bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating Pro-Surfactant Protein B as a Risk Biomarker for Lung Cancer
Authors: Taguchi Ayumu , Hanash Samir , Rundle Andrew , McKeague Ian W. , Tang Deliang , Darakjy Salima , Gaziano J. Michael , Sesso Howard D. , Perera Frederica
Published: July 2013

Background: Our prior studies of lung cancer suggested that a novel biomarker (pro-surfactant protein B or pro-SFTPB) might serve as a predictive marker for this disease. We aimed to determine the potential use of pro-SFTPB for distinguishing lung cancer cases from matched controls as a risk marker.

Methods: Study subjects were drawn from the longitudinal Physicians' Health Study (PHS). Cases (n = 188) included individuals who were cancer-free at study enrollment but developed lung cancer during follow-up. Controls (n = 337) were subjects who did not develop lung cancer. Cases and controls were matched on date of study enrollment, age at enrollment, and smoking status and amount. Baseline plasma samples drawn at enrollment were analyzed for pro-SFTPB using ELISA to detect differences in protein expression levels for cases and controls.

Results: Pro-SFTPB nondetectable status was significantly associated with lung cancer risk [OR = 5.88; 95% confidence interval (CI) 1.24–27.48]. Among subjects with detectable levels of the protein, increasing plasma concentration of pro-SFTPB was associated with higher lung cancer risk (OR = 1.41 per unit increase in log pro-SFTPB; 95% CI 1.08–1.84).

Conclusion: These results suggest a nonlinear, J-shaped association between plasma pro-SFTPB levels and lung cancer risk, with both nondetectable and higher levels of the marker being associated with lung cancer.

Impact: These results show promise of a risk marker that could contribute to predicting risk for lung cancer development and to narrowing the high-risk population for low-dose computed tomography screening. Cancer Epidemiol Biomarkers Prev; 22(10); 1756–61. ©2013 AACR.
Serum Antioxidant Nutrients, Vitamin A, and Mortality in U.S. Adults
Authors: Goyal Abhishek , Terry Mary Beth , Siegel Abby B.
Published: July 2013

Background: Observational studies have suggested that antioxidant nutrients may reduce cancer and overall mortality risks. However, most randomized trials have failed to show survival benefits. Examining nonlinear associations between antioxidant levels and health outcomes may help to explain these discrepant findings.

Methods: We evaluated all-cause, cancer, and cardiovascular mortality risks associated with quintiles (Q1–Q5) of serum antioxidant (vitamins C and E, β-carotene, and selenium) and vitamin A levels, in 16,008 adult participants of The Third National Health and Nutrition Examination Survey (NHANES III; 1988–1994).

Results: Over a median follow-up period of 14.2 years, there were 4,225 deaths, including 891 from cancer and 1,891 from cardiovascular disease. We observed a dose–response decrease in cancer and overall mortality risks with higher vitamin C levels. In contrast, for vitamin A, risk of cancer death decreased from Q1–Q2, with no further decline in risk at higher levels. For vitamin E, having levels in Q4 was associated with the lowest cancer mortality risk. Both vitamin A and E had U-shaped associations with all-cause mortality. Cancer mortality risks decreased from Q1–Q2 for β-carotene and from Q1–Q4 for selenium. However, for β-carotene and selenium, overall mortality risks decreased from Q1–Q2 but then did not change significantly with higher levels.

Conclusions: Antioxidant supplement use should be studied in the context of overall mortality and other competing mortality risks.

Impact: These data suggest the need for novel intervention studies where doses of these agents are individualized based on their serum levels, and possibly, markers of oxidative stress and systemic inflammatory response. Cancer Epidemiol Biomarkers Prev; 22(12); 2202–11. ©2013 AACR.
Prediagnostic Levels of Serum One-Carbon Metabolites and Risk of Hepatocellular Carcinoma
Authors: Butler Lesley M. , Arning Erland , Wang Renwei , Bottiglieri Teodoro , Govindarajan Sugantha , Gao Yu-Tang , Yuan Jian-Min
Published: July 2013

Background: Rats fed diets deficient in choline develop hepatocellular carcinoma. Tumor DNA from these animals is characteristically hypomethylated, suggesting that disruption of the one-carbon metabolism pathway is an underlying mechanism for hepatocarcinogenesis. Prospective studies in humans on circulating choline and other one-carbon metabolites and hepatocellular carcinoma risk have been lacking.

Methods: We prospectively examined the association between prediagnostic serum concentrations of one-carbon metabolites including betaine, choline, cystathionine, homocysteine, methionine, 5-methyltetrahydrofolate (5-MTHF), pyridoxal-5-phosphate (PLP, the bioactive form of vitamin B6) and S-adenosylmethionine (SAM), and risk of developing hepatocellular carcinoma based on a nested case–control study of 297 incident cases and 631 matched controls from a cohort of 18,244 men in Shanghai, China. Logistic regression methods were used to calculate ORs and 95% confidence intervals (CI) adjusted for established risk factors for hepatocellular carcinoma.

Results: Serum choline and PLP were associated with statistically significant reduced risk of hepatocellular carcinoma, whereas serum cystathionine, methionine, and SAM were associated with increased hepatocellular carcinoma risk (all Ptrend < 0.05). The inverse associations for hepatocellular carcinoma risk with choline and PLP remained statistically significant after adjusting for all potential confounders. The multivariate-adjusted ORs (95% CIs) for the highest versus lowest quintiles of serum choline and PLP were 0.35 (0.16–0.78; P = 0.010) and 0.44 (0.25–0.78; P = 0.005), respectively. There were no associations for hepatocellular carcinoma risk with 5-MTHF, betaine, or homocysteine.

