bluuebunny/crossref_metadata_2025 huggingface dataset:
VEGF-C mediates cyclic pressure-induced endothelial cell proliferation
Authors: Shin Hainsworth Y. , Smith Michael L. , Toy Karen J. , Williams P. Mickey , Bizios Rena , Gerritsen Mary E.
Published: March 2015

Mechanical forces modulate endothelial cell functions through several mechanisms including regulation of gene transcription. In the present study, gene transcription by human umbilical vein endothelial cells (HUVEC) either maintained under control pressure (that is, standard cell culture conditions equivalent to 0.15 mmHg sustained hydrostatic pressure) or exposed to 60/20 mmHg sinusoidal pressures at 1 Hz were compared using Affymetrix GeneChip microarrays to identify cellular/molecular mechanisms associated with endothelial cell responses to cyclic pressure. Cyclic pressure selectively affected transcription of 14 genes that included a set of mechanosensitive proteins involved in hemostasis (tissue plasminogen activator), cell adhesion (integrin-α2), and cell signaling (Rho B, cytosolic phospholipase A2), as well as a unique subset of cyclic pressure-sensitive genes such as vascular endothelial growth factor (VEGF)-C and transforming growth factor (TGF)-β2. The present study also provided first evidence that VEGF-C, the most highly induced gene under 60/20 mmHg, mediated HUVEC proliferation in response to this cyclic pressure. Cyclic pressure is, therefore, a mechanical force that modulates endothelial cell functions (such as proliferation) by activating a specific transcriptional program.
Genetic targeting for cardiovascular therapeutics: are we near the summit or just beginning the climb?
Authors: FRANCIS SHARON C. , RAIZADA MOHAN K. , MANGI ABEEL A. , MELO LUIS G. , DZAU VICTOR J. , VALE PETER R. , ISNER JEFFREY M. , LOSORDO DOUGLAS W. , CHAO JULIE , KATOVICH MICHAEL J. , BERECEK KATHLEEN H.
Published: March 2015

This article is based on an Experimental Biology symposium held in April 2001 and presents the current status of gene therapy for cardiovascular diseases in experimental studies and clinical trials. Evidence for the use of gene therapy to limit neointimal hyperplasia and confer myocardial protection was presented, and it was found that augmenting local nitric oxide (NO) production using gene transfer (GT) of NO synthase or interruption of cell cycle progression through a genetic transfer of cell cycle regulatory genes limited vascular smooth muscle hyperplasia in animal models and infra-inguinal bypass patients. The results of application of vascular endothelial growth factor (VEGF) GT strategies for therapeutic angiogenesis in critical limb and myocardial ischemia in pilot clinical trials was reviewed. In addition, experimental evidence was presented that genetic manipulation of peptide systems (i.e., the renin-angiotensin II system and the kallikrein-kinin system) was effective in the treatment of systemic cardiovascular diseases such as hypertension, heart failure, and renal failure. Although, as of yet, there are no well controlled human trials proving the clinical benefits of gene therapy for cardiovascular diseases, the data presented here in animal models and in human subjects show that genetic targeting is a promising and encouraging modality, not only for the treatment and long-term control of cardiovascular diseases, but for their prevention as well.
New quantitative trait loci that contribute to cholesterol gallstone formation detected in an intercross of CAST/Ei and 129S1/SvImJ inbred mice
Authors: Lyons Malcolm A. , Wittenburg Henning , Li Renhua , Walsh Kenneth A. , Leonard Monika R. , Churchill Gary A. , Carey Martin C. , Paigen Beverly
Published: March 2015

Cholesterol gallstone formation is a response to interactions between multiple genes and environmental stimuli. To determine the subset of cholesterol gallstone susceptibility ( Lith) genes possessed by strains CAST/Ei (susceptible) and 129S1/SvImJ (resistant), we conducted quantitative trait locus (QTL) analyses of an intercross between these strains. Parental strains and F1mice of both genders were evaluated for gallstone formation after consumption of a lithogenic diet for 8 wk. Gallstone susceptibility of strain CAST was predominantly due to cholesterol hypersecretion. Male intercross offspring were genotyped and phenotyped for cholesterol gallstone formation after consumption of the lithogenic diet for 10 wk. Linkage analysis was performed using PSEUDOMARKER software. One significant, new QTL was detected and named Lith13 [chromosome (Chr) 5, 30 cM]. Statistical analyses and QTL fine mapping suggest this QTL may comprise two closely linked loci. We confirmed the presence of Lith6 (Chr 6). Suggestive QTL were detected on Chrs 1, 2, 5, 14, and 16. The QTL on Chrs 2 and 16 confirmed previously identified, suggestive QTL. Therefore, they were named Lith12 (101 cM) and Lith14 (42 cM), respectively. We identified candidate genes based on known function and location and performed mRNA expression analyses using both parental strains and intercross progeny for preliminary evaluation of their contributions to gallstone formation. Cebpb ( Lith12), Pparg ( Lith6), and Slc21a1 ( Lith6) displayed expression differences. Our work continues to demonstrate the genetic complexity and to elucidate the pathophysiology of cholesterol gallstone formation. It should facilitate the development of new approaches for treating this common human disorder.
Renal medullary genes in salt-sensitive hypertension: a chromosomal substitution and cDNA microarray study
Authors: Liang Mingyu , Yuan Baozhi , Rute Elizabeth , Greene Andrew S. , Zou Ai-Ping , Soares Paulo , McQuestion Gregory D. , Slocum Glenn R. , Jacob Howard J. , Cowley Allen W.
Published: March 2015

