bluuebunny/crossref_metadata_2025 huggingface dataset:
Androgen- and Estrogen-Dependent Regulation of Insulin-Degrading Enzyme in Subcellular Fractions of Rat Prostate and Uterus
Authors: Udrisar Daniel P. , Wanderley Maria I. , Porto Regina C. C. , Cardoso Carla L. P. , Barbosa Maria C. L. , Camberos Maria C. , Cresto Juan C.
Published: July 2017

Innumerous data support the fact that insulin-degrading enzyme (IDE) is the primary enzymatic mechanism for initiating and controlling cellular insulin degradation. Nevertheless, insulin degradation is unlikely to be the only cellular function of IDE, because it appears that some cellular effects of insulin are mediated by IDE as a regulatory protein. Insulin-degrading enzyme shows a significant correlation with various cellular functions, such as cellular growth and differentiation, and the expression of IDE is developmentally regulated. Besides insulin, other substrates are also degraded by IDE, including various growth-promoting peptides. It has also been shown that IDE enhances the binding of androgen to DNA in the nuclear compartment. It is also known that the androgen hormones have a stimulatory effect on prostate growth, and that estradiol stimulates uterine growth. To establish whether IDE is regulated by a cellular prostate/uterine growth stimulus, the present study assessed whether IDE was modified in quantity and activity during proliferative conditions (castration + testosterone in the male rat, or castration + estradiol or the proestrus phase of the estrous cycle in the female rat) and autolysis (castration or the metestrus phase of the estrous cycle) using cytosolic and nuclear fractions of rat prostate and cytosolic fractions of rat uterus. The activity and amount of IDE decreased in the cytosolic fraction with castration and during metestrus, and increased with testosterone or estradiol treatment and during proestrus. In the nuclear fraction, the quantity of the IDE followed the same pattern observed in the cytosolic fraction, although without degradative activity. The data presented here suggest that IDE may participate in prostatic and uterine growth and that the testosterone or estradiol and/or prostate and uterus insulin-like growth factors may be important factors for the expression and regulation of IDE in the prostate and uterus
Type I Diabetes Affects Skeletal Muscle Glutamine Uptake in a Fiber-Specific Manner
Authors: Onan Marie C. , Fisher Jonathan S. , Ju Jeong-Sun , Fuchs Bryan C. , Bode Barrie P.
Published: July 2017

Skeletal muscle serves as the body's major glutamine repository, and releases glutamine at enhanced rates during diabetes, but whether all muscles are equally affected is unknown. System Nmactivity mediates most trans-sarcolemmal glutamine movement, and although two System N (SN) isoforms have been identified (SN1/sodium-coupled neutral amino acid transporter or System N and A transporters [SNAT]-3; and SN2/SNAT5), their expression in skeletal muscle remains controversial. Here, the impact of Type I diabetes on glutamine uptake and System N transporter expression were examined in fast- and slow-twitch skeletal muscle from spontaneously diabetic (BB/Wor-DP) rats. Net glutamine uptake in fast-twitch fibers was decreased 75%-95%, but enhanced more than 2-fold in slow-twitch muscle from diabetic animals relative to nondiabetic controls. Both SNAT3 and SNAT5 mRNA were expressed in both muscle fiber types and their abundance was unaffected by diabetes. This represents the first report of differential fiber-specific effects of diabetes on skeletal muscle glutamine transport and the co-expression of distinct System N transporters in skeletal muscle.
Involvement of Water Channels in Synaptic Vesicle Swelling
Authors: Jeremic Aleksandar , Cho Won Jin , Jena Bhanu P.
Published: July 2017

Vesicle swelling is critical for secretion; however, the underlying mechanism of synaptic vesicle (SV) swelling is unknown. A Gαl3-phospholipase A2 (PLA2)-mediated involvement of the water channel aquaporin-1 (AQP1) in the regulation of secretory vesicle swelling in the exocrine pancreas has been previously reported. In the present study, the association and involvement of water channels in SV swelling was explored. Results from the study demonstrate that water channels AQP1 and AQP6, and the heterotrimeric Goprotein are associated with SVs and participate in their swelling.
Amomum xanthiodes Inhibits Mast Cell-Mediated Allergic Reactions Through the Inhibition of Histamine Release and Inflammatory Cytokine Production
Authors: Kim Sang-Hyun , Shin Tae-Yong
Published: July 2017

In this study, we investigated the effect of Amomum xanthiodes (Zingiberaceae) extract (AXE) on the mast cell-mediated allergy model and studied the possible mechanism of action. We found that AXE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. Additionally, AXE decreased immunoglobulin E (IgE)-mediated local allergic reactions and passive cutaneous anaphylaxis (PCA), and AXE dose-dependently attenuated the release of histamine from rat peritoneal mast cells (RPMC) activated by compound 48/80 or IgE. The amounts of AXE needed for inhibition of compound 48/80-induced plasma histamine release and PCA were similar to disodium cromoglycate, the known anti-allergic drug. We found that AXE increased the cAMP levels and decreased the compound 48/80-induced intracellular Ca2+. Furthermore, AXE attenuated the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore (A23187)-stimulated tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 secretion in human mast cells. The inhibitory effect of AXE on the proinflammatory cytokines was nuclear factor-κB (NF-κB)-dependent. In addition, AXE decreased PMA plus A23187-induced degradation of IκBα and the nuclear translocation of NF-κB. Our findings provide evidence that AXE inhibits mast cell-derived immediate-type allergic reactions, and that cAMP, intracellular Ca2+, proinflammatory cytokines, and NF-κB are involved in these effects.
Effect of Long-Term Somatotropin Treatment on Body Composition and Life Span in Aging Obese Zucker Rats
Authors: Azain Michael J. , Broderson J. Roger , Martin Roy J.
Published: July 2017