Conclusion: The inverse associations between choline and vitamin B6 and the risk of hepatocellular carcinoma development are novel and warrant further investigation.

Impact: Identifying new modifiable factors for hepatocellular carcinoma prevention is warranted. Cancer Epidemiol Biomarkers Prev; 22(10); 1884–93. ©2013 AACR.
A Clinical Model for Identifying Radiosensitive Tumor Genotypes in Non–Small Cell Lung Cancer
Authors: Johung Kimberly L. , Yao Xiaopan , Li Fangyong , Yu James B. , Gettinger Scott N. , Goldberg Sarah , Decker Roy H. , Hess Judith A. , Chiang Veronica L. , Contessa Joseph N.
Published: July 2013

Purpose: Non–small cell lung cancer (NSCLC) includes a spectrum of radiosensitive and radioresistant tumors. However, little is known about the molecular determinants of cellular radiation responses. We examined clinical outcomes after gamma knife radiotherapy for NSCLC intracranial metastases to evaluate the use of this model for determining radiosensitive tumor genotypes.

Experimental Design: Between 2005 and 2012, 239 patients with NSCLC were enrolled in a prospective gamma knife data repository. Molecular pathology regarding EGF receptor (EGFR), ALK, and KRAS mutation status was available for 81 patients. Local and distant brain control was determined for 79 patients with 469 brain metastases. Modified Cox proportional hazards models were established to evaluate local control for treated lesions after serial gamma knife treatments.

Results: In total, 11% of patients developed in-field recurrence. No patients with metastases from tumors with EGFR mutations (0/164 lesions) or EML4-ALK translocations (0/61 lesions) recurred in-field. In contrast, 19% of patients without these mutations and 18% of patients with KRAS mutations recurred in-field (10/139 and 3/105 lesions, respectively). Rates of distant brain recurrence did not significantly differ across tumor genotypes. The predicted median in-field local control was significantly longer for EGFR-mutant and ALK-translocated tumors compared with other patients with NSCLC (P < 0.001), whereas distant brain recurrence time was equivalent (P = 0.97). On multivariate analysis, EGFR mutation, ALK translocation, and metastasis size were independent predictors for superior local control after gamma knife treatment.

Conclusions: This study suggests that EGFR kinase domain mutations and EML4-ALK translocations are radiosensitive NSCLC genotypes, and proposes a novel model to identify radiosensitive subtypes of NSCLC. Clin Cancer Res; 19(19); 5523–32. ©2013 AACR.
Carotid Artery Atherosclerotic Profile as a Predictor of the Aorta Atherosclerotic Profile in Patients with Cerebrovascular Events
Authors: Hueb João Carlos , Bazan Rodrigo , Pereira Braga Gabriel , Fusco Daniéliso Renato , Zanati Bazan Silméia Garcia , Bojikian Matsubara Beatriz
Published: July 2013

Background: It is well known that the presence of atheroma of the thoracic aorta is a risk factor for cerebrovascular events. We sought to evaluate whether the presence and the morphology of atherosclerotic plaque in the carotid artery detected by duplex ultrasonography is associated with disease in the proximal aorta visualized by transesophageal echocardiogram in patients with a cerebrovascular event. Methods: We carried out a cross-sectional prospective study including 147 consecutive patients with prior stroke or transient ischemic attack (TIA). Neurological evaluations were performed by an expert neurologist using clinical and tomographic diagnostic criteria including the definition of etiology and whether the patient suffered from stroke or TIA. Transthoracic and transesophageal echocardiograms and carotid artery duplex ultrasonography were performed by the same examiner. Patients with and without plaque in the carotid artery were compared using Student's t test or the χ2 test. Regression analysis was used to determine whether the presence of plaque in the carotid artery was predictive of the presence of plaque in the proximal aorta and to analyze the relationship between the echogenicity of carotid and aortic plaques. The significance level was set at p < 0.05. Results: All 147 patients (95 men) were included in the analysis. Patients' ages ranged from 23 to 85 years (65 ± 12.4 years). Most of the patients (58.5%) were Caucasian, while 41.5% were African-Brazilian. Arterial hypertension, diabetes and tobacco use were more frequent among patients with atherosclerotic plaque in the aorta. A normal carotid intima-media thickness halved the risk of atherosclerotic plaque in the aorta [odds ratio (OR) 0.46, 95% confidence interval (CI) 0.23-0.91; p = 0.026]. The presence of carotid plaque increased the risk of aortic plaque by 70-fold (OR 73.2, 95% CI 25.6-2,018.6; p < 0.001) in univariate analysis. The absence of atherosclerotic plaque in the carotid artery reduced the risk of plaque in the aorta to almost 0 (OR 0.014, 95% CI 0.004-0.041; p < 0.001). Considering the 86 patients with both aortic and carotid plaques, the presence of hypoechoic plaque in the carotid artery was a predictor of hypoechoic plaque in the aorta (OR 10.1, 95% CI 3.3-31.2; p < 0.001). Conclusions: The carotid artery atherosclerotic profile defined by ultrasonography is a strong predictor of the atherosclerotic profile of the proximal aorta. This should be taken into consideration before referring patients with acute cerebrovascular events for transesophageal echocardiogram.
Plasma Fatty Acid Composition and Incident Ischemic Stroke in Middle-Aged Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Yamagishi Kazumasa , Folsom Aaron R. , Steffen Lyn M. ,   for the ARIC Study Investigators
Published: July 2013

