bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained AS160 and TBC1D1 phosphorylations in human skeletal muscle 30 min after a single bout of exercise
Authors: Vendelbo M. H. , Møller A. B. , Treebak J. T. , Gormsen L. C. , Goodyear L. J. , Wojtaszewski J. F. P. , Jørgensen J. O. L. , Møller N. , Jessen N.
Published: May 2014

Background: phosphorylation of AS160 and TBC1D1 plays an important role for GLUT4 mobilization to the cell surface. The phosphorylation of AS160 and TBC1D1 in humans in response to acute exercise is not fully characterized. Objective: to study AS160 and TBC1D1 phosphorylation in human skeletal muscle after aerobic exercise followed by a hyperinsulinemic euglycemic clamp. Design: eight healthy men were studied on two occasions: 1) in the resting state and 2) in the hours after a 1-h bout of ergometer cycling. A hyperinsulinemic euglycemic clamp was initiated 240 min after exercise and in a time-matched nonexercised control condition. We obtained muscle biopsies 30 min after exercise and in a time-matched nonexercised control condition ( t = 30) and after 30 min of insulin stimulation ( t = 270) and investigated site-specific phosphorylation of AS160 and TBC1D1. Results: phosphorylation on AS160 and TBC1D1 was increased 30 min after the exercise bout, whereas phosphorylation of the putative upstream kinases, Akt and AMPK, was unchanged compared with resting control condition. Exercise augmented insulin-stimulated phosphorylation on AS160 at Ser341and Ser704270 min after exercise. No additional exercise effects were observed on insulin-stimulated phosphorylation of Thr642and Ser588on AS160 or Ser237and Thr596on TBC1D1. Conclusions: AS160 and TBC1D1 phosphorylations were evident 30 min after exercise without simultaneously increased Akt and AMPK phosphorylation. Unlike TBC1D1, insulin-stimulated site-specific AS160 phosphorylation is modified by prior exercise, but these sites do not include Thr642and Ser588. Together, these data provide new insights into phosphorylation of key regulators of glucose transport in human skeletal muscle.
Length-force characteristics of in vivo human muscle reflected by supersonic shear imaging
Authors: Sasaki Kazushige , Toyama Sho , Ishii Naokata
Published: May 2014

Recently, an ultrasound-based elastography technique has been used to measure stiffness (shear modulus) of an active human muscle along the axis of contraction. Using this technique, we explored 1) whether muscle shear modulus, like muscle force, is length dependent; and 2) whether the length dependence of muscle shear modulus is consistent between electrically elicited and voluntary contractions. From nine healthy participants, ankle joint torque and shear modulus of the tibialis anterior muscle were measured at five different ankle joint angles during tetanic contractions and during maximal voluntary contractions. Fascicle length, pennation angle, and tendon moment arm length of the tetanized tibialis anterior calculated from ultrasound images were used to reveal the length-dependent changes in muscle force and shear modulus. Over the range of joint angles examined, both force and shear modulus of the tetanized muscle increased with increasing fascicle length. Regression analysis of normalized data revealed a significant linear relationship between force and shear modulus ( R2= 0.52, n = 45, P < 0.001). Although the length dependence of shear modulus was consistent, irrespective of contraction mode, the slope of length-shear modulus relationship was steeper during maximal voluntary contractions than during tetanic contractions. These results provide novel evidence that length-force relationship, one of the most fundamental characteristics of muscle, can be inferred from in vivo imaging of shear modulus in the tibialis anterior muscle. Furthermore, the estimation of length-force relationship may be applicable to voluntary contractions in which neural and mechanical interactions of multiple muscles are involved.
Altered nutrient response of mTORC1 as a result of changes in REDD1 expression: effect of obesity vs. REDD1 deficiency
Authors: Williamson David L. , Li Zhuyun , Tuder Rubin M. , Feinstein Elena , Kimball Scot R. , Dungan Cory M.
Published: May 2014

Although aberrant mTORC1 signaling has been well established in models of obesity, little is known about its repressor, REDD1. Therefore, the initial goal of this study was to determine the role of REDD1 on mTORC1 in obese skeletal muscle. REDD1 expression (protein and message) and mTORC1 signaling (S6K1, 4E-BP1, raptor-mTOR association, Rheb GTP) were examined in lean vs. ob/ob and REDD1 wild-type (WT) vs. knockout (KO) mice, under conditions of altered nutrient intake [fasted and fed or diet-induced obesity (10% vs. 60% fat diet)]. Despite higher ( P < 0.05) S6K1 and 4E-BP1 phosphorylation, two models of obesity ( ob/ob and diet-induced) displayed elevated ( P < 0.05) skeletal muscle REDD1 expression compared with lean or low-fat-fed mouse muscle under fasted conditions. The ob/ob mice displayed elevated REDD1 expression ( P < 0.05) that coincided with aberrant mTORC1 signaling (hyperactive S6K1, low raptor-mTOR binding, elevated Rheb GTP; P < 0.05) under fasted conditions, compared with the lean, which persisted in a dysregulated fashion under fed conditions. REDD1 KO mice gained limited body mass on a high-fat diet, although S6K1 and 4E-BP1 phosphorylation remained elevated ( P < 0.05) in both the low-fat and high-fat-fed KO vs. WT mice. Similarly, the REDD1 KO mouse muscle displayed blunted mTORC1 signaling responses (S6K1 and 4E-BP1, raptor-mTOR binding) and circulating insulin under fed conditions vs. the robust responses ( P < 0.05) in the WT fed mouse muscle. These studies suggest that REDD1 in skeletal muscle may serve to limit hyperactive mTORC1, which promotes aberrant mTORC1 signaling responses during altered nutrient states.
Genome-Wide Screening of Cytogenetic Abnormalities in Multiple Myeloma Patients Using Array-CGH Technique: A Czech Multicenter Experience
Authors: Smetana Jan , Frohlich Jan , Zaoralova Romana , Vallova Vladimira , Greslikova Henrieta , Kupska Renata , Nemec Pavel , Mikulasova Aneta , Almasi Martina , Pour Ludek , Adam Zdenek , Sandecka Viera , Zahradová Lenka , Hajek Roman , Kuglik Petr
Published: June 2014

