bluuebunny/crossref_metadata_2025 huggingface dataset:
Local interneurons and projection neurons in the antennal lobe from a spiking point of view
Authors: Meyer Anneke , Galizia C. Giovanni , Nawrot Martin Paul
Published: September 2013

Local computation in microcircuits is an essential feature of distributed information processing in vertebrate and invertebrate brains. The insect antennal lobe represents a spatially confined local network that processes high-dimensional and redundant peripheral input to compute an efficient odor code. Social insects can rely on a particularly rich olfactory receptor repertoire, and they exhibit complex odor-guided behaviors. This corresponds with a high anatomical complexity of their antennal lobe network. In the honeybee, a large number of glomeruli that receive sensory input are interconnected by a dense network of local interneurons (LNs). Uniglomerular projection neurons (PNs) integrate sensory and recurrent local network input into an efficient spatio-temporal odor code. To investigate the specific computational roles of LNs and PNs, we measured several features of sub- and suprathreshold single-cell responses to in vivo odor stimulation. Using a semisupervised cluster analysis, we identified a combination of five characteristic features as sufficient to separate LNs and PNs from each other, independent of the applied odor-stimuli. The two clusters differed significantly in all these five features. PNs showed a higher spontaneous subthreshold activation, assumed higher peak response rates and a more regular spiking pattern. LNs reacted considerably faster to the onset of a stimulus, and their responses were more reliable across stimulus repetitions. We discuss possible mechanisms that can explain our results, and we interpret cell-type-specific characteristics with respect to their functional relevance.
Multiscale Image Representation and Texture Extraction Using Hierarchical Variational Decomposition
Authors: Tang Liming , He Chuanjiang
Published: September 2013

In order to achieve a mutiscale representation and texture extraction for textured image, a hierarchical(BV,Gp,L2)decomposition model is proposed in this paper. We firstly introduce the proposed model which is obtained by replacing the fixed scale parameter of the original(BV,Gp,L2)decomposition with a varying sequence. And then, the existence and convergence of the hierarchical decomposition are proved. Furthermore, we show the nontrivial property of this hierarchical decomposition. Finally, we introduce a simple numerical method for the hierarchical decomposition, which utilizes gradient decent for energy minimization and finite difference for the associated gradient flow equations. Numerical results show that the proposed hierarchical(BV,Gp,L2)decomposition is very appropriate for multiscale representation and texture extraction of textured image.
Evolutionary Relations of Hexanchiformes Deep-Sea Sharks Elucidated by Whole Mitochondrial Genome Sequences
Authors: Tanaka Keiko , Shiina Takashi , Tomita Taketeru , Suzuki Shingo , Hosomichi Kazuyoshi , Sano Kazumi , Doi Hiroyuki , Kono Azumi , Komiyama Tomoyoshi , Inoko Hidetoshi , Kulski Jerzy K. , Tanaka Sho
Published: September 2013

Hexanchiformes is regarded as a monophyletic taxon, but the morphological and genetic relationships between the five extant species within the order are still uncertain. In this study, we determined the whole mitochondrial DNA (mtDNA) sequences of seven sharks including representatives of the five Hexanchiformes, one squaliform, and one carcharhiniform and inferred the phylogenetic relationships among those species and 12 other Chondrichthyes (cartilaginous fishes) species for which the complete mitogenome is available. The monophyly of Hexanchiformes and its close relation with all other Squaliformes sharks were strongly supported by likelihood and Bayesian phylogenetic analysis of 13,749 aligned nucleotides of 13 protein coding genes and two rRNA genes that were derived from the whole mDNA sequences of the 19 species. The phylogeny suggested that Hexanchiformes is in the superorder Squalomorphi,Chlamydoselachus anguineus(frilled shark) is the sister species to all other Hexanchiformes, and the relations within Hexanchiformes are well resolved asChlamydoselachus, (Notorynchus, (Heptranchias, (Hexanchus griseus,H. nakamurai))). Based on our phylogeny, we discussed evolutionary scenarios of the jaw suspension mechanism and gill slit numbers that are significant features in the sharks.
A Hybrid Multiple Criteria Decision Making Model for Supplier Selection
Authors: Wu Chung-Min , Hsieh Ching-Lin , Chang Kuei-Lun
Published: September 2013

The sustainable supplier selection would be the vital part in the management of a sustainable supply chain. In this study, a hybrid multiple criteria decision making (MCDM) model is applied to select optimal supplier. The fuzzy Delphi method, which can lead to better criteria selection, is used to modify criteria. Considering the interdependence among the selection criteria, analytic network process (ANP) is then used to obtain their weights. To avoid calculation and additional pairwise comparisons of ANP, a technique for order preference by similarity to ideal solution (TOPSIS) is used to rank the alternatives. The use of a combination of the fuzzy Delphi method, ANP, and TOPSIS, proposing an MCDM model for supplier selection, and applying these to a real case are the unique features of this study.
Some Aspects of Anisotropic Quark-Gluon Plasma
Authors: Mandal Mahatsab , Roy Pradip
Published: September 2013