Background: The association of individual fatty acids with ischemic stroke has not been thoroughly studied, and results have been inconsistent. Few prospective studies have systematically explored the association of biomarkers of fatty acid intake with stroke. The aim of this study was to explore which individual plasma fatty acids would be associated with higher risk of ischemic stroke among whites. Methods: We studied 3,870 white men and women from the Minneapolis field center of the Atherosclerosis Risk in Communities (ARIC) Study, aged 45-64 years at baseline (1987-1989), who had plasma cholesterol ester (CE) and phospholipid (PL) fatty acids measured. Participants were followed through 2008 for incident ischemic stroke. Hazard ratios (HRs) with 95% confidence intervals (CIs) across quartiles of each fatty acid, measured as the percentage of total fatty acids, were calculated using the Cox proportional hazards model. Results: During a maximum of 22 years of follow-up, we identified 168 cases of ischemic stroke. After adjustment for age and sex, plasma levels of saturated fatty acids were associated positively: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 1.93 (1.23-3.04, p for trend = 0.01) and that for PL fraction was 1.64 (1.05-2.57, p for trend = 0.03). There was also a positive linear association with monounsaturated fatty acids, especially with palmitoleic acid: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 1.86 (1.20-2.87, p for trend = 0.003) and that for PL fraction was 1.52 (0.99-2.34, p for trend = 0.005). No associations of ω-3 and ω-6 polyunsaturated fatty acids with ischemic stroke were observed, but linoleic acid was inversely and nonlinearly associated with ischemic stroke: HR (95% CI) of the highest versus the lowest quartile for CE fraction was 0.64 (0.43-0.97, p for trend = 0.13) and that for PL fraction was 0.69 (0.45-1.05, p for trend = 0.24). These associations were generally unchanged after adjustment for cardiovascular risk factors. Conclusions: In this US cohort of whites, we found significant positive associations of plasma saturated and monounsaturated fatty acids, especially of palmitoleic acid, with ischemic stroke. We also found an inverse nonlinear association between linoleic acid and ischemic stroke.
Maintenance Hemodialysis Independently Increases the Risk of Early Death after Acute Intracerebral Hemorrhage
Authors: Shimoyama Takashi , Kimura Kazumi , Shibazaki Kensaku , Yamashita Shinji , Iguchi Yasuyuki
Published: July 2013

Background: It is unknown whether the clinical features and outcomes of intracerebral hemorrhage (ICH) patients who undergo maintenance hemodialysis (HD) at the time of ICH are similar to those of general ICH patients. Methods: We retrospectively examined the medical records of ICH patients admitted to the Stroke Center of Kawasaki Medical School Hospital within 7 days of ICH onset between April 2004 and June 2011. Patients were classed as HD or non-HD, and clinical characteristics were compared between the two groups. ICH volume was measured on admission CT and follow-up CT scan (<24 h after admission). Hematoma enlargement was defined as a hematoma that increased by more than 33% of its initial volume. Early death was defined as all-cause death within 14 days of ICH onset. The factors associated with early death were determined using multivariate logistic regression analysis. Results: Five hundred and seven patients (320 males; 69.0 years old, interquartile range 59.0-79.0) were enrolled in the study. Thirty-six (7.2%) were receiving maintenance HD at the time of ICH and formed the HD group, and the remaining 471 patients formed the non-HD group. Use of antithrombotic agents prior to ICH was more common in the HD group than in the non-HD group (41.7 vs. 21.9%; p = 0.012). Brainstem (30.6 vs. 11.3%; p = 0.003) and lobar (19.4 vs. 6.6%; p = 0.013) hematoma locations were more common in the HD group than in the non-HD group. Enlargement of ICH volume was more common in the HD group than in the non-HD group (25.8 vs. 10.2%; p = 0.015). Early death was more common in the HD group than in the non-HD group (33.3 vs. 9.3%; p < 0.001). On the multivariate logistic regression analysis adjusted for age, sex and renal dysfunction, National Institutes of Health Stroke Scale score >20 [odds ratio (OR) 27.40, 95% confidence interval (CI) 9.69-77.44; p < 0.001], ICH volume >30 ml (OR 9.53, 95% CI 3.82-23.77; p < 0.001), HD (OR 6.42, 95% CI 1.39-29.76; p = 0.017), the use of antithrombotic agents (OR 3.04, 95% CI 1.22-7.56; p = 0.017) and glucose >150 mg/dl (OR 2.51, 95% CI 1.01-6.26; p = 0.047) were independent factors associated with early death. Conclusion: Maintenance HD is independently associated with early death in ICH patients.
Obstetrical Outcome of Young Women with a Past History of Cerebral Venous Thrombosis
Authors: Ciron Jonathan , Godenèche Gaëlle , Vandamme Xavier , Rosier Marie-Pierre , Sharov Igor , Mathis Stéphane , Larrieu Delphine , Neau Jean-Philippe
Published: July 2013

