bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypoxia induces different genes in the lungs of rats compared with mice
Authors: Hoshikawa Yasushi , Nana-Sinkam Patrick , Moore Mark D. , Sotto-Santiago Sylk , Phang Tzulip , Keith Robert L. , Morris Kenneth G. , Kondo Takashi , Tuder Rubin M. , Voelkel Norbert F. , Geraci Mark W.
Published: March 2015

Different animal species have a varying response to hypoxia. Mice develop less pulmonary artery thickening after chronic hypoxia exposure than rats. We hypothesized that the lung tissue gene expression pattern displayed in hypoxic rats would differ from that of hypoxic mice. We exposed Sprague-Dawley rats and C57BL/6 mice to both 1 and 3 wk of hypobaric hypoxia. Although both species developed pulmonary hypertension, mice showed less pulmonary vascular remodeling than rats. Microarray gene analysis demonstrated a distinct pattern of gene expression between mice and rats when exposed to hypoxic conditions. In addition, some genes appeared to be more responsive at an earlier time point of 1 wk of hypoxia. Hypoxic conditions in the rat induce genes involved in endothelial cell proliferation, repression of apoptosis, and vasodilation. Mice exposed to hypoxic conditions decrease the expression of genes involved in vasodilation and in endothelial cell proliferation. Although we cannot determine whether the differential expression of genes during chronic hypoxia is cause or consequence of the differential pulmonary vascular remodeling, we propose that a balance between over- and under-expression of a selective group of genes may be responsible for lung vascular remodeling and vascular tone control.
Lifelong voluntary exercise in the mouse prevents age-related alterations in gene expression in the heart
Authors: Bronikowski A. M. , Carter P. A. , Morgan T. J. , Garland T. , Ung N. , Pugh T. D. , Weindruch R. , Prolla T. A.
Published: March 2015

We present the first quantitative gene expression analysis of cardiac aging under conditions of sedentary and active lifestyles using high-density oligonucleotide arrays representing 11,904 cDNAs and expressed sequence tags (ESTs). With these data, we test the hypothesis that exercise attenuates the gene expression changes that normally occur in the aging heart. Male mice ( Mus domesticus) were sampled from the 16th generation of selective breeding for high voluntary exercise. For the selective breeding protocol, breeders were chosen based on the maximum number of wheel revolutions run on days 5 and 6 of a test at 8 wk of age. For the colony sampled herein, mice were housed individually over their entire lifetimes (from weaning) either with or without access to running wheels. The hearts of these two treatment groups (active and sedentary) were assayed at middle age (20 mo) and old age (33 mo). Genes significantly affected by age in the hearts of the sedentary population by at least a 50% expression change ( n = 137) were distributed across several major categories, including inflammatory response, stress response, signal transduction, and energy metabolism. Genes significantly affected by age in the active population were fewer ( n = 62). Of the 42 changes in gene expression that were common to both treatment groups, 32 (72%) displayed smaller fold changes as a result of exercise. Thus exercise offset many age-related gene expression changes observed in the hearts of the sedentary animals. These results suggest that adaptive physiological mechanisms that are induced by exercise can retard many effects of aging on heart muscle at the transcriptional level.
Transcriptional adaptations of lipid metabolism in tibialis anterior muscle of endurance-trained athletes
Authors: Schmitt Beat , Flück Martin , Décombaz Jacques , Kreis Roland , Boesch Chris , Wittwer Matthias , Graber Franziska , Vogt Michael , Howald Hans , Hoppeler Hans
Published: March 2015

It was hypothesized that transcriptional reprogramming is involved in the structural and functional adaptations of lipid metabolism in human tibialis anterior muscle (TA) from endurance-trained male subjects. RT-PCR experiments demonstrated a significant upregulation of the mRNA level of key enzymes involved in 1) lipolytic mobilization of fatty acids (FA) from intramyocellular lipid (IMCL) stores via hormone-sensitive lipase (LIPE), 2) intramyocellular FA transport via muscle fatty acid binding protein (FABP3), and 3) oxidative phosphorylation (cytochrome c oxidase I, COI), in TA of endurance-trained vs. untrained subjects. In contrast, mRNAs for factors involved in glycolysis (muscle 6-phosphofructokinase, PFKM), intramyocellular storage of FA (diacylglycerol O-acyltransferase 1, DGAT), and β-oxidation (long-chain acyl-coenzyme A dehydrogenase, ACADL) were invariant between TA of trained and untrained subjects. Correlation analysis identified an association of LIPE with FABP3 and LPL (lipoprotein lipase) mRNA levels and indicated coregulation of the transcript level for LIPE, FABP3, and COI with the level of mRNA encoding peroxisome proliferator-activated receptor-α (PPAR-α), the master regulator of lipid metabolism. Moreover, a significant correlation existed between LPL mRNA and the absolute rate of IMCL repletion determined by magnetic resonance spectroscopy after exhaustive exercise. Additionally, the LIPE mRNA level correlated with ultrastructurally determined IMCL content and mitochondrial volume density. The present data point to a training-induced, selective increase in mRNA levels of enzymes which are involved in metabolization of intramuscular FA, and these data confirm the well-established phenomenon of enhanced lipid utilization during exercise at moderate intensity in muscles of endurance-trained subjects.
Cation channel regulation by COOH-terminal cytoplasmic tail of polycystin-1: mutational and functional analysis
Authors: Vandorpe David H. , Wilhelm Sabine , Jiang Lianwei , Ibraghimov-Beskrovnaya Oxana , Chernova Marina N. , Stuart-Tilley Alan K. , Alper Seth L.
Published: March 2015

