bluuebunny/crossref_metadata_2025 huggingface dataset:
Representing BRDFs using SOMs and MANs
Authors: Kurt Murat , Cinsdikici Muhammed Gökhan
Published: September 2008

High-quality Monte Carlo image synthesis needs to use realistic bidirectional reflectance distribution functions (BRDFs) based on acquired reflectance data. In this study, we propose a novel model that contributes to solving memory problems and measurement noise problems of BRDFs. The model is a composite associative memory model constructed by integration of Kohonen's Self Organizing Feature Map (SOM), Mass Attraction Network (MAN), and it has been tested on data set acquired by Matusik et al.. Because it is based on table-lookups, it can't be categorized in analytical reflectance models. We show that our approach has acceptable compactness. We also show that it has more accuracy than both analytical BRDF models and Lawrence et al.'s table-based model. In this work, we are able to create images efficiently under global illumination with less memory requirements.
Illustrative visualization
Authors: Rautek Peter , Bruckner Stefan , Gröller Eduard , Viola Ivan
Published: September 2008

The computer graphics group at TU Vienna has created some of most beautiful and effective illustrative visualizations. In this article, they share with us their unique perspective on illustrative visualization. --- Kwan-Liu Ma
Breaking the stereoscopic 3D paradox
Authors: Schneider Neil
Published: September 2008

In CG graphics circles, there is often confusion about what the difference is between 3D and stereoscopic 3D (S-3D). In the graphics world, 3D is the volumetric 3D that includes X, Y, and Z depth information. Stereoscopic 3D refers to the image capture of a volumetric object or scene from two camera perspectives, and the ability to display and view it with true 3D depth using special 3D monitors, glasses, HMDs, or projectors.
Dr. Robert Cailliau, co-developer of the WWW
Authors: Schneider Neil
Published: September 2008

The stereoscopic 3D industry almost seems to have exploded overnight. We have a growing number of stereoscopic 3D (S-3D) movie theaters, the S-3D gaming industry is taking off thanks to efforts by the S-3D manufacturers (e.g. iZ3D, TDVision Corp, etc.), leading names like James Cameron, Ubisoft, Electronic Arts Korea and additionally by the efforts of the Meant To Be Seen (MTBS) membership. Yet the more things change, the more things stay the same. What does the S-3D industry need to do to make stereoscopic 3D a success for the masses? What lessons can the past teach us to help move us along?
Dr. Robert Cailliau, co-developer of the WWW
Authors: Schneider Neil
Published: September 2008

In the first interview segment, Dr. Cailliau shared some information about his career, physics, and some history about how the World Wide Web was created. In part two, we talk about the politics of the web, Dr. Cailliau's personal experiences with stereoscopic 3D photography, and a sharp look at the relationship between the way the WWW was developed, and what ramifications this may hold for the stereoscopic 3D industry.
Phylogenetic Inference Using Whole Genomes
Authors: Rannala Bruce , Yang Ziheng
Published: September 2008

The availability of genome-wide data provides unprecedented opportunities for resolving difficult phylogenetic relationships and for studying population genetic processes of mutation, selection, and recombination on a genomic scale. The use of appropriate statistical models becomes increasingly important when we are faced with very large datasets, which can lead to improved precision but not necessarily improved accuracy if the analytical methods have systematic biases. This review provides a critical examination of methods for analyzing genomic datasets from multiple loci, including concatenation, separate gene-by-gene analyses, and statistical models that accommodate heterogeneity in different aspects of the evolutionary process among data partitions. We discuss factors that may cause the gene tree to differ from the species tree, as well as strategies for estimating species phylogenies in the presence of gene tree conflicts. Genomic datasets provide computational and statistical challenges that are likely to be a focus of research for years to come.
Infectious Disease in the Genomic Era
Authors: Yang Xiaonan , Yang Hongliang , Zhou Gangqiao , Zhao Guo-Ping
Published: September 2008

After half a century of success in combating infectious diseases with vaccination and antibiotics, emerging and reemerging epidemics present a new threat to human health. Meanwhile, the rapid pace of viral and microbial genomics research, largely based on the success of genomics technologies, offers new data-generating platforms and a revolutionary knowledge base for better understanding the diseases and the associated pathogens. Systematic molecular biology studies using genomics information and technologies have helped to elucidate mechanisms of virulence and pathogenicity, whereas genomics-based medical genetic studies have been used to better understand pathogen susceptibility. This progress may lead to the development of effective and safe vaccines in the future. Here we highlight the ongoing historical transition in the field of infectious disease research and clinical practice in the new era of genomics.
Transgenerational Epigenetic Effects
Authors: Youngson Neil A. , Whitelaw Emma
Published: September 2008

Transgenerational epigenetic effects include all processes that have evolved to achieve the nongenetic determination of phenotype. There has been a long-standing interest in this area from evolutionary biologists, who refer to it as non-Mendelian inheritance. Transgenerational epigenetic effects include both the physiological and behavioral (intellectual) transfer of information across generations. Although in most cases the underlying molecular mechanisms are not understood, modifications of the chromosomes that pass to the next generation through gametes are sometimes involved, which is called transgenerational epigenetic inheritance. There is a trend for those outside the field of molecular biology to assume that most cases of transgenerational epigenetic effects are the result of transgenerational epigenetic inheritance, in part because of a misunderstanding of the terms. Unfortunately, this is likely to be far from the truth.
Contributions of Long-Term Research and Time-Series Observations to Marine Ecology and Biogeochemistry
Authors: Ducklow Hugh W. , Doney Scott C. , Steinberg Deborah K.
Published: September 2008

