bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal stem cells contribute to vascular growth in skeletal muscle in response to eccentric exercise
Authors: Huntsman Heather D. , Zachwieja Nicole , Zou Kai , Ripchik Pauline , Valero M. Carmen , De Lisio Michael , Boppart Marni D.
Published: October 2012

The α7β1-integrin is an adhesion molecule highly expressed in skeletal muscle that can enhance regeneration in response to eccentric exercise. We have demonstrated that mesenchymal stem cells (MSCs), predominantly pericytes, accumulate in muscle (mMSCs) overexpressing the α7B-integrin (MCK:α7B; α7Tg) and contribute to new fiber formation following exercise. Since vascularization is a common event that supports tissue remodeling, we hypothesized that the α7-integrin and/or mMSCs may stimulate vessel growth following eccentric exercise. Wild-type (WT) and α7Tg mice were subjected to single or multiple (3 times/wk, 4 wk) bouts of downhill running exercise. Additionally, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) -labeled mMSCs were intramuscularly injected into WT recipients. A subset of recipient mice were run downhill before injection to recapitulate the exercised microenvironment. While total number of CD31+ vessels declined in both WT and α7Tg muscle following a single bout of exercise, the number of larger CD31+ vessels with a visible lumen was preferentially increased in α7Tg mice following eccentric exercise training ( P < 0.05). mMSC transplantation similarly increased vessel diameter and the total number of neuron-glial antigen-2 (NG2+) arterioles postexercise. Secretion of arteriogenic factors from mMSCs in response to mechanical strain, including epidermal growth factor and granulocyte macrophage-colony stimulating factor, may account for vessel remodeling. In conclusion, this study demonstrates that the α7-integrin and mMSCs contribute to increased vessel diameter size and arteriolar density in muscle in response to eccentric exercise. The information in this study has implications for the therapeutic treatment of injured muscle and disorders that result in vessel occlusion, including peripheral artery disease.
Phosphodiesterase-3 inhibition augments the myocardial infarct size-limiting effects of exenatide in mice with type 2 diabetes
Authors: Ye Yumei , Qian Jinqiao , Castillo Alexander C. , Ling Shukuan , Ye Hongmei , Perez-Polo Jose R. , Bajaj Mandeep , Birnbaum Yochai
Published: October 2012

Glucagon-like peptide (GLP)-1 receptor activation increases intracellular cAMP with downstream activation of PKA. Cilostazol (CIL), a phosphodiesterase-3 inhibitor, prevents cAMP degradation. We assessed whether CIL amplifies the exenatide (EX)-induced increase in myocardial cAMP levels and PKA activity and augments the infarct size (IS)-limiting effects of EX in db/ db mice. Mice fed a Western diet received oral CIL (10 mg/kg) or vehicle by oral gavage 24 h before surgery. One hour before surgery, mice received EX (1 μg/kg sc) or vehicle. Additional mice received H-89, a PKA inhibitor, alone or with CIL + EX. Mice underwent 30 min of coronary artery occlusion and 24 h of reperfusion. Both EX and CIL increased myocardial cAMP levels and PKA activity. Levels were significantly higher in the EX + CIL group. Both EX and CIL reduced IS. IS was the smallest in the CIL + EX group. H-89 completely blocked the IS-limiting effects of EX + CIL. EX + CIL decreased phosphatase and tensin homolog on chromosome 10 upregulation and increased Akt and ERK1/2 phosphorylation after ischemia-reperfusion. These effects were blocked by H-89. In conclusion, EX and CIL have additive effects on IS limitation in diabetic mice. The additive effects are related to cAMP-induced PKA activation, as H-89 blocked the protective effect of CIL + EX.
Marine n3 polyunsaturated fatty acids enhance resistance to mitochondrial permeability transition in heart failure but do not improve survival
Authors: Galvao Tatiana F. , Khairallah Ramzi J. , Dabkowski Erinne R. , Brown Bethany H. , Hecker Peter A. , O'Connell Kelly A. , O'Shea Karen M. , Sabbah Hani N. , Rastogi Sharad , Daneault Caroline , Des Rosiers Christine , Stanley William C.
Published: October 2012

Mitochondrial dysfunction in heart failure includes greater susceptibility to mitochondrial permeability transition (MPT), which may worsen cardiac function and decrease survival. Treatment with a mixture of the n3 polyunsaturated fatty acids (n3 PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is beneficial in heart failure patients and increases resistance to MPT in animal models. We assessed whether DHA and EPA have similar effects when given individually, and whether they prolong survival in heart failure. Male δ-sarcoglycan null cardiomyopathic hamsters were untreated or given either DHA, EPA, or a 1:1 mixture of DHA + EPA at 2.1% of energy intake. Treatment did not prolong survival: mean survival was 298 ± 15 days in untreated hamsters and 335 ± 17, 328 ± 14, and 311 ± 15 days with DHA, EPA, and DHA + EPA, respectively ( n = 27–32/group). A subgroup of cardiomyopathic hamsters treated for 26 wk had impaired left ventricular function and increased cardiomyocyte apoptosis compared with normal hamsters, which was unaffected by n3 PUFA treatment. Evaluation of oxidative phosphorylation in isolated subsarcolemmal and interfibrillar mitochondria with substrates for complex I or II showed no effect of n3 PUFA treatment. On the other hand, interfibrillar mitochondria from cardiomyopathic hamsters were significantly more sensitive to Ca2+-induced MPT, which was completely normalized by treatment with DHA and partially corrected by EPA. In conclusion, treatment with DHA or EPA normalizes Ca2+-induced MPT in cardiomyopathic hamsters but does not prolong survival or improve cardiac function. This suggest that greater susceptibility to MPT is not a contributor to cardiac pathology and poor survival in heart failure.
Spatial-temporal dynamics of pulmonary blood flow in the healthy human lung in response to altered FiO2
Authors: Asadi Amran K. , Cronin Matthew V. , Sá Rui Carlos , Theilmann Rebecca J. , Holverda Sebastiaan , Hopkins Susan R. , Buxton Richard B. , Prisk G. Kim
Published: October 2012