We review the various aspects of anisotropic quark-gluon plasma (AQGP) that have recently been discussed by a number of authors. In particular, we focus on the electromagnetic probes of AQGP, inter quark potential, quarkonium states in AQGP, and the nuclear modifications factor of various bottomonium states using this potential. In this context, we will also discuss the radiative energy loss of partons and nuclear modification factor of light hadrons in the context of AQGP. The features of the wake potential and charge density due to the passage of jet in AQGP will also be demonstrated.
Dynamic of Mutational Events in Variable Number Tandem Repeats ofEscherichia coliO157:H7
Authors: Bustamante A. V. , Sanso A. M. , Segura D. O. , Parma A. E. , Lucchesi P. M. A.
Published: September 2013

VNTRs regions have been successfully used for bacterial subtyping; however, the hypervariability in VNTR loci is problematic when trying to predict the relationships among isolates. Since few studies have examined the mutation rate of these markers, our aim was to estimate mutation rates of VNTRs specific for verotoxigenicE. coliO157:H7. The knowledge of VNTR mutational rates and the factors affecting them would make MLVA more effective for epidemiological or microbial forensic investigations. For this purpose, we analyzed nine loci performing parallel, serial passage experiments (PSPEs) on 9 O157:H7 strains. The combined 9 PSPE population rates for the 8 mutating loci ranged from 4.4 × 10−05to 1.8 × 10−03mutations/generation, and the combined 8-loci mutation rate was of 2.5 × 10−03mutations/generation. Mutations involved complete repeat units, with only one point mutation detected. A similar proportion between single and multiple repeat changes was detected. Of the 56 repeat mutations, 59% were insertions and 41% were deletions, and 72% of the mutation events corresponded to O157-10 locus. For alleles with up to 13 UR, a constant and low mutation rate was observed; meanwhile longer alleles were associated with higher and variable mutation rates. Our results are useful to interpret data from microevolution and population epidemiology studies and particularly point out that the inclusion or not of O157-10 locus or, alternatively, a differential weighting data according to the mutation rates of loci must be evaluated in relation with the objectives of the proposed study.
Thermally Induced Asymmetric Buckling of Circular Monolayer Graphene
Authors: Lee Haw-Long , Chang Win-Jin
Published: September 2013

The asymmetric buckling behaviors of circular monolayer graphene with clamped boundary condition subjected to temperature change are analytically studied based on the nonlocal elasticity theory, including the small length effect. The axisymmetrical and asymmetric critical buckling temperatures and mode shape of different order modes are obtained. According to the analysis, the asymmetric critical buckling temperature of monolayer graphene is larger than the axisymmetric one. The axisymmetrical and asymmetric critical buckling temperatures decrease with increasing nonlocal parameter. In addition, nodal diametrical lines and nodal circles can be found from the modal shapes. In order to avoid destruction of the sensors due to buckling of the structure, they can be placed at the nodal diametrical lines or nodal circles.
A Direct Approach Based on C2-IULOWA Operator for Group Decision Making with Uncertain Additive Linguistic Preference Relations
Authors: Peng Ding-Hong , Gao Zhi-Fang , Gao Chang-Yuan , Wang Hua
Published: September 2013

With respect to group decision making (GDM) problem with uncertain additive linguistic preference relations (UALPRs), we investigate the efficient aggregation of the uncertain additive linguistic preference information. First, we introduce two measures to assess the consistency level and the consensus level of uncertain additive linguistic preference information, respectively, and study some of their desirable properties. Then, based on both the two measures, we propose a coinduced uncertain linguistic ordered weighted averaging (IULOWA) operator, called the consistency and consensus coinduced uncertain linguistic ordered weighted averaging (C2-IULOWA) operator, to aggregate individual uncertain additive linguistic preference information, in which the consistency level and the consensus level synergistically serve as inducing variables and then guide the determination of the associated weights. We have proved the collective uncertain linguistic preference information aggregated by the C2-IULOWA operator that can maintain the fundamental properties of preference relation, such as indifference, reciprocity, and transitivity. By using the C2-IULOWA operator, we develop a direct GDM approach with UALPRs. Finally, an illustrative example on the selection of chief quality officer is used to demonstrate the effectiveness and rationalitly of the developed approach.
Thermohydraulic Analysis of Shell-and-Tube Heat Exchanger with Segmental Baffles
Authors: Singh Amarjit , Sehgal Satbir S.
Published: September 2013

In this study, the experimental analysis was performed on the shell-and-tube type heat exchanger containing segmental baffles at different orientations. In the current work, three angular orientations (θ) 0°, 30°, and 60° of the baffles were analyzed for laminar flow having the Reynolds number range 303–1516. It was observed that, with increase of Reynolds number from 303 to 1516, there was a 94.8% increase in Nusselt number and 282.9% increase in pressure drop. Due to increase of Reynolds number from 303 to 1516, there is a decrease in nondimensional temperature factor for cold water (ω) by 57.7% and hot water (ξ) by 57.1%, respectively.
Global Stability and Bifurcations of a Diffusive Ratio-Dependent Holling-Tanner System
Authors: Zuo Wenjie
Published: September 2013

The dynamics of a diffusive ratio-dependent Holling-Tanner predator-prey system subject to Neumann boundary conditions are considered. By choosing the ratio of intrinsic growth rates of predators to preys as a bifurcation parameter, the existence and stability of spatially homogeneous and nonhomogeneous Hopf bifurcations and steady state bifurcation are investigated in detail. Meanwhile, we show that Turing instability takes place at a certain critical value; that is, the stationary solution becomes unstable induced by diffusion. Particularly, the sufficient conditions of the global stability of the positive constant coexistence are given by the upper-lower solutions method.
Precision Calculations in Supersymmetric Theories
Authors: Mihaila L.
Published: September 2013

