.6% (P = 0.002) and smoking cessation increased by 3.3% (P = 0.006) shortly after the ban, but both measures tended to return to pre‐ban values in the following years. This occurred among both highly and low‐educated males. Among low‐educated females, the ban was followed by a 1.6% decrease (P = 0.120) in smoking prevalence and a 4.5% increase in quit ratios (P < 0.001). However, these favourable trends reversed over the following years. Among highly educated females, trends in smoking prevalence and cessation were not altered by the ban. Among both males and females, long‐term trends in the daily number of cigarettes, which were already declining well before the implementation of the policy, changed to a minor extent.

Conclusion  The impact of the Italian smoke‐free policy on smoking and inequalities in smoking was short‐term. Smoke‐free policies may not achieve the secondary effect of reducing smoking prevalence in the long term, and they may have limited effects on inequalities in smoking.
An agenda for UK clinical pharmacology: Integrating pharmacology and clinical pharmacology in universities
Authors: Buckingham Julia C.
Published: February 2012

Continuing development of safe and effective new medicines is critically important for global health, social prosperity and the economy. The drug discovery–development pipeline depends critically on close partnerships between scientists and clinicians and on educational programmes that ensure that the pharmacological workforce, in its broadest sense, is fit for purpose. Here I consider factors that have influenced the development of basic and clinical pharmacology in UK universities over the past 40 years and discuss ways in which basic pharmacologists, clinical pharmacologists and scientists from different disciplines can work together effectively, while retaining their professional identities and fostering developments in their disciplines. Specifically, I propose the establishment of Institutes of Drug Discovery and Development, whose activities could include development and implementation of a translational pharmacology research strategy, drawing on the collective expertise of the membership and the university as whole; provision of a forum for regular seminars and symposia to promote the discipline, encourage collaboration and develop a cohesive community; provision of a research advisory service, covering, for example, data management, applications for ethics permission, clinical trials design, statistics and regulatory affairs; liaison with potential funders and leadership of major funding bids, including funding for doctoral training; provision of advice on intellectual property protection and the commercialization of research; liaison with corporate partners to facilitate collaboration, knowledge transfer and effective translation; and leadership of undergraduate and postgraduate education in basic and clinical pharmacology and related sciences for medical and science students, including continuing professional development and transferable skills.
An agenda for UK clinical pharmacology: Development and delivery of clinical pharmacology in regulatory agencies
Authors: Breckenridge Alasdair
Published: February 2012

Medicines regulation is based on a foundation of science, policy and judgement. It operates within several frameworks (scientific, legal and public health), which are interdependent. While safety, quality and efficacy remain the criteria by which medicines are assessed, the benefit‐to‐harm balance for any medicine or medical device is of paramount importance. While the regulator was hitherto the gatekeeper who allowed a medicine on to the market, payers now require, in addition, assessment of cost and clinical effectiveness before use. As regulatory frameworks develop, several changes will occur, as follows: (i) formal benefit–harm assessment will become an integral part of submission for marketing authorizations; (ii) there will be greater use of surveillance for adverse reactions to new medicines using methods other than voluntary reporting; (iii) risk management plans will become benefit–risk management plans; (iv) life‐saving medicines will be approved earlier; and (v) regulation and health technology assessment will take place simultaneously. Clinical pharmacologists will play important roles in these developments.
An agenda for UK clinical pharmacology: Medication errors
Authors: Ferner Robin E.
Published: February 2012

Medication errors cause substantial harm to patients. We need good methods for counting errors, and we need to know how errors defined in different ways and ascertained by different methods are related to the harm that patients suffer. As errors arise within the complex and poorly designed systems of hospital and primary care, analysis of the factors that lead to error, for example by failure mode and effects analysis, may encourage better designs and reduce harms. There is almost no information on the best ways to train prescribers to be safe or to design effective computerized decision support to help them, although both are important in reducing medication errors and should be investigated. We also need to know how best to provide patients with the data they need to be part of initiatives for safer prescribing.
An agenda for UK clinical pharmacology: Research priorities in pharmacokinetics
Authors: Tucker Geoffrey T.
Published: February 2012