Background: This study was designed to review the obstetrical outcome of a consecutive series of cerebral venous thrombosis (CVT) affecting fertile women over a long period of time. Methods: From a computerized database of four hospitals of a French region (Poitou-Charentes), we selected patients admitted to hospital for CVT between January 1995 and February 2012. All the case notes were re-examined by two neurologists to confirm the initial diagnosis of CVT. The criterion of inclusion in our study was the occurrence of CVT in a woman ≤40 years of age. All the patients were recontacted by telephone in September 2012 and could be seen in an outpatient clinic. The data of interest were: occurrence of subsequent pregnancies, outcome of these pregnancies, their possible complications, their management with respect to preventive medication, details on the birth and the neonate. Results: Out of 190 consecutive patients hospitalized for CVT, 62 women aged ≤40 years were included (mean age 27.2 ± 6.7 years at the time of their cerebrovascular event). The mean duration of follow-up was 89.5 ± 60.6 months (median: 76 months). There were 45 pregnancies in 24 of the women. Among these 45 pregnancies, 1 was in progress, 24 were completed resulting in normal children, whereas 20 were terminated (5 voluntary abortions, 14 miscarriages and 1 medical abortion). During the pregnancies recorded, there was one recurrence of CVT and no extra-CVT. Various management strategies were adopted, depending on the identified cause(s) for CVT and the medical history of the patient. Conclusions: Our study confirms that the occurrence of a CVT in young women is not a contraindication for subsequent pregnancy. However, it points to a high incidence of miscarriage. Apart from this fact, there is no increase in materno-fetal complications during pregnancy and childbirth, and the neonates are healthy. The risk of recurrence of a CVT or extra-CVT during subsequent pregnancy is low but most of patients were on preventive antithrombotic medication.
Kleptomania in Patients with Neuro-Behçet's Disease
Authors: Shugaiv Erkingül , Kıyat-Atamer Aslı , Tüzün Erdem , Kürtüncü Murat , Baral-Kulaksızoğlu Işın , Akman Demir Gülşen
Published: July 2013

Objective: This study was conducted to characterize the prevalence and clinical features of kleptomania, an impulse control disorder, in patients with Behçet's disease involving the central nervous system. Subjects and Methods: Medical records of 350 patients with neuro-Behçet's disease were evaluated, and clinical and neuropsychological features of patients with kleptomania were noted. Results: Of the 350 neuro-Behçet's disease patients 6 (1.7%) had presented with symptoms that fulfilled the criteria of kleptomania according to the revised 4th version of the Diagnostic and Statistical Manual of Mental Disorders. The 6 patients (5 men, 1 woman) had parenchymal lesions and had developed kleptomania during remission. Magnetic resonance imaging done on the 6 patients before the onset of kleptomania mostly revealed brainstem lesions. Psychiatric assessment did not show any comorbid psychiatric disorders and neuropsychological evaluation showed executive dysfunction in all patients. Conclusion: The 6 patients with kleptomania had developed a frontal lobe syndrome.
Licochalcone A Enhances Geldanamycin-Induced Apoptosis through Reactive Oxygen Species-Mediated Caspase Activation
Authors: Kim Yun Jeong , Jung Eun Byul , Myung Soon Chul , Kim Wonyong , Lee Chung Soo
Published: July 2013

Background and Purpose: Geldanamycin and licochalcone A induce apoptosis in cancer cells. However, whether the combination of geldanamycin and licochalcone A-induced apoptosis in epithelial ovarian cancer cells is mediated by the formation of reactive oxygen species, leading to the activation of apoptotic caspase, has not been studied. Experimental Approach: Using the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3, we investigated the promoting effect of licochalcone A on geldanamycin-induced apoptosis. Results: Geldanamycin induced changes in apoptosis-related protein levels, loss of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases, cleavage of PARP-1, formation of reactive oxygen species and depletion of glutathione (GSH). Licochalcone A enhanced geldanamycin-induced apoptosis-related protein activation, formation of reactive oxygen species, caspase activation and cell death. The combined effect was inhibited by the addition of oxidant scavengers. Conclusions: Licochalcone A may potentiate the apoptotic effect of geldanamycin on ovarian carcinoma cell lines by the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated apoptotic pathway. The apoptosis-promoting effect of licochalcone A may be mediated by its stimulatory action on the formation of reactive oxygen species and the depletion of GSH, which results in the activation of caspases.
Stroke in Heart Failure in Sinus Rhythm: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction Trial
Authors: Pullicino Patrick M. , Thompson John L.P. , Sacco Ralph L. , Sanford Alexandra R. , Qian Min , Teerlink John R. , Haddad Haissam , Diek Monika , Freudenberger Ronald S. , Labovitz Arthur J. , Di Tullio Marco R. , Lok Dirk J. , Ponikowski Piotr , Anker Stefan D. , Graham Susan , Mann Douglas L. , Mohr J.P. , Homma Shunichi ,   for the WARCEF Investigators
Published: July 2013

