bluuebunny/crossref_metadata_2025 huggingface dataset:
Exendin-4, a Glucagon-Like Peptide-1 Receptor Agonist, Reduces Alzheimer Disease-Associated Tau Hyperphosphorylation in the Hippocampus of Rats with Type 2 Diabetes
Authors: Xu Weijie , Yang Yan , Yuan Gang , Zhu Wenjun , Ma Delin , Hu Shuhong
Published: October 2015

Background

Impaired insulin signaling pathway in the brain in type 2 diabetes (T2D) is a risk factor for Alzheimer disease (AD). Glucagon-like peptide-1 (GLP-1) and its receptor agonist are widely used for treatment of T2D. Here we studied whether the effects of exendin-4 (EX-4), a long-lasting GLP-1 receptor agonist, could reduce the risk of AD in T2D.

Materials and Methods

Type 2 diabetes rats were injected with EX-4 for 28 consecutive days. Blood glucose and insulin levels, as well as GLP-1 and insulin in cerebrospinal fluid, were determined during the experiment. The phosphorylation level of tau at individual phosphorylation sites, the activities of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT), and glycogen synthase kinase-3β (GSK-3β) were analyzed with Western blots.

Results

The levels of phosphorylated tau protein at site Ser199/202 and Thr217 level in the hippocampus of T2D rats were found to be raised notably and evidently decreased after EX-4 intervention. In addition, brain insulin signaling pathway was ameliorated after EX-4 treatment, and this result was reflected by a decreased activity of PI3K/AKT and an increased activity of GSK-3β in the hippocampus of T2D rats as well as a rise in PI3K/AKT activity and a decline in GSK-3β activity after 4 weeks intervention of EX-4.

Conclusions

These results demonstrate that multiple days with EX-4 appears to prevent the hyperphosphorylation of AD-associated tau protein due to increased insulin signaling pathway in the brain. These findings support the potential use of GLP-1 for the prevention and treatment of AD in individuals with T2D.
Associations of Fibroblast Growth Factor 23 and Fetuin-A with Coronary Plaque Burden and Plaque Composition in Young Adults
Authors: Akin Fatih , Celik Omer , Ayca Burak , Altun Ibrahim , Diker Vesile Ornek , Bıyık Ismail , Siriopol Dimitrie , Covic Adrian , Kanbay Mehmet
Published: October 2015

Objective

The total burden of subclinical coronary artery disease (CAD) is significant among young adults. Serum fibroblast growth factor 23 (FGF-23) and fetuin-A are established predictors of morbidity and mortality because of cardiovascular disease. The objective of the study was to evaluate the relationship between subclinical CAD and serum FGF-23 and fetuin-A concentrations among a population of young adults.

Methods

A total of 241 subjects younger than 45 years who had undergone coronary computed tomographic angiography (CCTA) were included in the study. In 117 patients, the CCTA detected subclinical CAD; the rest of the patients had no CAD detected on CCTA.

Results

Serum FGF-23 and fetuin-A levels were significantly increased in the CAD patients as compared with the non-CAD patients (26.7 [interquartile range, 22.4-31.9] vs 15.7 [interquartile range, 13.2-18.1] pg/mL and 904.7 [interquartile range, 695.5-1021.6] vs 469.6 [331.4-660.5] mg/L, respectively; P < 0.001 for both). Furthermore, a positive correlation was identified between FGF-23 and fetuin-A levels and the total number of plaques ( r = 0.21 and r = 0.28, respectively; P < 0.001 for both). In multivariate logistic regression analysis, age, smoking status, uric acid, FGF-23, and fetuin-A levels were found to be independently associated with the presence of CAD.

Conclusions

The presence of subclinical CAD is independently associated with FGF-23 and fetuin-A and could be used as novel risk markers of cardiovascular disease in the asymptomatic young adult population.
Emergency Department Visits for Acute Pancreatitis in Children
Authors: Pant Chaitanya , Deshpande Abhishek , Sferra Thomas J. , Gilroy Richard , Olyaee Mojtaba
Published: October 2015

Objective

The objective of this study was to describe the epidemiology and trends in pediatric acute pancreatitis (AP)–associated emergency department (ED) visits in the United States.

Methods

Estimates of AP–associated ED visits were calculated in children from birth to 19 years of age using the Nationwide Emergency Department Sample.

Results

From 2006 to 2011, there were an estimated total of 78,787 ED visits associated with the diagnosis of AP. The greatest number of ED visits occurred in children 15 to 19 years of age (67.0%). A majority of patients were subsequently admitted to the hospital for further care (74.1%). Risk factors independently associated with an increased rate of hospital admission included 3 or more comorbid conditions (adjusted odds ratio [aOR] 12.81; 95% confidence interval [CI], 11.29–14.56), children younger than 5 years (aOR, 1.73; 95% CI, 1.58–1.89), presentation to a teaching hospital (aOR, 1.68; 95% CI, 1.62–1.74) or a hospital in the Western region of the United States (aOR, 1.48; 95% 1.42–1.54), and health coverage with Medicaid (aOR, 1.23; 95% CI, 1.17–1.29). Acute pancreatitis–associated ED visits increased from 14.5 per 100,000 children in 2006 to 16.1 per 100,000 children in 2011 (11.42% increase; P < 0.01).

Conclusion

There has been an increasing incidence of AP-associated ED visits in children from 2006 to 2011.
Fractalkine (CX3CL1): A Biomarker Reflecting Symptomatic Severity in Patients with Knee Osteoarthritis
Authors: Huo Li Wei , Ye Yong Liang , Wang Guang Wei , Ye Yong Guang
Published: October 2015

Background

Elevated serum and synovial fluid (SF) fractalkine (CX3CL1) levels have been detected in patients with knee osteoarthritis (OA). The current study was carried out to investigate the association between serum and SF fractalkine levels with symptomatic severity in patients with knee OA.

