bluuebunny/crossref_metadata_2025 huggingface dataset:
OdDHL Inhibits T Cell Subset Differentiation and Delays Diabetes Onset in NOD Mice
Authors: Gaisford Wendy , Pritchard David I. , Cooke Anne
Published: June 2011

Some infectious diseases have been shown to halt the onset of autoimmune disease in animal models and have been suggested to also influence autoimmune pathology in humans. The isolation and study of small molecules and proteins from the infectious agents responsible for the protective effect will enable a mechanistic understanding of how these components may prevent or delay the onset of autoimmunity. In this study we confirm that the quorum-sensing signal molecule OdDHL fromPseudomonas aeruginosacan delay the onset of type 1 diabetes in the NOD mouse model. Furthermore, using an antigen-presenting cell-free system, we find not only that OdDHL inhibits the proliferation of naïve T cells but also that it directly inhibits the differentiation of T cell subsets. OdDHL was shown to have no effect on the inhibition of primed and committed differentiated T cell responses, suggesting that that immune mechanism mediated by this molecule may be more restricted to initial stages of infection.
A Live-Attenuated Chimeric Porcine Circovirus Type 2 (PCV2) Vaccine Is Transmitted to Contact Pigs but Is Not Upregulated by Concurrent Infection with Porcine Parvovirus (PPV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Is Efficacious in a PCV2b-PRRSV-PPV Challenge Model
Authors: Opriessnig T. , Shen H. G. , Pal N. , Ramamoorthy S. , Huang Y. W. , Lager K. M. , Beach N. M. , Halbur P. G. , Meng X. J.
Published: June 2011

The live chimeric porcine circovirus type 2 (PCV2) vaccine with the capsid gene of the emerging subtype 2b cloned in the genomic backbone of the nonpathogenic PCV1 is attenuatedin vivoand induces protective immunity against PCV2. To further determine the safety and efficacy of this experimental vaccine, we tested for evidence of pig-to-pig transmission by commingling nonvaccinated and vaccinated pigs, determined potential upregulation by simultaneous vaccination and infection with porcine parvovirus (PPV) and porcine reproductive and respiratory syndrome virus (PRRSV), and determined vaccine efficacy by challenging pigs 4 weeks after vaccination with PCV2b, PRRSV, and PPV. Forty-six 21-day-old, PCV2-naïve pigs were randomly assigned to one of six groups. Twenty-nine of 46 pigs were challenged with PCV2b, PRRSV, and PPV at day 28, 8/46 remained nonvaccinated and nonchallenged and served as negative controls, and 9/46 remained nonchallenged and served as vaccination controls. All animals were necropsied at day 49. PCV1-PCV2 viremia was detected in nonvaccinated contact pigs commingled with vaccinated pigs, indicating pig-to-pig transmission; however, PCV1-PCV2 DNA levels remained low in all vaccinated and contact pigs regardless of concurrent infection. Finally, vaccination 28 days before challenge resulted in significantly (P< 0.05) decreased amounts of PCV2 in tissues and sera and significantly (P< 0.05) reduced macroscopic and microscopic lesions. The results of this study indicate that the experimental live-attenuated chimeric PCV2 vaccine, although transmissible to contact pigs, remains attenuated in pigs concurrently infected with PRRSV and PPV and induces protective immunity against PCV2b when it is administered 28 days before PCV2 exposure.
Seroprevalence to Influenza A(H1N1) 2009 Virus—Where Are We?
Authors: Broberg Eeva , Nicoll Angus , Amato-Gauci Andrew
Published: June 2011

Age-specific seroprevalences for influenza virus make important contributions to estimating the burden of infection and determining the vulnerable populations. It is especially difficult to know the true clinical attack rates of the 2009 influenza A(H1N1) pandemic; however, we can estimate infection rates through analyses of seroprevalences based on national studies from different continents and countries with different demographics. After the 2009 influenza A(H1N1) pandemic, seroprevalence studies found 5 to 60% of populations across different continents and age groups having antibodies against the A(H1N1) 2009 virus. The seropositivity was highest in children and teenagers (20 to 60%) as well as in the elderly older than 80 years (20 to 40%). Preexisting cross-reactive antibodies against the virus were present mostly in sera of older people (born before 1950) who could have encountered viruses descended from the 1918 pandemic viruses. Experience with the 2009 pandemic indicates how essential early and timely serology data against the emerging virus can be for informing decisions on use of antivirals and vaccination campaigns, especially in regard to risk groups. The objectives of this review were to summarize the current data available on seroprevalence before and after the 2009 influenza A(H1N1) pandemic and the lessons learned for future pandemic preparedness.
Comparison of Two Molecular Methods for Rapid Diagnosis of Extrapulmonary Tuberculosis
Authors: Causse Manuel , Ruiz Pilar , Gutiérrez-Aroca Juan Bautista , Casal Manuel
Published: June 2011

Application of real-time PCR for the detection of
Mycobacterium tuberculosis
enables results to be obtained in about 2 h. A total of 340 nonrespiratory samples were processed using two real-time PCR assay kits: Xpert MTB/RIF and Cobas TaqMan MTB. The sensitivity and specificity of the Xpert assay were 95% and 100%, respectively, compared to 78% and 98% for the Cobas assay.
Rapid Identification of Cryptococcus neoformans and Cryptococcus gattii by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: McTaggart Lisa R. , Lei Eric , Richardson Susan E. , Hoang Linda , Fothergill Annette , Zhang Sean X.
Published: June 2011

