bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypotheses Regarding the Role of Pericytes in Regulating Movement of Fluid, Nutrients, and Hormones Across the Microcirculatory Endothelial Barrier
Authors: Lonigro Andrew J , McMurdo Lorraine , Stephenson Alan H , Sprague Randy S , Weintraub Neal L
Published: September 2013

A decade ago, we initiated studies to define relationship(s) between products of 5-lipoxygenase-mediated arachidonic acid metabolism and altered microvascular permeability. Patients with permeability (nonhydrostatic) pulmonary edema (adult respiratory distress syndrome) and intact animal models of permeability edema, produced with agents that required neutrophils (phorbol myristate acetate) and those that did not (ethchlorvynol), invariably revealed the presence of leukotrienes; in contrast, leukotrienes were not detected in cases of hydrostatic pulmonary edema. In isolated perfused canine lung, we identified increases in microvascular permeability coefficients in response to the injurious agent. Permeability coefficients were not increased when injurious agents were given in the presence of 5-lipoxygenase inhibitors. To define further the relationships between leukotriene generation and edema formation, we postulated that leukotrienes effected contraction of capillary pericytes, thereby increasing pore size of endothelial intercellular junctions and enhancing movement across the microvascular barrier. We isolated pericytes from bovine retinas, identified them morphologically and by staining characteristics, and, in preliminary experiments, found that they do not possess the 5-lipoxygenase enzyme; however, when cocultured with neutrophils, which possess 5-lipoxygenase but cannot synthesize sulfidopeptide leukotrienes because of their lack of glutathione S-transferase, sulfidopeptide leukotriene synthesis ensued. In view of the anatomic position of pericytes, evidence that they participate in endothelial transport, their ability to contract, and evidence of cell-to-cell communication, we propose that pericytes control the movement of fluid, solutes, hormones, and small and large molecules across the microvascular endothelium.
cAMP-Dependent Phosphorylation of the Cardiac-Type α1 Subunit of the Voltage-Dependent Ca2+ channel in a murine pancreatic β-cell line
Authors: Leiser Margarita , Fleischer Norman
Published: September 2013

Two voltage-dependent calcium channels (VDCCs) have been reported in pancreatic islets: the β-cell/endocrine-brain and cardiac subtypes. The cardiac-type α1 subunit was isolated from cultured beta TC3 cells, a murine pancreatic β-cell line, by immunoprecipitation with a specific polyclonal antibody. We have examined the effects of 1-isobutyl-3-methylxanthine (IBMX) and forskolin, agonists that elevate cAMP in these cells, on the phosphorylation of this subunit in intact beta TC3 cells using a sensitive back-phosphorylation technique. This technique allows quantitative detection of protein phosphorylation that is specifically stimulated by cAMP. The stimulation of intact beta TC3 cells with forskolin or IBMX resulted in the phosphorylation of the cardiac-type α 1 subunit as evidenced by a 40–60% decrease in the ability of the 257-kDa form to serve as a substrate in the in vitro back-phosphorylation reaction with [γ-32P]ATP and the catalytic subunit of cAMP-dependent protein kinase (PKA). The effects of forskolin were time- and concentration-dependent. The concentration-dependency of forskolin-induced phosphorylation of the cardiac-type α 1 subunit and the potentiation of glucose-induced insulin secretion were highly correlated, a finding that is consistent with a role for such phosphorylation in mediating at least some of the effects of cAMP on secretion.
The Effect of Glucagon-Like Peptide I (GLP-I) on Glucose Elimination in Healthy Subjects Depends on the Pancreatic Glucoregulatory Hormones
Authors: Toft-Nielson Mai-britt , Madsbad Sten , Holst Jens J
Published: September 2013

Glucagon-like peptide I (GLP-I) decreases plasma glucose in type II diabetic patients and in healthy subjects indirectly by stimulation of insulin and inhibition of glucagon secretion, whereby the hepatic glucose production decreases. However, recent studies indicate that GLP-I may also directly influence peripheral and hepatic glucose uptake. We infused somatostatin (SS) intravenously (500 or 1,000 μg/h) in 13 healthy subjects to suppress insulin and glucagon secretion from the endocrine pancreas, together with infusion of either GLP-I (50 pmol · kg−1 · h−1) or saline intravenously. After 30 min, a 25-g intravenous glucose tolerance test (IVGTT) was carried out, and plasma concentrations of glucose, insulin, glucagon, and GLP-I were measured during the following 2 h. IVGTT together with GLP-I infusion significantly elevated insulin during 500 μg/h SS but not during 1,000 μg/h SS. Plasma glucagon was strongly depressed in all experiments. During 500 μg/h SS, the glucose disappearance constant, Kg, was 0.49 ± 0.03% per minute with GLP-I and 0.39 ± 0.04% per minute with saline (n = 8, P = 0.004). With 1,000 μg/h SS, Kg was 0.42 ± 0.03% per minute with GLP-I and 0.40 ± 0.03% per minute without (NS). In conclusion, when endogenous insulin secretion is held at a constant low level, which may be accomplished only with very large doses of SS, GLP-I has no effect on glucose elimination. Thus, an insulin-independent effect of GLP-I on glucose disposal could not be demonstrated.
Genetic Absence of γ-Interferon Delays but Does Not Prevent Diabetes in NOD Mice
Authors: Hultgren Bruce , Huang Xiaojian , Dybdal Noel , Stewart Timothy A
Published: September 2013