Method

One hundred ninety-three patients with OA and 182 healthy controls were enrolled in this study. The symptomatic severity was assessed by the Western Ontario McMaster University Osteoarthritis scores.

Results

Fractalkine levels in SF and serum were both positively associated with self-reported greater pain and physical disability.

Conclusions

Fractalkine in SF and serum may serve as a biomarker for reflecting symptomatic severity. Therapeutic interventions that target fractalkine signaling pathways to delay OA-related symptoms deserve further study.
Serum Salusin-β Levels are Associated with the Presence and Severity of Coronary Artery Disease
Authors: Liu Jun , Ren Yin-gang , Zhang Li-hua , Tong Ya-wen , Kang Li
Published: October 2015

Objectives

We sought to assess whether serum salusin-β levels are correlated with the presence and severity of coronary artery disease (CAD).

Methods

We measured serum salusin-β levels in 278 consecutive patients undergoing coronary angiography (CAG) for the evaluation of CAD and in 126 healthy controls. Serum salusin-β levels were measured by enzyme-linked immunosorbent assay. The severity of CAD was assessed by angiographic coronary atherosclerosis index score system.

Results

Serum salusin-β levels were significantly higher in patients undergoing CAG (n = 278) than those in healthy controls (n = 126) (3.81 ± 0.99 vs 4.34 ± 1.40 nmol/L, P < 0.01). In patients undergoing CAG, patients with CAD (n = 160) had significantly higher serum salusin-β levels compared to patients without CAD (n = 118) (4.65 ± 1.44 vs 3.94 ± 1.23 nmol/L, P < 0.01). Multivariate logistic regression analysis revealed that serum salusin-β levels were independently associated with the presence of CAD (odds ratio, 1.439; 95% confidence interval, 1.176–1.760; P < 0.01). Serum salusin-β levels were positively correlated with the coronary atherosclerosis index score (r = 0.316, P < 0.001).

Conclusions

Serum salusin-β levels were associated with the presence and severity of CAD. Salusin-β in serum might serve as a potential biomarker for reflecting the development and progression of CAD. Therapeutic treatment by inhibiting salusin-β interaction to prevent CAD warrants further investigation.
Is High Weight Status Associated with Pediatric Forearm Fractures Requiring Anatomic Reduction?
Authors: Ryan Leticia Manning , Teach Stephen J. , Ezeibe Uchenna , Lall Ambika , Wood Rachel , Chamberlain James M.
Published: October 2015

Background

High weight status is associated with increased forearm fracture risk but its relationship to severity of fracture has not been evaluated. We compared the epidemiology of children's forearm fractures treated with fracture reduction to those not treated with reduction, hypothesizing that high weight status would be significantly associated with need for reduction.

Methods

This is a case-control study including Washington, DC children, ages 2 to 17 years, treated for isolated forearm fractures in an urban, tertiary care pediatric emergency department from 2003 to 2006. Descriptive statistics and logistic regression were conducted to compare patients with forearm fracture reductions to nonintervention controls.

Results

Of 888 forearm fractures, 330 (37.2%) required reduction (cases) whereas 558 (64.8%) did not (controls). Cases were more likely than controls to be male [adjusted odds ratio, 1.67 (95% confidence interval, 1.11–2.50)] and to have experienced a more severe mechanism of trauma [adjusted odds ratio, 2.11 (95% confidence interval, 1.14–3.90)]. The groups did not differ in weight status, age, or race/ethnicity.

Conclusions

The need for reduction among children with forearm fractures is significantly associated with male sex and major mechanisms of trauma but not with high weight status. Strategies to reduce severe forearm fractures should focus on preventing major mechanisms of trauma.
Persistence of Cardiovascular Risk Factors in Women with Previous Preeclampsia: A Long-term Follow-up Study
Authors: Aykas Fatma , Solak Yalcin , Erden Abdulsamet , Bulut Kadir , Dogan Selcuk , Sarli Bahadır , Acmaz Gokhan , Afsar Baris , Siriopol Dimitrie , Covic Adrian , Sharma Shailendra , Johnson Richard J. , Kanbay Mehmet
Published: October 2015

Background

Preeclampsia is a cardiovascular (CV) disease risk factor, and lifestyle modifications are recommended. It was suggested that preeclampsia may increase the prevalence of various CV disease risk factors such as metabolic syndrome, hypertension, insulin resistance, microalbuminuria, and endothelial dysfunction, among others. Here, we investigate the role of serum uric acid in preeclampsia in the development of CV complications.

Materials and Methods

This was an observational case-control study that compared women with history of preeclampsia (n = 25) with age-matched controls with uncomplicated pregnancies (n = 20) who were followed for at least 5 years. Measurements included clinical and ambulatory blood pressure monitoring, ultrasound-measured flow-mediated dilatation (FMD), microalbuminuria, carotid intima-media thickness (CIMT) and serum uric acid, as well as clinical and demographic features. Cardiovascular disease risk factors were compared in women with and without previous preeclampsia.