Time-series observations form a critical element of oceanography. New interdisciplinary efforts launched in the past two decades complement the few earlier, longer-running time series to build a better, though still poorly resolved, picture of lower-frequency ocean variability, the climate processes that drive variability, and the implications for food web dynamics, carbon storage, and climate feedbacks. Time series also enlarge our understanding of ecological processes and are integral for improving models of physical-biogeochemical-ecological ocean dynamics. The major time-series observatories go well beyond simple monitoring of core ocean properties, although that important activity forms the critical center of all time-series efforts. Modern ocean time series have major process and experimental components, entrain ancillary programs, and have integrated modeling programs for deriving a better understanding of the observations and the changing, three-dimensional ocean in which the observatories are embedded.
The Social Brain: Neural Basis of Social Knowledge
Authors: Adolphs Ralph
Published: September 2008

Social cognition in humans is distinguished by psychological processes that allow us to make inferences about what is going on inside other people—their intentions, feelings, and thoughts. Some of these processes likely account for aspects of human social behavior that are unique, such as our culture and civilization. Most schemes divide social information processing into those processes that are relatively automatic and driven by the stimuli, versus those that are more deliberative and controlled, and sensitive to context and strategy. These distinctions are reflected in the neural structures that underlie social cognition, where there is a recent wealth of data primarily from functional neuroimaging. Here I provide a broad survey of the key abilities, processes, and ways in which to relate these to data from cognitive neuroscience.
Phosphorylation of GTP dissociation inhibitor by PKA negatively regulates RhoA
Authors: Qiao Jing , Holian Oksana , Lee Bao-Shiang , Huang Fei , Zhang Jihang , Lum Hazel
Published: September 2008

The cAMP-PKA cascade is a recognized signaling pathway important in inhibition of inflammatory injury events such as endothelial permeability and leucocyte trafficking, and a critical target of regulation is believed to be inhibition of Rho proteins. Here, we hypothesize that PKA directly phosphorylates GTP dissociation inhibitor (GDI) to negatively regulate Rho activity. Amino acid analysis of GDIα showed two potential protein kinase A (PKA) phosphorylation motifs, Ser174 and Thr182. Using in vitro kinase assay and mass spectrometry, we found that the purified PKA catalytic subunit phosphorylated GDIα-GST fusion protein and PKA motif-containing GDIα peptide at Ser174, but not Thr182. Transfection of COS-7 cells with mutated full-length GDIα at Ser174 to Ala174 (GDIα-Ser174A) abrogated the ability of cAMP to phosphorylate GDIα. However, mutation of Thr182 to Ala182 (GDIα-Thr182A) did not abrogate, and cAMP increased phosphorylation of GDIα to a similar extent as wild-type GDIα transfectants. The mutant GDIα-Ser174A, but not GDIα-Thr182A, was unable to prevent cAMP-mediated inhibition of Rho-dependent serum-response element reporter activity. Furthermore, the mutant GDIα-Ser174A was unable to prevent the thrombin-induced RhoA activation. Coprecipitation studies indicated that neither mutation of the PKA consensus sites nor phosphorylation alter GDIα binding with RhoA, suggesting that phosphorylation of Ser174 regulated preformed GDIα-RhoA complexes. The findings provide strong support that the selective phosphorylation at Ser174 by PKA is a signaling pathway in the negative regulation of RhoA activity and therefore could be a potential protective mechanism for inflammatory injury.
Proinflammatory cytokines tumor necrosis factor-α and interferon-γ alter tight junction structure and function in the rat parotid gland Par-C10 cell line
Authors: Baker Olga J. , Camden Jean M. , Redman Robert S. , Jones Jonathan E. , Seye Cheikh I. , Erb Laurie , Weisman Gary A.
Published: September 2008

Sjögren's syndrome (SS) is an autoimmune disorder characterized by inflammation and dysfunction of salivary glands, resulting in impaired secretory function. The production of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) is elevated in exocrine glands of patients with SS, although little is known about the effects of these cytokines on salivary epithelial cell functions necessary for saliva secretion, including tight junction (TJ) integrity and the establishment of transepithelial ion gradients. The present study demonstrates that chronic exposure of polarized rat parotid gland (Par-C10) epithelial cell monolayers to TNF-α and IFN-γ decreases transepithelial resistance (TER) and anion secretion, as measured by changes in short-circuit current ( Isc) induced by carbachol, a muscarinic cholinergic receptor agonist, or UTP, a P2Y2 nucleotide receptor agonist. In contrast, TNF-α and IFN-γ had no effect on agonist-induced increases in the intracellular calcium concentration [Ca2+]i in Par-C10 cells. Furthermore, treatment of Par-C10 cell monolayers with TNF-α and IFN-γ increased paracellular permeability to normally impermeant proteins, altered cell and TJ morphology, and downregulated the expression of the TJ protein, claudin-1, but not other TJ proteins expressed in Par-C10 cells. The decreases in TER, agonist-induced transepithelial anion secretion, and claudin-1 expression caused by TNF-α, but not IFN-γ, were reversible by incubation of Par-C10 cell monolayers with cytokine-free medium for 24 h, indicating that IFN-γ causes irreversible inhibition of cellular activities associated with fluid secretion in salivary glands. Our results suggest that cytokine production is an important contributor to secretory dysfunction in SS by disrupting TJ integrity of salivary epithelium.
MDA-MB-231 produces ATP-mediated ICAM-1-dependent facilitation of the attachment of carcinoma cells to human lymphatic endothelial cells
Authors: Kawai Yoshiko , Kaidoh Maki , Ohhashi Toshio
Published: September 2008