Background: The Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial found no difference between warfarin and aspirin in patients with low ejection fraction in sinus rhythm for the primary outcome: first to occur of 84 incident ischemic strokes (IIS), 7 intracerebral hemorrhages or 531 deaths. Prespecified secondary analysis showed a 48% hazard ratio reduction (p = 0.005) for warfarin in IIS. Cardioembolism is likely the main pathogenesis of stroke in heart failure. We examined the IIS benefit for warfarin in more detail in post hoc secondary analyses. Methods: We subtyped IIS into definite, possible and noncardioembolic using the Stroke Prevention in Atrial Fibrillation method. Statistical tests, stratified by prior ischemic stroke or transient ischemic attack, were the conditional binomial for independent Poisson variables for rates, the Cochran-Mantel-Haenszel test for stroke subtype and the van Elteren test for modified Rankin Score (mRS) and National Institute of Health Stroke Scale (NIHSS) distributions, and an exact test for proportions. Results: Twenty-nine of 1,142 warfarin and 55 of 1,163 aspirin patients had IIS. The warfarin IIS rate (0.727/100 patient-years, PY) was lower than for aspirin (1.36/100 PY, p = 0.003). Definite cardioembolic IIS was less frequent on warfarin than aspirin (0.22 vs. 0.55/100 PY, p = 0.012). Possible cardioembolic IIS tended to be less frequent on warfarin than aspirin (0.37 vs. 0.67/100 PY, p = 0.063) but noncardioembolic IIS showed no difference: 5 (0.12/100 PY) versus 6 (0.15/100 PY, p = 0.768). Among patients experiencing IIS, there were no differences by treatment arm in fatal IIS, baseline mRS, mRS 90 days after IIS, and change from baseline to post-IIS mRS. The warfarin arm showed a trend to a lower proportion of severe nonfatal IIS [mRS 3-5; 3/23 (13.0%) vs. 16/48 (33.3%), p = 0.086]. There was no difference in NIHSS at the time of stroke (p = 0.825) or in post-IIS mRS (p = 0.948) between cardioembolic, possible cardioembolic and noncardioembolic stroke including both warfarin and aspirin groups. Conclusions: The observed benefits in the reduction of IIS for warfarin compared to aspirin are most significant for cardioembolic IIS among patients with low ejection fraction in sinus rhythm. This is supported by trends to lower frequencies of severe IIS and possible cardioembolic IIS in patients on warfarin compared to aspirin.
Inductive Ability of Human Developing and Differentiated Dental Mesenchyme
Authors: Zheng Liwei , Warotayanont Rungnapa , Stahl Jonathan , Kunimatsu Ryo , Klein Ophir , DenBesten Pamela K. , Zhang Yan
Published: July 2013

The development of cell-based therapeutic strategies to bioengineer tooth tissue is a promising approach for the treatment of lost or damaged tooth tissue. The lack of a readily available cell source for human dental epithelial cells (ECs) severely constrains the progress of tooth bioengineering. Previous studies in model organisms have demonstrated that developing dental mesenchyme can instruct nondental epithelium to differentiate into enamel-forming epithelium. In this study, we characterized the ability of fetal and adult human dental mesenchyme to promote differentiation of human embryonic stem cell (hESC)-derived ECs (ES-ECs) into ameloblast-lineage cells. ES-ECs were co-cultured either with human fetal dental mesenchymal cells (FDMCs) or with adult dental mesenchymal cells (ADMCs) in either a three-dimensional culture system, or in the renal capsules of SCID mice. When co-cultured with FDMCs in vitro, ES-ECs polarized and expressed amelogenin. Tooth organ-like structures assembled with epithelium and encased mesenchyme and developing enamel-like structures could be detected in the complexes resulting from in vitro and ex vivo co-culture of ES-ECs and FDMCs. In contrast, co-cultured ES-ECs and ADMCs formed amorphous spherical structures and occasionally formed hair. Transcription factors were significantly upregulated in FDMCs compared to ADMCs including MSX1, GLI1, LHX6, LHX8,LEF1 and TBX1. In summary, FDMCs but not ADMCs had the capacity to induce differentiation of ES-ECs into ameloblast lineage cells. Further characterization of the functional differences between these two types of dental mesenchyme could enable reprogramming of ADMCs to enhance their odontogenic inductive competence.
Endothelial Cell–Dependent Regulation of Arteriogenesis
Authors: Moraes Filipa , Paye Julie , Mac Gabhann Feilim , Zhuang Zhen W. , Zhang Jiasheng , Lanahan Anthony A. , Simons Michael
Published: July 2013

Rationale
:

Arteriogenesis is the process of formation of arterial conduits. Its promotion is an attractive therapeutic strategy in occlusive atherosclerotic diseases. Despite the functional and clinical importance of arteriogenesis, the biology of the process is poorly understood. Synectin, a gene previously implicated in the regulation of vascular endothelial cell growth factor signaling, offers a unique opportunity to determine relative contributions of various cell types to arteriogenesis.

Objective
:

We investigated the cell-autonomous effects of a synectin knockout in arterial morphogenesis.

Methods and Results
:

A floxed synectin knockin mouse line was crossbred with endothelial-specific (Tie2, Cdh5, Pdgfb) and smooth muscle myosin heavy chain–specific Cre driver mouse lines to produce cell type–specific deletions. Ablation of synectin expression in endothelial, but not smooth muscle cells resulted in the presence of developmental arterial morphogenetic defects (smaller size of the arterial tree, reduced number of arterial branches and collaterals) and impaired arteriogenesis in adult mice.

Conclusions
:

Synectin modulates developmental and adult arteriogenesis in an endothelial cell–autonomous fashion. These findings show for the first time that endothelial cells are central to both developmental and adult arteriogenesis and provide a model for future studies of factors involved in this process.
Reproducibility of Blood Pressure Responses to Dietary Sodium and Potassium Interventions
Authors: Gu Dongfeng , Zhao Qi , Chen Jing , Chen Ji-Chun , Huang Jianfeng , Bazzano Lydia A. , Lu Fanghong , Mu Jianjun , Li Jianxin , Cao Jie , Mills Katherine , Chen Chung-Shiuan , Rice Treva , Hamm L. Lee , He Jiang
Published: July 2013