Results

At the time of index gestation, preeclamptic women had higher serum uric acid values (4.36 ± 0.61 vs 2.27 ± 0.38 mg/dL, P < 0.001). Five years after pregnancy, the patients who had preeclampsia were more likely to have hypertension and had higher serum uric acid levels, higher microalbuminuria and CIMT levels, and lower FMD values than did the patients who did not have preeclampsia. The 2 groups were similar with regard to various ambulatory blood pressure parameters. Univariate associates of FMD were history of preeclampsia and the current hypertension status. Microalbuminuria correlated with gestational uric acid levels (coefficient of correlation of 0.40, P = 0.01 for FMD and coefficient of correlation of 0.37, P = 0.01 for CIMT, respectively).

Conclusions

Preeclampsia might be a risk factor for the development of cardiovascular risk factors at least 5 years after index pregnancy. Serum uric acid and microalbuminuria may be mechanistic mediators of heightened risk, along with impaired endothelial function in preeclampsia.
Aminopeptidase N Activity Predicts 5-Year Survival in Colorectal Cancer Patients
Authors: Sanz Begoña , Perez Itxaro , Beitia Maider , Errarte Peio , Fernández Ainhoa , Blanco Lorena , Estalella Itziar , Loizate Alberto , Irazusta Jon , López José I. , Larrinaga Gorka
Published: October 2015

Background

Aminopeptidase N (APN; EC 3.4.11.2) is a membrane dimeric metallopeptidase involved in differentiation, development, and proliferative processes of several tissues. Recent studies have demonstrated the increased expression and activity of this enzyme in several cancers. However, there are no available data about the impact of this peptidase in the biological aggressiveness and the survival of colorectal cancer (CRC) patients.

Methods

The activity and mRNA expression of APN in tumor tissue (n = 81) and plasma (n = 40) of patients with CRC of low and high grades and stages were prospectively analyzed by fluorimetric and quantitative reverse transcriptase–polymerase chain reaction methods. Data obtained in adenoma and CRC were compared with those from the surrounding normal mucosa. Classic clinical and pathological parameters were stratified following APN data and analyzed for 5-year survival.

Results

mRNA levels of APN ( ANPEP) were lower in colorectal adenomas and adenocarcinomas than in the surrounding uninvolved mucosa (Kruskal-Wallis, P < 0.001). Aminopeptidase N activity in CRC tissue was higher in patients with better overall survival (log-rank P < 0.05, Cox analysis P < 0.05). By contrast, higher plasmatic APN activity correlated with worse overall survival (log-rank P < 0.01, Cox analysis P < 0.05).

Conclusions

Aminopeptidase N activity in tissue and plasma from CRC patients is an independent prognostic factor of 5-year survival. The determination of APN activity levels in the plasma may be a safe, minimally invasive, and inexpensive way to define the aggressiveness of CRC in daily practice.
Sex-Specific Predictors of Metabolic Syndrome Independent of Its Components
Authors: Onat Altan , Can Günay , Çakır Hakan , Özpamuk-Karadeniz Fatma , Karadeniz Yusuf , Yüksel Hüsniye , Şimşek Barış , Ademoğlu Evin
Published: October 2015

To what extent is the metabolic syndrome (MetS) determined beyond its recognized components? In 1702, middle-aged men and women without MetS at baseline, MetS development was identified in 546 participants at a mean of 10.1-year follow-up. Participants subsequently developing MetS had, beyond higher values of MetS traits, significantly higher total and low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein (CRP), γ-glutamyl transferase (GGT), and lower high-density lipoprotein cholesterol. Females were significantly more frequent never smokers and males had lower values of total testosterone. In logistic regression analyses, adjusted for sex, age, and smoking status, MetS was predicted disparately in the sexes, whereas males exhibited, beyond abdominal obesity, CRP, GGT, and sex hormone-binding globulin (SHBG) as independent predictors, abdominal obesity was not an independent predictor in females in whom other than age, CRP conferred MetS risk, whereas SHBG was and current smoking tended to be protective. A surrogate of hepatic steatosis proved a major mediator of abdominal obesity in determining incident MetS (relative risk, 5.6 [95% confidence interval, 3.4-9.3]) in each sex. We confirm that GGT and SHBG are novel independent MetS determinants. Hepatic steatosis is the major predictor of MetS mediating adiposity in each sex. Abdominal obesity is not an independent determinant in Turkish women in whom autoimmune activation seems to prevail before MetS development.
Applying molecular epidemiology in pediatric leukemia
Authors: Schiffman Joshua D
Published: October 2015

Molecular epidemiology is the study of genetic and environmental risk for disease, with much effort centered on cancer. Childhood leukemia occurs in nearly a third of all patients newly diagnosed with pediatric cancer. only a small percentage of these new cases of childhood leukemia are associated with high penetrant hereditary cancer syndromes. Childhood leukemia, especially acute lymphoblastic leukemia, has been associated with a dysregulated immune system due to delayed infectious exposure at a young age. Identical twins with childhood leukemia suggest that acute lymphoblastic leukemia begins in utero and that the concordant presentation is due to a shared preleukemia subclone via placental transfer. Investigation of single nucleotide polymorphisms within candidate genes find that leukemia risk may be attributed to population-based polymorphisms affecting folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B-cell development. More recently, genome-wide association studies for leukemia risk has led investigators to genes associated with B-cell development. When describing leukemia predisposition due to hereditary cancer syndromes, the following 6 categories become apparent on the basis of biology and clinical presentation: (1) genetic instability/DNA repair syndromes, (2) cell cycle/differentiation syndromes, (3) bone marrow failure syndromes, (4) telomere maintenance syndromes, (5) immunodeficiency syndromes, and (6) transcription factor syndromes and pure familial leukemia. understanding the molecular epidemiology of childhood leukemia can affect the treatment and tumor surveillance strategies for these high risk patients and their family members.
Targeting hypoxia-inducible factor 1 to stimulate tissue vascularization
Authors: Semenza Gregg L
Published: October 2015