Characteristic recurrent copy number aberrations (CNAs) play a key role in multiple myeloma (MM) pathogenesis and have important prognostic significance for MM patients. Array-based comparative genomic hybridization (aCGH) provides a powerful tool for genome-wide classification of CNAs and thus should be implemented into MM routine diagnostics. We demonstrate the possibility of effective utilization of oligonucleotide-based aCGH in 91 MM patients. Chromosomal aberrations associated with effect on the prognosis of MM were initially evaluated by I-FISH and were found in 93.4% (85/91). Incidence of hyperdiploidy was 49.5% (45/91); del(13)(q14) was detected in 57.1% (52/91); gain(1)(q21) occurred in 58.2% (53/91); del(17)(p13) was observed in 15.4% (14/91); and t(4;14)(p16;q32) was found in 18.6% (16/86). Genome-wide screening using Agilent 44K aCGH microarrays revealed copy number alterations in 100% (91/91). Most common deletions were found at 13q (58.9%), 1p (39.6%), and 8p (31.1%), whereas gain of whole 1q was the most often duplicated region (50.6%). Furthermore, frequent homozygous deletions of genes playing important role in myeloma biology such as TRAF3, BIRC1/BIRC2, RB1, or CDKN2C were observed. Taken together, we demonstrated the utilization of aCGH technique in clinical diagnostics as powerful tool for identification of unbalanced genomic abnormalities with prognostic significance for MM patients.
The Roles of Regulatory B Cells in Cancer
Authors: He Yan , Qian Hongyan , Liu Yuan , Duan Lihua , Li Yan , Shi Guixiu
Published: June 2014

Regulatory B cells (Bregs), a newly described subset of B cells, have been proved to play a suppressive role in immune system. Bregs can inhibit other immune cells through cytokines secretion and antigen presentation, which give them the role in the pathogenesis of autoimmune diseases and cancers. There are no clear criteria to identify Bregs; different markers were used in the different experimental conditions. Massive researches had described the functions of immune cells such as regulatory T cells (Tregs), dendritic cells (DCs), and B cells in the autoimmune disorder diseases and cancers. More and more researches focused on the roles of Bregs and the cytokines such as Interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) secreted by Bregs. The aim of this review is to summarize the characteristics of Bregs and the roles of Bregs in cancer.
New Quasi-One-Dimensional Organic-Inorganic Hybrid Material: 1,3-Bis(4-piperidinium)propane Pentachlorobismuthate(III) Synthesis, Crystal Structure, and Spectroscopic Studies
Authors: Ferjani Hela , Boughzala Habib
Published: June 2014

The organic-inorganic hybrid compound (C13H28N2) BiCl5 was synthesized by solvothermal method. The crystal structure was solved by single-crystal X-ray diffraction. The compound crystallizes in the orthorhombic system space group Cmc21 with a=15.826(4) Å, b=18.746(6) Å, c=7.470(3) Å, and Z=4. The crystal structure was refined down to R=0.019. It consists of corrugated layers of [BiCl5]2− chains, separated by organic [H2TMDP]2+ cations (TMDP=1,3-Bis(4-piperidyl)propane = C13H26N2). The crystal cohesion is achieved by hydrogen bonds N–H⋯Cl joining the organic and inorganic layers. The influence of the organic cations' flexibility is discussed. Raman and infrared spectra of the title compound were recorded in the range of 50–400 and 400–4000 cm−1, respectively. Semiempirical parameter model three (PM3) method has been performed to derive the calculated IR spectrum. The crystal shape morphology was simulated using the Bravais-Friedel and Donnay-Harker model.
Comparison of Anterior Segment Measurements Obtained by Three Different Devices in Healthy Eyes
Authors: Lopez de la Fuente Carmen , Sanchez-Cano Ana , Segura Francisco , Pinilla Isabel
Published: June 2014

Purpose. To assess the normal values and the repeatability of the Galilei Dual Scheimpflug Analyzer (GDSA), the biometer IOL Master, and the autokerato/refractometer WAM 5500 in anterior segment examinations.Methods. Eighty-eight eyes from 88 healthy volunteers were prospectively and consecutively recruited. The repeatability was assessed, calculating the intraclass correlation coefficient (ICC).Results. The correlations among the repeated measurements showed nearly perfect reliability (ICC > 0.81) for all of the parameters, except corneal astigmatism Galilei (0.79) and WAM (0.68). There were statistically significant differences (P<0.001) between the values of the flat simulated keratometry (SimK) and the steep SimK measured by GDSA and the other methods; however, there were no statistically significant differences for the values obtained with the IOL Master and WAM 5500 (P=0.302andP=0.172, resp.) or between the values of the ACD (P<0.001) and WTW (P=0.007) measured by the IOL Master and GDSA.Conclusions. The anterior segment measurements from the IOL Master and WAM 5500 were highly repeatable, comparable, and well correlated. In healthy young persons, the evaluated parameters had very good repeatability, although significant differences were found between the GDSA and IOL Master and between the GDSA and WAM 5500.
Students’ Digital Photography Behaviors during a Multiday Environmental Science Field Trip and Their Recollections of Photographed Science Content
Authors: Lee Victor R.
Published: June 2014