The temporal dynamics of blood flow in the human lung have been largely unexplored due to the lack of appropriate technology. Using the magnetic resonance imaging method of arterial spin labeling (ASL) with subject-gated breathing, we produced a dynamic series of flow-weighted images in a single sagittal slice of the right lung with a spatial resolution of ∼1 cm3and a temporal resolution of ∼10 s. The mean flow pattern determined from a set of reference images was removed to produce a time series of blood flow fluctuations. The fluctuation dispersion (FD), defined as the spatial standard deviation of each flow fluctuation map, was used to quantify the changes in distribution of flow in six healthy subjects in response to 100 breaths of hypoxia (FiO2= 0.125) or hyperoxia (FiO2= 1.0). Two reference frames were used in calculation, one determined from the initial set of images (FDglobal), and one determined from the mean of each corresponding baseline or challenge period (FDlocal). FDlocalthus represented changes in temporal variability as a result of intervention, whereas FDglobalencompasses both FDlocaland any generalized redistribution of flow associated with switching between two steady-state patterns. Hypoxic challenge resulted in a significant increase (96%, P < 0.001) in FDglobalfrom the normoxic control period and in FDlocal(46%, P = 0.0048), but there was no corresponding increase in spatial relative dispersion (spatial standard deviation of the images divided by the mean; 8%, not significant). There was a smaller increase in FDglobalin response to hyperoxia (47%, P = 0.0015) for the single slice, suggestive of a more general response of the pulmonary circulation to a change from normoxia to hyperoxia. These results clearly demonstrate a temporal change in the sampled distribution of pulmonary blood flow in response to hypoxia, which is not observed when considering only the relative dispersion of the spatial distribution.
Inactivity, age, and exercise: single-muscle fiber power generation
Authors: Kim Jong-Hee , Thompson LaDora V.
Published: October 2012

We examined the effects of mild therapeutic exercise during a period of inactivity on size and contractile functions of myosin heavy chain (MHC) type I ( n = 204) and type II ( n = 419) single fibers from the medial gastrocnemius in three age groups. Young adult (5–12 mo), middle-aged (24–31 mo), and old (32–37 mo) F344BNF1 rats were assigned to one of three groups: weight-bearing control, non-weight bearing (NWB), and NWB plus exercise (NWBX). Fourteen days of hindlimb suspension were applied in NWB rats. The NWBX rats exercised on the treadmill for 15 min, four times a day, during the period of NWB. The NWBX did not improve peak power, but increased normalized power of MHC type I fibers in young adult rats. In MHC type II fibers, NWBX did not change peak power, isometric maximal force, Vmax, and fiber size from young adult and middle-aged rats. NWBX did not improve peak power and isometric maximal force and showed a dramatic decline in Vmaxand normalized power in the old rats. Collectively, mild treadmill exercise during a period of inactivity does not improve peak power of MHC type I or type II fiber from the gastrocnemius in young, middle-aged, and old rats. However, NWBX is beneficial in enhancing normalized power of MHC type I fibers in young adult rats, most likely due to the stimulus intensity and the ability of the individual fibers to adapt to the stimulus. In contrast, several factors, such as impaired adaptation potential, inappropriate exercise intensity, or increased susceptibility to muscle damage, may contribute to the lack of improvement in the older rats.
MicroRNA 138, let-7b, and 125a inhibitors differentially alter sleep and EEG delta-wave activity in rats
Authors: Davis Christopher J. , Clinton James M. , Krueger James M.
Published: October 2012

Sleep deprivation was previously reported to alter microRNA (miRNA) levels in the brain; however, the direct effects of any miRNA on sleep have only been described recently. We determined miRNA 138 (miR-138), miRNA let-7b (let-7b), and miRNA 125a-5p (miR-125a) levels in different brain areas at the transitions between light and dark. In addition, we examined the extent to which inhibiting these miRNAs affects sleep and EEG measures. We report that the levels of multiple miRNAs differ at the end of the sleep-dominant light period vs. the end of the wake-dominant dark period in cortical areas, hippocampus, and hypothalamus. For instance, in multiple regions of the cortex, miR-138, let-7b, and miR-125a expression was higher at the end of the dark period compared with the end of the light period. Intracerebroventricular injection of a specific inhibitor (antiMIR) to miR-138 suppressed sleep and nonrapid eye movement sleep (NREMS) EEG delta power. The antiMIR to let-7b did not affect time in state but decreased NREMS EEG delta power, whereas the antiMIR to miR-125a failed to affect sleep until after 3 days and did not affect EEG delta power on any day. We conclude that miRNAs are uniquely expressed at different times and in different structures in the brain and have discrete effects and varied timings on several sleep phenotypes and therefore, likely play a role in the regulation of sleep.
Aerobic exercise does not compromise muscle hypertrophy response to short-term resistance training
Authors: Lundberg Tommy R. , Fernandez-Gonzalo Rodrigo , Gustafsson Thomas , Tesch Per A.
Published: October 2012

