bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertension in response to CD4+ T cells from reduced uterine perfusion pregnant rats is associated with activation of the endothelin-1 system
Authors: Wallace Kedra , Novotny Sarah , Heath Judith , Moseley Janae , Martin James N. , Owens Michelle Y. , LaMarca Babbette
Published: May 2012

We have shown that adoptive transfer of CD4+ T cells from placental ischemia (reduction in uteroplacental perfusion, RUPP) rats causes hypertension and elevated inflammatory cytokines during pregnancy. In this study we tested the hypothesis that adoptive transfer of RUPP CD4+ T cells was associated with endothelin-1 activation as a mechanism to increase blood pressure during pregnancy. CD4+ T cells from RUPP or normal pregnant (NP) rats were adoptively transferred into NP rats on gestational day 13. Mean arterial pressure (MAP) was analyzed on gestational day 19, and tissues were collected for endothelin-1 analysis. MAP increased in placental ischemic RUPP rats versus NP rats (124.1 ± 3 vs. 96.2 ± 3 mmHg; P = 0.0001) and increased in NP recipients of RUPP CD4+ T cells (117.8 ± 2 mmHg; P = 0.001 compared with NP). Adoptive transfer of RUPP CD4+ T cells increased placental preproendothelin-1 mRNA 2.1-fold compared with NP CD4+ T cell rats and 1.7-fold compared with NP. Endothelin-1 secretion from endothelial cells exposed to NP rat serum was 52.2 ± 1.9 pg·mg−1·ml−1, 77.5 ± 4.3 pg·mg−1·ml−1 with RUPP rat serum ( P = 0.0003); 47.2 ± .16 pg·mg−1·ml−1 with NP+NP CD4+ T cell serum, and 62.2 ± 2.1 pg·mg−1·ml−1 with NP+RUPP CD4+ T cell serum ( P = 0.002). To test the role of endothelin-1 in RUPP CD4+ T cell-induced hypertension, pregnant rats were treated with an endothelin A (ETA) receptor antagonist (ABT-627, 5 mg/kg) via drinking water. MAP was 92 ± 2 mmHg in NP+ETA blockade and 108 ± 3 mmHg in RUPP+ETA blockade; 95 ± 5 mmHg in NP+NP CD4+ T cells+ETA blockade and 102 ± 2 mmHg in NP+RUPP CD4+ T cells+ETA blockade. These data indicate the importance of endothelin-1 activation to cause hypertension via chronic exposure to activated CD4+ T cells in response to placental ischemia.
Mechanisms of protein degradation in mantle muscle and proposed gill remodeling in starvedSepia officinalis
Authors: Lamarre Simon G. , Ditlecadet Delphine , McKenzie David J. , Bonnaud Laure , Driedzic William R.
Published: May 2012

Cephalopods have relatively high rates of protein synthesis compared to rates of protein degradation, along with minimal carbohydrate and lipid reserves. During food deprivation on board protein is catabolized as a metabolic fuel. The aim of the current study was to assess whether biochemical indices of protein synthesis and proteolytic mechanisms were altered in cuttlefish, Sepia officinalis, starved for 7 days. In mantle muscle, food deprivation is associated with a decrease in protein synthesis, as indicated by a decrease in the total RNA level and dephosphorylation of key signaling molecules, such as the eukaryote binding protein, 4E-BP1 (regulator of translation) and Akt. The ubiquitination-proteasome system (UPS) is activated as shown by an increase in the levels of proteasome β-subunit mRNA, polyubiquitinated protein, and polyubiquitin mRNA. As well, cathepsin activity levels are increased, suggesting increased proteolysis through the lysosomal pathway. Together, these mechanisms could supply amino acids as metabolic fuels. In gill, the situation is quite different. It appears that during the first stages of starvation, both protein synthesis and protein degradation are enhanced in gill. This is based upon increased phosphorylation of 4E-BP1 and enhanced levels of UPS indicators, especially 20S proteasome activity and polyubiquitin mRNA. It is proposed that an increased protein turnover is related to gill remodeling perhaps to retain essential hemolymph-borne compounds.
Differential effects of extracellular ATP on chloride transport in cortical collecting duct cells
Authors: Rajagopal Madhumitha , Kathpalia Paru P. , Widdicombe Jonathan H. , Pao Alan C.
Published: May 2012

Extracellular ATP in the cortical collecting duct can inhibit epithelial sodium channels (ENaC) but also stimulate calcium-activated chloride channels (CACC). The relationship between ATP-mediated regulation of ENaC and CACC activity in cortical collecting duct cells has not been clearly defined. We used the mpkCCDc14cortical collecting duct cell line to determine effects of ATP on sodium (Na+) and chloride (Cl−) transport with an Ussing chamber system. ATP, at a concentration of 10−6M or less, did not inhibit ENaC-mediated short-circuit current ( Isc) but instead stimulated a transient increase in Isc. The macroscopic current-voltage relationship for ATP-inducible current demonstrated that the direction of this ATP response changes from positive to negative when transepithelial voltage ( Vte) is clamped to less than −10 mV. We hypothesized that this negative Vtemight be found under conditions of aldosterone stimulation. We next stimulated mpkCCDc14cells with aldosterone (10−6M) and then clamped the Vteto −50 mV, the Vteof aldosterone-stimulated cells under open-circuit conditions. ATP (10−6M) induced a transient increase in negative clamp current, which could be inhibited by flufenamic acid (CACC inhibitor) and BAPTA-AM (calcium chelator), suggesting that ATP stimulates Cl−absorption through CACC. Together, our findings suggest that the status of ENaC activity, by controlling Vte, may dictate the direction of ATP-stimulated Cl−transport. This interplay between aldosterone and purinergic signaling pathways may be relevant for regulating NaCl transport in cortical collecting duct cells under different states of extracellular fluid volume.
An online tool for calculation of free-energy balance for the renal inner medulla
Authors: Vilbig Ryan L. , Sarkar Abhijit , Zischkau Joseph , Knepper Mark A. , Pisitkun Trairak
Published: May 2012