In this paper we report on the newest developments in precision calculations in supersymmetric theories. An important issue related to this topic is the construction of a regularization scheme preserving simultaneously gauge invariance and supersymmetry. In this context, we discuss in detail dimensional reduction in component field formalism as it is currently the preferred framework employed in the literature. Furthermore, we set special emphasis on the application of multi-loop calculations to the analysis of gauge coupling unification, the prediction of the lightest Higgs boson mass, and the computation of the hadronic Higgs production and decay rates in supersymmetric models. Such precise theoretical calculations up to the fourth order in perturbation theory are required in order to cope with the expected experimental accuracy on the one hand and to enable us to distinguish between the predictions of the Standard Model and those of supersymmetric theories on the other hand.
Hypertension Associated with Coarctation of the Aorta Revisited: Case-Based Update from Experience of Three Children
Authors: Baykan Ali , Argun Mustafa , Özyurt Abdullah , Pamukçu Özge , Üzüm Kazım , Narın Nazmi
Published: September 2013

Coarctation of the aorta (CoA) can present with different clinical pictures depending on the severity of the narrowness in the coarcted aortic segment in an age range between newborn and adolescence. Sometimes, it can cause intracranial hemorrhage or infarction when diagnosis and treatment are delayed. The aim of this report is taking attention to CoA as a cause of systemic hypertension and is also emphasizing the differences of diagnostic approach for hypertension in children from adults. Two cases of hypertensive cerebral hemorrhage and one case of hypertensive cerebellar infarction associated with CoA are reported. These cases help us to pay attention to the possibility of CoA in adolescents with hypertensive stroke. We want to emphasize the importance of physical examination for evaluation of hypertension and to impress the diagnostic approach for secondary hypertension in children.
Numerical Solutions of the Second-Order One-Dimensional Telegraph Equation Based on Reproducing Kernel Hilbert Space Method
Authors: Inc Mustafa , Akgül Ali , Kılıçman Adem
Published: September 2013

We investigate the effectiveness of reproducing kernel method (RKM) in solving partial differential equations. We propose a reproducing kernel method for solving the telegraph equation with initial and boundary conditions based on reproducing kernel theory. Its exact solution is represented in the form of a series in reproducing kernel Hilbert space. Some numerical examples are given in order to demonstrate the accuracy of this method. The results obtained from this method are compared with the exact solutions and other methods. Results of numerical examples show that this method is simple, effective, and easy to use.
Solid‐State Synthesis and Thermoelectric Properties of Mg2+xSi0.7Sn0.3Sbm
Authors: You Sin-Wook , Kim Il-Ho , Choi Soon-Mok , Seo Won-Seon
Published: September 2013

Mg2+xSi0.7Sn0.3Sbm (0  ≤  x  ≤  0.2, m  =  0 or 0.01) solid solutions have been successfully prepared by mechanical alloying and hot pressing as a solid‐state synthesis route. All specimens were identified as phases with antifluorite structure and showed n‐type conduction. The electrical conductivity of Mg‐excess solid solutions was enhanced due to increased electron concentrations. The absolute values of the Seebeck coefficient varied substantially with Sb doping and excess Mg, which was attributed to the change in carrier concentration. The onset temperature of bipolar conduction was shifted higher with Sb doping and excess Mg. The lowest thermal conductivity of 1.3 W/mK was obtained for Mg2Si0.7Sn0.3Sb0.01. A maximum ZT of 0.64 was achieved at 723 K for Mg2.2Si0.7Sn0.3Sb0.01.
Structural and Sequence Similarities of Hydra Xeroderma Pigmentosum A Protein to Human Homolog Suggest Early Evolution and Conservation
Authors: Barve Apurva , Ghaskadbi Saroj , Ghaskadbi Surendra
Published: September 2013

Xeroderma pigmentosum group A (XPA) is a protein that binds to damaged DNA, verifies presence of a lesion, and recruits other proteins of the nucleotide excision repair (NER) pathway to the site. Though its homologs from yeast,Drosophila, humans, and so forth are well studied, XPA has not so far been reported from protozoa and lower animal phyla. Hydra is a fresh-water cnidarian with a remarkable capacity for regeneration and apparent lack of organismal ageing. Cnidarians are among the first metazoa with a defined body axis, tissue grade organisation, and nervous system. We report here for the first time presence ofXPAgene in hydra. Putative protein sequence of hydra XPA contains nuclear localization signal and bears the zinc-finger motif. It contains two conserved Pfam domains and various characterized features of XPA proteins like regions for binding to excision repair cross-complementing protein-1 (ERCC1) and replication protein A 70 kDa subunit (RPA70) proteins. Hydra XPA shows a high degree of similarity with vertebrate homologs and clusters with deuterostomes in phylogenetic analysis. Homology modelling corroborates the very close similarity between hydra and human XPA. The protein thus most likely functions in hydra in the same manner as in other animals, indicating that it arose early in evolution and has been conserved across animal phyla.
A Fusion Protein between Streptavidin and the Endogenous TLR4 Ligand EDA Targets Biotinylated Antigens to Dendritic Cells and Induces T Cell ResponsesIn Vivo
Authors: Arribillaga Laura , Durantez Maika , Lozano Teresa , Rudilla Francesc , Rehberger Federico , Casares Noelia , Villanueva Lorea , Martinez Marta , Gorraiz Marta , Borrás-Cuesta Francisco , Sarobe Pablo , Prieto Jesús , Lasarte Juan José
Published: September 2013

