bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of iTRAQ labelling coupled to OFFGEL fractionation as a proteomic workflow to the analysis of microsomal proteins of Medicago truncatula roots
Authors: Abdallah Cosette , Sergeant Kjell , Guillier Christelle , Dumas-Gaudot Eliane , Leclercq Céline C , Renaut Jenny
Published: June 2012

Background

Shotgun proteomics represents an attractive technical framework for the study of membrane proteins that are generally difficult to resolve using two-dimensional gel electrophoresis. The use of iTRAQ, a set of amine-specific isobaric tags, is currently the labelling method of choice allowing multiplexing of up to eight samples and the relative quantification of multiple peptides for each protein. Recently the hyphenation of different separation techniques with mass spectrometry was used in the analysis of iTRAQ labelled samples. OFFGEL electrophoresis has proved its effectiveness in isoelectric point-based peptide and protein separation in solution. Here we describe the first application of iTRAQ-OFFGEL-LC-MS/MS on microsomal proteins from plant material. The investigation of the iTRAQ labelling effect on peptide electrofocusing in OFFGEL fractionator was carried out on Medicago truncatula membrane protein digests.

Results

In-filter protein digestion, with easy recovery of a peptide fraction compatible with iTRAQ labelling, was successfully used in this study. The focusing quality in OFFGEL electrophoresis was maintained for iTRAQ labelled peptides with a higher than expected number of identified peptides in basic OFFGEL-fractions. We furthermore observed, by comparing the isoelectric point (pI) fractionation of unlabelled versus labelled samples, a non-negligible pI shifts mainly to higher values.

Conclusions

The present work describes a feasible and novel protocol for in-solution protein digestion in which the filter unit permits protein retention and buffer removal. The data demonstrates an impact of iTRAQ labelling on peptide electrofocusing behaviour in OFFGEL fractionation compared to their native counterpart by the induction of a substantial, generally basic pI shift. Explanations for the occasionally observed acidic shifts are likewise presented.
Hybrid iterative method for finding common solutions of generalized mixed equilibrium and fixed point problems
Authors: Ceng Lu-Chuan , Guu Sy-Ming , Yao Jen-Chih
Published: June 2012

Recently, Colao et al. (J Math Anal Appl 344:340-352, 2008) introduced a hybrid viscosity approximation method for finding a common element of the set of solutions of an equilibrium problem and the set of fixed points of a finite family of nonexpansive mappings in a real Hilbert space. In this paper, by combining Colao, Marino and Xu's hybrid viscosity approximation method and Yamada's hybrid steepest-descent method, we propose a hybrid iterative method for finding a common element of the set GMEP of solutions of a generalized mixed equilibrium problem and the set

⋂

i
=
1

N

Fix (

S

i

)

of fixed points of a finite family of nonexpansive mappings

{

S

i

}

i
=
1

N

in a real Hilbert space. We prove the strong convergence of the proposed iterative algorithm to an element of

⋂

i
=
1

N

Fix (

S

i

)

∩
G
M
E
P

, which is the unique solution of a variational inequality.

AMS subject classifications: 49J40; 47J20; 47H09.
Differential Roles of Galanin on Mechanical and Cooling Responses at the Primary Afferent Nociceptor
Authors: Hulse Richard P , Donaldson Lucy F , Wynick David
Published: June 2012

Background:

Galanin is expressed in a small percentage of intact small diameter sensory neurons of the dorsal root ganglia and in the afferent terminals of the superficial lamina of the dorsal horn of the spinal cord. The neuropeptide modulates nociception demonstrating dose-dependent pro- and anti-nociceptive actions in the naïve animal. Galanin also plays an important role in chronic pain, with the anti-nociceptive actions enhanced in rodent neuropathic pain models. In this study we compared the role played by galanin and its receptors in mechanical and cold allodynia by identifying individual rat C-fibre nociceptors and characterising their responses to mechanical or acetone stimulation.

Results:

Mechanically evoked responses in C-fibre nociceptors from naive rats were sensitised after close intra-arterial infusion of galanin or Gal2-11 (a galanin receptor-2/3 agonist) confirming previous data that galanin modulates nociception via activation of GalR2. In contrast, the same dose and route of administration of galanin, but not Gal2-11, inhibited acetone and menthol cooling evoked responses, demonstrating that this inhibitory mechanism is not mediated by activation of GalR2. We then used the partial saphenous nerve ligation injury model of neuropathic pain (PSNI) and the complete Freund's adjuvant model of inflammation in the rat and demonstrated that close intra-arterial infusion of galanin, but not Gal2-11, reduced cooling evoked nociceptor activity and cooling allodynia in both paradigms, whilst galanin and Gal2-11 both decreased mechanical activation thresholds. A previously described transgenic mouse line which inducibly over-expresses galanin (Gal-OE) after nerve injury was then used to investigate whether manipulating the levels of endogenous galanin also modulates cooling evoked nociceptive behaviours after PSNI. Acetone withdrawal behaviours in naive mice showed no differences between Gal-OE and wild-type (WT) mice. 7-days after PSNI Gal-OE mice demonstrated a significant reduction in the duration of acetone-induced nociceptive behaviours compared to WT mice.