Concentrating models of the renal inner medulla can be classified according to external free-energy balance into passive models (positive values) and models that require an external energy source (negative values). Here we introduce an online computational tool that implements the equations of Stephenson and colleagues (Stephenson JL, Tewarson RP, Mejia R. Proc Natl Acad Sci USA 71: 1618–1622, 1974) to calculate external free-energy balance at steady state for the inner medulla ( http://helixweb.nih.gov/ESBL/FreeEnergy ). Here “external free-energy balance” means the sum of free-energy flows in all streams entering and leaving the inner medulla. The program first assures steady-state mass balance for all components and then tallies net external free-energy balance for the selected flow conditions. Its use is illustrated by calculating external free-energy balance for an example of the passive concentrating model taken from the original paper by Kokko and Rector (Kokko JP, Rector FC Jr. Kidney Int 2: 214–223, 1972).
The passive stiffness of the wrist and forearm
Authors: Formica Domenico , Charles Steven K. , Zollo Loredana , Guglielmelli Eugenio , Hogan Neville , Krebs Hermano I.
Published: May 2012

Because wrist rotation dynamics are dominated by stiffness (Charles SK, Hogan N. J Biomech 44: 614–621, 2011), understanding how humans plan and execute coordinated wrist rotations requires knowledge of the stiffness characteristics of the wrist joint. In the past, the passive stiffness of the wrist joint has been measured in 1 degree of freedom (DOF). Although these 1-DOF measurements inform us of the dynamics the neuromuscular system must overcome to rotate the wrist in pure flexion-extension (FE) or pure radial-ulnar deviation (RUD), the wrist rarely rotates in pure FE or RUD. Instead, understanding natural wrist rotations requires knowledge of wrist stiffness in combinations of FE and RUD. The purpose of this report is to present measurements of passive wrist stiffness throughout the space spanned by FE and RUD. Using a rehabilitation robot designed for the wrist and forearm, we measured the passive stiffness of the wrist joint in 10 subjects in FE, RUD, and combinations. For comparison, we measured the passive stiffness of the forearm (in pronation-supination), as well. Our measurements in pure FE and RUD agreed well with previous 1-DOF measurements. We have linearized the 2-DOF stiffness measurements and present them in the form of stiffness ellipses and as stiffness matrices useful for modeling wrist rotation dynamics. We found that passive wrist stiffness was anisotropic, with greater stiffness in RUD than in FE. We also found that passive wrist stiffness did not align with the anatomical axes of the wrist; the major and minor axes of the stiffness ellipse were rotated with respect to the FE and RUD axes by ∼20°. The direction of least stiffness was between ulnar flexion and radial extension, a direction used in many natural movements (known as the “dart-thrower's motion”), suggesting that the nervous system may take advantage of the direction of least stiffness for common wrist rotations.
Molecular Mechanisms of Same TCM Syndrome for Different Diseases and Different TCM Syndrome for Same Disease in Chronic Hepatitis B and Liver Cirrhosis
Authors: Guo Zhizhong , Yu Shuhao , Guan Yan , Li Ying-Ya , Lu Yi-Yu , Zhang Hui , Su Shi-Bing
Published: May 2012

Traditional Chinese medicine (TCM) treatment is based on the traditional diagnose method to distinguish the TCM syndrome, not the disease. So there is a phenomenon in the relationship between TCM syndrome and disease, called Same TCM Syndrome for Different Diseases and Different TCM Syndrome for Same Disease. In this study, we demonstrated the molecular mechanisms of this phenomenon using the microarray samples of liver-gallbladder dampness-heat syndrome (LGDHS) and liver depression and spleen deficiency syndrome (LDSDS) in the chronic hepatitis B (CHB) and liver cirrhosis (LC). The results showed that the difference between CHB and LC was gene expression level and the difference between LGDHS and LDSDS was gene coexpression in the G-protein-coupled receptor protein-signaling pathway. Therein genes GPER, PTHR1, GPR173, and SSTR1 were coexpressed in LDSDS, but not in LGDHS. Either CHB or LC was divided into the alternative LGDHS and LDSDS by the gene correlation, which reveals the molecular feature of Different TCM Syndrome for Same Disease. The alternatives LGDHS and LDSDS were divided into either CHB or LC by the gene expression level, which reveals the molecular feature of Same TCM Syndrome for Different Diseases.
Iron and Neurodegeneration: From Cellular Homeostasis to Disease
Authors: Batista-Nascimento Liliana , Pimentel Catarina , Andrade Menezes Regina , Rodrigues-Pousada Claudina
Published: May 2012