The development of tools for efficient targeting of antigens to antigen presenting cells is of great importance for vaccine development. We have previously shown that fusion proteins containing antigens fused to the extra domain A from fibronectin (EDA), an endogenous TLR4 ligand, which targets antigens to TLR4-expressing dendritic cells (DC), are highly immunogenic. To facilitate the procedure of joining EDA to any antigen of choice, we have prepared the fusion protein EDAvidin by linking EDA to the N terminus of streptavidin, allowing its conjugation with biotinylated antigens. We found that EDAvidin, as streptavidin, forms tetramers and binds biotin or biotinylated proteins with aKd~ 2.6 × 10−14 mol/L. EDAvidin favours the uptake of biotinylated green fluorescent protein by DC. Moreover, EDAvidin retains the proinflammatory properties of EDA, inducing NF-κβby TLR4-expressing cells, as well as the production of TNF-αby the human monocyte cell line THP1 and IL-12 by DC. More importantly, immunization of mice with EDAvidin conjugated with the biotinylated nonstructural NS3 protein from hepatitis C virus induces a strong anti-NS3 T cell immune response. These results open a new way to use the EDA-based delivery tool to target any antigen of choice to DC for vaccination against infectious diseases and cancer.
Oxidant-Antioxidant Balance in the Blood of Patients with Chronic Obstructive Pulmonary Disease After Smoking Cessation
Authors: Woźniak Alina , Górecki Dariusz , Szpinda Michał , Mila-Kierzenkowska Celestyna , Woźniak Bartosz
Published: September 2013

The effect of smoking cessation on the oxidative stress in patients with chronic obstructive pulmonary disease (COPD) was assessed. We recruited 73 smokers with COPD (study group), whose blood was analysed before smoking cessation, after the 1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35 smokers with COPD (Control II). Blood was taken once in Control I and 4 times (every month) in Control II. In the study group conjugated dienes (CDs) level in plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than in Control I, respectively (P<0.001), while thiobarbituric acid-reactive substances (TBARS) level was 89% (P<0.001) and 51% higher (P<0.01), respectively. Superoxide dismutase (SOD) activity was 40% higher (P<0.05) while glutathione peroxidase (GPx) was 41% lower (P<0.001) than in Control I. In Control II, the similar differences as compared to Control I were observed throughout the study. Smoking cessation resulted in decrease of CDs, TBARS, and SOD and GPx increase, with no changes in catalase and vitamins A and E. COPD is accompanied by oxidative stress. A three-month tobacco abstinence facilitated restoring the oxidant-antioxidant balance systemically, but it did not affect spirometric parameters.
Mechanical Behavior of Steel Fiber Reinforced Concrete Investigated by One-Stage Light Gas Gun Experiment
Authors: Jiang Guoping , Wu Xinhong
Published: September 2013

This paper presents shock Hugoniot compression data for several concrete materials obtained from flat plate impact experiments. The manganin pressure gauge was used to measure the pressure-time curves of the samples. The physical quantities were all obtained by the Lagrange method. Moreover, it is observed from the measured pressure-time curves that the rate sensitivity of the dynamic response to the concrete is not negligible. Based on the polynomial Grüneisen equation, the parameters of the equation of state of concrete were obtained. The steel fiber reinforcement effect was analyzed.
Resistance to CDK2 Inhibitors Is Associated with Selection of Polyploid Cells inCCNE1-Amplified Ovarian Cancer
Authors: Etemadmoghadam Dariush , Au-Yeung George , Wall Meaghan , Mitchell Chris , Kansara Maya , Loehrer Elizabeth , Batzios Crisoula , George Joshy , Ftouni Sarah , Weir Barbara A. , Carter Scott , Gresshoff Irma , Mileshkin Linda , Rischin Danny , Hahn William C. , Waring Paul M. , Getz Gad , Cullinane Carleen , Campbell Lynda J. , Bowtell David D.
Published: September 2013

Purpose: Amplification of cyclin E1 (CCNE1) is associated with poor outcome in breast, lung, and other solid cancers, and is the most prominent structural variant associated with primary treatment failure in high-grade serous ovarian cancer (HGSC). We have previously shown that CCNE1-amplified tumors show amplicon-dependent sensitivity to CCNE1 suppression. Here, we explore targeting CDK2 as a novel therapeutic strategy in CCNE1-amplified cancers and mechanisms of resistance.

Experimental Design: We examined the effect of CDK2 suppression using RNA interference and small-molecule inhibitors in SK-OV-3, OVCAR-4, and OVCAR-3 ovarian cancer cell lines. To identify mechanisms of resistance, we derived multiple, independent resistant sublines of OVCAR-3 to CDK2 inhibitors. Resistant cells were extensively characterized by gene expression and copy number analysis, fluorescence-activated cell sorting profiling and conventional karyotyping. In addition, we explored the relationship between CCNE1 amplification and polyploidy using data from primary tumors.

Results: We validate CDK2 as a therapeutic target in CCNE1-amplified cells by showing selective sensitivity to suppression, either by gene knockdown or using small-molecule inhibitors. In addition, we identified two resistance mechanisms, one involving upregulation of CDK2 and another novel mechanism involving selection of polyploid cells from the pretreatment tumor population. Our analysis of genomic data shows that polyploidy is a feature of cancer genomes with CCNE1 amplification.