The objective of this work was to test the hypothesis that a somatotropin (STH)-induced reduction in body fat would prolong the life span of the obese Zucker rat. Two experiments were conducted. In the first experiment, male and female, lean and obese Zucker rats were treated with STH (0 or 2 mg/d bovine STH) for 4 weeks, beginning at 7 months of age. Across phenotypes, STH treatment increased the growth rate by 159%, muscle weights by 14%, and circulating insulin-like growth factor (IGF)-1 by 23%, and decreased carcass fat by 21% (P < 0.05). The second experiment was a longevity trial to determine whether these changes in body composition would increase the life span of the obese rat. Beginning at 7 months of age, individually housed, male and female, lean and obese rats were assigned to daily STH treatments (0 or 2 mg/d). Rats were monitored daily, and sick or moribund rats were euthanized and necropsied to determine existing pathologies. The average life span of the lean rats was 661 days and was unaffected by STH treatment (639 days, NS) or gender. Average life span of the vehicle-injected obese rats (435 days) was less than that of the lean group (P < 0.001). STH treatment of the obese rats resulted in a further reduction of life span (349 days, P < 0.02). The predominant pathology observed across the treatment groups was renal disease, characterized by progressive glomerulonephropathy. Thus, although exogenous STH was able to reduce carcass lipid and to increase lean tissue mass in obese rats, there was no improvement in longevity. In contrast to the hypothesis, STH actually reduced the life span of the obese rat. It is likely that STH treatment accelerated the development of progressive glomerulonephropathy in the obese rat.
Arachidonic Acid Metabolites Mediate the Radiation-Induced Increase in Glomerular Albumin Permeability
Authors: Sharma Mukut , McCarthy Ellen T. , Sharma Ram , Fish Brian L. , Savin Virginia J. , Cohen Eric P. , Moulder John E.
Published: July 2017

Radiation-induced renal injury is characterized by proteinuria, hypertension, and progressive decline in renal function. We have previously shown that in vivo or in vitro irradiation of glomeruli with a single dose of radiation (9.5 Gy) increases glomerular albumin permeability (Palb) within 1 hr. The current studies tested the hypothesis that this early radiation-induced increase in Palb is caused by the release of arachidonic acid and by the generation of specific arachidonic acid metabolites. Glomeruli obtained from WAG/Rij/MCW rats and cultured rat glomerular epithelial and mesangial cells were studied after irradiation (9.5 Gy, single dose). Arachidonic acid release and eicosanoid synthesis by glomeruli or cultured glomerular cells were measured after irradiation, and the effect of inhibitors of phospholipase A2 (PLA2) and cyclooxygenase (COX) on the irradiation-induced increase in Palb was assessed. Arachidonic acid release was demonstrated within 10 mins of irradiation of isolated glomeruli and monolayer cultures of glomerular epithelial and mesangial cells. Prostaglandin F2α (PGF2α) and PGE2 release was increased after irradiation of isolated glomeruli. Blocking arachidonic acid release or COX activity before irradiation completely prevented the increase in Palb-COX inhibition immediately after irradiation also diminished the radiation-induced increase in Palb. We conclude that arachidonic acid and its COX metabolites play an essential role in the early cellular changes that lead to the radiation-induced increase in Palb. Understanding of the early epigenetic effects of irradiation may lead to new intervention strategies against radiation-induced injury of normal tissues.
Renal Thrombotic Microangiopathy in a Genetic Model of Hypertension in Mice
Authors: Sethi Sanjeev , Iida Shinichiro , Sigmund Curt D. , Heistad Donald D.
Published: July 2017

Our goal was to develop a model of accelerated hypertension with renal microangiopathy. Transgenic mice that are hypertensive because of overexpression of human renin (R+ mice) and human angiotensin (A+ mice) genes were studied. To Increase arterial pressure to levels comparable to those that may be seen in malignant hypertension, high salt was added to the diet and/or the nitric oxide synthase inhibitor, Nω-nitro-L-arginine methylester (L-NAME), was added to the drinking water. Renal lesions, decline in renal function, and proteinuria developed within 10 weeks in R+/A+ mice given both L-NAME and a high-salt diet, and within 24 weeks in mice given either L-NAME or a high-salt diet. Renal morphology showed features of severe thrombotic microangiopathy, with extensive vascular and glomerular lesions in all R+/A+ mice on high salt, L-NAME, or high salt plus L-NAME. Vascular lesions included fibrin thrombi and onion skinning of the vessel walls, whereas glomerular lesions Included segmental sclerosis, mesangiolysis, fibrin thrombi within glomerular capillaries, and double-contour formation of glomerular capillary walls. Renal morphology was normal in control mice fed high salt and/or L-NAME. No R+/A+ mice fed a normal diet developed vascular lesions, whereas a few mice developed mild focal glomerular lesions. In summary, these studies characterize vascular and glomerular lesions in R+/A+ mice fed high salt, L-NAME, or both high salt and L-NAME, and provide a murine model of malignant hypertension with renal thrombotic microangiopathy.
Sodium-Iodide Symporter Mediates Iodide Secretion in Rat Gastric Mucosa In Vitro
Authors: Josefsson Malin , Evilevitch Lena , Weström Björn , Grunditz Torsten , Ekblad Eva
Published: July 2017