Accumulation of iron (Fe) is often detected in the brains of people suffering from neurodegenerative diseases. High Fe concentrations have been consistently observed in Parkinson’s, Alzheimer’s, and Huntington’s diseases; however, it is not clear whether this Fe contributes to the progression of these diseases. Other conditions, such as Friedreich’s ataxia or neuroferritinopathy are associated with genetic factors that cause Fe misregulation. Consequently, excessive intracellular Fe increases oxidative stress, which leads to neuronal dysfunction and death. The characterization of the mechanisms involved in the misregulation of Fe in the brain is crucial to understand the pathology of the neurodegenerative disorders and develop new therapeutic strategies.Saccharomyces cerevisiae, as the best understood eukaryotic organism, has already begun to play a role in the neurological disorders; thus it could perhaps become a valuable tool also to study the metalloneurobiology.
Preparation and Properties of Biphasic Calcium Phosphate Scaffolds Multiply Coated with HA/PLLA Nanocomposites for Bone Tissue Engineering Applications
Authors: Nie Lei , Suo Jinping , Zou Peng , Feng Shuibin
Published: May 2012

A well‐developed BCP scaffolds coated with multilayer of HA/PLLA nanocomposites with interconnectivity, high porosity, and moderate compressive strength as well as good biocompatibility were fabricated for bone tissue engineering. After being multiply coated with HA/PLLA nanocomposites, the scaffolds maintained the BCP framework structure, and the porous network structure of scaffolds remained unchanged; however, the compressive strength was increased with the increase of coating layer number of HA/PLLA nanocomposites. The prepared scaffolds showed lower variation of pH values in SBF solution, and an increase of coating layer number led to the decrease of the biodegradation rate at different days. Moreover, the multilayer coating scaffolds had good cytocompatibility, showing no negative effects on cells growth and proliferation. Furthermore, the bone‐like apatite layer was built obviously in the interface of scaffold after 21 days after implantation in SD rat muscle. In conclusion, the BCP scaffold coated with multilayer of HA/PLLA nanocomposites could be a candidate as an excellent substitute for damaged or defect bone in bone tissue engineering.
Efficacy of Continuously Administered PEDF-Derived Synthetic Peptides against Osteosarcoma Growth and Metastasis
Authors: Broadhead Matthew L. , Choong Peter F. M. , Dass Crispin R.
Published: May 2012

The potent antiangiogenic pigment epithelium-derived factor (PEDF) has shown promise against osteosarcoma, a tumour that originates in the bone and metastasises to the lungs. Neurotrophic, antiangiogenic, antiproliferative, and antimetastatic properties of PEDF have been attributed to a number of functional epitopes on the PEDF glycoprotein. StVOrth-2 (residues 78–102) and StVOrth-3 (residues 90–114) are two PEDF-derived peptides based on these functional epitopes. StVOrth-2 has previously been shown to inhibit osteosarcoma cell proliferation, while StVOrth-3 increased osteosarcoma cell adhesion to collagen Iin vitro. In this paper, we have evaluated systemically and continuously delivered StVOrth-2 and StVOrth-3 using a clinically relevant murine model of osteosarcoma with spontaneous metastasis. Treatment with StVOrth-2 or StVOrth-3 with microosmotic pumps was initiated after primary osteosarcoma was established in the tibia. While treatment with StVOrth-2 and StVOrth-3 did not appear to affect local tumour invasion, tumour necrosis or apoptosis, StVOrth-2 predominantly restricted the growth of primary tumours, while StVOrth-3 restricted the burden of pulmonary metastatic disease. No peptide caused gross toxicity in mouse tissues as assessed by measuring weight of animals, serum biochemistry, and gross tissue observation. The differential effects exhibited by StVOrth-2 and StVOrth-3 in this orthotopic model of osteosarcoma may be related to the functional epitopes on the PEDF glycoprotein that they represent.
Comparison of Mortality between Japanese Peritoneal Dialysis and Hemodialysis Patients: A 5-Year Multicenter Follow-Up Study
Authors: Suzuki Kazuko , Konta Tsuneo , Ichikawa Kazunobu , Ikeda Ami , Niino Hiroki , Hoshikawa Masato , Takahashi Toshiyuki , Abiko Hiroshi , Ito Minoru , Masakane Ikuto , Matsunaga Tomohito , Kudo Kosuke , Sato Hiroko , Degawa Noriyuki , Kubota Isao
Published: May 2012

To examine the relationship between dialysis modality and prognosis in Japanese patients, we conducted a prospective multicenter observational study. We recruited 83 background-matched peritoneal dialysis (PD) and 83 hemodialysis (HD) patients (average age, 64.9 years; men, 53.6%; diabetic patients, 22.9%; median duration of dialysis, 48 months in all patients) and followed them for 5 years. During the follow-up period, 27 PD patients (16 cardiovascular and 11 non-cardiovascular deaths) and 27 HD patients died (14 cardiovascular and 13 non-cardiovascular deaths). There were 8 PD patients switched to HD, and 6 PD patients received renal transplantation. Kaplan-Meier analysis revealed that the crude survival rate was not significantly different at the end of 5 years (PD 67.5% versus 67.5%, log-rankP=0.719). The difference in cardiovascular and non-cardiovascular mortalities between PD and HD was not statistically significant. Multivariate Cox analysis showed that the independent predictors for death were age and serum albumin levels, but not the dialysis modality. This study showed that the overall mortality was not significantly different between PD and HD patients, which suggests that dialysis modality might not be an independent factor for survival in Japanese patients.
A Study on Mechanical Properties of CNT‐Reinforced Carbon/Carbon Composites
Authors: Li Yi-Luen , Shen Ming-Yuan , Su Huang-Suo , Chiang Chin-Lung , Yip Ming-Chuen
Published: May 2012

