bluuebunny/crossref_metadata_2025 huggingface dataset:
The Intrauterine and Nursing Period Is a Window of Susceptibility for Development of Obesity and Intestinal Tumorigenesis by a High Fat Diet inMin/+Mice as Adults
Authors: Ngo Ha Thi , Hetland Ragna Bogen , Steffensen Inger-Lise
Published: March 2015

We studied how obesogenic conditions during various life periods affected obesity and intestinal tumorigenesis in adult C57BL/6J-Min(multiple intestinal neoplasia)/+ mice. The mice were given a 10% fat diet throughout life (negative control) or a 45% fat dietin utero, during nursing, during bothin uteroand nursing, during adult life, or during their whole life-span, and terminated at 11 weeks for tumorigenesis (Min/+) or 23 weeks for obesogenic effect (wild-type). Body weight at 11 weeks was increased after a 45% fat diet during nursing, during bothin uteroand nursing, and throughout life, but had normalized at 23 weeks. In the glucose tolerance test, the early exposure to a 45% fat dietin utero, during nursing, or during bothin uteroand nursing, did not affect blood glucose, whereas a 45% fat diet given to adults or throughout life did. However, a 45% fat diet during nursing or duringin uteroand nursing increased the number of small intestinal tumors. So did exposures to a 45% fat diet in adult life or throughout life, but without increasing the tumor numbers further. The intrauterine and nursing period is a window of susceptibility for dietary fat-induced obesity and intestinal tumor development.
Physiological and Selective Attention Demands during an International Rally Motor Sport Event
Authors: Turner Anthony P. , Richards Hugh
Published: March 2015

Purpose. To monitor physiological and attention responses of drivers and codrivers during a World Rally Championship (WRC) event.Methods. Observational data were collected from ten male drivers/codrivers on heart rate (HR), core body (Tcore) and skin temperature (Tsk), hydration status (urine osmolality), fluid intake (self-report), and visual and auditory selective attention (performance tests). Measures were taken pre-, mid-, and postcompetition day and also during the precompetition reconnaissance.Results. In ambient temperatures of 20.1°C (in-car peak 33.9°C) mean (SD) peak HR andTcorewere significantly elevated (P<0.05) during rally compared to reconnaissance (166 (17) versus 111 (16) beats·min−1and 38.5 (0.4) versus 37.6 (0.2)°C, resp.). Values during competitive stages were substantially higher in drivers. High urine osmolality was indicated in some drivers within competition. Attention was maintained during the event but was significantly lower prerally, though with considerable individual variation.Conclusions. Environmental and physical demands during rally competition produced significant physiological responses. Challenges to thermoregulation, hydration status, and cognitive function need to be addressed to minimise potentially negative effects on performance and safety.
Exhaustive Exercise Attenuates the Neurovascular Coupling by Blunting the Pressor Response to Visual Stimulation
Authors: Yamaguchi Yuji , Ikemura Tsukasa , Hayashi Naoyuki
Published: March 2015

Neurovascular coupling (NVC) is assessed as an increase response to visual stimulation, and is monitored by blood flow of the posterior cerebral artery (PCA). To investigate whether exhaustive exercise modifies NVC, and more specifically, the relative contributions of vasodilatation in the downstream of PCA and the pressor response on NVC, we measured blood flow velocity in the PCA (PCAv) in 13 males using transcranial Doppler ultrasound flowmetry during a leg-cycle exercise at 75% of maximal heart rate until exhaustion. NVC was estimated as the relative change in PCAv from the mean value obtained during 20-s with the eyes closed to the peak value obtained during 40-s of visual stimulation involving looking at a reversed checkerboard. Conductance index (CI) was calculated by dividing PCAv by mean arterial pressure (MAP) to evaluate the vasodilatation. At exhaustion, PCAv was significantly decreased relative to baseline measurements, and the PCAv response to visual stimulation significantly decreased. Compared to baseline, exhaustive exercise significantly suppressed the increase in MAP to visual stimulation, while the CI response did not significantly change by the exercise. These results suggest that exhaustive exercise attenuates the magnitude of NVC by blunting the pressor response to visual stimulation.
Analysis of Chromosome 17 miRNAs and Their Importance in Medulloblastomas
Authors: López-Ochoa Sebastian , Ramírez-García Marina , Castro-Sierra Eduardo , Arenas-Huertero Francisco
Published: March 2015

MicroRNAs (miRNAs) are small sequences of nucleotides that regulate posttranscriptionally gene expression. In recent years they have been recognized as very important general regulators of proliferation, differentiation, adhesion, cell death, and others. In some cases, the characteristic presence of miRNAs reflects some of the cellular pathways that may be altered. Particularly medulloblastomas (MB) represent entities that undergo almost characteristic alterations of chromosome 17: from loss of discrete fragments and isochromosomes formation to complete loss of one of them. An analysis of the major loci on this chromosome revealed that it contains at least 19 genes encoding miRNAs which may regulate the development and differentiation of the brain and cerebellum. miRNAs are regulators of real complex networks; they can regulate from 100 to over 300 messengers of various proteins. In this review some miRNAs are considered to be important in MB studies. Some of them are miRNA-5047, miRNA-1253, miRNA-2909, and miRNA-634. Everyone can significantly affect the development, growth, and cell invasion of MB, and they have not been explored in this tumor. In this review, we propose some miRNAs that can affect some genes in MB, and hence the importance of its study.
Modelling Stochastic Route Choice Behaviours with a Closed-Form Mixed Logit Model
Authors: Lai Xinjun , Li Jun
Published: March 2015

