bluuebunny/crossref_metadata_2025 huggingface dataset:
Mammary Cancer and Social Interactions: Identifying Multiple Environments That Regulate Gene Expression Throughout the Life Span
Authors: McClintock Martha K. , Conzen Suzanne D. , Gehlert Sarah , Masi Christopher , Olopade Funmi
Published: June 2011

Now that the human genome has been sequenced, along with those of major animal models, there is an urgent need to define those environments that interact with genes. The traditional view focuses on ways that gene products interact with the nuclear environment to regulate cell function, causing the physiologic changes, behaviors, and diseases manifest throughout development and aging. Although this view is essential, it is equally essential to understand the converse relationship, namely, to identify those environments at higher levels of organization that regulate the expression of specific genes. Given the vastness of this problem, one effective strategy is to start with a trait for which some of the genes have already been identified, such as malignant disease. In rats, social isolation and hypervigilance increase the incidence of mammary tumors, accelerate aging, and shorten the life span. We propose that similar environmental regulation of gene expression may underlie the disproportionately high mortality from premenopausal breast cancer of Blacks, a minority group that can experience high levels of loneliness and hypervigilance. Our goal is to identify which environments—social, psychological, hormonal, and cellular—regulate genetic mechanisms of mammary cancer risk as well as the specific times in the life span when they do so.
Health Inequalities Among Minority Populations
Authors: Jackson Pamela Braboy
Published: June 2011

There are several challenges facing scholars studying health inequalities among minority populations. Primary among these challenges are developing adequate measures of social inequality and introducing appropriate strategies for eliminating health disparities. More research is sorely needed on both of these fronts as evidenced by the health paradox facing black, middle class men and women. This effort, however, can best move the study of health inequalities forward when juxtaposed against theoretical paradigms that embrace the complexity of the intersection of race, class, and gender.
Social Status and Risky Health Behaviors: Results From the Health and Retirement Study
Authors: Wray Linda A. , Alwin Duane F. , McCammon Ryan J.
Published: June 2011

Objectives. We focus on a hypothesized mechanism that may underlie the well-documented link between social status and health–behavioral health risks.

Methods. We use longitudinal data from representative samples of 6,106 middle-aged and 3,636 older adults from the Health and Retirement Study to examine the relationships between social status—including early life social status (e.g., parental schooling), ascribed social status (e.g., sex, race–ethnicity), and achieved social status (e.g., schooling, economic resources)—and behavioral health risks (e.g., weight, smoking, drinking, physical activity) to (1) assess how early life and ascribed social statuses are linked to behavioral health risks, (2) investigate the role of achieved factors in behavioral health risks, (3) test whether achieved status explains the contributions of early life and ascribed status, and (4) examine whether the social status and health risk relationships differ at midlife and older age.

Results. We find that early life, achieved, and ascribed social statuses strongly predict behavioral health risks, although the effects are stronger in midlife than they are in older age.

Discussion. Ascribed social statuses (and interactions of sex and race–ethnicity), which are important predictors of behavioral health risks even net of early life and achieved social status, should be explored in future research.
Cauda Equina Syndrome
Authors: Deniz Kenan , Pararajasingham Jonathan
Published: June 2011

Cauda equina syndrome (CES) is a relatively uncommon condition typically associated with a large space-occupying lesion within the canal of the lumbosacral spine. It is one of the few spinal surgical emergencies and its prompt diagnosis and surgical treatment are of paramount importance as, otherwise, patients could be left with permanent and disabling neurological deficits involving lower limb sensorimotor function, bladder, bowel and sexual function. Furthermore, and as a result of perceived delays in diagnosis and treatment culminating in a suboptimal functional outcome, CES carries a disproportionately high medicolegal profile. This article aims to provide a simple overview of lumbar disc prolapse, CES and its initial management in primary care.
Identification of an Operon, Pil-Chp, That Controls Twitching Motility and Virulence in Xylella fastidiosa
Authors: Cursino Luciana , Galvani Cheryl D. , Athinuwat Dusit , Zaini Paulo A. , Li Yaxin , De La Fuente Leonardo , Hoch Harvey C. , Burr Thomas J. , Mowery Patricia
Published: June 2011

Xylella fastidiosa is an important phytopathogenic bacterium that causes many serious plant diseases, including Pierce's disease of grapevines. Disease manifestation by X. fastidiosa is associated with the expression of several factors, including the type IV pili that are required for twitching motility. We provide evidence that an operon, named Pil-Chp, with genes homologous to those found in chemotaxis systems, regulates twitching motility. Transposon insertion into the pilL gene of the operon resulted in loss of twitching motility (pilL is homologous to cheA genes encoding kinases). The X. fastidiosa mutant maintained the type IV pili, indicating that the disrupted pilL or downstream operon genes are involved in pili function, and not biogenesis. The mutated X. fastidiosa produced less biofilm than wild-type cells, indicating that the operon contributes to biofilm formation. Finally, in planta the mutant produced delayed and less severe disease, indicating that the Pil-Chp operon contributes to the virulence of X. fastidiosa, presumably through its role in twitching motility.
Anesthetic Block of Pain-related Cortical Activity in Patients with Peripheral Nerve Injury Measured by Magnetoencephalography
Authors: Theuvenet Peter J. , de Munck Jan C. , Peters Maria J. , van Ree Jan M. , Lopes da Silva Fernando L. , Chen Andrew C. N.
Published: June 2011

Background

This study examined whether chronic neuropathic pain, modulated by a local anesthetic block, is associated with cortical magnetic field changes.