Carbon/carbon composites (C/C composites) possess superior characteristics of low density, high strength, extremely low coefficient of thermal expansion, and high fatigue resistance. In carbonization process, the high‐temperature pyrolysis made of carbon, hydrogen, oxygen, and other elements results in a lot of voids and cavities generated in the interior of C/C composites. Therefore, the C/C composites are densified to fill the voids by using repeated impregnation. But densification is a time‐wasting and complex process, which increases production costs in the manufacturing process. In this study, the multiwall carbon nanotubes (MWNTs) were adopted as a reinforcement material for C/C composites to reduce the existence of voids or cavities and enhance the mechanical properties of C/C composites. According to the experimental results, the CNT‐added C/C composite containing 1.2 wt% CNT possesses the greatest flexure strength, flexure modulus, and interlaminar shearing strength. Plus, the above‐mentioned strength and modulus are increased by 23%, 19.2%, and 30%, respectively.
What Can Domesticated Genes Tell Us about the Intron Gain in Mammals?
Authors: Kordiš Dušan , Kokošar Janez
Published: May 2012

Domesticated genes, originating from retroelements or from DNA-transposons, constitute an ideal system for testing the hypothesis on the absence of intron gain in mammals. Since single-copy domesticated genes originated from the intronless multicopy transposable elements, the ancestral intron state for domesticated genes is zero. A phylogenomic approach has been used to analyse all domesticated genes in mammals and chordates that originated from the coding parts of transposable elements. A significant amount of intron gain was found only in domesticated genes of placental mammals, where more than 70 cases were identified. De novo gained introns show clear positional bias, since they are distributed mainly in 5′ UTR and coding regions, while 3′ UTR introns are very rare. In the coding regions of some domesticated genes up to 8 de novo gained introns have been found. Surprisingly, the majority of intron gains have occurred in the ancestor of placental mammals. Domesticated genes could constitute an excellent system on which to analyse the mechanisms of intron gain. This paper summarizes the current understanding of intron gain in mammals.
Dynamic Inequalities on Time Scales with Applications in Permanence of Predator‐Prey System
Authors: Hu Meng , Wang Lili
Published: May 2012

By using the theory of calculus on time scales and some mathematical methods, several dynamic inequalities on time scales are established. Based on these results, we derive some sufficient conditions for permanence of predator‐prey system incorporating a prey refuge on time scales. Finally, examples and numerical simulations are presented to illustrate the feasibility and effectiveness of the results.
Physiopathology of Bone Modifications inβ-Thalassemia
Authors: Perisano Carlo , Marzetti Emanuele , Spinelli Maria Silvia , Callà Cinzia Anna Maria , Graci Calogero , Maccauro Giulio
Published: May 2012

β-thalassemia major (βTM) or Cooley anemia is characterized by significantly reduced or absent synthesis ofβ-globin chains, which induces important pathologic consequences including hemolytic anemia, altered erythropoiesis, and bone marrow overstimulation. The pathogenesis of bone changes in patients withβTM is not yet completely understood. However, an unbalance in bone mineral turnover resulting from increased resorption and suppression of osteoblast activity has been detected inβTM patients. The abnormal regulation of bone metabolism may be related to hormonal and genetic factors, iron overload and iron chelation therapy, nutritional deficits, and decreased levels of physical activity. Here, we review the most recent findings on the physiopathology of bone abnormalities inβTM. Clinical presentation and radiological features ofβTM-related bone changes are also discussed.
A DOG’s View of Fanconi Anemia: Insights fromC. elegans
Authors: Jones Martin , Rose Ann
Published: May 2012

C. elegansprovides an excellent model system for the study of the Fanconi Anemia (FA), one of the hallmarks of which is sensitivity to interstrand crosslinking agents. Central to our understanding of FA has been the investigation of DOG-1, the functional ortholog of the deadbox helicaseFANCJ. Here we review the current understanding of the unique role of DOG-1 in maintaining stability of G-rich DNA inC. elegansand explore the question of why DOG-1 animals are crosslink sensitive. We propose a dynamic model in which noncovalently linked G-rich structures form and un-form in the presence of DOG-1. When DOG-1 is absent but crosslinking agents are present the G-rich structures are readily covalently crosslinked, resulting in increased crosslinks formation and thus giving increased crosslink sensitivity. In this interpretation DOG-1 is neither upstream nor downstream in the FA pathway, but works alongside it to limit the availability of crosslink substrates. This model reconciles the crosslink sensitivity observed in the absence of DOG-1 function with its unique role in maintaining G-Rich DNA and will help to formulate experiments to test this hypothesis.
Properties of Certain Subclass of Multivalent Functions with Negative Coefficients
Authors: Yang Jingyu , Li Shuhai
Published: May 2012

Making use of a linear operator, which is defined by the Hadamard product, we introduce and study a subclassYa,c+(A,B;p,λ,α)of the classA+(p). In this paper, we obtain the coefficient inequality, distortion theorem, radius of convexity and starlikeness, neighborhood property, modified convolution properties of this class. Furthermore, an application of fractional calculus operator is given. The results are presented here would provide extensions of some earlier works. Several new results are also obtained.
Matrix‐Assisted Pulsed Laser Thin Film Deposition by Using Nd:YAG Laser
Authors: Bloisi Francesco , Barra Mario , Cassinese Antonio , Vicari Luciano Rosario Maria
Published: May 2012

