bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiviral treatments reduce severity of diabetes in Ljungan virus‐infected CD‐1 mice and delay onset in diabetes‐prone BB rats
Authors: Holmberg Rebecka , Klitz William , Blixt Martin , Berggren Per‐Olof , Juntti‐Berggren Lisa , Niklasson Bo 
Published: June 2009

ABSTRACTThe effects of LV in two different species, CD‐1 mice, without a genetic disposition for diabetes, and BB rats prone to T1D were examined. Male CD‐1 mice that had been exposed to LV in utero developed a type 2‐like diabetes with increased blood glucose, insulin levels and epididymal fat at the age of 10–15 weeks. Combination therapy including LV‐antiserum and an antiviral drug, Pleconaril, significantly reduced the levels of blood glucose and insulin and the amount of abdominal fat. In BB rats, LV has been found in both prediabetic‐ and diabetic diabetes‐prone rats, as well as in diabetes‐resistant rats. To evaluate whether the presence of LV has any influence on the onset of T1D, prediabetic BB rats were treated with an antiserum against LV or a combination of the antiviral drugs Pleconaril and Ribavirin. In the group treated with antiviral drugs, the onset was significantly delayed. These results indicate that the presence of LV can be involved in the pathogenesis of diabetes in these animal models.
Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea‐predominant irritable bowel syndrome
Authors: WEDLAKE L. , A’HERN R. , RUSSELL D. , THOMAS K. , WALTERS J. R. F. , ANDREYEV H. J. N. 
Published: June 2009

SummaryBackground  Recurrent, watery diarrhoea affects one‐third of patients diagnosed with irritable bowel syndrome (‘IBS‐D’). Idiopathic bile acid malabsorption (‘I‐BAM’) may be the cause.Aim  To determine the prevalence of I‐BAM in patients suffering from IBS‐D.Methods  A systematic search was performed of publications reporting patients presenting with IBS‐D type symptoms, who were subsequently confirmed as having I‐BAM by SeHCAT scanning.Results  Eighteen relevant studies, 15 prospective, comprising 1223 patients were identified. Five studies (429 patients) indicated that 10% (CI: 7–13) patients had severe bile acid malabsorption (SeHCAT 7 day retention <5% of baseline value). 17 studies (1073 patients) indicated that 32% (CI: 29–35) patients had moderate bile acid malabsorption (SeHCAT <10%). 7 studies (618 patients) indicated that 26% (CI: 23–30) patients had mild (SeHCAT <15%) bile acid malabsorption. Pooled data from 15 studies showed a dose‐response relationship according to severity of malabsorption to treatment with a bile acid binder: response to colestyramine occurred in 96% of patients with <5% retention, 80% at <10% retention and 70% at <15% retention.Conclusions  Idiopathic adult‐onset bile acid malabsorption is not rare. International guidelines for the management of irritable bowel syndrome need to be revised so that clinicians become more aware of this possibility.
In vitroandin vivoevaluation of the inhibition potential of risperidone toward clozapine biotransformation
Authors: Chetty Manoranjenni , D'Esposito Fabrizio , Zhang Wei V. , Glen John , Dore Glenys , Stankovic Zvijezdana , Edwards Robert J. , Ramzan Iqbal , Murray Michael 
Published: June 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The clozapine (CLZ)–risperidone (RISP) combination is effective in schizophrenic patients but may lead to elevated plasma CLZ concentrations and adverse effects.• Reports of potential inhibitory effects of RISP on cytochrome P450 (CYP)‐dependent CLZ oxidation have been inconsistent.• It has been suggested that variations in expression of CLZ/RISP oxidases, such as CYPs 1A2, 2D6 and 3A4, may influence inhibitory interactions.WHAT THIS STUDY ADDS• Inhibition of CLZ biotransformation by RISP was assessed in microsomal fractions that expressed varying amounts of CYPs 1A2, 2D6 and 3A4.• RISP did not inhibit the formation of major oxidized CLZ metabolites, regardless of the CYP expression profile; findings from anin vivostudy in patients were consistent with this finding.• Pharmacokinetic interactions due to the RISP–CLZ combination are unlikely to involve CYPs.AIMSTo study the impact of risperidone (RISP) on clozapine (CLZ) biotransformationin vitroin microsomal fractions containing varying expression of CYP oxidases andin vivoin patients.METHODSHuman liver microsomes (n= 11) were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes mediate RISP and CLZ oxidation. Inhibition of CLZ oxidation by RISP was assessed. Plasma CLZ elimination was estimated in patients with schizophrenia who received either CLZ alone or the CLZ–RISP combination (n= 10 per group).RESULTS(i) The CYP3A4 and CYP1A2 inhibitors ketoconazole and fluvoxamine inhibited CLZ oxidation to varying extents in individual microsomal fractions. (ii) RISP did not inhibit CLZ oxidation, regardless of variations in CYP expression. (iii) RISP co‐administration did not impair CLZ clearance.CONCLUSIONSNo evidence was found for CYP‐mediated inhibitory or pharmacokinetic interactions between RISP and CLZ. Occasional literature reports of such interactions may involve other pathways that participate in CLZ disposition.
Mental health inequalities and mental health nursing
Authors: ELLIOTT L. , MASTERS H. 
Published: June 2009