Methods

In a group of 20 patients with pain caused by unilateral traumatic peripheral nerve injury, a local block with lidocaine 1% was administered and the cortical effects were measured and compared with a control group. The global field power (GFP), describing distribution of cortical activation after median and ulnar nerve stimulation, was plotted and calculated. The effects on the affected hemisphere and the unaffected hemisphere (UH) before and after a block of the injured nerve were statistically evaluated.

Results

Major differences based on the GFP curves, at a component between 50 ms - 90 ms (M70), were found in patients: in the affected hemisphere the M70 GFP peak values were statistically significantly larger in comparison with the UH, and the GFP curves differed morphologically. Interestingly, the mean UH responses were reduced in comparison with the control group, a finding suggesting that the UH is also part of the cortical changes. At M70, the GFP curves and values in the affected hemisphere were modulated by a local block of the median or the ulnar nerve. The most likely location of cortical adaptation is in the primary somatosensory cortex.

Conclusions

Cortical activation is enhanced in the affected hemisphere compared with the UH and is modulated by a local block. The UH in neuropathic pain changes as well. Evoked fields may offer an opportunity to monitor the effectiveness of treatments of neuropathic pain in humans.
A Cost-Benefit Analysis of the ENIGMA Trial
Authors: Graham Alison M. , Myles Paul S. , Leslie Kate , Chan Matthew T.V. , Paech Michael J. , Peyton Philip , El Dawlatly Abdelazeem A.
Published: June 2011

Background

The ENIGMA trial was a prospective, randomized, multicenter study that evaluated the clinical consequences of including N₂O in general anesthesia. Patients who were given a N₂O-free anesthetic when undergoing major surgery for which the expected hospital stay was at least 3 days had lower rates of some postoperative complications. This suggests that, despite a higher consumption of potent inhalational agent, there could be a financial benefit when N₂O is avoided in such settings.

Methods

A retrospective cost analysis of the 2,050 patients recruited to the ENIGMA trial was performed. We measured costs from the perspective of an implementing hospital. Direct health care costs include the costs for maintaining anesthesia, daily medications, hospitalization, and complications. The primary outcome was the net financial savings from avoiding N₂O in major noncardiac surgery. Comparisons between groups were analyzed using Student t test and bootstrap methods. Sensitivity analyses were also performed.

Results

Rates of some serious complications were higher in the N₂O group. Total costs in the N₂O group were $16,203 and in the N₂O-free group $13,837, mean difference of $2,366 (95% CI: 841-3,891); P = 0.002. All sensitivity analyses retained a significant difference in favor of the N₂O-free group (all P ≤ 0.005).

Conclusions

Despite N₂O reducing the consumption of more expensive potent inhalational agent, there were marked additional costs associated with its use in adult patients undergoing major surgery because of an increased rate of complications. There is no cogent argument to continue using N₂O on the basis that it is an inexpensive drug.
Defecation Disorders in Children After Surgery for Hirschsprung Disease
Authors: Chumpitazi Bruno P , Nurko Samuel
Published: June 2011

Background and Objective:

The majority of children with Hirschsprung disease (HD) after corrective surgery (CS) develop protracted defecation disorders (DDs) such as constipation, fecal incontinence, and/or enterocolitis. The aim of this investigation was to determine the diagnoses, therapies, and long‐term clinical outcomes using a systematic algorithm to address protracted DD in children with HD after CS.

Methods:

Retrospective review of children with HD after CS cared for using a systematic algorithm at a tertiary care center. Potential anatomic etiologies were evaluated for first. Clinical outcome was categorized into 4 groups based on symptom severity, time interval from last enterocolitis episode, laxative usage, and/or rectal therapies at the time of last follow‐up.

Results:

Fifty‐seven children were identified, of whom 51 (89.5%) had obstructive symptoms and/or enterocolitis and 6 (10.5%) had nonretentive fecal incontinence. Nonintractable constipation responsive to laxatives was identified in 10 (17.5%), colonic dysmotility in 4 (7.0%), nonrelaxing anal sphincter as a primary etiology in 22 (38.6%), bacterial overgrowth in 2 (3.5%), food intolerance in 2 (3.5%), and rapid transit in 2 (3.5%). Further surgical intervention was undertaken in 22 (38.6%), including 9 (15.8%) for residual aganglionosis. Mean follow‐up was 41.4 ± 4.5 months. Clinical outcomes were excellent in 16 (28.1%), good in 22 (38.6%), fair in 1 (1.8%), and poor in 18 (31.6%). Children with enterocolitis were more likely to have an excellent or good clinical outcome.

Conclusions:

The majority of children with HD and protracted DD after CS have a favorable long‐term clinical outcome when following a systematic algorithm.
Urotensin II Levels Are an Important Marker for the Severity of Portal Hypertension in Children
Authors: Pawar Reshma , Kemp William , Roberts Stuart , Krum Henry , Yandle Tim , Hardikar Winita
Published: June 2011

Background and Aim:

Urotensin II (U‐II), a somatostatin‐like cyclic peptide, was recently identified as the most potent human vasoconstrictor peptide; however, the contribution of U‐II–mediated alterations in peripheral vascular tone in disease states such as chronic liver disease and portal hypertension is poorly characterised. There are no data examining U‐II in chronic liver disease in children. In this study, we aimed to determine whether U‐II levels in healthy children are ontogenically regulated and we explored the effect of chronic liver disease on peripheral circulating U‐II levels.