Blood pressure responses to dietary sodium and potassium interventions vary among individuals. We studied the long-term reproducibility of blood pressure responses to dietary sodium and potassium intake. We repeated the dietary sodium and potassium interventions among 487 Chinese adults 4.5 years after the original dietary intervention. The identical dietary intervention protocol, which included a 7-day low-sodium feeding (51.3 mmol/d), a 7-day high-sodium feeding (307.8 mmol/d), and a 7-day high-sodium feeding with oral potassium supplementation (60.0 mmol/d), was applied in both the initial and repeated studies. Three blood pressure measurements were obtained during each of the 3 days of baseline observation and on days 5, 6, and 7 of each intervention period. The results from the 24-hour urinary excretion of sodium and potassium showed excellent compliance with the study diet. Blood pressure responses to dietary intervention in the original and repeated studies were highly correlated. For example, the correlation coefficients (95% confidence interval) for systolic blood pressure levels were 0.77 (0.73–0.80) at baseline, 0.79 (0.75–0.82) during low sodium, 0.80 (0.77–0.83) during high sodium, and 0.82 (0.79–0.85) during high sodium and potassium supplementation interventions (all
P
<0.0001). The correlation coefficients for systolic blood pressure changes were 0.37 (0.29–0.44) from baseline to low sodium, 0.37 (0.29–0.44) from low to high sodium, and 0.28 (0.20–0.36) from high sodium to high sodium plus potassium supplementation (all
P
<0.0001). These data indicate that blood pressure responses to dietary sodium and potassium interventions have long-term reproducibility and stable characteristics in the general population.
A Novel Interaction Between Sympathetic Overactivity and Aberrant Regulation of Renin by miR-181a in BPH/2J Genetically Hypertensive Mice
Authors: Jackson Kristy L. , Marques Francine Z. , Watson Anna M.D. , Palma-Rigo Kesia , Nguyen-Huu Thu-Phuc , Morris Brian J. , Charchar Fadi J. , Davern Pamela J. , Head Geoffrey A.
Published: July 2013

Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin–angiotensin system. Our aim was to determine the contribution of the renin–angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg IP) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg IP) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (
P
=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA;
P
=0.02) and 0.8-fold lower abundance of micro-RNA-181a (
P
=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (
r
=0.99;
P
=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin–angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin–angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.
Discussion on the systematic position of the oxyteline rove beetle Anotylus archaicus Yue, Makranczy & Ren, 2012 (Coleoptera: Staphylinidae)
Authors: Cai Chenyang , Huang Diying
Published: July 2013

A remarkable oxyteline rove beetle species, Anotylus archaicus Yue, Makranczy & Ren, 2012, has recently been described based on several exquisitely preserved fossil impressions from the Lower Cretaceous Yixian Formation of Liaoning, northeast China. Based on our two new specimens and a comprehensive comparison with extant Anotylus species, we here suggest that all the previously-reported and new specimens, bearing separated gular sutures, sub-contiguous mesocoxae, 5-segmented metatarsi, short and poorly-sclerotized abdominal segment II, and abdominal segments III–VII each with one pair of paratergites, represent a new genus and belong to the basal oxyteline tribe Euphaniini rather than Oxytelini. In addition, it was suggested as the earliest fossil rove beetle demonstrating sexual dimorphism, the male with strong projections of the anterior pronotal angles. However, we suggest that the sexual dimorphism is probably misinterpreted, since the so-called projections can also be found in a female specimen. The projections actually formed when the anterior pronotal margin broke, a condition when the head is retracted into the pronotum.
New mantidflies (Neuroptera: Mantispidae) from the Upper Jurassic of Kazakhstan
Authors: Khramov Alexander V.
Published: July 2013

Two new species of Mantispidae, Mesithone carnaria sp.n. and M. monstruosa sp.n., from the Upper Jurassic deposits at Karatau (Kazakhstan) are described. These new species are assigned to the extinct subfamily Mesithoninae. M. proteaPanfilov, 1980 and M. gracilisPanfilov, 1980 are excluded from Mesithone. The family Mesithonidae is synonymized with Mantispidae and the relationship of Mesithoninae with the four recent mantispid subfamilies is briefly discussed.
The first diplatyid earwig in Tertiary amber (Dermaptera: Diplatyidae): A new species from Miocene Mexican amber
Authors: Ross Andrew J. , Engel Michael S.
Published: July 2013

The first earwig (Dermaptera) to be described from Mexican (Miocene) amber is named Haplodiplatys crightoni Ross & Engel sp.n., represented by an adult female and constituting the second record of the basal family Diplatyidae in the fossil record. Brief comments are made regarding the biogeographic implications of the fossil and the evolutionary history of Diplatyidae.
Revision of the genus Stichelia Zikán (Riodinidae: Riodininae: Symmachiini), with the description of a new species from southern Brazil
Authors: Silva Dias Fernando Maia , Dolibaina Diego Rodrigo , Mielke Olaf Hermann Hendrik , Casagrande Mirna Martins
Published: July 2013

A new species from southern Brazil, Stichelia catarinensis sp. nov., is described and lectotypes for Charis dukinfieldia Schaus, 1902 and Phaenochitonia bocchoris suavis Stichel, 1911 are designated. Phaenochitonia bocchoris suavis Stichel, 1911 syn. nov. is considered synonymous with Amarynthis bocchoris Hewitson, 1876. Two species groups are recognized: "cuneifascia" species group, including S. cuneifascia and S. catarinensis sp. nov., and "bocchoris" species group, including S. bocchoris, S. dukinfieldia and S. pelotensis. Additionally, a taxonomic dichotomous key and morphologic illustration for the species of the genus are provided.
A taxonomic review of Oberthueria Kirby, 1892 (Lepidoptera, Bombycidae: Oberthuerinae) with description of three new species
Authors: ZOLOTUHIN VADIM V. , WANG XING
Published: July 2013