This study tested the hypothesis that chronic aerobic and resistance exercise (AE+RE) would elicit greater muscle hypertrophy than resistance exercise only (RE). Ten men (25 ± 4 yr) performed 5 wk unilateral knee extensor AE+RE. The opposing limb was subjected to RE. AE completed 6 hr prior to RE consisted of ∼45 min one-legged cycle ergometry. RE comprised 4 × 7 maximal concentric-eccentric knee extensions. Various indexes of in vivo knee extensor function were measured before and after training. Magnetic resonance imaging (MRI) assessed m. quadricep femoris (QF) cross-sectional area (CSA), volume, and signal intensity (SI). Biopsies obtained from m. vastus lateralis determined fiber CSA, enzyme levels, and gene expression of myostatin, atrogin-1, MuRF-1, PGC-1α, and VEGF. Increases ( P < 0.05) in isometric strength and peak power, respectively, were comparable in AE+RE (9 and 29%) and RE (11 and 24%). AE+RE showed greater increase (14%; P < 0.05) in QF volume than RE (8%). Muscle fiber CSA increased 17% after AE+RE ( P < 0.05) and 9% after RE ( P > 0.05). QF SI increased (12%; P < 0.05) after AE+RE, but not RE. Neither AE+RE nor RE showed altered mRNA levels. Citrate synthase activity increased ( P < 0.05) after AE+RE. The results suggest that the increased aerobic capacity shown with AE+RE was accompanied by a more robust increase in muscle size compared with RE. Although this response was not carried over to greater improvement in muscle function, it remains that intense AE can be executed prior to RE without compromising performance outcome.
Mitochondrial morphology, topology, and membrane interactions in skeletal muscle: a quantitative three-dimensional electron microscopy study
Authors: Picard Martin , White Kathryn , Turnbull Douglass M.
Published: October 2012

Dynamic remodeling of mitochondrial morphology through membrane dynamics are linked to changes in mitochondrial and cellular function. Although mitochondrial membrane fusion/fission events are frequent in cell culture models, whether mitochondrial membranes dynamically interact in postmitotic muscle fibers in vivo remains unclear. Furthermore, a quantitative assessment of mitochondrial morphology in intact muscle is lacking. Here, using electron microscopy (EM), we provide evidence of interacting membranes from adjacent mitochondria in intact mouse skeletal muscle. Electron-dense mitochondrial contact sites consistent with events of outer mitochondrial membrane tethering are also described. These data suggest that mitochondrial membranes interact in vivo among mitochondria, possibly to induce morphology transitions, for kiss-and-run behavior, or other processes involving contact between mitochondrial membranes. Furthermore, a combination of freeze-fracture scanning EM and transmission EM in orthogonal planes was used to characterize and quantify mitochondrial morphology. Two subpopulations of mitochondria were studied: subsarcolemmal (SS) and intermyofibrillar (IMF), which exhibited significant differences in morphological descriptors, including form factor (means ± SD for SS: 1.41 ± 0.45 vs. IMF: 2.89 ± 1.76, P < 0.01) and aspect ratio (1.97 ± 0.83 vs. 3.63 ± 2.13, P < 0.01) and circularity (0.75 ± 0.16 vs. 0.45 ± 0.22, P < 0.01) but not size (0.28 ± 0.31 vs. 0.27 ± 0.20 μm2). Frequency distributions for mitochondrial size and morphological parameters were highly skewed, suggesting the presence of mechanisms to influence mitochondrial size and shape. In addition, physical continuities between SS and IMF mitochondria indicated mixing of both subpopulations. These data provide evidence that mitochondrial membranes interact in vivo in mouse skeletal muscle and that factors may be involved in regulating skeletal muscle mitochondrial morphology.
Oxygen, pH, and mitochondrial oxidative phosphorylation
Authors: Wilson David F. , Harrison David K. , Vinogradov Sergei A.
Published: October 2012

The oxygen dependence of mitochondrial oxidative phosphorylation was measured in suspensions of isolated rat liver mitochondria using recently developed methods for measuring oxygen and cytochrome c reduction. Cytochrome- c oxidase (energy conservation site 3) activity of the mitochondrial respiratory chain was measured using an artificial electron donor ( N, N, N′, N′-tetramethyl- p-phenylenediamine) and ascorbate to directly reduce the cytochrome c, bypassing sites 1 and 2. For mitochondrial suspensions with added ATP, metabolic conditions approximating those in intact cells and decreasing oxygen pressure both increased reduction of cytochrome c and decreased respiratory rate. The kinetic parameters [ KMand maximal rate ( VM)] for oxygen were determined from the respiratory rates calculated for 100% reduction of cytochrome c. At 22°C, the KMfor oxygen is near 3 Torr (5 μM), 12 Torr (22 μM), and 18 Torr (32 μM) at pH 6.9, 7.4, and 7.9, respectively, and VMcorresponds to a turnover number for cytochrome c at 100% reduction of near 80/s and is independent of pH. Uncoupling oxidative phosphorylation increased the respiratory rate at saturating oxygen pressures by twofold and decreased the KMfor oxygen to <2 Torr at all tested pH values. Mitochondrial oxidative phosphorylation is an important oxygen sensor for regulation of metabolism, nutrient delivery to tissues, and cardiopulmonary function. The decrease in KMfor oxygen with acidification of the cellular environment impacts many tissue functions and may give transformed cells a significant survival advantage over normal cells at low-pH, oxygen-limited environment in growing tumors.
Extensive inflammatory cell infiltration in human skeletal muscle in response to an ultraendurance exercise bout in experienced athletes
Authors: Marklund Peter , Mattsson C. Mikael , Wåhlin-Larsson Britta , Ponsot Elodie , Lindvall Björn , Lindvall Lisbeth , Ekblom Björn , Kadi Fawzi
Published: October 2012