A closed-form mixed Logit approach is proposed to model the stochastic route choice behaviours. It combines both the advantages of Probit and Logit to provide a flexible form in alternatives correlation and a tractable form in expression; besides, the heterogeneity in alternative variance can also be addressed. Paths are compared by pairs where the superiority of the binary Probit can be fully used. The Probit-based aggregation is also used for a nested Logit structure. Case studies on both numerical and empirical examples demonstrate that the new method is valid and practical. This paper thus provides an operational solution to incorporate the normal distribution in route choice with an analytical expression.
The Formation of Biofilms byPseudomonas aeruginosa: A Review of the Natural and Synthetic Compounds Interfering with Control Mechanisms
Authors: Rasamiravaka Tsiry , Labtani Quentin , Duez Pierre , El Jaziri Mondher
Published: March 2015

P. aeruginosais an opportunistic pathogenic bacterium responsible for both acute and chronic infections. Beyond its natural resistance to many drugs, its ability to form biofilm, a complex biological system, renders ineffective the clearance by immune defense systems and antibiotherapy. The objective of this report is to provide an overview (i) onP. aeruginosabiofilm lifestyle cycle, (ii) on the main key actors relevant in the regulation of biofilm formation byP. aeruginosaincluding QS systems,GacS/GacAandRetS/LadStwo-component systems and C-di-GMP-dependent polysaccharides biosynthesis, and (iii) finally on reported natural and synthetic products that interfere with control mechanisms of biofilm formation byP. aeruginosawithout affecting directly bacterial viability. Concluding remarks focus on perspectives to consider biofilm lifestyle as a target for eradication of resistant infections caused byP. aeruginosa.
Physiological Impact of Abnormal Lipoxin A4Production on Cystic Fibrosis Airway Epithelium and Therapeutic Potential
Authors: Higgins Gerard , Ringholz Fiona , Buchanan Paul , McNally Paul , Urbach Valérie
Published: March 2015

Lipoxin A4has been described as a major signal for the resolution of inflammation and is abnormally produced in the lungs of patients with cystic fibrosis (CF). In CF, the loss of chloride transport caused by the mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) Cl−channel gene results in dehydration, mucus plugging, and reduction of the airway surface liquid layer (ASL) height which favour chronic lung infection and neutrophil based inflammation leading to progressive lung destruction and early death of people with CF. This review highlights the unique ability of LXA4to restore airway surface hydration, to stimulate airway epithelial repair, and to antagonise the proinflammatory program of the CF airway, circumventing some of the most difficult aspects of CF pathophysiology. The report points out novel aspects of the cellular mechanism involved in the physiological response to LXA4, including release of ATP from airway epithelial cell via pannexin channel and subsequent activation of and P2Y11 purinoreceptor. Therefore, inadequate endogenous LXA4biosynthesis reported in CF exacerbates the ion transport abnormality and defective mucociliary clearance, in addition to impairing the resolution of inflammation, thus amplifying the vicious circle of airway dehydration, chronic infection, and inflammation.
Power Load Prediction Based on Fractal Theory
Authors: Jian-Kai Liang , Cattani Carlo , Wan-Qing Song
Published: March 2015

The basic theories of load forecasting on the power system are summarized. Fractal theory, which is a new algorithm applied to load forecasting, is introduced. Based on the fractal dimension and fractal interpolation function theories, the correlation algorithms are applied to the model of short-term load forecasting. According to the process of load forecasting, the steps of every process are designed, including load data preprocessing, similar day selecting, short-term load forecasting, and load curve drawing. The attractor is obtained using an improved deterministic algorithm based on the fractal interpolation function, a day’s load is predicted by three days’ historical loads, the maximum relative error is within 3.7%, and the average relative error is within 1.6%. The experimental result shows the accuracy of this prediction method, which has a certain application reference value in the field of short-term load prediction.
Layer-by-Layer Assembly of Polysaccharides and 6,10-Ionene for Separation of Nitrogen-Containing Pharmaceuticals and Their Enantiorecognition by Capillary Electrophoresis
Authors: Ioutsi Anna , Shapovalova Elena , Prokhorova Aleksandra , Shpigun Oleg
Published: March 2015

Two silica capillaries modified layer-by-layer with 6,10-ionene and N-(3-sulfo-3-carboxy)-propionylchitosan (SCPC) and with 6,10-ionene and dextran sulfate (DS) were prepared and investigated. Dynamic coating of the capillary efficiently reduces the adsorption of the background electrolyte, sample matrix components, and analytes on its inner wall. Such coatings effect good reproducibility and sensitivity of determination. We demonstrate that separation of betablockers, calcium channel blockers, alpha-adrenergic agonists, H1-blockers, and diuretics was the most efficient and rapid separation with a capillary modified with dextran sulfate. Tetrahydrozoline, carbinoxamine, and furacilin, which are commonly employed as treatments for allergic rhinitis, were identified in human urea. Their concentrations, independently verified by HPLC, were found to be5.3±0.8,6.6±0.5, and0.9±0.2 μg mL−1, withLOD=0.07, 0.03, 0.10 μg mL−1, andLOQ=1.0, 0.8, 0.6 μg mL−1, respectively.
Traumatic Hip Dislocation with Associated Femoral Head Fracture
Authors: Dortaj H. , Emamifar A.
Published: March 2015