When tissue perfusion is impaired, the resulting reduction in O2 availability activates hypoxia-inducible factor 1 (HIF-1), which mediates increased transcription of genes encoding multiple angiogenic factors including vascular endothelial growth factor, stromal-derived factor 1, placental growth factor, and angiopoietins, leading to the mobilization of bone marrow-derived angiogenic cells, increased angiogenesis, and arterial remodeling. These HIF- 1-dependent responses are impaired by aging or loss of function mutations at the locus encoding the HIF-1α subunit. in mouse models of limb ischemia and lung transplant rejection, the augmentation of HIF-1 activity by gene therapy or chemical inducers was associated with maintenance of tissue perfusion that prevented limb amputation and allograft rejection, respectively. Thus, targeting HIF-1 may be of therapeutic benefit in these clinical contexts and others in which impaired tissue perfusion plays a role in disease pathogenesis.
Six-Week Oral Guanidinoacetic Acid Administration Improves Muscular Performance in Healthy Volunteers
Authors: Ostojic Sergej M. , Stojanovic Marko D. , Hoffman Jay R.
Published: October 2015

Background

Guanidinoacetic acid (GAA), a natural precursor of creatine, is a new promising dietary supplement, yet its performance-enhancing effect, if any, has yet to be established. The purpose of this pilot study was to evaluate the effects of supplemental GAA on muscle strength, anaerobic performance, and aerobic performance in healthy men and women.

Method

The study enrolled 48 young participants (age, 22.3 ± 1.5 years; height, 176.4 ± 10.0 cm; weight, 71.9 ± 14.3 kg), who received oral doses of GAA (1.2, 2.4, or 4.8 g/d) for 6 weeks in a randomized, double-blind, placebo-controlled trials.

Results

Significant differences were observed between treatment groups for handgrip strength among participants receiving 1.2 g of GAA per day and 2.4 g of GAA per day, as compared with placebo ( P < 0.05). In addition, muscle endurance expressed as the change from baseline in repetitions performed in the bench press exercise was significantly greater in the 1.2 g/d dose of GAA ( P = 0.01) and the 4.8 g/d dose ( P = 0.01) compared with placebo. No dose-response differences were found between trials.

Conclusions

Results from this preliminary study indicate that supplemental GAA ingested in young individuals can improve exercise performance, even at low doses (1.2 g/d).
Dopamine-Induced Changes in Serum Erythropoietin and Creatinine Clearance Reflect Risk Factors for Progression of IgA Nephropathy
Authors: Sulikowska Beata , Johnson Richard J. , Wiechecka-Korenkiewicz Joanna , Korenkiewicz Jadwiga , Marszalek Andrzej , Odrowaz-Sypniewska Grazyna , Manitius Jacek
Published: October 2015

Introduction

The infusion of low-dose dopamine is normally associated with an increase in creatinine clearance, thereby allowing one to assess renal functional reserve. Increased renal blood flow is also associated with a reduction in erythropoietin (EPO) levels.

Objectives

We evaluated the use of dopamine infusion in subjects with IgA nephropathy to determine if these functional changes correlate with risk factors for progression and compared this to the renal biopsy findings.

Patients and Methods

Changes in creatinine clearance and EPO levels were determined in 46 non-nephrotic IgA patients with relative preserved renal function after the infusion of low dose dopamine. Control subjects (n = 15) were evaluated using similar protocols.

Results

Subjects with IgA nephropathy could be separated into those who showed a fall in EPO levels (n = 24) and those who showed no change or a rise in EPO levels (n = 22). Subjects showing the expected fall in EPO demonstrated a higher increase in creatinine clearance, similar to that observed in control subjects. Most importantly, subjects who showed a fall in EPO had less proteinuria, less N-acetyl-β-D-glucosaminidase excretion, lower serum uric acid, blood pressure, and less features of metabolic syndrome despite similar inflammation and fibrosis on biopsy as compared to the others.

Conclusions

A decrease in EPO in response to dopamine is associated with a clinical phenotype that is less likely to develop progressive renal disease. These studies suggest that a fall in EPO in response to dopamine likely reflects preserved tubulointerstitial function that cannot be assessed by renal biopsy alone.
Prediction by Low Plasma HbA1c of Mortality, Cardiac and Noncardiac Disease Risk: Modulation by Diabetic Status and Sex
Authors: Altay Servet , Onat Altan , Karadeniz Yusuf , Özpamuk-Karadeniz Fatma , Can Günay
Published: October 2015

Aim

The aim of the study was to evaluate the predictive value of HbA1c for risk of overall mortality or a composite endpoint of death and nonfatal events.

Methods

Logistic regression retrospectively assessed the longitudinal association of measured HbA1c with outcome in 746 middle-aged adults, recruited from a tertiary health center and stratified to absence or presence of type 2 diabetes, using the recent American Diabetes Association criteria.

Results

A total of 70 deaths and additional incident nonfatal events in 82 cases were recorded at a median of 3.1-year follow-up. Multivariable linear regression revealed among nondiabetic individuals HbA1c to be significantly associated—independent of fasted glucose—inversely with triglycerides and high-density lipoprotein cholesterol, distinct from the diabetic sample. Sex and diabetes status differed in baseline HbA1c values with respect to the development of outcome. Nondiabetic men who subsequently died exhibited significantly lower HbA1c, as did men and women with incident coronary heart disease. Similar difference was observed for incident hypothyroidism and nondiabetic subjects developing malignancy. In logistic regression analysis, adjusted for sex, age, and fasting glucose, each 0.7% (SD, 1) decrement of baseline HbA1c predicted the composite endpoint in the nondiabetic sample (risk estimates, 1.49%; 95% confidence interval, 1.07–2.04), but not in the diabetic sample, whereas overall mortality in the whole sample was increased (risk estimates, 1.51%; 95% confidence interval, 1.05–2.17).