Cytoldnes, particularly interferons, may participate in the development of type I diabetes. This involvement could be from direct cytotoxic actions of the interferons on the pancreatic (β-cells or from an indirect influence on the number, activity, or type of inflammatory cells that invade the islets in type I diabetes. To examine directly the role of interferon (IFN)-γ in a mouse model of type I diabetes, we have introduced an inactivating mutation in the IFN-γ gene (ifg) into NOD mice. The genetic absence of IFN-γ does not prevent either insulitis or diabetes in the NOD mice, but it does increase the time to onset. Although it might have been predicted that the absence of IFN-γ in these mice would lead to an increase in expression of Th2 T-helper cell-related cytoldnes, we found instead a profound decrease in the expression of two of the characteristic Th2 cytoldnes, interleukin (IL)-4 and EL-1O. We also demonstrate that the splenocytes taken from IFN-γ–deficient diabetic mice are fully capable of transferring diabetes to naive recipients.
Association Between αβTCR+CD4−CD8− T-Cell Deficiency and IDDM in NOD/Lt Mice
Authors: Baxter Alan G , Kinder Simon J , Hammond Kirsten J L , Scollay Roland , Godfrey Dale I
Published: September 2013

NOD mice develop spontaneous IDDM as a result of T-cell–mediated autoimmune destruction of pancreatic β-cells. It is not known why these T-cells become autoreactive, nor is it clear whether the breakdown in self-tolerance reflects a general problem in T-cell development or a selective defect in an as yet undefined regulatory cell population. In this study, we showed that NOD mice, although relatively normal with regard to most thymocyte subsets, exhibit a marked deficiency in αβTCR+CD4−CD8− (αβ+DN) T-cells in the thymus and, to a lesser extent, in the periphery. These T-cells have been termed NKT cells (NK1.1+-like T-cells) because they share some cell surface markers with conventional natural killer (NK) cells. To examine the role of these cells in the pathogenesis of IDDM, semiallogeneic or syngeneic double-negative (DN) thymocytes, enriched for NKT cells, were transferred into intact 4-week-old NOD recipients; the onset of diabetes was then monitored over the ensuing 30 weeks. Mice receiving NKT-enriched thymocytes did not develop diabetes, whereas mice receiving unfractionated thymocytes or phosphate-buffered saline developed diabetes at the normal rate. NKT cells represent a distinct T-cell lineage that has been shown to play a role in immunoregulation in vivo. The deficiency of these cells observed in NOD mice may therefore contribute to destruction of pancreatic islet cells by conventional T-cells.
Novel Insulinoma Cell Lines Produced by Iterative Engineering of GLUT2, Glucokinase, and Human Insulin Expression
Authors: Clark Samuel A , Quaade Christian , Constantly Heba , Hansen Pernille , Halban Philippe , Ferber Sarah , Newgard Christopher B , Normington Karl
Published: September 2013

Cellular engineering studies in our group are directed at creating insulin-secreting cell lines that simulate the performance of the normal islet β-cell. The strategy described in this article involves the stepwise stable introduction of genes relevant to β-cell performance into the RIN 1046-38 insulinoma cell line, a process that we term “iterative engineering.” RIN cells stably engineered to contain multiple copies of the human insulin gene exhibit a large increase in insulin content, such that they approach the content of human islets assayed in parallel. Analysis by high-performance liquid chromatography demonstrates that these engineered cell lines process human proinsulin to mature insulin with high efficiency. Cell lines that are further engineered to express the GLUT2 and glucokinase genes demonstrate stable expression of the three transgenes for the full lifetime of the lines produced to date (6 months to 1 year in continuous culture). Transplantation of the engineered cell lines into nude rats reveals that stably integrated genes are expressed at constant levels in the in vivo environment over the full duration of experiments performed (48 days). Several endogenous genes expressed in normal β-cell, including rat insulin, amylin, sulfonyhirea receptor, and glucokinase, are stably expressed in the insulinoma lines during these in vivo studies. Endogenous GLUT2 expression, in contrast, is rapidly extinguished during in vivo passage. The loss of GLUT2 is overcome in engineered cell lines in which transporter expression is provided by a stably transfected trans gene. These results suggest that a potential advantage of the iterative engineering approach may be to preserve stability of function and phenotype, particularly in the in vivo setting.
Empirical Risk for Insulin-dependent Diabetes (IDD) in Sibs: Further Definition of Genetic Heterogeneity
Authors: Chern M M , Anderson V E , Barbosa J
Published: September 2013

We have studied the effect of age at diagnosis in the proband and parental status [normal versus non-insulin-dependent diabetes (NIDD)] on the cumulative risk to age 40 (CR40) for insulin-dependent diabetes (IDD) in sibs of IDD probands in 493 families. We found a significantly increased cumulative risk to age 40 for IDD in sibs of probands with disease diagnosed before age 10 (8.5 ± 2.0%) as compared with that in sibs of probands with disease diagnosed after age 10 (4.6 ± 0.8%) (×2 = 7.6, P = 0.006). Within the family subset with probands of earlier IDD onset (before age 10) we also found an increased CR40 for IDD in the sibs of the probands in families with an NIDD parent (with NIDD parent: CR40 = 24.7 ± 10.7%; with normal parents: CR40 = 7.5 ± 2.0%, ×2 = 12.8, P < 0.0005). These data are compatible with the theory of heterogeneity (genetic and/or environmental) of IDD and a possible relationship between IDD and NIDD.
Islet Cell Thymidine Kinase Activity as Indicator of Islet Cell Proliferation in Rat Pancreas
Authors: Swenne Ingemar
Published: September 2013