Conclusions: These findings suggest that cyclinE1/CDK2 is an important therapeutic target in HGSC, but that resistance to CDK2 inhibitors may emerge due to upregulation of CDK2 target protein and through preexisting cellular polyploidy. Clin Cancer Res; 19(21); 5960–71. ©2013 AACR.
Coamplification and Cooperation: Toward Identifying Biologically Relevant Oncogenes
Authors: Huang Guochang , Singh Bhuvanesh
Published: September 2013

Identification of biologically relevant genes from genomic assays is limited by the complexity of changes present in most solid tumors. Assessing for coactivation of functionally related genes resulted in the identification of SENP2, DCUN1D1, and DVL3—consensus candidates that drive selection for 3q amplification in lung squamous cell carcinomas. Clin Cancer Res; 19(20); 5549–51. ©2013 AACR.
Better Performance of CARs Deprived of the PD-1 Brake
Authors: Morales-Kastresana Aizea , Labiano Sara , Quetglas José I. , Melero Ignacio
Published: September 2013

Immunotherapies often permit combinations to increase efficacy. Two approaches are currently leading our field: adoptive therapy with T cells transfected with chimeric antigen receptors and monoclonal antibodies blocking the PD-1/PD-L1 (B7-H1) axis. In this issue of Clinical Cancer Research, preclinical evidence for a synergistic combination of such approaches is reported. Clin Cancer Res; 19(20); 5546–8. ©2013 AACR.
Regeneration of Spermatogenesis after Testicular Cancer Chemotherapy
Authors: Suzuki Kotaro , Yumura Yasushi , Ogawa Takehiko , Saito Kazuo , Kinoshita Yuzo , Noguchi Kazumi
Published: September 2013

Purpose: Azoospermia is a common side effect of chemotherapy. Although most patients restore spermatogenesis over time, the exact time course has not been well described. We analyzed the recovery of spermatogenesis in testicular cancer patients following chemotherapy. Patients and Methods: 49 patients, consisting of 45 treated with a bleomycin, etoposide and cisplatin (BEP) regimen and 4 with high-dose chemotherapy, were followed up with occasional semen analyses. The primary endpoint of this study was the confirmation of motile spermatozoa in the patients' semen. Results: Among 45 patients treated with BEP, 44 recovered spermatogenesis. The recovery of spermatogenesis was delayed depending on the increase in BEP cycles. In groups of patients who received 1-2, 3 and 4 cycles, the recovery rates of spermatogenesis within 2 year were 83.3, 80.0 and 66.7%, respectively. In the group with 5-6 cycles of BEP, re-spermatogenesis was significantly delayed and no patients re-established spermatogenesis within 2 years. The patients' age and semen parameters before chemotherapy were not useful as predictive factors for the recovery of spermatogenesis. Conclusion: The recovery of spermatogenesis was rather fast and was often observed as early as several months after BEP treatment when the number of cycles was <4.
SOD1-G93A Mice Exhibit Muscle-Fiber-Type-Specific Decreases in Glucose Uptake in the Absence of Whole-Body Changes in Metabolism
Authors: Smittkamp Susan E. , Morris Jill K. , Bomhoff Gregory L. , Chertoff Mark E. , Geiger Paige C. , Stanford John A.
Published: September 2013

Background: Skeletal muscles play an important role in systemic glucose homeostasis and are purported to be the origin of the altered metabolic state observed in amyotrophic lateral sclerosis (ALS). Objective: The purpose of this study was to evaluate whole-body and muscle-specific glucose metabolism in the SOD1-G93A mouse model of ALS. Methods: We assessed glucose tolerance in early-, middle-, and late-stage SOD1-G93A and control mice using an intraperitoneal glucose tolerance test. We then measured the respiratory exchange ratio (CO2 production/O2 consumption) as a function of fasting and feeding using indirect calorimetry in a subset of male mice at these time points. Finally, muscles from all mice were harvested to evaluate basal and insulin-stimulated glucose transport in fast- and slow-twitch muscles. Results: No changes in systemic glucose clearance were observed in SOD1-G93A mice at any stage, nor were there changes in fasting insulin levels. Indirect calorimetry revealed an increase in the respiratory exchange ratio during the fed state at middle, but not at early or late stages of disease. Middle-stage SOD1-G93A mice exhibited decreased insulin-stimulated glucose uptake in fast-twitch, but not slow-twitch, skeletal muscle. Late-stage SOD1-G93A mice exhibited decreased insulin-stimulated glucose uptake in both fast- and slow-twitch muscle, as well as increased basal (non-insulin-stimulated) glucose uptake. Conclusions: These results suggest that alterations in muscle metabolism occur in a fiber-type-specific manner in ALS, but do not necessarily lead to whole-body metabolic changes in SOD1-G93A mice.
Immune Activation in Amyloid-β-Related Angiitis Correlates with Decreased Parenchymal Amyloid-β Plaque Load
Authors: Bogner S. , Bernreuther C. , Matschke J. , Barrera-Ocampo A. , Sepulveda-Falla D. , Leypoldt F. , Magnus T. , Haag F. , Bergmann M. , Brück W. , Vogelgesang S. , Glatzel M.
Published: September 2013