Dislocation of the hip is a critical injury that results from high-energy trauma. This paper describes a case of posterior dislocation of the right hip in a 35-year-old woman with associated ipsilateral femoral head fracture. Initial treatment included reduction of the right hip through posterior approach and fixation of the femoral head fracture with three absorbable screws. After 15-month follow-up, a full range of motion has been achieved and there are no signs of avascular necrosis, hip instability, or limping. The authors describe their method of surgery.
The Plant Growth-Promoting BacteriaAzospirillum amazonense: Genomic Versatility and Phytohormone Pathway
Authors: Cecagno Ricardo , Fritsch Tiago Ebert , Schrank Irene Silveira
Published: March 2015

The rhizosphere bacteriumAzospirillum amazonenseassociates with plant roots to promote plant growth. Variation in replicon numbers and rearrangements is common amongAzospirillumstrains, and characterization of these naturally occurring differences can improve our understanding of genome evolution. We performed anin silicocomparative genomic analysis to understand the genomic plasticity ofA. amazonense. The number ofA. amazonense-specific coding sequences was similar when compared with the six closely related bacteria regarding belonging or not to theAzospirillumgenus. Our results suggest that the versatile gene repertoire found inA. amazonensegenome could have been acquired from distantly related bacteria from horizontal transfer. Furthermore, the identification of coding sequence related to phytohormone production, such as flavin-monooxygenase and aldehyde oxidase, is likely to represent the tryptophan-dependent TAM pathway for auxin production in this bacterium. Moreover, the presence of the coding sequence for nitrilase indicates the presence of the alternative route that uses IAN as an intermediate for auxin synthesis, but it remains to be established whether the IAN pathway is the Trp-independent route. Future investigations are necessary to support the hypothesis that its genomic structure has evolved to meet the requirement for adaptation to the rhizosphere and interaction with host plants.
Adaptive Synchronization of Chaotic SC-CNN with Uncertain State Template
Authors: Dam Thanh Phuong , Pham Thuong Cat
Published: March 2015

The problem of synchronization of chaotic State Controlled Cellular Neural Network (SC-CNN) with uncertain state template is investigated. In detail, the following three cases are solved: firstly, synchronization of two identical chaotic SC-CNNs with uncertain state template, secondly, synchronization of two nonidentical chaotic SC-CNNs with all uncertain state templates, and, thirdly, synchronization between chaotic SC-CNN with uncertain state template and different uncertain parameter chaotic systems. The controllers and update laws proposed in each case are proved closely based on Lyapunov stability theory. In addition, some illustrative corresponding examples are presented to demonstrate the effectiveness and usefulness of the proposed control laws.
Cell Membrane Fluid–Mosaic Structure and Cancer Metastasis
Authors: Nicolson Garth L.
Published: March 2015

Cancer cells are surrounded by a fluid–mosaic membrane that provides a highly dynamic structural barrier with the microenvironment, communication filter and transport, receptor and enzyme platform. This structure forms because of the physical properties of its constituents, which can move laterally and selectively within the membrane plane and associate with similar or different constituents, forming specific, functional domains. Over the years, data have accumulated on the amounts, structures, and mobilities of membrane constituents after transformation and during progression and metastasis. More recent information has shown the importance of specialized membrane domains, such as lipid rafts, protein–lipid complexes, receptor complexes, invadopodia, and other cellular structures in the malignant process. In describing the macrostructure and dynamics of plasma membranes, membrane-associated cytoskeletal structures and extracellular matrix are also important, constraining the motion of membrane components and acting as traction points for cell motility. These associations may be altered in malignant cells, and probably also in surrounding normal cells, promoting invasion and metastatic colonization. In addition, components can be released from cells as secretory molecules, enzymes, receptors, large macromolecular complexes, membrane vesicles, and exosomes that can modify the microenvironment, provide specific cross-talk, and facilitate invasion, survival, and growth of malignant cells. Cancer Res; 75(7); 1169–76. ©2015 AACR.
Prognostic Significance of Tryptophan Catabolism in Adult T-cell Leukemia/Lymphoma
Authors: Masaki Ayako , Ishida Takashi , Maeda Yasuhiro , Suzuki Susumu , Ito Asahi , Takino Hisashi , Ogura Hiroka , Totani Haruhito , Yoshida Takashi , Kinoshita Shiori , Narita Tomoko , Ri Masaki , Kusumoto Shigeru , Inagaki Atsushi , Komatsu Hirokazu , Niimi Akio , Ueda Ryuzo , Utsunomiya Atae , Inagaki Hiroshi , Iida Shinsuke
Published: March 2015

Purpose: Indoleamine 2,3-dioxygenase 1 (IDO1: IDO), an enzyme catabolizing tryptophan (Trp) into the kynurenine (Kyn) pathway, is increasingly being recognized as an important microenvironmental factor suppressing antitumor immune responses. The purpose of the present study was to determine the prognostic significance of Trp catabolism in adult T-cell leukemia/lymphoma (ATL).

Experimental Design: We quantified serum Trp and Kyn in 96 ATL patients, 38 human T-cell lymphotropic virus type-1 asymptomatic carriers (HTLV-1 ACs), and 40 healthy adult volunteer controls. The relationships between various clinical parameters including overall survival were analyzed. IDO expression was evaluated in the affected lymph nodes of ATL patients.

Results: Serum Kyn concentrations and Kyn/Trp ratios were significantly higher in HTLV-1 ACs than healthy controls. Both increased significantly with progression from HTLV-1 AC to ATL. However, there were no significant differences in the serum Trp concentrations between ATL patients, HTLV-1 ACs, and controls. IDO was possibly produced by ATL and/or cells of the microenvironment. Multivariate analyses demonstrated that a high serum Kyn/Trp ratio and high Kyn level, but not a high Trp level, were significantly independent detrimental prognostic factors in ATL, as well as in that subset of patients with aggressive variant ATL.