Materials and Methods:

U‐II levels from healthy controls (n = 129) were compared with a healthy adult population (n = 80) in addition to a well‐characterised cohort of children with chronic liver disease (n = 20). U‐II was measured by radioimmunoassay.

Results:

There was no correlation between U‐II and age in healthy children (r2 = 0, P = 0.8). U‐II levels were similar between the paediatric and the adult control populations (1.35 ± 0.96 vs 1.25 ± 0.78, P = 0.8). U‐II was significantly elevated in children with liver disease compared with controls (1.35 ± 0.96 pmol/L vs 3.56 ± 2.21 pmol/L; P < 0.001). In addition, U‐II levels positively correlated with severity of liver disease as determined by Child‐Pugh score (P < 0.05) and paediatric end‐stage liver disease score (P < 0.001). Levels of U‐II also correlated with long‐term clinical outcome.

Conclusions:

These data suggest that U‐II is an important marker of severity of portal hypertension in children. It is independent of age and may be a potential therapeutic target in the chronic liver disease population.
Supplementation of N‐3 LCPUFA to the Diet of Children Older Than 2 Years: A Commentary by the ESPGHAN Committee on Nutrition
Authors:   ESPGHAN Committee on Nutrition:, Agostoni Carlo , Braegger Christian , Decsi Tamás , Kolacek Sanja , Mihatsch Walter , Moreno Luis A , Puntis John , Shamir Raanan , Szajewska Hania , Turck Dominique , van Goudoever Johannes
Published: June 2011

The aim of this commentary is to review data on the effect of supplementation of paediatric patients ages 2 years or older with n‐3 long‐chain polyunsaturated fatty acids (LCPUFA). Some evidence for a positive effect on functional outcome in children with attention‐deficit/hyperactivity disorder (ADHD) was found; however, benefit was seen in only about half of the randomised controlled trials (RCT), and studies varied widely not only in dose and form of supplementation but also in the functional outcome parameter tested. The committee concludes that there are insufficient data to recommend n‐3 LCPUFA supplementation in the treatment of children with ADHD, but further research on n‐3 LCPUFA supplementation in ADHD may be worthwhile. The committee was unable to find evidence of a favourable effect of n‐3 LCPUFA supplementation on cognitive function in children. Although no benefit of n‐3 LCPUFA supplementation was seen for major clinical outcome parameters in children with cystic fibrosis, a potentially beneficial shift towards less‐inflammatory eicosanoid profiles seen in 2 studies provides grounds for further investigation; it is possible that earlier and longer supplementation periods may be needed to demonstrate clinical effect. For children with phenylketonuria, the limited data available suggest that supplementation of n‐3 LCPUFA to the diet is both feasible and safe, but offers only transient benefit in visual function. For children with bronchial asthma there are insufficient data to suggest that LCPUFA supplementation has a beneficial effect. The committee advises paediatricians that most health claims about supplementation of n‐3 LCPUFA in various diseases in children and adolescents are not supported by convincing scientific data.
Thalidomide Use and Outcomes in Pediatric Patients With Crohn Disease Refractory to Infliximab and Adalimumab
Authors: Felipez Lina M. , Gokhale Ranjana , Tierney Matthew P. , Kirschner Barbara S.
Published: June 2011

Objective:

The aim of the study was to evaluate thalidomide as rescue therapy for pediatric patients with severe refractory Crohn disease (CD) who failed to respond to antitumor necrosis factor (TNF) biologic agents.

Patients and Methods:

A computerized database was used to identify children with CD who had failed conventional immunosuppression therapy and received thalidomide rescue therapy. Twelve patients, mean age at diagnosis 10 years, were identified. Eight children had disease localized to the ileum and colon and 4 to the gastroduodenal area and colon. Five cases were complicated by strictures and 7 by fistulae. Previous drug therapy included azathioprine/6‐mercaptopurine (11/12), methotrexate (7/12), and anti‐TNF biologics (12/12). Outcome measures were Harvey‐Bradshaw Index, change in prednisone dose, hospitalizations, bowel resections, and incision and drainage procedures. Laboratory evaluations were calculated before and after 1 to 6 months of thalidomide.

Results:

Mean Harvey‐Bradshaw Index score improved from 11.8 to 3.9 (P = 0.0004), mean prednisone dose decreased from 13.9 to 2.3 mg/day (P = 0.001), mean number of hospitalizations decreased from 6.3 to 1.3 (P = 0.002), and erythrocyte sedimentation rate decreased from 35 to 14 mm/h (P = 0.02). The surgery rate pre‐thalidomide was 0.031 and on thalidomide was 0.004. Of the 7 patients with fistulae, 5 had complete fistula closure, 1 had partial closure, and 1 showed no improvement. Adverse reactions that resulted in discontinuation of thalidomide are as follows: 42% peripheral neuropathy, 17% worsening of the CD, 8% dizziness, and 8% allergic reaction. All 5 patients who developed peripheral neuropathy had clinical resolution of the neurologic symptoms within 2 to 3 months after stopping thalidomide.