The activity of thymidine kinase (TK; EC 2.7.1.21) in homogenates of isolated rat islets of Langerhans was measured and correlated with the DNA replicatory activity of the islet cells. Adult and fetal rat islets were cultured in medium with 2.7 or 16.7 mM glucose or 16.7 mM glucose and 1 μg/ml human growth hormone. In both types of islets, 16.7 mM glucose doubled [3H]thymidine incorporation compared with 2.7 mM glucose, and the addition of growth hormone caused a further increase in DNA replication. TK activity in the islets showed similar changes in response to glucose and growth hormone. The correlation between [3H]thymidine incorporation and TK activity was thus highly significant. Cell-cycle analysis of cultured fetal rat islets showed that TK activity was preferentially expressed during the S phase of the cell cycle. TK activity of freshly isolated islets declined with the age of the animal. In pancreatic sections, the islet cell autoradiographic labeling index after [3H]thymidine administration in vivo likewise declined with age and was correlated with the TK activity in freshly isolated islets. It is suggested that measurements of islet TK activity can be used as an index of islet cell proliferation; this method has the distinct advantage of avoiding the cumbersome procedure of preparing and scoring autoradiograms.
‘Ossian fürs Frauenzimmer’? Lengefeld, Günderrode, and the Portuguese Translations of ‘Alcipe’ and Adelaide Prata
Authors: Bär Gerald
Published: September 2013

This article examines German and Portuguese Ossian translations by female writers, particularly translations of Dar-thula, one of Macpherson's most popular pieces. Charlotte von Lengefeld's and Karoline von Günderrode's German translations raise the question of whether Ossian was considered a suitable subject for women, offering further insights into the reasons for the astonishing popularity of Macpherson's publications in German-speaking countries. The Portuguese versions of the Marquesa de Alorna and Adelaide Prata and their favourable reviews shed light on their acceptance in nineteenth-century Portugal. Comparison of the different approaches and objectives of these four translators together with the analysis of their different source texts and skills is intended to contribute to debate on translation and gender studies.
Ossian in the North
Authors: Kristmannsson Gauti
Published: September 2013

The Poems of Ossian were instrumental in putting the North in Europe into a new and elevated cultural perspective. The first part of this essay examines how the general aesthetic development in the North of Europe was in many ways determined by the paradigm shift ushered in by the poems, despite latter-day denials. Two case studies are briefly presented: the first is the modern denial of Ossianic influence on Danish arts, literature, music and visual art; the second the actual reception in Iceland, the country which, for some, represented the Northern ‘counter example’ to Ossian, with the manuscripts of Eddas and Sagas.
Stagger: an Open-Source Part of Speech Tagger for Swedish
Authors: Östling Robert
Published: September 2013

This work presents Stagger, a new open-source part of speech tagger for Swedish based on the Averaged Perceptron. By using the SALDO morphological lexicon and semi-supervised learning in the form of Collobert andWeston embeddings, it reaches an accuracy of 96.4% on the standard Stockholm-Umeå Corpus dataset, making it the best single part of speech tagging system reported for Swedish. Accuracy increases to 96.6% on the latest version of the corpus, where the annotation has been revised to increase consistency. Stagger is also evaluated on a new corpus of Swedish blog posts, investigating its out-of-domain performance.
SUC-CORE: A Balanced Corpus Annotated with Noun Phrase Coreference
Authors: Nilsson Björkenstam Kristina
Published: September 2013

This paper describes SUC-CORE, a subset of the Stockholm Ume°a Corpus and the Swedish Treebank annotated with noun phrase coreference. While most coreference annotated corpora consist of exts of similar types within related domains, SUC-CORE consists of both informative and imaginative prose and covers a wide range of literary genres and domains. This allows for exploration of coreference cross different text types, but it also means that there are limited amounts of data within each type. Future work on coreference resolution for Swedish should include making more annotated data vailable for the research community.
Lipophilic Constituents of Rumex vesicarius L. and Rumex dentatus L.
Authors: Elfotoh Mona , Shams Khaled , Anthony Kevin , Shahat Abdelaaty , Ibrahim Magda , Abdelhady Nevein , Azim Nahla , Hammouda Faiza , El-Missiry Mostafa , Saleh Mahmoud
Published: September 2013

Rumex dentatus L. and Rumex vesicarius L., of the family Polygonaceae, are edible herbs growing wild in Egypt. Their lipoid constituents were examined by both liquid chromatography/mass spectrometry (LC/MS) and by gas chromatography/mass spectrometry (GC/MS). Their essential oil compositions consisted mainly of thujene, limonene, fenchon, estragole, and anethole but at largely different concentration. Fatty acid compositions were similar among the two species and consisting of palmitic, oleic, linoleic and linolenic acids, with R. vesicarius containing much higher level of omega-3-fatty acids. Both of the crude lipid extracts of the two species showed strong antioxidant activity as a radical quenching agent against 2,2-diphenyl-1-picrylhydrazyl (DPPH) systems. Antioxidant activities were mostly associated with the polar lipid fractions. High performance thin layer chromatography (HPTLC), both in the normal and reversed phase,as well as liquid chromatography/mass spectrometry (LC/MS) in the positive and negative electrospray ionization (ESI), showed unique chemical profile for each species that can be useful for species identification and quality control of herbal drug formulations. R. vesicarius was characterized by abundances of flavonoids and R. dentatus was abundant in anthraquinones and chromones.
A Self-Referencing Detection of Microorganisms Using Surface Enhanced Raman Scattering Nanoprobes in a Test-in-a-Tube Platform
Authors: Xiao Nan , Wang Chao , Yu Chenxu
Published: September 2013