Background: Primary angiitis of the central nervous system (PACNS) is a rare but serious condition. A fraction of patients suffering from PACNS concurrently exhibit pronounced cerebral amyloid angiopathy (CAA) which is characterized by deposits of amyloid-β (Aβ) in and around the walls of small and medium-sized arteries of the brain. PACNS with CAA has been identified as a distinct disease entity, termed Aβ-related angiitis (ABRA). Evidence points to an immune reaction to vessel wall Aβ as the trigger of vasculitis. Objective: To investigate whether the inflammatory response to Aβ has (1) any effect on the status of immune activation in the brain parenchyma and (2) leads to clearance of Aβ from brain parenchyma. Methods: We studied immune activation and Aβ load by quantitative immunohistochemical analysis in brain parenchyma adjacent to affected vessels in 11 ABRA patients and 10 matched CAA controls. Results: ABRA patients showed significantly increased immune activation and decreased Aβ loads in the brain parenchyma adjacent to affected vessels. Conclusion: Our results are in line with the hypothesis of ABRA being the result of an excessive immune response to Aβ and show that this can lead to enhanced clearance of Aβ from the brain parenchyma by immune-mediated mechanisms.
Interleukin-17 Signalling in a Murine Model of Mild Chronic Asthma
Authors: Herbert Cristan , Shadie Alexander M. , Kumar Rakesh K.
Published: September 2013

Background: The role of Th17 cell-derived cytokines in the pathogenesis of airway inflammation and remodelling in mild asthma remains unclear. We investigated this in a mouse model which reproduces most of the features of the human disease. Methods: Systemically sensitised BALB/c mice were challenged via the airways with a low mass concentration of ovalbumin aerosol for 8 weeks to induce lesions of mild chronic asthma. Changes were compared with those in animals deficient in signalling via the interleukin (IL)-17 receptor A (IL-17R). Low-passage airway epithelial cells (AEC) and fibroblasts were cultured with IL-17A, or with media from Th17-polarised cells, to assess activation. Results: In CD4+ T cells from chronically challenged mice, expression of mRNA for Th17 cytokines IL-17A, IL-17F, IL-21 and IL-22 was significantly increased. Both recombinant IL-17A and media from Th17 cells significantly stimulated the production of various pro-inflammatory and pro-remodelling cytokines by AEC and fibroblasts. In the mouse model, abrogation of IL-17R signalling had no effect on the development of airway inflammation or on most changes of remodelling. However, numbers of mucus-producing cells and expression of mRNA for Gob-5 were attenuated in the absence of IL-17R signalling. Conclusions: Although IL-17A and Th17 cells stimulate cytokine production by structural cells of the airways, and Th17 cells are induced in our model of mild chronic asthma, signalling via IL-17R did not contribute significantly to the development of airway inflammation and most changes of remodelling in this model. However, in mild asthma, IL-17A appears to have a role in the goblet cell response in the airways.
Arxula adeninivorans Recombinant Urate Oxidase and Its Application in the Production of Food with Low Uric Acid Content
Authors: Trautwein-Schult Anke , Jankowska Dagmara , Cordes Arno , Hoferichter Petra , Klein Christina , Matros Andrea , Mock Hans-Peter , Baronian Keith , Bode Rüdiger , Kunze Gotthard
Published: September 2013

Hyperuricemia and its symptoms are becoming increasingly common worldwide. Elevated serum uric acid levels are caused by increased uric acid synthesis from food constituents and reduced renal excretion. Treatment in most cases involves reducing alcohol intake and consumption of meat and fish or treatment with pharmaceuticals. Another approach could be to reduce uric acid level in food, either during production or consumption. This work reports the production of recombinant urate oxidase by Arxula adeninivorans and its application to reduce uric acid in a food product. The A. adeninivorans urate oxidase amino acid sequence was found to be similar to urate oxidases from other fungi (61-65% identity). In media supplemented with adenine, hypoxanthine or uric acid, induction of the urate oxidase (AUOX) gene and intracellular accumulation of urate oxidase (Auoxp) was observed. The enzyme characteristics were analyzed from isolates of the wild-type strain A. adeninivorans LS3, as well as from those of transgenic strains expressing the AUOX gene under control of the strong constitutive TEF1 promoter or the inducible AYNI1 promoter. The enzyme showed high substrate specificity for uric acid, a broad temperature and pH range, high thermostability and the ability to reduce uric acid content in food.
Obesity - A Promoter of Allergy?
Authors: Baumann Susanne , Lorentz Axel
Published: September 2013

The prevalence of both obesity and allergy has been increasing throughout the world, leading to the hypothesis that the two are linked to one another. This overview summarizes the results of 34 studies from 2002 to 2012 that investigated a possible contributing effect of increasing body mass on the development and prevalence of various atopic diseases. Obesity was found to clearly affect bronchial asthma. However, the correlation was stronger in the nonatopic asthma phenotype. Obesity was found to be associated with the development of atopic dermatitis in children only. No clear association was found between obesity and the prevalence of allergic rhinitis or allergic conjunctivitis or increased sensitization to food allergens. This review sums up our study results and discusses a possible role of obesity in the promotion of allergy and asthma.
Sleep Disturbances and Refractory Gastroesophageal Reflux Disease Symptoms in Patients Receiving Once-Daily Proton Pump Inhibitors and Efficacy of Twice-Daily Rabeprazole Treatment
Authors: Fujiwara Yasuhiro , Habu Yasuki , Ashida Kiyoshi , Kusano Motoyasu , Higuchi Kazuhide , Arakawa Tetsuo
Published: September 2013