Conclusions:

Thalidomide is a potentially effective rescue therapy for severe refractory CD in children who fail to respond to anti‐TNF medications.
Medication Knowledge
Authors: Fishman Laurie N. , Houtman Dirk , van Groningen Julia , Arnold Janis , Ziniel Sonja
Published: June 2011

Objective:

Adolescents with chronic illness need to develop skills to independently manage their own health. Knowledge of medication is an early step in this process. We explored which factors affect acquisition of medication knowledge in adolescents with inflammatory bowel disease (IBD).

Patients and Methods:

Consecutive patients with IBD older than 10 years received a confidential survey at an outpatient visit including questions regarding medication name, dose, and adverse effects. Results were compared with the medical record. Demographic characteristics obtained included age, sex, disease duration, and type of IBD.

Results:

Completed surveys were returned by 294 patients (65% of those approached). Overall, 95% of patients could name their medication and 54% could identify their correct dose. Of 95 patients receiving biologics, 88% could identify the medicine and 50% could report either dose or timing. Of 139 patients on immunomodulator therapy, 94% could name medicine and 68% reported correct dose. Sex, type, or duration of disease did not affect name or dose knowledge. Generally, older patients did not demonstrate better medication or dosage knowledge than younger patients, although there was a significant trend toward improved knowledge of side effects for older patients. However, <32% of all of the patients could report a single major medication side effect.

Conclusion:

Medication knowledge is an early stage of self‐management, yet many adolescents cannot report the dose of IBD medications, nor know the side effects of immunosuppression. This finding persists into late adolescence, which has ramifications for patients as they separate from parents for college or work.
Short‐course Ondansetron for the Prevention of Methotrexate‐induced Nausea in Children With Crohn Disease
Authors: Kempinska Anna , Benchimol Eric I. , Mack Amanda , Barkey Janice , Boland Margaret , Mack David R.
Published: June 2011

Objectives:

Methotrexate (MTX) is an effective treatment for Crohn disease (CD); however, its application may be limited by the occurrence of nausea. We assessed whether a short course of ondansetron minimized this adverse event.

Patients and Methods:

A retrospective case‐control study of patients with CD who received MTX at the Children's Hospital of Eastern Ontario between 2001 and 2009 was conducted.

Results:

Sixty‐four patients received MTX during this time period. The mean age of diagnosis was 12.0 ± 3.0 years (± standard deviation), and the mean age when MTX was initiated was 13.6 ± 2.6 years. Those receiving only 1 or 2 doses of MTX (N = 4) and stopped for reasons other than development of nausea were not included in the analysis. Fifty patients received ondansetron premedication using a 4‐ to 8‐week tapering schedule with MTX, and only 1 patient (2.0%) developed nausea within the first 3 months of MTX. In contrast, 6 of 10 patients (60.0%, P < 0.001) not premedicated with ondansetron reported nausea following MTX within 3 months. Four of these 6 patients subsequently received ondansetron and had no further complaints. Following ondansetron discontinuation, 5 of 50 (10%) patients developed nausea with subsequent MTX injections, but responded to reinstitution of ondansetron. Some children developed anticipatory nausea (6/60, 10%) and 3 experienced nausea relief after initiating premedication with ondansetron.

Conclusions:

Nausea following MTX is a common complaint in patients with CD. For most, this adverse effect may be prevented through the use of a short‐course ondansetron as premedication. Ondansetron to treat MTX‐induced nausea also can be successfully used but a proactive preventive strategy can be achieved.
A naturally occurring human adenovirus type 7 variant with a 1743 bp deletion in the E3 cassette
Authors: Marinheiro Juliana C. , dos Santos Tatiana G. , Siqueira-Silva Joselma , Lu Xiaoyan , Carvalho Daniela , da Camara Ataíde A. , Arruda Eurico , Arruda Karla , Erdman Dean D. , Hársi Charlotte M.
Published: June 2011

Human adenovirus type 7 (HAdV-7) is an important cause of acute respiratory disease (ARD). Different genomic variants of HAdV-7 have been described, designated 7a–7l. In a previous study to investigate risk factors for ARD and wheezing, nasopharyngeal samples were collected from 90 ill children seeking medical attention in Ribeirão Preto, São Paulo, Brazil. HAdVs were identified in 31 samples and were characterized by serum neutralization and genome restriction analysis. Eleven HAdVs were identified as being HAdV-7, five of which were classified as being of genome type 7p (Gomen). Six other HAdV-7 isolates gave new restriction profiles with all enzymes used and were classified as being a new genomic variant, 7m. These isolates were further characterized by sequencing. The hexon and fiber genes of the 7m variant were nearly identical to the prototype, 7p. However, nucleotide sequences from the E3 cassette revealed a 1743 bp deletion affecting the 16.1K, 19K, 20.1K and 20.5K ORFs.
A single amino acid change, Q114R, in the cleavage-site sequence of Newcastle disease virus fusion protein attenuates viral replication and pathogenicity
Authors: Samal Sweety , Kumar Sachin , Khattar Sunil K. , Samal Siba K.
Published: June 2011