Anisotropic nanoparticles (i.e., silver nanocubes) were functionalized with target-specific antibodies and Raman active tags to serve as nanoprobes for the rapid detection of bacteria in a test-in-a-tube platform. A self-referencing scheme was developed and implemented in which surface enhanced Raman spectroscopic (SERS) signatures of the targets were observed superimposed with the SERS signals of the Raman tags. The assessment through the dual signals (superimposed target and tag Raman signatures) supported a specific recognition of the targets in a single step with no washing/separation needed to a sensitivity of 102 CFU/mL, even in the presence of non-target bacteria at a 10 times higher concentration. The self-referencing protocol implemented with a portable Raman spectrometer potentially can become an easy-to-use, field-deployable spectroscopic sensor for onsite detection of pathogenic microorganisms.
Comparing Designers’ Problem-Solving Behavior in a Parametric Design Environment and a Geometric Modeling Environment
Authors: Yu Rongrong , Gu Ning , Ostwald Michael
Published: September 2013

This paper presents the results of a protocol study which compares designers’ behavior in a parametric design environment (PDE) and a geometric modeling environment (GME). An experiment was conducted in which seven designers were required to complete two architectural conceptual design tasks with similar complexity respectively in a PDE and GME. Protocol analysis is employed to compare the cognitive behavior of designers in these two environments. By analyzing the designers’ actions, including shifting between “problem” and “solution” spaces, it was possible to compare their cognitive activities in PDEs and GMEs. Results of this research suggest that designers put similar effort into the design problem space and the solution space in PDE and GME and that interaction between these two spaces also appears similar in the two design environments. However, different Problem-Solution index values and discontinuity ratios are found across design stages of the two design environments.
Pericytes, Mesenchymal Stem Cells and the Wound Healing Process
Authors: Mills Stuart , Cowin Allison , Kaur Pritinder
Published: September 2013

Pericytes are cells that reside on the wall of the blood vessels and their primary function is to maintain the vessel integrity. Recently, it has been realized that pericytes have a much greater role than just the maintenance of vessel integrity essential for the development and formation of a vascular network. Pericytes also have stem cell-like properties and are seemingly able to differentiate into adipocytes, chondrocytes, osteoblasts and granulocytes, leading them to be identified as mesenchymal stem cells (MSCs). More recently it has been suggested that pericytes play a key role in wound healing, whereas the beneficial effects of MSCs in accelerating the wound healing response has been recognized for some time. In this review, we collate the most recent data on pericytes, particularly their role in vessel formation and how they can affect the wound healing process.
The Complex Nature of Adherence in the Management of HIV/AIDS as a Chronic Medical Condition
Authors: Adefolalu Adegoke , Nkosi Zerish
Published: September 2013

The introduction of antiretroviral therapy (ART) in the management of HIV infection has resulted in a significant reduction in the morbidity and mortality associated with the disease. The fact that a nearly perfect adherence is required in ART has remained a major challenge to people infected with HIV. This review underscores the impact of adherence to antiretroviral therapy and highlights recent advances in adherence monitoring and enhancement among people infected with HIV who are on lifelong antiretroviral therapy.
Analysis and Visualization of Seismic Data Using Mutual Information
Authors: Machado José , Lopes António
Published: September 2013

Seismic data is difficult to analyze and classical mathematical tools reveal strong limitations in exposing hidden relationships between earthquakes. In this paper, we study earthquake phenomena in the perspective of complex systems. Global seismic data, covering the period from 1962 up to 2011 is analyzed. The events, characterized by their magnitude, geographic location and time of occurrence, are divided into groups, either according to the Flinn-Engdahl (F-E) seismic regions of Earth or using a rectangular grid based in latitude and longitude coordinates. Two methods of analysis are considered and compared in this study. In a first method, the distributions of magnitudes are approximated by Gutenberg-Richter (G-R) distributions and the parameters used to reveal the relationships among regions. In the second method, the mutual information is calculated and adopted as a measure of similarity between regions. In both cases, using clustering analysis, visualization maps are generated, providing an intuitive and useful representation of the complex relationships that are present among seismic data. Such relationships might not be perceived on classical geographic maps. Therefore, the generated charts are a valid alternative to other visualization tools, for understanding the global behavior of earthquakes.
Appraisal of Hygiene Indicators and Farming Practices in the Production of Leafy Vegetables by Organic Small-Scale Farmers in uMbumbulu (Rural KwaZulu-Natal, South Africa)
Authors: Mdluli Fezile , Thamaga-Chitja Joyce , Schmidt Stefan
Published: September 2013