We examined the effects of supernatants of culture media of MDA-MB-231 and MCF-7 cells on the expression of adhesion molecules on human lymphatic endothelial cells (LECs) and evaluated whether the overexpression of adhesion molecules facilitated the attachment of carcinoma cells to LECs. The 48-h stimulation of MDA-MB-231, but not MCF-7, supernatant produced a significant expression of ICAM-1 on human LECs but little or no expression of E-selectin. Chemical treatment with dialyzed substances of <1,000 molecular weight (MW) caused a complete reduction of the supernatant-mediated response. In contrast, pretreatment with heating, digestion with protease, or chemical treatment with dialyzed substances of <500 MW produced no significant effect on the supernatant-mediated response. ATP (10−7M) caused overexpression of ICAM-1 on human LECs similar to that produced by the supernatant of MDA-MB-231. The ATP- and MDA-MB-231 supernatant-mediated responses were significantly reduced by treatment with 10−6M suramin (a purinergic P2X and P2Y receptor antagonist). In attachment assays, 10−7M ATP or MDA-MB-231 supernatant produced a significant increase in the attachment of carcinoma cells to human LECs. The treatment with 10−6M suramin caused a significant reduction of ATP- and supernatant-mediated facilitation of the attachment responses. Additional treatment with anti-ICAM-1 antibody also caused a significant reduction of ATP- and supernatant-mediated facilitation of the attachment responses. The experimental findings suggest that MDA-MB-231 may release or leak ATP, which produces the overexpression of ICAM-1 on human LECs through activation of purinergic P2X and/or P2Y receptors and then facilitates ICAM-1-mediated attachment of carcinoma cells to LECs.
How strict is the correlation between STIM1 and Orai1 expression, puncta formation, andICRACactivation?
Authors: Gwozdz Tomasz , Dutko-Gwozdz Joanna , Zarayskiy Vladislav , Peter Krisztina , Bolotina Victoria M.
Published: September 2008

Stromal interaction molecule 1 (STIM1) and Orai1 have been identified as crucial elements of the store-operated Ca2+entry (SOCE) pathway, but the mechanism of their functional interaction remains controversial. It is now well established that, upon depletion of the stores, both molecules can accumulate and colocalize in specific areas (puncta) where the endoplasmic reticulum comes in close proximity to the plasma membrane. Some models propose a direct interaction between STIM1 and Orai1 as the most straightforward mechanism for signal transduction from the stores to the plasma membrane. To test some of the predictions of a conformational coupling model, we assessed how tight the relationships are between STIM1 and Orai1 expression, puncta formation, and SOCE activation. Here we present evidence that STIM1 accumulates in puncta equally well in the presence or absence of Orai1 expression, that STIM1 accumulation is not sufficient for Orai1 accumulation in the same areas, and that normal Ca2+release-activated Ca2+current ( ICRAC) can be activated in STIM1-deficient cells. These data challenge the idea of direct conformational coupling between STIM1 and Orai1 as a viable mechanism of puncta formation and SOCE activation and uncover greater complexity in their relationship, which may require additional intermediate elements.
Contrasting effect of exercise and angiotensin II hypertension on in vivo and in vitro cardiac angiogenesis in rats
Authors: Belabbas Hassiba , Zalvidea Santiago , Casellas Daniel , Molès Jean-Pierre , Galbes Olivier , Mercier Jacques , Jover Bernard
Published: September 2008

Cardiac vessel density (β-actin immunolabeling) and angiogenic capacity of coronary artery explants (culture in collagen gel) was determined in hypertrophied heart obtained by exercise training (10 wk) or ANG II infusion for 10 days. A group of rats received ANG II the last 10 days of training. The heart weight index was similarly elevated after exercise, and ANG II-hypertension compared with controls (3.16 ± 0.09 and 3.11 ± 0.11 vs. 2.68 ± 0.08 mg/g, respectively), whereas tail cuff pressure (TCP) increased only in sedentary rats infused with ANG II. Vessel density was increased by 36% in trained rats and reduced by 30% in ANG II-infused rats. The number of sprouts generated by coronary rings was reduced by 50% in ANG II-infused rats and increased by 50% in exercise trained rats compared with controls (35 ± 4 and 113 ± 5 vs. 71 ± 1 sprouts per ring, respectively). Exercise-training partly prevented the hypertensive effect of ANG II (TCP of 141 ± 5 mmHg), whereas heart weight index (3.66 ± 0.06 mg/g body wt) was not lowered. Myocardial vessel density was normalized, and sprouting from coronary rings increased by 50% in trained rats infused with ANG II compared with sedentary normotensive rats. Cardiac VEGF (Western blot analysis) was higher in hypertensive rats and not affected by exercise. Facing a similar increase in cardiac mass, intense training, but not ANG II hypertension, is accompanied by an increase in vascular density of the heart. The effect of training is unlikely related to changes in resting VEGF and may represent enhanced angiogenic capacity of the coronary vascular bed.
Food deprivation increases the mRNA expression of μ-opioid receptors in the ventral medial hypothalamus and arcuate nucleus
Authors: Barnes Maria J. , Primeaux Stefany D. , Bray George A.
Published: September 2008