Polycystin-1 (PKD1) mutations account for ∼85% of autosomal dominant polycystic kidney disease (ADPKD). We have shown previously that oocyte surface expression of a transmembrane fusion protein encoding part of the cytoplasmic COOH terminus of PKD1 increases activity of a Ca2+-permeable cation channel. We show here that human ADPKD mutations incorporated into this fusion protein attenuated or abolished encoded cation currents. Point mutations and truncations showed that cation current expression requires integrity of a region encompassing the putative coiled coil domain of the PKD1 cytoplasmic tail. Whereas these loss-of-function mutants did not exhibit dominant negative phenotypes, coexpression of a fusion protein expressing the interacting COOH-terminal cytoplasmic tail of PKD2 did suppress cation current. Liganding of the ectodomain of the PKD1 fusion protein moderately activated cation current. The divalent cation permeability and pharmacological profile of the current has been extended. Inducible expression of the PKD1 fusion in EcR-293 cells was also associated with activation of cation channels and increased Ca2+entry.
Familial hypertrophic cardiomyopathy mutations in troponin I (K183Δ, G203S, K206Q) enhance filament sliding
Authors: Köhler Jan , Chen Ying , Brenner Bernhard , Gordon Albert M. , Kraft Theresia , Martyn Donald A. , Regnier Michael , Rivera Anthony J. , Wang Chien-Kao , Chase P. Bryant
Published: March 2015

A major cause of familial hypertrophic cardiomyopathy (FHC) is dominant mutations in cardiac sarcomeric genes. Linkage studies identified FHC-related mutations in the COOH terminus of cardiac troponin I (cTnI), a region with unknown function in Ca2+regulation of the heart. Using in vitro assays with recombinant rat troponin subunits, we tested the hypothesis that mutations K183Δ, G203S, and K206Q in cTnI affect Ca2+regulation. All three mutants enhanced Ca2+sensitivity and maximum speed ( smax) of filament sliding of in vitro motility assays. Enhanced smax(pCa 5) was observed with rabbit skeletal and rat cardiac (α-MHC or β-MHC) heavy meromyosin (HMM). We developed a passive exchange method for replacing endogenous cTn in permeabilized rat cardiac trabeculae. Ca2+sensitivity and maximum isometric force did not differ between preparations exchanged with cTn(cTnI,K206Q) or wild-type cTn. In both trabeculae and motility assays, there was no loss of inhibition at pCa 9. These results are consistent with COOH terminus of TnI modulating actomyosin kinetics during unloaded sliding, but not during isometric force generation, and implicate enhanced cross-bridge cycling in the cTnI-related pathway(s) to hypertrophy.
Microsatellite variation associated with prolactin expression and growth of salt-challenged tilapia
Authors: Streelman J. T. , Kocher T. D.
Published: March 2015

Biologists have long argued that runs of alternating purines and pyrimidines could form alternative DNA structures, which might regulate transcription. Here, we report that simple sequence repeat polymorphisms in the tilapia prolactin 1 ( prl 1) promoter are associated with differences in prl 1 gene expression and the growth response of salt-challenged fishes. Individuals homozygous for long microsatellite alleles express less prl 1 in fresh water but more prl 1 in half-seawater than fishes with other genotypes. Our work provides the first in vivo evidence that differences in microsatellite length among individuals may indeed affect gene expression and that variance in expression has concomitant physiological consequences. These results suggest that dinucleotide microsatellites represent an under-appreciated source of genetic variation for regulatory evolution.
Hyperphagia, not hypometabolism, causes early onset obesity in melanocortin-4 receptor knockout mice
Authors: Weide Karin , Christ Nicole , Moar Kim M. , Arens Janine , Hinney Anke , Mercer Julian G. , Eiden Sandra , Schmidt Ingrid
Published: March 2015

Previous studies on mice with melanocortin-4 receptor gene ( MC4r) knockout have focused on obese adults. Because humans with functional MC4r mutations show early-onset obesity, we determined the onset of excessive fat deposition in 10- to 56-day-old mice, taking into account sex and litter influences. Total body fat content of MC4r−/−on day 35 and MC4r+/−on day 56 significantly exceeds that of MC4r+/+. Plasma leptin levels increase in proportion to fat mass. According to cumulative food intake and energy expenditure measurements from day 21 to 35, onset of excessive fat deposition in MC4r−/−is fueled by hyperphagia and counteracted partially by hypermetabolism. In 35- to 56-day-old mice, arcuate nucleus neuropeptide Y (NPY) mRNA decreases and pro-opiomelanocortin (POMC) mRNA increases with fat content and plasma leptin levels independently of genotype. Taking into account fat content by ANCOVA reveals, however, increases in both NPY mRNA and POMC mRNA due to melanocortin-4 receptor (MC4R) deficiency. We conclude that hyperphagia, not hypometabolism, is the primary disturbance initiating excessive fat deposition in MC4R-deficient mice at weaning and that the overall changes in NPY and POMC expression tend to antagonize the onset of excessive fat deposition.
Quantitative assessment of the importance of dye switching and biological replication in cDNA microarray studies
Authors: Liang Mingyu , Briggs Amy G. , Rute Elizabeth , Greene Andrew S. , Cowley Allen W.
Published: March 2015