Accessible summary

Current research clearly shows that mental health problems occur more frequently in some social groups than others. These inequalities in mental health affect people in many developed countries. For example, depression and anxiety are more common among poorer people than richer people. Depression is more common among women while suicide is more common among men. There are higher rates of certain mental health problems among ethnic minorities. People with long‐term mental health problems also have poorer physical health compared with those in the general population. These differences are thought to be determined by a person's economic, social and cultural position in society. There is additional evidence that mental health inequalities can be made worse by poor service provision or by people not using the existing services.
This paper examines what mental health nurses might do to address inequalities in mental health. It concludes that mental health nurses have a key role to play in helping to shape existing physical and mental health services so that these services are more accessible and helpful for those who use them. However, we also conclude that health services, including nursing, may not be powerful enough to tackle some of the underlying causes of mental health inequalities. One such cause is poverty, which needs extensive government action. We also think that these limitations are not clearly stated in current policy for mental health nurses and should be set out more clearly in policy and indeed training initiatives.

AbstractReducing inequalities in health, including mental health, is of high priority in many national policies. However, it is not yet known how mental health nurses might respond to these policies. Using examples from the available evidence, we argue that the causes of mental health inequalities are complex and thought to arise from fundamental divisions in society. These divisions are formed by social relationships, which areinfluenced by deep social structures, such as the economy or culture. The extensive range of social determinants means that there is no single explanation of why inequalities in mental health might occur. It also suggests that these determinants may act synergistically to create pockets of inequity where health needs are most complex. This poses difficult challenges for mental health nurses who undoubtedly have a key role in addressing mental health inequalities, although their role is likely to be restricted to service redesign and delivery. Mental health nurses are unlikely to address some of the deeper structural determinants of mental health inequalities, such as poverty, which can only be tackled through government‐led reforms. Furthermore, we must be mindful of the possibility that services offered by mental nurses may have an uneven uptake across social classes, which in turn could serve to maintain or worsen mental health inequalities. Therefore, a key question for mental health nursing, policy and training is whether these limitations are clearly recognized.
Self‐help CBT for depression: opportunities for primary care mental health nurses?
Authors: WARRILOW A. E. , BEECH B. 
Published: June 2009

Accessible summary

There is currently a big demand for effective and accessible treatments for common mental health problems, but waiting lists are often long.
The aim of this review is to discover whether self‐help cognitive behavioural therapy materials are effective in the treatment of depression.
It explores a possible role for mental health nurses within primary care to provide access to and low‐level support with, these materials.
A possible model for organizing such a service is suggested.