A key determinant of Newcastle disease virus (NDV) virulence is the amino acid sequence at the fusion (F) protein cleavage site. The NDV F protein is synthesized as an inactive precursor, F0, and is activated by proteolytic cleavage between amino acids 116 and 117 to produce two disulfide-linked subunits, F1 and F2. The consensus sequence of the F protein cleavage site of virulent [112(R/K)-R-Q-(R/K)-R↓F-I118] and avirulent [112(G/E)-(K/R)-Q-(G/E)-R↓L-I118] strains contains a conserved glutamine residue at position 114. Recently, some NDV strains from Africa and Madagascar were isolated from healthy birds and have been reported to contain five basic residues (R-R-R-K-R↓F-I/V or R-R-R-R-R↓F-I/V) at the F protein cleavage site. In this study, we have evaluated the role of this conserved glutamine residue in the replication and pathogenicity of NDV by using the moderately pathogenic Beaudette C strain and by making Q114R, K115R and I118V mutants of the F protein in this strain. Our results showed that changing the glutamine to a basic arginine residue reduced viral replication and attenuated the pathogenicity of the virus in chickens. The pathogenicity was further reduced when the isoleucine at position 118 was substituted for valine.
Spatial and reversal learning in the Morris water maze are largely resistant to six hours of REM sleep deprivation following training
Authors: Walsh Christine M. , Booth Victoria , Poe Gina R.
Published: June 2011

This first test of the role of REM (rapid eye movement) sleep in reversal spatial learning is also the first attempt to replicate a much cited pair of papers reporting that REM sleep deprivation impairs the consolidation of initial spatial learning in the Morris water maze. We hypothesized that REM sleep deprivation following training would impair both hippocampus-dependent spatial learning and learning a new target location within a familiar environment: reversal learning. A 6-d protocol was divided into the initial spatial learning phase (3.5 d) immediately followed by the reversal phase (2.5 d). During the 6 h following four or 12 training trials/day of initial or reversal learning phases, REM sleep was eliminated and non-REM sleep left intact using the multiple inverted flowerpot method. Contrary to our hypotheses, REM sleep deprivation during four or 12 trials/day of initial spatial or reversal learning did not affect training performance. However, some probe trial measures indicated REM sleep-deprivation–associated impairment in initial spatial learning with four trials/day and enhancement of subsequent reversal learning. In naive animals, REM sleep deprivation during normal initial spatial learning was followed by a lack of preference for the subsequent reversal platform location during the probe. Our findings contradict reports that REM sleep is essential for spatial learning in the Morris water maze and newly reveal that short periods of REM sleep deprivation do not impair concurrent reversal learning. Effects on subsequent reversal learning are consistent with the idea that REM sleep serves the consolidation of incompletely learned items.
Inositol Polyphosphate 5-Phosphatase7 Regulates the Production of Reactive Oxygen Species and Salt Tolerance in Arabidopsis
Authors: Kaye Yuval , Golani Yael , Singer Yaniv , Leshem Yehoram , Cohen Gil , Ercetin Mustafa , Gillaspy Glenda , Levine Alex
Published: June 2011

Plants possess remarkable ability to adapt to adverse environmental conditions. The adaptation process involves the removal of many molecules from organelles, especially membranes, and replacing them with new ones. The process is mediated by an intracellular vesicle-trafficking system regulated by phosphatidylinositol (PtdIns) kinases and phosphatases. Although PtdIns comprise a fraction of membrane lipids, they function as major regulators of stress signaling. We analyzed the role of PtdIns 5-phosphatases (5PTases) in plant salt tolerance. The Arabidopsis (Arabidopsis thaliana) genome contains 15 At5PTases. We analyzed salt sensitivity in nine At5ptase mutants and identified one (At5ptase7) that showed increased sensitivity, which was improved by overexpression. At5ptase7 mutants demonstrated reduced production of reactive oxygen species (ROS). Supplementation of mutants with exogenous PtdIns dephosphorylated at the D5′ position restored ROS production, while PtdIns(4,5)P2, PtdIns(3,5)P2, or PtdIns(3,4,5)P3 were ineffective. Compromised salt tolerance was also observed in mutant NADPH Oxidase, in agreement with the low ROS production and salt sensitivity of PtdIns 3-kinase mutants and with the inhibition of NADPH oxidase activity in wild-type plants. Localization of green fluorescent protein-labeled At5PTase7 occurred in the plasma membrane and nucleus, places that coincided with ROS production. Analysis of salt-responsive gene expression showed that mutants failed to induce the RD29A and RD22 genes, which contain several ROS-dependent elements in their promoters. Inhibition of ROS production by diphenylene iodonium suppressed gene induction. In summary, our results show a nonredundant function of At5PTase7 in salt stress response by regulating ROS production and gene expression.
Conserved and Divergent Rhythms of Crassulacean Acid Metabolism-Related and Core Clock Gene Expression in the Cactus Opuntia ficus-indica
Authors: Mallona Izaskun , Egea-Cortines Marcos , Weiss Julia
Published: June 2011