Conclusions:

These data identify a novel galaninergic mechanism that inhibits cooling evoked neuronal activity and nociceptive behaviours via a putative GalR1 mode of action that would also be consistent with a TRP channel-dependent mechanism.
LINE-1 methylation status and its association with tetralogy of fallot in infants
Authors: Sheng Wei , Wang Huijun , Ma Xiaojing , Qian Yanyan , Zhang Ping , Wu Yao , Zheng Fengyun , Chen Long , Huang Guoying , Ma Duan
Published: June 2012

Background

Methylation levels of long interspersed nucleotide elements (LINE-1) are representative of genome-wide methylation status and play an important role in maintaining genomic stability and gene expression. To derive insight into the association between genome-wide methylation status and tetralogy of fallot (TOF), we compared the methylation status of LINE-1 element between TOF patients and controls. The methylation of the NKX 2–5, HAND 1, and TBX 20 promoter regions was also evaluated.

Methods

Genomic DNA from right ventricular tissue samples was obtained from 32 patients with TOF and 15 control subjects. Sequenom MassARRAY platform was performed to examine the methylation levels of LINE-1, NKX2-5, HAND1 and TBX20. Mann–Whitney U test was used to compare differences in methylation levels between two groups.

Results

The methylation level of LINE-1 was significantly lower in patients with TOF, with a median of 57.95% (interquartile range [IQR]: 56.10%–60.04%), as opposed to 59.70% in controls (IQR: 59.00%–61.30%; P = 0.0021). The highest LINE-1 methylation level was 61.3%. The risk of TOF increased in subjects with the lowest methylation levels (less than or equal to 59.0%; OR = 14.7, 95% CI: 1.8–117.7, P = 0.014) and in those with medium methylation levels (59.0%–61.3%; OR = 2.0, 95% CI: 0.3–14.2, P = 0.65). An ROC curve analysis showed a relatively high accuracy of using the LINE-1 methylation level in predicting the presence of TOF (AUC = 0.78, 95% CI: 0.65–0.91; P = 0.002). The association of the LINE-1 methylation level with TOF was only observed in males (P = 0.006) and not in females (P = 0.25). Neither age nor gender was found to be associated with the LINE-1 methylation level in patients or controls. Higher methylation levels of NKX2-5 and HAND1 and lower methylation levels of TBX20 were also observed in patients with TOF than in controls. No association was found between the methylation levels of NKX2-5, HAND1 and TBX 20 with the LINE-1 methylation level.

Conclusions

Lower LINE-1 methylation levels are associated with increased risk of TOF and may provide important clues for the development of TOF.
Establishment and characterization of a sustained delayed-type hypersensitivity model with arthritic manifestations in C57BL/6J mice
Authors: Atkinson Sara M , Usher Pernille A , Kvist Peter H , Markholst Helle , Haase Claus , Nansen Anneline
Published: June 2012

Introduction

Rheumatoid arthritis (RA) is a chronic progressive, inflammatory and destructive autoimmune disease, characterised by synovial joint inflammation and bone erosion. To better understand the pathophysiology and underlying immune mechanisms of RA various models of arthritis have been developed in different inbred strains of mice. Establishment of arthritis models with components of adaptive immunity in the C57BL/6J strain of mice has been difficult, and since most genetically modified mice are commonly bred on this background, there is a need to explore new ways of obtaining robust models of arthritis in this strain. This study was undertaken to establish and characterise a novel murine model of arthritis, the delayed-type hypersensitivity (DTH)-arthritis model, and evaluate whether disease can be treated with compounds currently used in the treatment of RA.

Methods

DTH-arthritis was induced by eliciting a classical DTH reaction in one paw with methylated bovine serum albumin (mBSA), with the modification that a cocktail of type II collagen monoclonal antibodies was administered between the immunisation and challenge steps. Involved cell subsets and inflammatory mediators were analysed, and tissue sections evaluated histopathologically. Disease was treated prophylactically and therapeutically with compounds used in the treatment of RA.

Results

We demonstrate that DTH-arthritis could be induced in C57BL/6 mice with paw swelling lasting for at least 28 days and that disease induction was dependent on CD4+ cells. We show that macrophages and neutrophils were heavily involved in the observed pathology and that a clear profile of inflammatory mediators associated with these cell subsets was induced locally. In addition, inflammatory markers were observed systemically. Furthermore, we demonstrate that disease could be both prevented and treated.

Conclusions

Our findings indicate that DTH-arthritis shares features with both collagen-induced arthritis (CIA) and human RA. DTH-arthritis is dependent on CD4+ cells for induction and can be successfully treated with TNFα-blocking biologics and dexamethasone. On the basis of our findings we believe that the DTH-arthritis model could hold potential in the preclinical screening of novel drugs targeting RA. The model is highly reproducible and has a high incidence rate with synchronised onset and progression, which strengthens its potential.
Effect of antidepressive therapy on retinal contrast processing
in depressive disorder
Authors: Bubl Emanuel , Ebert Dieter , Kern Elena , van Elst Ludger Tebartz , Bach Michael
Published: June 2012

Background

Recently, we reported a reduced retinal contrast gain in unmedicated and
medicated patients with major depression.

Aims

To analyse whether the contrast gain normalises after successful
antidepressive therapy by recording the pattern electroretinogram (PERG)
in healthy controls and patients with depression before and after
antidepressive therapy.

Method

Fourteen patients diagnosed with major depression were repeatedly scanned
and the results compared with that from 40 matched controls.

Results

The retinal contrast gain was lower at baseline in patients with
depression, was normalised with remission and correlated with the
severity of depression. Patients who did not achieve remission retained
significantly lower contrast gain at follow-up.