Matrix‐Assisted Pulsed Laser Evaporation (MAPLE) is a deposition technique, developed from Pulsed Laser Deposition (PLD) especially well suited for producing organic/polymeric thin films, which can take advantage from using Nd:YAG laser. Depending on the relative values of light absorption coefficients of the solvent and of the molecules to be deposited, laser energy is directly absorbed by the solvent or is transferred to it, providing a softer desorption mechanism with respect to PLD. In PLD ultraviolet laser radiation is commonly used, but in MAPLE, since easily damaged molecules are usually involved, the use of Nd:YAG laser offers the advantage to allow selecting laser wavelength from ultraviolet (266 nm or 355 nm, corresponding to 4.66 eV or 3.49 eV photon energies, resp.) to visible (532 nm, 2.33 eV) to infrared (1064 nm, 1.17 eV).
In this paper, the MAPLE technique is described in details, together with a survey of current and possible future applications for both organic and biomaterial deposition taking into account the advantages of using an Nd:YAG laser. Beside other results, we have experimental confirmation that MAPLE applications are not limited to transparent molecules highly soluble in light absorbing solvent, thus allowing deposition of poorly soluble light absorbing molecules suspended in a light transparent liquid.
Directed Fusion of Mesenchymal Stem Cells with Cardiomyocytes via VSV-G Facilitates Stem Cell Programming
Authors: Kouris Nicholas A. , Schaefer Jeremy A. , Hatta Masato , Freeman Brian T. , Kamp Timothy J. , Kawaoka Yoshihiro , Ogle Brenda M.
Published: May 2012

Mesenchymal stem cells (MSCs) spontaneously fuse with somatic cellsin vivo, albeit rarely, and the fusion products are capable of tissue-specific function (mature trait) or proliferation (immature trait), depending on the microenvironment. That stem cells can be programmed, or somatic cells reprogrammed, in this fashion suggests that stem cell fusion holds promise as a therapeutic approach for the repair of damaged tissues, especially tissues not readily capable of functional regeneration, such as the myocardium. In an attempt to increase the frequency of stem cell fusion and, in so doing, increase the potential for cardiac tissue repair, we expressed the fusogen of the vesicular stomatitis virus (VSV-G) in human MSCs. We found VSV-G expressing MSCs (vMSCs) fused with cardiomyocytes (CMs) and these fusion products adopted a CM-like phenotype and morphologyin vitro.In vivo, vMSCs delivered to damaged mouse myocardium via a collagen patch were able to home to the myocardium and fuse to cells within the infarct and peri-infarct region of the myocardium. This study provides a basis for the investigation of the biological impact of fusion of stem cells with CMsin vivoand illustrates how viral fusion proteins might better enable such studies.
Inhibition of Gene Expression of Organic Cation/Carnitine Transporter and Antioxidant Enzymes in Oxazaphosphorines-Induced Acute Cardiomyopathic Rat Models
Authors: Sayed-Ahmed Mohamed M. , Aldelemy Meshan Lafi , Hafez Mohamed M. , Al-Shabanah Othman A.
Published: May 2012

It is well documented that high therapeutic doses of oxazaphosphorines, cyclophosphamide (CP) and ifosfamide (IFO), are associated with cardiomyopathy. This study investigated whether oxazaphosphorines alter the expression of organic cation/carnitine transporter (OCTN2) and antioxidant genes and if so, whether these alterations contribute to CP and IFO-induced cardiotoxicity. Adult male Wistar albino rats were assigned to one of six treatment groups namely, control, L carnitine, CP, IFO, CP plus L carnitine and IFO plus L carnitine. In cardiac and kidney tissues, CP and IFO significantly decreased mRNA and protein expression of OCTN2. Oxazaphosphorines significantly increased serum acyl-carnitine/free carnitine ratio and urinary carnitine excretion and significantly decreased total carnitine in cardiac tissues. Interestingly, carnitine supplementation completely reversed the biochemical and gene expression changes-induced by oxazaphosphorines to the control values, except OCTN2 expression remained inhibited by IFO. Data from this study suggest that: (1) Oxazaphosphorines decreased myocardial carnitine content following the inhibition of OCTN2 mRNA and protein expression in cardiac tissues. (2) Oxazaphosphorine therapy increased urinary loss of carnitine secondary to the inhibition of OCTN2 mRNA and protein expression in proximal tubules of the kidney. (3) Carnitine supplementation attenuates CP but not IFO-induced inhibition of OCTN2 mRNA and protein expression in heart and kidney tissues.
A Protein-Based Ferritin Bio-Nanobattery
Authors: Watt Gerald D. , Kim Jae-Woo , Zhang Bo , Miller Timothy , Harb John N. , Davis Robert C. , Choi Sang H.
Published: May 2012

Nanostructured materials are increasingly important for the construction of electrochemical energy storage devices that will meet the needs of portable nanodevices. Here we describe the development of a nanoenergy storage system based on inorganic mineral phases contained in ferritin proteins. The electrochemical cell consists of an anode containing~2000 iron atoms as Fe(OH)2in the hollow protein interior of ferritin and a cathode containing~2000 of Co(OH)3in a separate ferritin molecule. The achieved initial voltage output from a combination of Fe2+- and Co3+-ferritins adsorbed on gold electrodes was~500 mV, while a combination of Fe2+- and Co3+-ferritins immobilized on gold produced a voltage of 350–405 mV. When fully discharged, Fe(OH)3and Co(OH)2are the products of a single electron transfer per metal atom from anode to cathode. The spent components can be regenerated by chemical or electrochemical methods restoring battery function. The properties of ferritins are presented and their unique characteristics are described, which have led to the development of a functional bio-nanobattery.
Wood Volume Production and Use of 10 Woody Species in Semiarid Zones of Northeastern Mexico
Authors: Foroughbakhch Rahim , Carrillo Parra Artemio , Hernández Piñero Jorge Luis , Alvarado Vázquez Marco Antonio , Rocha Estrada Alejandra , Cardenas Ma Luisa
Published: May 2012