Conclusions: Quantification of serum Kyn and Trp is useful for predicting prognosis of an individual ATL patient. Furthermore, ATL, especially in patients with a high serum Kyn/Trp ratio, is an appropriate disease for testing novel cancer immunotherapies targeting IDO. Clin Cancer Res; 21(12); 2830–9. ©2015 AACR.
Identification of a Candidate Gene Panel for the Early Diagnosis of Prostate Cancer
Authors: Leyten Gisele H.J.M. , Hessels Daphne , Smit Frank P. , Jannink Sander A. , de Jong Hans , Melchers Willem J.G. , Cornel Erik B. , de Reijke Theo M. , Vergunst Henk , Kil Paul , Knipscheer Ben C. , Hulsbergen-van de Kaa Christina A. , Mulders Peter F.A. , van Oort Inge M. , Schalken Jack A.
Published: March 2015

Purpose: Serum PSA (sPSA) testing has led to the identification of patients with indolent prostate cancer, and inevitably overtreatment has become a concern. Progensa PCA3 urine testing was shown to improve the diagnosis of prostate cancer, but its diagnostic value for aggressive prostate cancer is limited. Therefore, urinary biomarkers that can be used for prediction of Gleason score ≥7 prostate cancer in biopsies are urgently needed.

Experimental Design: Using gene expression profiling data, 39 prostate cancer biomarkers were identified. After quantitative PCR analysis on tissue specimens and urinary sediments, eight promising biomarkers for the urinary detection of prostate cancer were selected (ONECUT2, HOXC4, HOXC6, DLX1, TDRD1, NKAIN1, MS4A8B, PPFIA2). The hypothesis that biomarker combinations improve the diagnostic value for aggressive prostate cancer was tested on 358 urinary sediments of an intention-to-treat cohort.

Results: A urinary three-gene panel (HOXC6, TDRD1, and DLX1) had higher accuracy [area under the curve (AUC), 0.77; 95% confidence interval (CI), 0.71–0.83] to predict Gleason score ≥7 prostate cancer in biopsies compared with Progensa PCA3 (AUC, 0.68; 95% CI, 0.62–0.75) or sPSA (AUC, 0.72; 95% CI, 0.65–0.78). Combining the three-gene panel with sPSA further improved the predictive accuracy (AUC, 0.81; 95% CI, 0.75–0.86). The accuracy of the three-gene predictive model was maintained in subgroups with low sPSA concentrations.

Conclusions: The urinary three-gene panel (HOXC6, TDRD1, and DLX1) represents a promising tool to identify patients with aggressive prostate cancer, also in those with low sPSA values. The combination of the urinary three-gene panel with sPSA bears great potential for the early diagnosis of patients with clinically significant prostate cancer. Clin Cancer Res; 21(13); 3061–70. ©2015 AACR.
A Phase I/II Trial of BNC105P with Everolimus in Metastatic Renal Cell Carcinoma
Authors: Pal Sumanta , Azad Arun , Bhatia Shailender , Drabkin Harry , Costello Brian , Sarantopoulos John , Kanesvaran Ravindran , Lauer Richard , Starodub Alexander , Hauke Ralph , Sweeney Christopher J. , Hahn Noah M. , Sonpavde Guru , Richey Stephen , Breen Timothy , Kremmidiotis Gabriel , Leske Annabell , Doolin Elizabeth , Bibby David C. , Simpson Jeremy , Iglesias Jose , Hutson Thomas
Published: March 2015

Purpose: BNC105P inhibits tubulin polymerization, and preclinical studies suggest possible synergy with everolimus. In this phase I/II study, efficacy and safety of the combination were explored in patients with metastatic renal cell carcinoma (mRCC).

Experimental Design: A phase I study in patients with clear cell mRCC and any prior number of therapies was conducted using a classical 3 + 3 design to evaluate standard doses of everolimus with increasing doses of BNC105P. At the recommended phase II dose (RP2D), patients with clear cell mRCC and one to two prior therapies (including ≥ 1 VEGF-TKI) were randomized to BNC105P with everolimus (arm A) or everolimus alone (arm B). The primary endpoint of the study was 6-month progression-free survival (6MPFS). Secondary endpoints included response rate, PFS, overall survival, and exploratory biomarker analyses.

Results: In the phase I study (N = 15), a dose of BNC105P at 16 mg/m2 with everolimus at 10 mg daily was identified as the RP2D. In the phase II study, 139 patients were randomized, with 69 and 67 evaluable patients in arms A and B, respectively. 6MPFS was similar in the treatment arms (arm A: 33.82% vs. arm B: 30.30%, P = 0.66) and no difference in median PFS was observed (arm A: 4.7 mos vs. arm B: 4.1 mos; P = 0.49). Changes in matrix metalloproteinase-9, stem cell factor, sex hormone-binding globulin, and serum amyloid A protein were associated with clinical outcome with BNC105P.