Compared to DNA sequence analysis, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) correctly identified 100% of
Cryptococcus
species, distinguishing the notable pathogens
Cryptococcus neoformans
and
C. gattii
. Identification was greatly enhanced by supplementing a commercial spectral library with additional entries to account for subspecies variability.
Diagnostic Consequences of Cytomegalovirus Glycoprotein B Polymorphisms
Authors: Novak Zdenek , Chowdhury Nazma , Ross Shannon A. , Pati Sunil K. , Fowler Karen , Boppana Suresh B.
Published: June 2011

Failure of a cytomegalovirus (CMV) real-time PCR assay targeting glycoprotein B (gB) was investigated. A multiplex assay targeting gB and immediate-early 2 (IE2) genes showed discordant results (gB negative and IE positive or a >10-fold-higher viral load with IE primers) in saliva from 14.6% of CMV-infected newborns. Sequencing revealed 3 patterns of gB variations.
Characterization of Glycosylation Profiles of HIV-1 Transmitted/Founder Envelopes by Mass Spectrometry
Authors: Go Eden P. , Hewawasam Geetha , Liao Hua-Xin , Chen Haiyan , Ping Li-Hua , Anderson Jeffrey A. , Hua David C. , Haynes Barton F. , Desaire Heather
Published: June 2011

The analysis of HIV-1 envelope carbohydrates is critical to understanding their roles in HIV-1 transmission as well as in binding of envelope to HIV-1 antibodies. However, direct analysis of protein glycosylation by glycopeptide-based mass mapping approaches involves structural simplification of proteins with the use of a protease followed by an isolation and/or enrichment step before mass analysis. The successful completion of glycosylation analysis is still a major analytical challenge due to the complexity of samples, wide dynamic range of glycopeptide concentrations, and glycosylation heterogeneity. Here, we use a novel experimental workflow that includes an up-front complete or partial enzymatic deglycosylation step before trypsin digestion to characterize the glycosylation patterns and maximize the glycosylation coverage of two recombinant HIV-1 transmitted/founder envelope oligomers derived from clade B and C viruses isolated from acute infection and expressed in 293T cells. Our results show that both transmitted/founder Envs had similar degrees of glycosylation site occupancy as well as similar glycan profiles. Compared to 293T-derived recombinant Envs from viruses isolated from chronic HIV-1, transmitted/founder Envs displayed marked differences in their glycosylation site occupancies and in their amounts of complex glycans. Our analysis reveals that the glycosylation patterns of transmitted/founder Envs from two different clades (B and C) are more similar to each other than they are to the glycosylation patterns of chronic HIV-1 Envs derived from their own clades.
ON MANIFOLDS ADMITTING THE CONSISTENT LAGRANGIAN FORMULATION FOR HIGHER SPIN FIELDS
Authors: BUCHBINDER I. L. , KRYKHTIN V. A. , LAVROV P. M.
Published: June 2011

We study a possibility of Lagrangian formulation for free massive higher spin bosonic totally symmetric tensor field on the background manifold characterizing by the arbitrary metric, vector and third-rank tensor fields in the framework of BRST approach. Assuming analytical dependence on the mass, curvatures and the other background fields in the Lagrangian and using the most general linearized ansatz for transversality condition, we prove that the consistent formulation is possible only in constant curvature space and that there is only a trivial possibility to include the vector and third-rank tensor in the theory. This result finally proves that the consistent Lagrangian formulation at the conditions under consideration is possible only in constant curvature Riemann space.
TeV SCALE MODELS OF NEUTRINO MASSES AND THEIR PHENOMENOLOGY
Authors: CHEN MU-CHUN , HUANG JINRUI
Published: June 2011

We review various TeV scale models for neutrino masses utilizing different types of seesaw mechanisms, higher dimensional operators, expanded gauge symmetries, or low scale extra dimensions. In addition, we discuss the implications of these models for the collider experiments and low energy lepton flavor violation searches.
SYMMETRY REDUCTIONS AND EXPLICIT SOLUTIONS OF (3+1)-DIMENSIONAL BURGERS SYSTEM
Authors: LV NA , MEI JIAN-QIN , ZHANG HONG-QING
Published: June 2011

With the aid of symbolic computation, we use the Lie group method to find the Lie point symmetries of (3+1)-dimensional Burgers system, and reduce the system with the obtained symmetries. As a result, many kinds of new symmetry reductions have been presented. And some explicit solutions are given due to the Riccati equation method.
VARIATIONAL ANALYSIS OF FLAT-TOP SOLITONS IN BOSE–EINSTEIN CONDENSATES
Authors: BAIZAKOV B. B. , BOUKETIR A. , MESSIKH A. , BENSEGHIR A. , PUMAROV B. A.
Published: June 2011

Static and dynamic properties of matter-wave solitons in dense Bose–Einstein condensates, where three-body interactions play a significant role, have been studied by a variational approximation (VA) and numerical simulations. For experimentally relevant parameters, matter-wave solitons may acquire a flat-top shape, which suggests employing a super-Gaussian trial function for VA. Comparison of the soliton profiles, predicted by VA and those found from numerical solution of the governing Gross–Pitaevskii equation shows good agreement, thereby validating the proposed approach.
N-ORDER SQUEEZING AND POISSONIAN STATISTICS OF A FOUR-LEVEL W-TYPE ATOM INTERACTING WITH ONE-MODE CAVITY FIELD
Authors: ABDEL-WAHAB N. H.
Published: June 2011