Conclusions

Inverse association of HbA1c with adverse outcomes in men and nondiabetic people indicates the involvement of HbA1c levels in autoimmune activation. The weaker inverse association with prevalent diabetes and in women is consistent with the operation of more pronounced confounding autoimmune processes.
Targeting hypoxia in inflammatory bowel disease
Authors: Colgan Sean P
Published: October 2015

In this review, I summarize some of the recent insight into pharmacological targeting of hypoxia in disease models. Studies from cultured cell systems, animal models, and translation to human patients have revealed that posttranslational modifications of individual proteins within NF-κB and hypoxia-inducible factor pathways serve as ideal targets for analysis in disease models. Studies defining differences and similarities between these responses have taught us a number of important lessons about the complexity of the inflammatory response. A clearer definition of these pathways has provided new insight into disease pathogenesis and, importantly, the potential for new therapeutic targets.
Serum Sclerostin Levels in Newborns Born to Mothers with Vitamin D Deficiency
Authors: Sandal Gonca , Pirgon Ozgur , Dundar Bumin , Cetin Hasan , Bayram Halil Ibrahim
Published: October 2015

Aim

Sclerostin inhibits osteoblast functions, differentiations, and survival rates. The aim of this study was to investigate the association between circulating sclerostin (an emerging biomarker and important regulator of bone formation) and neonatal parameters in mothers with vitamin D deficiency.

Method

Forty-five mothers and their newborns were recruited in the study. The mothers were divided into 2 groups as vitamin D–deficient group 25(OH)D (25-hydroxyvitamin D3 < 20 ng/mL) and vitamin D–sufficient group 25(OH)D (>20 ng/mL). Their newborns had measurements of weight, height, calcium, phosphate, alkaline phosphatase, sclerostin, and 25(OH)D at birth.

Results

The mothers with vitamin D deficiency had significantly lower vitamin D levels than the mothers with vitamin D sufficiency (8.7 [3.4] ng/mL vs 26.7 [4.0] ng/mL, P < 0.001). There were no significant differences between women with vitamin D deficiency and women with vitamin D sufficiency for sclerostin concentrations (205.4 [64.8] pg/mL vs 291.6 [122.9] pg/mL). However, 25(OH)D (10.1 [8.1] ng/mL vs 33.4 [11.6] ng/mL, P < 0.001) and sclerostin concentrations (182.9 [15.3] pg/mL vs 288.8 [32.3] pg/mL, P = 0.01) were lower in newborns born by mothers with vitamin D deficiency compared and with newborns of mothers with vitamin D sufficiency. Circulating sclerostin measurements were not associated with 25(OH)D levels of both mothers and their newborns.

Conclusions

We found significantly lower sclerostin levels in newborns born by women with vitamin D deficiency compared with newborns of nondeficient mothers.
Increased Plasma Levels of Asymmetric Dimethylarginine in Nonalcoholic Fatty Liver Disease: Relation with Insulin Resistance, Inflammation, and Liver Histology
Authors: Boga Salih , Alkim Huseyin , Koksal Ali Riza , Bayram Mehmet , Ozguven Muveddet Banu Yilmaz , Ergun Meltem , Neijmann Sebnem Tekin , Ozgon Gulay , Alkim Canan
Published: October 2015

Background and Aim

Cardiovascular disease (CVD) is the most frequent cause of death in nonalcoholic fatty liver disease (NAFLD). Insulin resistance, hepatic dysfunction, and chronic inflammation are factors interacting in explaining the increased CVD incidence in NAFLD. We aimed to evaluate the effects of insulin resistance and inflammatory biomarkers on asymmetric dimethylarginine (ADMA) levels, a predictor of CVD. We also investigated relationship between these markers and histological findings in patients with NAFLD.

Patients and Methods

Plasma ADMA, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured in 70 patients with histologically verified NAFLD (53 with nonalcoholic steatohepatitis [NASH], 17 with non-NASH) and 12 controls.

Results

The HOMA-IR (5.3 [3.9] vs 1.9 [1], P < 0.001), hs-CRP (5.6 [4.2] vs 2.2 [2.3] mg/L, P < 0.001), ADMA (0.81 [0.25] vs 0.48 [0.24] μmol/L, P = 0.005), and IL-6 (4.1 [1.2] vs 1.0 [0.4] pg/mL, P < 0.001) levels were all found higher in the NAFLD group than the control group. The ADMA levels were significantly higher in patients with NAFLD independent from HOMA-IR and body composition ( P = 0.02). The IL-6 and HOMA-IR levels of the NASH group were found significantly higher than those of the non-NASH group. The only determinant significantly correlated to ADMA was HOMA-IR.

