bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Influence of Light on Microtubule Dynamics and Alignment in the Arabidopsis Hypocotyl
Authors: Sambade Adrian , Pratap Amitesh , Buschmann Henrik , Morris Richard J. , Lloyd Clive 
Published: February 2012

Abstract
Light and dark have antagonistic effects on shoot elongation, but little is known about how these effects are translated into changes of shape. Here we provide genetic evidence that the light/gibberellin–signaling pathway affects the properties of microtubules required to reorient growth. To follow microtubule dynamics for hours without triggering photomorphogenic inhibition of growth, we used Arabidopsis thaliana light mutants in the gibberellic acid/DELLA pathway. Particle velocimetry was used to map the mass movement of microtubule plus ends, providing new insight into the way that microtubules switch between orthogonal axes upon the onset of growth. Longitudinal microtubules are known to signal growth cessation, but we observed that cells also self-organize a strikingly bipolarized longitudinal array before bursts of growth. This gives way to a radial microtubule star that, far from being a random array, seems to be a key transitional step to the transverse array, forecasting the faster elongation that follows. Computational modeling provides mechanistic insight into these transitions. In the faster-growing mutants, the microtubules were found to have faster polymerization rates and to undergo faster reorientations. This suggests a mechanism in which the light-signaling pathway modifies the dynamics of microtubules and their ability to switch between orthogonal axes.
Effects of angiotensin receptor blockers on endothelial nitric oxide release: the role of eNOS variants
Authors: Mason R. Preston , Jacob Robert F. , Kubant Ruslan , Jacoby Adam , Louka Febee , Corbalan J. Jose , Malinski Tadeusz 
Published: January 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Angiotensin II receptor blockers improve endothelial cell‐dependent vasodilation in patients with hypertension through suppression of angiotensin II type 1 receptors but may have additional and differential effects on endothelial nitric oxide synthase (eNOS) function.WHAT THIS STUDY ADDS• The key finding from this study is that angiotensin II receptor blockers (ARBs) differentially enhanced nitric oxide (NO) release in a manner influenced by certain genetic variants of eNOS. This finding provides new insights into the effects of ARBs on endothelial cell‐dependent vasodilation and eNOS function that are of high importance in vascular medicine and clinical pharmacology.AIM Angiotensin II receptor blockers (ARBs) improve endothelial cell (EC)‐dependent vasodilation in patients with hypertension through suppression of angiotensin II type 1 receptors but may have additional and differential effects on endothelial nitric oxide (NO) synthase (eNOS) function. To investigate this question, we tested the effects of various ARBs on NO release in ECs from multiple donors, including those with eNOS genetic variants linked to higher cardiovascular risk.METHODS The effects of ARBs (losartan, olmesartan, telmisartan, valsartan), at 1 µm, on NO release were measured with nanosensors in human umbilical vein ECs obtained from 18 donors. NO release was stimulated with calcium ionophore (1 µm) and its maximal concentration was correlated with eNOS variants. The eNOS variants were determined by a single nucleotide polymorphism in the promoter region (T‐786C) and in the exon 7 (G894T), linked to changes in NO metabolism.RESULTS All of the ARBs caused an increase in NO release as compared with untreated samples (P < 0.01, n= 4–5 in all eNOS variants). However, maximal NO production was differentially influenced by eNOS genotype. Olmesartan increased maximal NO release by 30%, which was significantly greater (P < 0.01, n= 4–5 in all eNOS variants) than increases observed with other ARBs.CONCLUSIONS The ARBs differentially enhanced NO release in ECs in a manner influenced by eNOS single nucleotide polymorphisms. These findings provide new insights into the effects of ARBs on EC‐dependent vasodilation and eNOS function.
Non‐steroidal anti‐inflammatory drugs and the risk of Clostridium difficile‐associated disease
Authors: Suissa Daniel , Delaney Joseph A. C. , Dial Sandra , Brassard Paul 
Published: January 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Increasing age, length of hospital stay and previous antibiotic use have been established as important risk factors in the development of Clostridium difficile associated disease (CDAD). Several case reports over the past 30 years have linked diclofenac, a non‐steroidal anti‐inflammatory drug (NSAID) with CDAD. We assessed whether NSAID use in general, and diclofenac use in particular, is associated with an increased risk of CDAD.WHAT THIS STUDY ADDS• In this population based study, the use of diclofenac was associated with a 35% increase in the risk of developing CDAD. This association persisted when we limited the analysis to non‐hospitalized patients. No association was found between the use of any other NSAIDs and the risk of CDAD.AIM Several case reports have linked diclofenac, a non‐steroidal anti‐inflammatory drug (NSAID), with Clostridium difficile associated disease (CDAD). We assessed whether NSAID use in general, and diclofenac use in particular, is associated with an increased risk of CDAD.METHODS We used the United Kingdom's General Practice Research Database (GPRD) to conduct a population‐based case–control study. All cases of CDAD occurring between 1994 and 2005 were identified and were matched to 10 controls each. Conditional logistic regression was used to estimate the odds ratio of CDAD associated with current NSAID use, adjusting for covariates.RESULTS We identified 1360 CDAD cases and 13 072 controls. We found an increased risk of CDAD associated with diclofenac (adjusted odds ratio (RR) 1.35, 95% confidence interval (CI) 1.10, 1.67). We did not observe an increased risk of CDAD with use of any other NSAID. No dose–response for diclofenac exposure was found. When we analyzed only patients who were not hospitalized in the year before the index date, we found diclofenac to have a similar effect on CDAD risk (adjusted RR 1.43, 95% CI 1.11, 1.84).CONCLUSION Diclofenac use is associated with a modest increase in the risk of CDAD. In patients at risk of CDAD, other NSAIDs could be prescribed.
Effects of genetic variation in the P2RX7 gene on pharmacodynamics of a P2X7 receptor antagonist: a prospective genotyping approach
Authors: McHugh Simon M. , Roman Shilina , Davis Bill , Koch Annelize , Pickett Alison M. , Richardson Jill C. , Miller Sam R. , Wetten Sally , Cox Charles J. , Karpe Fredrik , Todd John A. , Bullmore Edward T. 
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Analysis of allelic variation in large populations has identified numerous single nucleotide polymorphisms (SNPs) in the P2RX7 gene. In vitro transfection has demonstrated SNP‐dependent alterations (gain or loss) of P2X7 receptor function, as measured by ATP‐induced ethidium uptake and interleukin‐1β production.WHAT THIS STUDY ADDS• We provide definitive evidence of SNP‐dependent alteration in P2X7 receptor pharmacodynamics to a specific antagonist (GSK1370319A) in a small sample of prospectively genotyped subjects. These effects on drug response underline the importance of genetic stratification in drug development of P2X7 receptor antagonists.AIMS To investigate the effects of two single nucleotide polymorphisms (SNPs) in the human P2X7 receptor gene (P2RX7) – 1068G>A (A348T) and 1513A>C (E496A) – on P2X7 receptor function, using a specific receptor antagonist (GSK1370319A) and prospective genetic stratification.METHODS Lipopolysaccharide‐ and ATP‐stimulated interleukin‐1β production was determined in the presence or absence of GSK1370319A in blood culture from 32 prospectively genotyped subjects.RESULTS There was approximately 6.7‐fold difference (P < 0.0001) in IC50 for inhibition of ATP‐stimulated interleukin‐1β release by GSK1370319A between individuals with the homozygous gain‐ (1068A) and loss‐of‐function (1513C) genotypes (expressing the 348T, 496E and 348A, 496A alleles, respectively).CONCLUSIONS Leukocyte P2X7 receptors had significantly altered pharmacodynamic responses to a specific antagonist (GSK1370319A), directly related to SNP genotype.
Seasonal bryophyte productivity in the sub‐Arctic: a comparison with vascular plants
Authors: Street Lorna E. , Stoy Paul C. , Sommerkorn Martin , Fletcher Benjamin J. , Sloan Victoria L. , Hill Timothy C. , Williams Mathew 
Published: February 2012