Conclusions

The study provides evidence for a state-dependent modulation of retinal
contrast gain in patients with major depression. Reduced contrast gain
normalised after therapy. A PERG-based contrast gain could serve as a
state marker of depression.
Cardiovascular fitness in males at age 18 and risk of serious depression in adulthood: Swedish prospective population-based study
Authors: Åberg Maria A. I. , Waern Margda , Nyberg Jenny , Pedersen Nancy L. , Bergh Ylva , Åberg N. David , Nilsson Michael , Kuhn H. Georg , Torén Kjell
Published: June 2012

Background

Studies suggest a role for cardiovascular fitness in the prevention of affective disorders.

Aims

To determine whether cardiovascular fitness at age 18 is associated with future risk of serious affective illness.

Method

Population-based Swedish cohort study of male conscripts (n= 1 117 292) born in 1950–1987 with no history of mental illness who were followed for 3–40 years. Data on cardiovascular fitness at conscription were linked with national hospital registers to calculate future risk of depression (requiring in-patient care) and bipolar disorder.

Results

In fully adjusted models low cardiovascular fitness was associated with increased risk for serious depression (hazard ratios (HR)=1.96, 95%, CI 1.71–2.23). No such association could be shown for bipolar disorder (HR=1.11, 95% CI 0.84–1.47).

Conclusions

Lower cardiovascular fitness at age 18 was associated with increased risk of serious depression in adulthood. These results strengthen the theory of a cardiovascular contribution to the aetiology of depression.
Epigenomic Silencing of the BMP-4 Gene in Pituitary Adenomas: A Potential Target for Epidrug-Induced Re-expression
Authors: Yacqub-Usman Kiren , Duong Cuong V. , Clayton Richard N. , Farrell William E.
Published: June 2012

Bone morphogenetic protein (BMP)-4 is a key mediator of anterior pituitary organogenesis. However, through inappropriate expression patterns, BMP-4 is also pathogenic in a pituitary adenoma subtype-specific context. In these cases, increase or decrease in BMP-4 in lactotroph- and corticotroph-derived adenomas, respectively, is consistent with a bifunction role for this protein toward either promotion or inhibition of cell proliferation and hormone secretion. To gain insight into the aberrations responsible for differential expression, we examined BMP-4 transcript and protein expression patterns in the major adenomas subtypes. BMP-4 transcript and protein are differentially expressed and show increase in the majority of prolactinomas relative to normal pituitary, whereas the majority of other adenoma subtypes show reduced expression relative to both prolactinoma and normal pituitaries. Reduced expression of BMP-4 is not associated with change in CpG island methylation status. However, histone tail modifications are apparent, as enrichment for a modification associated with silent genes, H3K27me3, and depletion of a modification associated with active genes, H3K9Ac. In pituitary cell lines, reduced BMP-4 expression is also associated with similar histone tail modifications and contemporaneous increase in CpG island methylation. In these cells, coincubation with the demethylating agent zebularine and histone deacetylase inhibitor, trichostatin A, reversed epigenetic changes and restored expression of BMP-4. These studies show that, in contrast to prolactinomas, other adenoma subtypes show reduced expression of BMP-4 where epidrug induced reexpression, alone or in combination with conventional therapies, may offer new treatment strategies.
Tackling the Health Divide in Europe: The Role of the World Health Organization
Authors: Hunter David J.
Published: June 2012

Europe faces major health challenges in addition to its well-reported economic and financial difficulties. Despite the overall improvement in population health, significant inequalities remain, with a growing gap between rich and poor. WHO Europe, covering fifty-three member states, is committed to helping European governments meet the complex challenge posed by the “silent epidemic” of noncommunicable diseases. In September 2012 WHO launched Health 2020, an ambitious new health policy framework and strategy. Its success requires a whole-of-government and whole-of-society approach to improving health and well-being, informed by the latest evidence on cost-effective interventions. This review considers the prospects for success.
Sertoli-cell-specific knockout of connexin 43 leads to multiple alterations in testicular gene expression in prepubertal mice
Authors: Giese Sarah , Hossain Hamid , Markmann Melanie , Chakraborty Trinad , Tchatalbachev Svetlin , Guillou Florian , Bergmann Martin , Failing Klaus , Weider Karola , Brehm Ralph
Published: June 2012

A significant decline in human male reproductive function has been reported for the past 20 years but the molecular mechanisms remain poorly understood. However, recent studies showed that the gap junction protein connexin-43 (CX43; also known as GJA1) might be involved. CX43 is the predominant testicular connexin (CX) in most species, including in humans. Alterations of its expression are associated with different forms of spermatogenic disorders and infertility. Men with impaired spermatogenesis often exhibit a reduction or loss of CX43 expression in germ cells (GCs) and Sertoli cells (SCs). Adult male transgenic mice with a conditional knockout (KO) of the Gja1 gene [referred to here as connexin-43 (Cx43)] in SCs (SCCx43KO) show a comparable testicular phenotype to humans and are infertile. To detect possible signaling pathways and molecular mechanisms leading to the testicular phenotype in adult SCCx43KO mice and to their failure to initiate spermatogenesis, the testicular gene expression of 8-day-old SCCx43KO and wild-type (WT) mice was compared. Microarray analysis revealed that 658 genes were significantly regulated in testes of SCCx43KO mice. Of these genes, 135 were upregulated, whereas 523 genes were downregulated. For selected genes the results of the microarray analysis were confirmed using quantitative real-time PCR and immunostaining. The majority of the downregulated genes are GC-specific and are essential for mitotic and meiotic progression of spermatogenesis, including Stra8, Dazl and members of the DM (dsx and map-3) gene family. Other altered genes can be associated with transcription, metabolism, cell migration and cytoskeleton organization. Our data show that deletion of Cx43 in SCs leads to multiple alterations of gene expression in prepubertal mice and primarily affects GCs. The candidate genes could represent helpful markers for investigators exploring human testicular biopsies from patients showing corresponding spermatogenic deficiencies and for studying the molecular mechanisms of human male sterility.
A meta-analysis of lymph node metastasis rate for patients with thoracic oesophageal cancer and its implication in delineation of clinical target volume for radiation therapy
Authors: Ding X , Zhang J , Li B , Wang Z , Huang W , Zhou T , Wei Y , Li H
Published: June 2012