The cactus Opuntia ficus-indica is a constitutive Crassulacean acid metabolism (CAM) species. Current knowledge of CAM metabolism suggests that the enzyme phosphoenolpyruvate carboxylase kinase (PPCK) is circadian regulated at the transcriptional level, whereas phosphoenolpyruvate carboxylase (PEPC), malate dehydrogenase (MDH), NADP-malic enzyme (NADP-ME), and pyruvate phosphate dikinase (PPDK) are posttranslationally controlled. As little transcriptomic data are available from obligate CAM plants, we created an expressed sequence tag database derived from different organs and developmental stages. Sequences were assembled, compared with sequences in the National Center for Biotechnology Information nonredundant database for identification of putative orthologs, and mapped using Kyoto Encyclopedia of Genes and Genomes Orthology and Gene Ontology. We identified genes involved in circadian regulation and CAM metabolism for transcriptomic analysis in plants grown in long days. We identified stable reference genes for quantitative polymerase chain reaction and found that OfiSAND, like its counterpart in Arabidopsis (Arabidopsis thaliana), and OfiTUB are generally appropriate standards for use in the quantification of gene expression in O. ficus-indica. Three kinds of expression profiles were found: transcripts of OfiPPCK oscillated with a 24-h periodicity; transcripts of the light-active OfiNADP-ME and OfiPPDK genes adapted to 12-h cycles, while transcript accumulation patterns of OfiPEPC and OfiMDH were arrhythmic. Expression of the circadian clock gene OfiTOC1, similar to Arabidopsis, oscillated with a 24-h periodicity, peaking at night. Expression of OfiCCA1 and OfiPRR9, unlike in Arabidopsis, adapted best to a 12-h rhythm, suggesting that circadian clock gene interactions differ from those of Arabidopsis. Our results indicate that the evolution of CAM metabolism could be the result of modified circadian regulation at both the transcriptional and posttranscriptional levels.
An investigation of the safety and pharmacokinetics of the novel TRPV1 antagonist XEN‐D0501 in healthy subjects
Authors: Round Patrick , Priestley Anthony , Robinson Jan
Published: June 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Transient receptor potential vanilloid 1(TRPV1) receptor antagonists have the potential to be used in a wide variety of indications. Whilst many compounds have been evaluated pre‐clinically, published clinical data are sparse. A possible dose‐limiting effect of TRPV1 antagonists is their potential to cause hyperthermia.

WHAT THIS STUDY ADDS

• This study reports the safety and pharmacokinetic data for XEN‐D0501, a novel TRPV1 antagonist, in healthy subjects including effects on body temperature.

AIMS XEN‐D0501, a novel TRPV1 antagonist, is being developed to treat overactive bladder. This study investigated the safety and pharmacokinetics of repeat‐dose XEN‐D0501 in healthy subjects.

METHODS The study was conducted in two parts. Part 1 was a double‐blind, randomized, placebo‐controlled, two‐way crossover study in three cohorts of 12 young male subjects. Each subject received XEN‐D0501 and placebo (in random order) twice daily for 13 days, with a final single dose on day 14. Doses of 1, 2.5 and 5 mg XEN‐D0501 were investigated. Part 2 was an open‐label, randomized, two‐way crossover study in male and female subjects (45 to 65 years). Subjects received single doses of 5 mg XEN‐D0501 under fasted and fed conditions in random order. Blood sampling and safety assessments were conducted throughout the study.

RESULTS XEN‐D0501 was rapidly absorbed (tmax generally 0.5–4 h post dose). XEN‐D0501 exposure increased less than proportionally to dose over the range studied and exhibited minimal accumulation with twice daily dosing. Food had no clinically relevant effects on the pharmacokinetics of XEN‐D0501. There were no severe or serious adverse events and all doses were well tolerated. A dose‐related increase in body temperature was seen with XEN‐D0501 which attenuated over time. Differences from placebo in mean maximum core body temperatures were 0.22°C, 0.5°C and 0.74°C following 1 mg, 2.5 mg and 5 mg twice daily XEN‐D0501. The observed increase in body temperature was not considered to be of clinical concern.

CONCLUSIONS XEN‐D0501 appeared safe and well tolerated at doses up to 5 mg twice daily for 14 days in healthy subjects.
Novel filaggrin mutation but no other loss-of-function variants found in Ethiopian patients with atopic dermatitis
Authors: Winge M.C.G. , Bilcha K.D. , Liedén A. , Shibeshi D. , Sandilands A. , Wahlgren C.-F. , McLean W.H.I. , Nordenskjöld M. , Bradley M.
Published: June 2011

Background Filaggrin is a key protein involved in maintaining skin barrier function and hydration. Mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris (IV) and are a major predisposing factor for atopic dermatitis (AD) in individuals of European and Asian descent. It has been proposed that FLG mutations are population specific and a difference in the spectra of mutations between different ancestral groups has been described. However, it is unknown whether FLG mutations in the African population are a causative genetic factor for IV and predispose to AD, or whether other mechanisms are more prominent.

Objectives The present aim was to investigate the role of FLG mutations as predisposing factors for IV or AD among individuals from Ethiopia.

Methods A case series of Ethiopian patients with AD (n = 103) and IV (n = 7) together with controls (n = 103; subjects without past or present history of AD, dry skin or atopic manifestations) was collected at the outpatient dermatology clinics at ALERT Dermatology Hospital, Tikur Anbessa Hospital and Gondar University Hospital, Ethiopia. AD was diagnosed by a dermatologist using the U.K. Working Party’s diagnostic criteria. The IV diagnosis was based on clinical examination and genetic testing of the steroid sulphatase gene to exclude X-linked recessive ichthyosis. Patients were studied with direct sequencing (n = 40) and/or allelic discrimination (n = 110). Immunohistochemical analysis was performed for filaggrin expression in the skin of patients (n = 7) and controls (n = 2).