Activation of μ-opioid receptors makes animals hyperphagic and increases their preference for a high-fat diet. Previous studies have suggested that this receptor population plays a role in mediating the hyperphagia that is associated with food deprivation. In this paper, we tested the hypothesis that food deprivation will increase the expression of μ-opioid receptors in the ventral medial hypothalamus and arcuate nucleus (VMH/ARC). Food deprivation resulted in a significant increase in the mRNA expression of μ-opioid receptors in the VMH/ARC and the lateral hypothalamus (LH) after 48 h of fasting but not after 24 or 12 h of fasting in either the light or dark. We did not observe a change in the mRNA expression of κ- or δ-opioid receptors after food deprivation. When food-deprived animals were given a choice between a low-fat diet and a high-fat diet, they were hyperphagic and consumed significantly more of the high-fat diet. When the μ-opioid receptors were blocked with β-funaltrexamine (selective μ-opioid receptor antagonist), prior to giving food-deprived animals access to both a low-fat and high-fat diet, it significantly decreased the percentage of high-fat diet consumed. These data demonstrate that hypothalamic μ-opioid receptors may contribute to the hyperphagia and increased preference for a high-fat diet that is associated with food deprivation.
Differential effects of airway afferent nerve subtypes on cough and respiration in anesthetized guinea pigs
Authors: Chou Yang-Ling , Scarupa Mark D. , Mori Nanako , Canning Brendan J.
Published: September 2008

The hypothesis that respiratory reflexes, such as cough, reflect the net and often opposing effects of activation of multiple afferent nerve subpopulations throughout the airways was evaluated. Laryngeal and tracheal mucosal challenge with either citric acid or mechanical probing reliably evoked coughing in anesthetized guinea pigs. No other stimulus reliably evoked coughing in these animals, regardless of route of administration and despite some profound effects on respiration. Selectively activating vagal C-fibers arising from the nodose ganglia with either adenosine or 2-methyl-5-HT evoked only tachypnea. Selectively activating vagal afferents arising from the jugular ganglia induced respiratory slowing and apnea. Nasal afferent nerve activation by capsaicin, citric acid, hypertonic saline, or histamine evoked only respiratory slowing. Histamine, which activates intrapulmonary rapidly adapting receptors but not airway or lung C-fibers or tracheal bronchial cough receptors induced bronchospasm and tachypnea, but no coughing. The results indicate that the reflexes initiated by stimuli thought to be selective for some afferent nerve subtypes will likely depend on the net and potentially opposing effects of multiple afferent nerve subpopulations throughout the airways. The data also provide further evidence that the afferent nerves regulating cough in anesthetized guinea pigs are distinct from either C-fibers or intrapulmonary rapidly adapting receptors.
Circulatory limits to oxygen supply during an acute temperature increase in the Chinook salmon (Oncorhynchus tshawytscha)
Authors: Clark Timothy D. , Sandblom Erik , Cox Georgina K. , Hinch Scott G. , Farrell Anthony P.
Published: September 2008

This study was undertaken to provide a comprehensive set of data relevant to disclosing the physiological effects and possible oxygen transport limitations in the Chinook salmon (Oncorhynchus tshawytscha) during an acute temperature change. Fish were instrumented with a blood flow probe around the ventral aorta and catheters in the dorsal aorta and sinus venosus. Water temperature was progressively increased from 13°C in steps of 4°C up to 25°C. Cardiac output increased from 29 to 56 ml·min−1·kg−1between 13 and 25°C through an increase in heart rate (58 to 105 beats/min). Systemic vascular resistance was reduced, causing a stable dorsal aortic blood pressure, yet central venous blood pressure increased significantly at 25°C. Oxygen consumption rate increased from 3.4 to 8.7 mg·min−1·kg−1during the temperature increase, although there were signs of anaerobic respiration at 25°C in the form of increased blood lactate and decreased pH. Arterial oxygen partial pressure was maintained during the heat stress, although venous oxygen partial pressure (PvO2) and venous oxygen content were significantly reduced. Cardiac arrhythmias were prominent in three of the largest fish (>4 kg) at 25°C. Given the switch to anaerobic metabolism and the observation of cardiac arrhythmias at 25°C, we propose that the cascade of venous oxygen depletion results in a threshold value for PvO2of around 1 kPa. At this point, the oxygen supply to systemic and cardiac tissues is compromised, such that the oxygen-deprived and acidotic myocardium becomes arrhythmic, and blood perfusion through the gills and to the tissues becomes compromised.
Inhibiting parabrachial fatty acid amide hydrolase activity selectively increases the intake of palatable food via cannabinoid CB1 receptors
Authors: DiPatrizio Nicholas V. , Simansky Kenny J.
Published: September 2008