An opinion is expressed on the past, present and future roles of pharmacokinetic–pharmacodynamic research in the context of UK clinical pharmacology. On the basis of its current constitution, it seems unlikely that this area of research will be driven from within academic clinical pharmacology in the UK. Therefore, in order to bring its expertise and experience to bear effectively on the evolving emphasis on translational medicine and modelling and simulation, this community would need to reach out beyond its current preoccupations to increase interactions with the next generation of pharmacokineticists and pharmacometricians.
An agenda for UK clinical pharmacology: Integrating pharmacology and clinical pharmacology in pharmaceutical companies
Authors: Hunter Jackie A.
Published: February 2012

Integration of clinical and preclinical pharmacology in pharmaceutical companies could be improved by several key recommendations:

Companies should ensure that there is an adequate pool of trained clinical pharmacologists and preclinical pharmacologists. Training should include topics that allow clinical pharmacologists to be cognizant of the methods, issues and challenges faced by the preclinical pharmacologists and vice versa.

Companies should incentivize such integration internally by aligning objectives and metrics/incentives.

In academic medicine and the NHS there should be support for involvement of clinical pharmacologists in basic academic research and industrial R & D and new ways of facilitating and incentivizing preclinical pharmacologists and clinical pharmacologists to move between these various environments should be sought.
An agenda for UK clinical pharmacology: An Australian perspective
Authors: Smith Anthony J.
Published: February 2012

Discussing the future of UK clinical pharmacology, eight Australasian clinical pharmacologists emphasized the need to make the discipline ‘indispensable’ in key areas. The visibility of clinical pharmacology in Australasia has been improved by working with the Consumers’ Health Forum in Australia in the construction of the national Policy on Quality Use of Medicines and, later, of the formal National Medicines Policy. Our expertise in clinical pharmacology, combined with the Health Forum's political skills, proved a potent force for launching these policies. A second example was the construction of the national prescribing curriculum in partnership with the National Prescribing Service. This is being used in all medical schools with senior students. At a local level we found that taking over clinical toxicology services (that other clinicians wanted to jettison) provided a stimulus to clinical research and later the formation of a productive subgroup to study the special problems of envenomation. Fourthly, we note that no clinical pharmacology unit in UK is designated as a WHO collaborating centre. Considerable difference can be made to national problems with medicines by clinical pharmacologists willing to work for periods within developing countries. This has given a greater profile to several groups in Australia. The principle of stepping out of conventional settings and actively seeking collaboration with other groups beyond our discipline has enhanced the profile of the discipline in Australasia and could do the same in the UK.
An agenda for UK clinical pharmacology: Public understanding of drug therapy
Authors: Herxheimer Andrew
Published: February 2012

Knowing some basic principles about medicines would help patients to understand drug therapy and to help and encourage them to use it well. These principles relate to the categories and names of drugs, their different uses, how they reach the site of action (absorption, distribution, fate), how they produce their effects, both beneficial and harmful, the time courses of drug actions, how the pattern and intensity of the effects of a drug depend on dose and timing, drug interactions, how drug effects are demonstrated and investigated and sources of information and their trustworthiness.

These basic principles are an essential part of health literacy and understanding them would enable individuals to comprehend better the information that they are likely to receive about medicines that they will take. Different populations need different types of education. For schoolchildren, the principles could fit into biology and domestic science teaching, starting in the later years of primary school or early in secondary school. A teaching package would also be needed for their teachers. For adults, web‐based learning seems the most practical option. Web‐based programmes could be supported by the NHS and professional bodies and through public libraries and local community health services. Specific groups for targeting could include young mothers and carers of chronically ill people. For retired people, one could envisage special programmes, perhaps in collaboration with the University of the Third Age. Conversations between patients and professionals would then become more effective and help shared decision making.
An agenda for UK clinical pharmacology: UK medicines policy: the role of clinical pharmacologists
Authors: Webb David J.
Published: February 2012

Clinical pharmacologists are the only medical specialists whose training focuses specifically on the safe, effective and cost‐effective use of medicines, underpinned by an understanding of drug discovery, drug regulation, pharmacology, translational medicine and the performance of clinical trials. This unique perspective has allowed them to provide expertise and leadership in medicines regulation, medicines policy, health technology assessment and drug pricing. Clinical pharmacologists assisted in the creation of the Committee on Safety of Medicines (now the Commission on Human Medicines), the Yellow Card Scheme, the National Institute of Health and Clinical Excellence (NICE) and related organizations in Scotland and Wales, and contributed to clinical guidelines (through the Scottish Intercollegiate Guidelines Network) and the British National Formulary. Their research work has contributed substantially, through translational medicine and therapeutics, to the development of new medicines and, as a result, creation of health and wealth in the UK. Their work in medicines policy has served to protect patients from harms associated with the use of medicines. A reduction in the number of able junior doctors attracted to a career in clinical pharmacology, a reduction in the number of training posts, and an ageing population of academic trainers, puts the future of the specialty, and its contribution to patient safety and UK wealth creation, at substantial risk. Urgent measures are needed to convince the NHS and government that these essential skills should be protected and nurtured.
An agenda for UK clinical pharmacology: Pharmacoeconomics
Authors: Hughes Dyfrig A.
Published: February 2012