Dye switching and biological replication substantially increase the cost and the complexity of cDNA microarray studies. The objective of the present analysis was to quantitatively assess the importance of these procedures to provide a quantitative basis for decision-making in the design of microarray experiments. Taking advantage of the unique characteristics of a published data set, the impact of these procedures on the reliability of microarray results was calculated. Adding a second microarray with dye switching substantially increased the correlation coefficient between observed and predicted ln(ratio) values from 0.38 ± 0.06 to 0.62 ± 0.04 ( n = 12) and the outlier concordance from 21 ± 3% to 43 ± 4%. It also increased the correlation with the entire set of microarrays from 0.60 ± 0.04 to 0.79 ± 0.04 and the outlier concordance from 31 ± 6% to 58 ± 5% and tended to improve the correlation with Northern blot results. Adding a second microarray to include biological replication also improved the performance of these indices but often to a lesser degree. Inclusion of both procedures in the second microarray substantially improved the consistency with the entire set of microarrays but had minimal effect on the consistency with predicted results. Analysis of another data set generated using a different cDNA labeling method also supported a significant impact of dye switching. In conclusion, both dye switching and biological replication substantially increased the reliability of microarray results, with dye switching likely having even greater benefits. Recommendations regarding the use of these procedures were proposed.
The angiotensin II receptor (Agtr1a): functional regulatory polymorphisms in a locus genetically linked to blood pressure variation in the mouse
Authors: Wong Clifford , Mahapatra Nitish R. , Chitbangonsyn Surin , Mahboubi Payam , Mahata Manjula , Mahata Sushil K. , O'Connor Daniel T.
Published: March 2015

Hypertension is a complex trait with multiple genetic determinants. A previous genome-wide linkage study of systolic blood pressure in a mouse genetic backcross implicated a region of chromosome 13 (LOD = 3.3 at 16.0 cM) as a determinant of blood pressure differences between a hereditary low blood pressure strain of Mus musculus (BPL/1) and Mus spretus (SPRET); at this locus, the unexpected effect of the BPL/1 allele was to increase blood pressure. A plausible candidate locus encoding angiotensin II receptor isoform 1a (Agtr1a) is also located at 16.0 cM on chromosome 13. We therefore investigated structural and functional differences at Agtr1a between BPL/1 and SPRET, as well as the BPH/2 strain. Resequencing Agtr1a in the three strains established the exon/intron and proximal promoter structure of the mouse gene. Coding exon 3 spanned 1,960 bp (with 26 SNPs), including the 1,077-bp/359-amino acid ORF (with 5 cSNPs, all of which were synonymous). Promoter sequences revealed a consensus TATA box, conserved G/C-rich regions, and a striking, lengthy simple sequence repeat region, composed of di-, tri-, tetra-, and penta-nucleotide repeats, whose overall length varied markedly among the strains. Twenty-five other SNPs and three single nucleotide deletions differentiated the strains’ promoters, six of which were in likely functional promoter motifs. Agtr1a mRNA abundance in the adrenal gland in vivo was greater ( P < 0.05) in BPL/1 than SPRET, consistent with the predicted effect of the BPL/1 allele to confer higher blood pressure. When Agtr1a promoters were subcloned into luciferase reporter plasmids and transfected into PC12 chromaffin cells, basal promoter expression was higher ( P < 0.001) in BPL/1 than in SPRET, consistent with the endogenous mRNA results. In summary, Agtr1a on chromosome 13 is highly polymorphic between mouse strains, although the amino acid sequence specified by the ORF is invariant, even across mouse species. We conclude that polymorphisms in the Agtr1a promoter account for differences in gene expression in vivo between BPL/1 and SPRET, in a way consistent with the effects of alleles at this locus on chromosome 13 to affect blood pressure in the mouse genome-wide linkage study.
HIF-1 is required for heat acclimation in the nematode Caenorhabditis elegans
Authors: Treinin Millet , Shliar Judith , Jiang Huaqi , Powell-Coffman Jo Anne , Bromberg Zohar , Horowitz Michal
Published: March 2015

Chronic exposure to environmental heat improves tolerance via heat acclimation (AC). Our previous data on mammals indicate that reprogramming the expression of genes coding for stress proteins and energy-metabolism enzymes plays a major role. Knowledge of pathways leading to AC is limited. For their identification, we established a Caenorhabditis elegans AC model and tested mutants in which signaling pathways pertinent to acclimatory responses are mutated. AC attained by maintaining adult C. elegans at 25°C for 18 h enhanced heat endurance of wild-type worms subjected to heat stress (35°C) and conferred protection against hypoxia and cadmium. Survival curves demonstrated that both daf-2 (insulin receptor pathway) showing enhanced heat tolerance and daf-16 loss-of-function (a transcription factor mediating DAF-2 signaling) mutants benefit from AC, suggesting that the insulin receptor pathway does not mediate AC. In contrast, the hif-1 (hypoxia inducible factor) loss-of-function strain did not show acclimation, and non-acclimated vhl-1 and egl-9 mutants (overexpressing HIF-1) had greater heat endurance than the wild type. Like mammals, HIF-1 and HSP72 levels increased in the wild-type AC nematodes. HSP72 upregulation in AC hif-1 mutants was also observed; however, it was insufficient to improve heat/stress tolerance, suggesting that HIF-1 upregulation is essential for acclimation, whereas HSP72 upregulation in the absence of HIF-1 is inadequate. We conclude that HIF-1 upregulation is both an evolutionarily conserved and a necessary component of heat acclimation. The known targets of HIF-1 imply that metabolic adaptations are essential for AC-dependent tolerance to heat and heavy metals, in addition to their known role in hypoxic adaptation.
Identification of endothelial cell genes by combined database mining and microarray analysis
Authors: Ho Michael , Yang Eugene , Matcuk George , Deng David , Sampas Nick , Tsalenko Anya , Tabibiazar Raymond , Zhang Ying , Chen Mary , Talbi Said , Ho Yen Dong , Wang James , Tsao Philip S. , Ben-Dor Amir , Yakhini Zohar , Bruhn Laurakay , Quertermous Thomas
Published: March 2015