Substitution of chromosome 13 from Brown Norway BN/SsNHsd/Mcw (BN/Mcw) rats into the Dahl salt-sensitive SS/JrHsd/Mcw (SS/Mcw) rats resulted in substantial reduction of blood pressure salt sensitivity in this consomic rat strain designated SSBN13. In the present study, we attempted to identify genes associated with salt-sensitive hypertension by utilizing a custom, known-gene cDNA microarray to compare the mRNA expression profiles in the renal medulla (a tissue playing a pivotal role in long-term blood pressure regulation) of SS/Mcw and SSBN13 rats on either low-salt (0.4% NaCl) or high-salt (4% NaCl, 2 wk) diets. To increase the reliability of microarray data, we designed a four-way comparison experiment incorporating several levels of replication and developed a conservative yet robust data analysis method. Using this approach, from the 1,751 genes examined (representing more than 80% of all currently known rat genes), we identified 80 as being differentially expressed in at least 1 of the 4 comparisons. Substantial agreements were found between the microarray results and the results predicted on the basis of the four-way comparison as well as the results of Northern blots of 20 randomly selected genes. Analysis of the four-way comparison further indicated that ∼75% of the 80 differentially expressed genes were likely related to salt-sensitive hypertension. Many of these genes had not previously been recognized to be important in hypertension, whereas several genes/pathways known to be involved in hypertension were confirmed. These results should provide an informative source for designing future functional studies in salt-sensitive hypertension.
Identification of gene expression profile in tolerizing murine cardiac allograft by costimulatory blockade
Authors: Matsui Yuichi , Saiura Akio , Sugawara Yasuhiko , Sata Masataka , Naruse Katsutoshi , Yagita Hideo , Kohro Takahide , Mataki Chikage , Izumi Akashi , Yamaguchi Takuhiro , Minami Takashi , Sakihama Toshiko , Ihara Sigeo , Aburatani Hiroyuki , Hamakubo Takao , Kodama Tatsuhiko , Makuuchi Masatoshi
Published: March 2015

The induction of specific tolerance would be the ultimate achievement in transplant immunology, but the precise mechanisms of immunologic tolerance remain largely unknown. Here, we investigated global gene expression analysis in tolerizing murine cardiac allografts by means of oligonucleotide microarrays. Tolerance induction was achieved in cardiac allografts from BALB/c to C57BL/6 mice by daily intraperitoneal injection of anti-CD80 and anti-CD86 monoclonal antibodies (mAbs). Comparative analysis revealed 64 genes to be induced more extensively in the tolerizing than in the syngeneic isografts, and 16 genes than in the rejecting allografts. Two genes were specifically upregulated in the tolerizing allografts. In the tolerizing allografts there were induced marked expressions of a number of genes for pro-inflammatory factors, including interferon-γ-inducible cytokines and chemokines, as well as apoptosis-related genes, which were also upregulated in the rejecting allografts. Moreover, these gene expression patterns continued to be upregulated more than 70 days posttransplant. These results provide evidence that immunologic tolerance can be induced and maintained in the presence of prominent pro-inflammatory gene expression in vivo.
Gene expression tomography
Authors: BROWN VANESSA M. , OSSADTCHI ALEX , KHAN ARSHAD H. , GAMBHIR SANJIV S. , CHERRY SIMON R. , LEAHY RICHARD M. , SMITH DESMOND J.
Published: March 2015

Gene expression tomography, or GET, is a new method to increase the speed of three-dimensional (3-D) gene expression analysis in the brain. The name is evocative of the method’s dual foundations in high-throughput gene expression analysis and computerized tomographic image reconstruction, familiar from techniques such as positron emission tomography (PET) and X-ray computerized tomography (CT). In GET, brain slices are taken using a cryostat in conjunction with axial rotation about independent axes to create a series of “views” of the brain. Gene expression information obtained from the axially rotated views can then be used to recreate 3-D gene expression patterns. GET was used to successfully reconstruct images of tyrosine hydroxylase gene expression in the mouse brain, using both RNase protection and real-time quantitative reverse transcription PCR (QRT-PCR). A Monte-Carlo analysis confirmed the good quality of the GET image reconstruction. By speeding acquisition of gene expression patterns, GET may help improve our understanding of the genomics of the brain in both health and disease.
Abnormal contractile activity and calcium cycling in cardiac myocytes isolated from dmpk knockout mice
Authors: Pall Gurman S. , Johnson Keith J. , Smith Godfrey L.
Published: March 2015