The impact of a 24-h ultraendurance exercise bout on systemic and local muscle inflammatory reactions was investigated in nine experienced athletes. Blood and muscle biopsies were collected before (Pre), immediately after the exercise bout (Post), and after 28 h of recovery (Post28). Circulating blood levels of leukocytes, creatine kinase (CK), C-reactive protein (CRP), and selected inflammatory cytokines were assessed together with the evaluation of the occurrence of inflammatory cells (CD3+, CD8+, CD68+) and the expression of major histocompatibility complex class I (MHC class I) in skeletal muscle. An extensive inflammatory cell infiltration occurred in all athletes, and the number of CD3+, CD8+, and CD68+ cells were two- to threefold higher at Post28 compared with Pre ( P < 0.05). The inflammatory cell infiltration was associated with a significant increase in the expression of MHC class I in muscle fibers. There was a significant increase in blood leukocyte count, IL-6, IL-8, CRP, and CK at Post. At Post28, total leukocytes, IL-6, and CK had declined, whereas IL-8 and CRP continued to increase. Increases in IL-1β and TNF-α were not significant. There were no significant associations between the magnitude of the systemic and local muscle inflammatory reactions. Signs of muscle degenerative and regenerative events were observed in all athletes with various degrees of severity and were not affected by the 24-h ultraendurance exercise bout. In conclusion, a low-intensity but very prolonged single-endurance exercise bout can generate a strong inflammatory cell infiltration in skeletal muscle of well-trained experienced ultraendurance athletes, and the amplitude of the local reaction is not proportional to the systemic inflammatory response.
Glucocorticoid treatment of astrocytes results in temporally dynamic transcriptome regulation and astrocyte-enriched mRNA changes in vitro
Authors: Carter Bradley S. , Meng Fan , Thompson Robert C.
Published: October 2012

While general effects of glucocorticoids are well established, the specific cellular mechanisms by which these hormones exert tissue-dependent effects continue to be elaborated. Diseases that demonstrate altered glucocorticoid signaling have been associated with alterations in astrocytes, yet relatively little is known about the effects of glucocorticoids upon this cell type. We have analyzed mRNA expression patterns following glucocorticoid treatment of mouse primary astrocyte cultures. Microarray analysis of cortical astrocyte cultures treated with dexamethasone over an eight-point, 24 h time course identified 854 unique genes with ≥twofold change in mRNA expression at one or more time points. Clustering analysis associated subsets of these mRNA expression changes with gene ontology categories known to be impacted by glucocorticoids. Numerous mRNAs regulated by dexamethasone were also regulated by the natural ligand corticosterone; all of the mRNAs regulated ≥twofold by corticosterone were substantially attenuated by cotreatment with the glucocorticoid receptor antagonist RU486. Of the mRNAs demonstrating ≥twofold expression change in response to both glucocorticoids, 33 mRNAs were previously associated with glucocorticoid regulation, and 36 mRNAs were novel glucocorticoid targets. All genes tested by qPCR for glucocorticoid regulation in cortical astrocyte cultures were also regulated by glucocorticoids in hippocampal astrocyte cultures (18/18). Interestingly, a portion of glucocorticoid-regulated genes were astrocyte enriched; the percentage of astrocyte-enriched genes per total number of regulated genes was highest for the early time points and steadily decreased over the time course. These findings suggest that astrocytes in vitro may initially deploy cell type-specific patterns of mRNA regulatory responses to glucocorticoids and subsequently activate additional cell type-independent responses.
Accuracy and Quality Assessment of EUS-FNA: A Single-Center Large Cohort of Biopsies
Authors: Bluen Benjamin Ephraim , Lachter Jesse , Khamaysi Iyad , Kamal Yassin , Malkin Leonid , Keren Ruth , Epelbaum Ron , Kluger Yoram
Published: October 2012

Introduction. Thorough quality control (QC) study with systemic monitoring and evaluation is crucial to optimizing the effectiveness of EUS-FNA. Methods. Retrospective analysis was composed of investigating consecutive patient files that underwent EUS-FNA. QC specifically focused on diagnostic accuracy, impacts on preexisting diagnoses, and case management. Results. 268 patient files were evaluated. EUS-FNA cytology helped establish accurate diagnoses in 92.54% (248/268) of patients. Sensitivity, specificity, PPV, NPV, and accuracy were 83%, 100%, 100%, 91.6%, and 94%, respectively. The most common biopsy site was the pancreas (68%). The most accurate location for EUS-FNA was the esophagus, 13/13 (100%), followed by the pancreas (89.6%). EUS-FNA was least informative for abdominal lymph nodes (70.5%). After FNA and followup, eight false negatives for tumors were found (3%), while 7.5% of samples still lacked a definitive diagnosis. Discussion. QC suggests that the diagnostic accuracy of EUS-FNA might be improved further by (1) taking more FNA passes from suspected lesions, (2) optimizing needle selection (3) having an experienced echo-endoscopist available during the learning curve, and (4) having a cytologist present during the procedure. QC also identified remediable reporting errors. In conclusion, QC study is valuable in identifying weaknesses and thereby augmenting the effectiveness of EUS-FNA.
The Nude Mouse as Model for Liver Deficiency Study and Treatment and Xenotransplantation
Authors: Vidal Isabelle , Richert Lysiane
Published: October 2012