A research strategy was established to analyze the structure of timber trees in terms of forest productivity (volume and wood density) of 10 species. The native speciesAcacia farnesiana, Acacia schaffneri,Bumelia celastrina,Cercidium macrun,Condalia hookeri,Ebenopsis ebano,Helietta parvifolia, andProsopis laevigataand the exotic speciesEucalyptus camaldulensisandLeucaena leucocephalawere chosen due to their ecological and economic importance to the rural villages of northeastern Mexico. Measurements of different growth parameters and volume of trees were evaluated. The introduced speciesE. camaldulensisandL. leucocephalashowed the best performance in wood volume production per tree and per hectare when compared to the native species. Likewise, among the native species,E. ebano,P. laevigata,C. hookeri, andA. farnesianatended to show better characteristics in terms of wood volume production in comparison toH. parvifolia,A. schaffneri,C. macrum, andB. celastrina. Results showed a high diversity on the properties studied. The high biomass produced by most of the species considered in this study revealed their great energetic potential when used as wood and firewood or vegetal charcoal.
Biodegradable Polymer‐Coated, Gelatin Hydrogel/Bioceramics Ternary Composites for Antitubercular Drug Delivery and Tissue Regeneration
Authors: Xue Mintao , Hu Hongtao , Jiang Yuanquan , Liu Jichun , He Hailong , Ye Xiaojian
Published: May 2012

A simple and effective strategy for the treatment of osteoarticular tuberculosis is proposed through combining tissue engineering approach with anti‐tuberculosis drug therapy. A series of tricalcium phosphate bioceramics (TPB) composites, coated by degradable polymer outside and loaded with rifampicin (RFP)‐containing gelatin hydrogel inside, were thus fabricated and successfully applied to deliver antitubercular drug RFP into osseous lesion and concomitantly to induce tissue regeneration. RFP‐loaded gelatin hydrogel/TPB composites could be readily prepared by filling RFP‐containing gelatin solution into TPB and then in situ crosslinking of gelatin with calcium ions. Depending on the concentrations of RFP, the loading efficiency of RFP in the composites varied in the range from approximately 2% to 5%. Moreover, the surface of these binary composites could be further coated by a biodegradable polymer, yielding biodegradable polymer‐coated, RFP‐containing gelatin hydrogel/TPB ternary composites. It was shown that in vitro release of RFP from the ternary composites could be effectively sustained for a long period of time. Besides, these composites revealed good biocompatibility towards the survival of MC‐3T3 cells in vitro and could be used for tissue regeneration in vivo in a rabbit model. The results indicate that TPB ternary composites have great potential for the treatment of osteoarticular tuberculosis.
Prevalence of Falls and Its Associated Factors among Elderly Diabetes in a Tertiary Center, Malaysia
Authors: Azidah A. K. , Hasniza H. , Zunaina E.
Published: May 2012

The purpose of this study is to determine the prevalence of falls and its associated factors among elderly diabetes type 2 patients attending a tertiary center in Malaysia. We conducted a cross-sectional study among 288 elderly diabetes type 2. The data collected includes data on sociodemographic, diabetes history, comorbid diseases, drug use, and activity of daily living (Barthel’s index). The patient also was examined physically, and balance and gait assessment was carried out. Prevalence of falls among elderly diabetes was 18.8%. Female gender (OR: 2.54,P<0.05), age group more than 75 (OR: 2.97,P<0.05), retinopathy (OR: 2.19,P<0.05), and orthostatic hypotension (OR: 2.87,P<0.05) were associated with higher risk for falls. High balance and gait score was associated with reduced risk of fall in elderly diabetes (OR: 0.89,P<0.05). In conclusion, the factors that are associated with higher risk for falls among elderly diabetes were female sex, age group more than 75, presence of retinopathy, and orthostatic hypotension. Those who had higher balance and gait score were found to be less likely to fall compared with those with lower score.
Ezetimibe and Simvastatin Reduce Cholesterol Levels in Zebrafish Larvae Fed a High-Cholesterol Diet
Authors: Baek Ji Sun , Fang Longhou , Li Andrew C. , Miller Yury I.
Published: May 2012

Cholesterol-fed zebrafish is an emerging animal model to study metabolic, oxidative, and inflammatory vascular processes relevant to pathogenesis of human atherosclerosis. Zebrafish fed a high-cholesterol diet (HCD) develop hypercholesterolemia and are characterized by profound lipoprotein oxidation and vascular lipid accumulation. Using optically translucent zebrafish larvae has the advantage of monitoring vascular pathology and assessing the efficacy of drug candidates in live animals. Thus, we investigated whether simvastatin and ezetimibe, the principal drugs used in management of hypercholesterolemia in humans, would also reduce cholesterol levels in HCD-fed zebrafish larvae. We found that ezetimibe was well tolerated by zebrafish and effectively reduced cholesterol levels in HCD-fed larvae. In contrast, simvastatin added to water was poorly tolerated by zebrafish larvae and, when added to food, had little effect on cholesterol levels in HCD-fed larvae. Combination of low doses of ezetimibe and simvastatin had an additive effect in reducing cholesterol levels in zebrafish. These results suggest that ezetimibe exerts in zebrafish a therapeutic effect similar to that in humans and that the hypercholesterolemic zebrafish can be used as a low-cost and informative model for testing new drug candidates and for investigating mechanisms of action for existing drugs targeting dyslipidemia.
Mechanism ofTrypanosoma cruziPlacenta Invasion and Infection: The Use of Human Chorionic Villi Explants
Authors: Fretes Ricardo E. , Kemmerling Ulrike
Published: May 2012