Dysfunction of the gene encoding DMPK (myotonic dystrophy protein kinase) has been implicated in the human neuromuscular disease myotonic dystrophy (DM1). The cardiac features of the disease include progressive conduction defects and ventricular arrhythmias. These defects have been observed in hearts of mice deficient for DMPK function. We have investigated the role of DMPK in the function of ventricular cardiomyocytes using dmpk knockout (KO) mice. A deficit in DMPK caused enhanced basal contractility of single cardiomyocytes and an associated increase in intracellular Ca2+, measured using fura-2. Biochemical measurements indicated hyperphosphorylation of phospholamban (PLB) in KO mice. This suggests increased Ca2+ uptake into the sarcoplasmic reticulum (SR) as the underlying cause of enhanced contractility. This conclusion was supported by the larger amplitude of caffeine-induced Ca2+ release from the SR in KO cardiomyocytes. Concurrent with hyperphosphorylated PLB, the response to isoprenaline was reduced. These observations suggest dmpk has a modulatory role in the control of intracellular Ca2+ concentration in mouse ventricular cardiomyocytes, loss of which may contribute to cardiac dysfunction in DM1.
Heterogeneity of gene expression in human atheroma unmasked using cDNA representational difference analysis
Authors: Tyson Kerry L. , Weissberg Peter L. , Shanahan Catherine M.
Published: March 2015

The rupture of an atherosclerotic plaque can have profound consequences, such as myocardial or cerebrovascular infarction. The complex interactions of vascular smooth muscle cells (VSMCs) with inflammatory and immune cells are thought to contribute to both plaque genesis and stability. Key to our understanding of these processes is the identification of genes expressed in human atheromatous lesions. We have employed cDNA representational difference analysis (RDA) to investigate the differences in gene expression between normal and atherosclerotic human vessels. Thirty-one cDNA clones representing sequences expressed in atheroma were isolated, many of which encoded components of inflammatory and immune pathways. The reciprocal experiment, to identify genes expressed in the healthy vasculature, identified two genes associated with the contractile functions of VSMCs. Semiquantitative RT-PCR analysis of expression of these genes in forty samples, derived from healthy and atheromatous vessels, demonstrated marked heterogeneity of gene expression between lesions, although several of the genes were preferentially expressed in atherosclerotic lesions. In situ hybridization identified subsets of macrophages at sites of neovascularization within the lesion and intimal VSMCs as expressing the disease-associated genes. In conclusion, cDNA RDA is a useful, fast, and efficient technique for studying differential gene expression particularly when clinical material is limiting.
Genomic analysis of alachlor-induced oncogenesis in rat olfactory mucosa
Authors: Genter Mary Beth , Burman Dawn M. , Vijayakumar Soundarapandian , Ebert Cathy L. , Aronow Bruce J.
Published: March 2015

Alachlor induces olfactory mucosal tumors in rats in a highly ordered temporal process. We used GeneChip analysis to test the hypothesis that histological progression and oncogenic transformation are accompanied by gene expression changes that might yield clues as to the molecular pathogenesis of tumor formation. Acute alachlor exposure caused upregulation of matrix metalloproteinases (MMP)-2 and -9, tissue inhibitor of metalloproteinase-1, carboxypeptidase Z, and other genes related to extracellular matrix homeostasis. Heme oxygenase was upregulated acutely and maintained elevated expression. Expression of ebnerin, related to the putative human tumor suppressor gene DMBT1, progressively increased in alachlor-treated olfactory mucosa. Progression from adenomas to adenocarcinoma was correlated with upregulation of genes in the wnt signaling pathway. Activated wnt signaling was confirmed by immunohistochemical localization of β-catenin to nuclei of adenocarcinomas, but not earlier lesions. These observations suggest that initiation and progression of alachlor-induced olfactory mucosal tumors is associated with alterations in extracellular matrix components, induction of oxidative stress, upregulation of ebnerin, and final transformation to a malignant state by wnt pathway activation.
Distinct gene-sex interactions regulate adult rat cardiomyocyte width and length independently
Authors: Boutin-Ganache I. , Picard S. , Deschepper C. F.
Published: March 2015

Wistar-Kyoto (WKY) and WKY-derived hyperactive (WKHA) rats are two genetically-related inbred strains of rats that are both normotensive yet exhibit differences in left ventricular mass (LVM). We had shown previously that cardiomyocytes from male WKHA are wider than that of male WKY, and that there was genetic linkage between LVM and a locus on chromosome 5 (RNO5) in the male progeny of a F2 WKHA/WKY cross. We show here that cardiomyocyte width is linked to the same RNO5 locus in male reciprocal congenic rats derived from WKHA and WKY. Contrary to males, we found no genetic linkage between LVM and the RNO5 locus in female rats. However, ventricular hypertrophy in females might be of a different nature, because cardiomyocytes from female WKHA were shorter than their WKY counterparts (with no difference in width). The RNO5 locus contains that of the natriuretic peptide precursor A (Nppa) gene. In male congenic rats, changes in cardiomyocyte width always correlated with reciprocal changes in the LV concentration of atrial natriuretic factor (ANF, i.e., the peptide product of Nppa). Taken together with other functional data, the small size of the RNO5 locus (∼63 cR) increased the likelihood that both cardiomyocyte width and LV ANF concentration could be linked to only one gene (possibly Nppa) in male rats. Moreover, our results support the notion that genes and sex interact to regulate cardiomyocyte width and length independently from one another.
Proteomic approach to coronary atherosclerosis shows ferritin light chain as a significant marker: evidence consistent with iron hypothesis in atherosclerosis
Authors: You Sun-Ah , Archacki Stephen R. , Angheloiu George , Moravec Christine S. , Rao Shaoqi , Kinter Michael , Topol Eric J. , Wang Qing
Published: March 2015