Taking photographs to document the experiences of an educational field trip is becoming a common activity for teachers and students alike. Considering the regular creation of photographic artifacts, our goal in this paper is to explore students’ picture taking behavior and their recollections of science content associated with their photographs. In this study, we partnered with a class of fifth-grade students in the United States and provided each student with a digital camera to document their experiences during an environmental science field trip at a national park. We report the frequency of photography behaviors according to which activities were most often documented by the students and specifically that students tended to document more of their experiences when they were in outdoor, natural spaces rather than inside of visitor centers or museums. Also, through an analysis of students’ comments about the science content captured in their photographs we observe that students’ comments about photographs of the outdoors tended to show greater depth and complexity than those that were taken in indoor, museum-like spaces.
q-Extensions for the Apostol Type Polynomials
Authors: Mahmudov Nazim I. , Eini Keleshteri Marzieh
Published: June 2014

The aim of this work is to introduce an extension forq-standard notations. Theq-Apostol type polynomials and study some of their properties. Besides, some relations between the mentioned polynomials and some other known polynomials are obtained.
The Effects and Measures of Auricular Acupressure and Interactive Multimedia for Smoking Cessation in College Students
Authors: Yeh Mei-Ling , Wang Pei-Lan , Lin Jaung-Geng , Chung Mei-Ling
Published: June 2014

The earlier one starts to smoke, the more likely it is that one’s tobacco use will increase. Either auricular acupressure or multimedia education could improve physiological health status and reduce smoking for young smokers. This study aimed to evaluate the effects of a 10‐week auricular acupressure (AA) and interactive multimedia (IM) on smoking cessation in college smokers. A pre‐ and posttest control research design with two experiments (AA and IM) and one control was used. Thirty‐two participants were in each of three groups. A significant difference from pretest to posttest among three groups was exhibited on carbon monoxide (CO), cotinine, and nicotine dependence. Scheffe’s post hoc test found significances on CO in the AA between the IM and the control and cotinine and nicotine dependence between the AA and the control. After controlling the covariates, the main effect of the group was no difference in all outcomes. The interventions, especially AA, may contribute to a decrease of CO, cotinine, and nicotine dependence along with the time change. An analysis without controlling influences may overestimate interventional effects.
Prevalence and Direct Economic Losses from Bovine Tuberculosis in Makurdi, Nigeria
Authors: Ejeh E. F. , Raji M. A. , Bello M. , Lawan F. A. , Francis M. I. , Kudi A. C. , Cadmus S. I. B.
Published: June 2014

A retrospective study was conducted to investigate the prevalence of bovine tuberculosis and direct economic losses (DEL) from tuberculosis in cattle slaughtered in Makurdi abattoirs from 2008 to 2012, using abattoir records obtained from the Ministry of Agriculture and Natural Resources. Out of 61654 cattle slaughtered during the study period 1172 (1.90%) were positive for tuberculosis lesions. The annual prevalence of bovine tuberculosis ranges from 0.90% in 2008 to 4.04% in 2012. There was significant (P<0.05) difference in annual prevalence of bovine tuberculosis. It was also observed that there was no seasonal difference in the prevalence of bovine tuberculosis. A total of 1935 affected organs by BTB weighing 3046.50 kg, amounting to 2.91 × 106 Naira (1.82 × 104 USD), were condemned within the study period. Seasonal variation in organ condemnation due to bovine tuberculosis was significantly different (Mann-WhitneyUstatistics = 774 × 103,P=0.034). It was concluded that bovine tuberculosis is prevalent in Makurdi and accounts for heavy economic losses due to condemnation of edible organs.
ABC and IFC: Modules Detection Method for PPI Network
Authors: Lei Xiujuan , Wu Fang-Xiang , Tian Jianfang , Zhao Jie
Published: June 2014

Many clustering algorithms are unable to solve the clustering problem of protein-protein interaction (PPI) networks effectively. A novel clustering model which combines the optimization mechanism of artificial bee colony (ABC) with the fuzzy membership matrix is proposed in this paper. The proposed ABC-IFC clustering model contains two parts: searching for the optimum cluster centers using ABC mechanism and forming clusters using intuitionistic fuzzy clustering (IFC) method. Firstly, the cluster centers are set randomly and the initial clustering results are obtained by using fuzzy membership matrix. Then the cluster centers are updated through different functions of bees in ABC algorithm; then the clustering result is obtained through IFC method based on the new optimized cluster center. To illustrate its performance, the ABC-IFC method is compared with the traditional fuzzy C-means clustering and IFC method. The experimental results on MIPS dataset show that the proposed ABC-IFC method not only gets improved in terms of several commonly used evaluation criteria such asprecision,recall, andPvalue, but also obtains a better clustering result.
Mast Cell–Derived Prostaglandin D2 Inhibits Colitis and Colitis-Associated Colon Cancer in Mice
Authors: Iwanaga Koichi , Nakamura Tatsuro , Maeda Shingo , Aritake Kosuke , Hori Masatoshi , Urade Yoshihiro , Ozaki Hiroshi , Murata Takahisa
Published: May 2014