Congenital Chagas disease, a neglected tropical disease, endemic in Latin America, is associated with premature labor and miscarriage. During vertical transmission the parasiteTrypanosoma cruzi(T. cruzi) crosses the placental barrier. However, the exact mechanism of the placental infection remains unclear. We review the congenital transmission ofT. cruzi, particularly the role of possible local placental factors that contribute to the vertical transmission of the parasite. Additionally, we analyze the different methods available for studying the congenital transmission of the parasite. In that context, theex vivoinfection withT. cruzitrypomastigotes of human placental chorionic villi constitutes an excellent tool for studying parasite infection strategies as well as possible local antiparasitic mechanisms.
Response Analysis on Electrical Pulses under Severe Nuclear Accident Temperature Conditions Using an Abnormal Signal Simulation Analysis Module
Authors: Koo Kil-Mo , Song Jin-Ho , Kim Sang-Baik , Ahn Kwang-Il , Baek Won-Pil , Oh Kil-Nam , Kim Gyu-Tae
Published: May 2012

Unlike design basis accidents, some inherent uncertainties of the reliability of instrumentations are expected while subjected to harsh environments (e.g., high temperature and pressure, high humidity, and high radioactivity) occurring in severe nuclear accident conditions. Even under such conditions, an electrical signal should be within its expected range so that some mitigating actions can be taken based on the signal in the control room. For example, an industrial process control standard requires that the normal signal level for pressure, flow, and resistance temperature detector sensors be in the range of 4~20 mA for most instruments. Whereas, in the case that an abnormal signal is expected from an instrument, such a signal should be refined through a signal validation process so that the refined signal could be available in the control room. For some abnormal signals expected under severe accident conditions, to date, diagnostics and response analysis have been evaluated with an equivalent circuit model of real instruments, which is regarded as the best method. The main objective of this paper is to introduce a program designed to implement a diagnostic and response analysis for equivalent circuit modeling. The program links signal analysis tool code to abnormal signal simulation engine code not only as a one body order system, but also as a part of functions of a PC-based ASSA (abnormal signal simulation analysis) module developed to obtain a varying range of theR-Ccircuit elements in high temperature conditions. As a result, a special function for abnormal pulse signal patterns can be obtained through the program, which in turn makes it possible to analyze the abnormal output pulse signals through a response characteristic of a 4~20 mA circuit model and a range of the elements changing with temperature under an accident condition.
Design of a Takagi‐Sugeno Fuzzy Regulator for a Set of Operation Points
Authors: Santim Máira P. A. , Teixeira Marcelo C. M. , Souza Wallysonn A. de , Cardim Rodrigo , Assunção Edvaldo
Published: May 2012

The paper proposes a new design method based on linear matrix inequalities (LMIs)
for tracking constant signals (regulation) considering nonlinear plants described by the Takagi‐Sugeno fuzzy models. The procedure consists in designing a single controller that stabilizes
the system at operation points belonging to a certain range or region, without the need of
remaking the design of the controller gains at each new chosen equilibrium point. The
control system design of a magnetic levitator illustrates the proposed methodology.
The Importance of Definitive Diagnosis in Chronic Schistosomiasis, with Reference toSchistosoma haematobium
Authors: Shiff Clive
Published: May 2012

Schistosomes are long-lived parasites, hence schistosomiasis is a chronic disease with severe long-term implications. However, definitive diagnosis of active infection has been difficult because demonstration of infection has depended on detecting parasite eggs in urine and/or stool. In the case ofSchistosoma haematobiumwhich parasitizes the urinogenital system, this method has low sensitivity in adults. Detection of parasite-specific DNA in urine has been demonstrated and this has similar specificity but improved sensitivity. The implications of this new procedure and the impact on diagnosis are discussed.
Gait Parameter Adjustments for Walking on a Treadmill at Preferred, Slower, and Faster Speeds in Older Adults with Down Syndrome
Authors: Smith Beth A. , Kubo Masayoshi , Ulrich Beverly D.
Published: May 2012

The combined effects of ligamentous laxity, hypotonia, and decrements associated with aging lead to stability-enhancing foot placement adaptations during routine overground walking at a younger age in adults with Down syndrome (DS) compared to their peers with typical development (TD). Our purpose here was to examine real-time adaptations in older adults with DS by testing their responses to walking on a treadmill at their preferred speed and at speeds slower and faster than preferred. We found that older adults with DS were able to adapt their gait to slower and faster than preferred treadmill speeds; however, they maintained their stability-enhancing foot placements at all speeds compared to their peers with TD. All adults adapted their gait patterns similarly in response to faster and slower than preferred treadmill-walking speeds. They increased stride frequency and stride length, maintained step width, and decreased percent stance as treadmill speed increased. Older adults with DS, however, adjusted their stride frequencies significantly less than their peers with TD. Our results show that older adults with DS have the capacity to adapt their gait parameters in response to different walking speeds while also supporting the need for intervention to increase gait stability.
Poor Dissociation of Patient-Evaluated Apathy and Depressive Symptoms
Authors: Njomboro Progress , Deb Shoumitro
Published: May 2012