Summary1. Arctic ecosystems are experiencing rapid climate change, which could result in positive feedbacks on climate warming if ecosystem carbon (C) loss exceeds C uptake through plant growth. Bryophytes (mosses, liverworts and hornworts) are important components of Arctic vegetation, but are currently not well represented in terrestrial C models; in particular, seasonal patterns in bryophyte C metabolism compared to vascular plant vegetation are poorly understood.2. Our objective was to quantify land‐surface CO2 fluxes for common sub‐Arctic bryophyte patches (dominated by Polytrichum piliferum and Sphagnum fuscum) in spring (March–May) and during the summer growing season (June–August) and to develop a simple model of bryophyte gross primary productivity fluxes (PB). We use the model to explore the key environmental controls over PB for P. piliferum and S. fuscum and compare seasonal patterns of productivity with those of typical vascular plant communities at the same site.3. The modelled total gross primary productivity (ΣPB) over 1 year (March – November) for P. piliferum was c. 360 g C m−2 ground and for S. fuscum c. 112 g C m−2 ground, c. 90% and 30% of total gross primary productivity for typical vascular plant communities (ΣPV) over the same year. In spring (March–May), when vascular plant leaves are not fully developed, ΣPB for P. piliferum was 3 × ΣPV.4. Model sensitivity analysis indicated that bryophyte turf water content does not significantly affect (March–November) ΣPB for P. piliferum and S. fuscum, at least for periods without sustained lack of precipitation. However, we find that seasonal changes in bryophyte photosynthetic capacity are important in determining ΣPB for both bryophyte species.5. Our study implies that models of C dynamics in the Arctic must include a bryophyte component if they are intended to predict the effects of changes in the timing of the growing season, or of changes in vegetation composition, on Arctic C balance.
An exploration of the experience of mental health service users when they decide they would like to change or withdraw from prescribed medications
Authors: GALE C. , BALDWIN L. , STAPLES V. , MONTAGUE J. , WALDRAM D. 
Published: February 2012