In this paper we consider a four-level W-type atom interacting with a single-mode quantized electromagnetic field in the presence of the Kerr medium. The atom and the field are initially prepared in the excited state and coherent state, respectively. The influence of the Kerr medium on the N-order squeezing and Poissonian statistics is investigated. We found that the maximum value of squeezing decreases by increasing the order N. Also, we noticed that the Kerr-like medium decreases the amount of squeezing and increases the sub-Poissonian statistics.
THERMOCHROMIC BEHAVIOR OF A NOVEL NEMATIC LIQUID CRYSTAL MIXTURE: EFFECTS OF CHIRAL DOPING
Authors: KAPILA SHIKHA , RAINA K. K.
Published: June 2011

Chirality was induced in a room temperature nematic liquid crystalline mixture. The phase transitions of doped samples were studied and thermochromic response of the mixture was investigated via RGB (Red-Green-Blue) and Hue measurements.
FLOW OVER FRACTALS: DRAG FORCES AND NEAR WAKES
Authors: KANG HYUNG SUK , DENNIS DUANE , MENEVEAU CHARLES
Published: June 2011

An experimental study of interactions between a high Reynolds number fluid flow and multi-scale, fractal, objects is performed. Studying such interactions is required to improve our current understanding of wind or ocean current effects on vegetation elements, which often display fractal-like branching geometries. The main objectives of the study are to investigate the effects of the range of scales (generation numbers) of the fractal object and of the incoming flow condition on the drag force and drag coefficient, and to observe flow features in the near wake region resulting from the interaction. In this study, Sierpinski carpets and triangles with the scale ratios of 1/3 and 1/2, respectively, are employed. The fractal dimensions of the Sierpinski carpet and triangle are D = 1.893 and 1.585, respectively. Each pre-fractal object is mounted on a load cell at the centerline in a wind tunnel. Two types of inflow conditions are considered: laminar flow and high-turbulence level, active-grid-generated, flow. As a first approximation, we find the drag coefficients are approximately constant of order unity, and do not depend upon generation number of the pre-fractal when defined using the actual frontal area that varies as function of generation number. Still, the drag coefficient of the Sierpinski carpet increases weakly with number of generations indicating that the drag force decreases less than the cross-sectional area. For the Sierpinski triangle a similar trend is observed at large scales. However, the drag coefficient displays a peak at the third generation and then shows a decreasing trend as smaller scales are included for higher generation cases. The drag coefficient for the turbulent flow is larger than that for the laminar flow for all the fractal generations observed. Flow features (mean velocity, mean vorticity, and turbulence root-mean-square distributions) are measured by using stereoscopic Particle Image Velocimetry to observe various scales of the motion in the near wake of the pre-fractal objects. Strong shear layers are formed behind the fractal objects depending on the hole locations of different generations, which results in the formation of various length scales of the dominant turbulence structures. The smaller scale wakes are found to merge behind the Sierpinski carpet, whereas they are merely damped behind the Sierpinski triangle.
A COMPARATIVE STUDY OF BAYESIAN AND MAXIMUM LIKELIHOOD APPROACHES FOR ARCH MODELS WITH EVIDENCE FROM BRAZILIAN FINANCIAL SERIES
Authors: ANDRADE MARINHO G. , OLIVEIRA SANDRA C.
Published: June 2011

The purpose of this study is to address the inference problem of the parameters of autoregressive conditional heteroscedasticity (ARCH) models. Specifically, we present a comparison of the two approaches — Bayesian and Maximum Likelihood (ML) for ARCH models, and the specific mathematical and algorithmic formulations of these approaches. In the ML, estimation we obtain confidence intervals by using the Bootstrap simulation technique. In the Bayesian estimation, we present a reparametrization of the model which allows us to apply prior normal densities to the transformed parameters. The posterior estimates are obtained using Monte Carlo Markov Chain (MCMC) methods. The methodology is exemplified by considering two Brazilian financial time series: the Bovespa Stock Index — IBovespa and the Telebrás series. The order of each ARCH model is selected by using the Bayesian Information Criterion (BIC).
Activation of P2Y1 and P2Y2 receptors induces chloride secretion via calcium-activated chloride channels in kidney inner medullary collecting duct cells
Authors: Rajagopal Madhumitha , Kathpalia Paru P. , Thomas Sheela V. , Pao Alan C.
Published: June 2011

Dysregulation of urinary sodium chloride (NaCl) excretion can result in extracellular fluid (ECF) volume expansion and hypertension. Recent studies demonstrated that urinary nucleotide excretion increases in mice ingesting a high-salt diet and that these increases in extracellular nucleotides can signal through P2Y2 receptors in the kidney collecting duct to inhibit epithelial Na+ channels (ENaC). However, under conditions of ECF volume expansion brought about by high-dietary salt intake, ENaC activity should already be suppressed. We hypothesized that alternative pathways exist by which extracellular nucleotides control renal NaCl excretion. We used an inner medullary collecting duct (mIMCD-K2) cell line in an Ussing chamber system as a model to study additional ion transport pathways that are regulated by extracellular nucleotides. When ENaC was inhibited, the addition of adenosine triphosphate (ATP) to the basal side of cell sheets activated both P2Y1 and P2Y2 receptors, inducing a transient increase in short-circuit current ( Isc); addition of ATP to the apical side activated only P2Y2 receptors, inducing first a transient and then a sustained increase in Isc. The ATP-induced increases in Isc were blocked by pretreatment with a phospholipase C (PLC) inhibitor, a calcium (Ca2+) chelator, or Ca2+-activated Cl− channel (CACC) inhibitors, suggesting that ATP signals through both PLC and intracellular Ca2+ to activate CACC. We propose that P2Y1 and P2Y2 receptors operate in tandem in IMCD cells to provide an adaptive mechanism for enhancing urinary NaCl excretion in the setting of high-dietary NaCl intake.
Development of new peptide-based tools for studying synaptic ribbon function
Authors: Francis Adam A. , Mehta Bhupesh , Zenisek David
Published: June 2011