Apathy has traditionally been conceptualised as part of depression. The appropriateness of this conceptualisation has now been questioned, with the realization that apathy constitutes a distinct neuropsychiatric condition, with separate rehabilitation and patient-care implications to depression. Research on the relationship between apathy and depression has, however, produced mixed results. One reason for this inconsistency may lie behind who does the apathy evaluation. In this study we investigated whether the relationship between apathy and depression would differ when apathy was evaluated by the patients or an informant. A total of 49 brain damaged patients were assessed on self- and informant-rated Apathy Evaluation Scales. The relationship between the apathy scores and depressive symptoms was then investigated. Patient-rated, and not informant-rated apathy significantly correlated with depression. We discuss the implication of these results on the relationship between the two neuropsychiatric conditions and also in relation to the utility of patient self-evaluations in apathy.
Executive Dysfunction in MCI: Subtype or Early Symptom
Authors: Reinvang Ivar , Grambaite Ramune , Espeseth Thomas
Published: May 2012

Mild cognitive impairment (MCI) may take several forms, and amnestic MCI (aMCI) has been recognized as an early stage of Alzheimer’s Disease (AD). Impairment in executive functions including attention (eMCI) may be indicative of several neurodegenerative conditions. Executive impairment is frequently found in aMCI, it is significant for prognosis, and patients with eMCI may go on to develop AD. Recent studies have found changes in white matter integrity in patients with eMCI to be more sensitive than measures of cortical atrophy. Studies of genetic high-risk groups using sensitive cognitive neuroscience paradigms indicate that changes in executive function may be a cognitive marker useful for tracking development in an AD pathophysiological process.
Design Space of Flexible Multigigabit LDPC Decoders
Authors: Schläfer Philipp , Weis Christian , Wehn Norbert , Alles Matthias
Published: May 2012

Multigigabit LDPC decoders are demanded by standards like IEEE 802.15.3c and IEEE 802.11ad. To achieve the high throughput while supporting the needed flexibility, sophisticated architectures are mandatory. This paper comprehensively presents the design space for flexible multigigabit LDPC applications for the first time. The influence of various design parameters on the hardware is investigated in depth. Two new decoder architectures in a 65 nm CMOS technology are presented to further explore the design space. In the past, the memory domination was the bottleneck for throughputs of up to 1 Gbit/s. Our systematic investigation of column‐ versus row‐based partially parallel decoders shows that this is no more a bottleneck for multigigabit architectures. The evolutionary progress in flexible multigigabit LDPC decoder design is highlighted in an extensive comparison of state‐of‐the‐art decoders.
Celiac Disease and Dermatologic Manifestations: Many Skin Clue to Unfold Gluten-Sensitive Enteropathy
Authors: Caproni Marzia , Bonciolini Veronica , D'Errico Antonietta , Antiga Emiliano , Fabbri Paolo
Published: May 2012

Cutaneous manifestations of intestinal diseases are increasingly reported both in the adult and in the children, and this association cannot longer be considered a simple random. Besides the well-known association between celiac disease (CD) and dermatitis herpetiformis (DH), considered as the cutaneous manifestation of gluten-dependent enteropathy, is more frequently reported also the association with other mucocutaneous diseases. Among these there are both autoimmune, allergic, and inflammatory diseases, but also a more heterogeneous group called miscellaneous. The knowledge about pathogenic, epidemiological, clinical, and diagnostic aspects of CD is increasing in recent years as well as those about DH, but some aspects still remain to be defined, in particular the possible pathogenetic mechanisms involved in the association between both CD and DH and CD and other immunological skin diseases. The aim of this paper is to describe the skin diseases frequently associated with CD, distinguishing them from those which have a relationship probably just coincidental.
FGFR4 Blockade Exerts Distinct Antitumorigenic Effects in Human Embryonal versus Alveolar Rhabdomyosarcoma
Authors: Crose Lisa E.S. , Etheridge Katherine T. , Chen Candy , Belyea Brian , Talbot Lindsay J. , Bentley Rex C. , Linardic Corinne M.
Published: May 2012

Purpose: Rhabdomyosarcoma (RMS) is a malignancy with features of skeletal muscle, and the most common soft tissue sarcoma of childhood. Survival for high-risk groups is approximately 30% at 5 years and there are no durable therapies tailored to its genetic aberrations. During genetic modeling of the common RMS variants, embryonal RMS (eRMS) and alveolar RMS (aRMS), we noted that the receptor tyrosine kinase (RTK) fibroblast growth factor receptor 4 (FGFR4) was upregulated as an early event in aRMS. Herein, we evaluated the expression of FGFR4 in eRMS compared with aRMS, and whether FGFR4 had similar or distinct roles in their tumorigenesis.

Experimental Design: Human RMS cell lines and tumor tissue were analyzed for FGFR4 expression by immunoblot and immunohistochemistry. Genetic and pharmacologic loss-of-function of FGFR4 using virally transduced short hairpin RNA (shRNA) and the FGFR small-molecule inhibitor PD173074, respectively, were used to study the role of FGFR4 in RMS cell lines in vitro and xenografts in vivo. Expression of the antiapoptotic protein BCL2L1 was also examined.

Results: FGFR4 is expressed in both RMS subtypes, but protein expression is higher in aRMS. The signature aRMS gene fusion product, PAX3-FOXO1, induced FGFR4 expression in primary human myoblasts. In eRMS, FGFR4 loss-of-function reduced cell proliferation in vitro and xenograft formation in vivo. In aRMS, it diminished cell survival in vitro. In myoblasts and aRMS, FGFR4 was necessary and sufficient for expression of BCL2L1 whereas in eRMS, this induction was not observed, suggesting differential FGFR4 signaling.

Conclusion: These studies define dichotomous roles for FGFR4 in RMS subtypes, and support further study of FGFR4 as a therapeutic target. Clin Cancer Res; 18(14); 3780–90. ©2012 AACR.