We aimed at reviewing the various uses of Nude mouse for the development of liver deficiency models and evaluation of efficacy of hepatic cell xenotransplantation. The first part records the large range of liver deficiency models that can be developed in Nude mice: surgical partial hepatectomy, acute toxic liver deficiency, chronic cirrhosis, and transgenic liver injury. The second part tackles the outcome of rat hepatocyte as well as human cell transplantation, both mature hepatocyte and hepatic progenitor, into Nude mouse submitted to liver injury. Results are discussed and compared to other available immunodeficient mouse models. The issue of humanized liver creation is also addressed. Altogether, these results show that Nude mouse appears to be a suitable small animal model to expand our insight into liver cell engraftment and regeneration.
The Dirichlet Problem for the 2D Laplace Equation in a Domain with Cracks without Compatibility Conditions at Tips of the Cracks
Authors: Krutitskii P. A.
Published: October 2012

We study the Dirichlet problem for the 2D Laplace equation in a domain bounded by smooth closed curves and smooth cracks. In the formulation of the problem, we do not require compatibility conditions for Dirichlet's boundary data at the tips of the cracks. However, if boundary data satisfies the compatibility conditions at the tips of the cracks, then this is a particular case of our problem. The cases of both interior and exterior domains are considered. The well-posed formulation of the problem is given, theorems on existence and uniqueness of a classical solution are proved, and the integral representation for a solution is obtained. It is shown that weak solution of the problem does not typically exist, though the classical solution exists. The asymptotic formulae for singularities of a solution gradient at the tips of the cracks are presented.
Suppression of Diet-Induced Hypercholesterolemia by Turtle Jelly, A Traditional Chinese Functional Food, in Rats
Authors: Wu Jian-Hong , Wang Qing-Hua , Li Fan , Shu Yuan-Lan , Chan Chi-On , Mok Daniel Kam-Wah , Chan Shun-Wan
Published: October 2012

Consumption of functional foods for lowering serum cholesterol has globally gained acceptance by the general public. Turtle jelly (TJ), also called gui-ling-gao, is a popular traditional functional food in southern China. The hypocholesterolemic effect of consuming TJ was investigated in rats fed with normal diet, high-cholesterol diet or high-cholesterol diet supplemented with simvastatin (3 mg/kg bw per day, p.o.) or TJ (3.3 or 10 mL/kg bw per day, p.o.) for 30 days. TJ markedly reversed the increased serum total cholesterol, increased high-density lipoprotein, and decreased high-density lipoprotein induced by hypercholesterolemic diet with a dose-dependent improvement on the atherogenic index. It also demonstrated good hepatoprotective function by reducing fat depositions and overall lipid contents in the liver and increasing the activities of hepatic antioxidative enzymes. The blunted nitric oxide/endothelium-mediated aortic relaxation in rats fed with hypercholesterolemic diet was partially restored after TJ consumption. It is postulated that the hypocholesterolemic effect is the primary beneficial effect given by TJ; it then leads to secondary beneficial effects such as vasoprotective and hepatoprotective functions. The results revealed that TJ could block the downregulation of LDLR and PEPCK and upregulation of PPARαmRNA and protein expressions in the livers of rats fed with hypercholesterolemic diet.
On Certain Classes of Biharmonic Mappings Defined by Convolution
Authors: Chen J. , Wang X.
Published: October 2012

We introduce a class of complex‐valued biharmonic mappings, denoted by BH0(ϕk; σ, a, b), together with its subclass TBH0(ϕk; σ, a, b), and then generalize the discussions in Ali et al. (2010) to the setting of BH0(ϕk; σ, a, b) and TBH0(ϕk; σ, a, b) in a unified way.
Field Enhancement in a Grounded Dielectric Slab by Using a Single Superstrate Layer
Authors: Valagiannopoulos Constantinos A. , Tsitsas Nikolaos L.
Published: October 2012

The addition of a dielectric layer on a slab configuration is frequently utilized in various electromagnetic devices in order to give them certain desired operational characteristics. In this work, we consider a grounded dielectric film-slab, which is externally excited by a normally-incident Gaussian beam. On top of the film-slab, we use an additional suitably selected single isotropic superstrate layer in order to increase the field concentration inside the slab and hence achieve optimal power transfer from the external source to the internal region. We define a quantity of interest, called “enhancement factor,” expressing the increase of the field concentration in the film-slab when the superstrate is present compared to the case that it is absent. It is shown that large enhancement factor values may be achieved by choosing properly the permittivity, the permeability, and the thickness of the superstrate. In particular, it is demonstrated that the field in the film-slab is significantly enhanced when the slab is composed by an ϵ-near-zero (ENZ) or low-index metamaterial.
CC-Chemokine CCL15 Expression and Possible Implications for the Pathogenesis of IgE-Related Severe Asthma
Authors: Shimizu Yasuo , Dobashi Kunio
Published: October 2012