Objectives

The objective of this study was to pool the lymph node metastasis rate (LNMR) in patients with thoracic oesophageal cancer (TOC) and to determine which node level should be included when undergoing radiation therapy.

Methods

Qualified studies were identified on Medline, Embase, CBM and the Cochrane Library through to the end of April 2011. Pooled estimates of LNMR were obtained through a random-effect model. Possible effect modifiers which might lead to the statistical heterogeneity were identified through meta-regression, and further subgroup analyses of factors influencing LNMR were performed.

Results

45 observational studies with a total of 18 415 patients were included in the meta-analysis. The pooled estimates of LNMR in upper, middle and lower TOC were 30.7%, 16.8% and 11.0% cervical, 42.0%, 21.1% and 10.5% upper mediastinal, 12.9%, 28.1% and 19.6% middle mediastinal, 2.6%, 7.8% and 23.0% lower mediastinal, and 9%, 21.4% and 39.9% abdominal, respectively. Lymph node metastasis most frequently happened to paratracheal, paraoesophageal, perigastric 106recR and station 7. The most obvious difference (≥15%) of LNMR between two-field and three-field lymphatic dissection occurred in cervical, paratracheal, 106recR and 108.

Conclusions

Through the meta-analysis, more useful information was obtained about clinical target volume (CTV) delineation of TOC patients treated with radiotherapy. However, our study is predominantly a description of squamous carcinoma and the results may not be valid for adenocarcinoma.
Factors influencing the degree of enhancement of prostate cancer on contrast-enhanced transrectal ultrasonography: correlation with biopsy and radical prostatectomy specimens
Authors: Jiang J , Chen Y-Q , Zhu Y-K , Yao X-H , Qi J
Published: June 2012

Objectives

This study was designed to identify factors that influenced the degree of enhancement of prostate cancer on contrast-enhanced transrectal ultrasonography (CETRUS).

Methods

139 patients suspected of prostate cancer were evaluated with CETRUS followed by systematic and targeted transrectal ultrasound-guided biopsies. The degree of enhancement of the lesions was objectively measured using peak intensity with time–intensity curve analysis software. Ultrasound findings were correlated with clinical characteristics as well as biopsy and radical prostatectomy findings.

Results

Prostate cancers were detected in 230 biopsy sites from 91 patients. The mean peak intensity value of prostate cancer was significantly higher than that of the benign lesions (9.82±3.73 vs 7.51±2.97; p<0.001), and the peak intensity value of the cancer foci varied across the prostate. The mixed model analysis revealed that the location and Gleason score of tumour foci were the influencing factors of the peak intensity value, and the former had a stronger influence upon peak intensity than the latter (p=0.000 and 0.040, respectively). However, age, prostate volume or serum prostate-specific antigen of the patient had no significant influence on the peak intensity value (p>0.05). Furthermore, the peak intensity value of tumours larger than 5 mm diameter was significantly higher than tumours of 5 mm or smaller diameter (9.28±2.46 vs 6.69±2.65; p<0.001).

Conclusions

The prostate cancer lesions with a higher Gleason score and larger tumour size which were located in the lateral peripheral zone (PZ) were more likely to show a marked enhancement. Lesions with lower peak intensity that are located in the medial PZ should also be treated as suspicious.
In the zone: understanding zona reticularis function and its transformation by adrenarche
Authors: Bird Ian M
Published: June 2012

The human adrenal cortex comprises three distinct zones with unique steroid products, namely the zona glomerulosa, which secretes the mineralocorticoids, the zona fasciculate, which secretes the glucocorticoids and the zona reticularis (ZR), which at adrenarche, begins to produce the so-called adrenal androgens. Of all the adrenal zones, we still understand control of ZR emergence the least, and yet the consequences of such dysregulation can be devastating. Premature adrenarche is a growing problem and the correspondingly inappropriate emergence of ZR function can negatively influence puberty and lead to adult infertility. Our understanding is limited and more needs to be done. The purpose of these three reviews is to provide a survey of where we are in our current understanding of what adrenarche is, and indeed if it is unique to humans at all. Furthermore, these reviews describe what is also known of how the functional ZR emerges during adrenarche and what steroids of physiologic relevance result beyond the widely known DHEA and DHEAS elevated at this time. Such advances in human, primate and indeed stem-cell biology are clearly laying the foundation for new directions in the hunt for the factors involved in the regulation and functional emergence of a ZR at the appropriate time, as well as insight into how they may fail. Given support for these new directions, considerable progress can clearly be made.
Viscoelastic behavior of biodegradable polyhydroxyalkanoates
Authors: Domínguez-Díaz Maraolina , Romo-Uribe Angel
Published: June 2012