Compared with prostaglandin E2, which has an established role in cancer, the role of the COX metabolite prostaglandin D2 (PGD2) in chronic inflammation leading to tumorigenesis is uncertain. In this study, we investigated the role of PGD2 in colitis and colitis-associated colon cancer (CAC) using genetically modified mice and an established model of inflammatory colon carcinogenesis. Systemic genetic deficiency in hematopoietic PGD synthase (H-PGDS) aggravated colitis and accelerated tumor formation in a manner associated with increased TNFα expression. Treatment with a TNFα receptor antagonist attenuated colitis regardless of genotype. Histologic analysis revealed that infiltrated mast cells strongly expressed H-PGDS in inflamed colons. Mast cell–specific H-PGDS deficiency also aggravated colitis and accelerated CAC. In contrast, treatment with a PGD2 receptor agonist inhibited colitis and CAC. Together, our results identified mast cell–derived PGD2 as an inhibitor of colitis and CAC, with implications for its potential use in preventing or treating colon cancer. Cancer Res; 74(11); 3011–9. ©2014 AACR.
Involvement of Extracellular Vesicle Long Noncoding RNA (linc-VLDLR) in Tumor Cell Responses to Chemotherapy
Authors: Takahashi Kenji , Yan Irene K. , Wood Joseph , Haga Hiroaki , Patel Tushar
Published: May 2014

Hepatocellular cancer (HCC) is a highly treatment-refractory cancer and is also highly resistant to adverse cellular stress. Although cell behavior can be modulated by noncoding RNAs (ncRNA) within extracellular vesicles (EV), the contributions of long noncoding RNAs (lncRNAs) are largely unknown. To this end, the involvement and functional roles of lncRNAs contained within EVs during chemotherapeutic stress in human HCC were determined. Expression profiling identified a subset of lncRNAs that were enriched in tumor cell–derived vesicles released from two different cell lines. Of these, lincRNA-VLDLR (linc-VLDLR) was significantly upregulated in malignant hepatocytes. Exposure of HCC cells to diverse anticancer agents such as sorafenib, camptothecin, and doxorubicin increased linc-VLDLR expression in cells as well as within EVs released from these cells. Incubation with EVs reduced chemotherapy-induced cell death and also increased linc-VLDLR expression in recipient cells. RNAi-mediated knockdown of linc-VLDLR decreased cell viability and abrogated cell-cycle progression. Moreover, knockdown of VLDLR reduced expression of ABCG2 (ATP-binding cassette, subfamily G member 2), whereas overexpression of this protein reduced the effects of VLDLR knockdown on sorafenib-induced cell death. Here, linc-VLDLR is identified as an EV-enriched lncRNA that contributes to cellular stress responses.

Implications: These findings provide new insight into the role of EVs and demonstrate the capacity of lncRNAs to mediate chemotherapeutic stress response in HCC. Mol Cancer Res; 12(10); 1377–87. ©2014 AACR.
Transplantation of Bone Marrow Mesenchymal Stem Cells for the Treatment of Type 2 Diabetes in a Macaque Model
Authors: Pan Xing-hua , Song Qiao-qiao , Dai Jie-jie , Yao Xiang , Wang Jin-xiang , Pang Rong-qing , He Jie , Li Zi-an , Sun Xiao-mei , Ruan Guang-ping
Published: June 2014

Bone marrow mesenchymal stem cells (BMSCs) are self-renewing, multipotent cells that can migrate to pathological sites and thereby provide a new treatment in diabetic animals. Superparamagnetic iron oxide/4′,6-diamidino-2-phenylindole (DAPI) double-labeled BMSCs were transplanted into the pancreatic artery of macaques to treat type 2 diabetes mellitus (T2DM). The treatment efficiency of BMSCs was also evaluated. After successful induction of the T2DM model, the treatment group received double-labeled BMSCs via the pancreatic artery. Six weeks after BMSC transplantation, the fasting blood glucose and blood lipid levels measured in the treatment group were significantly lower (p < 0.05) than in the model group, although they were not reduced to normal levels (p < 0.05). Additionally, the serum C-peptide levels were significantly increased (p < 0.05). An intravenous glucose tolerance test and C-peptide release test had significant changes to the area under the curve. Within 14 days of the transplantation of labeled cells, the pancreatic and kidney tissue of the treatment group emitted a negative signal that was visible on magnetic resonance imaging (MRI). Six weeks after transplantation, DAPI signals appeared in the pancreatic and kidney tissue, which indicates that the BMSCs were mainly distributed in damaged tissue. Labeled stem cells can be used to track migration and distribution in vivo by MRI. In conclusion, the transplantation of BMSCs for the treatment of T2DM is safe and effective.
Clinical Pharmacology in Neonates: Small Size, Huge Variability
Authors: Allegaert Karel , van den Anker John N.
Published: June 2014

Drug therapy is a powerful tool for improving neonatal outcome. Despite this, neonatologists still routinely prescribe off-label compounds developed for adults and extrapolate doses from those used for children or adults. Knowledge integration through pharmacokinetic modeling is a method that could improve the current situation. Such predictive models may convert neonatal pharmacotherapy from explorative to confirmatory. This can be illustrated by research projects related to the prediction of neonatal renal clearance and neonatal glucuronidation. This type of model will also improve the current knowledge of neonatal (patho)physiology. In the meanwhile, the fields of clinical pharmacology (e.g. pharmacokinetic/pharmacodynamic modeling and pharmacogenetics) and neonatology (e.g. whole-body cooling and the lower limit of viability) have both matured, resulting in new research topics. However, in order for the modeling and the newly emerging topics to become effective tools, they need to be tailored to the specific characteristics of neonates. Consequently, the field of neonatal pharmacotherapy needs dedicated neonatologists who continue to raise the awareness that off-label practices, eminence-based dosing regimens and the absence of neonatal drug formulations all reflect suboptimal care.
The Molecular Era of Surfactant Biology
Authors: Whitsett Jeffrey A.
Published: June 2014