In vivo studies on rats have demonstrated that considerable amounts of iodide are transported from the bloodstream into the gastric lumen. The mechanisms for and functional significance of this transport are poorly understood. Active (driven by Na+/K+-ATPase) iodide transport into thyroid follicular cells is mediated by the sodium-iodide symporter (NIS), which is also abundantly expressed in gastric mucosa. We aimed to further investigate the iodide transport in gastric mucosa and the Possible role of NIS in this transport process. Iodide transport in rat gastric mucosa was studied in vitro in an Ussing chamber system using 125I as a marker. The system allows measurements in both directions over a mucosal specimen. A considerable transport of iodide (from the serosal to the mucosal side) was established across the gastric mucosa, whereas in the opposite direction (mucosa to serosa), iodide transport was negligible. Sodium Perchlorate (NaClO4), a competitive inhibitor of NIS, and ouabain, an inhibitor of the Na+/K+-ATPase, both attenuated gastric iodide transport from the serosal to the mucosal side. To investigate a possible neuroendocrine regulation of the iodide transport identified to occur from the serosal to the mucosal side of the stomach, thyroid-stimulating hormone (TSH), thyrotropin-releasing hormone (TRH), vasoactive intestinal peptide (VIP), histamine, or nitric oxide donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) was added. None of these substances influenced the iodide transport. We conclude that iodide is actively transported into the gastric lumen and that this transport is at least partly mediated by NIS. Additional investigations are needed to understand the regulation and significance of this transport.
Cross-Linking Cell Surface Chemokine Receptors Leads to Isolation, Activation, and Differentiation of Monocytes into Potent Dendritic Cells
Authors: Nimura Fumikazu , Zhang Li Feng , Okuma Kazu , Tanaka Reiko , Sunakawa Hajime , Yamamoto Naoki , Tanaka Yuetsu
Published: July 2017

Monocytes express on the cell surface several kinds of chemokine receptors that facilitate chemotaxis followed by differentiation in target tissues. In the present study, we found that a large number of monocytes from peripheral blood mononuclear cells (PBMCs) tightly adhered to plastic cell culture plates precoated with a monoclonal antibody (mAb, clone T312) specific for human CCR5 but not an isotype control after overnight incubation. Soluble T312 did not induce such adhesion, indicating that cross-linking of CCR5 is required for the enhanced adhesion of monocytes. The adhesion was blocked by a PI3-K inhibitor and an anti-CD18 blocking mAb. Following the cross-linking of CCR5, monocytes synthesized high levels of M-CSF, RANTES, MIP-1α, and MIP-1β associated with a readily detectable downmodulation of CD14, CD4, CCR5, and CXCR4 expression. The T312-enriched monocytes differentiated into dendritic cells (DCs) in the presence of interleukin-4 alone. After maturation with β-interferon, the T312-induced DCs stimulated proliferation of allogeneic naïve CD4+T cells accompanied by the synthesis of high levels of γ-interferon in vitro. Furthermore, the T312-induced DCs were capable of stimulating antigen-specific human T- and B-cell immune responses in our hu-PBL-SCID mouse system. Finally, screening of other anti-chemokine receptor mAbs showed that select clones of mAbs against CXCR4 and CCR3 were also capable of facilitating enrichment of monocytes similar to T312. These results show that cross-linking of chemokine receptors on monocytes by appropriate mAbs leads to activation and differentiation of monocytes and that the method described herein provides an alternate simple strategy for adherence-based isolation of monocytes and generation of functional DCs.
Double Null of Selenium-Glutathione Peroxidase-1 and Copper, Zinc-Superoxide Dismutase Enhances Resistance of Mouse Primary Hepatocytes to Acetaminophen Toxicity
Authors: Zhu Jian-Hong , Lei Xin Gen
Published: July 2017

This study was conducted to determine the impact of knockout of selenium (Se)–dependent glutathione peroxidase-1 (GPX1 /) or double knockout of GPX1 and copper, zinc (Cu, Zn)–superoxide dismutase (SOD1) on cell death induced by acetaminophen (APAP) and its major toxic metabolite N-acetyl-P-benzoquinoneimine (NAPQI). Primary hepatocytes were isolated from GPX1 /. double knockout of GPX1 and SOD1 (DKO), and their wild-type (WT) mice and were treated with 5 mM APAP or 100 μM NAPQI for 0, 6, and 12 hrs. Compared with the WT cells, the GPX1 / and DKO hepatocytes were more resistant (P < 0.05) to the APAP-induced cell death but less resistant to the NAPQI-induced cell death. The APAP-mediated glutathione (GSH) depletion was greater (P < 0.05) at 6 hrs in the WT cells than in the GPX1 / and DKO cells, whereas there was no genotype effect on the NAPQI-mediated GSH depletion. The DKO cells had lower (P < 0.05) microsomal cytochrome P450 2E1 activities, but higher (P < 0.05) glutathione reductase and thioredoxin reductase activities than the WT cells at 0 hrs, and they responded differently to the APAP and NAPQI treatments. Glutathione-S-transferase activity was not affected by genotypes or treatments. Neither APAP nor NAPQI induced nitric oxide production or protein nitration in cells of any genotype. However, the GPX1 and DKO cells were more resistant to peroxynitrite-mediated protein nitration than were the WT cells. In conclusion, double null of GPX1 and SOD1 enhanced the resistance of mouse primary hepatocytes to APAP toxicity by affecting events prior to or at NAPQI formation. While the double knockout attenuated the peroxynitrite-mediated protein nitration in hepatocytes, no protein nitration was detected in these cells treated with APAP or NAPQI.
Selective Compensatory Induction of Hepatic HMG-CoA Reductase in Response to Inhibition of Cholesterol Absorption
Authors: Ness Gene C. , Holland Reed C. , Lopez Dayami
Published: July 2017