Synaptic ribbons are proteinaceous specialized electron-dense presynaptic structures found in nonspiking sensory cells of the vertebrate nervous system. Understanding the function of these structures is an active area of research (reviewed in Matthews G, Fuchs P. Nat Rev Neurosci 11: 812–822, 2010). Previous work had shown that ribbons could be effectively labeled and visualized using peptides that bind to the synaptic ribbon protein RIBEYE via a PXDLS motif (Zenisek D, Horst NK, Merrifield C, Sterling P, Matthews G. J Neurosci 24: 9752–9759, 2004). Here, we expand on the previous work to develop new tools and strategies for 1) better visualizing synaptic ribbons, and 2) monitoring and manipulating calcium on the synaptic ribbon. Specifically, we developed a new higher-affinity peptide-based label for visualizing ribbons in live cells and two strategies for localizing calcium indicators to the synaptic ribbon.
Information conveyed by inferior colliculus neurons about stimuli with aligned and misaligned sound localization cues
Authors: Slee Sean J. , Young Eric D.
Published: June 2011

Previous studies have demonstrated that single neurons in the central nucleus of the inferior colliculus (ICC) are sensitive to multiple sound localization cues. We investigated the hypothesis that ICC neurons are specialized to encode multiple sound localization cues that are aligned in space (as would naturally occur from a single broadband sound source). Sound localization cues including interaural time differences (ITDs), interaural level differences (ILDs), and spectral shapes (SSs) were measured in a marmoset monkey. Virtual space methods were used to generate stimuli with aligned and misaligned combinations of cues while recording in the ICC of the same monkey. Mutual information (MI) between spike rates and stimuli for aligned versus misaligned cues were compared. Neurons with best frequencies (BFs) less than ∼11 kHz mostly encoded information about a single sound localization cue, ITD or ILD depending on frequency, consistent with the dominance of ear acoustics by either ITD or ILD at those frequencies. Most neurons with BFs >11 kHz encoded information about multiple sound localization cues, usually ILD and SS, and were sensitive to their alignment. In some neurons MI between stimuli and spike responses was greater for aligned cues, while in others it was greater for misaligned cues. If SS cues were shifted to lower frequencies in the virtual space stimuli, a similar result was found for neurons with BFs <11 kHz, showing that the cue interaction reflects the spectra of the stimuli and not a specialization for representing SS cues. In general the results show that ICC neurons are sensitive to multiple localization cues if they are simultaneously present in the frequency response area of the neuron. However, the representation is diffuse in that there is not a specialization in the ICC for encoding aligned sound localization cues.
Impaired sensory nerve function and axon morphology in mice with diabetic neuropathy
Authors: Lennertz Richard C. , Medler Karen A. , Bain James L. , Wright Douglas E. , Stucky Cheryl L.
Published: June 2011

Diabetes is the most prevalent metabolic disorder in the United States, and between 50% and 70% of diabetic patients suffer from diabetes-induced neuropathy. Yet our current knowledge of the functional changes in sensory nerves and their distal terminals caused by diabetes is limited. Here, we set out to investigate the functional and morphological consequences of diabetes on specific subtypes of cutaneous sensory nerves in mice. Diabetes was induced in C57Bl/6 mice by a single intraperitoneal injection of streptozotocin. After 6–8 wk, mice were characterized for behavioral sensitivity to mechanical and heat stimuli followed by analysis of sensory function using teased nerve fiber recordings and histological assessment of nerve fiber morphology. Diabetes produced severe functional impairment of C-fibers and rapidly adapting Aβ-fibers, leading to behavioral hyposensitivity to both mechanical and heat stimuli. Electron microscopy images showed that diabetic nerves have axoplasm with more concentrated organelles and frequent axon-myelin separations compared with control nerves. These changes were restricted to the distal nerve segments nearing their innervation territory. Furthermore, the relative proportion of Aβ-fibers was reduced in diabetic skin-nerve preparations compared with nondiabetic control mice. These data identify significant deficits in sensory nerve terminal function that are associated with distal fiber loss, morphological damage, and behavioral hyposensitivity in diabetic C57Bl/6 mice. These findings suggest that diabetes damages sensory nerves, leading to functional deficits in sensory signaling that underlie the loss of tactile acuity and pain sensation associated with insensate diabetic neuropathy.
Hybrid PSO‐SA Type Algorithms for Multimodal Function Optimization and Reducing Energy Consumption in Embedded Systems
Authors: Idoumghar Lhassane , Melkemi Mahmoud , Schott René , Aouad Maha Idrissi
Published: June 2011