Advances in the physiology, biochemistry, molecular and cell biology of the pulmonary surfactant system transformed the clinical care and outcome of preterm infants with respiratory distress syndrome. The molecular era of surfactant biology provided genetic insights into the pathogenesis of pulmonary disorders, previously termed ‘idiopathic', that affect newborn infants, children and adults. Knowledge related to the structure and function of the surfactant proteins and their roles in alveolar homeostasis has provided new diagnostic, prognostic and therapeutic tools to advance our understanding of the causes and treatments of acute and chronic lung diseases. Severe lung disease in newborn infants and older patients is caused by mutations in genes regulating alveolar epithelial cells and surfactant homeostasis. Mutations in genes encoding the surfactant proteins, transcription factors critical for alveolar morphogenesis and surfactant clearance, are now known to play important roles in the pathogenesis of chronic lung diseases. Identification of the genes underlying the diseases of alveolar homeostasis is useful for the diagnosis of lung disease before and after birth.
Multiple Sclerosis in Gulf War Era Veterans. 2. Military Deployment and Risk of Multiple Sclerosis in the First Gulf War
Authors: Wallin Mitchell T. , Kurtzke John F. , Culpepper William J. , Coffman Parisa , Maloni Heidi , Haselkorn Jodie K. , Mahan Clare M. ,   for the Veterans Affairs Multiple Sclerosis Centers of Excellence Epidemiology Group
Published: June 2014

Background: Concern has been raised that US veterans of the 1990-1991 Gulf War (GW1) may be at increased risk to develop neurologic disease. Methods: An incident cohort of multiple sclerosis (MS) and other demyelinating disease (ODD) was assembled from the US military comprising the Gulf War era (1990-2007). Cases of MS and ODD meeting standard diagnostic criteria were matched to a database of all active duty personnel from the Department of Defense. Relative risk (RR) estimates for MS and all demyelinating disease based on onset, deployment status, and exposures were calculated. Results: For GW1, a total of 1,841 incident cases of definite MS and ODD were identified, with 387 among 696,118 deployed and 1,454 among 1,786,215 nondeployed personnel. The RR for MS alone among those deployed compared to those nondeployed was 0.69 (confidence interval, CI: 0.61-0.78), with 0.72 (CI: 0.62-0.83) in men and 0.96 (CI: 0.75-1.22) in women. Deployment was also nonsignificant or protective as an MS risk factor across racial groups, all age groups, and each military service. RRs for MS by service were: Air Force 0.71 (CI: 0.53-0.96), Army 0.80 (CI: 0.67-0.96), Marines 0.96 (CI: 0.63-1.47), and Navy 0.56 (CI: 0.43-0.74). Conclusion: Military deployment to GW1 was not a risk factor for developing MS.
Lipoprotein Subfractions Highly Associated With Renal Damage in Familial Lecithin:Cholesterol Acyltransferase Deficiency
Authors: Kuroda Masayuki , Holleboom Adriaan G. , Stroes Erik S.G. , Asada Sakiyo , Aoyagi Yasuyuki , Kamata Kouju , Yamashita Shizuya , Ishibashi Shun , Saito Yasushi , Bujo Hideaki
Published: May 2014

Objective—

In familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD), deposition of abnormal lipoproteins in the renal stroma ultimately leads to renal failure. However, fish-eye disease (FED) does not lead to renal damage although the causative mutations for both FLD and FED lie within the same
LCAT
gene. This study was performed to identify the lipoproteins important for the development of renal failure in genetically diagnosed FLD in comparison with FED, using high-performance liquid chromatography with a gel filtration column.

Approach and Results—

Lipoprotein profiles of 9 patients with LCAT deficiency were examined. Four lipoprotein fractions specific to both FLD and FED were identified: (1) large lipoproteins (>80 nm), (2) lipoproteins corresponding to large low-density lipoprotein (LDL), (3) lipoproteins corresponding to small LDL to large high-density lipoprotein, and (4) to small high-density lipoprotein. Contents of cholesteryl ester and triglyceride of the large LDL in FLD (below detection limit and 45.8±3.8%) and FED (20.7±6.4% and 28.0±6.5%) were significantly different, respectively. On in vitro incubation with recombinant LCAT, content of cholesteryl ester in the large LDL in FLD, but not in FED, was significantly increased (to 4.2±1.4%), whereas dysfunctional high-density lipoprotein was diminished in both FLD and FED.

Conclusions—

Our novel analytic approach using high-performance liquid chromatography with a gel filtration column identified large LDL and high-density lipoprotein with a composition specific to FLD, but not to FED. The abnormal lipoproteins were sensitive to treatment with recombinant LCAT and thus may play a causal role in the renal pathology of FLD.
Cardiac and Kidney Markers for Cardiovascular Prediction in Individuals With Chronic Kidney Disease
Authors: Matsushita Kunihiro , Sang Yingying , Ballew Shoshana H. , Astor Brad C. , Hoogeveen Ron C. , Solomon Scott D. , Ballantyne Christie M. , Woodward Mark , Coresh Josef
Published: May 2014

Objective—

Traditional predictors suboptimally predict cardiovascular disease (CVD) in individuals with chronic kidney disease (CKD). This study compared 5 nontraditional cardiac and kidney markers on the improvement of cardiovascular prediction among those with CKD.