The effect of the potent inhibitor of cholesterol absorption, ezetimibe, on serum cholesterol levels was tested in diabetic and thyroidectomized male Sprague-Dawley rats. Feeding diets supplemented with 1% cholesterol to the diabetic rats raised serum cholesterol levels from 132 to 514 mg/dl while decreasing hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase protein and mRNA levels. Addition of 10 mg/kg/day of ezetimibe to the diets of these animals lowered the serum cholesterol level to 90 mg/dl and produced a large compensatory increase in hepatic HMG-CoA reductase protein without significantly increasing mRNA levels, indicating a post-transcriptional effect. Hepatic LDL receptor protein levels in these diabetic rats were unaffected by ezetimibe treatment. In contrast, ezetimibe treatment of these young normal Sprague-Dawley rats, known to express high levels of hepatic HMG-CoA reductase, did not lower serum cholesterol levels. In thyroidectomized rats, dietary cholesterol increased serum cholesterol levels from 116 to 135 mg/dl and ezetimibe treatment lowered these elevated cholesterol levels to 85 mg/dl. Cholesterol feeding of thyroidectomized rats severely reduced hepatic HMG-CoA reductase protein, while ezetimibe treatment restored reductase protein to normal levels. Again, hepatic LDL receptor protein levels were unaffected by ezetimibe treatment of cholesterol-fed thyroidectomized rats. The data demonstrate that the cholesterol absorption inhibitor ezetimibe profoundly lowers serum cholesterol levels in animals expressing very low rates of hepatic cholesterol synthesis and produces large compensatory increases in hepatic HMG-CoA reductase expression without significantly affecting expression of hepatic LDL receptors. This indicates that ezetimibe should be most effective in lowering serum cholesterol levels in people with low rates of cholesterol synthesis/high rates of cholesterol absorption.
Developmental Changes in Ovine Myocardial Glucose Transporters and Insulin Signaling Following Hyperthermia-Induced Intrauterine Fetal Growth Restriction
Authors: Barry James S. , Davidsen Meredith L. , Limesand Sean W. , Galan Henry L. , Friedman Jacob E. , Regnault Timothy R. H. , Hay William W.
Published: July 2017

Developmental changes in ovine myocardial glucose transporters and insulin signaling following hyperthermia-induced intrauterine fetal growth restriction (IUGR) were the focus of our study. Our objective was to test the hypothesis that the fetal ovine myocardium adapts during an IUGR gestation by increasing glucose transporter protein expression, plasma membrane-bound glucose transporter protein concentrations, and insulin signal transduction protein concentrations. Growth measurements and whole heart tissue were obtained at 55 days gestational age (dGA), 90 dGA, and 135 dGA (term = 145 dGA) in fetuses from control (C) and hyperthermic (HT) pregnant sheep. Additionally, in 135 dGA animals, arterial blood was obtained and Doppler ultrasound was used to determine umbilical artery systolic (S) and diastolic (D) flow velocity waveform profiles to calculate pulsatility (S – D/mean) and resistance (S – D/S) indices. Myocardial Glut-1, Glut-4, insulin signal transduction proteins involved in Glut-4 translocation, and glycogen content were measured. Compared to age-matched controls, HT 90-dGA fetal body weights and HT 135-dGA fetal weights and gross heart weights were lower. Heart weights as a percent of body weights were similar between C and HT sheep at 135 dGA. HT 135-dGA animals had (i) lower fetal arterial plasma glucose and insulin concentrations, (ii) lower arterial blood oxygen content and higher plasma lactate concentrations, (iii) higher myocardial Glut-4 plasma membrane (PM) protein and insulin receptor β protein (IRβ) concentrations, (iv) higher myocardial glycogen content, and (v) higher umbilical artery Doppler pulsatility and resistance indices. The HT ovine fetal myocardium adapts to reduced circulating glucose and insulin concentrations by increasing plasma membrane Glut-4 and IRβ protein concentrations. The increased myocardial Glut-4 PM and IRβ protein concentrations likely contribute to or increase the intracellular delivery of glucose and, together with the increased lactate concentrations, enhance glycogen synthesis, which allows for maintained myocardial growth commensurate with fetal body growth.
Nuclear Accumulations of p53 and Mdm2 are Accompanied by Reductions in c-Abl and p300 in Zinc-Depleted Human Hepatoblastoma Cells
Authors: Alshatwi Ali A. , Han Chung-Ting , Schoene Norberta W. , Lei Kai Y.
Published: July 2017

The influence of zinc status on the expression of proteins known to be involved in the stability of p53, the human tumor suppressor gene product, was examined in hepatoblastoma (HepG2) cells. Cells were cultured in zinc-deficient (ZD0.2, ZD0.4), zinc normal (ZN), zinc adequate (ZA), or zinc-supplemented (ZS) medium, which contained 0.2, 0.4, 4, 16, or 32 μM zinc, respectively. Nuclear p53 levels were almost 100% and 40% higher in ZD0.2 and ZD0.4 cells, respectively, than in ZN cells. Mdm2 protein, which mediates p53 degradation, was 174% and 148% higher in the nucleus of ZD0.2 and ZD0.4 cells, respectively, than in ZN cells. In addition, the observed reductions of nuclear c-Abl in ZD0.2 and ZD0.4 cells to 50% and 60% of ZN cells, respectively, may be a cellular response attempting to normalize nuclear p53 accumulation because nuclear c-Abl is known to down-regulate ubiquitination and nuclear export of p53. Moreover, no changes in total cellular p53, Mdm2, and c-Abl or nuclear Mdmx were observed among the treatment groups. Furthermore, in ZD0.2 and ZD0.4 cells, the reduction in total and nuclear p300, which is known to complex with CREB-binding protein and Mdm2 in the nucleus for the generation of degradable polyubiquitinated form of p53, may have depressed the degradation pathway for p53 and Mdm2, and contributed to the nuclear accumulation of these proteins in ZD cells.
The Future of Interdisciplinary Research and Training: How to Conquer the Silo Guardians
Authors: Goodman Steven R. , Blake Charles A.
Published: July 2017