Vascular endothelial cells maintain the interface between the systemic circulation and soft tissues and mediate critical processes such as inflammation in a vascular bed-selective fashion. To expand our understanding of the genetic pathways that underlie these specific functions, we have focused on the identification of novel genes that are differentially expressed in all endothelial cells, as well as restricted groups of this cell type. Virtual subtraction was conducted employing gene expression data deposited in public databases and 384 genes identified.11 The microarray data derived through these experiments have been deposited in the GEO expression database at the NCBI and has been given the accession number GPL217 , with others pending. Primary data and supplementary material associated with this manuscript are being deposited at the following website: http://quertermous.stanford.edu . These genes were spotted on custom microarrays, along with 288 genes identified through subtraction cloning from TGF-β-stimulated endothelial cells. Arrays were evaluated with RNA samples representing endothelial cells cultured from four vascular sources and five non-endothelial cell types. These studies identified 64 pan-endothelial markers that were differentially expressed with at least a threefold difference (range 3- to 55-fold). In addition, differences in gene expression profiles among endothelial cells from different vascular beds were identified. Validation of these findings was performed by RNA blot expression studies, and a number of the novel genes were shown to be expressed under angiogenic conditions in the developing mouse embryo. The combined tools of database mining and transcriptional profiling thus provide expanded knowledge of endothelial cell gene expression and endothelial cell biology.
Cardiac Chamber Formation: Development, Genes, and Evolution
Authors: MOORMAN ANTOON F. M. , CHRISTOFFELS VINCENT M.
Published: March 2015

Moorman, Antoon F. M., and Vincent M. Christoffels. Cardiac Chamber Formation: Development, Genes, and Evolution. Physiol Rev 83: 1223-1267, 2003; 10.1152/physrev.00006.2003.—Concepts of cardiac development have greatly influenced the description of the formation of the four-chambered vertebrate heart. Traditionally, the embryonic tubular heart is considered to be a composite of serially arranged segments representing adult cardiac compartments. Conversion of such a serial arrangement into the parallel arrangement of the mammalian heart is difficult to understand. Logical integration of the development of the cardiac conduction system into the serial concept has remained puzzling as well. Therefore, the current description needed reconsideration, and we decided to evaluate the essentialities of cardiac design, its evolutionary and embryonic development, and the molecular pathways recruited to make the four-chambered mammalian heart. The three principal notions taken into consideration are as follows. 1) Both the ancestor chordate heart and the embryonic tubular heart of higher vertebrates consist of poorly developed and poorly coupled “pacemaker-like” cardiac muscle cells with the highest pacemaker activity at the venous pole, causing unidirectional peristaltic contraction waves. 2) From this heart tube, ventricular chambers differentiate ventrally and atrial chambers dorsally. The developing chambers display high proliferative activity and consist of structurally well-developed and well-coupled muscle cells with low pacemaker activity, which permits fast conduction of the impulse and efficacious contraction. The forming chambers remain flanked by slowly proliferating pacemaker-like myocardium that is temporally prevented from differentiating into chamber myocardium. 3) The trabecular myocardium proliferates slowly, consists of structurally poorly developed, but well-coupled, cells and contributes to the ventricular conduction system. The atrial and ventricular chambers of the formed heart are activated and interconnected by derivatives of embryonic myocardium. The topographical arrangement of the distinct cardiac muscle cells in the forming heart explains the embryonic electrocardiogram (ECG), does not require the invention of nodes, and allows a logical transition from a peristaltic tubular heart to a synchronously contracting four-chambered heart. This view on the development of cardiac design unfolds fascinating possibilities for future research.
Unique Structural Features That Influence Neutrophil Emigration Into the Lung
Authors: Burns Alan R. , Smith C. Wayne , Walker David C.
Published: March 2015

Neutrophil emigration in the lung differs substantially from that in systemic vascular beds where extravasation occurs primarily through postcapillary venules. Migration into the alveolus occurs directly from alveolar capillaries and appears to progress through a sequence of steps uniquely influenced by the cellular anatomy and organization of the alveolar wall. The cascade of adhesive and stimulatory events so critical to the extravasation of neutrophils from postcapillary venules in many tissues is not evident in this setting. Compelling evidence exists for unique cascades of biophysical, adhesive, stimulatory, and guidance factors that arrest neutrophils in the alveolar capillary bed and direct their movement through the endothelium, interstitial space, and alveolar epithelium. A prominent path accessible to the neutrophil appears to be determined by the structural interactions of endothelial cells, interstitial fibroblasts, as well as type I and type II alveolar epithelial cells.
Survey of Accepted Practice following Failed Intubation for Emergency Caesarean Delivery
Authors: Soltanifar Daniel , Bogod David , Harrison Sally , Carvalho Brendan , Sultan Pervez
Published: March 2015