AbstractMental health treatments that are effective and accessible to the general population are in high demand. Cognitive behavioural therapy (CBT) has been shown to be effective and is popular but such treatments are difficult to access especially within primary care, causing delay, frustration and suffering. One approach to meeting demand would be through the use of self‐help CBT materials that aim to address common mental health problems such as depression. The aim of this review is to discover whether self‐help CBT materials are effective in the treatment of depression and how mental health nurses within primary care can use their skills to provide access and low‐level support. Studies critiqued within this literature review indicate that self‐help CBT is effective for the treatment of depression. However, there is a lack of evidence that specifically considers self‐help CBT for the treatment of depression in primary care. This review addresses the question of how much nurse client contact is needed to provide adequate support for the facilitation of self‐help CBT in depression with primary care patients and recommends the use of a service delivery model. However, more research needs to be carried out on the application of self‐help CBT for depression in primary care.
Increase in serum haptoglobin and apolipoprotein M in patients with obstructive sleep apnoea
Authors: KIM JINKWAN , LEE SEUNGGWAN , IN KWANGHO , KIM JEHYEONG , YOU SEHWA , KANG KYUNGHO , SIM JAEJEONG , LEE SANGYEUB , YOON DAEWUI , LEE JUNGBOK , SHIN CHOL 
Published: June 2009

SummaryObstructive sleep apnoea (OSA) is a common syndrome, which is associated with a number of medical problems that impact morbidity and mortality. Although the precise mechanisms that underlie these associations are not fully understood, previous studies have suggested that patients with OSA show elevations of several biomarkers that are associated with cardiovascular risk. This study was undertaken to identify serum proteins associated with OSA by using a proteomics technique and to examine changes in identified protein levels after continuous positive airway pressure treatment. The study participants consisted of 40 male patients (aged 40–49 years) with severe OSA and 34 male control subjects matched for age and body mass index. All subjects underwent polysomnography. Using a proteomics approach, we identified nine proteins that were differentially expressed in patients with severe OSA and controls. Three of these nine proteins, haptoglobin, paraoxonase‐1 and apolipoprotein M, were quantified by using enzyme‐linked immunosorbent assays, kinetic assays and by using Western blotting. Multiple regression analysis showed that haptoglobin and apolipoprotein M levels are independently related to apnoea–hypopnoea index (P < 0.01). A further study is required to determine the nature of associations between these identified proteins and OSA in a large population.
The Plasmodium falciparum protein Pfg27 is dispensable for gametocyte and gamete production, but contributes to cell integrity during gametocytogenesis
Authors: Olivieri Anna , Camarda Grazia , Bertuccini Lucia , Van De Vegte‐Bolmer Marga , Luty Adrian J. F. , Sauerwein Robert , Alano Pietro 
Published: June 2009

SummaryIn the human malaria parasite Plasmodium falciparum, gametocyte maturation is a process remarkably longer than in other malaria species, accompanied by expression of 2–300 sexual stage‐specific proteins. Disruption of several of their encoding genes so far showed that only the abundant protein Pfg27, produced at the onset of sexual differentiation, is essential for gametocyte production. In contrast with what has been previously described, here we show that P. falciparum pfg27 disruptant lines are able to undergo all stages of gametocyte maturation, and are able to mature into gametes. A fraction of Pfg27‐defective gametocytes show, however, distinct abnormalities in intra‐ and extra‐cellular membranous compartments, such as accumulation of parasitophorous vacuole‐derived vesicles in the erythrocyte cytoplasm, large intracellular vacuoles and discontinuities in their trilaminar cell membrane. This work revises current knowledge on the role of Pfg27, indicating that the protein is not required for parasite entry into sexual differentiation, and suggesting that it is instead involved in maintaining cell integrity in the uniquely long gametocytogenesis of P. falciparum.
Activation and repression of a σN‐dependent promoter naturally lacking upstream activation sequences
Authors: Porrúa Odil , García‐González Vicente , Santero Eduardo , Shingler Victoria , Govantes Fernando 
Published: June 2009

