bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of Tir, EspA, and NleB in the colonization of cattle by Shiga toxin producingEscherichia coliO26:H11
Authors: Misyurina Olga , Asper David J. , Deng Wanyin , Finlay B. Brett , Rogan Dragan , Potter Andrew A.
Published: October 2010

Shiga toxin producing Escherichia coli (STEC) O26:H11 is an enteric pathogen capable of causing severe hemorrhagic colitis that can lead to hemolytic uremic syndrome. This organism is able to colonize cattle and human intestinal epithelial cells by secreting effectors via a type III secretion system (T3SS). In this investigation, we examined the role of 2 effectors, Tir and NleB, and the structural translocator component EspA in the adherence of STEC to epithelial cells and in the colonization of cattle. Isogenic deletion mutants were constructed and using microscopy and flow cytometry compared to the wild-type strain in their ability to adhere to HEp-2 cells. A competitive assay was also used to measure the capacity of the mutants to colonize the intestinal tract of cattle, where both the mutant and the parental strains were introduced orally at the same time. Genomic DNA was extracted from enriched fecal samples collected at various time points, and quantitative real-time PCR was used to quantify bacteria. A significant reduction in fecal shedding was observed, and adherence to HEp-2 cells was decreased for the tir and espA mutants. Deletion of the nleB gene did not have a significant effect on the adherence of HEp-2 cells; however, in an in vivo model, it strongly reduced the ability of STEC O26:H11 to colonize the bovine intestinal tract.
Development and pilot evaluation of a novel probiotic mixture for the management of seasonal allergic rhinitis
Authors: Koyama Tara , Kirjavainen Pirkka V. , Fisher Cale , Anukam Kingsley , Summers Kelly , Hekmat Sharareh , Reid Gregor
Published: October 2010

Microbial exposure may direct the immune system away from allergic-type responses, but until now probiotic interventions have had limited success in the prevention and treatment of allergic diseases. In this study, a novel probiotic mixture was specifically created based on preliminary in vitro investigations on pollen-induced immune responses. A mixture with Lactobacillus rhamnosus GR-1 and a novel fecal Bifidobacterium adolescentis isolate was formulated into a yogurt and tested for its effects in 36 subjects with allergic rhinitis over 2 pollen seasons in a double-blind, placebo-controlled trial. The new formulation was well tolerated, but did not have significant effects on the quality of life scores, use of antihistamines, or eosinophil cationic protein concentration in nasal lavage. However, at the end of the grass pollen season, serum IL-10 and IL-12 levels were increased in the probiotic group compared to the controls. During the ragweed season, the serum TGF-β levels were significantly higher in the probiotic group than in the controls. In conclusion, the novel probiotic formulation had potentially desirable effects on the cytokine profile of patients with allergic rhinitis, but provided few clinical benefits. The study highlights the challenges in designing efficient immunomodulatory probiotic therapies based upon in vitro findings.
Invasive aspergillosis promotes tumor growth and severity in a tumor-bearing mouse model
Authors: Sohrabi Nooshin , Hassan Zuhair Muhammad , Khosravi Ali Reza , Tebianian Majid , Mahdavi Mehdi , Tootian Zahra , Ebrahimi Seyyed Mahmoud , Yadegari Mohammad Hosein , Gheflati Zahra
Published: October 2010