Background. There is no consensus on the optimum management of failed tracheal intubation in emergency cesarean delivery performed for fetal compromise. The decision making process on whether to wake the patient or continue anesthesia with a supraglottic airway device is an underexplored area. This survey explores perceptions and experiences of obstetric anesthetists managing failed intubation.Methods. Anesthetists attending the Group of Obstetric Anaesthetists London (GOAL) Meeting in April 2014 were surveyed.Results. Ninety-three percent of anesthetists surveyed would not always wake the patient in the event of failed intubation for emergency cesarean delivery performed for fetal compromise. The median (interquartile range) of perceived acceptability of continuing anesthesia with a well-fitting supraglottic airway device, assessed using a visual analogue scale (0–100; 0 completely unacceptable; 100 completely acceptable), was 90 [22.5]. Preoperative patient consent regarding the use of a supraglottic airway device for surgery in the event of failed intubation would affect the decision making of 40% of anaesthetists surveyed.Conclusion. These results demonstrate that a significant body of anesthetists with a subspecialty interest in obstetric anesthesia in the UK would not always wake up the patient and would continue with anesthesia and surgery with a supraglottic airway device in this setting.
FDTD Modelling of Silver Nanoparticles Embedded in Phase Separation Interface of H‐PDLC
Authors: Gui Kun , Zheng Jihong , Wang Kangni , Li Daoping , Zhuang Songlin
Published: March 2015

We report localized surface plasmon resonance (LSPR) of silver nanoparticles (NPs) embedded in interface of phase separation of holographic polymer‐dispersed liquid crystal (H‐PDLC) gratings using Finite‐Difference Time Domain method. We show that silver NPs exhibit double resonance peak at the interface, and these peaks are influenced by the angle of incident light. We observe a blue shift of the wavelength of resonance peak as the incident angle increases. However, the location of silver NPs at the interface has nearly no effect on the wavelength of resonance peak. Also we show near‐field and far‐field properties surrounding silver NPs and find that field distribution can be controlled through rotation of incident angle. Therefore, LSPR properties of silver NPs within H‐PDLC gratings can be excited by appropriate wavelength and angle of the incident light.
Frequency Resource Sharing and Allocation Scheme Based on Coalition Formation Game in Hybrid D2D-Cellular Network
Authors: Ou Qing , Zhang Rongqing , Luan Xi , Cheng Yuxin , Wu Jun , Wu Jianjun
Published: March 2015

A distributed cooperation scheme on frequency resource sharing is proposed to improve the quality of service (QoS) in device-to-device (D2D) communications underlaying cellular networks. Specifically, we formulate the resource allocation problem as a coalition formation game with transferable utility, in which all users have the incentive to cooperate with some others and form a competitive group to maximize the probability of obtaining their favorite spectrum resources. Taking the cost for coalition formation into account, such as the path loss for data sharing, we prove that the core of the proposed game is empty, which shows the impossibility of grand coalition. Hence, we propose a distributed merge-and-split based coalition formation algorithm based on a new defined Max-Coalition order to effectively solve the coalition game. Compared with the exhaustive search, our algorithm has much lower computer complexity. In addition, we prove that stability and convergence of the proposed algorithm using the concept of a defection function. Finally, the simulation results show that the proposed scheme achieves a suboptimal performance in terms of network sum rate compared with the centralized optimal resource allocation scheme obtained via exhaustive search.
Acquisition and Monitoring System for TEG Characterization
Authors: Ando O. H. , Izidoro C. L. , Gomes J. M. , Correia J. H. , Carmo J. P. , Schaeffer L.
Published: March 2015

This paper presents an acquisition system for measuring and characterization of thermoelectric generators (TEGs) for energy harvesting purposes on wireless sensors networks (WSNs). This system can monitor and characterize up to three TEGs simultaneously and is comprised of two main electronic circuits: the first one is composed of 12 input channels being three for reading voltage, three for reading current by making use of instrumentation amplifiers (ACS712), and six thermocouples for signal reading (<400°C). The second electronic circuit consists of a proportional-integral-derivative (PID) controller with two pulse width modulation (PWM) input channels for controlling the heat (thermoresistance) and cooling (controlled cooler) sources, respectively, following a predefined temperature gradient. The TEG measured data for the voltage, current, and temperature can be acquired in real-time with an application written on Delphi language and displayed both through a numeric and graphical display. In order to validate the precision and accuracy two commercial TEG modules (inbC1-127.08HTS) compatible with temperatures up to 200°C without signal degradation were used in series. The functional prototype of the implemented system had a cost under ≈430 USD, making it suitable where a good knowledge of the electrical characteristics of TEGs is of major interest, especially on cogeneration systems.
Blockade of Vascular Endothelial Growth Factor Receptor 1 Prevents Inflammation and Vascular Leakage in Diabetic Retinopathy
Authors: He Jianbo , Wang Hong , Liu Ying , Li Wen , Kim Dorothy , Huang Hu
Published: March 2015

Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. The objective of this study is to investigate the effects of vascular endothelial growth factor receptor 1 (VEGFR1) blockade on the complications of DR. Experimental models of diabetes were induced with streptozotocin (STZ) treatment or Insulin2 gene mutation (Akita) in mice. Protein expression and localization were examined by western blots (WB) and immunofluorescence (IF). mRNA expression was quantified by PCR array and real-time PCR. The activity of VEGFR1 signaling was blocked by a neutralizing antibody called MF1. Vascular leakage was evaluated by measuring the leakage of [3H]-mannitol tracer into the retina and the IF staining of albumin. VEGFR1 blockade significantly inhibited diabetes-related vascular leakage, leukocytes-endothelial cell (EC) adhesion (or retinal leukostasis), expression of intercellular adhesion molecule- (ICAM-) 1 protein, abnormal localization and degeneration of the tight junction protein zonula occludens- (ZO-) 1, and the cell adhesion protein vascular endothelial (VE) cadherin. In addition, VEGFR1 blockade interfered with the gene expression of 10 new cytokines and chemokines: cxcl10, il10, ccl8, il1f6, cxcl15, ccl4, il13, ccl6, casp1, and ccr5. These results suggest that VEGFR1 mediates complications of DR and targeting this signaling pathway represents a potential therapeutic strategy for the prevention and treatment of DR.
Analysis of the Serum Bile Acid Composition for Differential Diagnosis in Patients with Liver Disease
Authors: Sugita Tomonori , Amano Katsushi , Nakano Masanori , Masubuchi Noriko , Sugihara Masahiro , Matsuura Tomokazu
Published: March 2015

Objectives. We determined the serum bile acid (BA) composition in patients with liver diseases and healthy volunteers to investigate the relationship between the etiologies of liver disease and BA metabolism.Material and Methods. Sera from 150 patients with liver diseases and 46 healthy volunteers were obtained. The serum concentrations of the 16 different BAs were determined according to the LC-MS/MS method and were compared between the different liver diseases.Results. A total of 150 subjects, including patients with hepatitis C virus (HCV) (n=44), hepatitis B virus (HBV) (n=23), alcoholic liver disease (ALD) (n=21), biliary tract disease (n=20), nonalcoholic fatty liver disease (NAFLD) (n=13), and other liver diseases (n=29), were recruited. The levels of UDCA and GUDCA were significantly higher in the ALD group, and the levels of DCA and UDCA were significantly lower in the biliary tract diseases group than in viral hepatitis group. In the UDCA therapy (−) subgroup, a significantly lower level of TLCA was observed in the ALD group, with lower levels of CDCA, DCA, and GLCA noted in biliary tract diseases group compared to viral hepatitis group.Conclusions. Analysis of the BA composition may be useful for differential diagnosis in liver disease.
Host Age Is a Systemic Regulator of Gene Expression Impacting Cancer Progression
Authors: Beheshti Afshin , Benzekry Sébastien , McDonald J. Tyson , Ma Lili , Peluso Michael , Hahnfeldt Philip , Hlatky Lynn
Published: March 2015

Aging is the major determinant of cancer incidence, which, in turn, is likely dictated in large part by processes that influence the progression of early subclinical (occult) cancers. However, there is little understanding of how aging informs changes in aggregate host signaling that favor cancer progression. In this study, we provide direct evidence that aging can serve as an organizing axis to define cancer progression-modulating processes. As a model system to explore this concept, we employed adolescent (68 days), young adult (143 days), middle-aged (551 days), and old (736 days) C57BL/6 mice as syngeneic hosts for engraftment of Lewis lung cancer to identify signaling and functional processes varying with host age. Older hosts exhibited dysregulated angiogenesis, metabolism, and apoptosis, all of which are associated with cancer progression. TGFβ1, a central player in these systemic processes, was downregulated consistently in older hosts. Our findings directly supported the conclusion of a strong host age dependence in determining the host tumor control dynamic. Furthermore, our results offer initial mechanism-based insights into how aging modulates tumor progression in ways that may be actionable for therapy or prevention. Cancer Res; 75(6); 1134–43. ©2015 AACR.
Iodine, Thyroid Autoimmunity and Cancer
Authors: Fiore Emilio , Latrofa Francesco , Vitti Paolo
Published: March 2015

This review focuses on two different topics: (a) iodine and autoimmune thyroid disease (AITD) and (b) AITD and papillary thyroid carcinoma (PTC). Iodine intake modifies the expression of thyroid diseases and has been associated with induction of AITD. Thyroglobulin (Tg) is an important target in iodine-induced autoimmune response due to post-translational modifications of iodinated Tg, as suggested in animal models. We have shown that the unmasking of a cryptic epitope on Tg contributes to iodine-induced thyroid autoimmunity in humans. The relationship between AITD and PTC has been suggested in many studies. The presence of two different mechanisms has been hypothesized, one typical of AITD and the other of an immune reaction to PTC. We have shown that in AITD, the pattern of Tg recognition by anti-Tg antibodies (TgAb) is ‘restricted' to the immunodominant regions of Tg, while in patients with non-AITD, such as nodular goiter and PTC devoid of thyroid lymphocytic infiltration at histology, TgAb show a less restricted epitopic pattern and bind also to other regions of Tg. Thyroid function may also affect the frequency of PTC, the risk of cancer increasing with serum TSH levels. We have shown that this mechanism, rather than thyroiditis per se, plays a major role in the association of PTC with Hashimoto's thyroiditis, as a consequence of the autoimmune process leading to a progressive increase of serum TSH in these patients.
Laparoscopic versus Open Obesity Surgery: A Meta-Analysis of Pulmonary Complications
Authors: Antoniou Stavros Athanasios , Antoniou George Athanasios , Koch Oliver Owen , Köhler Gernot , Pointner Rudolph , Granderath Frank-Alexander
Published: March 2015