Pharmacoeconomics is an essential component of health technology assessment and the appraisal of medicines for use by UK National Health Service (NHS) patients. As a comparatively young discipline, its methods continue to evolve. Priority research areas for development include methods for synthesizing indirect comparisons when head‐to‐head trials have not been performed, synthesizing qualitative evidence (for example, stakeholder views), addressing the limitations of the EQ‐5D tool for assessing quality of life, including benefits not captured in quality‐adjusted life years (QALYs), ways of assessing valuation methods (for determining utility scores), extrapolation of costs and benefits beyond those observed in trials, early estimation of cost‐effectiveness (including mechanism‐based economic evaluation), methods for incorporating the impact of non‐adherence and the role of behavioural economics in influencing patients and prescribers.
Use of specific peaks obtained by diffuse reflectance Fourier transform mid‐infrared spectroscopy to study the composition of organic matter in a Haplic Chernozem
Authors: Demyan M. S. , Rasche F. , Schulz E. , Breulmann M. , Müller T. , Cadisch G.
Published: February 2012

This study assessed specific peaks obtained by diffuse reflectance Fourier transform mid‐infrared spectroscopy (DRIFTS) for characterizing the soil organic matter (SOM) composition of a Haplic Chernozem. Soils were collected from the Static Fertilization Experiment, Bad Lauchstädt, Germany, during 5 years from the farmyard manure (FYM), mineral fertilizer (NPK), combination (FYM + NPK) and no fertilizer (Control) treatments. Soils were extracted with hot water (HWE), and fractionated by size and density. Bulk soil and fractions were analysed by DRIFTS. Peak areas at 2930, 1620, 1530 and 1159 cm−1 were selected as a range of organic functional groups (with limited mineral interference), integrated with a local baseline (corrected peak area) and each was divided by the summed area of the four peaks (relative peak area). Positive correlations between carbon (C) in fractions representing labile OM (<1.8 g cm−3, 1.8–2.0 g cm−3, CHWE) and the corrected peak area at 2930 cm−1 (3010–2800 cm−1) in the bulk soil indicated that this aliphatic peak corresponded to the more labile C compounds. Negative correlations between the same fractions and the corrected area of the predominantly aromatic peak at 1620 cm−1 (1660–1580 cm−1) in the bulk soil suggested a relationship with more stable SOM compounds. All relative peak areas were significantly affected by fertilizer treatment, with an increasing relative peak area at 2930 cm−1 in FYM compared with non‐FYM treatments. The ratio of the peaks at 1620 and 2930 cm−1 was positively correlated with the ratio of stable C (sum of C in >1.8 g cm−3 and clay fractions) to labile C (C content of <1.8 g cm−3 fraction) and thus taken as an indicator of SOM stability. The DRIFTS peak area method reflected changes in SOM quality and composition under long‐term management as measured by size and density fractionation, indicating heterogeneous chemical composition of the latter. Further, the DRIFTS analysis of undiluted soil samples can be used to assess SOM composition in small sample sets if specular reflection and mineral interferences are considered.
Influence of experimental venue on phenotype: multiple traits reveal multiple answers
Authors: Winkler Jasmin D. , Van Buskirk Josh
Published: February 2012

1. Experiments in ecology occur in the laboratory, mesocosm or field. The choice of venue can influence the outcome and may be associated with trade‐offs involving realism and precision.

2. We evaluated these trade‐offs in an experiment measuring effects of venue on larval traits ofRana temporariatadpoles. The design included laboratory, mesocosm and field venues, crossed with two treatments (presence and absence of cagedAnax imperatordragonfly larvae). Realism of venues was evaluated by comparing experimental with wild tadpoles.