The paper presents a novel hybrid evolutionary algorithm that combines Particle Swarm Optimization (PSO) and Simulated Annealing (SA) algorithms.
When a local optimal solution is reached with PSO, all particles gather around it, and escaping from this local optima becomes difficult. To avoid premature convergence of PSO, we present a new hybrid evolutionary algorithm, called HPSO‐SA, based on the idea that PSO ensures fast convergence, while SA brings the search out of local optima because of its strong local‐search ability. The proposed HPSO‐SA algorithm is validated on ten standard benchmark multimodal functions for which we obtained significant improvements. The results are compared with these obtained by existing hybrid PSO‐SA algorithms. In this paper, we provide also two versions of HPSO‐SA (sequential and distributed) for minimizing the energy consumption in embedded systems memories. The two versions, of HPSO‐SA, reduce the energy consumption in memories from 76% up to 98% as compared to Tabu Search (TS). Moreover, the distributed version of HPSO‐SA provides execution time saving of about 73% up to 84% on a cluster of 4 PCs.
Ursolic Acid Inhibits Proliferation and Induces Apoptosis of Cancer Cells In Vitro and In Vivo
Authors: Wang Xuemei , Zhang Fan , Yang Ling , Mei Ying , Long Hai , Zhang Xiaowen , Zhang Jialing , Qimuge-Suyila  , Su Xiulan
Published: June 2011

The aims of the study are to explore the effect of ursolic acid (UA) on the growth of gastric cancer cell line BGC‐803 and hepatocellular cancer cell H22 xenograft and to understand the mechanism. UA inhibits growth of BGC‐803 cells in vitro in dose‐dependent and time‐dependent manner. Treated with UA in vivo, tumor cells can be arrested to G0/G1 stage. The apoptotic rate was significantly increased in tumor cells treated with UA both in vitro and in vivo. DNA fragmentation was found in BGC‐803 cells exposed to UA. UA activated caspase‐3, ‐8, and ‐9 and down regulated expression of Bcl‐2 in BGC‐803 cells. The expression of caspase‐3 and ‐8 was elevated in tumor cells from xenograft treated with UA. 18F‐FLT PET‐CT imaging confirmed tumor model and UA effectiveness. Our results indicated that UA inhibits growth of tumor cells both in vitro and in vivo by decreasing proliferation of cells and inducing apoptosis.
Pancreas Transplantation: Does Age Increase Morbidity?
Authors: Afaneh Cheguevara , Rich Barrie S. , Aull Meredith J. , Hartono Choli , Leeser David B. , Kapur Sandip
Published: June 2011

Introduction. Pancreas transplantation (PTx) is the only definitive intervention for type 1 diabetes. Medical advancements in diabetes care have led to an aging PTx candidate pool. We report our experience with patients ≥50 years of age undergoing PTx.Methods. We reviewed 136 consecutive PTx patients at our institution from 1996–2010; 17 were ≥50 years of age. We evaluated demographics, surgical complications, acute rejection (AR) rates, nonsurgical infections, and survival outcomes.Results. Demographic data was similar () between groups, excluding age. The two groups had comparable major and minor surgical complication rates ( and , resp.). The older group had a lower 1-year and overall AR rate ( and , resp.). The incidence of non-surgical infections and overall patient and graft survival was similar between groups ().Conclusion. Older patients with type 1 diabetes are feasible candidates for PTx, as surgical morbidity, incidence of infections, and AR rates are low.
Necessary and Sufficient Conditions for Positive Solutions of Second‐Order Nonlinear Dynamic Equations on Time Scales
Authors: Zhu Zhi-Qiang
Published: June 2011

This paper is concerned with the existence of nonoscillatory solutions for
the nonlinear dynamic equation on time scales. By making use of the generalized Riccati transformation technique, we
establish some necessary and sufficient criteria to guarantee the existence. The last examples show that our results can be applied on the differential equations, the difference equations, and the q‐difference equations.
Interleukin-1α Mediates the Antiproliferative Effects of 1,25-Dihydroxyvitamin D3 in Prostate Progenitor/Stem Cells
Authors: Maund Sophia L. , Barclay Wendy W. , Hover Laura D. , Axanova Linara S. , Sui Guangchao , Hipp Jason D. , Fleet James C. , Thorburn Andrew , Cramer Scott D.
Published: June 2011

Vitamin D3 is a promising preventative and therapeutic agent for prostate cancer, but its implementation is hampered by a lack of understanding about its mechanism of action. Upon treatment with 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3, vitamin D3], the metabolically active form of vitamin D3, adult prostate progenitor/stem cells (PrP/SC) undergo cell-cycle arrest, senescence, and differentiation to an androgen receptor–positive luminal epithelial cell fate. Microarray analyses of control- and vitamin D3–treated PrP/SCs revealed global gene expression signatures consistent with induction of differentiation. Interestingly, one of the most highly upregulated genes by vitamin D3 was the proinflammatory cytokine interleukin-1α (IL-1α). Systems biology analyses supported a central role for IL-1α in the vitamin D3 response in PrP/SCs. siRNA-mediated knockdown of IL-1α abrogated vitamin D3–induced growth suppression, establishing a requirement for IL-1α in the antiproliferative effects of vitamin D3 in PrP/SCs. These studies establish a system to study the molecular profile of PrP/SC differentiation, proliferation, and senescence, and they point to an important new role for IL-1α in vitamin D3 signaling in PrP/SCs. Cancer Res; 71(15); 5276–86. ©2011 AACR.
Art Therapy May Reduce Psychopathology in Schizophrenia by Strengthening the Patients’ Sense of Self: A Qualitative Extended Case Report
Authors: Teglbjaerg Hanne Stubbe
Published: June 2011