We have entered a new era in biomedical research in which large interdisciplinary teams are being established to answer important scientific questions. Scientists of multidisciplinary backgrounds within universities are combining forces and inter-institutional consortia that include alliances between academia and industry are springing up around the country to generate breakthrough advances. A number of driving forces are at work to establish these collaborative research approaches. By contrast, there also are barriers to be surmounted by institutions with silo mentalities for effective partnerships to be established. In order for this new era of research to reach maximal effectiveness, new approaches to education of the young and retraining of established administrators and scientists must take place. These issues were explored thoroughly at the 2006 annual meeting of the Association of Anatomy, Cell Biology and Neurobiology Chairpersons (AACBNC) that was held in Aruba from January 18 to 21. The theme of this historic meeting was the Future of Interdisciplinary Research and Training: Breaking Down the Barriers. In this introductory article, we discuss the formation of a trendsetting Institute of Biomedical Sciences and Technology, the concept of the AACBNC meeting, and the influence of the Institute on the content of the meeting. The proceedings of this meeting, including Nobel Laureate Papers and Nobel Round-Table Discussions on the future of interdisciplinary research and training, are contained in this special issue of Experimental Biology and Medicine, a journal dedicated to the publication of multidisciplinary and interdisciplinary research in the biomedical sciences.
Issues on Research Integrity: A Perspective
Authors: Pascal Chris B.
Published: July 2017

This paper discusses several key issues that are relevant to the integrity and success of the biomedical research enterprise. Attention to these issues will improve research outcomes and reduce negative consequences in research. Subjects addressed include normative practices in research; the importance of quality data; mentoring of young scientists; how to proceed when a member of the scientific community discovers misconduct or other breaches of integrity; and the level of harm to public confidence in research due to misconduct and lack of transparency in research findings.
Flavonoids Attenuate Cardiovascular Disease, Inhibit Phosphodiesterase, and Modulate Lipid Homeostasis in Adipose Tissue and Liver
Authors: Peluso Michael R.
Published: July 2017

Plant flavonoids are widely distributed polyphenolic compounds of the human diet. They consist of six major classes based on specific structural differences: flavonols, flavones, flavanones, catechins, anthocyanidins, and isoflavones. All of the major classes of flavonoids are comprised of three six-membered rings: an aromatic A-ring fused to a heterocyclic C-ring that is attached through a single carbon-carbon bond to an aromatic B-ring. Population studies have shown that flavonoid intake is inversely correlated with mortality from cardiovascular disease, and numerous flavonoids of dietary significance have been shown to beneficially impact parameters associated with atherosclerosis, including lipoprotein oxidation, blood platelet aggregation, and vascular reactivity. Therapeutic effects of flavonoids on platelet aggregability and blood pressure have been attributed to competitive inhibition of cyclic nucleotide phosphodiesterase (PDE), an elevation in cAMP level, and subsequent activation of protein kinase A (cAMP-dependent protein kinase). In addition, flavonoids may Induce neutral lipid hydrolysis from lipid stores through PDE inhibition in adipose tissue and liver. Indeed, the three-dimensional structure of many flavonoids is sterically and electrostatically compatible with the catalytic site of cAMP PDE3 and PDE4. Flavonoids have also been reported to suppress pathways of lipid biosynthesis and of very low-density lipoprotein production in cultured hepatocytes. Continued studies of the biochemical mechanisms underlying the biological effects of plant flavonoids may uncover new strategies for the treatment of cardiovascular disease, as well as associated conditions such as obesity, hepatic steatosis, and Type 2 diabetes.
Sodium Pump Reduction Correlates with Aortic Clamp Time in Pediatric Heart Surgery
Authors: Pavlovic Mladen , Schaller André , Ammann Roland A. , Pfammatter Jean-Pierre , Berdat Pascal , Carrel Thierry , Gallati Sabina
Published: July 2017

Myocardial depression after cardiac surgery is modulated by cardiopulmonary bypass (CPB) and the underlying heart disease. The sodium pump is a key component for myocardial function. We hypothesized that the change in sodium pump expression during CPB correlates with intraoperative and postoperative laboratory and clinical parameters in neonates and children with various congenital heart defects. Sodium pump isoforms alpha1 (ATP1A1) and alpha3 (ATP1A3) mRNA expression in right atrial myocardium, excised before and after CPB, was quantified. Groups were assigned according to presence (VO group, n = 8) or absence (NO group, n = 8) of right atrial volume overload. CPB and aortic clamp time correlated with postoperative troponin-1 values and ICU stay. ATP1A1 (P = 0.008) and ATP1A3 (P = 0.038) mRNA expression were significantly reduced during CPB. Longer aortic clamp times were associated with lower postoperative ATP1A1 (P = 0.045) and ATP1A3 (P = 0.002) mRNA expression. Low postoperative ATP1A1 (P = 0.043) and ATP1A3 (P = 0.002) expressions were associated with high troponin-I values. These results were restricted to the VO group. No correlation of sodium pump mRNA expression was found with the duration of ICU stay or ventilation. The postoperative troponin-I and clinical parameters correlated with the length of CPB, regardless of volume overload. In contrast, only dilated right atrium seemed to be susceptible to CPB in terms of sodium pump expression, showing a reduction during the operation and a correlation of sodium pump with postoperative troponin-I values.
Antioxidants and Phase 2 Enzymes in Cardiomyocytes: Chemical Inducibility and Chemoprotection Against Oxidant and Simulated Ischemia-Reperfusion Injury
Authors: Cao Zhuoxiao , Zhu Hong , Zhang Li , Zhao Xue , Zweier Jay L. , Li Yunbo
Published: July 2017