This research focuses on the study of the thermal properties, microstructure, and rheology of biodegradable poly(3-hydroxybutyrate) (PHB) and copolymers containing 5% and 12% of 3-hydroxyvalerate. The attractiveness of the study of these materials is based primarily on the characteristics of biocompatibility and biodegradability of the materials, for their use as substitutes for conventional polymers and in biomedical applications, for which one needs to understand the relationship between their structure and properties. The materials were studied by infrared spectroscopy, thermogravimetric and differential scanning calorimeter analysis, hot-stage polarized optical microscopy, and rheology. The results showed that PHB is not stable in the molten state thus making melt processing difficult. However, 3-hydroxyvalerate reduced the melting transition but increased the thermal stability, opening up the possibility of melt processing. Rheological studies showed that the copolymers display a linear viscoelastic regime, molten 5% 3-hydroxyvalerate exhibited a predominantly elastic behavior, whereas 12% 3-hydroxyvalerate induced a predominantly viscous behavior.
A Prospective Study on the Use of Warfarin in the United Arab Emirates
Authors: Shehab Abdulla , Elnour Asim , Abdulle Abdishakur , Souid Abdul-Kader
Published: June 2012

Objectives:

The aims of this study were to evaluate adherence of patients and medical staff to warfarin guidelines and assess clinical outcome and predictors of treatment failure.

Methods:

This cross-sectional survey involved out- and in-patient subjects receiving warfarin. Patient attentiveness, compliance, co-morbidities, complications, and international normalized ratio (INR) as well as adherence of medical staff to established warfarin treatment guidelines were recorded.

Results:

One-hundred-sixty patients were recruited (mean ± SD age = 54 ± 1.3 years; 46% males; 77% overweight/obese). Indications for warfarin were atrial fibrillation (35%), deep vein thrombosis (28%), prosthetic heart valve (20%) and stroke or dilated cardiomyopathy (12%). “Warfarin booklets” were made available to 25% of the patients, and ~80% of the recipients reported inadequate understanding of its content. INR was strictly monitored in 23% of the patients; ~70% never received Information Leaflets; ~88% were unaware of warning labels; and ~58% were unaware that over-thecounter medications may affect warfarin. Therapeutic INR (2.9 ± 0.2; 76 days) was achieved in 73%; 20% had high INR (3.7 ± 0.1; 18.6 days) and 7% had low INR (1.6 ± 0.1; 16.7 days). Of the patients with high INR, 2.5% had major bleeding events. Of the patients with low INR, 5% had thromboembolic events. Poor compliance and co-morbidities were associated with adverse events (p=0.01).

Conclusions:

Attentiveness and adherence to warfarin treatment and monitoring guidelines are suboptimal among patients and medical staff. Novel strategies are necessary to alert patients, pharmacists and physicians on the seriousness of warfarin treatment failure.
FGF-23 Levels in Patients with AKI and Risk of Adverse Outcomes
Authors: Leaf David E. , Wolf Myles , Waikar Sushrut S. , Chase Herbert , Christov Marta , Cremers Serge , Stern Leonard
Published: June 2012

Background and objectives

Fibroblast growth factor 23 plays an important role in regulating phosphate and vitamin D homeostasis. Elevated levels of fibroblast growth factor 23 are independently associated with mortality in patients with CKD and ESRD. Whether fibroblast growth factor 23 levels are elevated and associated with adverse outcomes in patients with AKI has not been studied.

Design, setting, participants, & measurements

This study had 30 participants with AKI, which was defined as an increase in serum creatinine≥0.3 mg/dl or ≥50% from baseline, and 30 controls from the general hospital wards and intensive care units. Plasma levels of C-terminal fibroblast growth factor 23 and vitamin D metabolites were measured within 24 hours of AKI onset and 5 days later. The composite endpoint was death or need for renal replacement therapy.

Results

Enrollment fibroblast growth factor 23 levels were significantly higher among participants with AKI than controls (median [interquartile range]=1471 [224–2534] versus 263 [96–574] RU/ml, P=0.003). Enrollment fibroblast growth factor 23 correlated negatively with 25-hydroxyvitamin D (r=−0.43, P<0.001) and 1,25-dihydroxyvitamin D (r=−0.39, P=0.003) and positively with phosphate (r=0.32, P=0.02) and parathyroid hormone (r=0.37, P=0.005). Among participants with AKI, enrollment fibroblast growth factor 23 (but not other serum parameters) was significantly associated with the composite endpoint, even after adjusting for age and enrollment serum creatinine (11 events; adjusted odds ratio per 1 SD higher ln[fibroblast growth factor 23]=13.73, 95% confidence interval=1.75–107.50).

Conclusions

Among patients with AKI, fibroblast growth factor 23 levels are elevated and associated with greater risk of death or need for renal replacement therapy.
Doc2b Is a Key Effector of Insulin Secretion and Skeletal Muscle Insulin Sensitivity
Authors: Ramalingam Latha , Oh Eunjin , Yoder Stephanie M. , Brozinick Joseph T. , Kalwat Michael A. , Groffen Alexander J. , Verhage Matthijs , Thurmond Debbie C.
Published: June 2012