Coronary artery disease (CAD) is the leading cause of mortality and morbidity in developed nations. We hypothesized that CAD is associated with distinct patterns of protein expression in the coronary arteries, and we have begun to employ proteomics to identify differentially expressed proteins in diseased coronary arteries. Two-dimensional (2-D) gel electrophoresis of proteins and subsequent mass spectrometric analysis identified the ferritin light chain as differentially expressed between 10 coronary arteries from patients with CAD and 7 coronary arteries from normal individuals. Western blot analysis indicated significantly increased expression of the ferritin light chain in the diseased coronary arteries (1.41 vs. 0.75; P = 0.01). Quantitative real-time PCR analysis showed that expression of ferritin light chain mRNA was decreased in diseased tissues (0.70 vs. 1.17; P = 0.013), suggesting that increased expression of ferritin light chain in CAD coronary arteries may be related to increased protein stability or upregulation of expression at the posttranscriptional level in the diseased tissues. Ferritin light chain protein mediates storage of iron in cells. We speculate that increased expression of the ferritin light chain may contribute to pathogenesis of CAD by modulating oxidation of lipids within the vessel wall through the generation of reactive oxygen species. Our results provide in situ proteomic evidence consistent with the “iron hypothesis,” which proposes an association between excessive iron storage and a high risk of CAD. However, it is also possible that the increased ferritin expression in diseased coronary arteries is a consequence, rather than a cause, of CAD.
Upregulation of PKC genes and isozymes in cardiovascular tissues during early stages of experimental diabetes
Authors: Guo Mingzhang , Wu Mack H. , Korompai Ferenc , Yuan Sarah Y.
Published: March 2015

The protein kinase C (PKC) pathway has recently been recognized as an important mechanism in the development of diabetic complications including cardiomyopathy and angiopathy. Although an increase in PKC kinase activity has been detected in the cardiovascular system of diabetic patients and animals, it is unclear whether the same pathological condition alters PKC at the transcriptional and translational levels. In this study we assessed quantitatively the mRNA and protein expression profiles of PKC isozymes in the heart and vascular tissues from streptozotocin-induced diabetic pigs. Partial regions of the porcine PKCα, β1, and β2 mRNAs were sequenced, and real-time RT-PCR assays were developed for PKC mRNA quantification. The results showed a significant increase in the mRNA levels of PKCα, β1, and β2 in the heart at 4–8 wk of diabetes. In concomitance, the PKCβ1 and β2 genes, but not the PKCα gene, were upregulated in the diabetic aorta. Correspondingly, there was a significant increase in the protein expression of PKCα and β2 in the heart and PKCβ2 in the aorta with a time course correlated to that of mRNA expression. In summary, PKCβ2 was significantly upregulated in the heart and aorta at both the transcriptional and translational levels during early stages of experimental diabetes, suggesting that PKCβ2 may be a prominent target of diabetic injury in the cardiovascular system.
Connective molecular pathways of experimental bladder inflammation
Authors: Dozmorov Igor , Saban Marcia R. , Knowlton Nicholas , Centola Michael , Saban Ricardo
Published: March 2015

Inflammation is an inherent response of the organism that permits its survival despite constant environmental challenges. The process normally leads to recovery from injury and to healing. However, if targeted destruction and assisted repair are not properly phased, chronic inflammation can result in persistent tissue damage. To better understand the inflammatory process, we recently introduced a profiling methodology to identify common genes involved in bladder inflammation. The method represents a complementation to the classic quantification of inflammation and provides information regarding the early, intermediate, and late events in gene regulation. However, gene profiling fails to describe the molecular pathways and their interconnections involved in the particular inflammatory response. The present work introduces a new statistical technique for inferring functional interconnections between inflammatory pathways underlying classic models of bladder inflammation and permits the modeling of the inflammatory network. This new statistical method is based on variants of cluster analysis, Boolean networking, differential equations, Bayesian networking, and partial correlation. By applying partial correlation analysis, we developed mosaics of gene expression that permitted a global visualization of common and unique pathways elicited by different stimuli. The significance of these processes was tested from both biological and statistical viewpoints. We propose that connective mosaic may represent the necessary simplification step to visualize cDNA array results.
Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array
Authors: Zhou Xianghong , Krueger James G. , Kao Ming-Chih J. , Lee Ed , Du Fenghe , Menter Alan , Wong Wing Hung , Bowcock Anne M.
Published: March 2015