The increasing recognition of the role for oxidative stress in cardiac disorders has led to extensive investigation on the protection by exogenous antioxidants against oxidative cardiac injury. On the other hand, another strategy for protecting against oxidative cardiac injury may be through upregulation of the endogenous antioxidants and phase 2 enzymes in the myocardium by chemical inducers. However, our current understanding of the chemical inducibility of cardiac cellular antioxidants and phase 2 enzymes is very limited. In this study, using rat cardiac H9c2 cells we have characterized the concentration- and time-dependent induction of cellular antioxidants and phase 2 enzymes by 3H-1,2-dithiole-3-thione (D3T), and the resultant chemoprotective effects on oxidative cardiac cell injury. Incubation of H9c2 cells with D3T resulted in a marked concentration- and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes, including catalase, reduced glutathione (GSH), GSH peroxidase, glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). D3T treatment of H9c2 cells also caused an increase in mRNA expression of catalase, γ-glutamylcysteine ligase catalytic subunit, GR, GSTA1, M1 and P1, and NQO1. Moreover, both mRNA and protein expression of Nrf2 were induced in D3T-treated cells. D3T pretreatment led to a marked protection against H9c2 cell injury elicited by various oxidants and simulated ischemia-reperfusion. D3T pretreatment also resulted in decreased intracellular accumulation of reactive oxygen in H9c2 cells after exposure to the oxidants as well as simulated ischemia-reperfusion. This study demonstrates that a series of endogenous antioxidants and phase 2 enzymes in H9c2 cells can be induced by D3T in a concentration- and time-dependent fashion, and that the D3T-upregulated cellular defenses are accompanied by a markedly increased resistance to oxidative cardiac cell injury.
Inhibition of Dipeptidyl-Peptidase IV Does Not Increase Circulating IGF-1 Concentrations in Growing Pigs
Authors: Faidley T. D. , Leiting B. , Pryor K. D. , Lyons K. , Hickey G. J. , Thompson D. R.
Published: July 2017

The enzyme dipeptidyl peptidase-IV (DPP-IV) inactivates a variety of bioactive peptides, including glucagon-like peptide-1 (GLP-1) and growth hormone releasing hormone (GHRH). Inhibiting DPP-IV in order to increase circulating GLP-1 is of interest as a treatment for Type II diabetes. Inactivation of DPP-IV may also increase circulating GHRH, potentially enhancing growth in domestic animals. To test the hypothesis that inhibition of DPP-IV activity will influence the growth hormone/IGF-1 axis, growing pigs (Sus scrofa domesticus, 78 kg) were treated with a DPP-IV inhibitor (Compound 1, the 2,5-difluorophenyl analog of the triazolopiperazine MK0431, sitagliptin), and plasma concentrations of IGF-1 were monitored. Pigs were administered either sterile saline (0.11 ml/kg followed by a continuous infusion at 2 ml/hr for 72 hrs, controls, n = 2), Compound 1 (2.78 mg/kg followed by a continuous infusion at 0.327 mg/kg·hr for 72 hrs, n = 4) or GHRH (0.11 ml/kg sterile saline, followed by a continuous infusion of GHRH at 2.5 μg/kg hr for 48 hrs, n = 4). Plasma concentrations of Compound 1 were maintained at 1 μM, which resulted in a 90% inhibition of circulating DPP-IV activity. Relative to the predose 24-hr period, area under the IGF-1 concentration curve (AUC) tended to be lower (P = 0.062) with Compound 1 (–79 ± 130 ng/ml hr) than controls (543 ± 330 ng/ml hr). GHRH treatment increased the IGF-1 AUC (1210 ± 160 ng/ml hr, P = 0.049 vs. controls and P = 0.001 vs. Compound 1). We conclude that inhibition of DPP-IV does not alter the circulating levels of IGF-1 in the growing pig.
Mesenteric Vascular Responsiveness in a Rat Model of Pregnancy-Induced Hypertension
Authors: Anderson Cindy M. , Lopez Faye , Zhang Hai-Ying , Shirasawa Yuichi , Pavlish Kristin , Benoit Joseph N.
Published: July 2017