The clinical effects of laparoscopy in the pulmonary function of obese patients have been poorly investigated in the past. A systematic review was undertaken, with the objective to identify published evidence on pulmonary complications in laparoscopic surgery in the obese. Outcome measures included pulmonary morbidity, pulmonary infection and mortality. The random effects model was used to calculate combined overall effect sizes of pooled data. Data are presented as the odds ratio (OR) with 95% confidence interval (CI). A total of 6 randomized and 14 observational studies were included, which reported data on 185,328 patients. Pulmonary complications occurred in 1.6% of laparoscopic and in 3.6% of open procedures (OR 0.45, 95% CI 0.34-0.60). Pneumonia was reported in 0.5% and in 1.1%, respectively (OR 0.45, 95% CI 0.40-0.51). Available evidence suggests lower pulmonary morbidity for laparoscopic surgery in obese patients; further quality studies are however necessary to consolidate these findings.
Epidermal Growth Factor Receptor Is Critical For Angiotensin II–Mediated Hypertrophy in Cerebral Arterioles
Authors: Chan Siu-Lung , Umesalma Shaikamjad , Baumbach Gary L.
Published: March 2015

Angiotensin II (Ang II) is a major determinant of vascular remodeling in the cerebral circulation during chronic hypertension, which is an important risk factor for stroke. We examined the molecular mechanism of Ang II–mediated cerebrovascular remodeling that involves the epidermal growth factor receptor (EGFR) pathway. Mutant EGFR mice (waved-2), their heterozygous control (wild-type [WT]), and C57BL/6J mice were infused with Ang II (1000 ng kg
−1
min
−1
) or saline via osmotic minipumps for 28 days (n=8 per group). Eight of the Ang II–infused C57BL/6J mice were cotreated with AG1478 (12 mg/kg per day, IP), a specific EGFR tyrosine kinase inhibitor. Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of cerebral arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined in pressurized fixed cerebral arterioles. Expression of phosphorylated EGFR (p-EGFR), caveolin-1 (Cav-1), and c-Src was determined by western blotting and immunohistochemistry. Mutation of EGFR or AG1478 treatment did not affect Ang II–induced hypertension. Ang II increased the expression of p-EGFR in WT mice, confirming the activation of EGFR. Ang II induced hypertrophy and inward remodeling of cerebral arterioles in WT mice. Hypertrophy, but not remodeling, was prevented in waved-2 and AG1478-treated C57BL/6J mice. Ang II increased p-EGFR, Cav-1, and c-Src expression in WT but not in waved-2 or AG1478-treated C57BL/6J mice. These results suggest that Ang II–induced hypertrophy in cerebral arterioles involves EGFR-dependent signaling and may include Cav-1 and nonreceptor tyrosine kinase c-Src. This signaling pathway seems to be limited to Ang II–induced hypertrophy, but not inward remodeling, and is independent of blood pressure.
"SERVING THEM BACK" YOUTH EVANGELISM IN A SECULAR AND POSTMODERN WORLD
Authors: Nel Malan
Published: March 2015

Youth evangelism has never been high on the agenda of churches. Culture has often, more than what churches would want to admit, determined the ruling attitude towards youth and even more so inactive and/or alienated youth. In many churches even the absence of younger members from normal and weekly church activities are not even registered. What is evenly tragic is that when and wherever churches do reach out to alienated youth it is often still in an authoritarian, propositional and even confrontational way. The church is and remains, in spite of its inadequacies, God's intended people to reach the world. This paper is about the conversion of the evangelist (the church) in order to reach out in a different way. It is about becoming and being a servant, serving people back, in the Name of the One who did not come to be served but to serve (Mark 10:45). The question is about the integrity and quality of discipleship in the church.
No Longer Guests: On the Dynamics of Agency and Formation in Ministry with Older Adolescents
Authors: Meter Tim Van , Turpin Katherine
Published: March 2015

This article considers spiritual formation amongst older adolescents. The authors, drawing particularly on the theories of Paulo Freire and Seyla Benhabib, locate their thoughts within a pragmatic case study from a summer academy experience at Emory University's Youth Theological Initiative.
Invitational Leadership: A Model for the Future
Authors: Coats Keith
Published: March 2015

This article explores the desire of the author to find appropriate frameworks and processes for individuals and companies to think strategically and explore models of leadership. He is concerned to use corporate models in developing such strategies in the church context generally and the youth ministry context specifically.
A Martyr to the Cause: Learning from Dietrich Bonhoeffer
Authors: Nash Sally
Published: March 2015

In this fascinating article, Dr Sally Nash explores the life of Dietrich Bonhoeffer and draws out for the reader a number of conclusions that can be applied to our youth ministry practice.
Theology on the Rocks? On how popular music challenges theology
Authors: Ardui Johan
Published: March 2015

Practitioners of youth ministry have long recognised the importance of engagement with popular music for creative ministry. What is desperately needed, however, is a firm ideological foundation upon which to build that practice. In this article, Johan Ardui explores the relationship between theology and popular music through vital trends of thought in both theology and philosophy. His conclusions are both rigorous and helpful.
Developing Contextual Models of Youth Ministry, Part 1
Authors: Gapes Christine
Published: March 2015