SummaryThe Pseudomonas sp. strain ADP protein AtzR is a LysR‐type transcriptional regulator required for activation of the atzDEF operon in response to nitrogen limitation and cyanuric acid. Transcription of atzR is directed by the σN‐dependent promoter PatzR, activated by NtrC and repressed by AtzR. Here we use in vivo and in vitro approaches to address the mechanisms of PatzR activation and repression. Activation by NtrC did not require any promoter sequences other than the σN recognition motif both in vivo and in vitro, suggesting that NtrC activates PatzR in an upstream activation sequences‐independent fashion. Regarding AtzR‐dependent autorepression, our in vitro transcription experiments show that the concentration of AtzR required for repression of the PatzR promoter in vitro correlates with AtzR affinity for its binding site. In addition, AtzR prevents transcription from PatzR when added to a preformed E‐σN–PatzR closed complex, but isomerization to an open complex prevents repression. Gel mobility shift and DNase I footprint assays indicate that DNA‐bound AtzR and E‐σN are mutually exclusive. Taken together, these results strongly support the notion that AtzR represses transcription from PatzR by competing with E‐σN for their overlapping binding sites. There are no previous reports of a similar mechanism for repression of σN‐dependent transcription.
4‐Nitrotryptophan is a substrate for the non‐ribosomal peptide synthetase TxtB in the thaxtomin A biosynthetic pathway
Authors: Johnson Evan G. , Krasnoff Stuart B. , Bignell Dawn R. D. , Chung Wen‐Chuan , Tao Tao , Parry Ronald J. , Loria Rosemary , Gibson Donna M. 
Published: June 2009

SummaryThaxtomin A, a cyclic dipeptide with a nitrated tryptophan moiety, is a phytotoxic pathogenicity determinant in scab‐causing Streptomyces species that inhibits cellulose synthesis by an unknown mechanism. Thaxtomin A is produced by the action of two non‐ribosomal peptide synthetase modules (TxtA and TxtB) and a complement of modifying enzymes, although the order of biosynthesis has not yet been determined. Analysis of a thaxtomin dual module knockout mutant and single module knockout mutants revealed that 4‐nitrotryptophan is an intermediate in thaxtomin A biosynthesis prior to backbone assembly. The 4‐nitrotryptophan represents a novel substrate for non‐ribosomal peptide synthetases. Through identification of N‐methyl‐4‐nitrotryptophan in a single module knockout and the use of adenylation domain specificity prediction software, TxtB was identified as the non‐ribosomal peptide synthetase module specific for 4‐nitrotryptophan.
IRREGULAR TRICHOME BRANCH 2 (ITB2) encodes a putative aminophospholipid translocase that regulates trichome branch elongation in Arabidopsis
Authors: Zhang Xiaoguo , Oppenheimer David G. 
Published: June 2009

SummaryThe P4 ATPase family in Arabidopsis consists of 12 members that encode putative aminophospholipid translocases (ALA1–12). Until recently, no mutations in these genes have been shown to cause a visible phenotype, although reduced expression of ALA1 in transgenic plants expressing an antisense construct has been shown to result in reduced plant size when plants were grown under cold conditions. During a genetic screen for mutations that affect trichome shape, we isolated several alleles of the irregular trichome branch 2 (itb2) mutation. Subsequent positional cloning of this locus showed that ITB2 encoded ALA3. Phenotypic and genetic analyses of multiple itb2 alleles, including the T‐DNA insertion alleles, showed that the loss of ITB2/ALA3 function leads to aberrant trichome expansion, reduced primary root growth and longer root hairs. We also found that itb2/ala3 mutant pollen does not grow as well as wild‐type pollen, leading to severe segregation distortion. Our results suggest that aminophospholipid translocases play an important role in the polar growth of plant cells, which is consistent with the proposed role of ALA3 in membrane trafficking. Furthermore, itb2/ala3 mutants provide a convenient visible phenotype for further genetic analysis of the ALA family in Arabidopsis.
Lipid microdomain polarization is required for NADPH oxidase‐dependent ROS signaling in Picea meyeri pollen tube tip growth
Authors: Liu Peng , Li Rui‐Li , Zhang Liang , Wang Qin‐Li , Niehaus Karsten , Baluška František , Šamaj Jozef , Lin Jin‐Xing 
Published: June 2009