A global picture of gene expression in the common immune-mediated skin disease, psoriasis, was obtained by interrogating the full set of Affymetrix GeneChips with psoriatic and control skin samples. We identified 1,338 genes with potential roles in psoriasis pathogenesis/maintenance and revealed many perturbed biological processes. A novel method for identifying transcription factor binding sites was also developed and applied to this dataset. Many of the identified sites are known to be involved in immune response and proliferation. An in-depth study of immune system genes revealed the presence of many regulating cytokines and chemokines within involved skin, and markers of dendritic cell (DC) activation in uninvolved skin. The combination of many CCR7+ T cells, DCs, and regulating chemokines in psoriatic lesions, together with the detection of DC activation markers in nonlesional skin, strongly suggests that the spatial organization of T cells and DCs could sustain chronic T-cell activation and persistence within focal skin regions.
Evaluation and applications of radiotelemetry in small laboratory animals
Authors: Kramer Klaas , Kinter Lewis B.
Published: March 2015

Radiotelemetry is the “state of the art” for monitoring physiological functions in awake and freely moving laboratory animals, while minimizing stress artifacts. For researchers, especially those in the fields of pharmacology and toxicology, the technique provides a valuable tool for defining the physiological and pathophysiological consequences derived from advances molecular, cellular, and tissue biology and in predicting the effectiveness and safety of new compounds in humans. There is ample evidence that radiotelemetry systems for measuring physiological functions has been sufficiently validated. Today, the technology is an important tool for collection of a growing number of physiological parameters, for contributing to animal welfare (reduction and refinement alternatives), and for reducing overall animal research costs.
Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion
Authors: de Wit Cor , Roos Frederik , Bolz Steffen-Sebastian , Pohl Ulrich
Published: March 2015

Gap-junctional communication coordinates the behavior of individual cells in arterioles. Gap junctions are formed by connexins 40 (Cx40), Cx43, Cx37, and Cx45 in the vasculature. Previously, we have shown that lack of Cx40 impairs conduction of dilatory signals along arterioles. Herein, we examined whether hypertension is present in conscious animals and whether this is a direct effect or due to secondary mechanisms. Mean arterial pressure was elevated by 20–25 mmHg in conscious Cx40-deficient mice (Cx40−/−) compared with wild-type controls in both sexes. Differences in heart rate were not observed. Blockade of NO synthase increased pressure equally in both genotypes. Conversely, the angiotensin AT1-receptor antagonist, candesartan, decreased pressure to similar extents in Cx40−/− and wild-type mice. Acetylcholine and sodium nitroprusside (0.05–15 nmol) were equally potent and effective in decreasing pressure and inducing dilatory responses in the microcirculation. However, in contrast to wild type, Cx40−/− arterioles exhibited spontaneous, irregular vasomotion leading temporarily to complete vessel closure. We conclude that loss of Cx40 is associated with hypertension independent of the action of angiotensin II. It is also not related to an altered efficacy of NO or other endothelial dilators. However, the observed irregular vasomotion suggests that peripheral vascular resistance is affected.
Evaluation of hypothalamic gene expression in mice divergently selected for heat loss
Authors: Wesolowski Stephanie R. , Allan Mark F. , Nielsen Merlyn K. , Pomp Daniel
Published: March 2015

Mouse lines divergently selected for heat loss were evaluated for correlated responses in the hypothalamic transcriptome. High (MH) heat loss mice have ∼50% greater heat loss, ∼35% less body fat, ∼20% greater feed intake, ∼100% greater locomotor activity levels, and higher core body temperature compared with low (ML) heat loss mice. We evaluated hypothalamic expression between inbred lines derived from MH and ML lines (IH and IL, respectively) using cDNA microarrays and selected genes previously isolated in a large differential-display PCR experiment. Northern analysis was used to confirm differences, revealing higher hypothalamic mRNA expression of oxytocin ( Oxt) and tissue inhibitor of metalloproteinase 2 ( Timp-2) in the IH line. Real-time PCR assays were developed for Oxt, Timp-2, and ribosomal protein L3 ( Rpl3, previously found to be upregulated in IL) and confirmed differential expression of these genes with potential physiological relevance in energy balance. These results provide information on correlated responses in the transcriptome of mice selected for high and low energy expenditure and reveal new information regarding genetic regulation of energy balance.
Cell Junction Dynamics in the Testis: Sertoli-Germ Cell Interactions and Male Contraceptive Development
Authors: Cheng C. Yan , Mruk Dolores D.
Published: March 2015

Spermatogenesis is an intriguing but complicated biological process. However, many studies since the 1960s have focused either on the hormonal events of the hypothalamus-pituitary-testicular axis or morphological events that take place in the seminiferous epithelium. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli-germ cell communication, and junction dynamics. In this review, we discuss the physiology and biology of junction dynamics in the testis, in particular how these events affect interactions of Sertoli and germ cells in the seminiferous epithelium behind the blood-testis barrier. We also discuss how these events regulate the opening and closing of the blood-testis barrier to permit the timely passage of preleptotene and leptotene spermatocytes across the blood-testis barrier. This is physiologically important since developing germ cells must translocate across the blood-testis barrier as well as traverse the seminiferous epithelium during their development. We also discuss several available in vitro and in vivo models that can be used to study Sertoli-germ cell anchoring junctions and Sertoli-Sertoli tight junctions. An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives.
Receptor Protein Tyrosine Phosphatases in Nervous System Development
Authors: Johnson Karl G. , Van Vactor David
Published: March 2015