The genus Oberthueria Kirby, 1892 is revised and three new species are described: O. yandu Zolotuhin & Xing Wang, sp. nov. (TL: China, Sichuan, Volong Reserve, Siguliang Shan), O. jiatongae Zolotuhin & Xing Wang, sp. nov. (TL: China, prov. Shaanxi, Taibaishan Mts (S), Tsinling Mts., Foping NT), and O. lunwan Zolotuhin & Xing Wang, sp. nov. (TL: Yunnan prov. (NW), Dali Bai autonom pref., Yulong county).
A new ectoparasitic distichodontid of the genus Eugnathichthys (Characiformes: Citharinoidei) from the Congo basin of central Africa, with a molecular phylogeny for the genus
Authors: STIASSNY MELANIE L.J. , DENTON JOHN S.S. , IYABA RAOUL J.C. MONSEMBULA
Published: July 2013

A new species of ectoparasitic distichodontid, Eugnathichthys virgatus, is described from localities in the central and western Congo basin. The new species is a fin-eater even at small sizes and, in common with congeners, is capable of biting off sections of heavily ossified fin-rays of large prey species. Prior to the present study, two species were included in this distinctive distichodontid genus: the type species, Eugnathichthys eetveldii, and a second species, E. macroterolepis, both of which are widely distributed throughout much of the Congo basin. Morphologically, E. virgatus is readily distinguished from its two congeners based on a combination of meristic and morphometric attributes. The new species possesses a unique pigmentation pattern, a reduced number of pectoral-fin rays, and a markedly reduced dentition on the fifth ceratobranchial elements of the pharynx, all of which are derived features considered diagnostic for the new species. With molecular data the species is further diagnosed by four apomorphic, non-synonomous nucleotide transitions in two sampled genes (NADH dehydrogenase subunit 2 and glycosyltransferase). Phylogenetic analysis of those mtDNA and ncDNA markers supports a sister-group relationship between E. virgatus and E. eetveldii rather than with E. macroterolepis, the species with which it bears closest phenetic similarity.
The first teresomatan caecilian (Amphibia: Gymnophiona) from the Eastern Ghats of India—a new species of Gegeneophis Peters, 1880
Authors: AGARWAL ISHAN , WILKINSON MARK , MOHAPATRA PRATYUSH P. , DUTTA SUSHIL K. , GIRI VARAD B. , GOWER DAVID J.
Published: July 2013

A new species of caecilian amphibian, Gegeneophis orientalis sp. nov., is described based on a series of nine specimens from high elevation (ca. 1,200 m) habitats in the Eastern Ghats in the states of Andhra Pradesh and Odisha, India. This species differs from all other congeners in having only bicuspid teeth in the outer as well as inner rows. The new species is the first caecilian reported from the state of Odisha, the first teresomatan caecilian from the Eastern Ghats, and is the only Indian indotyphlid known from outside the Western Ghats region.
Studies on subterranean amphipod crustaceans of Primory, Russia. Part 1. Three new species of the genus Pseudocrangonyx from springs and other groundwater habitats in far eastern Russia
Authors: SIDOROV DMITRY A. , GONTCHAROV ANDREY A.
Published: July 2013

Three new species of the subterranean amphipod of the genus Pseudocrangonyx: P. tiunovi sp. nov., P. holsingeri sp. nov., P. sympatricus sp. nov. and male specimen for P. kseniae Sidorov, 2012 from the South Primory, Far East of Russia are described. The species were found in springs and related groundwater habitats of several river systems belonging to the Japan Sea basin. Phylogenetic analysis based on mt-cox1 sequences supported the species distinctness. A key for the South Primory species of Pseudocrangonyx is provided.
On the Initial Development of Asymmetric Vertical Motion and Horizontal Relative Flow in a Mature Tropical Cyclone Embedded in Environmental Vertical Shear
Authors: Xu Yamei , Wang Yuqing
Published: July 2013

In this paper, the authors focus on the initial development of asymmetric vertical motion and horizontal relative flow in a mature tropical cyclone (TC) embedded in an environmental vertical shear. The fully compressible, nonhydrostatic TC model was used to perform a series of numerical experiments with a mature TC with different intensities embedded in shear with different magnitudes and different vertical profiles.

Results show that the development of both the wavenumber-1 asymmetric vertical motion and horizontal relative flow for a TC embedded in vertical shear is quite sensitive to both the magnitude and the vertical profile of wind shear, as well as the intensity of the TC itself. Diagnostic analysis based on the quasi-balanced potential vorticity inversion indicates that the balanced dynamics can only explain a small portion of the asymmetric vertical motion and relative flow. The unbalanced processes contribute predominantly to the development of the asymmetric flow in the simulations. It is shown that the eyewall of a mature TC plays a role somewhat like a material cylinder embedded in an environmental flow with vertical shear. The interaction between the environmental shear and the eyewall produces vertical gradient of convergence/divergence of horizontal wind around the lateral edge of the eyewall. This forces much stronger asymmetric vertical motion than the balanced processes do and drives significant horizontal relative divergent flow over the storm core, which opposes vertical shear and reduces the vertical tilt of the storm axis. In addition, the budget analysis for the axisymmetric tangential wind demonstrates that the asymmetric flow plays a dominant role in weakening the storm top down.
The Influence of Environmental Low-Level Shear and Cold Pools on Tornadogenesis: Insights from Idealized Simulations
Authors: Markowski Paul M. , Richardson Yvette P.
Published: July 2013

Idealized, dry simulations are used to investigate the roles of environmental vertical wind shear and baroclinic vorticity generation in the development of near-surface vortices in supercell-like “pseudostorms.” A cyclonically rotating updraft is produced by a stationary, cylindrical heat source imposed within a horizontally homogeneous environment containing streamwise vorticity. Once a nearly steady state is achieved, a heat sink, which emulates the effects of latent cooling associated with precipitation, is activated on the northeastern flank of the updraft at low levels. Cool outflow emanating from the heat sink spreads beneath the updraft and leads to the development of near-surface vertical vorticity via the “baroclinic mechanism,” as has been diagnosed or inferred in actual supercells that have been simulated and observed.