Background: Many forms of artistic expression and art therapy are widely used in psychiatric treatment, but we lack an understanding of how artistic expression may interfere with psychopathology. Method: Art therapy inspired by the Expressive Arts was offered for 1 year to two groups of outpatients. One group consisted of patients with severe schizophrenia and the other group of 5 nonpsychotic psychiatric patients with depression and/or personality disorders. The course of therapy was described systematically, and the experience of each patient was examined using interviews and written evaluations before and after therapy and at a 1-year follow-up. A qualitative analysis was done to determine how art therapy affects the psychopathology of the patients. Results: The patients used the art therapy in many different ways. The most important benefit of the art therapy was a strengthening of the patients’ sense of self. This was accomplished by engagement in the artistic process and by aesthetic reflections on the painted images. The stronger sense of self diminished the tension arising from interpersonal contact, boosting their self-esteem and thereby improving their social competences. Conclusion: All patients reported a very good outcome, and the qualitative analysis showed that the positive effect of art therapy is mainly due to a strengthening of the patients’ minimal sense of self.
Hemoperfusion Treatment in a Septic Shock Patient with Autosomal Dominant Polycystic Kidney Disease and Increased HMGB1 Protein Levels
Authors: Nakamura Tsukasa , Kawagoe Yasuhiro , Ueda Yoshihiko , Yamada Shingo , Koide Hikaru
Published: June 2011

This case report describes polymyxin B-immobilized fiber (PMX-F) treatment of septic shock caused by pyelonephritis in a 68-year-old woman with autosomal dominant polycystic kidney disease. She was admitted for severe lower left abdominal pain, high fever (40°C) and gross hematuria. Her endotoxin and high-mobility group box-1 protein (HMGB1) levels were extremely elevated. Her blood pressure was 68/36 mm Hg. Urinalysis revealed innumerable white blood cells (WBCs). Blood and urine cultures were positive for Klebsiella pneumoniae and Pseudomonas aeruginosa. Plain abdominal radiography showed large kidney shadows and calcium deposition. Septic shock with endotoxemia was diagnosed. Her symptoms of septic shock persisted for 3 days with antibiotics, γ-globulin and dopamine. Direct hemoperfusion was performed twice with a PMX-F column. The patient’s body temperature, WBC count and C-reactive protein level decreased. Her blood endotoxin level and blood HMGB1 level also decreased to an almost normal level. She was discharged on day 23 after admission.
Distribution of Isoflavones in Samples of Serum, Liver and Mammary Glands of Rats or Pigs Fed Dietary Isoflavones
Authors: Farmer Chantal , Dyck Monica , Robertson Patrick , Dahiya Jagroop , Sepehr Estatira , Fan Li , Nicolidakis Helen , Curran Ivan , Cooke Gerard M.
Published: June 2011

Background/Aims: There has been great interest in the potential beneficial and adverse health effects of dietary isoflavones. Determination of tissue concentrations of isoflavone metabolites provides an insight into the potential bioactivity of dietary isoflavones. However, data on the distribution of isoflavones in animal models fed dietary isoflavones are limited. In this study, additional data on the distribution of isoflavones in serum and/or tissues of rats and pigs fed dietary isoflavones were generated. Methods: Rats (male and female) were fed a casein control diet (containing no isoflavones) and an isoflavone-supplemented diet (containing an alcohol-washed soy protein isolate plus NOVASOY, providing a total of 1,047 mg/kg of total isoflavones). Female pigs were fed a control diet (without soy) containing 17.5 mg/kg of isoflavones, a soy diet containing 582.8 mg/kg of isoflavones or a soy diet supplemented with a daily dose of 2.3 g (equivalent to 42.0 and 14.5 mg/kg of body weight at the onset and end of treatment, respectively) of crystalline genistein. The concentrations of isoflavones in serum and tissues (liver and mammary gland) and in tissues (liver and mammary gland) of pigs were determined via a sensitive and rapid method using liquid chromatography/mass spectrometry. Results: Rats fed the control diet containing no isoflavones had nondetectable levels of isoflavone metabolites in serum, liver and mammary gland samples. Rats fed the isoflavone-supplemented diet had the greatest levels of equol, followed by genistein, daidzein and glycitein, respectively, in their serum, livers and mammary glands. The concentrations of total isoflavones (daidzein, equol and genistein plus glycitein) in serum were significantly (p < 0.05) greater in male rats vs. female rats, but the reverse was true in the case of livers. Concentrations of daidzein, equol, genistein and glycitein were lowest (p < 0.05) in the livers of pigs fed the control diet, and in the mammary glands of female pigs there was only an effect of feeding soy plus genistein on the concentrations of daidzein and equol (p <0.05). Conclusions: The current data therefore show gender as well as species differences in the tissue distribution of isoflavones.
Platelets regulate CD4+ T-cell differentiation via multiple chemokines in humans
Authors: Gerdes Norbert , Zhu Linjing , Ersoy Maria , Hermansson Andreas , Hjemdahl Paul , Hu Hu , Hansson Göran K. , Li Nailin
Published: June 2011

Atherosclerosis is an inflammatory and thrombotic disease. Both platelets and lymphocytes play important roles in atherogenesis. However, information on their interaction is limited. We therefore studied how platelets regulate CD4+ T cell activation and differentiation. Human CD4+ T cells and autologous platelets were co-cultured. Platelets concentration-dependently enhanced anti-CD3/CD28-induced IFNγ production by CD4+ T cells, but attenuated their proliferation. Abrogation of heterotypic cell-cell contact partially reversed the enhancement, and supernatant from activated platelets partially mimicked the enhancement, suggesting that platelets exert their effects via both soluble mediators and direct cell-cell contact. Platelets enhanced the production of IL-10 and cytokines characteristic for type 1 T helper (TH1) (IFNγ/ TNFα) and TH17 (IL-17) cells, but influenced TH2 cytokines (IL-4/IL-5) little. The cytokine responses were accompanied by enhanced TH1/TH17/TReg differentiation. Using neutralising antibodies and recombinant PF4, RANTES, and TGFβ, we found that platelet-derived PF4 and RANTES enhanced both pro- and anti-inflammatory cytokine production, whilst recombinant TGFβ enhanced IL-10 but not TNFα production. In conclusion, platelets enhance the differentiation and cytokine production of anti-CD3/CD28-stimulated CD4+ T cells via both multiple chemokines and direct cell-cell contact. Our study provides new insights into the cross-talk between thrombosis and adaptive immunity, and indicates that platelets can enhance T-effector cell development.
Cultural Construction of Success and Epistemic Motives Moderate American-Chinese Differences in Reward Allocation Biases
Authors: Leung Angela K.- y. , Kim Young-Hoon , Zhang Zhi-Xue , Tam Kim-Pong , Chiu Chi-yue
Published: June 2011