Accessible summary
This study reports on a small collaborative research project started by service users, and on a subject chosen by them, and then carried out with staff from a local NHS Trust and University.
It looks at the choices people make in changing or stopping mental health medications, and their experiences of how professional staffs were either helpful or unhelpful in advising and helping them with these choices. Some of the themes generated in the focus groups are examined in detail and recommendations made for practice including the need for better information giving to support choice.
The themes examined include ‘the two faces of service provision’ which looks at positive and less positive experiences of service provision, the general practice/mental health divide which points out differences and difficulties between general practice and specialist practice, and ‘becoming an informed service user’ which examines the many sources of information available to service users and how they use these.
AbstractThis paper reports on a collaborative research project initiated by service user representatives and led by clinicians from the mental health service in Derbyshire. The study explored the experiences of mental health service users when they either changed or terminated their use of mental health‐related medications. Three focus groups were conducted with mental health service users from across the county. An inductive thematic analysis identified six key themes, three of which are reported here: the ‘two faces’ of service provision, describing the positive and negative experiences of services; the general practice/mental health divide, relating to the lack of continuity between the two services; and becoming an informed service user, where participants discussed the importance of seeking information. It is important that mental health professionals always consider presenting their ‘best face’ to service users, and facilitate the prescribing process with general practitioners. The findings also highlight the potential for supporting service users in using different sources of information to become more informed about medication.
Psychosocial and cultural correlates of depression among Hispanic men with HIV infection: a pilot study
Authors: DE SANTIS J.P. , GONZALEZ‐GUARDA R. M. , VASQUEZ E. P. 
Published: February 2012

Accessible summary
Depression is a common mental health condition among people living with HIV infection.
About one third of the study's participants were depressed.
A history of substance abuse and child/adult violence was common among the participants.
Healthcare providers need awareness of the intersection of HIV, substance abuse, and violence among Hispanic men with HIV infection.
AbstractDepression is a common mental health condition among persons with human immunodeficiency virus (HIV) infection. Depression influences quality of life, social relationships and adherence to medication therapy. Little is known about depression among Hispanic men with HIV infection. The purpose of this pilot study was to describe the relationships of depression to other psychosocial factors (self‐esteem, Hispanic stress, substance abuse and violence) and cultural factors (familism and Hispanic stress) among a sample of Hispanic men with HIV infection. Using a cross‐sectional, descriptive research design a convenience sample of 46 Hispanic men with HIV infection was recruited and surveyed from the South Florida area of the USA. The majority of the participants (65%; n = 30) were depressed. In addition, the majority of participants reported high familism and self‐esteem and low Hispanic stress. A history of substance abuse and childhood and adult violence were common. Significant relationships were noted between depression, and self‐esteem, Hispanic stress, substance abuse, and adult physical violence. Healthcare providers need to be aware of the high rates of depression, substance abuse and violence that may occur among Hispanic men with HIV infection. More research is needed to further explore the relationship of these factors, as well as to determine the impact that these variables have on adherence to medication therapy among Hispanic men with HIV infection.
An Aspergillus nidulans bZIP response pathway hardwired for defensive secondary metabolism operates through aflR
Authors: Yin Wen‐Bing , Amaike Saori , Wohlbach Dana J. , Gasch Audrey P. , Chiang Yi‐Ming , Wang Clay C. C. , Bok Jin Woo , Rohlfs Marko , Keller Nancy P. 
Published: January 2012