Background: Nighttime acid reflux that influences refractory symptoms is strongly associated with sleep disturbances. The aim of this study was to examine the associations between sleep disturbances and refractory gastroesophageal reflux disease (GERD) symptoms in patients receiving once daily proton pump inhibitors (PPI) and the efficacy of twice-daily rabeprazole treatment. Method: In a multicenter survey, 433 GERD patients receiving once-daily PPI treatment completed a self-report questionnaire that included the Frequency Scale for the Symptoms of GERD (FSSG) and questions about sleep disturbances. Study cases were defined as patients with an FSSG score ≥8. Of the 222 study cases, 106 individuals received rabeprazole 10 mg twice daily for 4-8 weeks. Results: Of the 433 subjects, 222 patients revealed FSSG scores of ≥8. Use of a half dose of PPI was associated with such cases. PPI-refractory symptoms were found in 46% of patients with standard-dose PPI treatment. Nighttime symptoms (OR = 2.56), daytime sleepiness (OR = 1.64), and poorer sleep quality (OR = 1.67) were significantly associated with refractory GERD symptoms. Twice-daily rabeprazole treatment significantly improved FSSG scores and sleep disturbances. Conclusion: About half of the GERD patients receiving once-daily standard-dose PPI treatment had refractory GERD symptoms. Sleep disturbances were significantly associated with refractory GERD symptoms. Twice-daily rabeprazole treatment was effective in such cases.
Prevalence and Etiology of Congenital Hypothyroidism Detected through an Argentine Neonatal Screening Program (1997-2010)
Authors: Chiesa Ana , Prieto Laura , Mendez Virginia , Papendieck Patricia , Calcagno María de Luján , Gruñeiro-Papendieck Laura
Published: September 2013

Introduction: We retrospectively assessed the incidence of congenital hypothyroidism (CH) detected through our neonatal screening program between 1997 and 2010. We describe the diagnostic characteristics of the detected population and verify the impact of a TSH cutoff (CO) change. Patients and Methods: Screening was based on TSH determination on dried blood spot on filter paper samples (IFMA) using a 15 mU/l blood CO until 12/2002 (P1) and 10 mU/l thereafter (P2). Patients were classified as having transient or permanent CH (athyreotic, ectopic, eutopic, with goiter and unknown etiology). Global and diagnostic-related incidences were calculated for the whole studied period with the same CO, and P1 and P2 were compared. Results: Incidences of permanent CH were 1:3,108 (P1) and 1:2,367 (P2). The lower CO detected 22 extra CH, 13 of them definitive (70% with eutopic glands). Only a significant increase (p < 0.05) in eutopic CH was found, partially related to the lower CO applied. A statistically significant association with time was seen for total definitive and ectopic cases (p < 0.05). Conclusion: Our findings revealed some changes in the detected population partially related to the CO applied, with only eutopic dysfunctional disorders being more prevalent in the later years. Total permanent CH and ectopic thyroid disorders showed a trend toward higher detection over time, but their prevalence has not changed significantly in our screening program.
Common Blue Nevus withSatellite Lesions Needs aDifferential Diagnosis from Malignant Melanoma
Authors: Yonei Nozomi , Kimura Ayako , Furukawa Fukumi
Published: September 2013

Malignant blue nevus is rare, and a common blue nevus rarely needs a differential diagnosis from malignant melanoma. Although a melanocytic nevus with a satellite lesion is usually suggestive of a peripherally disseminating malignant melanoma, very few cases of blue nevus with satellite lesions have been reported thus far. To our knowledge, this is the seventh case of a blue nevus with satellitosis. Periappendageal and perivascular concentrations of the nevus cells were observed in the main papule as well as in the satellite lesions. These findings suggest that blue nevus cells could infiltrate along the perivascular area in the dermis and form multiple satellite lesions. Blue nevus should be considered as a differential diagnosis when a locally disseminating malignant melanoma is suspected.
The heart in hypertension: unresolved conceptual challenges. Special lecture.
Authors: Frohlich E D
Published: September 2013

Much has been learned over the past 25 years concerning the role of the heart in hypertension. In a multiplicity of areas a great deal has been clarified but a number of issues remain unresolved. This personal overview outlines some of these challenging areas for investigation, including questions relating to the cardiogenic reflexes, mechanisms underlying total body autoregulation that may involve not only the adaptation of arterioles but also venoconstriction in hypertension, postcapillary constriction also involving the efferent glomerular arterioles, the mechanisms underlying the development and regression of hypertrophy as well as the function of the hypertrophied and "regressed hypertrophy" heart, and the precise hemodynamic actions of atrial natriuretic factor.
Review of salt restriction and the response to antihypertensive drugs. Satellite symposium on calcium antagonists.
Authors: Luft F C , Weinberger M H
Published: September 2013