During October, November and December 2011 (when highest sales of Agri-Hub fresh produce are observed), irrigation water, compost, lettuce and spinach sampled from four different farmer cooperatives supplying the local Agri-Hub in uMbumbulu (KwaZulu-Natal, South Africa) were analyzed monthly for the presence of total and fecal coliforms and Escherichia coli using the most probable number (MPN) technique. The pH values for all irrigation water samples analyzed were within the acceptable range of 6.5–8.5 for agricultural use. Fecal coliform levels were <1,000 MPN per 100 mL irrigation water and <1,000 MPN per g of compost. The vegetables produced by Agri-Hub small-scale farmers met the requirements for total coliforms of <200/g set by the South African Department of Health at the time of sampling. E. coli MPN values for irrigation water and vegetables were below the limit of detection. In addition, the farming practices of 73 farmers were assessed via a survey. The results revealed that more than 40% of farmers used microbiologically safe tap water for irrigation and that trained farmers have a significantly better understanding of the importance of production hygiene than untrained farmers. These results reiterate the importance of interventions that build capacity in the area of food safety and hygiene of small-scale farmers for market access of formal value chains.
New Zealand’s Drug Development Industry
Authors: Lockhart Michelle , Babar Zaheer-Ud-Din , Carswell Christopher , Garg Sanjay
Published: September 2013

The pharmaceutical industry’s profitability depends on identifying and successfully developing new drug candidates while trying to contain the increasing costs of drug development. It is actively searching for new sources of innovative compounds and for mechanisms to reduce the enormous costs of developing new drug candidates. There is an opportunity for academia to further develop as a source of drug discovery. The rising levels of industry outsourcing also provide prospects for organisations that can reduce the costs of drug development. We explored the potential returns to New Zealand (NZ) from its drug discovery expertise by assuming a drug development candidate is out-licensed without clinical data and has anticipated peak global sales of $350 million. We also estimated the revenue from NZ’s clinical research industry based on a standard per participant payment to study sites and the number of industry-sponsored clinical trials approved each year. Our analyses found that NZ’s clinical research industry has generated increasing foreign revenue and appropriate policy support could ensure that this continues to grow. In addition the probability-based revenue from the out-licensing of a drug development candidate could be important for NZ if provided with appropriate policy and financial support.
Oleic Acid Increases Synthesis and Secretion of VEGF in Rat Vascular Smooth Muscle Cells: Role of Oxidative Stress and Impairment in Obesity
Authors: Doronzo Gabriella , Viretto Michela , Barale Cristina , Russo Isabella , Mattiello Luigi , Anfossi Giovanni , Trovati Mariella
Published: September 2013

Obesity is characterized by poor collateral vessel formation, a process involving vascular endothelial growth factor (VEGF) action on vascular smooth muscle cells (VSMC). Free fatty acids are involved in the pathogenesis of obesity vascular complications, and we have aimed to clarify whether oleic acid (OA) enhances VEGF synthesis/secretion in VSMC, and whether this effect is impaired in obesity. In cultured aortic VSMC from lean and obese Zucker rats (LZR and OZR, respectively) we measured the influence of OA on VEGF-A synthesis/secretion, signaling molecules and reactive oxygen species (ROS). In VSMC from LZR we found the following: (a) OA increases VEGF-A synthesis/secretion by a mechanism blunted by inhibitors of Akt, mTOR, ERK-1/2, PKC-beta, NADPH-oxidase and mitochondrial electron transport chain complex; (b) OA activates the above mentioned signaling pathways and increases ROS; (c) OA-induced activation of PKC-beta enhances oxidative stress, which activates signaling pathways responsible for the increased VEGF synthesis/secretion. In VSMC from OZR, which present enhanced baseline oxidative stress, the above mentioned actions of OA on VEGF-A, signaling pathways and ROS are impaired: this impairment is reproduced in VSMC from LZR by incubation with hydrogen peroxide. Thus, in OZR chronically elevated oxidative stress causes a resistance to the action on VEGF that OA exerts in LZR by increasing ROS.
Potential of the Angiotensin Receptor Blockers (ARBs) Telmisartan, Irbesartan, and Candesartan for Inhibiting the HMGB1/RAGE Axis in Prevention and Acute Treatment of Stroke
Authors: Kikuchi Kiyoshi , Tancharoen Salunya , Ito Takashi , Morimoto-Yamashita Yoko , Miura Naoki , Kawahara Ko-ichi , Maruyama Ikuro , Murai Yoshinaka , Tanaka Eiichiro
Published: September 2013

Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs.
Emulsifying Activity and Stability of a Non-Toxic Bioemulsifier Synthesized by Microbacterium sp. MC3B-10
Authors: Camacho-Chab Juan , Guézennec Jean , Chan-Bacab Manuel , Ríos-Leal Elvira , Sinquin Corinne , Muñiz-Salazar Raquel , De la Rosa-García Susana , Reyes-Estebanez Manuela , Ortega-Morales Benjamín
Published: September 2013