Conclusions: Although the primary endpoint was not met in an unselected population, correlative studies suggest several biomarkers that warrant further prospective evaluation. Clin Cancer Res; 21(15); 3420–7. ©2015 AACR.
Training a New Generation of Speech-Language Pathologists with Competences in the Management of Literacy Disorders and Learning Disabilities in Hong Kong
Authors: Yuen Kevin C.P.
Published: March 2015

One of the recent developments in the education of speech-language pathology is to include literacy disorders and learning disabilities as key training components in the training curriculum. Disorders in reading and writing are interwoven with disorders in speaking and listening, which should be managed holistically, particularly in children and adolescents. With extensive training in clinical linguistics, language disorders, and other theoretical knowledge and clinical skills, speech-language pathologists (SLPs) are the best equipped and most competent professionals to screen, identify, diagnose, and manage individuals with literacy disorders. To tackle the challenges of and the huge demand for services in literacy as well as language and learning disorders, the Hong Kong Institute of Education has recently developed the Master of Science Programme in Educational Speech-Language Pathology and Learning Disabilities, which is one of the very first speech-language pathology training programmes in Asia to blend training components of learning disabilities, literacy disorders, and social-emotional-behavioural-developmental disabilities into a developmentally and medically oriented speech-language pathology training programme. This new training programme aims to prepare a new generation of SLPs to be able to offer comprehensive support to individuals with speech, language, literacy, learning, communication, and swallowing disorders of different developmental or neurogenic origins, particularly to infants and adolescents as well as to their family and educational team.
Changing Etiological Trends in Male Precocious Puberty: Evaluation of 100 Cases with Central Precocious Puberty over the Last Decade
Authors: Alikasifoglu Ayfer , Vuralli Dogus , Gonc E. Nazli , Ozon Alev , Kandemir Nurgun
Published: March 2015

Background/Aims: There are few studies in the literature that have evaluated the etiological factors in boys with central precocious puberty (CPP), and these studies are limited in terms of the sample size. In the present study, we aimed to evaluate the etiological factors in male CPP cases. Methods: One hundred male CPP subjects, aged between 9 months and 10.5 years, were included. The medical records were screened, and age at diagnosis, bone age, body weight, height, pubertal stage, imaging findings of the pituitary gland, testosterone, and basal and stimulated gonadotropin levels were recorded. Results: There was no underlying cause in 74% of the cases, and an organic cause was determined in only 26%. Most of the organic cases had been diagnosed before the age of 7 years, whereas most of the idiopathic cases had been diagnosed after the age of 7 years. Conclusion: An organic cause was determined in 26% of the male patients with CPP. This rate is one of the lowest rates in the literature and indicates that the number of idiopathic male CPP cases is increasing over time. When a boy is diagnosed with CPP above the age of 7 years, the odds of detecting an underlying pathology are very low, and these cases are mostly idiopathic.
DNA, histones and neutrophil extracellular traps exert anti-fibrinolytic effects in a plasma environment
Authors: Varjú Imre , Longstaff Colin , Szabó László , Farkas Ádám Zoltán , Varga-Szabó Veronika Judit , Tanka-Salamon Anna , Machovich Raymund , Kolev Krasimir
Published: March 2015

In response to various inflammatory stimuli, neutrophils secrete neutrophil extracellular traps (NETs), web-like meshworks of DNA, histones and granular components forming supplementary scaffolds in venous and arterial thrombi. Isolated DNA and histones are known to promote thrombus formation and render fibrin clots more resistant to mechanical forces and tissue-type plasminogen activator (tPA)-induced enzymatic digestion. The present study extends our earlier observations to a physiologically more relevant environment including plasma clots and NET-forming neutrophils. A range of techniques was employed including imaging (scanning electron microscopy (SEM), confocal laser microscopy, and photoscanning of macroscopic lysis fronts), clot permeability measurements, turbidimetric lysis and enzyme inactivation assays. Addition of DNA and histones increased the median fibre diameter of plasma clots formed with 16 nM thrombin from 108 to 121 and 119 nm, respectively, and decreased their permeability constant from 6.4 to 3.1 and 3.7×10−9 cm2. Histones effectively protected thrombin from antithrombin-induced inactivation, while DNA inhibited plasminogen activation on the surface of plasma clots and their plasmin-induced resolution by 20 and 40 %, respectively. DNA and histones, as well as NETs secreted by phorbol-myristate-acetate-activated neutrophils, slowed down the tPA-driven lysis of plasma clots and the latter effect could be reversed by the addition of DNase (streptodornase). SEM images taken after complete digestion of fibrin in NET-containing plasma clots evidenced retained NET scaffold that was absent in DNase-treated clots. Our results show that DNA and histones alter the fibrin architecture in plasma clots, while NETs contribute to a decreased lytic susceptibility that can be overcome by DNase.
ApoA-I/HDL-C levels are inversely associated with abdominal aortic aneurysm progression
Authors: Molina-Sánchez Pedro , Jorge Inmaculada , Martinez-Pinna Roxana , Blanco-Colio Luis Miguel , Tarin Carlos , Torres-Fonseca Monica Maria , Esteban Margarita , Laustsen Jesper , Ramos-Mozo Priscila , Calvo Enrique , Lopez Juan Antonio , Ceniga Melina Vega de , Michel Jean-Baptiste , Egido Jesus , Andrés Vicente , Vazquéz Jesús , Meilhac Olivier , Burillo Elena , Lindholt Jes S. , Martin-Ventura Jose Luis
Published: March 2015