When the relative contribution of the self and the group to a group success is unclear, Americans tend to exhibit a self-serving bias (rewarding the self more than what the self deserves), whereas the Chinese tend to exhibit an other-serving bias (rewarding the group more than the group deserves). In a study comparing the reward allocation biases of Americans and Chinese in different group outcome conditions, the authors showed that the abovementioned cultural difference is found (a) only for culturally congruent success experience (attaining approach goals for Americans and avoidance goals for Chinese) and (b) among individuals who are motivated by the need for cognitive closure to exhibit culturally typical responses. This finding has important implications for understanding the dynamic nature of cultural influences on social behaviors.
Experiences of Self-Esteem in Outpatients Diagnosed With Psychosis
Authors: Frank Denise M. , Davidson Larry
Published: June 2011

The aim of the article is explore the meaning of self-esteem for individuals with psychotic disorders. To understand how individuals with psychosis experience self-esteem, eight participants (four females and four males) were interviewed using a semistructured open-ended format with scripted questions. Individuals with psychotic disorders maintained a sense of self by pursuing social and interpersonal activities that sustained and enhanced their self-esteem. Neither the positive symptoms nor the negative symptoms commonly associated with psychotic disorders appeared to diminish self-esteem. Also, participants did not describe their sense of self-esteem as being contingent on, or as a direct function of, having a psychotic disorder. For the individuals in this pilot study, self-esteem did not appear to be affected by having a psychotic disorder or by the stigma associated with having been given such a diagnosis. Individuals were able to engage in and maintain social and interpersonal relationships that contributed to their having a positive sense of self-worth. Further study is required to confirm and elaborate on this surprising set of findings.
“Instant Success”
Authors: Kroese Floor M. , Adriaanse Marieke A. , Evers Catharine , De Ridder Denise T. D.
Published: June 2011

Contrary to lay intuition, counteractive control theory posits that tempting food cues can help individuals to act in accordance with their long-term dieting goal. However, studies have shown that temptations trigger goal-directed behavior only in successful but not in unsuccessful self-regulators. The aim of the present study was to test whether it is possible to create facilitated temptation–goal associations in unsuccessful dieters using implementation intentions (e.g., “If I see or smell chocolate then I will follow my goal to diet”) and whether this indeed stimulates more successful self-regulation. It was found that implementation intentions linking a temptation to a dieting goal lead to self-perceived improved resistance to (Study 1) as well as reduced consumption (Study 2) of tempting snacks compared to a control condition. Moreover, Study 2 revealed that the reduced snack consumption was indeed related to facilitated temptation–goal associations in participants who had formed implementation intentions.
Accounting for Methodological, Structural, and Parameter Uncertainty in Decision-Analytic Models
Authors: Bilcke Joke , Beutels Philippe , Brisson Marc , Jit Mark
Published: June 2011

Accounting for uncertainty is now a standard part of decision-analytic modeling and is recommended by many health technology agencies and published guidelines. However, the scope of such analyses is often limited, even though techniques have been developed for presenting the effects of methodological, structural, and parameter uncertainty on model results. To help bring these techniques into mainstream use, the authors present a step-by-step guide that offers an integrated approach to account for different kinds of uncertainty in the same model, along with a checklist for assessing the way in which uncertainty has been incorporated. The guide also addresses special situations such as when a source of uncertainty is difficult to parameterize, resources are limited for an ideal exploration of uncertainty, or evidence to inform the model is not available or not reliable. Methods for identifying the sources of uncertainty that influence results most are also described. Besides guiding analysts, the guide and checklist may be useful to decision makers who need to assess how well uncertainty has been accounted for in a decision-analytic model before using the results to make a decision.
Anti-diabetic and anti-oxidative effects of 4-hydroxypipecolic acid in C57BL/KsJ-db/db mice
Authors: Singh AB , Khaliq T , Chaturvedi JP , Narender T , Srivastava AK
Published: June 2011

Hypoglycemic effect of ethanol extracts of Peganum harmala (commonly known as ‘Harmal’) seeds has been reported on normal and streptozotocin-induced diabetic rats. In the present study, the authors determine anti-diabetic and anti-oxidative properties of 4-hydroxypipecolic acid (4-HPA) isolated from seeds of P. harmala in C57BL/KsJ- db/db mice. Twelve week old male mice were administered 50 mg/kg body weight (4-HPA suspension were made in 1% gum acacia) for the period of 10 days, and a significant reduction in the fasting blood glucose, plasma triglycerides (TG), cholesterol, free fatty acid, low-density lipoprotein-cholesterol and a significant increase in high-density lipoprotein-cholesterol level was observed with respect to vehicle-treated db/db mice. The anti-oxidant activity of 4-hydroxypipecolic acid was studied in liver and kidney tissues by assessing malondialdehyde levels for lipid peroxidation and enzyme activity of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). Treatment of 4-HPA significantly lowered the lipid peroxidation in hepatic and renal tissue and increased the activity of CAT, GSH-Px and SOD in treated mice.
A nested multiplex polymerase chain reaction assay for the differential identification of three zooanthroponotic chlamydial strains in porcine swab samples
Authors: Li Yingguo , Wang Yu , Nie Fuping , Xiao Jinwen , Wang Guoming , Yuan Ling , Li Zhengguo
Published: June 2011