Invasive aspergillosis increases in chronic immunosuppressive diseases such as cancer. There is little information about the mechanisms by which Aspergillus infection affects the immune regulation and microenvironment of cancer cells. Hence, this study was aimed at investigating the effect of invasive aspergillosis on immunosurveillance, metastasis, and prognosis of cancer in tumor-bearing mice. After implantation of mouse mammary tumor in BALB/c mice, they were infected with Aspergillus conidia intravenously. For comparison, groups of mice were experimentally infected with Aspergillus conidia or implanted with tumor cells separately. Seven days after Aspergillus infection, the serum levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by ELISA, and subsequently regulatory T lymphocytes were analyzed by flow cytometry. The survival of animals and mean tumor size were then determined. Our results indicated that tumor sizes in mice increased significantly after infection with Aspergillus conidia. Moreover, invasive aspergillosis enhanced the population of regulatory lymphocytes and level of TIMP-1. This study supports the idea that massive Aspergillus infection could stimulate tumor growth and increases the possibility of a bad prognosis. As a result, treatment of Aspergillus infection could be considered an important issue for efficient cancer therapy.
Maximum growth potential in loblolly pine: results from a 47-year-old spacing study in Hawaii
Authors: Samuelson Lisa J. , Eberhardt Thomas L. , Butnor John R. , Stokes Tom A. , Johnsen Kurt H.
Published: October 2010

Growth, allocation to woody root biomass, wood properties, leaf physiology, and shoot morphology were examined in a 47-year-old loblolly pine ( Pinus taeda L.) density trial located in Maui, Hawaii, to determine if stands continued to carry the high density, basal area, and volume reported at younger ages and to identify potential factors controlling expression of maximum growth potential. Basal area and volume were similar among spacings (square: 1.8, 2.4, 3.0, and 3.7 m) and averaged 93 m2·ha–1 and 1076 m3·ha–1, respectively, and were double the maxima reported for loblolly pine in its native range. Spacing had a significant influence on density, quadratic mean diameter, and height. Ring-specific gravity and percent latewood were similar among spacing treatments but values were high compared to mainland stands. Leaf light-saturated net photosynthesis, dark respiration, stomatal conductance, and quantum yield were comparable with values reported for loblolly pine in its native range. Foliar calcium concentrations, specific leaf area, and flush number were high in the Hawaii study. Higher carrying capacity in Hawaii may be related to a more favorable climate conducive to year-round leaf carbon gain, high nutrient availability, increased flushing, and less allocation to belowground mass.
Molecular identification of ectomycorrhizas associated with ponderosa pine seedlings in Patagonian nurseries (Argentina)
Authors: Barroetaveña C. , Pildain M. B. , Salgado Salomón M. E. , Eberhart J. L.
Published: October 2010

Ponderosa pine ( Pinus ponderosa Dougl. ex P. & C. Laws.), an ectomycorrhiza (EM) dependent species, has been widely introduced in Patagonia, Argentina. This study used morphotyping, restriction analysis, and sequencing of EM root tips from ponderosa pine seedlings in two nurseries to assess the complete EM fungus (EMF) richness, to confirm doubtful identities of commonly reported morphotypes, and to evaluate the efficiency of morphotyping compared with molecular analysis. This interdisciplinary approach together with the fact that is the first study in which Patagonian nurseries EMF are genetically evaluated contributes to the general knowledge of this important group of fungi. Sequencing revealed the presence of 11 taxa. Basidiomycetes included Thelephoraceae ( Tomentella sp.), Atheliaceae ( Amphinema byssoides (Pers.) J. Erikss.), Hydnangiaceae ( Laccaria sp.), Rhizopogonaceae ( Rhizopogon roseolus (Corda) Th. Fr.), and Cortinariaceae ( Hebeloma mesophaeum (Pers.) Quel.). Ascomycetes included Pezizaceae ( Wilcoxina mikolae (Chin S. Yang & H.E. Wilcox) Chin S. Yang & Korf and Wilcoxina sp.) and Tuberaceae ( Tuber sp.). Morphotyping proved to be useful for certain EMF species (R. roseolus, H. mesophaeum, A. byssoides, and to a lesser extent Tuber sp.) in which some morphological features are conspicuous and unique. Our detection of W. mikolae and Wilcoxina sp. are new records for ponderosa pine in Patagonia. All of the EM taxa identified are common to pine plantations and nurseries around the world, and no indigenous EM associated with native Nothofagus spp. were found.
Nitrate stimulates root suckering in trembling aspen (Populus tremuloides)
Authors: Landhäusser Simon M. , Wan Xianchong , Lieffers Victor J. , Chow Pak S.
Published: October 2010