These studies investigated feeding responses to indirect activation of parabrachial cannabinoid CB1 receptors. Arachidonoyl serotonin (AA5HT), an inhibitor of the endocannabinoid degradative enzyme, fatty acid amide hydrolase (FAAH), was infused into the parabrachial nucleus of male Sprague-Dawley rats, and intakes of high-fat/sucrose pellets and standard rodent chow were subsequently evaluated under various feeding schedules. FAAH blockade stimulated the intake of high-fat/sucrose pellets that were presented daily for 4 h during the light period, with compensatory decreases in the consumption of standard chow during the ensuing 20 h. These diet-selective changes were repeated on the next day, indicating a shift in feeding toward the more palatable diet that lasted for 48 h after a single infusion. The cannabinoid CB1 receptor antagonist, AM251, blocked the orexigenic actions of AA5HT, implicating CB1 receptors in mediating the feeding responses to FAAH inactivation. When the feeding schedule was reversed, AA5HT produced nominal increases in the consumption of standard chow for the 4-h access period, but substantial increases in the intake of high-fat/sucrose during the following 20-h interval. When presented with only high-fat/sucrose diet for 24 h, AA5HT increased 24-h food intake. In contrast, when given 24-h access only to standard chow, AA5HT failed to affect intake. Therefore, indirectly activating parabrachial CB1 receptors by blocking the degradation of native ligands selectively stimulates the intake of palatable food, with differential actions on total energy intake depending upon the feeding schedule. Our results support a role for parabrachial cannabinoid mechanisms in providing physiological regulation to neural substrates modulating feeding, energy balance, and behavioral responses for natural reward.
Vascular circadian rhythms in a mouse vascular smooth muscle cell line (Movas-1)
Authors: Chalmers Jennifer A. , Martino Tami A. , Tata Nazneen , Ralph Martin R. , Sole Michael J. , Belsham Denise D.
Published: September 2008

The circadian system in mammals is a hierarchy of oscillators throughout the organism that are coordinated by the circadian clock in the hypothalamic suprachiasmatic nucleus. Peripheral clocks act to integrate time-of-day information from neural or hormonal signals, regulating gene expression, and, subsequently, organ physiology. However, the mechanisms by which the central clock communicates with peripheral oscillators are not understood and are likely tissue specific. In this study, we establish a mouse vascular cell model suitable for investigations of these mechanisms at a molecular level. Using the immortalized vascular smooth muscle cell line Movas-1, we determined that these cells express the circadian clock machinery with robust rhythms in mRNA expression over a 36-h period after serum shock synchronization. Furthermore, norepinephrine and forskolin were able to synchronize circadian rhythms in bmal1. With synchronization, we observed cycling of specific genes, including the tissue inhibitor of metalloproteinase 1 and 3 ( timp1, timp3), collagen 3a1 ( col3a1), transgelin 1 ( sm22α), and calponin 1 ( cnn1). Diurnal expression of these genes was also found in vivo in mouse aortic tissue, using microarray and real-time RT-PCR analysis. Both of these revealed ultradian rhythms in genes similar to the cycling observed in Movas-1 in vitro. These findings highlight the cyclical nature of structurally important genes in the vasculature that is similar both in vivo and in vitro. This study establishes the Movas-1 cells as a novel cell model from which to further investigate the molecular mechanisms of clock regulation in the vasculature.
Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome
Authors: Artunc Ferruh , Nasir Omaima , Amann Kerstin , Boini Krishna M. , Häring Hans-Ulrich , Risler Teut , Lang Florian
Published: September 2008

Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 μg/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 ( sgk1−/−) and their wild-type littermates ( sgk1+/+). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1+/+and 15/44 of sgk1−/−mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1+/+mice. Urinary sodium excretion reached signficantly lower values in sgk1+/+mice (15 ± 5 μmol/mg crea) than in sgk1−/−mice (35 ± 5 μmol/mg crea) and was associated with a significantly higher body weight gain in sgk1+/+compared with sgk1−/−mice (+6.6 ± 0.7 vs. +4.1 ± 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1−/−mice than in sgk1+/+mice leading to uremia and a reduced median survival in sgk1−/−mice (29 vs. 40 days in sgk1+/+mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.
Visfatin: a new player in mesangial cell physiology and diabetic nephropathy
Authors: Song Hye Kyoung , Lee Mi Hwa , Kim Bo Kyung , Park Yun Gyu , Ko Gang Jee , Kang Young Sun , Han Jee Young , Han Sang Youb , Han Kum Hyun , Kim Hyoung Kyu , Cha Dae Ryong
Published: September 2008

Visfatin is an adipocytokine that improves insulin resistance and has an antidiabetic effect. However, the role of visfatin in the kidney has not yet been reported. In this experiment, the synthesis and physiological action of visfatin in cultured mesangial cells (MCs) were studied to investigate the role of visfatin in diabetic nephropathy. Visfatin was found synthesized in MCs as well as adipocytes. Visfatin synthesis was markedly increased, not by angiotensin II, but by high glucose stimuli. In addition, visfatin treatment induced a rapid uptake of glucose, peaking at 20 min after visfatin treatment in a dose-dependent manner. A small inhibiting RNA against insulin receptor significantly blocked visfatin-mediated glucose uptake. Visfatin stimuli also enhanced intracellular NAD levels, and treatment with FK866, which is a specific inhibitor of nicotinamide phosphoribosyltransferase (Nampt), significantly inhibited visfatin-induced NAD synthesis and glucose uptake. Visfatin treatment increased glucose transporter-1 (GLUT-1) protein expression in isolated cellular membranes, and pretreatment with cytochalasin B completely inhibited visfatin-induced glucose uptake. Moreover, immunofluorescent microscopy showed the migration of cytosolic GLUT-1 into cellular membranes after visfatin treatment. In accordance with these results, the activation of protein kinase B was detected after visfatin treatment. Furthermore, visfatin treatment dramatically increased the synthesis of profibrotic molecules including transforming growth factor-β1, plasminogen activator inhibitor-1, and type I collagen, and pretreatment with cytochalasin B completely inhibited visfatin-induced upregulation of profibrotic molecules. These results suggest that visfatin is produced in MCs, which are a novel target for visfatin, and play an important role in the pathogenesis of diabetic nephropathy.
Functional immunoassay technology (FIT), a new approach for measuring physiological functions: application of FIT to measure glomerular filtration rate (GFR)
Authors: Reinhardt Christopher Peter , Germain Michael J. , Groman Ernest V. , Mulhern Jeffrey G. , Kumar Rajesh , Vaccaro Dennis E.
Published: September 2008