SummaryThe polarization of sterol‐enriched lipid microdomains has been linked to morphogenesis and cell movement in diverse cell types. Recent biochemical evidence has confirmed the presence of lipid microdomains in plant cells; however, direct evidence for a functional link between these microdomains and plant cell growth is still lacking. Here, we reported the involvement of lipid microdomains in NADPH oxidase (NOX)‐dependent reactive oxygen species (ROS) signaling in Picea meyeri pollen tube growth. Staining with di‐4‐ANEPPDHQ or filipin revealed that sterol‐enriched microdomains were polarized to the growing tip of the pollen tube. Sterol sequestration with filipin disrupted membrane microdomain polarization, depressed tip‐based ROS formation, dissipated tip‐focused cytosolic Ca2+ gradient and thereby arrested tip growth. NOX clustered at the growing tip, and corresponded with the ordered membrane domains. Immunoblot analysis and native gel assays demonstrated that NOX was partially associated with detergent‐resistant membranes and, furthermore, that NOX in a sterol‐dependent fashion depends on membrane microdomains for its enzymatic activity. In addition, in vivo time‐lapse imaging revealed the coexistence of a steep tip‐high apical ROS gradient and subapical ROS production, highlighting the reported signaling role for ROS in polar cell growth. Our results suggest that the polarization of lipid microdomains to the apical plasma membrane, and the inclusion of NOX into these domains, contribute, at least in part, to the ability to grow in a highly polarized manner to form pollen tubes.
Plasma membrane‐associated proline‐rich extensin‐like receptor kinase 4, a novel regulator of Ca2+ signalling, is required for abscisic acid responses in Arabidopsis thaliana
Authors: Bai Ling , Zhang Guozeng , Zhou Yun , Zhang Zhaopei , Wang Wei , Du Yanyan , Wu Zhongyi , Song Chun‐Peng 
Published: June 2009

SummaryPlant roots respond to environmental stresses or the exogenous plant hormone abscisic acid (ABA) by undergoing marked physiological and morphological changes. We show here that PERK4, a gene that encodes a member of the Arabidopsis thaliana proline‐rich extensin‐like receptor kinase family, plays an important role in ABA responses. Mutation of PERK4 by T‐DNA insertion decreased sensitivity to ABA with respect to seed germination, seedling growth and primary root tip growth. The effect on root growth was due to enhanced cell elongation rather than cell division. The cytosolic free calcium concentration and Ca2+ channel currents were lower in perk4 root cells than in wild‐type cells in the presence of ABA. Root growth was similar in wild‐type and perk4 plants after the application of a Ca2+ channel blocker. PERK4 localised to the plasma membrane, and was shown to be an ABA‐ and Ca2+‐activated protein kinase. Our data suggest that the receptor‐like kinase encoded by PERK4 functions at an early stage of ABA signalling to inhibit root cell elongation by perturbing Ca2+ homeostasis.
A role for circadian evening elements in cold‐regulated gene expression in Arabidopsis
Authors: Mikkelsen Michael D. , Thomashow Michael F. 
Published: June 2009

SummaryThe plant transcriptome is dramatically altered in response to low temperature. The cis‐acting DNA regulatory elements and trans‐acting factors that regulate the majority of cold‐regulated genes are unknown. Previous bioinformatic analysis has indicated that the promoters of cold‐induced genes are enriched in the Evening Element (EE), AAAATATCT, a DNA regulatory element that has a role in circadian‐regulated gene expression. Here we tested the role of EE and EE‐like (EEL) elements in cold‐induced expression of two Arabidopsis genes, CONSTANS‐like 1 (COL1; At5g54470) and a gene encoding a 27‐kDa protein of unknown function that we designated COLD‐REGULATED GENE 27 (COR27; At5g42900). Mutational analysis indicated that the EE/EEL elements were required for cold induction of COL1 and COR27, and that their action was amplified through coupling with ABA response element (ABRE)‐like (ABREL) motifs. An artificial promoter consisting solely of four EE motifs interspersed with three ABREL motifs was sufficient to impart cold‐induced gene expression. Both COL1 and COR27 were found to be regulated by the circadian clock at warm growth temperatures and cold‐induction of COR27 was gated by the clock. These results suggest that cold‐ and clock‐regulated gene expression are integrated through regulatory proteins that bind to EE and EEL elements supported by transcription factors acting at ABREL sequences. Bioinformatic analysis indicated that the coupling of EE and EEL motifs with ABREL motifs is highly enriched in cold‐induced genes and thus may constitute a DNA regulatory element pair with a significant role in configuring the low‐temperature transcriptome.