Receptor protein tyrosine phosphatases (RPTPs) are key regulators of neuronal morphogenesis in a variety of different vertebrate and invertebrate systems, yet the mechanisms by which these proteins regulate central nervous system development are poorly understood. In the past few years, studies have begun to outline possible models for RPTP function by demonstrating in vivo roles for RPTPs in axon outgrowth, guidance, and synaptogenesis. In addition, the crystal structures of several RPTPs have been solved, numerous downstream effectors of RPTP signaling have been identified, and a small number of RPTP ligands have been described. In this review, we focus on how RPTPs transduce signals from the extracellular environment to the cytoplasm, using a detailed comparative analysis of the different RPTP subfamilies. Focusing on the roles RPTPs play in the development of the central nervous system, we discuss how the elucidation of RPTP crystal structures, the biochemical analysis of phosphatase enzyme catalysis, and the characterization of complex signal transduction cascades downstream of RPTPs have generated testable models of RPTP structure and function.
Clinical, Cellular, and Molecular Aspects of Cancer Invasion
Authors: Mareel Marc , Leroy Ancy
Published: March 2015

Invasion causes cancer malignancy. We review recent data about cellular and molecular mechanisms of invasion, focusing on cross-talk between the invaders and the host. Cancer disturbs these cellular activities that maintain multicellular organisms, namely, growth, differentiation, apoptosis, and tissue integrity. Multiple alterations in the genome of cancer cells underlie tumor development. These genetic alterations occur in varying orders; many of them concomitantly influence invasion as well as the other cancer-related cellular activities. Examples discussed are genes encoding elements of the cadherin/catenin complex, the nonreceptor tyrosine kinase Src, the receptor tyrosine kinases c-Met and FGFR, the small GTPase Ras, and the dual phosphatase PTEN. In microorganisms, invasion genes belong to the class of virulence genes. There are numerous clinical and experimental observations showing that invasion results from the cross-talk between cancer cells and host cells, comprising myofibroblasts, endothelial cells, and leukocytes, all of which are themselves invasive. In bone metastases, host osteoclasts serve as targets for therapy. The molecular analysis of invasion-associated cellular activities, namely, homotypic and heterotypic cell-cell adhesion, cell-matrix interactions and ectopic survival, migration, and proteolysis, reveal branching signal transduction pathways with extensive networks between individual pathways. Cellular responses to invasion-stimulatory molecules such as scatter factor, chemokines, leptin, trefoil factors, and bile acids or inhibitory factors such as platelet activating factor and thrombin depend on activation of trimeric G proteins, phosphoinositide 3-kinase, and the Rac and Rho family of small GTPases. The role of proteolysis in invasion is not limited to breakdown of extracellular matrix but also causes cleavage of proinvasive fragments from cell surface glycoproteins.
α-2-Macroglobulin in Saliva Is Associated with Glycemic Control in Patients with Type 2 Diabetes Mellitus
Authors: Aitken Juan Pablo , Ortiz Carolina , Morales-Bozo Irene , Rojas-Alcayaga Gonzalo , Baeza Mauricio , Beltran Caroll , Escobar Alejandro
Published: March 2015

Background. Subjects with type 2 diabetes mellitus (DM2) require an adequate glycemic control to avoid diabetic complications. Currently, saliva biomarkers are used as a diagnostic tool and can be indicative of the degree of progression and control of various diseases. Several studies indicate thatα-2-macroglobulin levels are elevated in diabetic patients.Methods. 120 subjects with DM2 were enrolled and classified into two groups according to their glycemic control (percentage of glycated hemoglobin-A1c (HbA1c), <7% adequate glycemic control group; >7% inadequate glycemic control group). The relationship betweenα-2-macroglobulin levels from saliva samples and HbA1c was subsequently evaluated.Results. We found a positive correlation betweenα-2-macroglobulin and HbA1c (r=0.778andP<0.0001). Area under the receivers operating characteristic (ROC) curve ofα-2-macroglobulin indicated a positive discrimination threshold ofα-2-macroglobulin (AUC = 0.903, CI 95%: 0.847–0.959,P<0.0001) to diagnose glycemic control.Conclusions. Our data strongly suggest that the level of salivaα-2-macroglobulin is an indicator for the degree of glycemic control in diabetic patients and represents a promising alternative method to evaluate this parameter.
Electroacupuncture Treatment Improves Learning-Memory Ability and Brain Glucose Metabolism in a Mouse Model of Alzheimer’s Disease: Using Morris Water Maze and Micro-PET
Authors: Jiang Jing , Gao Kai , Zhou Yuan , Xu Anping , Shi Suhua , Liu Gang , Li Zhigang
Published: March 2015