This is the first description of functional immunoassay technology (FIT), which as a diagnostic tool has broad application across the whole spectrum of physiological measurements. In this paper, FIT is used to measure the renal clearance of an ultra low-dose administration of a clinically available contrast reagent for the purpose of obtaining an accurate glomerular filtration rate (GFR) measurement. Biomarker-based GFR estimates offer convenience, but are not accurate and are often misleading. FIT overcomes previous analytic barriers associated with obtaining an accurate GFR measurement. We present the performance characteristics of this diagnostic test and demonstrate the method by directly comparing GFR values obtained by FIT to those obtained by an FDA approved nuclear test in 20 adults. Two subjects were healthy volunteers and the remaining 18 subjects had diagnosed chronic kidney disease, with 12 being kidney transplant recipients. Measured GFR values were calculated by the classic UV/P method and by the blood clearance method. GFR obtained by FIT and the nuclear test correlated closely over a wide range of GFR values (10.9–102.1 ml·min−1·1.73 m−2). The study demonstrates that FIT-GFR provides an accurate and reproducible measurement. This nonradioactive, immunoassay-based approach offers many advantages, chiefly that most laboratories already have the equipment and trained personnel necessary to run an ELISA, and therefore this important diagnostic measurement can more readily be obtained. The FIT-GFR test can be used throughout the pharmaceutical development pipeline: preclinical and clinical trials.
Skeletal muscle adaptation and performance responses to once a day versus twice every second day endurance training regimens
Authors: Yeo Wee Kian , Paton Carl D. , Garnham Andrew P. , Burke Louise M. , Carey Andrew L. , Hawley John A.
Published: September 2008

We determined the effects of a cycle training program in which selected sessions were performed with low muscle glycogen content on training capacity and subsequent endurance performance, whole body substrate oxidation during submaximal exercise, and several mitochondrial enzymes and signaling proteins with putative roles in promoting training adaptation. Seven endurance-trained cyclists/triathletes trained daily (High) alternating between 100-min steady-state aerobic rides (AT) one day, followed by a high-intensity interval training session (HIT; 8 × 5 min at maximum self-selected effort) the next day. Another seven subjects trained twice every second day (Low), first undertaking AT, then 1–2 h later, the HIT. These training schedules were maintained for 3 wk. Forty-eight hours before and after the first and last training sessions, all subjects completed a 60-min steady-state ride (60SS) followed by a 60-min performance trial. Muscle biopsies were taken before and after 60SS, and rates of substrate oxidation were determined throughout this ride. Resting muscle glycogen concentration (412 ± 51 vs. 577 ± 34 μmol/g dry wt), rates of whole body fat oxidation during 60SS (1,261 ± 247 vs. 1,698 ± 174 μmol·kg−1·60 min−1), the maximal activities of citrate synthase (45 ± 2 vs. 54 ± 1 mmol·kg dry wt−1·min−1), and β-hydroxyacyl-CoA-dehydrogenase (18 ± 2 vs. 23 ± 2 mmol·kg dry wt−1·min−1) along with the total protein content of cytochrome c oxidase subunit IV were increased only in Low (all P < 0.05). Mitochondrial DNA content and peroxisome proliferator-activated receptor-γ coactivator-1α protein levels were unchanged in both groups after training. Cycling performance improved by ∼10% in both Low and High. We conclude that compared with training daily, training twice every second day compromised high-intensity training capacity. While selected markers of training adaptation were enhanced with twice a day training, the performance of a 1-h time trial undertaken after a 60-min steady-state ride was similar after once daily or twice every second day training programs.
The Human Dorsal Stream Adapts to Real Actions and 3D Shape Processing: A Functional Magnetic Resonance Imaging Study
Authors: Króliczak G. , McAdam T. D. , Quinlan D. J. , Culham J. C.
Published: September 2008

We tested whether the control of real actions in an ever-changing environment would show any dependence on prior actions elicited by instructional cues a few seconds before. To this end, adaptation of the functional magnetic resonance imaging signal was measured while human participants sequentially grasped three-dimensional objects in an event-related design, using grasps oriented along the same or a different axis of either the same or a different object shape. We found that the bilateral anterior intraparietal sulcus, an area previously linked to the control of visually guided grasping, along with other areas of the intraparietal sulcus, the left supramarginal gyrus, and the right mid superior parietal lobe showed clear adaptation following both repeated grasps and repeated objects. In contrast, the left ventral premotor cortex and the bilateral dorsal premotor cortex, the two premotor areas often linked to response selection, action planning, and execution, showed only grasp-selective adaptation. These results suggest that, even in real action guidance, parietofrontal areas demonstrate differential involvement in visuomotor processing dependent on whether the action or the object has been previously experienced.
Sensory Regulation of Network Components Underlying Ciliary Locomotion inHermissenda
Authors: Crow Terry , Tian Lian-Ming
Published: September 2008