Airway inflammation is accompanied by infiltration of inflammatory cells and an abnormal response of airway smooth muscle. These cells secrete chemokines and express the cell surface chemokine receptors that play an important role in the migration and degranulation of inflammatory cells. Omalizumab is a monoclonal antibody directed against immunoglobulin E, and its blocking of IgE signaling not only reduces inflammatory cell infiltration mediated by the Th2 immune response but also inhibits other immune responses. The chemokine CCL15 is influenced by omalizumab, and the source of CCL15 has been reported to be airway smooth muscle cells and basophils. CCL15 binds to its receptor CCR1, which has been reported to be expressed by various inflammatory cells and also by airway smooth muscle cells. Therefore, CCL15/CCR1 signaling could be a target for the treatment of asthma. We review the role of CCL15 in the pathogenesis of asthma and also discuss the influence of IgE-mediated immunomodulation via CCL15 and its receptor CCR1.
Link Characteristics Measuring in 2.4 GHz Body Area Sensor Networks
Authors: Sun Guodong , Qiao Guofu , Xu Bin
Published: October 2012

With the increasing demands on the remote healthcare and the rich human-machine interacting, body area sensor network (BASN) has been attracting more and more attention. In practice, understanding the link performance and its dynamics in the emerging BASN applications is very important to design reliable, real-time, and energy-efficient protocols. In this paper we study the link characteristics of body area sensor network (BASN) through extensive experiments with very realistic configurations. We evaluate the packet reception ratio, RSSI, LQI, and movement intensity of body under indoor and outdoor environments, all of which can provide direct insights to practical account.
Transnational Involvement: Reading Quantitative Studies in Light of Qualitative Data
Authors: Paasche Erlend , Fangen Katrine
Published: October 2012

Studies of migrant transnationalism are dominated by qualitative case studies. To take the field further, there is a need for more quantitative studies and for connecting quantitative and qualitative studies through a reiterative feedback loop. In order to contribute to this, we take two refined and original quantitative studies, one by Snel et al. and one by Portes et al., as a vantage point, commenting on the authors’ organization of analytical categories and their operationalization of key concepts, in light of our own, qualitative data. These data come from a research project, EUMARGINS, where we analyze processes of inclusion and exclusion of young adult immigrants and descendants in seven European countries, using participant observation and life-story interviews in combination with statistical data. We conclude that the process whereby young migrants identify themselves in terms of ethnicity and belonging is context-specific, multidimensional, and hard to study quantitatively.
A Hybrid Human Dynamics Model on Analyzing Hotspots in Social Networks
Authors: Xiao Yunpeng , Wang Bai , Wu Bin , Yan Zhixian , Jia Shousheng , Liu Yanbing
Published: October 2012

The increasing development of social networks provides a unique source
for analyzing human dynamics in the modern age. In this paper, we analyze
the top‐one Internet forum in China (“Tianya Club”) and identify the statistical properties of hotspots, which can promptly reflect the crowd events
in people′s real‐life. Empirical observations indicate that the interhotspot
distribution follows a power law. To further understand the mechanism of
such dynamic phenomena, we propose a hybrid human dynamic model that
combines “memory” of individual and “interaction” among people. To build
a rich simulation and evaluate this hybrid model, we apply three different
network datasets (i.e., WS network, BA network, and Karate‐Club). Our
simulation results are consistent with the empirical studies, which indicate
that the model can provide a good understanding of the dynamic mechanism
of crowd events using such social networking data. We additionally analyze
the sensitivity of model parameters and find the optimal model settings.
Pharmacists’ Research Contributions in the Fight against HIV/AIDs
Authors: Horace Alexis E.
Published: October 2012

Pharmacists have made many contributions to HIV/AIDs research and are still showing their significance as members of the healthcare team through innovative clinical trials. Pharmacists are showing advances in several healthcare settings including inpatient, outpatient, and community pharmacies. Because of the complex regimens of highly active antiretroviral therapy (HAART), the increased life span of patients living with HIV, and other concomitant medications taken for comorbid disease states, there is a high risk for health-related complications and the development of adverse events. These adverse events may lead to decreased adherence to HAART, which may cause the development of HIV drug resistance. Pharmacists are providing examples through growing research on how they help combat medication-related errors and also continue to contribute as healthcare providers as a part of a holistic healthcare team.
Undecomposed Twigs in the Leaf Litter as Nest-Building Resources for Ants (Hymenoptera: Formicidae) in Areas of the Atlantic Forest in the Southeastern Region of Brazil
Authors: Fernandes Tae Tanaami , Silva Rogério Rosa da , Souza Débora Rodrigues de , Araújo Natália , Morini Maria Santina de Castro
Published: October 2012

In tropical forests, the leaf-litter stratum exhibits one of the greatest abundances of ant species. This diversity is associated with the variety of available locations for nest building. Ant nests can be found in various microhabitats, including tree trunks and fallen twigs in different stages of decomposition. In this study, we aimed to investigate undecomposed twigs as nest-building resources in the leaf litter of dense ombrophilous forest areas in the southeastern region of Brazil. Demographic data concerning the ant colonies, the physical characteristics of the nests, and the population and structural of the forest were observed. Collections were performed manually over four months in closed canopy locations that did not have trails or flooded areas. A total of 294 nests were collected, and 34 ant species were recorded.Pheidole,Camponotus, andHypoponerawere the richest genera observed; these genera were also among the most populous and exhibited the greatest abundance of nests. We found no association between population size and nest diameter. Only tree cover influenced the nest abundance and species richness. Our data indicate that undecomposed twigs may be part of the life cycle of many species and are important for maintaining ant diversity in the leaf litter.
Patient Engagement as an Emerging Challenge for Healthcare Services: Mapping the Literature
Authors: Barello Serena , Graffigna Guendalina , Vegni Elena
Published: October 2012