Porcine chlamydial infection is an enzootic infectious disease caused by multiple members of the family Chlamydiaceae (e.g. Chlamydophila abortus, Chlamydia suis, and Chlamydophila pneumoniae). Rapid and accurate differentiation of these pathogens is critical in the control and prevention of disease. The aim of the current study was to develop a nested multiplex polymerase chain reaction (nmPCR) assay to simultaneously detect the 3 chlamydial pathogens in clinical samples. In the first round of the nmPCR, 1 pair of family-specific primers were used to amplify the 1,100 base pair (bp) fragment of chlamydial ompA gene. In the second round of the nmPCR, 4 inner primers were designed for Ch. abortus, C. suis, and Ch. pneumoniae. Each pathogen produced a speciﬁc amplicon with a size of 340 bp, 526 bp, and 267 bp respectively. The assay was sensitive and speciﬁc for detecting target pathogens in both cell cultures and clinical specimens. The results, incorporated with the improved rapid DNA extraction protocol, suggest that the nmPCR could be a promising assay for differential identification of different chlamydial strains in pigs.
School Nurses' Role in Identifying and Referring Children at Risk of Noise-Induced Hearing Loss
Authors: Hendershot Candace , Pakulski Lori A. , Thompson Amy , Dowling Jamie , Price James H.
Published: June 2011

Young people are likely to experience noise-induced hearing loss (NIHL), as the use of personal listening devices and other damaging factors (e.g., video games) increases. Little research has examined the role of school health personnel in the prevention and early identification of hearing impairment. A 32-item, valid and reliable survey was developed regarding elementary and middle school nurses' practices concerning hearing loss screening and prevention. The survey instrument was based on the Stages of Change theory and the Health Belief Model. A random sample of 800 nurses was obtained from The National Association of School Nurses. A two-wave mailing was used to achieve a 58% response rate. Forty eight percent indicated there were not many educational programs that addressed NIHL in students. Performing hearing screenings routinely can help identify those students at risk. School nurses need to become advocates for policies and programs that mandate hearing screenings and educational programs to help reduce hearing loss.
Investigation of Correlation Among Safety Biomarkers in Serum, Histopathological Examination, and Toxicogenomics
Authors: Wang Tao , Papoutsi Maria , Wiesmann Marion , DeCristofaro Marc , Keselica M. Craig , Skuba Elizabeth , Spaet Robert , Markovits Judit , Wolf Armin , Moulin Pierre , Pognan Francois , Vancutsem Paul , Petryk Lew , Sutton James , Chibout Salah-Dine , Kluwe William
Published: June 2011

This article addresses the issue of miscorrelation between hepatic injury biomarkers and histopathological findings in the drug development context. Our studies indicate that the use of toxicogenomics can aid in the drug development decision-making process associated with such miscorrelated data. BLZ945 was developed as a Colony-Stimulating Factor 1 Receptor (CSF-1R) inhibitor. Treatment of BLZ945 in rats and monkeys increased serum alanine aminotransferase (ALT) and aspartate transaminase (AST). However, liver hypertrophy was the only histopathological liver finding in rats, and there was no change in the livers of monkeys. Longer treatment of BLZ945 in rats for 6 weeks caused up to 6-fold elevation of ALT, yet hepatocyte necrosis was not detected microscopically. Toxicogenomic profiling of liver samples demonstrated that the genes associated with early response to liver injury, apoptosis/necrosis, inflammation, oxidative stress, and metabolic enzymes were upregulated. Studies are ongoing to evaluate the mechanisms underlying BL945-induced ALT and AST elevations.
Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets
Authors: Wong Kok Loon , Tai June Jing-Yi , Wong Wing-Cheong , Han Hao , Sem Xiaohui , Yeap Wei-Hseun , Kourilsky Philippe , Wong Siew-Cheng
Published: June 2011

New official nomenclature subdivides human monocytes into 3 subsets: the classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes. This introduces new challenges, as monocyte heterogeneity is mostly understood based on 2 subsets, the CD16− and CD16+ monocytes. Here, we comprehensively defined the 3 circulating human monocyte subsets using microarray, flow cytometry, and cytokine production analysis. We find that intermediate monocytes expressed a large majority (87%) of genes and surface proteins at levels between classical and nonclassical monocytes. This establishes their intermediary nature at the molecular level. We unveil the close relationship between the intermediate and nonclassic monocytes, along with features that separate them. Intermediate monocytes expressed highest levels of major histocompatibility complex class II, GFRα2 and CLEC10A, whereas nonclassic monocytes were distinguished by cytoskeleton rearrangement genes, inflammatory cytokine production, and CD294 and Siglec10 surface expression. In addition, we identify new features for classic monocytes, including AP-1 transcription factor genes, CLEC4D and IL-13Rα1 surface expression. We also find circumstantial evidence supporting the developmental relationship between the 3 subsets, including gradual changes in maturation genes and surface markers. By comprehensively defining the 3 monocyte subsets during healthy conditions, we facilitate target identification and detailed analyses of aberrations that may occur to monocyte subsets during diseases.