Conclusions

Our data suggested that although ADMA levels are independently higher in NAFLD, the only determinant correlated to ADMA is HOMA-IR and not inflammatory biomarkers (hs-CRP, IL-6) or presence/absence of NASH.
AMPK/p53 Axis is Essential for α-Lipoic Acid–Regulated Metastasis in Human and Mouse Colon Cancer Cells
Authors: Park Sunmi , Choi Seung Kug , Choi Yura , Moon Hyun-Seuk
Published: October 2015

α-Lipoic acid (ALA) has an anticancer property of lung, cervix, and prostate cancer cells. However, direct evidence that ALA contributes to the development of colon cancer has not been fully elucidated. In addition, no previous studies have evaluated whether ALA may regulate malignant potential, such as adhesion, invasion, and colony formation of colon cancer cells. To address the aforementioned questions, we conducted in vitro ALA signaling studies using human (HT29) and mouse (MCA38) colon cancer cell lines. We observed that cell proliferation is reduced by ALA administration in a dose-dependent manner in human and mouse colon cancer cell lines. Specifically, 0.5 to 1 mM concentration of ALA significantly decreased cell proliferation when compared with control. Similarly, we found that ALA downregulates adhesion, invasion, and colony formation. Finally, we observed that ALA activates p53 and AMPK signaling pathways in human and mouse colon cancer cells. We found for the first time that ALA suppresses cell proliferation and malignant potential via p53 and AMPK signaling pathways in human and mouse colon cancer cells. These new and early mechanistic studies provide a causal role of ALA in colon cancer, suggesting that ALA might be a useful agent in the management or chemoprevention of colon cancer.
Spirituality in Arab Muslim Hematopoietic Stem Cell Transplantation Survivors
Authors: Alaloul Fawwaz , Schreiber Judith A. , Al Nusairat Taghreed S. , Andrykowski Michael A.
Published: October 2015

Background:

A cancer diagnosis and treatment can be a stressful, life-altering experience that can pose a threat to life and raise existential challenges. Spirituality may influence the process of coping with the stress of the cancer experience. Studies of the role of spirituality for Muslim cancer patients and survivors are limited.

Objective:

The aim of this study was to understand the role of spirituality in the cancer experience among Arab Muslim hematopoietic stem cell transplant (HSCT) survivors.

Methods:

In this qualitative, descriptive study, 63 HSCT survivors (mean, 20.2 months) responded to 2 open-ended, self-report questions on the role of spirituality in their HSCT experience. Thematic analysis was used to identify themes related to spirituality.

Results:

Three dimensions that helped patients cope with their experiences were identified: sickness viewed in light of belief in God, use of religious/spiritual resources, and support from family and community. Two general themes described changes in their faith as a result of having the HSCT procedure: strengthening of faith in God and greater reliance on religious/spiritual activities.

Conclusion:

Spirituality was important to the Arab Muslim survivors in coping with cancer and HSCT treatment. Muslim cancer survivors are often deeply connected to their religion.

Implications for Practice:

Healthcare providers in the United States and other Western countries need to be aware of the unique religious and spiritual needs of Muslim cancer survivors in order to provide them with culturally sensitive care. More research on the spiritual needs of Muslim cancer patients and survivors residing in Western countries is needed.
Proposal to change Recommendation 12c of the International Code of Nomenclature of Prokaryotes
Authors: Oren Aharon , Garrity George M. , Schink Bernhard
Published: October 2015

We propose changing Recommendation 12c of the International Code of Nomenclature of Prokaryotes to clarify the ways species and subspecies can be named to honour persons.
Isolation and identification of bat viruses closely related to human, porcine and mink orthoreoviruses
Authors: Yang Xing-Lou , Tan Bing , Wang Bo , Li Wen , Wang Ning , Luo Chu-Ming , Wang Mei-Niang , Zhang Wei , Li Bei , Peng Cheng , Ge Xing-Yi , Zhang Li-Biao , Shi Zheng-Li
Published: October 2015

Bats have been identified as natural reservoirs of many viruses, including reoviruses. Recent studies have demonstrated the interspecies transmission of bat reoviruses to humans. In this study, we report the isolation and molecular characterization of six strains of mammalian orthoreovirus (MRV) from Hipposideros and Myotis spp. These isolates were grouped into MRV serotype 1, 2 or 3 based on the sequences of the S1 gene, which encodes the outer coat protein σ1. Importantly, we found that three of six bat MRV strains shared high similarity with MRVs isolated from diseased minks, piglets or humans based on the S1 segment, suggesting that interspecies transmission has occurred between bats and humans or animals. Phylogenetic analyses based on the 10 segments showed that the genomic segments of these bat MRVs had different evolution lineages, suggesting that these bat MRVs may have arisen through reassortment of MRVs of different origins.
Individual-Based Integral Projection Models: The Role of Size-Structure on Extinction Risk and Establishment Success
Authors: Schreiber Sebastian J. , Ross Noam
Published: October 2015

Abstract

Matrix models or integral projection models (IPMs) are commonly used to study the dynamics of structured populations, where discrete or continuous traits influence survival, growth, or reproduction. When a population’s size is small, as is often the case for threatened species or potentially invasive species arriving in novel habitats, extinction risk may be substantial due to demographic stochasticity.

Branching processes, which are individual-based counterparts to matrix models and IPMs, allow one to quantify these risks of extinction. For discretely structured populations, the theory of multi-type branching processes provides analytic methods to compute how extinction risk changes over time and how it depends on the size and composition of the population. Building on prior work on continuous-state branching processes, we extend these analytic methods to individual-based models accounting for any mixture of discrete and continuous population structure.

The individual-based IPMs are defined by probabilistic update rules at the level of the individual which determine how each individual with a given trait value dies, changes trait value (e.g. grows in size), or produces individuals with the same or other trait values. Probabilities of extinction are shown to be analytically determined by probability generating functionals associated with the individual-based IPMs. In particular, we present analytical expressions for how extinction probabilities change over time and depend on the initial abundance and trait distribution of the population. We illustrate how to numerically implement these methods using data from the short-lived desert shrub speciesCryptantha flava, and provide a more general discussion of how to implement these methods to other data sets including those involving fluctuating environmental conditions.