An intense cyclonic vortex forms in the simulations in which the environmental low-level wind shear is strong and the heat sink is of intermediate strength relative to the other heat sinks tested. Intermediate heat sinks result in the development (baroclinically) of substantial near-surface circulation, yet the cold pools are not excessively strong. Moreover, the strong environmental low-level shear lowers the base of the midlevel mesocyclone, which promotes strong dynamic lifting of near-surface air that previously resided in the heat sink. The superpositioning of the dynamic lifting and circulation-rich, near-surface air having only weak negative buoyancy facilitates near-surface vorticity stretching and vortex genesis. An intense cyclonic vortex fails to form in simulations in which the heat sink is excessively strong or weak or if the low-level environmental shear is weak.
Comments on “Current GCMs' Unrealistic Negative Feedback in the Arctic”
Authors: Pithan Felix , Mauritsen Thorsten
Published: July 2013

In contrast to prior studies showing a positive lapse-rate feedback associated with the Arctic inversion, Boé et al. reported that strong present-day Arctic temperature inversions are associated with stronger negative longwave feedbacks and thus reduced Arctic amplification in the model ensemble from phase 3 of the Coupled Model Intercomparison Project (CMIP3). A permutation test reveals that the relation between longwave feedbacks and inversion strength is an artifact of statistical self-correlation and that shortwave feedbacks have a stronger correlation with intermodel spread. The present comment concludes that the conventional understanding of a positive lapse-rate feedback associated with the Arctic inversion is consistent with the CMIP3 model ensemble.
Atmosphere–Ocean Interactions at Strong Couplings in a Simple Model of El Niño
Authors: Navarra A. , Tribbia J. , Conti G.
Published: July 2013

The understanding of the dynamics of the El Niño–La Niña phenomenon in the tropical Pacific has been the subject of an impressive number of works in the last 20 years. The delayed oscillator theory provides an interpretative framework that has allowed enormous advances in understanding. Much evidence that stochastic forcing does play a role in the dynamics of ENSO has been discussed and it is possible to shape a theory of El Niño as a stochastically forced linear system. However, it is still uncertain if El Niño is a self-sustained nonlinear oscillatory system, a chaotic system, or a stochastically forced linear system. The authors propose in this paper that it is possible to have realistic El Niño probability distributions assuming that the system is a nonlinear stochastically forced system. In this paper a simple system is proposed that retains the main characteristics of the El Niño–La Niña variations, such as the skewness and the autocorrelation, and it is shown how solutions for the probability distribution can be obtained using a Fokker–Planck equation.
Greenhouse Gas–Induced Changes in Summer Precipitation over Colorado in NARCCAP Regional Climate Models*
Authors: Alexander Michael A. , Scott James D. , Mahoney Kelly , Barsugli Joseph
Published: July 2013

Precipitation changes between 32-yr periods in the late twentieth and mid-twenty-first centuries are investigated using regional climate model simulations provided by the North American Regional Climate Change Assessment Program (NARCCAP). The simulations generally indicate drier summers in the future over most of Colorado and the border regions of the adjoining states. The decrease in precipitation occurs despite an increase in the surface specific humidity. The domain-averaged decrease in daily summer precipitation occurs in all of the models from the 50th through the 95th percentile, but without a clear agreement on the sign of change for the most extreme (top 1% of) events.
The Development of a Statistical Forecast Model for Changma
Authors: Lee Seung-Eon , Seo Kyong-Hwan
Published: July 2013

Forecasting year-to-year variations in East Asian summer monsoon (EASM) precipitation is one of the most challenging tasks in climate prediction because the predictors are not sufficiently well known and the forecast skill of the numerical models is poor. In this paper, a statistical forecast model for changma (the Korean portion of the EASM system) precipitation is proposed that was constructed with three physically based predictors. A forward-stepwise regression was used to select the predictors that included sea surface temperature (SST) anomalies over the North Pacific, the North Atlantic, and the tropical Pacific Ocean. Seasonal predictions with this model showed high forecasting capabilities that had a Gerrity skill score of ~0.82. The dynamical processes associated with the predictors were examined prior to their use in the prediction scheme. All predictors tended to induce an anticyclonic anomaly to the east or southeast of Japan, which was responsible for transporting a large amount of moisture to the southern Korean Peninsula. The predictor in the North Pacific formed an SST front to the east of Japan during the summertime, which maintained a lower-tropospheric baroclinicity. The North Atlantic SST anomaly induced downstream wave propagation in the upper troposphere, developing anticyclonic activity east of Japan. Forcing from the tropical Pacific SST anomaly triggered a cyclonic anomaly over the South China Sea, which was maintained by atmosphere–ocean interactions and induced an anticyclonic anomaly via northward Rossby wave propagation. Overall, the model used for forecasting changma precipitation performed well (R = 0.85) and correctly predicted information for 16 out of 19 yr of observational data.