3. Venue influenced nearly every trait we measured, but some were more sensitive to venue than others. Larval and metamorphic performance, external morphology and predator‐induced plasticity in many traits varied among venues, while behaviour was less dependent on venue. Tadpoles in mesocosms were most similar to those in field enclosures and the wild, although the phenotypic response to predation risk was greatest in the mesocosm venue. The laboratory environment triggered highly distinctive morphology. Precision was not higher in the laboratory than in other venues.

4. This study suggests that both constraints and research questions must be considered when choosing an appropriate experimental venue.
Influence of family carers on haemodialyzed patients’ adherence to dietary and fluid restrictions: an observational study
Authors: Cicolini Giancarlo , Palma Elisabetta , Simonetta Concettoni , Di Nicola Marta
Published: February 2012

cicolini g., palma e., simonetta c. & di nicola m. (2012) Influence of family carers on haemodialyzed patients’ adherence to dietary and fluid restrictions: an observational study. Journal of Advanced Nursing68(11), 2410–2417.

Aim.  To determine the influence of a family carer on haemodialyzed patients’‘adherence’.

Background.  There is extensive evidence showing that successful treatment of patients with end‐stage renal disease is directly related to patients’‘adherence’. The parameters indicative of a good adherence are potassium and phosphate serum levels and the interdialytic weight gain. Haemodialyzed patients may have scarce adherence to food and fluid intake restrictions, and medications schedule.

Design.  Case–control study carried out in a haemodialysis centre in Italy.

Data sources.  The data were collected during 2010.

Methods.  A total of 72 subjects with end‐stage renal disease participated in the study. The subjects assisted by a family carer were identified as cases (n = 36), whereas those who did not have a family carer, as controls (n = 36). All subjects were followed up (4 months) and checked up regarding interdialytic weight gain, and serum levels of potassium and phosphate. Important differences in potassium and phosphate serum level and interdialytic weight gain between the two groups were evaluated separately using a repeated measures anova test.

Results.  Participants in the case group showed significantly lower phosphate and potassium serum levels and a lower interdialytic weight gain during follow‐up when compared to controls.

Conclusions.  The presence of a family carer improves patients’ adherence, particularly as far as phosphate levels are concerned, since phosphate intake plays a fundamental role in avoiding long‐term complications in end‐stage renal disease patients.
ERES (ER exit sites) and the “Secretory Unit Concept”
Authors: LANGHANS M. , MECKEL T. , KRESS A. , LERICH A. , ROBINSON D. G.
Published: February 2012

The higher plant Golgi apparatus consists of hundreds of individual Golgi stacks which move along the cortical ER, propelled by the actomysin system. Anterograde and retrograde transport between the endoplasmic reticulum (ER) and the plant Golgi occurs over a narrow interface (around 500 nm) and is generally considered to be mediated by COP‐coated vesicles. Previously, ER exit sites (ERES) have been identified on the basis of to localization of transiently expressed COPII‐coat proteins. As a consequence it has been held that ERES in higher plants are intimately associated with Golgi stacks, and that both move together as an integrated structure: the “secretory unit”. Using a new COPII marker, as well as YFP‐SEC24 (a bona fide COPII coat protein), we have made observations on tobacco leaf epidermis at high resolution in the CLSM. Our data clearly shows that COPII fluorescence is associated with the Golgi stacks rather than the surface of the ER and probably represents the temporary accumulation of COPII vesicles in the Golgi matrix prior to fusion with the cis‐Golgi cisternae. We have calculated the numbers of COPII vesicles which would be required to provide a typical Golgi‐associated COPII‐fluorescent signal as being much less than 20. We have discussed the consequences of this and question the continued usage of the term “secretory unit”.
Cosmopolitanism of microbial eukaryotes in the global deep seas
Authors: CREER SIMON , SINNIGER FREDERIC
Published: February 2012

Deep sea environments cover more than 65% of the earth’s surface and fulfil a range of ecosystem functions, yet they are also amongst the least known habitats on earth. Whilst the discovery of key geological processes, combined with technological developments, has focused interest onto geologically active areas such as hydrothermal vents, most abyssal biodiversity remains to be discovered (Danovaro et al. 2010). However, as for terrestrial reservoirs of biodiversity, the world’s largest biome is under threat from anthropogenic activities ranging from environmental change to the exploitation of minerals and rare‐earth elements (Kato et al. 2011). It is therefore important to understand the magnitude, nature and composition of deep sea biological communities to inform us of levels of local adaptation, functionality and resilience with respect to future environmental perturbation. In this issue of Molecular Ecology, Bik et al. utilize 454 Roche metagenetic environmental sequencing to assess microbial metazoan community composition and phylogenetic identity across deep sea depth gradients and between ocean basins. The analyses suggest that although the majority of microbial eukaryotic taxa are regionally restricted, a small percentage might maintain cosmopolitan deep sea distributions, and an even smaller fraction appear to be eurybathic (live across depth gradients).
Out in the cold – how big and how old? Genetic fingerprinting reveals long‐lived individuals withstand climatic oscillations in the arctic‐alpine
Authors: MILLER ALLISON
Published: February 2012