In a greenhouse experiment, we tested whether the initiation, density, and growth of trembling aspen ( Populus tremuloides Michx.) root suckers are related to postdisturbance soil nutrient availability. After decapitation of functional 2-year-old aspen root systems, nutrient solutions adjusted for various concentrations and forms of mineral N, different concentrations of Ca2+, K+, or PO43–, and different pH were applied to the roots and their suckering response was assessed after 35 days. Root systems treated with NO3– at concentrations of 1.5 and 7.5 mmol/L produced nearly double the sucker density compared with an unfertilized control, while fertilizing with N in the form of NH4+ did not affect sucker numbers, regardless of concentrations. The best growth of suckers was achieved with a mixture of 15 mmol/L NO3– + NH4+whereas the lowest growth was observed with 15 mmol/L NH4+. Neither Ca2+, K+, and PO43– nor the pH tested in this study impacted sucker density or growth. This has implications for understanding the impacts of disturbance on forest succession and the subsequent regeneration of aspen stands. The results suggest that the amount of nitrification, depending on the type and severity of disturbances, will influence the regeneration density of aspen.
In vitro myometrial inhibition by the partitioned aqueous fraction ofAnthocleista djalonensisleaves
Authors: Bafor Enitome Evi , Okunrobo Lucky Osaro
Published: October 2010

This study investigated the effect on the uterus of the aqueous fraction of the partitioned methanol crude extract of the leaves of Anthocleista djalonensis (AD) and the possible mechanism of AD activity. AD inhibited the concentration–response curves induced by oxytocin and CaCl2on the rat uterus in vitro and significantly reduced the EC50in a concentration-dependent manner (p < 0.05). A similar effect was observed with salbutamol and verapamil on the concentration–response curves obtained for oxytocin and CaCl2. The inhibitory effect of AD was not attenuated in the presence of propranolol. AD, salbutamol, and verapamil also produced a concentration-dependent relaxation on K+-induced sustained uterine contraction. In Ca2+-free medium, AD and salbutamol similarly inhibited oxytocin-induced contraction, but verapamil failed to produce this effect. The present results suggest that AD, being a mixture of phytochemicals, probably exerts inhibitory activity on in vitro uterine contractions of the nonpregnant, diethylstilboestrol-treated rat by multiple mechanisms that do not involve interaction with β-adrenergic receptors and do not solely depend on inhibition of calcium influx.
Effects of proanthocyanidins from grape seed on treatment of recurrent ulcerative colitis in rats
Authors: Wang Yan-Hong , Yang Xiao-Lai , Wang Li , Cui Ming-Xia , Cai Yong-Qing , Li Xiao-Li , Wu Yong-Jie
Published: October 2010

The aim of the present study was to investigate the therapeutic effect and mechanism of proanthocyanidins from grape seed (GSPE) in the treatment of recurrent ulcerative colitis (UC) in rats. To induce recurrent colitis, rats were instilled with 2,4,6-trinitrobenzenesulfonic acid (TNBS) (80 mg/kg) into the colon through the cannula in the first induced phase, and then the rats were instilled a second time with TNBS (30 mg/kg) into the colon on the sixteenth day after the first induction UC. Rats were intragastrically administered GSPE (200 mg/kg) per day for 7 days after twice-induced colitis by TNBS. Sulfasalazine at 500 mg/kg was used as a positive control drug. Rats were killed 7 days after GSPE treatment. The colonic injury and inflammation were assessed by macroscopic and macroscopic damage scores, colon weight/length ratio (mg/cm), and myeloperoxidase activity. Then, superoxide dismutase, glutathione peroxidase, inducible nitric oxide synthase (iNOS) activities, and the levels of malonyldialdehyde, glutathione, and nitric oxide in serum and colonic tissues were measured. Compared with the recurrent UC group, GSPE treatment facilitated recovery of pathologic changes in the colon after induction of recurrent colitis, as demonstrated by reduced colonic weight/length ratio and macroscopic and microscopic damage scores. The myeloperoxidase and iNOS activities with malonyldialdehyde and nitric oxide levels in serum and colon tissues of colitis rats were significantly decreased in the GSPE group compared with those in the recurrent UC group. In addition, GSPE treatment was associated with notably increased superoxide dismutase, glutathione peroxidase activities, and glutathione levels of colon tissues and serum of rats. GSPE exerted a protective effect on recurrent colitis in rats by modifying the inflammatory response, inhibiting inflammatory cell infiltration and antioxidation damage, promoting damaged tissue repair to improve colonic oxidative stress, and inhibiting colonic iNOS activity to reduce the production of nitric oxide.
Scaffolds in tissue engineering of blood vessels
Authors: Pankajakshan Divya , Agrawal Devendra K.
Published: October 2010