Exocytosis of intracellular vesicles, such as insulin granules, is carried out by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) and Sec1/Munc18 (SM) proteins. An additional regulatory protein, Doc2b (double C2 domain), has recently been implicated in exocytosis from clonal β-cells and 3T3-L1 adipocytes. Here, we investigated the role of Doc2b in insulin secretion, insulin sensitivity, and the maintenance of whole-body glucose homeostasis. Doc2b heterozygous (Doc2b+/−) and homozygous (Doc2b−/−) knockout mice exhibited significant whole-body glucose intolerance and peripheral insulin resistance, compared with wild-type littermates. Correspondingly, Doc2b+/− and Doc2b−/− mice exhibited decreased responsiveness of pancreatic islets to glucose in vivo, with significant attenuation of both phases of insulin secretion ex vivo. Peripheral insulin resistance correlated with ablated insulin-stimulated glucose uptake and GLUT4 vesicle translocation in skeletal muscle from Doc2b-deficient mice, which was coupled to impairments in Munc18c-syntaxin 4 dissociation and in SNARE complex assembly. Hence, Doc2b is a key positive regulator of Munc18c-syntaxin 4–mediated insulin secretion as well as of insulin responsiveness in skeletal muscle, and thus a key effector for glucose homeostasis in vivo. Doc2b’s actions in glucose homeostasis may be related to its ability to bind Munc18c and/or directly promote fusion of insulin granules and GLUT4 vesicles in a stimulus-dependent manner.
Alagebrium Reduces Glomerular Fibrogenesis and Inflammation Beyond Preventing RAGE Activation in Diabetic Apolipoprotein E Knockout Mice
Authors: Watson Anna M.D. , Gray Stephen P. , Jiaze Li , Soro-Paavonen Aino , Wong Benedict , Cooper Mark E. , Bierhaus Angelika , Pickering Raelene , Tikellis Christos , Tsorotes Despina , Thomas Merlin C. , Jandeleit-Dahm Karin A.M.
Published: June 2012

Advanced glycation end products (AGEs) are important mediators of diabetic nephropathy that act through the receptor for AGEs (RAGE), as well as other mechanisms, to promote renal inflammation and glomerulosclerosis. The relative contribution of RAGE-dependent and RAGE-independent signaling pathways has not been previously studied in vivo. In this study, diabetic RAGE apoE double-knockout (KO) mice with streptozotocin-induced diabetes were treated with the AGE inhibitor, alagebrium (1 mg/kg/day), or the ACE inhibitor, quinapril (30 mg/kg/day), for 20 weeks, and renal parameters were assessed. RAGE deletion attenuated mesangial expansion, glomerular matrix accumulation, and renal oxidative stress associated with 20 weeks of diabetes. By contrast, inflammation and AGE accumulation associated with diabetes was not prevented. However, treatment with alagebrium in diabetic RAGE apoE KO mice reduced renal AGE levels and further reduced glomerular matrix accumulation. In addition, even in the absence of RAGE expression, alagebrium attenuated cortical inflammation, as denoted by the reduced expression of monocyte chemoattractant protein-1, intracellular adhesion molecule-1, and the macrophage marker cluster of differentiation molecule 11b. These novel findings confirm the presence of important RAGE-independent as well as RAGE-dependent signaling pathways that may be activated in the kidney by AGEs. This has important implications for the design of optimal therapeutic strategies for the prevention of diabetic nephropathy.
Associations Between the Ankle-Brachial Index and Cardiovascular and All-Cause Mortality Are Similar in Individuals Without and With Type 2 Diabetes
Authors: Hanssen Nordin M.J. , Huijberts Maya S. , Schalkwijk Casper G. , Nijpels Giel , Dekker Jacqueline M. , Stehouwer Coen D.A.
Published: June 2012

OBJECTIVE

In the general population, a low ankle-brachial index (ABI) (<0.9) is strongly associated with (cardiovascular) mortality. However, the association between the ABI and mortality may be weaker in individuals with diabetes, as ankle pressures may be elevated by medial arterial calcification and arterial stiffening, which occur more frequently in diabetes. Therefore, the aim of this study was to compare the association between ABI and mortality in individuals without and with diabetes.

RESEARCH DESIGN AND METHODS

We studied the associations between ABI and cardiovascular and all-cause mortality in 624 individuals from the Hoorn study, a population-based cohort of 50- to 75-year-old individuals (155 with diabetes and 469 without) followed for a median period of 17.2 years. Data were analyzed using Cox proportional hazards models.

RESULTS

During the follow-up period, 289 of 624 (46.3%) participants died (97 of 155 with and 192 of 469 without diabetes and 52 of 65 with and 237 of 559 without ABI <0.9): 85 (29.4%) of CVD (30 of 155 with and 55 of 469 without diabetes and 20 of 65 with and 65 of 559 without ABI <0.9). A low ABI was strongly associated with cardiovascular mortality (relative risk 2.57 [95% CI 1.50–4.40]) and all-cause mortality (2.02 [1.47–2.76]), after adjustment for Framingham risk factors. The associations of the ABI with mortality did not differ between individuals without and with diabetes for cardiovascular (Pinteraction = 0.45) or all-cause (Pinteraction = 0.63) mortality.