Reduced perfusion to the placenta in early pregnancy is believed to be the initiating factor in the development of preeclampsia, triggering local ischemia and systemic vascular hyperresponsiveness. This sequence of events creates a predisposition to the development of altered vascular function and hypertension. This study was designed to determine the influence of placental insufficiency on the responsiveness of mesenteric resistance arteries in an animal model of preeclampsia. Placental insufficiency was induced by reduction in uteroplacental perfusion pressure (RUPP) in experimental Sprague-Dawley rat dams. The uterine branches of the ovarian arteries and the abdominal aortae of pregnant rats were surgically constricted on gestational Day 14. Dams in the control group underwent a sham procedure. Rats were euthanized on gestational Day 20, followed by removal of the small intestine and adjacent mesentery. First-order mesenteric resistance arteries were mounted on a small vessel wire myograph and challenged with incremental concentrations of vasoconstrictors and vasorelaxants. Mesenteric arteries in dams with placental insufficiency demonstrated an increased maximal tension to phenylephrine (7.15 ± 0.15 vs. 5.4 ± 0.27 mN/mm, P < 0.001); potassium chloride at 60 mM (3.43 ± 0.11 vs. 2.77 ± 0.14 mN/mm, P < 0.01) and 120 mM (3.92 ± 0.18 vs. 2.97 ± 0.16 mN/mm, P < 0.01); and angiotensin II (2.59 ± 0.42 vs. 1.51 ± 0.22 mN/mm, P < 0.05). Maximal relaxation to endothelium-dependent relaxants acetylcholine and calcium lonophore (A23187) was not significantly reduced. Data suggest that placental insufficiency leads to hyperresponsiveness to vasoconstrictor stimuli in mesenteric arteries.
Psychological Capital for Leader Development
Authors: Pitichat Thiraput , Reichard Rebecca J. , Kea-Edwards Amber , Middleton Eric , Norman Steven M.
Published: July 2017

The continual development of leaders is one effective strategy for organizations to compete in today’s rapidly changing society. Despite awareness of this need, human resource professionals and managers find it challenging to promote or encourage ongoing development among leaders. Addressing the need for continuous learning, we extend the construct of psychological capital to the context of leader development. Specifically, leader development psychological capital (LD PsyCap) is defined as an individual’s motivational propensity to develop as a leader and consists of efficacy, hope, optimism, and resilience toward leader development. Using an online survey of 120 leaders, we found that LD PsyCap predicted leader development behaviors beyond other individual differences. We also found that LD PsyCap mediated the relationship between learning climate, organizational support, social support, and workload on leader development behaviors. Promoting LD PsyCap can help facilitate ongoing leader development in organizations.
Attrition rates and maneuver in agent-based simulation models
Authors: Ormrod David , Turnbull Benjamin
Published: July 2017

Agent-based military combat simulation models make use of a variety of methods to determine individual engagement and casualty effects. The agent-based approach differs to the deterministic approach of Lanchester and Osipov, whose combat attrition calculations pre-dated computationally intensive physics-based simulation models. Deterministic approaches to analyze force attrition rates and the outcomes of combat have been noted by many authors to lack realism and to ignore many fundamental aspects of modern combat. However, there is little available evidence to suggest that modern simulations provide a more realistic attrition rate, despite their complexity.

This paper seeks to explain the importance of understanding the implications of the tactical aspects of multiple simulation packages and to ensure these are considered within the underlying combat model. The principle factor this paper will discuss is attrition and its relationship to maneuver. This work analyzes the macro-attrition rates emergent within a number of unclassified agent-based simulations using the Helmbold space. The results demonstrate insufficient sensitivity to the influence of maneuver and the inconsistent influence of force ratios on combat outcomes. Simulation supported by well-documented testing and validation is necessary for analysts to support the military training imperative and provide realistic experimental engagement results.
TBAS: Token-based authorization service architecture in Internet of things scenarios
Authors: Lee Shih-Hsiung , Huang Ko-Wei , Yang Chu-Sing
Published: July 2017

Internet of things refers to billions of interconnected devices that are generally equipped with sensors and communication devices. How to make Internet of things become a smart terminal is an important topic. By connecting cloud services, the devices can receive more accurate information so as to be applied in people’s daily life. However, the smart terminal devices access the cloud services via Representational State Transfer (RESTful) application programming interfaces, and how the cloud server authenticates and authorizes billions of devices is an immense challenge. Additionally, individual use of smart terminal devices is accompanied by such problems as privacy data or security. This article presents a token-based authorization service framework. The devices can have a safer access to cloud services through the token. Token is released by a third-party authentication center to improve its reliability and security and is featured by a high degree of privacy that sensitive data are not easily leaked. Furthermore, the token is valid only within a period of time or it will not work after the token count exceeds the threshold defined by the system, thereby lowering the devices’ risk of being hacked. The framework proposed in this article is applied to medical wearable devices. The advantages of this framework are practical and secure which are explained in the experimental chapter.
In-vehicle sensor-assisted platoon formation by utilizing vehicular communications
Authors: Su Dongliang , Ahn Sanghyun
Published: July 2017

These days, vehicles are equipped with in-vehicle sensors so that they can collect the situation-related information, such as velocity, heading, and position. From the viewpoint of intelligent transportation system, platooning is getting more attention because of its advantages of increased road capacity, fuel saving, safety, and so on. In this article, we propose a mechanism that allows vehicles to form platoons based on their own and 1-hop neighbors’ sensory information obtained from vehicular communications. Within a platoon, the front vehicle is the leader whose role is leading the platoon, so the stability of the leader is the most critical performance factor of platooning. To achieve this, we propose to use relative mobility information of vehicles computed from the sensory information for the leader election. The performance of our platooning mechanism is evaluated by carrying out ns-3-based simulations, especially from the perspective of leader stability and road capacity.
Abdominal Wall Expanding System Obviates the Need for Lateral Release in Giant Incisional Hernia and Laparostoma
Authors: Eucker Dietmar , Zerz Andreas , Steinemann Daniel C.
Published: July 2017