SummaryThe eukaryotic bZIP transcription factors are critical players in organismal response to environmental challenges. In fungi, the production of secondary metabolites (SMs) is hypothesized as one of the responses to environmental insults, e.g. attack by fungivorous insects, yet little data to support this hypothesis exists. Here we establish a mechanism of bZIP regulation of SMs through RsmA, a recently discovered YAP‐like bZIP protein. RsmA greatly increases SM production by binding to two sites in the Aspergillus nidulans AflR promoter region, a C6 transcription factor known for activating production of the carcinogenic and anti‐predation SM, sterigmatocystin. Deletion of aflR in an overexpression rsmA (OE:rsmA) background not only eliminates sterigmatocystin production but also significantly reduces asperthecin synthesis. Furthermore, the fungivore, Folsomia candida, exhibited a distinct preference for feeding on wild type rather than an OE:rsmA strain. RsmA may thus have a critical function in mediating direct chemical resistance against predation. Taken together, these results suggest RsmA represents a bZIP pathway hardwired for defensive SM production.
Comparative analysis of phase III migrating motor complexes in stomach and small bowel using wireless motility capsule and antroduodenal manometry
Authors: Brun R. , Michalek W. , Surjanhata B. C. , Parkman H. P. , Semler J. R. , Kuo B. 
Published: February 2012

AbstractBackground  Assessment of phase III MMC is often not performed due to the invasive nature of antroduodenal manometry used to detect it. The aim of the study was to evaluate the ability of wireless motility capsule (WMC) to detect phase III MMC and correlate it with the simultaneous measurements by antroduodenal manometry (ADM).Methods  Eighteen patients underwent simultaneous ADM and WMC. MMCs were identified first on ADM and then correlated with WMC events occurring simultaneously. Frequency of contractions per min, AUC, MI, and criteria for amplitude thresholds of contractions representing MCCs on WMC tracings were defined.Key Results  In 18 patients, a total of 29 MMCs were recorded by ADM. WMC detected 86% of MMC events measured by ADM. Hundred percent (10/10) of MMCs in stomach were detected by WMC, whereas 79% (15/19) of MMCs were detected in SB. The sensitivity and specificity of WMC high amplitude contractions to represent phase III MMC were 90% and 71.8% in the stomach; 73.7% and 84.7% in SB, respectively, and negative predictive value was 99.9% in both regions.Conclusions & Inferences  Wireless motility capsule was able to detect the phase III MMCs as the high amplitude contractions with good fidelity. WMC does not detect the propagation of MMC. Using the pressure thresholds, WMC can detect high amplitude contraction representing phase III MMC with favorable sensitivity/specificity profile and 99.9% negative predictive value. This observation may have clinical significance, as the absence of high amplitude contractions recorded by WMC during fasting state suggests absence of MMCs.
Short‐term electrical stimulation of the lower esophageal sphincter increases sphincter pressure in patients with gastroesophageal reflux disease
Authors: Rodríguez L. , Rodríguez P. , Neto M. G. , Ayala J. C. , Saba J. , Berel D. , Conklin J. , Soffer E. 
Published: February 2012