Results The Ethiopian patients and controls were genotyped for the four previously described common European FLG null mutations (R501X, 2282del4, S3247X, R2447X) and no carriers were found. In one patient with AD a novel heterozygous 2-bp deletion, 632del2, leading to a premature stop codon was revealed by direct sequencing. No additional carrier of this deletion or other mutations was found. In addition, no difference in filaggrin expression was detected in AD or IV skin compared with healthy control skin.

Conclusions Our results indicate that FLG loss-of-function-variants are less common in patients with IV and AD in the Ethiopian population, suggesting that other factors may be of importance in the pathogenesis in this ethnic group.
Variation in personality and behavioural plasticity across four populations of the great tit Parus major
Authors: Dingemanse Niels J. , Bouwman Karen M. , van de Pol Martijn , van Overveld Thijs , Patrick Samantha C. , Matthysen Erik , Quinn John L.
Published: June 2011

1. Interest in the evolutionary origin and maintenance of individual behavioural variation and behavioural plasticity has increased in recent years.

2. Consistent individual behavioural differences imply limited behavioural plasticity, but the proximate causes and wider consequences of this potential constraint remain poorly understood. To date, few attempts have been made to explore whether individual variation in behavioural plasticity exists, either within or between populations.

3. We assayed ‘exploration behaviour’ among wild‐caught individual great tits Parus major when exposed to a novel environment room in four populations across Europe. We quantified levels of individual variation within and between populations in average behaviour, and in behavioural plasticity with respect to (i) repeated exposure to the room (test sequence), (ii) the time of year in which the assays were conducted and (iii) the interval between successive tests, all of which indicate habituation to novelty and are therefore of functional significance.

4. Consistent individual differences (‘I’) in behaviour were present in all populations; repeatability (range: 0·34–0·42) did not vary between populations. Exploration behaviour was also plastic, increasing with test sequence – but less so when the interval between subsequent tests was relatively large – and time of year; populations differed in the magnitude of plasticity with respect to time of year and test interval. Finally, the between‐individual variance in exploration behaviour increased significantly from first to repeat tests in all populations. Individuals with high initial scores showed greater increases in exploration score than individuals with low initial scores; individual by environment interaction (‘I × E’) with respect to test sequence did not vary between populations.

5. Our findings imply that individual variation in both average level of behaviour and behavioural plasticity may generally characterize wild great tit populations and may largely be shaped by mechanisms acting within populations. Experimental approaches are now needed to confirm that individual differences in behavioural plasticity (habituation) – not other hidden biological factors – caused the observed patterns of I × E. Establishing the evolutionary causes and consequences of this variation in habituation to novelty constitutes an exciting future challenge.
Female caregivers' perceptions of reasons for violent behaviour among nursing home residents
Authors: GRANEHEIM U. H. , HÖRNSTEN Å. , ISAKSSON U.
Published: June 2011

Accessible summary

Threats and violence against professional caregivers present a growing health and safety problem in elderly care.

Caregivers attribute violent behaviour in the elderly to patient characteristics, caregiver approach and disorder in the environment.

Caregivers involved in a violent situation should strive to see the person behind the behaviour and the frustration that may have prompted it, to understand what the behaviour is meant to communicate, and to tailor interventions to the individual.

Threats and violence against professional caregivers present a growing health and safety problem in elderly care. We aimed to explore female caregivers' perceptions of reasons for violent behaviour among nursing home residents. Forty‐one caregivers at three nursing homes were interviewed and their responses were subjected to qualitative content analysis, which revealed three content areas of perceived reasons for patient violence: patient characteristics, caregiver approach and environmental aspects. The caregivers' perceptions were formulated in three core statements: ‘they (the residents) are not who they used to be’, ‘we (the caregivers) have acted inappropriately’ and ‘we (residents and caregivers) are all surrounded by disorder’. Our findings indicate that the reasons for violence are complex and multifactorial, so interventions should be individually tailored. Caregivers involved in a violent situation need to see the person behind the behaviour, try to interpret what the behaviour is meant to communicate and adjust the intervention according to individual need.
Transition of stable isotope ratios of leaf water under simulated dew formation
Authors: KIM KYOUNGHEE , LEE XUHUI
Published: June 2011

Dew formation, a common meteorological phenomenon, is expected to intensify in the future. Dew can influence the H218O and HDO isotopic compositions of leaf water (δL), but the phenomenon has been neglected in many experimental and modelling studies. In this study, the dew effect on δL was investigated with a dark plant chamber in which dew formation was introduced. The H218O and HDO compositions of water vapour, dew water and leaf water of five species were measured for up to 48 h of dew exposure. Our results show that the exchanges of H218O and HDO in leaf water with the air continued in the darkness when the net H216O flux was zero. Our estimates of the leaf conductance using the isotopic mass balance method ranged from 0.035 to 0.087 mol m−2 s−1, in broad agreement of the night‐time stomatal conductance reported in the literature. In our experiments, the conductance of the C4 species was 0.04 ± 0.01 mol m−2 s−1 and that of the C3 plants was 0.10 ± 0.04 mol m−2 s−1. At the end of 16 h dew exposure, 72 (±17) and 94 (±11)% of the leaf water came from dew according to the 18O and D tracer, respectively.
High temperature triggers the metabolism of S‐nitrosothiols in sunflower mediating a process of nitrosative stress which provokes the inhibition of ferredoxin–NADP reductase by tyrosine nitration
Authors: CHAKI MOUNIRA , VALDERRAMA RAQUEL , FERNÁNDEZ‐OCAÑA ANA M. , CARRERAS ALFONSO , GÓMEZ‐RODRÍGUEZ MARIA V. , LÓPEZ‐JARAMILLO JAVIER , BEGARA‐MORALES JUAN C. , SÁNCHEZ‐CALVO BEATRIZ , LUQUE FRANCISCO , LETERRIER MARINA , CORPAS FRANCISCO J. , BARROSO JUAN B.
Published: June 2011