A previously reported bacterial bioemulsifier, here termed microbactan, was further analyzed to characterize its lipid component, molecular weight, ionic character and toxicity, along with its bioemulsifying potential for hydrophobic substrates at a range of temperatures, salinities and pH values. Analyses showed that microbactan is a high molecular weight (700 kDa), non-ionic molecule. Gas chromatography of the lipid fraction revealed the presence of palmitic, stearic, and oleic acids; thus microbactan may be considered a glycolipoprotein. Microbactan emulsified aromatic hydrocarbons and oils to various extents; the highest emulsification index was recorded against motor oil (96%). The stability of the microbactan-motor oil emulsion model reached its highest level (94%) at 50 °C, pH 10 and 3.5% NaCl content. It was not toxic to Artemia salina nauplii. Microbactan is, therefore, a non-toxic and non-ionic bioemulsifier of high molecular weight with affinity for a range of oily substrates. Comparative phylogenetic assessment of the 16S rDNA gene of Microbacterium sp. MC3B-10 with genes derived from other marine Microbacterium species suggested that this genus is well represented in coastal zones. The chemical nature and stability of the bioemulsifier suggest its potential application in bioremediation of marine environments and in cosmetics.
Minor Role of Mitochondrial Respiration for Fatty-Acid Induced Insulin Secretion
Authors: Schulz Nadja , Kluth Oliver , Jastroch Martin , Schürmann Annette
Published: September 2013

An appropriate insulin secretion by pancreatic beta-cells is necessary to maintain glucose homeostasis. A rise in plasma glucose leads to increased metabolism and an elevated cytoplasmic ATP/ADP ratio that finally triggers insulin granule exocytosis. In addition to this triggering pathway, one or more amplifying pathways—activated by amino acids or fatty acid—enhance secretion by promoting insulin granule recruitment to, and priming at, the plasma membrane. The aim of this study was to clarify the impact of the mitochondrial respiratory activity on fatty acid-induced insulin secretion that was assessed by an extracellular flux analyzer. Treatment of isolated mouse islets with glucose (20 mM) increased insulin secretion 18-fold and correlated with ATP-synthesizing respiration. Furthermore, oxygen consumption rate (OCR) significantly increased by 62% in response to glucose, whereas the addition of palmitate resulted only in a minor increase of OCR at both 2.8 mM (11%) and 20 mM glucose (21%). The addition of palmitate showed a pronounced increase of coupling efficiency (CE) at 2.8 mM glucose but no further insulin secretion. However, treatment with palmitate at 20 mM glucose increased insulin secretion about 32-fold accompanied by a small increase in CE. Thus, fatty acid induced respiration has a minor impact on insulin secretion. Our data clearly demonstrate that fatty acids in contrast to glucose play a minor role for respiration-mediated insulin secretion. In the presence of high glucose, fatty acids contribute partially to amplifying pathways of insulin secretion by further increasing mitochondrial activity in the islets of Langerhans.
hnRNP A1: The Swiss Army Knife of Gene Expression
Authors: Jean-Philippe Jacques , Paz Sean , Caputi Massimo
Published: September 2013

Eukaryotic cells express a large variety of RNA binding proteins (RBPs), with diverse affinities and specificities towards target RNAs. These proteins play a crucial role in almost every aspect of RNA biogenesis, expression and function. The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a complex and diverse family of RNA binding proteins. hnRNPs display multiple functions in the processing of heterogeneous nuclear RNAs into mature messenger RNAs. hnRNP A1 is one of the most abundant and ubiquitously expressed members of this protein family. hnRNP A1 plays multiple roles in gene expression by regulating major steps in the processing of nascent RNA transcripts. The transcription, splicing, stability, export through nuclear pores and translation of cellular and viral transcripts are all mechanisms modulated by this protein. The diverse functions played by hnRNP A1 are not limited to mRNA biogenesis, but extend to the processing of microRNAs, telomere maintenance and the regulation of transcription factor activity. Genomic approaches have recently uncovered the extent of hnRNP A1 roles in the development and differentiation of living organisms. The aim of this review is to highlight recent developments in the study of this protein and to describe its functions in cellular and viral gene expression and its role in human pathologies.
Basic Amino Acid Residues of Human Eosinophil Derived Neurotoxin Essential for Glycosaminoglycan Binding
Authors: Hung Ta-Jen , Chang Wei-Tang , Tomiya Noboru , Lee Yuan-Chuan , Chang Hao-Teng , Chen Chien-Jung , Kuo Ping-Hsueh , Fan Tan-chi , Chang Margaret
Published: September 2013

Human eosinophil derived neurotoxin (EDN), a granule protein secreted by activated eosinophils, is a biomarker for asthma in children. EDN belongs to the human RNase A superfamily possessing both ribonucleolytic and antiviral activities. EDN interacts with heparin oligosaccharides and heparin sulfate proteoglycans on bronchial epithelial Beas-2B cells. In this study, we demonstrate that the binding of EDN to cells requires cell surface glycosaminoglycans (GAGs), and the binding strength between EDN and GAGs depends on the sulfation levels of GAGs. Furthermore, in silico computer modeling and in vitro binding assays suggest critical roles for the following basic amino acids located within heparin binding regions (HBRs) of EDN 34QRRCKN39 (HBR1), 65NKTRKN70 (HBR2), and 113NRDQRRD119 (HBR3) and in particular Arg35, Arg36, and Arg38 within HBR1, and Arg114 and Arg117 within HBR3. Our data suggest that sulfated GAGs play a major role in EDN binding, which in turn may be related to the cellular effects of EDN.
Isolation and Identification of Two Novel Attractant Compounds from Chinese Cockroach (Eupolyphaga sinensis Walker) by Combination of HSCCC, NMR and CD Techniques
Authors: Jiang Wei , Wu Xiaodan , Wu Bin
Published: September 2013