In long‐lived, clonally reproducing species, assessing organism size is a nontrivial endeavour because each genetically distinct entity (genet) may comprise multiple modular units (ramets). Attributes of clonally reproducing populations, such as genet size, longevity and clonal diversity (the number of genets in a population), have significant implications for the persistence of populations over time. In the context of climate change, population persistence contributes to community stability and ecosystem resilience. Do clonal individuals persist through periods of climatic oscillations? Are clonal populations composed of a few large and persistent clones, or do they include clones of different sizes and ages? In this issue, de Witte et al. (2012) present an exciting analysis of clonal diversity and genet longevity in populations of four arctic‐alpine plant species with contrasting life histories: Carex curvula, Dryas octopetala, Salix herbacea and Vaccinium uliginosum. Using amplified fragment length polymorphism (AFLP) data, the authors demonstrate that genet size ranged from a few centimetres to 18 metres and age estimates for the largest genets ranged from 500 to 4900 years. These data reveal that clonally reproducing populations include individuals that have outlived significant changes in climate. Despite the longevity of some individuals, clonal diversity within populations was high, with most individuals existing as small, relatively young genets. Long‐lived individuals, together with high numbers of younger plants, ensure repeated recruitment and population persistence over time. This study represents a novel and timely contribution to a growing body of work aimed at understanding population persistence in changing climates.
Increase in fecal primary bile acids and dysbiosis in patients with diarrhea‐predominant irritable bowel syndrome
Authors: Duboc H. , Rainteau D. , Rajca S. , Humbert L. , Farabos D. , Maubert M. , Grondin V. , Jouet P. , Bouhassira D. , Seksik P. , Sokol H. , Coffin B. , Sabaté J. M.
Published: February 2012

Background  Irritable bowel syndrome (IBS) is a multifactorial disease for which a dysbiosis of the gut microbiota has been described. Bile acids (BA) could play a role as they are endogenous laxatives and are metabolized by gut microbiota. We compared fecal BA profiles and microbiota in healthy subjects (HS) and patients with diarrhea‐predominant IBS (IBS‐D), and we searched for an association with symptoms.

Methods  Clinical features and stool samples were collected in IBS‐D patients and HS. Fecal BA profiles were generated using HPLC coupled to tandem mass spectrometry. The fecal microbiota composition was assessed by q‐PCR targeting dominant bacterial groups and species implicated in BA transformation.

Key Results  Fourteen IBS‐D patients and 18 HS were included. The two groups were comparable in terms of age and sex. The percentage of fecal primary BA was significantly higher in IBS‐D patients than in HS, and it was significantly correlated with stool consistency and frequency. Fecal counts of all bacteria, lactobacillus, coccoides, leptum and Faecalibacterium prausnitzii were similar. There was a significant increase of Escherichia coli and a significant decrease of leptum and bifidobacterium in IBS‐D patients.

Conclusions & Inferences  We report an increase of primary BA in the feces of IBS‐D patients compared to HS, correlated with stool consistency and frequency. A dysbiosis of different bacterial groups was detected, some of them involved in BA transformation. As the gut microbiota is the exclusive pathway to transform primary into secondary BA, this suggests a functional consequence of dysbiosis, leading to lower BA transformation.
Microvascular changes in late‐life schizophrenia and mood disorders: stereological assessment of capillary diameters in anterior cingulate cortex
Authors: Sinka L. , Kovari E. , Santos M. , Herrmann F. R. , Gold G. , Hof P. R. , Bouras C. , Giannakopoulos P.
Published: February 2012

L. Sinka, E. Kovari, M. Santos, F. R. Herrmann, G. Gold, P. R. Hof, C. Bouras and P. Giannakopoulos (2012) Neuropathology and Applied Neurobiology38, 696–709

Microvascular changes in late‐life schizophrenia and mood disorders: stereological assessment of capillary diameters in anterior cingulate cortex