As most IPM studies have the necessary data to parameterize individual-based IPMs, these methods provide a computationally efficient means to explore how continuously structured populations differing in their evolutionary history and environmental context may differ in their vulnerability to extinction or ability to colonize new habitats.
Dissecting the genetic basis of a complexcis-regulatory adaptation
Authors: Naranjo Santiago , Smith Justin D. , Artieri Carlo G. , Zhang Mian , Zhou Yiqi , Palmer Michael E. , Fraser Hunter B.
Published: October 2015

Although single genes underlying several evolutionary adaptations have been identified, the genetic basis of complex, polygenic adaptations has been far more challenging to pinpoint. Here we report that the budding yeastSaccharomyces paradoxushas recently evolved resistance to citrinin, a naturally occurring mycotoxin. Applying a genome-wide test for selection oncis-regulation, we identified five genes involved in the citrinin response that are constitutively up-regulated inS. paradoxus.Four of these genes are necessary for resistance, and are also sufficient to increase the resistance of a sensitive strain when over-expressed. Moreover,cis-regulatory divergence in the promoters of these genes contributes to resistance, while exacting a cost in the absence of citrinin. Our results demonstrate how the subtle effects of individual regulatory elements can be combined, via natural selection, into a complex adaptation. Our approach can be applied to dissect the genetic basis of polygenic adaptations in a wide range of species.

Author Summary

Adaptation via natural selection has been a subject of great interest for well over a century, yet we still have little understanding of its molecular basis. What are the genetic changes that are actually being selected? While single genes underlying several adaptations have been identified, the genetic basis of complex, polygenic adaptations has been far more challenging to pinpoint. The complex trait that we study here is the resistance ofSaccharomycesyeast to a mycotoxin called citrinin, which is produced by many other species of fungi, and is a common food contaminant for both humans and livestock. We found that sequence changes in the promoters of at least three genes have contributed to citrinin resistance, by up-regulating their transcription even in the absence of citrinin. Higher expression of these genes confers a fitness advantage in the presence of citrinin, while exacting a cost in its absence— a fitness tradeoff. Our results provide a detailed view of a complex adaptation, and our approach can be applied to polygenic adaptations in a wide range of species.
An integrated homeostatic reinforcement learning theory of motivation explains the transition to cocaine addiction
Authors: Keramati Mehdi , Durand Audrey , Girardeau Paul , Gutkin Boris , Ahmed Serge
Published: October 2015

Drugs of abuse implicate both reward learning and homeostatic regulation mechanisms of the brain. Theories of addiction, thus, have mostly depicted this phenomenon as pathology in either habit-based learning system or homeostatic mechanisms. Showing the limits of those accounts, we hypothesize that compulsive drug seeking arises from drugs hijacking a system that integrates homeostatic regulation mechanism with goal-directed action/behavior. Building upon a recently developed homeostatic reinforcement learning theory, we present a computational theory proposing that cocaine reinforces goal-directed drug-seeking due to its rapid homeostatic corrective effect, whereas its chronic use induces slow and long-lasting changes in homeostatic setpoint. Our theory accounts for key behavioral and neurobiological features of addiction, most notably, escalation of cocaine use, drug-primed craving and relapse, and individual differences underlying susceptibility to addiction. The theory also generates unique predictions about the mechanisms of cocaine-intake regulation and about cocaine-primed craving and relapse that are confirmed by new experiments.

Significance

Chronic use of addictive drugs renders increased motivation in planning to obtain and consume the drugs, despite their adverse social, occupational, and health consequences. It is as if addicts gradually develop a strong need for the drug and use their cognitive abilities and the knowledge of their environment in order to fulfil that need. In this paper, we build a mathematical model of this conception of addiction and show through quantitative simulations that such a model actually behaves in the same way that human addicts or laboratory animals that are exposed to cocaine behave. For example, the model shows gradually increasing motivation for drugs, relapse after long periods of abstinence, and individual differences in susceptibility to addiction.
Massive memory revisited: Limitations on storage capacity for object details in visual long-term memory
Authors: Cunningham Corbin A. , Yassa Michael A. , Egeth Howard E.
Published: October 2015

Previous work suggests that visual long-term memory (VLTM) is highly detailed and has a massive capacity. However, memory performance is subject to the effects of the type of testing procedure used. The current study examines detail memory performance by probing the same memories within the same subjects, but using divergent probing methods. The results reveal that while VLTM representations are typically sufficient to support performance when the procedure probes gist-based information, they are not sufficient in circumstances when the procedure requires more detail. We show that VLTM capacity, albeit large, is heavily reliant on gist as well as detail. Thus, the nature of the mnemonic representations stored in VLTM is important in understanding its capacity limitations.
Forming competing fear learning and extinction memories in adolescence makes fear difficult to inhibit
Authors: Baker Kathryn D. , Richardson Rick
Published: October 2015