Ciliary locomotion in the nudibranch mollusk Hermissenda is modulated by the visual and graviceptive systems. Components of the neural network mediating ciliary locomotion have been identified including aggregates of polysensory interneurons that receive monosynaptic input from identified photoreceptors and efferent neurons that activate cilia. Illumination produces an inhibition of type Ii(off-cell) spike activity, excitation of type Ie(on-cell) spike activity, decreased spike activity in type IIIiinhibitory interneurons, and increased spike activity of ciliary efferent neurons. Here we show that pairs of type Iiinterneurons and pairs of type Ieinterneurons are electrically coupled. Neither electrical coupling or synaptic connections were observed between Ieand Iiinterneurons. Coupling is effective in synchronizing dark-adapted spontaneous firing between pairs of Ieand pairs of Iiinterneurons. Out-of-phase burst activity, occasionally observed in dark-adapted and light-adapted pairs of Ieand Iiinterneurons, suggests that they receive synaptic input from a common presynaptic source or sources. Rhythmic activity is typically not a characteristic of dark-adapted, light-adapted, or light-evoked firing of type I interneurons. However, burst activity in Ieand Iiinterneurons may be elicited by electrical stimulation of pedal nerves or generated at the offset of light. Our results indicate that type I interneurons can support the generation of both rhythmic activity and changes in tonic firing depending on sensory input. This suggests that the neural network supporting ciliary locomotion may be multifunctional. However, consistent with the nonmuscular and nonrhythmic characteristics of visually modulated ciliary locomotion, type I interneurons exhibit changes in tonic activity evoked by illumination.
A Time‐Series Approach to Non‐Self‐Financing Hedging in a Discrete‐Time Incomplete Market
Authors: Josephy N. , Kimball L. , Steblovskaya V.
Published: September 2008

We present an algorithm producing a dynamic non‐self‐financing hedging strategy in an incomplete
market corresponding to investor‐relevant risk criterion. The optimization is a two‐stage process
that first determines market calibrated model parameters that correspond to the market price of the
option being hedged. In the second stage, an optimal set of model parameters is chosen from the
market calibrated set. This choice is based on stock price simulations using a time‐series model
for stock price jump evolution. Results are presented for options traded on the New York Stock
Exchange.
PPARγ: The Portrait of a Target Ally to Cancer Chemopreventive Agents
Authors: Sainis Ioannis , Vareli Katerina , Karavasilis Vasilios , Briasoulis Evangelos
Published: September 2008

Peroxisome proliferator‐activated receptor‐gamma (PPARγ), one of three ligand‐activated transcription factors named PPAR, has been identified as a molecular target for cancer chemopreventive agents. PPARγ was initially understood as a regulator of adipocyte differentiation and glucose homeostasis while later on, it became evident that it is also involved in cell differentiation, apoptosis, and angiogenesis, biological processes which are deregulated in cancer. It is now established that PPARγ ligands can induce cell differentiation and yield early antineoplastic effects in several tumor types. Moreover, several bioactive natural products with cancer protecting potential are shown to operate through activation of PPARγ. Overall, PPARγ appears to be a prevalent target ally to cancer chemopreventive agents and therefore pursuing research in this area is of great relevance.
Overview of Contemporary Penile Rehabilitation Therapies
Authors: Hinh Peter , Wang Run
Published: September 2008

Introduction. Post-prostatectomy erectile dysfunction affects a considerable number of men and is a significant quality of life issue. There has been a substantial amount of research on the treatment of post-prostatectomy ED, and now there is a rising interest in the concept of penile rehabilitation. The goal of penile rehabilitation is to moderate the destructive processes that occur after prostatectomy in order to preserve erectile function, either through spontaneous or assisted means.Methods. We reviewed published data and experiences of post-prostatectomy penile rehabilitation using regimented interventions of phosphodiesterase inhibitors, vacuum erectile device, and intracavernosal agents, and we present and analyze the research conducted.Results. These studies show improved objective and subjective clinical outcomes in regards to physical parameters, sexual satisfaction, and rates of spontaneous erections.Conclusion. These studies are often limited by small size, study period, and study design. There continues to be a need for large, randomized, placebo controlled trials with adequate followup to fully evaluate the efficacy and cost-effectiveness of the various proposed penile rehabilitation regiments before a clear standard can be established.
The Puzzling Life of Autistic Toddlers: Design Guidelines from the LINKX Project
Authors: van Rijn Helma , Stappers Pieter Jan
Published: September 2008

This paper presents guidelines for designers to help them consider what children with autism value in interactions with their environment. The guidelines were developed during the LINKX project in order to design a language learning toy for these children and are based on literature study, expert interviews, generative techniques, and prototype testing with users. We present both the theoretical or practical background of each guideline together with a discussion how the guideline was evident in the prototype of LINKX. Testing the prototype in the real world helped us to shape the prototype and the guidelines. This paper aims to share our guidelines with the design research community, so that others can use them as steppingstones in their work.
CXCR4 in Cancer and Its Regulation by PPARγ
Authors: Richard Cynthia Lee , Blay Jonathan
Published: September 2008