Aims: Previous neuroimaging reports described morphological and functional abnormalities in anterior cingulate cortex (ACC) in schizophrenia and mood disorders. In earlier neuropathological studies, microvascular changes that could affect brain perfusion in these disorders have rarely been studied. Here, we analysed morphological parameters of capillaries in this area in elderly cases affected by these psychiatric disorders. Methods: We analysed microvessel diameters in the dorsal and subgenual parts of the ACC in eight patients with schizophrenia, 10 patients with sporadic bipolar disorder, eight patients with sporadic major depression, and seven age‐ and gender‐matched control cases on sections stained with modified Gallyas silver impregnation using a stereological counting approach. All individuals were drug‐naïve or had received psychotropic medication for less than 6 months, and had no history of substance abuse. Statistical analysis included Kruskal–Wallis group comparisons with Bonferroni correction as well as multivariate regression models. Results: Mean capillary diameter was significantly decreased in the dorsal and subgenual parts of areas 24 in bipolar and unipolar depression cases, both in layers III and V, whereas schizophrenia patients were comparable with controls. These differences persisted when controlling for age, local neuronal densities, and cortical thickness. In addition, cortical thickness was significantly smaller in both layers in schizophrenia patients. Conclusions: Our findings indicate that capillary diameters in bipolar and unipolar depression but not in schizophrenia are reduced in ACC. The significance of these findings is discussed in the light of the cytoarchitecture, brain metabolism and perfusion changes observed in ACC in mood disorders.
Volatile pheromone signalling in Drosophila
Authors: SMITH DEAN P.
Published: February 2012

Once captured by the antenna, the male‐specific pheromone 11‐cis vaccenyl acetate (cVA) binds to an extracellular binding protein called LUSH that undergoes a conformational shift upon cVA binding. The stable LUSH–cVA complex is the activating ligand for pheromone receptors present on the dendrites of the aT1 neurones, comprising the only class of neurones that detect volatile cVA pheromone. This mechanism can explain the single molecule sensitivity of pheromone detection. The receptor that recognizes activated LUSH consists of a complex of several proteins, including Or67d, a member of the tuning odourant receptor family, Orco, a co‐receptor ion channel, and SNMP, a CD36 homologue that may be an inhibitory subunit. In addition, genetic screens and reconstitution experiments reveal additional factors that are important for pheromone detection. Identification and functional dissection of these factors in Drosophila melanogaster Meigen should permit the identification of homologous factors in pathogenic insects and agricultural pests, which, in turn, may be viable candidates for novel classes of compounds to control populations of target insect species without impacting beneficial species.
Potential of high‐density pheromone‐releasing microtraps for control of codling moth Cydia pomonella and obliquebanded leafroller Choristoneura rosaceana
Authors: REINKE MICHAEL D. , MILLER JAMES R. , GUT LARRY J.
Published: February 2012

Recent large‐cage studies with codling moth Cydia pomonella (L.) reveal that the removal of moths from an apple orchard using pheromone‐releasing traps is more effective at reducing capture in a central monitoring trap than is a mating disruption protocol without kill/capture. The present study uses open orchard 0.2‐ha plots comparing a high‐density trapping scenario with mating disruption to confirm those results. Two tortricid moth pests of tree fruit are studied: codling moth and obliquebanded leafroller Choristoneura rosaceana (Harris). Codling moth treatments include Isomate CM FLEX (ShinEtsu Ltd, Japan), nonsticky traps baited with Trécé CM lures (Trécé, Inc., Adair, Oklahoma), and sticky traps baited with Trécé CM lures, all at equal application rates of 500 dispensers ha−1, as well as a no pheromone control. These microtraps are of a novel design, small and easy to apply, and potentially inexpensive to produce. Mating disruption using Isomate CM FLEX and nonsticky traps reduces codling moth capture in standard monitoring traps by 58% and 71%, respectively. The attract‐and‐remove treatment with sticky traps reduces capture by 92%. Obliquebanded leafroller treatments include Isomate OBLR/PLR Plus and Pherocon IIB microtraps baited with Trécé OBLR lures, both applied at 500 dispensers ha−1, as well as a no pheromone control. Mating disruption reduces capture in monitoring traps by 69%. The attract‐and‐remove treatment reduces capture by 85%. Both studies suggest that an attract‐and‐remove approach has the potential to provide superior control of moth populations compared with that achieved by mating disruption operating by competitive attraction.