Tissue engineering of small diameter (<5 mm) blood vessels is a promising approach for developing viable alternatives to autologous vascular grafts. It involves in vitro seeding of cells onto a scaffold on which the cells attach, proliferate, and differentiate while secreting the components of extracellular matrix that are required for creating the tissue. The scaffold should provide the initial requisite mechanical strength to withstand in vivo hemodynamic forces until vascular smooth muscle cells and fibroblasts reinforce the extracellular matrix of the vessel wall. Hence, the choice of scaffold is crucial for providing guidance cues to the cells to behave in the required manner to produce tissues and organs of the desired shape and size. Several types of scaffolds have been used for the reconstruction of blood vessels. They can be broadly classified as biological scaffolds, decellularized matrices, and polymeric biodegradable scaffolds. This review focuses on the different types of scaffolds that have been designed, developed, and tested for tissue engineering of blood vessels, including use of stem cells in vascular tissue engineering.
Coping with human disturbance: spatial and temporal tactics of the brown bear (Ursus arctos)
Authors: Martin Jodie , Basille Mathieu , Van Moorter Bram , Kindberg Jonas , Allainé Dominique , Swenson Jon E.
Published: October 2010

In human-dominated landscapes, species with large spatial requirements, such as large carnivores, have to deal with human infrastructure and activities within their home ranges. This is the case for the brown bear ( Ursus arctos L., 1758) in Scandinavia, which is colonizing more human-dominated landscapes, leading inevitably to an overlap between their home ranges and anthropogenic structures. In this study, we investigated fine-scale habitat selection by brown bears to examine how they deal with this potential disturbance. Using Global Positioning System (GPS) data, we studied (i) habitat selection of female brown bears within their home range and (ii) the influence of diurnal variation in human disturbance on fine-scale habitat use. As expected, females selected habitats within their home range that provided abundant food resources and minimized human-caused disturbance. In addition, our temporal analysis of habitat selection revealed an avoidance of disturbed areas and a selection of slopes by bears during periods of highest human activities, i.e., during daylight hours. We clearly demonstrate the importance of considering the fluctuations in human activity when studying habitat selection, especially at fine spatial scales. Failing to do so may considerably reduce the power to detect important fine-scale habitat-selection behaviors.
An investigation of yolk-protein localization in the testes of the starfish Pisaster ochraceus
Authors: Reunov Arkadiy A. , Crawford Bruce J. , Reunova Yulia A.
Published: October 2010