Patients’ engagement in healthcare is at the forefront of policy and research practice and is now widely recognized as a critical ingredient for high-quality healthcare system. This study aims to analyze the current academic literature (from 2002 to 2012) about patient engagement by using bibliometric and qualitative content analyses. Extracting data from the electronic databases more likely to cover the core research publications in health issues, the number of yearly publications, the most productive countries, and the scientific discipline dealing with patient engagement were quantitatively described. Qualitative content analysis of the most cited articles was conducted to distinguish the core themes. Our data showed that patient engagement is gaining increasing attention by all the academic disciplines involved in health research with a predominance of medicine and nursing. Engaging patients is internationally recognized as a key factor in improving health service delivery and quality. Great attention is up to now paid to the clinical and organizational outcomes of engagement, whereas there is still a lack of an evidence-based theoretical foundation of the construct as well as of the organizational dimensions that foster it.
Role of CA‐EDTA on the Synthesizing Process of Cerate‐Zirconate Ceramics Electrolyte
Authors: Abdullah Nur Athirah , Hasan Sharizal , Osman Nafisah
Published: October 2012

The role of a combination between citric acid (CA) and ethylenediaminetetra acetic acid (EDTA) as chelating agents in preparation of BaCe0.54Zr0.36Y0.1O2.95 powder by a modified sol‐gel method is reported. The precursor solutions were prepared from metal nitrate salts (M+), chelating agents (C), and ethylene glycol (EG) at molar ratio of M+ : C : EG = 3 : 2 : 3. Chemical and phase transformation of samples during thermal decomposition were analyzed by thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy. TGA results show that the sample prepared by a combination of CA‐EDTA exhibited the lowest thermal decomposition temperature, Ttd since there was no significant weight loss after 750°C. After calcined at 1100°C, the carbonates residue remained in the samples as proven by FTIR results. It was found that the used combination of CA‐EDTA acts as a better combustion reagent to increase the reaction rate and influence the thermal decomposition behaviour compared to a single citric acid and EDTA, respectively. Apparently, calcination temperatures above 1100°C are needed to produce a pure perovskitic BaCe0.54Zr0.36Y0.1O2.95.
Association between VEGF Splice Isoforms and Progression-Free Survival in Metastatic Colorectal Cancer Patients Treated with Bevacizumab
Authors: Bates David O. , Catalano Paul J. , Symonds Kirsty E. , Varey Alex H.R. , Ramani Pramila , O'Dwyer Peter J. , Giantonio Bruce J. , Meropol Neal J. , Benson Al Bowen , Harper Steven J.
Published: October 2012

Purpose: Bevacizumab improves survival for patients with metastatic colorectal cancer with chemotherapy, but no proven predictive markers exist. The VEGF-A splice form, VEGF165b, anti-angiogenic in animal models, binds bevacizumab. We tested the hypothesis that prolonged progression-free survival (PFS) would occur only in patients with low relative VEGF165b levels treated with bevacizumab.

Experimental Design: Blinded tumor samples from the phase III trial of FOLFOX4 ± bevacizumab were assessed for VEGF165b and VEGFtotal by immunohistochemistry and scored relative to normal tissue. A predictive index (PI) was derived from the ratio of VEGF165b:VEGFtotal for 44 samples from patients treated with FOLFOX + bevacizumab (arm A) and 53 samples from patients treated with FOLFOX4 (arm B), and PFS, and overall survival (OS) analyzed on the basis of PI relative to median ratio.

Results: Unadjusted analysis of PFS showed significantly better outcome for individuals with VEGF165b:VEGFtotal ratio scores below median treated with FOLFOX4 + bevacizumab compared with FOLFOX4 alone (median, 8.0 vs. 5.2 months; P < 0.02), but no effect of bevacizumab on PFS in patients with VEGF165b:VEGFtotal ratio >median (5.9 vs. 6.3 months). These findings held after adjustment for other clinical and demographic features. OS was increased in arm A (median, 13.6 months) compared with arm B (10.6 months) in the low VEGF165b group, but this did not reach statistical significance. There was no difference in the high VEGF165b:VEGFtotal group between FOLFOX + bevacizumab (10.8 months) and FOLFOX alone (11.3months).

Conclusion: Low VEGF165b:VEGFtotal ratio may be a predictive marker for bevacizumab in metastatic colorectal cancer, and individuals with high relative levels may not benefit. Clin Cancer Res; 18(22); 6384–91. ©2012 AACR.
Simultaneous Targeting of COX-2 and AKT Using Selenocoxib-1-GSH to Inhibit Melanoma
Authors: Gowda Raghavendra , Madhunapantula SubbaRao V. , Desai Dhimant , Amin Shantu , Robertson Gavin P.
Published: October 2012