In this article, I outline an argument that the many models of youth ministry on offer are helpful guides but rarely implemented well in a local situation because of a number of factors that interfere with their translocation. Models Of youth ministry multiply like rabbits out of a hat! Youth workers can become confused and overwhelmed by the variety. In this article, I do not propose a new model, but offer a method (a game!) to enable youth work students and those in youth ministry to reflect critically on and to analyze the models they use so that more effective application may occur. An approach that suited to the complex reality in which we minister. My reflections are based on experiences of playing the game at the IASYM conference in London (Jan 2005). These illustrate the premise and promise of the game for analysing models of youth ministry.
Body Modification: Adolescence, Popular Culture & Practical Theology
Authors: Latini Theresa F.
Published: March 2015

This article explores the relationship between popular culture and practical theology through an analysis of body modification. The first section describes the practice of body modification in its various forms-from tattoos to extreme piercing and implants to ritual dance and suspension. The second section interprets this practice using both a sociological and a psychological lens, while the third section highlights the theological (spiritual) questions embedded in body mod. Finally, the article encourages Christian educators and youth ministers to address the spiritual needs and questions of adolescents related embodiment in their ministerial practice.
The Rise of English Youth Churches: What the Global Church Can Learn From This Latest British Invention
Authors: Lamport Mark A.
Published: March 2015

The United Kingdom, where only ten percent of youth attend church weekly, has recently witnessed an upstart missional strategy. called "Youth Churches." It is as the name implies-churches composed entirely of youth and marketed to attract this alienated group through popular music and worship. The author attended an international conference at Oxford University at which lectures were presented on this growing phenomenon. It provoked such an interest that he subsequently traveled to England and spent some time doing field research, including interviews with leaders of several denominations. This paper presents what the author discovered. It is written as primarily a journalistic, theological reflection piece based upon observations and face-to-face interviews with protagonists and thoughtful commentators connected with youth church movements in the UK.1 It does not claim to be a fully formed theoretical treatment of the topic!2
Towards a Humanistic Theology of Youth Development: growing through the work of the Romanian theologian Dumitru Staniloae
Authors: Bates Dana
Published: March 2015

This article will introduce to an international and ecumenical audience the Romanian Orthodox theologian Dumitru Staniloae and the Eastern Orthodox approach to salvation. By then correlating Staniloae's theology with current development theories it will demonstrate Orthodoxy's importance for issues young people's development and participation in society, primarily in developing countries. This will be accomplished by correlating Staniloae's Trinitarian theology with two increasingly important development test cases: increasing social capital and reducing corruption. A critical theme to be explored is Orthodoxy's ability to bridge the conceptual chasm between humanistic concerns of the development world (natural theology), and those of salvation and redemption (revealed theology) with several concomitant practical implications for youth work spelled out.
Reality and Scope of Youth Association Work
Authors: Münchmeier Richard
Published: March 2015

This article is an overview of a qualitative and quantitative analysis of evangelical youth work in Germany - focused around the organized work of Arbeitsgemeinschaft der Evangelischen Jugend in der Bundesrepublik Deutschland. The paper reports on the methodology and key findings of this research, highlighting young people as co-producers, active agents who. participate in shaping youth organizations.
Adolescent Experiences of Christ's Presence and Activity in the Evangelical Lutheran Church in America
Authors: Myers Jeremy
Published: March 2015

The National Study of Youth and Religion (NSYR) claims moralistic therapeutic deism as the popular religion among our youth.1 The Study of Exemplary Congregations in Youth Ministry (EYM) discovered that exemplary congregations are one's who speak about God as one who is present and active.2 The God of moralistic therapeutic deism can not be present and active. Is God present and active? If so, how do our youth experience and interpret this presence and activity? This article gives voice to the ways in which youth of the Evangelical Lutheran Church in America (ELCA) experience Christ's presence and activity. It finds that placing their subjective interpretations of these experiences into conversation with their tradition's interpretation of Christ's presence and activity as represented by Gustaf Wingren's creation-faith enhances both how they and their tradition understand God's work in our world. The exemplar descriptor for the experiences heard among these youth is referred to as proleptic vocational recapitulation.
Can the Christian gospel speak to the experience of young people today?
Authors: Goodliff Andy
Published: March 2015

Soteriology is at the heart of all Christian ministry. Soteriology underpins all effective Christian youth ministry. In this article, Andy Goodliff explores traditional and contemporary models of soteriology in an attempt to find a theological language that speaks to young people today.
The State of Youth Research in South Africa
Authors: Swartz Sharlene
Published: March 2015

In such a fast-moving and ever-changing environment as youth ministry, it is difficult to remain up to date with trends and new analysis. In this article, Sharlene Swartz writes a definitive piece on the state of youth research in South Africa to 2004. Whilst this piece concentrates on that country alone, there are many trends and issues that will overlap with the experience of readers in other countries, making this a widely applicable piece of research.
Towards an Adolescent Hermeneutic
Authors: Kaethler Andrew
Published: March 2015

This article brings together two distinct and seemingly disparate fields of adolescent faith development and philosophical hermeneutics. The dialogue between these provides a potential framework ( an adolescent hermeneutic) to address whether youth approach the Bible with a unique agenda shaped by their stage in life as adolescents. The article proposes four "markers" of an adolescent hermeneutic that are identified and tested against the themes of narrative and temporality from philosophical hermeneutics and then applied to a reading of a Gospel text.