CONCLUSIONS

In the Hoorn Study, associations between ABI and cardiovascular and all-cause mortality were similar in individuals without and with diabetes. Future studies should investigate, in both individuals without and with diabetes, whether measurement of ABI can be used to guide treatment decisions.
Promoting Pollution Prevention in Small Businesses: Costs and Benefits of the “Enviroclub” Initiative
Authors: Lanoie Paul , Rochon-Fabien Alexandra
Published: June 2012

The Enviroclub initiative was developed by three federal government agencies—Canada Economic Development for Quebec Regions, Environment Canada, and the National Research Council Canada—and launched in 2001 to assist small and medium-sized enterprises (SMEs) in improving their profitability and competitiveness through enhanced environmental performance. An Enviroclub consists of a group of 10 to 15 SMEs involved in training sessions on environmental management and carrying out at least one profitable in-plant pollution prevention project. The objective of this article is to provide a cost-benefit analysis (CBA) of this original initiative in order to inform policy-makers as to the social desirability of such programs. One of the main social benefits of this initiative is to reduce emissions of various pollutants, so that one of our largest challenges is to place a value on these environmental improvements. To do so, we use the “environmental value transfer” method to obtain values from previous relevant studies. We conduct our CBA at three different levels: we consider the costs and benefits first for the whole of society, then from the participating firms' point of view and, finally, from governments' perspective. We conclude that, whichever perspective we choose, the Enviroclub initiative has been highly profitable.
Long-term radiosurgical control of subtotally resected adult pineocytomas
Authors: Wilson David A. , Awad Al-Wala , Brachman David , Coons Stephen W. , McBride Heyoung , Youssef Emad , Nakaji Peter , Shetter Andrew G. , Smith Kris A. , Spetzler Robert F. , Sanai Nader
Published: June 2012

Object

The optimal management of pineocytomas remains controversial. Although the value of complete microsurgical removal is well accepted, gross-total resection is not always feasible. Data regarding the role of postoperative adjuvant stereotactic radiosurgery (SRS) for residual disease is limited and conflicting. Here, the authors review the largest single-institution experience with multimodal pineocytoma management in an effort to quantify the utility of adjuvant radiosurgical treatment of residual disease.

Methods

The medical records and radiographic studies for all patients with histologically confirmed pineocytoma at the Barrow Neurological Institute between 1999 and 2011 were retrospectively reviewed. Clinical and radiographic data, including the volumetric extent of resection, were collected retrospectively, and Kaplan-Meier analysis was used to identify progression-free survival.

Results

Fourteen adults with newly diagnosed pineocytomas were surgically treated in the period from 1999 to 2011. The median clinical and radiographic follow-ups were 44 and 53 months, respectively. Twelve patients (86%) underwent microsurgical removal and 2 (14%) underwent endoscopic biopsy. Five patients (36%) had complete resections and 9 (64%) demonstrated residual disease. Three patients (21%) presented with radiographic recurrence at a median interval of 43 months after initial treatment (range 13–83 months). At the time of recurrence, the median preoperative tumor volume was 2.6 cm3. Adjuvant SRS was used to treat 3 subtotally resected tumors (33%) following initial presentation and 2 (66%) at the time of recurrence. Among patients with subtotally resected tumors, progression-free survival was significantly longer (p < 0.05) for those who did as compared with those who did not undergo adjuvant radiosurgery. To date, no patient who underwent adjuvant radiosurgery has demonstrated radiographic or clinical evidence of disease progression.

Conclusions

Microsurgical removal remains the definitive treatment for pineocytomas, yet residual disease can be effectively controlled using adjuvant SRS.
An Examination of the Sensitivity of Sulfur Dioxide, Nitric Oxide, and Nitrogen Dioxide Concentrations to the Important Factors Affecting Air Quality Inside a Public Transportation Bus
Authors: Kadiyala Akhil , Kumar Ashok
Published: June 2012

The present study examined the sensitivity of sulfur dioxide (SO2), nitric oxide (NO), and nitrogen dioxide (NO2) concentrations to the important factors affecting air quality inside a public transportation bus. Additionally, this study quantified the in-bus contaminant concentrations in relation to the ranked statistically significant variables. The independent variables to which the monitored contaminant concentrations are the most sensitive to were determined using regression trees and the analysis of variance. A comprehensive one-year database, of the monitored contaminant concentrations and the independent factors that affect an indoor microenvironment (meteorology, monitoring periods, outdoor sources, and ventilation settings) was developed to study the sensitivity of monitored in-bus contaminants. SO2 concentrations were extremely sensitive to the month, weather conditions, and heavy vehicles. NO concentrations were sensitive to the month/season, ventilation, and ambient temperature; while NO2 concentrations were additionally sensitive to the monitoring period and the ambient mixing ratio. Quantified in-bus relationships revealed NO and NO2 concentrations to be less than 0.6 ppm and 0.1 ppm, respectively. SO2 concentrations of 0.4 ppm were observed in the fall-winter months, when the lead heavy vehicles were at a minimum density of 56 per hour; < 0.4 ppm SO2 concentrations remained for the rest of the year.
Gradings, Braidings, Representations, Paraparticles: Some Open Problems
Authors: Kanakoglou Konstantinos
Published: June 2012

A research proposal on the algebraic structure, the representations and the possible applications of paraparticle algebras is structured in three modules: The first part stems from an attempt to classify the inequivalent gradings and braided group structures present in the various parastatistical algebraic models. The second part of the proposal aims at refining and utilizing a previously published methodology for the study of the Fock-like representations of the parabosonic algebra, in such a way that it can also be directly applied to the other parastatistics algebras. Finally, in the third part, a couple of Hamiltonians is proposed, suitable for modeling the radiation matter interaction via a parastatistical algebraic model.
Spreading Behavior and Morphology of Ethylene Methacrylic Acid (EMAA) Deposits via the Flame Spray Process
Authors: Xie Wei , Wang James , Berndt Christopher C.
Published: June 2012