Approach and Results—

Among 8622 participants aged 52 to 75 years in the Atherosclerosis Risk in Communities (ARIC) Study, cardiac troponin T, N-terminal pro-B-type natriuretic peptide, cystatin C, β
2
-microglobulin, and β-trace protein were compared for improvement in predicting incident CVD after stratifying by CKD status (940 participants with CKD [kidney dysfunction or albuminuria]). During a median follow-up of 11.9 years, there were 1672 CVD events including coronary disease, stroke, and heart failure (336 cases in CKD). Every marker was independently associated with incident CVD in participants with and without CKD. The adjusted hazard ratios (per 1 SD) were larger for cardiac markers than for kidney markers, particularly in CKD (1.61 [95% confidence interval, 1.43–1.81] for cardiac troponin T, 1.50 [1.34–1.68] for N-terminal pro-B-type natriuretic peptide, and <1.26 for kidney markers). Particularly in CKD group, cardiac markers compared with kidney markers contributed to greater c-statistic increment (0.032–0.036 versus 0.012–0.015 from 0.679 with only conventional predictors in CKD and 0.008–0.011 versus 0.002–0.010 from 0.697 in non-CKD) and categorical net reclassification improvement (0.086–0.127 versus 0.020–0.066 in CKD and 0.057–0.077 versus 0.014–0.048 in non-CKD). The superiority of cardiac markers was largely consistent in individual CVD outcomes.

Conclusions—

A greater improvement in cardiovascular prediction was observed for cardiac markers than for kidney markers in people with CKD. These results suggest that cardiac troponin T and N-terminal pro-B-type natriuretic peptide are useful for better CVD risk classification in this population.
Super-Suppression of Mitochondrial Reactive Oxygen Species Signaling Impairs Compensatory Autophagy in Primary Mitophagic Cardiomyopathy
Authors: Song Moshi , Chen Yun , Gong Guohua , Murphy Elizabeth , Rabinovitch Peter S. , Dorn Gerald W.
Published: May 2014

Rationale
:

Mitochondrial reactive oxygen species (ROS) are implicated in aging, chronic degenerative neurological syndromes, and myopathies. On the basis of free radical hypothesis, dietary, pharmacological, and genetic ROS suppression has been tested to minimize tissue damage, with remarkable therapeutic efficacy. The effects of mitochondrial-specific ROS suppression in primary mitophagic dysfunction are unknown.

Objective
:

An in vivo dose-ranging analysis of ROS suppression in an experimental cardiomyopathy provoked by defective mitochondrial clearance.

Methods and Results
:

Mice lacking mitofusin 2 (Mfn2) in hearts have impaired parkin-mediated mitophagy leading to accumulation of damaged ROS-producing organelles and progressive heart failure. As expected, cardiomyocyte-directed expression of mitochondrial-targeted catalase at modest levels normalized mitochondrial ROS production and prevented mitochondrial depolarization, respiratory impairment, and structural degeneration in Mfn2 null hearts. In contrast, catalase expression at higher levels that supersuppressed mitochondrial ROS failed to improve either mitochondrial fitness or cardiomyopathy, revealing that ROS toxicity is not the primary mechanism for cardiac degeneration. Lack of benefit from supersuppressing ROS was associated with failure to invoke secondary autophagic pathways of mitochondrial quality control, revealing a role for ROS signaling in mitochondrial clearance. Mitochondrial permeability transition pore function was normal, and genetic inhibition of mitochondrial permeability transition pore function did not alter mitochondrial or cardiac degeneration, in Mfn2 null hearts.

Conclusions
:

Local mitochondrial ROS (1) contribute to mitochondrial degeneration and (2) activate mitochondrial quality control mechanisms. A therapeutic window for mitochondrial ROS suppression should minimize the former while retaining the latter, which we achieved by expressing lower levels of catalase.
The CAVE Score for Predicting Late Seizures After Intracerebral Hemorrhage
Authors: Haapaniemi Elena , Strbian Daniel , Rossi Costanza , Putaala Jukka , Sipi Tuulia , Mustanoja Satu , Sairanen Tiina , Curtze Sami , Satopää Jarno , Roivainen Reina , Kaste Markku , Cordonnier Charlotte , Tatlisumak Turgut , Meretoja Atte
Published: May 2014

Background and Purpose—

Seizures are a common complication of intracerebral hemorrhage (ICH). We developed a novel tool to quantify this risk in individual patients.

Methods—

Retrospective analysis of the observational Helsinki ICH Study (n=993; median follow-up, 2.7 years) and the Lille Prognosis of InTra-Cerebral Hemorrhage (n=325; 2.2 years) cohorts of consecutive ICH patients admitted between 2004 and 2010. Helsinki ICH Study patients’ province-wide electronic records were evaluated for early seizures occurring within 7 days of ICH and among 7-day survivors (n=764) for late seizures (LSs) occurring >7 days from ICH. A Cox regression model estimating risk of LSs was used to derive a prognostic score, validated in the Prognosis of InTra-Cerebral Hemorrhage cohort.

Results—

Of the Helsinki ICH Study patients, 109 (11.0%) had early seizures within 7 days of ICH. Among the 7-day survivors, 70 (9.2%) patients developed LSs. The cumulative risk of LSs was 7.1%, 10.0%, 10.2%, 11.0%, and 11.8% at 1 to 5 years after ICH, respectively. We created the CAVE score (0–4 points) to estimate the risk of LSs, with 1 point for each of cortical involvement, age <65 years, volume >10 mL, and early seizures within 7 days of ICH. The risk of LSs was 0.6%, 3.6%, 9.8%, 34.8%, and 46.2% for CAVE scores 0 to 4, respectively. The c-statistic was 0.81 (0.76–0.86) and 0.69 (0.59–0.78) in the validation cohort.

Conclusions—

One in 10 patients will develop seizures after ICH. The risk of this adverse outcome can be estimated by a simple score based on baseline variables.
Primary Preventive Potential for Stroke by Avoidance of Major Lifestyle Risk Factors
Authors: Tikk Kaja , Sookthai Disorn , Monni Stefano , Gross Marie-Luise , Lichy Christoph , Kloss Manja , Kaaks Rudolf
Published: May 2014

Background and Purpose—

Because primary prevention of stroke is a priority, our aim was to assess the primary preventive potential of major lifestyle risk factors for stroke in middle-aged women and men.