High temperature (HT) is considered a major abiotic stress that negatively affects both vegetative and reproductive growth. Whereas the metabolism of reactive oxygen species (ROS) is well established under HT, less is known about the metabolism of reactive nitrogen species (RNS). In sunflower (Helianthus annuus L.) seedlings exposed to HT, NO content as well as S‐nitrosoglutathione reductase (GSNOR) activity and expression were down‐regulated with the simultaneous accumulation of total S‐nitrosothiols (SNOs) including S‐nitrosoglutathione (GSNO). However, the content of tyrosine nitration (NO2‐Tyr) studied by high‐performance liquid chromatography with tandem mass spectrometry (LC–MS/MS) and by confocal laser scanning microscope was induced. Nitroproteome analysis under HT showed that this stress induced the protein expression of 13 tyrosine‐nitrated proteins. Among the induced proteins, ferredoxin–NADP reductase (FNR) was selected to evaluate the effect of nitration on its activity after heat stress and in vitro conditions using 3‐morpholinosydnonimine (SIN‐1) (peroxynitrite donor) as the nitrating agent, the FNR activity being inhibited. Taken together, these results suggest that HT augments SNOs, which appear to mediate protein tyrosine nitration, inhibiting FNR, which is involved in the photosynthesis process.
Powdery scab resistance in Solanum tuberosum: an assessment of cultivar × environment effect
Authors: Merz U. , Lees A. K. , Sullivan L. , Schwärzel R. , Hebeisen T. , Kirk H. G. , Bouchek‐Mechiche K. , Hofferbert H. R.
Published: June 2011

Powdery scab of potato caused by Spongospora subterranea is one of the main disease problems in many potato production regions of the world. However, no efficient and economically sound control method is currently available. Host resistance will be a key component of the integrated management of powdery scab, but there are discrepancies in published powdery scab resistance ratings of cultivars between countries. In order to identify the main factors causing such discrepancies, 10 reference cultivars thought to have a range of susceptibility to powdery scab and potato mop‐top virus were cropped over 4 years in four to six locations across Europe and disease levels on roots and tubers were assessed using standardized scoring scales. Soil contamination was tested using real‐time PCR and ELISA. The cultivars performed as expected according to previous characterization, with one exception. No relationship was found between tuber and root susceptibility. Assessment of powdery scab symptoms 1 month before harvest gave results comparable to those assessed 2 months after harvest. Neither real‐time PCR nor ELISA soil test results were closely related to disease index data. The field trial results indicate that different scoring methods are the main factor for the discrepancy in resistance ratings, and that environmental conditions and/or soil inoculum level play a minor role. Furthermore, there was either no difference between the pathogen populations in each location or the resistance of most of the cultivars is polygenic.
Characterization and interpretation of discontinuity surfaces in a Jurassic ramp setting (High Atlas, Morocco)
Authors: CHRIST NICOLAS , IMMENHAUSER ADRIAN , AMOUR FRÉDÉRIC , MUTTI MARIA , TOMÁS SARA , AGAR SUSAN M. , ALWAY ROBERT , KABIRI LAHCEN
Published: June 2011

Discontinuity surfaces are widely recognized but often poorly understood features of epeiric carbonate settings. In sedimentary systems, these features often represent hiatus surfaces below biostratigraphic resolution and may represent a considerable portion of the time contained in the sediment record. From an applied perspective, discontinuities may represent horizontal flow barriers and result in reservoir compartmentalization. Here, a total of 80 condensed surfaces (S1), firmgrounds (S2) and hardgrounds (S3) from a Jurassic (Middle and Upper Bajocian Assoul Formation) ramp setting of the High Atlas in Morocco are carefully documented with respect to their morphology, their secondary impregnation by Fe and Mn oxides and phosphates and their palaeoecological record. A statistical frequency distribution of two surfaces of the S1 type, 1·1 surfaces of the S2 type and 0·4 surfaces of the S3 type per 10 section metres is observed along a 220 m long carbonate succession. Based on two stratigraphically and spatially separated study windows and correlative sections, the stratigraphic frequency distribution, the lateral extent and the nature of facies change across discontinuities are documented in a quantitative manner. Specific features of the study site include the considerable stratigraphic thickness of the Assoul Formation and the conspicuous absence of subaerial‐exposure‐related features. Based on the data presented here, firmground and hardground surfaces are best interpreted as maximum‐regression‐related features. Relative sea‐level lowstand results in a lowered wave base, and wave orbitals and currents result in sea floor omission and lithification. Care must be taken to avoid overly simplistic interpretations, as differences in bathymetry and carbonate facies result in marked changes in discontinuity characteristics in proximal–distal transects. The data shown here are of significance for those concerned with the interpretation of shoal water carbonate environments and are instrumental in the building of more realistic carbonate reservoir flow models.