High-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hextane-ethyl acetate-methanol-water (1.5:1:1.5:1, v/v/v/v) was applied to the isolation and purification of attractants from Chinese cockroach, Eupolyphaga sinensis Walker. Two new attractants with attractant activity towards the male insects were obtained from the extract sample in a one-step separation. Their purities were determined by HPLC. Subsequent MS, NMR and CD analyses have led to the characterization of (R)-3-ethyl-6,8-dihydroxy-7-methyl-3,4-dihydroisochromen-1-one (1) and (R)-6,8-dihydroxy-3,7-dimethyl-3,4-dihydroisochromen-1-one (2), two novel isocumarin type attractants. Based on these results, it is concluded that HSCCC is a viable separation method option for purifying insect attractants, while effectively maintaining the attracting activity of the isolates. This is the first attempt to apply counter-current chromatography technique to separate attractants from Chinese cockroach.
Anticancer and Antifungal Compounds from Aspergillus, Penicillium and Other Filamentous Fungi
Authors: Bladt Tanja , Frisvad Jens , Knudsen Peter , Larsen Thomas
Published: September 2013

This review covers important anticancer and antifungal compounds reported from filamentous fungi and in particular from Aspergillus, Penicillium and Talaromyces. The taxonomy of these fungi is not trivial, so a focus of this review has been to report the correct identity of the producing organisms based on substantial previous in-house chemotaxonomic studies.
A New Lignan Glucoside from the Whole Plants of Salvia Scapiformis
Authors: Lai Yongji , Ding Shuiping , Qian Huiqin , Zhang Jinwen , Xue Yongbo , Luo Zengwei , Yao Guangmin , Zhang Yonghui
Published: September 2013

Phytochemical investigation of the whole plants of Salvia scapiformis Hance afforded eight compounds, including one new lignan, (+)-8α-hydroxypinoresinol-8-O-[6′′-O-(4′′′-hydroxybenzoyl)]-β-d-glucopyranoside (1), four known lignans, (+)-8α-hydroxy-pinoresinol-8-O-β-d-glucopyranoside (2), (+)-8α-hydroxypinoresinol (3), (+)-pinoresinol (4), and (+)-medioresinol (5), and three known triterpenoids, ursolic acid (6), 4-epi-niga-ichigoside F1 (7), and niga-ichigoside F1 (8). Their structures were determined on the basis of extensive spectroscopic analyses and comparison with spectroscopic data in the literature. The absolute configuration of the new compound 1 was determined by chemical transformation and GC analysis.
Biological Variability and Impact of Oral Contraceptives on Vitamins B6, B12 and Folate Status in Women of Reproductive Age
Authors: McArthur Jennifer , Tang HoMan , Petocz Peter , Samman Samir
Published: September 2013

Vitamins B6, B12 and folate play crucial metabolic roles especially during the reproductive years for women. There is limited reporting of within-subject variability of these vitamins. This study aimed to determine the within and between subject variability in serum vitamins B6, B12, folate and erythrocyte folate concentrations in young women; identify factors that contribute to variability; and determine dietary intakes and sources of these vitamins. Data were obtained from the control group of a trial aimed at investigating the effect of iron on the nutritional status of young women (age 25.2 ± 4.2 year; BMI 21.9 ± 2.2 kg/m2). The coefficients of variability within-subject (CVI) and between-subject (CVG) for serum vitamins B6, B12 and folate, and erythrocyte folate were calculated. Food frequency questionnaires provided dietary data. CVI and CVG were in the range 16.1%–25.7% and 31.7%–62.2%, respectively. Oral contraceptive pill (OCP) use was associated (P = 0.042) with lower serum vitamin B12 concentrations. Initial values were 172 ± 16 pmol/L and 318 ± 51 pmol/L for OCP and non-OCP users, respectively; with differences maintained at four time points over 12 weeks. BMI, age, physical activity, alcohol intake and haematological variables did not affect serum or erythrocyte vitamin concentrations. Vitamin B12 intakes were derived from traditional and unexpected sources including commercial energy drinks. Young women using OCP had significantly lower serum vitamin B12 concentrations. This should be considered in clinical decision making and requires further investigation.
Detecting Zimbabwe’s Decadal Economic Decline Using Nighttime Light Imagery
Authors: Li Xi , Ge Linlin , Chen Xiaoling
Published: September 2013

Zimbabwe’s economy declined between 2000 and 2009. This study detects the economic decline in different regions of Zimbabwe using nighttime light imagery from the Defense Meteorological Satellite Program’s Operational Linescan System (DMSP-OLS). We found a good correlation (coefficient = 0.7361) between Zimbabwe’s total nighttime light (TNL) and Gross Domestic Product (GDP) for the period 1992 to 2009. Therefore, TNL was used as an indicator of regional economic conditions in Zimbabwe. Nighttime light imagery from 2000 and 2008 was compared at both national and regional scales for four types of regions. At the national scale, we found that nighttime light in more than half of the lit area decreased between 2000 and 2008. Moreover, within the four region types (inland mining towns, inland agricultural towns, border towns and cities) we determined that the mining and agricultural sectors experienced the most severe economic decline. Some of these findings were validated by economic survey data, proving that the nighttime light data is a potential data source for detecting the economic decline in Zimbabwe.
A New Position Measurement System Using a Motion-Capture Camera for Wind Tunnel Tests
Authors: Park Hyo , Kim Ji , Kim Jin , Choi Se , Kim Yousok
Published: September 2013