Abdominal aortic aneurysm (AAA) evolution is unpredictable, and there is no therapy except surgery for patients with an aortic size > 5 cm (large AAA). We aimed to identify new potential biomarkers that could facilitate prognosis and treatment of patients with AAA. A differential quantitative proteomic analysis of plasma proteins was performed in AAA patients at different stages of evolution [small AAA (aortic size=3�5cm) vs large AAA] using iTRAQ labelling, highthroughput nano-LC-MS/MS and a novel multi-layered statistical model. Among the proteins identified, ApoA-I was decreased in patients with large AAA compared to those with small AAA. These results were validated by ELISA on plasma samples from small (n=90) and large AAA (n=26) patients (150 ± 3 vs 133 ± 5 mg/dl, respectively, p< 0.001). ApoA-I levels strongly correlated with HDL-Cholesterol (HDL-C) concentration (r=0.9, p< 0.001) and showed a negative correlation with aortic size (r=-0.4, p< 0.01) and thrombus volume (r=-0.3, p< 0.01), which remained significant after adjusting for traditional risk factors. In a prospective study, HDL-C independently predicted aneurysmal growth rate in multiple linear regression analysis (n=122, p=0.008) and was inversely associated with need for surgical repair (Adjusted hazard ratio: 0.18, 95 % confidence interval: 0.04�0.74, p=0.018). In a nation-wide Danish registry, we found lower mean HDL-C concentration in large AAA patients (n=6,560) compared with patients with aorto-iliac occlusive disease (n=23,496) (0.89 ± 2.99 vs 1.59 ± 5.74 mmol/l, p< 0.001). Finally, reduced mean aortic AAA diameter was observed in AngII-infused mice treated with ApoA-I mimetic peptide compared with saline-injected controls. In conclusion, ApoAI/ HDL-C systemic levels are negatively associated with AAA evolution. Therapies targeting HDL functionality could halt AAA formation.
Dedicator of Cytokinesis 2, A Novel Regulator for Smooth Muscle Phenotypic Modulation and Vascular Remodeling
Authors: Guo Xia , Shi Ning , Cui Xiao-Bing , Wang Jia-Ning , Fukui Yoshinori , Chen Shi-You
Published: March 2015

Rationale:

Vascular smooth muscle cell (SMC) phenotypic modulation and vascular remodeling contribute to the development of several vascular disorders such as restenosis after angioplasty, transplant vasculopathy, and atherosclerosis. The mechanisms underlying these processes, however, remain largely unknown.

Objective:

The objective of this study is to determine the role of dedicator of cytokinesis 2 (DOCK2) in SMC phenotypic modulation and vascular remodeling.

Methods and Results:

Platelet-derived growth factor-BB induced DOCK2 expression while modulating SMC phenotype. DOCK2 deficiency diminishes platelet-derived growth factor-BB or serum-induced downregulation of SMC markers. Conversely, DOCK2 overexpression inhibits SMC marker expression in primary cultured SMC. Mechanistically, DOCK2 inhibits myocardin expression, blocks serum response factor nuclear location, attenuates myocardin binding to serum response factor, and thus attenuates myocardin-induced smooth muscle marker promoter activity. Moreover, DOCK2 and Kruppel-like factor 4 cooperatively inhibit myocardin–serum response factor interaction. In a rat carotid artery balloon-injury model, DOCK2 is induced in media layer SMC initially and neointima SMC subsequently after vascular injury. Knockdown of DOCK2 dramatically inhibits the neointima formation by 60%. Most importantly, knockout of DOCK2 in mice markedly blocks ligation-induced intimal hyperplasia while restoring SMC contractile protein expression.

Conclusions:

Our studies identified DOCK2 as a novel regulator for SMC phenotypic modulation and vascular lesion formation after vascular injury. Therefore, targeting DOCK2 may be a potential therapeutic strategy for the prevention of vascular remodeling in proliferative vascular diseases.
Coronary Artery Bypass Grafting in Patients 50 Years or Younger
Authors: Dalén Magnus , Ivert Torbjörn , Holzmann Martin J. , Sartipy Ulrik
Published: March 2015

Background—

There are limited data regarding long-term results after coronary artery bypass grafting (CABG) in young adults. We performed a nationwide population-based cohort study to analyze long-term survival, major adverse cardiovascular events, and factors associated with elevated risk in young adults undergoing CABG.

Methods and Results—

We included all adult patients ≤50 years of age who underwent primary isolated CABG in Sweden between 1997 and 2013 from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) register. Patient data were linked from national Swedish health data registers to create a study database. We identified 4086 young adults with a mean age of 46 years and 18% women. During a median follow-up time of 10.9 years (interquartile range, 6.4–14.1) 490 (12%) patients died. Survival at 5, 10, and 15 years was 96% (95% CI, 95–96), 90% (95% CI, 89–91), and 82% (95%CI, 80–83), respectively, which was significantly better in comparison with patients aged 51 to 70 years and >70 years who underwent CABG during the same period. The cumulative incidence of death or a major adverse cardiovascular event during 17 years after CABG was mainly driven by myocardial infarction or the need for repeat revascularization. The most important risk factors for all-cause mortality were chronic kidney disease, reduced left ventricular ejection fraction, peripheral vascular disease, or chronic obstructive pulmonary disease.