Methods—

Among 23 927 persons, 551 (195 women and 356 men) had a first diagnosis of stroke during an average follow-up of 12.7 years. Using Cox proportional hazards models, we estimated the associations of adiposity, smoking, physical activity, alcohol consumption, and diet with risk of developing stroke. A competing risk model built from cause-specific proportional hazards models accounting for concurrent risk of death was used to calculate relative and absolute reductions in stroke occurrences that could have been achieved by maintaining a healthy lifestyle pattern.

Results—

Obesity, smoking, alcohol consumption, diet, and physical inactivity were each identified as modifiable lifestyle risk factors for stroke. About 38% of stroke cases were estimated as preventable through adherence to a healthy lifestyle profile (never smoking, maintaining optimal body mass index and waist circumference, performing physical exercise, consuming a moderate quantity of alcohol, and following a healthy dietary pattern). Age-specific estimates of 5-year incidence rates for stroke in the actual cohort and in a hypothetical, comparable cohort of individuals following a healthy lifestyle would be reduced from 153 to 94 per 100 000 women and from 261 to 161 per 100 000 men for the age group 60 to 65 years.

Conclusions—

Our analysis confirms the strong primary prevention potential for stroke based on avoidance of excess body weight, smoking, heavy alcohol consumption, unhealthy diet, and physical inactivity.
Unexplained Early Neurological Deterioration After Intravenous Thrombolysis
Authors: Seners Pierre , Turc Guillaume , Tisserand Marie , Legrand Laurence , Labeyrie Marc-Antoine , Calvet David , Meder Jean-François , Mas Jean-Louis , Oppenheim Catherine , Baron Jean-Claude
Published: May 2014

Background and Purpose—

Early neurological deterioration (END) after anterior circulation stroke is a serious clinical event strongly associated with poor outcome. Regarding specifically END occurring within 24 hours of intravenous recombinant tissue-type plasminogen activator, apart from definite causes such as symptomatic intracranial hemorrhage and malignant edema whose incidence, predictors, and clinical management are well established, little is known about END without clear mechanism (END
unexplained
).

Methods—

We analyzed 309 consecutive patients thrombolysed intravenously ≤4.5 hours from onset of anterior circulation stroke. END
unexplained
was defined as a ≥4-point deterioration on 24-hour National Institutes of Health Stroke Scale, without definite mechanism on concomitant imaging. END
unexplained
and no-END patients were compared for pretreatment clinical and imaging (including magnetic resonance diffusion and diffusion/perfusion mismatch volumes) data and 24-hour post-treatment clinical (including blood pressure and glycemic changes) and imaging (24-hour recanalization) data, using univariate logistic regression. Exploratory multivariate analysis was also performed after variable reduction, with bootstrap analysis for internal validation.

Results—

Among 33 END patients, 23 (7% of whole sample) had END
unexplained
. END
unexplained
was associated with poor 3-month outcome (
P
<0.01). In univariate analysis, admission predictors of END
unexplained
included no prior use of antiplatelets (
P
=0.02), lower National Institutes of Health Stroke Scale score (
P
<0.01), higher glycemia (
P
=0.03), larger mismatch volume (
P
=0.03), and proximal occlusion (
P
=0.01), with consistent results from the multivariate analysis. Among factors recorded during the first 24 hours, only no recanalization was associated with END
unexplained
in multivariate analysis (
P
=0.02).

Conclusions—

END
unexplained
affected 7% of patients and accounted for most cases of END. Several predictors and associated factors were identified, with important implications regarding underlying mechanisms and potential prevention of this ominous event.
Tonically Balancing Intracortical Excitation and Inhibition by GABAergic Gliotransmission
Authors: Zheng Meihong , Matsuo Takami , Miyamoto Ai , Hoshino Osamu
Published: May 2014

For sensory cortices to respond reliably to feature stimuli, the balancing of neuronal excitation and inhibition is crucial. A typical example might be the balancing of phasic excitation within cell assemblies and phasic inhibition between cell assemblies. The former controls the gain of and the latter the tuning of neuronal responses. A change in ambient GABA concentration might affect the dynamic behavior of neurons in a tonic manner. For instance, an increase in ambient GABA concentration enhances the activation of extrasynaptic receptors, augments an inhibitory current, and thus inhibits neurons. When a decrease in ambient GABA concentration occurs, the tonic inhibitory current is reduced, and thus the neurons are relatively excited. We simulated a neural network model in order to examine whether and how such a tonic excitatory-inhibitory mechanism could work for sensory information processing. The network consists of cell assemblies. Each cell assembly, comprising principal cells (P), GABAergic interneurons (Ia, Ib), and glial cells (glia), responds to one particular feature stimulus. GABA transporters, embedded in glial plasma membranes, regulate ambient GABA levels. Hypothetical neuron-glia signaling via inhibitory (Ia-to-glia) and excitatory (P-to-glia) synaptic contacts was assumed. The former let transporters import (remove) GABA from the extracellular space and excited stimulus-relevant P cells. The latter let them export GABA into the extracellular space and inhibited stimulus-irrelevant P cells. The main finding was that the glial membrane transporter gave a combinatorial excitatory-inhibitory effect on P cells in a tonic manner, thereby improving the gain and tuning of neuronal responses. Interestingly, it worked cooperatively with the conventional, phasic excitatory-inhibitory mechanism. We suggest that the GABAergic gliotransmission mechanism may provide balanced intracortical excitation and inhibition so that the best perceptual performance of the cortex can be achieved.
Anatomical Constraints on Lateral Competition in Columnar Cortical Architectures
Authors: Muir Dylan R. , Cook Matthew
Published: May 2014