Melanoma is a highly metastatic and deadly disease. An agent simultaneously targeting the COX-2, PI3K/Akt, and mitogen-activated protein kinase (MAPK) signaling pathways that are deregulated in up to 70% of sporadic melanomas might be an effective treatment, but no agent of this type exists. To develop a single drug inhibiting COX-2 and PI3K/Akt signaling (and increasing MAPK pathway activity to inhibitory levels as a result of Akt inhibition), a selenium-containing glutathione (GSH) analogue of celecoxib, called selenocoxib-1-GSH was synthesized. It killed melanoma cells with an average IC50 of 7.66 μmol/L compared with control celecoxib at 55.6 μmol/L. The IC50 range for normal cells was 36.3 to 41.2 μmol/L compared with 7.66 μmol/L for cancer cells. Selenocoxib-1-GSH reduced development of xenografted tumor by approximately 70% with negligible toxicity by targeting COX-2, like celecoxib, and having novel inhibitory properties by acting as a PI3K/Akt inhibitor (and MAPK pathway activator to inhibitory levels due to Akt inhibition). The consequence of this inhibitory activity was an approximately 80% decrease in cultured cell proliferation and an approximately 200% increase in apoptosis following 24-hour treatment with 15.5 μmol/L of drug. Thus, this study details the development of selenocoxib-1-GSH, which is a nontoxic agent that targets the COX-2 and PI3K/Akt signaling pathways in melanomas to inhibit tumor development. Mol Cancer Ther; 12(1); 3–15. ©2012 AACR.
Oestrogen Alpha-Receptor Variant and Two-Year Memory Decline in Midlife Australian Women
Authors: Bousman Chad A. , Szoeke Cassandra , Chen Karren , Dennerstein Lorraine , Henderson Victor W. , Everall Ian P.
Published: October 2012

Objective: To prospectively examine the influence of the oestrogen-α receptor (ESR1)PvuII polymorphism on changes in memory performance over a 2-year period among 80 midlife postmenopausal Australian women. Methods: Healthy women aged 56–67 years were administered a battery of four memory (verbal and non-verbal) tasks at baseline and 2 years later. Results: Carriers of the ESR1 p allele had significantly greater declines in logical memory compared to participants with the PP genotype, independent of demographic characteristics (e.g. age), chronic illness (e.g. hypertension), sleep aid usage, hormone levels, apolipoprotein E e4 status and prospective changes in mood, smoking and alcohol consumption. Conclusion: These findings provide preliminary evidence for larger and longer prospective trials that will be able to determine if the p allele of the ESR1PvuII polymorphism is a potential biomarker of logical memory decline among aging women.
Mitochondrial Motility and Vascular Smooth Muscle Proliferation
Authors: Chalmers Susan , Saunter Christopher , Wilson Calum , Coats Paul , Girkin John M. , McCarron John G.
Published: October 2012

Objective—

Mitochondria are widely described as being highly dynamic and adaptable organelles, and their movement is thought to be vital for cell function. Yet, in various native cells, including those of heart and smooth muscle, mitochondria are stationary and rigidly structured. The significance of the differences in mitochondrial behavior to the physiological function of cells is unclear and was studied in single myocytes and intact resistance-sized cerebral arteries. We hypothesized that mitochondrial dynamics is controlled by the proliferative status of the cells.

Methods and Results—

High-speed fluorescence imaging of mitochondria in live vascular smooth muscle cells shows that the organelle undergoes significant reorganization as cells become proliferative. In nonproliferative cells, mitochondria are individual (≈2 μm by 0.5 μm), stationary, randomly dispersed, fixed structures. However, on entering the proliferative state, mitochondria take on a more diverse architecture and become small spheres, short rod-shaped structures, long filamentous entities, and networks. When cells proliferate, mitochondria also continuously move and change shape. In the intact pressurized resistance artery, mitochondria are largely immobile structures, except in a small number of cells in which motility occurred. When proliferation of smooth muscle was encouraged in the intact resistance artery, in organ culture, the majority of mitochondria became motile and the majority of smooth muscle cells contained moving mitochondria. Significantly, restriction of mitochondrial motility using the fission blocker mitochondrial division inhibitor prevented vascular smooth muscle proliferation in both single cells and the intact resistance artery.

Conclusion—

These results show that mitochondria are adaptable and exist in intact tissue as both stationary and highly dynamic entities. This mitochondrial plasticity is an essential mechanism for the development of smooth muscle proliferation and therefore presents a novel therapeutic target against vascular disease.
Circulating Nucleosomes and Neutrophil Activation as Risk Factors for Deep Vein Thrombosis
Authors: van Montfoort Maurits L. , Stephan Femke , Lauw Mandy N. , Hutten Barbara A. , Van Mierlo Gerard J. , Solati Shabnam , Middeldorp Saskia , Meijers Joost C.M. , Zeerleder Sacha
Published: October 2012

Objective—

The formation of neutrophil extracellular traps and the exposure of nucleosomes on these neutrophil extracellular traps contribute to coagulation activation and the propagation of deep vein thrombosis (DVT) in animal models. However, no data are available on the role of neutrophil extracellular traps or nucleosomes in patients with thrombosis.

Methods and Results—

We conducted a case–control study, in which levels of circulating nucleosomes and neutrophil elastase–α1-antitrypsin complexes were assessed in plasma from 150 patients with objectified symptomatic DVT (cases) and compared with 195 patients with a clinical suspicion of DVT but in whom DVT was excluded (controls). We explored the association between both nucleosomes and elastase–α1-antitrypsin complexes, and the presence of DVT by calculating the odds ratio with corresponding 95% CIs. Elevated levels of both circulating nucleosomes and elastase–α1-antitrypsin complexes were associated with a 3-fold risk of DVT, and the associations remained similar after adjustment for potential confounders (malignancy, smoking, recent immobilization, recent hospitalization). The risk increased with higher nucleosome and elastase–α1-antitrypsin complex levels, suggesting a dose-dependent relationship among circulating nucleosomes, activated neutrophils, and DVT.

Conclusion—

Our study suggests an association among circulating nucleosomes, activated neutrophils, and presence of DVT in humans, which might have implications for treatment and prevention.