The distribution of the yolk epitope, PY4F8, was studied in the testes of the starfish Pisaster ochraceus (Brandt, 1835). Western blots have revealed that testes only show one 180 kDa band, whereas ovaries exhibit four PY4F8 bands at 90, 110, 120, and 180 kDa. This finding suggests that male yolk is less complex than female yolk. It was shown that PY4F8-positive material abounds in the hemal sinus of testes. Moreover, this epitope was found in the basal lamina, in the lumen of the testes, and in the cytoplasm of auxiliary and spermatogenic cells. It is likely that a hemal testis barrier is absent in P. ochraceus, and this lack allows direct penetration of nutrition to sustain metabolism of both spermatogenic and auxiliary cells. Morphologically, this penetration is possible through the gaps between adjacent auxiliary cell bases. Yolk granules containing the PY4F8 epitope are located in spermatogonia and spermatocytes, but not in spermatids and sperm. Therefore, yolk may play an important role in early spermatogenesis, but it does not participate at the final stage of sperm formation.
OPTICAL TRANSITION RADIATION IN PRESENCE OF ACOUSTIC WAVES
Authors: MKRTCHYAN A. R. , PARAZIAN V. V. , SAHARIAN A. A.
Published: October 2010

Transition radiation from relativistic electrons is investigated in an ultrasonic superlattice excited in a finite thickness plate. In the quasi-classical approximation, formulae are derived for the vector potential of the electromagnetic field and for the spectral-angular distribution of the radiation intensity. The acoustic waves generate new resonance peaks in the spectral and angular distribution of the radiation intensity. The heights of the peaks can be tuned by choosing the parameters of the acoustic wave.
EXACT SOLUTIONS FOR DIFFERENTIAL-DIFFERENCE EQUATIONS BY BÄCKLUND TRANSFORMATION OF RICCATI EQUATION
Authors: HON Y. C. , ZHANG YUFENG , MEI JIANQIN
Published: October 2010

Based on a Bäcklund transformation of the Riccati equation and its known soliton solutions, we obtain in this paper some exact traveling-wave solutions, including triangle function solutions and hyperbolic function solutions, of a hybrid lattice equation. The proposed method can be easily extended to locate exact solitary wave solutions for other types of differential-difference equations.
PROTON-IRRADIATION INDUCED DEFECTS IN Te-DOPED GaSb STUDIED BY PHOTOLUMINESCENCE AND POSITRON ANNIHILATION SPECTROSCOPY
Authors: ZHOU KAI , LI HUI , WANG ZHU
Published: October 2010

Proton-irradiation induced defects in Te -doped GaSb have been studied by photoluminescence (PL) and positron annihilation spectroscopy (PAS). A 2.6 MeV proton irradiation with fluences of 1×1014 cm-2, and 3×1015 cm-2 was used to produce defects in the Te -doped GaSb samples with free electron concentration of 1×1017 cm-3 and 1×1018 cm-3 respectively. The change of S parameters in Te -doped samples irradiated with different proton fluences, indicates that the defects induced by proton irradiation are most likely the V Ga -related defects. The PL spectra of Te -doped GaSb with different proton irradiation doses were measured at 77 K. The results show that the V Ga -related defects induced by proton irradiation are acceptors in Te -doped GaSb . We have also found that the dopant-induced vacancies which are related to Te have existed in unirradiated samples.
PLANE-WAVE PSEUDOPOTENTIAL DENSITY FUNCTIONAL THEORY PERIODIC SLAB CALCULATIONS OF NO ADSORPTION ON Ag(001) SURFACE
Authors: AGHAIE H. , GHOLAMI M. R. , KHAZALI F. , ZARE K. , MONAJJEMI M. , AGHAIE M.
Published: October 2010

Plane-wave pseudopotential density functional theory (DFT) periodic slab calculations were performed using the generalized gradient approximation (GGA) to investigate the adsorption of nitric oxide (NO) on the (001) surface of Ag . We examined three different adsorption sites perpendicular with respect to the surface and a position that the axis of NO molecule was tilted from the upright. The adsorption of NO in the fourfold hollow site was favored, with a binding energy of 45.47 kJ/mol.
MESOSCOPIC SIMULATION ON THE PHASE STRUCTURE OF PLURONIC P105 AQUEOUS SOLUTION
Authors: DONG SHIJIN , ZHANG HAITAO , CUI XUEJUN , SUI ZHENYING , XU JIA , WANG HONGYAN
Published: October 2010