Conclusions—

Long-term survival and freedom from major cardiovascular events after CABG was better in young adults than in older patients. Factors significantly associated with an elevated long-term risk of death or adverse outcome were similar to well-known risk factors for older age groups following CABG.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02276950.
Essentialism or an Anthropological Approach: The Role and Function of the Scientific Study of Religion in a Historical Perspective
Authors: Hjärpe Jan
Published: March 2015

The study of religion has its historical origin in the confessional education of religious functionaries, which has influenced the structuring of the study. The order of the topics studied has been, as a rule, first, languages relevant for the study of the normative texts, then the interpretation of these texts, followed by the historical development within the religion, its doctrines (systematic theology), and its practical application (ethics, practical theology). This order of the study is very relevant for priests, pastors, and preachers. It has a certain normative purpose. But it is problematic when the same structure is followed in the empirical study, description, and analysis of how religious tradition is selected and functions in the contemporary, modern, globalized society. A more appropriate structuring is a combination of psychological, sociological, and political approaches, taking into account that religions constitute very changing phenomena, that religious belonging is only one of an individual’s many “identities,” and that religious leaders and their pronouncements are not very representative for the actual functions of religion for the individual, the society, and the political life. The problematic is illustrated by a number of doctoral dissertations from the late twentieth and early twenty-first centuries.
Recognition of Minority Denominations in Denmark: Negotiations in Religion, Identity and Judicial Process
Authors: Geertz Armin W.
Published: March 2015

The Constitution of Denmark of 1849 establishes the Evangelical Lutheran Church as the Church of Denmark, which “shall as such be supported by the State.” A handful of other denominations enjoyed recognition by royal decree until this practice was ended in 1970 with the new Marriage Act which allowed church weddings with civil validity to take place not only in the Church of Denmark but also in recognized denominations and other religious communities that obtain authorization from the Minister of Ecclesiastical Affairs. In 1998 an expert committee was established to advise the Minister on applications for denominational recognition. The committee consisted of myself, a historian of religions and chairman, sociologist of religion Ole Riis, later replaced by Margit Warburg, Church historian Jørgen Stenbæk, later replaced by Per Ingesman and professor of law Eva Smith, later replaced by Jens Elo Rytter. In the fall of 2007, a cabinet reorganization in the Liberal-Conservative Government led to a reorganization of the legal body responsible for the recognition of minority denominations. Thus the judicial process, including the expert committee, was transferred to the Department of Justice under the Section of Family Affairs. Since 2014, jurisdiction is under the Ministry of Child, Equality, Integration and Social Affairs, Permanent Under-Secretarial Department, Office of Family Affairs. This paper will describe the judicial and pragmatic aspects of our deliberations. Furthermore, a few key cases will be described which demonstrate how the recognition process sometimes influences the negotiation of religious identity among applicant denominations.
Negotiating as a Group Representative: Constraints and Opportunities
Authors: Druckman Daniel
Published: March 2015

Research on negotiating representatives has been a popular topic since the 1960s. The early experimental studies revealed a variety of situational influences on the decisions made by representatives. Construed as constraints, these variables are shown to move negotiating processes in the direction of agreement or impasse. More recent research extends the portfolio of influences by examining the roles of trust, immoral behavior, group status, and divided constituencies. Of particular interest is the finding that hawkish constituents have more influence on representatives than dovish constituents. The effect is, however, weaker when the hawks have low group status. It is also weakened when representatives are primed to have a pro-social orientation. Another recent line of research focuses on collective representation and shows how several features of constituencies influence those decisions. The article concludes with a summary of key findings and a suggestion for bridging the behavioral and interpretative traditions of scholarship on representation.
Negotiating Hostages with Terrorists: Paradoxes and Dilemmas
Authors: Faure Guy Olivier
Published: March 2015

There are few negotiations where it is so necessary to be fast and effective than in those that deal with hostages. This is an almost unfeasible task that has to be carried out with the most unlikely negotiator, the terrorist, in an extremely hostile context. Considering the issues at stake – the freedom of the hostages and, very often, their lives – a negotiator has to manage many challenges. There are seven dilemmas and paradoxes in reaching agreement. A negotiator has to solve a Shakespearian dilemma, manage contradictory objectives, deal with incompatible rationales, handle the toughness dilemma, come to grips with contradictions between empathy and assertiveness, handle cultural dilemmas, and cope with a moral dilemma.
Nomenclature, morphometry, karyology and SEM cypselae analysis of Carduus brutius (Asteraceae) and its relatives
Authors: Peruzzi Lorenzo , Astuti Giovanni , Carta Angelino , Roma-Marzio Francesco , Dolci David , Caldararo Franco , Bartolucci Fabrizio , Bernardo Liliana
Published: March 2015

The systematic relationships between Carduus brutius and its putatively relative taxa, i.e. Carduus affinis and C. defloratus subsp. carlinifolius, were assessed by means of morphological, morphometric and karyological analyses. Our results highlighted a diploid status (2n = 2x = 22) for all the three involved taxa and a higher morphological similarity between C. brutius and C. affinis, which are also completely allopatric (but collectively sympatric with C. defloratus subsp. carlinifolius). The names Carduus affinis Guss., C. affinis var. brutius Fiori, C. affinis var. vulturius Fiori and C. affinis f. pollinensis Fiori were typified. At the present state of knowledge, a subspecific status seems the most appropriate for C. brutius, as C. affinis subsp. brutius. This taxon can be regarded as schizoendemic, restricted to southern Italy (Montea-Caramolo mountain area, Calabria).
Notes on Malesherbia (Passifloraceae) in Peru: a new species from southern Peru, a new record and a first report on interspecific hybridization in Malesherbia
Authors: Weigend Maximilian , Jossberger Thomas , Beltrán Hamilton
Published: March 2015