Introduction. Alzheimer’s disease (AD) causes progressive hippocampus dysfunctions leading to the impairment of learning and memory ability and low level of uptake rate of glucose in hippocampus. What is more, there is no effective treatment for AD. In this study, we evaluated the beneficial and protective effects of electroacupuncture in senescence-accelerated mouse prone 8 (SAMP8).Method. In the electroacupuncture paradigm, electroacupuncture treatment was performed once a day for 15 days on 7.5-month-old SAMP8 male mice. In the normal control paradigm and AD control group, 7.5-month-old SAMR1 male mice and SAMP8 male mice were grabbed and bandaged while electroacupuncture group therapy, in order to ensure the same treatment conditions, once a day, 15 days.Results. From the Morris water maze (MWM) test, we found that the treatment of electroacupuncture can improve the spatial learning and memory ability of SAMP8 mouse, and from the micro-PET test, we proved that after the electroacupuncture treatment the level of uptake rate of glucose in hippocampus was higher than normal control group.Conclusion. These results suggest that the treatment of electroacupuncture may provide a viable treatment option for AD.
Understanding Transferable Supply Chain Lessons and Practices to a “High‐Tech” Industry Using Guidelines from a Primary Sector Industry: A Case Study in the Food Industry Supply Chain
Authors: Coronado Mondragon Adrian E. , Coronado Mondragon Christian E. , Coronado Etienne S.
Published: March 2015

Flexibility and innovation at creating shapes, adapting processes, and modifying materials characterize composites materials, a “high‐tech” industry. However, the absence of standard manufacturing processes and the selection of materials with defined properties hinder the configuration of the composites materials supply chain. An interesting alternative for a “high‐tech” industry such as composite materials would be to review supply chain lessons and practices in “low‐tech” industries such as food. The main motivation of this study is to identify lessons and practices that comprise innovations in the supply chain of a firm in a perceived “low‐tech” industry that can be used to provide guidelines in the design of the supply chain of a “high‐tech” industry, in this case composite materials. This work uses the case study/site visit with analogy methodology to collect data from a Spanish leading producer of fresh fruit juice which is sold in major European markets and makes use of a cold chain. The study highlights supply base management and visibility/traceability as two elements of the supply chain in a “low‐tech” industry that can provide guidelines that can be used in the configuration of the supply chain of the composite materials industry.
Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy
Authors: Prea Selwyn M. , Chan Elsa C. , Dusting Gregory J. , Vingrys Algis J. , Bui Bang V. , Liu Guei-Sheung
Published: March 2015

Age-related macular degeneration (AMD) is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or “wet”) form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF). However, the long-term success of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration (usually monthly), potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins.
Soft Sensor for Oxide Scales on the Steam Side of Superheater Tubes under Uneven Circumferential Load
Authors: Li Qing Wei , Yao Gui Huan
Published: March 2015

A soft sensor for oxide scales on the steam side of superheater tubes of utility boiler under uneven circumferential loading is proposed for the first time. First finite volume method is employed to simulate oxide scales growth temperature on the steam side of superheater tube. Then appropriate time and spatial intervals are selected to calculate oxide scales thickness along the circumferential direction. On the basis of the oxide scale thickness, the stress of oxide scales is calculated by the finite element method. At last, the oxide scale thickness and stress sensors are established on support vector machine (SMV) optimized by particle swarm optimization (PSO) with time and circumferential angles as inputs and oxide scale thickness and stress as outputs. Temperature and stress calculation methods are validated by the operation data and experimental data, respectively. The soft sensor is applied to the superheater tubes of some power plant. Results show that the soft sensor can give enough accurate results for oxide scale thickness and stress in reasonable time. The forecasting model provides a convenient way for the research of the oxide scale failure.
Improvement in Overall Survival from Extremity Soft Tissue Sarcoma over Twenty Years
Authors: Jacobs Andrew J. , Michels Ryan , Stein Joanna , Levin Adam S.
Published: March 2015

Several patient demographic factors, including marital status, have been demonstrated to have prognostic significance for survival in extremity soft tissue sarcoma (ESTS). A study population of 12,546 adult patients diagnosed with ESTS from 1991 to 2010 was identified from the SEER database, a large population-based registry, in order to determine whether overall survival had changed over this recent 20-year period. The study population was divided into three groups by year of diagnosis: 1991–1996, 1997–2003, and 2004–2010. We used the Kaplan-Meier method and Cox proportional hazards regression to assess survival differences between different demographic groups and prognostic clinical characteristics. Over the course of time, the 5-year overall survival rates have increased from 28% in the earliest time period to 62% in the latest(P<0.0001). On multivariate analysis, the mortality rate progressively declined from the 1991–1996 group (HR: 3.02, CI: 2.78–3.29) to the 1997–2003 group (HR: 2.21, CI: 2.06–2.37), with the 2004–2010 group having the best overall survival, despite increases in the proportion of patients with tumors greater than 5 cm in size(P<0.0001), and those presenting with metastasis(P<0.0001).
Traffic Speed Data Imputation Method Based on Tensor Completion
Authors: Ran Bin , Tan Huachun , Feng Jianshuai , Liu Ying , Wang Wuhong
Published: March 2015