Competition is a well-studied and powerful mechanism for information processing in neuronal networks, providing noise rejection, signal restoration, decision making and associative memory properties, with relatively simple requirements for network architecture. Models based on competitive interactions have been used to describe the shaping of functional properties in visual cortex, as well as the development of functional maps in columnar cortex. These models require competition within a cortical area to occur on a wider spatial scale than cooperation, usually implemented by lateral inhibitory connections having a longer range than local excitatory connections. However, measurements of cortical anatomy reveal that the spatial extent of inhibition is in fact more restricted than that of excitation. Relatively few models reflect this, and it is unknown whether lateral competition can occur in cortical-like networks that have a realistic spatial relationship between excitation and inhibition. Here we analyze simple models for cortical columns and perform simulations of larger models to show how the spatial scales of excitation and inhibition can interact to produce competition through disynaptic inhibition. Our findings give strong support to the direct coupling effect—that the presence of competition across the cortical surface is predicted well by the anatomy of direct excitatory and inhibitory coupling and that multisynaptic network effects are negligible. This implies that for networks with short-range inhibition and longer-range excitation, the spatial extent of competition is even narrower than the range of inhibitory connections. Our results suggest the presence of network mechanisms that focus on intra-rather than intercolumn competition in neocortex, highlighting the need for both new models and direct experimental characterizations of lateral inhibition and competition in columnar cortex.
Subliminal Cueing of Selection Behavior in a Virtual Environment
Authors: Aranyi Gabor , Kouider Sid , Lindsay Alan , Prins Hielke , Ahmed Imtiaj , Jacucci Giulio , Negri Paolo , Gamberini Luciano , Pizzi David , Cavazza Marc
Published: May 2014

The performance of current graphics engines makes it possible to incorporate subliminal cues within virtual environments (VEs), providing an additional way of communication, fully integrated with the exploration of a virtual scene. In order to advance the application of subliminal information in this area, it is necessary to explore in the psychological literature how techniques previously reported as rendering information subliminal can be successfully implemented in VEs. Previous literature has also described the effects of subliminal cues as quantitatively modest, which raises the issue of their inclusion in practical tasks. We used a 3D rendering engine (Unity3D) to implement a masking paradigm within the context of a realistic scene and a familiar (kitchen) environment. We report significant effects of subliminal cueing on the selection of objects in a virtual scene, demonstrating the feasibility of subliminal cueing in VEs. Furthermore, we show that multiple iterations of masked objects within a trial, as well as the speeding of selection choices, can substantially reinforce the impact of subliminal cues. This is consistent with previous findings suggesting that the effect of subliminal stimuli fades rapidly. We conclude by proposing, as part of further work, possible mechanisms for the inclusion of subliminal cueing in intelligent interfaces to maximize their effects.
Subliminal Response Priming in Mixed Reality: The Ecological Validity of a Classic Paradigm of Perception
Authors: Cetnarski Ryszard , Betella Alberto , Prins Hielke , Kouider Sid , Verschure Paul F. M. J.
Published: May 2014

Subliminal stimuli can affect perception, decision-making, and action without being accessible to conscious awareness. Most evidence supporting this notion has been obtained in highly controlled laboratory conditions. Hence, its generalization to more realistic and ecologically valid contexts is unclear. Here, we investigate the impact of subliminal cues in an immersive navigation task using the so-called eXperience Induction Machine (XIM), a human accessible mixed-reality system. Subjects were asked to navigate through a maze at high speed. At irregular intervals, one group of subjects was exposed to subliminal aversive stimuli using the masking paradigm. We hypothesized that these stimuli would bias decision-making. Indeed, our results confirm this hypothesis and indicate that a subliminal channel of interaction exists between the user and the XIM. These results are relevant in our understanding of the bandwidth of communication that can be established between humans and their physical and social environment, thus opening up to new and powerful methods to interface humans and artefacts.
Redescription of immatures and bionomy of the Palaearctic species Dicladispa testacea (Linnaeus, 1767) (Coleoptera: Chrysomelidae: Cassidinae: Hispini), a leaf-mining hispine beetle
Authors: ŚWIĘTOJAŃSKA JOLANTA , BOROWIEC LECH , STACH MAŁGORZATA
Published: May 2014

Dicladispa testacea (Linnaeus, 1767) is a member of the tribe Hispini Gyllenhal, 1813 associated with plants of the family Cistaceae Juss. and is widely distributed in the Mediterranean Basin. Immature stages are described in detail, including line drawings, chaetotaxy, sculpture of integument, and SEM photos of morphological details. This is the first detailed description of immatures in the tribe Hispini, and this can be regarded as a model description for studies of other species in the tribe. Diagnostic characters for this species in comparison with other described larvae and pupae of the genus Dicladispa and the sympatric Hispa atra Linnaeus, 1767 are discussed. Some remarks on the biology of Dicladispa testacea, such as host plants, feeding patterns of adults, structure of larval and pupal mines, are also given.
A new species of Corydalus Latreille, 1802 (Megaloptera, Corydalidae) and first record of C. clavijoi Contreras-Ramos, 2002 and C. nubilus Erichson, 1848 from Colombia
Authors: ARDILA-CAMACHO ADRIAN
Published: May 2014

A new species of the dobsonfly genus Corydalus from the Colombian Andean region is described and illustrated. This species is unique in having the longest tenth gonostyli of all known species of the genus and is apparently closely related to members of the C. nubilus group. In addition, C. clavijoi Contreras-Ramos and C. nubilus Erichson are recorded for the first time from Colombia and new Colombian locality records are provided for other known species. A key to Colombian species of Corydalus is included.