The mesoscopic dynamic simulation (MesoDyn) has been carried out to investigate the phase structure and the aggregate properties of triblock copolymers (ethylene oxide)37 (propylene oxide)56 (ethylene oxide)37 (P105) in aqueous solution. A Gaussian chain model is successfully built according to the equivalent chain method and the Flory–Huggins interaction parameters, χ, used for determining the repulsions between different chain segments are computed. Simulation results show that P105 can form several microstructures including spherical micelles, ellipsoid micellar cluster, worm-like micelles, defective bicontinuous phase, and bicontinuous phase with increasing concentration. A special transition phase structure of P105 is found in the spherical micellar region. The dynamic evolution processes of spherical micelles are investigated by observing the induction time before phase separation and the changing of isosurface during phase separation. The influence of P105 concentration on the density of micelles at equilibrium state is also discussed, which shows that the increase of P105 concentration will lead to the decrease of micelles' amount. Two kinds of growth mechanisms during phase separation are discussed by MesoDyn simulation.
STUDY ON THE INTERACTIONS OF Smac MIMETICS WITH XIAP-BIR3 DOMAIN BY DOCKING AND MOLECULAR DYNAMICS SIMULATIONS
Authors: LING BAOPING , ZHANG RUI , WANG ZHIGUO , LIU YONGJUN , LIU CHENGBU
Published: October 2010

Upon receiving an apoptotic stimulus, the mature mitochondrial protein second mitochondria-derived activator of caspases (Smac)/direct IAP-binding protein with low PI (DIABLO), which could be released from mitochondria into the cytosol together with cytochrome C , specifically binds to inhibitor of apoptosis proteins (IAPs) and relieves the inhibitory effect of caspase, thus promotes cell death. Some artificial small molecules (called Smac mimetics) can mimic the N-terminal four residues Ala1-Val2-Pro3-Ile4 (AVPI) sequence of mitochondrial protein Smac, and competitively bind to X-linked inhibitor of apoptosis protein baculoviral IAP repeats (XIAP-BIR3) domain with caspase-9, which leads to the removal of the inhibition of caspase-9 by XIAP and induce apoptosis. To gain an insight into the nature of XIAP-BIR3 domain recognizing Smac mimetics, we used docking and molecular dynamics simulations methods to study four representative Smac mimetics. The docking results show that the orientations of these backbones of ligands are identical with that of AVPI in the binding pocket. Each ligand corresponds to two competitive conformations, which are called extended and bended conformations. The results of molecular dynamics simulations show that the extended conformation is more stable, and the calculations of energy decomposition reveal that the residue Thr308 makes the strongest interaction with XIAP-BIR3. In addition, Asp309, Glu314, and Trp323 are indispensable for XIAP-BIR3 recognizing and binding Smac mimetics.
ANHARMONIC EFFECT OF UNIMOLECULAR REACTION:HCO2→H+CO2WITH RRKM THEORY
Authors: GU LINGZHENG , YAO LI , SHAO YING , ZHONG HAIYANG , YANG KUN , ZHONG JINGJUN
Published: October 2010

Anharmonic and harmonic rate constants were calculated in the unimolecular reaction HCO2→ H + CO2with Yao and Lin (YL) method. In microcanonical case, the total number of states and density of states increase reasonably with the increasing of the total energy and the temperature. Both in microcanonical and canonical cases, the harmonic rate constants are much higher than those for anharmonic cases, especially in the case of high total energy and temperature, which indicates that anharmonic effect of the reaction is so significant that it is not negligible. The results obtained in this research show that the YL method works well for such unimolecular reactions.
ABOVE THRESHOLD IONIZATION OF POLAR NaK MOLECULES DRIVEN BY FEW-CYCLE LASER PULSE
Authors: YU JIE , SHU CHUAN-CUN , HU WEN-HUI , CONG SHU-LIN
Published: October 2010