Malesherbia fatimae is described as a new species from the Province Condesuyos, Department of Arequipa, Peru. The new species is clearly differentiated from all know species of the genus by forming a strictly erect, laxly branched shrub with densely tomentose indument and from the perennial Peruvian members by an absence of the glandular trichomes. No clear affinities to know species present themselves, but the new species evidently belongs to Malesherbia sect. Malesherbia. At the type locality a putative hybrid with the morphologically highly divergent Malesherbia tenuifolia was observed, showing morphologically intermediate characters between M. fatimae and M. tenuifolia. Malesherbia tenuifolia is here for the first time reported from Peru, bringing the species total for the county to 12. A second putative interspecific hybrid, Malesherbia ardens × M. arequipensis, is reported from Department Moquegua. This indicates that species of Malesherbia may hybridize when eco-geographical separation breaks down due to habitat modification. The new species and the two novel hybrids are described and illustrated.
Molecular phylogenetic analysis reveals two new species of Discosia from Italy
Authors: Li Wenjing , Liu Jian-kui , Bhat D. Jayarama , Camporesi Erio , DAI Dong-QING , Mortimer Peter E , Xu Jian-chu , Hyde Kevin D. , Chomnunti Putarak
Published: March 2015

Two fresh collections of Discosia were made from dead leaves of Fagus sylvatica in Italy. As these collections could not be cultured, the fruiting bodies were directly used for sequencing using a Forensic DNA Extraction Kit. Based on analyses of the concatenated internal transcribed spacer regions of the nrDNA operon (ITS) and large subunit rDNA (LSU) gene sequences, as well as morphological characters, the fresh collections are introduced as two new species, namely D. italica and D. fagi. Phylogenetically, these two species are distinct from all other Discosia species. Morphologically, D. italica is somewhat similar with D. fagi, but can be distinguished using dimension of conidiomata and conidiogenous cells. Descriptions and illustrations of the new taxa are provided herein.
Verbascum shahsavarensis (Scrophulariaceae), a new species for Flora of Iran
Authors: SOTOODEH Arash , Civeyrel Laure , Attar Farideh
Published: March 2015

A new endemic species, Verbascum shahsavarensis, is described from north of Iran. Based on two unique characters of this species, these being two anterior longitudinally obliquely inserted anthers and an ebracteolate pedicel, we compared it to species described by Murbeck in 1933. The new species can be easily distinguished from the other Iranian species by having bi-colored hairs on the stamen filaments and the unique anther and pedicel characters. A distribution map is provided. The name of new species comes from Shahsavar, the ancient name of Tonekabon, an old coastal city on the Caspian Sea.
The assassin bug subfamily Tribelocephalinae (Hemiptera: Heteroptera:
Reduviidae) from Japan, with descriptions of eight new species in the genera Opistoplatys and Abelocephala
Authors: Ishikawa Tadashi , Cai Wanzhi , Tomokuni Masaaki
Published: March 2015

We examined the Japanese species of the reduviid subfamily Tribelocephalinae. We identified two species of Opistoplatys Westwood, which is the genus with the second largest number of species, and six species of Abelocephala Maldonado, which to date has been referred to as a monotypic genus. All the identified species represent new species and they are described herein under the following names: Opistoplatys minimus sp. nov., Opistoplatys flavolineatus sp. nov., Abelocephala albula sp. nov., Abelocephala araiorum sp. nov., Abelocephala nakatai sp. nov., Abelocephala yaeyamensis sp. nov., Abelocephala major sp. nov., and Abelocephala longiceps sp. nov. Species of Abelocephala can be distinguished from each other based on multiple morphological characters such as body length, ratio of the length to the width of the head, color of the posterior pronotal lobe, shading and pattern of color in the hemelytral basal part, and acuteness or roundness in the apical angle of the outer (larger) cell on the hemelytral membranes. We confirmed that the Japanese tribelocephalines are ground inhabitants living under and within the forest leaf litter. Our results inferred that species of Opistoplatys have positive phototaxis but generally move by walking, whereas species of Abelocephala have negative phototaxis but frequently fly above the forest floor.
Biogeographical regionalisation of the Andean region
Authors: MORRONE JUAN J.
Published: March 2015

A biogeographic regionalisation of the Andean region is proposed as a hierarchical classification of sub-regions, provinces, sub-provinces and districts. It is based on biogeographic analyses of terrestrial plant and animal taxa, and seeks to provide universality, objectivity and stability. The Andean region is currently comprised of the Central Chilean, Subantarctic and Patagonian sub-regions and the South American transition zone, 15 provinces, five sub-provinces and 81 districts. Complete synonymies and brief descriptions of the areas are provided, as well as the endemic taxa that diagnose the provinces.
Rethinking the Lower Bound on Aerosol Radiative Forcing
Authors: Stevens Bjorn
Published: March 2015

Based on research showing that in the case of a strong aerosol forcing, this forcing establishes itself early in the historical record, a simple model is constructed to explore the implications of a strongly negative aerosol forcing on the early (pre-1950) part of the instrumental record. This model, which contains terms representing both aerosol–radiation and aerosol–cloud interactions, well represents the known time history of aerosol radiative forcing as well as the effect of the natural state on the strength of aerosol forcing. Model parameters, randomly drawn to represent uncertainty in understanding, demonstrate that a forcing more negative than −1.0 W m−2 is implausible, as it implies that none of the approximately 0.3-K temperature rise between 1850 and 1950 can be attributed to Northern Hemisphere forcing. The individual terms of the model are interpreted in light of comprehensive modeling, constraints from observations, and physical understanding to provide further support for the less negative (−1.0 W m−2) lower bound. These findings suggest that aerosol radiative forcing is less negative and more certain than is commonly believed.