AbstractBackground  Electrical stimulation (ES) of the lower esophageal sphincter (LES) increases resting LES pressure (LESP) in animal models. Our aims were to evaluate the safety of such stimulation in humans, and test the hypothesis that ES increases resting LESP in patients with gastroesophageal reflux disease (GERD).Methods  A total of 10 subjects (nine female patients, mean age 52.6 years), with symptoms of GERD responsive to PPIs, low resting LES pressure, and abnormal 24‐h intraesophageal pH test were enrolled. Those with hiatal hernia >2 cm and/or esophagitis >Los Angeles Grade B were excluded. Bipolar stitch electrodes were placed longitudinally in the LES during an elective laparoscopic cholecystectomy, secured by a clip and exteriorized through the abdominal wall. Following recovery, an external pulse generator delivered two types of stimulation for periods of 30 min: (i) low energy stimulation; pulse width of 200 μs, frequency of 20 Hz and current of 5–15 mA (current was increased up to 15 mA if LESP was less than 15 mmHg), and (ii) high energy stimulation; pulse width of 375 ms, frequency of 6 cpm, and current 5 mA. Resting LESP, amplitude of esophageal contractions and residual LESP in response to swallows were assessed before and after stimulation. Symptoms of chest pain, abdominal pain, and dysphagia were recorded before, during, and after stimulation and 7‐days after stimulation. Continuous cardiac monitoring was performed during and after stimulation.Key Results  All patients were successfully implanted nine subjects received high frequency, low energy, and four subjects received low frequency, high energy stimulation. Both types of stimulation significantly increased resting LESP: from 8.6 mmHg (95% CI 4.1–13.1) to 16.6 mmHg (95% CI 10.8–19.2), P < 0.001 with low energy stimulation and from 9.2 mmHg (95% CI 2.0–16.3) to 16.5 mmHg (95% CI 2.7–30.1), P = 0.03 with high energy stimulation. Neither type of stimulation affected the amplitude of esophageal peristalsis or residual LESP. No subject complained of dysphagia. One subject had retrosternal discomfort with stimulation at15 mA that was not experienced with stimulation at 13 mA. There were no adverse events or any cardiac rhythm abnormalities with either type of stimulation.Conclusions & Inferences  Short‐term stimulation of the LES in patients with GERD significantly increases resting LESP without affecting esophageal peristalsis or LES relaxation. Electrical stimulation of the LES may offer a novel therapy for patients with GERD.
Low mortality risk but high loss to follow‐up among patients in the Tanzanian national HIV care and treatment programme
Authors: Somi G. , Keogh S. C. , Todd J. , Kilama B. , Wringe A. , van den Hombergh J. , Malima K. , Josiah R. , Urassa M. , Swai R. , Zaba B. 
Published: February 2012

AbstractObjective  To analyse survival and retention rates of the Tanzanian care and treatment programme.Methods  Routine patient‐level data were available from 101 of 909 clinics. Kaplan–Meier probabilities of mortality and attrition after ART initiation were calculated. Mortality risks were corrected for biases from loss to follow‐up using Egger’s nomogram. Smoothed hazard rates showed mortality and attrition peaks. Cox regression identified factors associated with death and attrition. Median CD4 counts were calculated at 6 month intervals.Results  In 88,875 adults, 18% were lost to follow up 12 months after treatment initiation, and 36% after 36 months. Cumulative mortality reached 10% by 12 months (15% after correcting for loss to follow‐up) and 14% by 36 months. Mortality and attrition rates both peaked within the first six months, and were higher among males, those under 45 kg and those with CD4 counts below 50 cells/μl at ART initiation. In the first year on ART, median CD4 count increased by 126 cells/μl, with similar changes in both sexes.Conclusion  Earlier diagnoses through expanded HIV testing may reduce high mortality and attrition rates if combined with better patient tracing systems. Further research is needed to explore reasons for attrition.
Integrating genomic and epigenomic information: a promising strategy for identifying functional DNA variants of human disease
Authors: Zaina S , Lund G 
Published: February 2012

Zaina S, Lund G. Integrating genomic and epigenomic information: a promising strategy for identifying functional DNA variants of human disease.In a clinical setting diagnosis, heritability, risk and outcome of human disease rely heavily on the use of markers present in specific tissues. In the past decade, the development of genome‐wide, non‐hypothesis driven methods to identify molecular markers associated with disease have led to the discovery of numerous genetic variations associated with specific human diseases, the majority of which map within non‐coding regions of the genome. In parallel, whole‐genome studies focused on the role of gene regulatory epigenetic modifications such as DNA methylation and histone modifications are providing a conceptual framework for understanding the functional significance of sequence variation in human disease. This review highlights selected recent development in epigenetics and discusses their implications with respect to the identification of functional or novel single nucleotide polymorphisms.