We evaluated the response to salt restriction in hypertensive patients receiving drugs. By restricting their salt intake to less than 80 mmol of sodium per day for 3 months, 50% of patients reaching goal compliance were able to discontinue diuretics. The literature also reveals responses to a low salt diet. Salt restriction augmented the hypotensive effect of chlorthalidone in two investigations, but not in another, and the hypotensive effect of beta-blockers in three trials. Sodium intake of 10 mmol/day caused a much greater decrease in blood pressure in response to a single dose of captopril than did a sodium diet of 200 mmol/day. In patients receiving various fixed regimens for 2 months, salt restriction decreased blood pressure in all but those receiving calcium blockers. A single dose of nifedipine lowered blood pressure more in patients receiving 350 mmol of sodium per day than in the same patients given 150 or 10 mmol/day. Verapamil for 3 days was more effective in patients receiving 212 mmol of sodium per day than in the same subjects receiving 9 mmol/day. Nitrendipine caused a greater decrease in diastolic blood pressure in patients who did not reduce salt intake compared to those who did. Salt restriction appears useful in salt-sensitive patients who receive beta-blockers, diuretics, converting enzyme inhibitors, or centrally acting drugs. Calcium channel entry blockers may not require salt restriction to maximize their effect.
Contribution of vasopressin in dexamethasone-induced hypertension in rats.
Authors: Iijima F , Malik K U
Published: September 2013

Our previous finding that dexamethasone-induced hypertension in rats is associated with enhanced reactivity of mesenteric arteries to arginine vasopressin but not to angiotensin II (Ang II) or norepinephrine has led us to postulate that vasopressin contributes to the development or maintenance of glucocorticoid-induced hypertension. To test this view, we investigated the effects of vasopressin, Ang II, norepinephrine, and the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP on mean arterial blood pressure and heart rate with and without ganglionic blockade with hexamethonium and angiotensin I (Ang I) converting enzyme inhibition with MK 421 in pentobarbital-anesthetized rats made hypertensive by treatment with dexamethasone (1.8 mg/kg/wk for 14 days). Administration of vasopressin, Ang II, or norepinephrine (0.003-3 microgram i.v.) produced a dose-related increase in arterial blood pressure. The pressor response to vasopressin, but not to Ang II or norepinephrine, was greater in dexamethasone-treated than in vehicle-treated animals, and this difference became more pronounced in rats that received hexamethonium and MK 421. Administration of the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)AVP significantly reduced arterial pressure in dexamethasone-treated but not in vehicle-treated animals. Hexamethonium and MK 421 reduced arterial blood pressure in dexamethasone-treated as well as in vehicle-treated rats; however, arterial blood pressure remained higher in the former. Administration of the vasopressin V1 receptor antagonist produced a greater reduction in arterial blood pressure in dexamethasone-treated than in vehicle-treated rats. These data suggest that vasopressin contributes to glucocorticoid-induced hypertension, which is probably due to enhanced vascular reactivity to the peptide.
The C1 area of the brainstem in tonic and reflex control of blood pressure. State of the art lecture.
Authors: Reis D J , Morrison S , Ruggiero D A
Published: September 2013

Recent studies have demonstrated that the neurons of the lower brainstem that are responsible for maintaining normal levels of arterial pressure reside in a specific area of the rostral ventrolateral medulla. In rat, the critical zone corresponds to a small region containing a subpopulation of the adrenergic C1 group, defined immunocytochemically by the presence of the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase. Neurons of this region (the C1 area), possibly including the adrenergic neurons, directly innervate preganglionic neurons in the spinal cord, and are tonically active and sympathoexcitatory. The excitatory transmitter released into the spinal cord is unknown. The discharge of C1 area neurons is locked to the cardiac cycle and, in turn, leads to firing of sympathetic preganglionic neurons. The C1 area neurons are inhibited by baroceptor input and mediate the vascular component of baroceptor reflexes. They also mediate somato-sympathetic pressor responses from skin and muscle and participate in reflex responses to hypoxia. The neurons are directly innervated by local neurons containing gamma-aminobutyric acid, acetylcholine, enkephalin, and substance P, all of which modulate arterial pressure. The C1 area is the site of the hypotensive actions of clonidine. Clonidine appears to act on imidazole receptors in the C1 area to lower arterial pressure. The natural ligand for these receptors may be a newly defined substance in brain, clonidine-displacing substance. Neurons of the C1 area appear to be the critical neuronal group governing the normal resting and reflex control of arterial pressure. They may play a critical role in the maintenance of elevated arterial pressure in hypertension and as a site of action of antihypertensive drugs.
Sex hormone modulation of ventricular hypertrophy in sinoaortic denervated rats.
Authors: Cabral A M , Vasquez E C , Moysés M R , Antonio A
Published: September 2013

The influence of sex hormones on the development of left ventricular hypertrophy was investigated in baroreceptor-denervated rats. A significant increase (p less than 0.01) in the left ventricular weight/body weight ratio was observed in male but not in female rats 15 days after operation, compared to age- and sex-matched sham-operated rats. This differential hypertrophy occurred despite the development of a significant elevation in arterial blood pressure in both sexes. Castration prior to sinoaortic denervation did not change the level of arterial hypertension but caused a significant reduction (p less than 0.01) in left ventricular weight in male rats and a significant increase (p less than 0.01) in female rats. The pretreatment of male and female sinoaortic denervated and castrated rats with testosterone resulted in ventricular hypertrophy similar to that observed in intact male sinoaortic denervated rats. Pretreatment with estradiol, however, suppressed the left ventricular hypertrophy in intact male rats but did not change the normal ventricular mass observed in intact female sinoaortic denervated rats. These results indicate that the development of left ventricular hypertrophy in sinoaortic denervated rats is modulated by sex hormones, and that testosterone exerts a facilitatory and estradiol an inhibitory action.