Fear inhibition is markedly impaired in adolescent rodents and humans. The present experiments investigated whether this impairment is critically determined by the animal's age at the time of fear learning or their age at fear extinction. Male rats (n = 170) were tested for extinction retention after conditioning and extinction at different ages. We examined neural correlates of impaired extinction retention by detection of phosphorylated mitogen-activated protein kinase immunoreactivity (pMAPK-IR) in several brain regions. Unexpectedly, adolescent rats exhibited good extinction retention if fear was acquired before adolescence. Further, fear acquired in adolescence could be successfully extinguished in adulthood but not within adolescence. Adolescent rats did not show extinction-induced increases in pMAPK-IR in the medial prefrontal cortex or the basolateral amygdala, or a pattern of reduced caudal central amygdala pMAPK-IR, as was observed in juveniles. This dampened prefrontal and basolateral amygdala MAPK activation following extinction in adolescence occurred even when there was no impairment in extinction retention. In contrast, only adolescent animals that exhibited impaired extinction retention showed elevated pMAPK-IR in the posterior paraventricular thalamus. These data suggest that neither the animal's age at the time of fear acquisition or extinction determines whether impaired extinction retention is exhibited. Rather, it appears that forming competing fear conditioning and extinction memories in adolescence renders this a vulnerable developmental period in which fear is difficult to inhibit. Furthermore, even under conditions that promote good extinction, the neural correlates of extinction in adolescence are different than those recruited in animals of other ages.
Changes in the Phosphoproteome and Metabolome Link Early Signaling Events to Rearrangement of Photosynthesis and Central Metabolism in Salinity and Oxidative Stress Response in Arabidopsis
Authors: Chen Yanmei , Hoehenwarter Wolfgang
Published: October 2015

Salinity and oxidative stress are major factors affecting and limiting the productivity of agricultural crops. The molecular and biochemical processes governing the plant response to abiotic stress have often been researched in a reductionist manner. Here, we report a systemic approach combining metabolic labeling and phosphoproteomics to capture early signaling events with quantitative metabolome analysis and enzyme activity assays to determine the effects of salt and oxidative stress on plant physiology. K+ and Na+ transporters showed coordinated changes in their phosphorylation pattern, indicating the importance of dynamic ion homeostasis for adaptation to salt stress. Unique phosphorylation sites were found for Arabidopsis (Arabidopsis thaliana) SNF1 kinase homolog10 and 11, indicating their central roles in the stress-regulated responses. Seven Sucrose Non-fermenting1-Related Protein Kinase2 kinases showed varying levels of phosphorylation at multiple serine/threonine residues in their kinase domain upon stress, showing temporally distinct modulation of the various isoforms. Salinity and oxidative stress also lead to changes in protein phosphorylation of proteins central to photosynthesis, in particular the kinase State Transition Protein7 required for state transition and light-harvesting II complex proteins. Furthermore, stress-induced changes of the phosphorylation of enzymes of central metabolism were observed. The phosphorylation patterns of these proteins were concurrent with changes in enzyme activity. This was reflected by altered levels of metabolites, such as the sugars sucrose and fructose, glycolysis intermediates, and amino acids. Together, our study provides evidence for a link between early signaling in the salt and oxidative stress response that regulates the state transition of photosynthesis and the rearrangement of primary metabolism.
Crystal structure of 2-(4-chlorobenzamido)benzoic acid
Authors: Moreno-Fuquen Rodolfo , Melo Vanessa , Ellena Javier
Published: October 2015

In the title molecule, C14H10ClNO3, the amide C=O bond isantito theo-carboxy substituent in the adjacent benzene ring, a conformation that facilitates the formation of an intramolecular amide-N—H...O(carbonyl) hydrogen bond that closes anS(6) loop. The central amide segment is twisted away from the carboxy- and chloro-substituted benzene rings by 13.93 (17) and 15.26 (15)°, respectively. The most prominent supramolecular interactions in the crystal packing are carboxylic acid-H...O(carboxyl) hydrogen bonds that lead to centrosymmetric dimeric aggregates connected by eight-membered {...HOC=O}2synthons.
Crystal structure of 4,4′,4′′-(1,3,5-triazine-2,4,6-triyl)tripyridinium trichloride 2.5-hydrate
Authors: Ling Bo-Kai , Feng Xiao-Long , Li Yang , Luan Tian-Gang
Published: October 2015

The asymmetric unit of the title compound, C18H15N63+·3Cl−·2.5H2O, contains two independent (1,3,5-triazine-2,4,6-triyl)tripyridinium cations. Both cations are approximately planar, the r.m.s. deviations of fitted non-H atoms being 0.045 and 0.051 Å. In the crystal, extensive O—H...Cl, O—H...O, N—H...Cl and N—H...O hydrogen bonds and weak C—H...Cl and C—H...O interactions link the organic cations, Cl−anions and water molecules into a three-dimensional supramolecular architecture. π–π stacking between the pyridine rings of adjacent cations is also observed, the centroid-to-centroid distance being 3.7578 (8) Å.
Crystal and molecular structure of aflatrem
Authors: Lenta Bruno N. , Ngatchou Jules , Kenfack Patrice T. , Neumann Beate , Stammler Hans-Georg , Sewald Norbert
Published: October 2015

The crystal structure of the title compound, C32H39NO4, confirms the absolute configuration of the seven chiral centres in the molecule. The molecule has a 1,1-dimethylprop-2-enyl substituent on the indole nucleus and this nucleus shares one edge with the five-membered ring which is, in turn, connected to a sequence of three edge-shared fused rings. The skeleton is completed by the 7,7-trimethyl-6,8-dioxabicyclo[3.2.1]oct-3-en-2-one group connected to the terminal cyclohexene ring. The two cyclohexane rings adopt chair and half-chair conformations, while in the dioxabicyclo[3.2.1]oct-3-en-2-one unit, the six-membered ring has a half-chair conformation. The indole system of the molecule exhibits a tilt of 2.02 (1)° between its two rings. In the crystal, O—H...O hydrogen bonds connect molecules into chains along [010]. Weak N—H...π interactions connect these chains, forming sheets parallel to (10-1).