Chemokines are peptide mediators involved in normal development, hematopoietic and immune regulation, wound healing, and inflammation. Among the chemokines is CXCL12, which binds principally to its receptor CXCR4 and regulates leukocyte precursor homing to bone marrow and other sites. This role of CXCL12/CXCR4 is “commandeered” by cancer cells to facilitate the spread of CXCR4‐bearing tumor cells to tissues with high CXCL12 concentrations. High CXCR4 expression by cancer cells predisposes to aggressive spread and metastasis and ultimately to poor patient outcomes. As well as being useful as a marker for disease progression, CXCR4 is a potential target for anticancer therapies. It is possible to interfere directly with the CXCL12:CXCR4 axis using peptide or small‐molecular‐weight antagonists. A further opportunity is offered by promoting strategies that downregulate CXCR4 pathways: CXCR4 expression in the tumor microenvironment is modulated by factors such as hypoxia, nucleosides, and eicosanoids. Another promising approach is through targeting PPAR to suppress CXCR4 expression. Endogenous PPARγsuch as 15‐deoxy‐Δ12,14‐PGJ2and synthetic agonists such as the thiazolidinediones both cause downregulation of CXCR4 mRNA and receptor. Adjuvant therapy using PPARγagonists may, by stimulating PPARγ‐dependent downregulation of CXCR4 on cancer cells, slow the rate of metastasis and impact beneficially on disease progression.
Change in Long‐Spacing Collagen in Descemet′s Membrane of Diabetic Goto‐Kakizaki Rats and Its Suppression by Antidiabetic Agents
Authors: Akimoto Yoshihiro , Sawada Hajime , Ohara-Imaizumi Mica , Nagamatsu Shinya , Kawakami Hayato
Published: September 2008

We examined changes in the ultrastructure and localization of major extracellular matrix components, including 5 types of collagen (type I, III, IV, VI, and VIII), laminin, fibronectin, and heparan sulfate proteoglycan in Descemet′s membrane of the cornea of diabetic GK rats. In the cornea of diabetic GK rats, more long‐spacing collagen fibrils were observed in Descemet′s membrane than in the membrane of the nondiabetic Wistar rats. Both GK and Wistar rats showed an age‐dependent increase in the density of the long‐spacing collagen. Immunoelectron microscopy showed that type VIII collagen was localized in the internodal region of the long‐spacing collagen, which was not labelled by any of the other antibodies used. The antidiabetic agents nateglinide and glibenclamide significantly suppressed the formation of the long‐spacing collagen in the diabetic rats. Long‐spacing collagen would thus be a useful indicator for studying diabetic changes in the cornea and the effect of antidiabetic agents.
The Management of Sacral Schwannoma: Report of Four Cases and Review of Literature
Authors: Chandhanayingyong Chandhanarat , Asavamongkolkul Apichat , Lektrakul Nittaya , Muangsomboon Sorranart
Published: September 2008

Sacral schwannoma is a rare retrorectal tumor in adults. Postoperative sacral neurological deficit is difficult to avoid. Currently, there is no established consensus regarding best treatment options. We present the management and outcomes of sacral schwannoma in 4 patients treated with intralesional curettage and postoperative radiation. There were 3 women and one man (average age: 45.5 years) with long duration of lumbosacral pain with or without radiculopathy. Intralesional curettage was performed by posterior approach and adjuvant radiation therapy with dosage of 5000–6600 cGy was given after surgery. The mean follow-up time was 18 months (range 4–23 months). Symptoms of radiculopathy had decreased in all patients. The recent radiographic findings show evidence of sclerosis at the sacrum one year postoperatively, but the size was unchanged. Intralesional curettage and adjuvant radiation therapy can be used in the treatment of sacral schwannoma to relieve symptoms and preserve neurological function.
Mechanism of In vitro Pancreatic Cancer Cell Growth Inhibition by Melanoma Differentiation–Associated Gene-7/Interleukin-24 and Perillyl Alcohol
Authors: Lebedeva Irina V. , Su Zhao-zhong , Vozhilla Nichollaq , Chatman Lejuan , Sarkar Devanand , Dent Paul , Athar Mohammad , Fisher Paul B.
Published: September 2008

The death rate for pancreatic cancer approximates the number of new cases each year, and when diagnosed, current therapeutic regimens provide little benefit in extending patient survival. These dire statistics necessitate the development of enhanced single or combinatorial therapies to decrease the pathogenesis of this invariably fatal disease. Melanoma differentiation–associated gene-7/interleukin-24 (mda-7/IL-24) is a potent cancer gene therapeutic because of its broad-spectrum cancer-specific apoptosis-inducing properties as well as its multipronged indirect antitumor activities. However, pancreatic cancer cells show inherent resistance to mda-7/IL-24 that is caused by a block of translation of mda-7/IL-24 mRNA in these tumor cells. We now reveal that a dietary agent perillyl alcohol (POH) in combination with Ad.mda-7 efficiently reverses the mda-7/IL-24 “protein translational block” by inducing reactive oxygen species, thereby resulting in mda-7/IL-24 protein production, growth suppression, and apoptosis. Pharmacologic inhibitor and small interfering RNA studies identify xanthine oxidase as a major source of superoxide radical production causing these toxic effects. Because both POH and Ad.mda-7 are being evaluated in clinical trials, combining a dietary agent and a virally delivered therapeutic cytokine provides an innovative approach for potentially treating human pancreatic cancer. [Cancer Res 2008;68(18):7439–47]