Traffic speed data plays a key role in Intelligent Transportation Systems (ITS); however, missing traffic data would affect the performance of ITS as well as Advanced Traveler Information Systems (ATIS). In this paper, we handle this issue by a novel tensor-based imputation approach. Specifically, tensor pattern is adopted for modeling traffic speed data and then High accurate Low Rank Tensor Completion (HaLRTC), an efficient tensor completion method, is employed to estimate the missing traffic speed data. This proposed method is able to recover missing entries from given entries, which may be noisy, considering severe fluctuation of traffic speed data compared with traffic volume. The proposed method is evaluated on Performance Measurement System (PeMS) database, and the experimental results show the superiority of the proposed approach over state-of-the-art baseline approaches.
Fe-Based Amorphous Composite Coating Prepared by Plasma Remelting
Authors: Li Zhisheng , Liu Zongde , Wang Yongtian , Liu Shunv , Jiang Runsen , Wang Yang
Published: March 2015

Fe-based amorphous composite coating was deposited on the carbon steel substrate by arc spraying and then remelted by a plasma remelting system, in order to improve the mechanical properties of the coatings. The composition, microstructure, and properties of the composite coating were analyzed by means of the metallographic microscope, scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), and microhardness tester. The results showed that the amorphous composite coatings had more homogeneous and finer microstructure after the plasma remelting. The coating is metallurgically bonded with the substrate, and the hardness of the Fe-based amorphous composite coating is up to 1220 HV. The internal relationship between microhardness and microstructure has been discussed.
Gene Network Exploration of Crosstalk between Apoptosis and Autophagy in Chronic Myelogenous Leukemia
Authors: Wang Fengfeng , Cho William C. S. , Chan Lawrence W. C. , Wong S. C. Cesar , Tsui Nancy B. Y. , Siu Parco M. , Yip S. P. , Yung Benjamin Y. M.
Published: March 2015

Background. Gene expression levels change to adapt the stress, such as starvation, toxin, and radiation. The changes are signals transmitted through molecular interactions, eventually leading to two cellular fates, apoptosis and autophagy. Due to genetic variations, the signals may not be effectively transmitted to modulate apoptotic and autophagic responses. Such aberrant modulation may lead to carcinogenesis and drug resistance. The balance between apoptosis and autophagy becomes very crucial in coping with the stress. Though there have been evidences illustrating the apoptosis-autophagy interplay, the underlying mechanism and the participation of the regulators including transcription factors (TFs) and microRNAs (miRNAs) remain unclear.Results. Gene network is a graphical illustration for exploring the functional linkages and the potential coordinate regulations of genes. Microarray dataset for the study of chronic myeloid leukemia was obtained from Gene Expression Omnibus. The expression profiles of those genes related to apoptosis and autophagy, including MCL1, BCL2, ATG, beclin-1, BAX, BAK, E2F, cMYC, PI3K, AKT, BAD, and LC3, were extracted from the dataset to construct the gene networks.Conclusion. The network analysis of these genes explored the underlying mechanisms and the roles of TFs and miRNAs for the crosstalk between apoptosis and autophagy.
Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury
Authors: Zhang Wei , Gao Yuan , Zhou Yan , Liu Jianheng , Zhang Licheng , Long Anhua , Zhang Lihai , Tang Peifu
Published: March 2015

Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degradedin vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Bothin vitroandin vivorelease assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery.
Thermal Tomography Imaging in Photonic Traditional Chinese Medicine Information Therapy with Holistic Effect for Health Whole Nursing
Authors: Ye Binggang , Guo Zhouyi , Huang Hanchuan , Yang Xicheng
Published: March 2015

A photonic traditional Chinese medicine (TCM) information therapy was developed that has applications in whole health nursing including the prevention and treatment of ischemic cardiovascular and cerebrovascular diseases as well as the conditioning of the subhealth state. This therapy utilizes the beam of a 630 nm LED light to irradiate the oropharynx, while simultaneously employing two beams of 650 nm LED light to irradiate corresponding acupuncture points resulting in a synergistic outcome. This method was named “1 + 2 phototherapy.” The principle mechanism of the therapy is a series of photon induced biological effects that are triggered by stimulating the photosensitive tissues of the oropharynx. This tissue includes the oral mucosa, capillaries, lymph nodes, saliva glands, nerves, and Jingluo and is stimulated by light beams of certain photon energy and imitative acupuncture information. Thermal tomography imaging shows that the average temperature of the upper-body was improved significantly after oropharyngeal irradiation under irradiation of “Futu point”: the heat radiation of the spine, as well as chest, shoulders, arms, and clavicle, increased under irradiation of “Hoku,” whereas the overall average temperature was below the temperature before irradiation. The experiment indicates that this therapy can promote blood circulation, regulate varied physiological parameters, and have holistic effects in whole health nursing.