Considering the characteristics of wind tunnel tests, a position measurement system that can minimize the effects on the flow of simulated wind must be established. In this study, a motion-capture camera was used to measure the displacement responses of structures in a wind tunnel test, and the applicability of the system was tested. A motion-capture system (MCS) could output 3D coordinates using two-dimensional image coordinates obtained from the camera. Furthermore, this remote sensing system had some flexibility regarding lab installation because of its ability to measure at relatively long distances from the target structures. In this study, we performed wind tunnel tests on a pylon specimen and compared the measured responses of the MCS with the displacements measured with a laser displacement sensor (LDS). The results of the comparison revealed that the time-history displacement measurements from the MCS slightly exceeded those of the LDS. In addition, we confirmed the measuring reliability of the MCS by identifying the dynamic properties (natural frequency, damping ratio, and mode shape) of the test specimen using system identification methods (frequency domain decomposition, FDD). By comparing the mode shape obtained using the aforementioned methods with that obtained using the LDS, we also confirmed that the MCS could construct a more accurate mode shape (bending-deflection mode shape) with the 3D measurements.
A Dry Membrane Protection Technique to Allow Surface Acoustic Wave Biosensor Measurements of Biological Model Membrane Approaches
Authors: Reder-Christ Katrin , Schmitz Patrick , Bota Marian , Gerber Ursula , Falkenstein-Paul Hildegard , Fuss Christian , Enachescu Marius , Bendas Gerd
Published: September 2013

Model membrane approaches have attracted much attention in biomedical sciences to investigate and simulate biological processes. The application of model membrane systems for biosensor measurements is partly restricted by the fact that the integrity of membranes critically depends on the maintenance of an aqueous surrounding, while various biosensors require a preconditioning of dry sensors. This is for example true for the well-established surface acoustic wave (SAW) biosensor SAM®5 blue. Here, a simple drying procedure of sensor-supported model membranes is introduced using the protective disaccharide trehalose. Highly reproducible model membranes were prepared by the Langmuir-Blodgett technique, transferred to SAW sensors and supplemented with a trehalose solution. Membrane rehydration after dry incorporation into the SAW device becomes immediately evident by phase changes. Reconstituted model membranes maintain their full functionality, as indicated by biotin/avidin binding experiments. Atomic force microscopy confirmed the morphological invariability of dried and rehydrated membranes. Approximating to more physiological recognition phenomena, the site-directed immobilization of the integrin VLA-4 into the reconstituted model membrane and subsequent VCAM-1 ligand binding with nanomolar affinity were illustrated. This simple drying procedure is a novel way to combine the model membrane generation by Langmuir-Blodgett technique with SAW biosensor measurements, which extends the applicability of SAM®5 blue in biomedical sciences.
Adolescent Callous-Unemotional Traits Mediates the Longitudinal Association between Conduct Problems and Media Violence Exposure
Authors: Fanti Kostas. , Hadjicharalambous Maria-Zoe , Katsimicha Evita
Published: September 2013

The current study investigates the bidirectional longitudinal association between conduct problems (CPs) and media violence exposure (MVE), with callous-unemotional (CU) traits as a potential mediator of this association. The sample consisted of 1,451 (49.9% boys) Greek Cypriot adolescents. CPs and MVE were measured at Year 1 and Year 3 and CU traits were measured at Year 2, enabling the examination of longitudinal associations and indirect effects between these variables. A bidirectional association between CPs and MVE was identified. Further, both CPs and MVE at Year 1 were positively associated with Year 2 CU traits, and youth high on CU traits at Year 2 were more likely to exhibit CP behaviors and to be exposed to media violence at Year 3. Finally, two indirect pathways were identified, suggesting that the longitudinal bidirectional association between CPs and MVE was partially mediated by CU traits. These findings suggest that CU traits constitute an underlying mechanism explaining the longitudinal association between CPs and MVE.
A Comparison between Australian Football League (AFL) Injuries in Australian Indigenous versus Non-indigenous Players
Authors: Orchard Jessica , Orchard John , Seward Hugh
Published: September 2013

It has previously been shown that being of aboriginal descent is a risk factor for hamstring injuries in Australian football. The aim of this study was to review the Australian Football League (AFL) injury database to determine whether there were any injuries where indigenous players had different relative risks to non-indigenous players. Analysis was conducted using data from the AFL injury database, which included data from 4,492 players over 21 years (1992–2012), covering 162,683 player-matches at AFL level, 91,098 matches at lower levels and 328,181 weeks (possible matches) of exposure. Compared to non-indigenous players, indigenous players had a significantly higher risk of hamstring injuries (RR 1.52, 95% CI 1.32–1.73) and calf strains (RR 1.30, 95% CI 1.00–1.69). Conversely, indigenous players had a significantly lower risk of lumbar/thoracic spine injuries (RR 0.61, 95% CI 0.41–0.91), groin strains/osteitis pubis (RR 0.75, 95% CI 0.58–0.96) and Achilles tendon injuries (RR 0.32, 95% CI 0.12–0.86). The results for the above injuries were also significant in terms of games missed. There was no difference between overall risk of injury (RR 1.03, 95% CI 0.96–1.10) or missed games (RR 1.00, 95% CI 0.97–1.04). This suggests that indigenous AFL players have the same overall number of injuries and missed games, but a slightly different injury profile.