Background:In large incisional hernias and after laparostoma midline closure may be impossible. A novel abdominal wall expander system (AWEX) is proposed and evaluated. Methods: In patients with large incisional hernias and laparostoma where primary midline closure was impossible, AWEX was used. Patients undergoing abdominal wall reconstruction using AWEX between May 2012 and December 2015 were included. Intraoperative the abdominal wall was stretched by attaching the midline fascia borders to a retraction system under tension for 30 minutes. Length and width of the hernia defect were measured in preoperative computed tomography. Width gain after AWEX procedure, operative time, morbidity, and presence of remaining midline gap was evaluated. Patients were followed for hernia recurrence. Results: Ten patients with incisional hernias (N = 4) and grafted laparostoma (N = 6) underwent abdominal wall reconstruction using AWEX. Median (interquartile range) length and width of the hernia defect was 18.0 (15.0-20.5) and 12.0 (11.8-13.3) cm. Width gain after AWEX was 8.5 (8.0-10.5) cm. Operative time was 270 (135-379) minutes. The major morbidity was 20%. In 4 patients a gap of 4 (4-5) cm was bridged by intraperitoneal onlay mesh. After a median follow-up of 21 (7-36) months no hernia recurrence was observed. Conclusions: Stretching of the abdominal wall that has been shown successful using progressive restressed retention sutures and progressive preoperative pneumoperitoneum is reduced from days and weeks to 30 minutes in AWEX. AWEX is a promising alternative to component separation in repair of large incisional hernias. After refinement of the system prospective evaluation is required.
Investigating the Reliability and Factor Structure of Kalichman’s “Survey 2: Research Misconduct” Questionnaire: A Post Hoc Analysis Among Biomedical Doctoral Students in Scandinavia
Authors: Holm Søren , Hofmann Bjørn
Published: July 2017

A precondition for reducing scientific misconduct is evidence about scientists’ attitudes. We need reliable survey instruments, and this study investigates the reliability of Kalichman’s “Survey 2: research misconduct” questionnaire. The study is a post hoc analysis of data from three surveys among biomedical doctoral students in Scandinavia (2010-2015). We perform reliability analysis, and exploratory and confirmatory factor analysis using a split-sample design as a partial validation. The results indicate that a reliable 13-item scale can be formed (Cronbach’s α = .705), and factor analysis indicates that there are four reliable subscales each tapping a different construct: (a) general attitude to misconduct (α = .768), (b) attitude to personal misconduct (α = .784), (c) attitude to whistleblowing (α = .841), and (d) attitude to blameworthiness/punishment (α = .877). A full validation of the questionnaire requires further research. We, nevertheless, hope that the results will facilitate the increased use of the questionnaire in research.
The Evolution of Theory: A Case Study
Authors: Carlson Elizabeth D. , Engebretson Joan , Chamberlain Robert M.
Published: July 2017

International attention is currently focused on alleviating health disparities through the adoption of new paradigms of research and the development of culturally relevant theories of health and illness. Yet, in spite of consistent calls to inform these deficiencies, the methodological trajectory from problem identification to theoretical development has remained relatively elusive. In this article, the authors present a case study of a systematic research methodology that resulted in a refined theory of social capital with practical relevance for health disparities research. Their purpose is to demonstrate how the stages and strategies of the hybrid model of concept development were extended as a research trajectory.
Clipping and Coding Audio Files: A Research Method to Enable Participant Voice
Authors: Crichton Susan , Childs Elizabeth
Published: July 2017

Qualitative researchers have long used ethnographic methods to make sense of complex human activities and experiences. Their blessing is that through them, researchers can collect a wealth of raw data. Their challenge is that they require the researcher to find patterns and organize the various themes and concepts that emerge during the analysis stage into a coherent narrative that a reader can follow. In this article, the authors introduce a technology-enhanced data collection and analysis method based on clipped audio files. They suggest not only that the use of appropriate software and hardware can help in this process but, in fact, that their use can honor the participants' voices, retaining the original three-dimensional recording well past the data collection stage.
Intersubjectivity, Hermeneutics, and the Production of Knowledge in Qualitative Mennonite Scholarship
Authors: Unger Matthew Peter
Published: July 2017

In this article, the author explores the nature of interpretation as it pertains to qualitative methods of inquiry. He elaborates on the epistemological problems that occur in discussions of the nature of human and social sciences as distinct from the theoretical foundations of the natural sciences. The examination of Mennonite scholarship provides an interesting case study as to the requirements of a hermeneutical social science because of the range of scholarly frameworks and varying locations of identity of the scholars in relation to the broader Mennonite community. The author argues that Mennonite scholarship is novel in the manner by which Mennonite scholars contribute to and participate within broad Mennonite intersubjective understandings. By extension, Mennonite scholars are able to deal with common epistemological problems and dichotomies that arise in the context of the researcher and the object of study.
Sampling Hurdles: “Borderline Illegitimate” to Legitimate Data
Authors: Garg Anupama
Published: July 2017

In this paper the author discusses how sampling access and recruitment problems encountered in an in-depth interview study heightened her sensitivity to “borderline illegitimate” data. The term illegitimate data usually refers to the data collected during a covert study, whereas “legitimate” data are collected during an overt study. Hence, data collected during any nonconsented period(s) of an overt study lie on the borderline of illegitimacy and legitimacy, and constitute what the author calls borderline illegitimate data. Such data need legitimization before use. The borderline illegitimate data were collected during the pre- and postinterview stages of her study as they explained how medical and ethnic cultures and sensitivity to racism as a topic combined to create sample recruitment difficulties of the study. The author later legitimized them by sharing them with the participants, guaranteeing anonymity, and asking their permission to use them.