A single splat is the building block of a thermal spray coating; thus, investigating single splats is essential to understanding thermal spray coatings and their properties. In this study, the spreading behavior and the morphology of flame sprayed ethylene methacrylic acid (EMAA) splats, deposited at various stand-off distances (SODs) onto glass and mild steel substrates were investigated using optical microscopy, back scattered scanning electron microscopy and secondary electron scanning electron microscopy. The results of this study indicate that the spread factor increases with an increase in the stand-off distance up to 30 cm for glass and 25 cm for steel substrates. Further increase of the stand-off distance results in a decreased spread factor. The aspect ratio of EMAA single splats on both glass and mild steel substrates decreases with increased stand-off distances, indicating that more circular shapes occur at higher stand-off distances. On mild steel substrates, the minimum unevenness ratio (η) occurs at 35 cm SOD. The unevenness ratio (η) on glass substrates decreases from 1.9 (at 20 cm SOD) to 1.77 (at 25 cm SOD), and from 1.8 (at 30 cm SOD) to 1.3 (at 35 cm SOD). The lowest unevenness ratio (η) is found at 35 cm SOD. The highest unevenness ratio (η) is at 25 cm SOD. This paper discusses the effect of surface chemistry on the underside of an EMAA single splat morphology. It includes Raman spectrum analysis of EMAA and the X-ray diffraction of the EMAA powder. This work analyses the splat morphology and classifies the taxonomy of single splats of EMAA.
NIR Spectroscopic Properties of Aqueous Acids Solutions
Authors: Omar Ahmad Fairuz , Atan Hanafi , MatJafri Mohd Zubir
Published: June 2012

Acid content is one of the important quality attributes in determining the maturity index of agricultural product, particularly fruits. Despite the fact that much research on the measurement of acidity in fruits through non-destructive spectroscopy analysis at NIR wavelengths between 700 to 1,000 nm has been conducted, the same response towards individual acids is not well known. This paper presents NIR spectroscopy analysis on aqueous citric, tartaric, malic and oxalic solutions through quantitative analysis by selecting a set of wavelengths that can best be used to measure the pH of the solutions. The aquaphotomics study of the acid solutions has generated R2 above 0.9 for the measurement of all acids. The most important wavelengths for pH are located at 918–925 nm and 990–996 nm, while at 975 nm for water.
License Plate Recognition Algorithm for Passenger Cars in Chinese Residential Areas
Authors: Jin Lisheng , Xian Huacai , Bie Jing , Sun Yuqin , Hou Haijing , Niu Qingning
Published: June 2012

This paper presents a solution for the license plate recognition problem in residential community administrations in China. License plate images are pre-processed through gradation, middle value filters and edge detection. In the license plate localization module the number of edge points, the length of license plate area and the number of each line of edge points are used for localization. In the recognition module, the paper applies a statistical character method combined with a structure character method to obtain the characters. In addition, more models and template library for the characters which have less difference between each other are built. A character classifier is designed and a fuzzy recognition method is proposed based on the fuzzy decision-making method. Experiments show that the recognition accuracy rate is up to 92%.
Fandom meets activism: Rethinking civic and political participation
Authors: Brough Melissa M. , Shresthova Sangita
Published: June 2012

Fan activism lies at the intersection of cultural and political participation. The study of fan activism can inform our understanding of contemporary collective action more broadly. We suggest four key areas for analysis: the relationships between cultural and political participation; the tension between participation and resistance in the context of fan activism; affect and the role of content worlds in civic and political mobilization; and evaluation of the impacts of fan activism. By drawing on work across several disciplines including media studies and social movement literature, the analysis of fan activism through these lenses offers insights for theorizing contemporary cultures and modes of collective action.
Wonder Woman for a day: Affect, agency, and Amazons
Authors: Yockey Matt
Published: June 2012

I consider the ways in which the feminist utopian ethos of Wonder Woman, as defined by her creator, William Marston, has been used to actualize real-life social change. Specifically, I examine fan Andy Mangels's creation of Wonder Woman Day, a charity event held annually at a Portland, Oregon, comic book store to raise funds for local domestic violence programs. I look at how an affective bond with Wonder Woman informs and guides an affective attachment to one's local and national communities, actualizing the utopian promise of self, commodity icon, and America. These utopian iterations are primarily defined by a celebration of pluralism, and thus Wonder Woman is used to validate the inherent pluralism of the self in relation to society, an empowering strategy for all consumer-citizens.
Flash activism: How a Bollywood film catalyzed civic justice toward a murder trial
Authors: Mehta Ritesh
Published: June 2012

Rang De Basanti's box office success served as a catalyst for flash activism surrounding the Jessica Lall murder trials.
Fan activism for social mobilization: A critical review of the literature
Authors: Bennett Lucy
Published: June 2012

Social media allows fans a chance to know celebrities through the illusion of intimacy, and to effectively organize and mobilize fan activist groups.
"Fan fiction and copyright: Outside works and intellectual property protection," by Aaron Schwabach
Authors: Lantagne Stacey Marie
Published: June 2012

Review of Aaron Schwabach. Fan fiction and copyright: Outside works and intellectual property protection. London: Ashgate, 2011. Hardcover, $89.95 (184p) ISBN 978-0754679035.
Up, up, and away! The power and potential of fan activism
Authors: Jenkins Henry , Shresthova Sangita
Published: June 2012

Editorial for Transformative Works and Cultures, No. 10, special issue, "Transformative Works and Fan Activism."
Iglesia y transición en la diócesis de Orihuela-Alicante
Authors: Moreno Seco Mónica
Published: June 2012

Este artículo estudia la situación de la Iglesia en la diócesis de Orihuela- Alicante durante los años de la transición española. En él se observan las distintas actitudes de la jerarquía, el clero y los movimientos seglares ante la nueva situación política que nacía en 1975.