We investigate theoretically the above-threshold ionization (ATI) of the polar NaK molecule exposed in few-cycle laser field by numerically solving the time-dependent Schrödinger equation including the vibrational and rotational degrees of freedom. The left and right ATI spectra are calculated by integrating the ionization continuum wave function over the left and the right half spheres along the laser polarization. We find that the left and right ATI spectra are asymmetric, and this asymmetry depends strongly on the molecular orientation and the carrier-envelope phase (CEP) of the laser pulse. Moreover, we also perform the calculation for different initially rotational states to study the effect of rotational temperature on the ATI dynamics.
[Retracted] NKT Cells in Sepsis
Authors: Leung Briana , Harris Hobart W.
Published: October 2010

Sepsis is currently a leading cause of death in hospital intensive care units. Previous studies suggest that the pathophysiology of sepsis involves the hyperactivation of complex proinflammatory cascades that include the activation of various immune cells and the exuberant secretion of proinflammatory cytokines by these cells. Natural killer T‐cells (NKTs) are a sublineage of T cells that share characteristics of conventional T cells and NK cells and bridge innate and adaptive immunity. More recently, NKT cells have been implicated in microbial immunity, including the onset of sepsis. Moreover, apolipoprotein E (apoE), a component of triglyceride‐rich lipoproteins, has been shown to be protective in endotoxemia and gram‐negative infections in addition to its well‐known role in lipid metabolism. Here, we will review the role of NKT cells in sepsis and septic shock, the immunoregulatory role of apoE in the host immune response to infection, and propose a mechanism for this immunoregulation.
Weak Convergence Theorems for a Countable Family of Strict Pseudocontractions in Banach Spaces
Authors: Cholamjiak Prasit , Suantai Suthep
Published: October 2010

We investigate the convergence of Mann-type iterative scheme for a countable family of strict pseudocontractions in a uniformly convex Banach space with the Fréchet differentiable norm. Our results improve and extend the results obtained by Marino-Xu, Zhou, Osilike-Udomene, Zhang-Guo and the corresponding results. We also point out that the condition given by Chidume-Shahzad (2010) is not satisfied in a real Hilbert space. We show that their results still are true under a new condition.
Activation of PPARsα,β/δ, andγImpairs TGF-β1-Induced Collagens' Production and Modulates the TIMP-1/MMPs Balance in Three-Dimensional Cultured Chondrocytes
Authors: Poleni Paul-Emile , Etienne Stephanie , Velot Emilie , Netter Patrick , Bianchi Arnaud
Published: October 2010

Background and Purpose. We investigated the potency of Peroxisome Proliferators-Activated Receptors (PPARs)α,β/δ, andγagonists to modulate Transforming Growth Factor-β1 (TGF-β1-) induced collagen production or changes in Tissue Inhibitor of Matrix Metalloproteinase- (TIMP-) 1/Matrix Metalloproteinase (MMP) balance in rat chondrocytes embedded in alginate beads.Experimental Approach. Collagen production was evaluated by quantitative Sirius red staining, while TIMP-1 protein levels and global MMP (-1, -2, -3, -7, and -9) or specific MMP-13 activities were measured by ELISA and fluorigenic assays in culture media, respectively. Levels of mRNA for type II collagen, TIMP-1, and MMP-3 & 13 were quantified by real-time PCR.Key Results. TGF-β1 increased collagen deposition and type II collagen mRNA levels, while inducing TIMP-1 mRNA and protein expression. In contrast, it decreased global MMP or specific MMP-13 activities, while decreasing MMP-3 or MMP-13 mRNA levels. PPAR agonists reduced most of the effects of TGF-β1 on changes in collagen metabolism and TIMP-1/MMP balance in rat in a PPAR-dependent manner, excepted for Wy14643 on MMP activities.Conclusions and Implications. PPAR agonists reduce TGF-β1-modulated ECM turnover and inhibit chondrocyte activities crucial for collagen biosynthesis, and display a different inhibitory profile depending on selectivity for PPAR isotypes.
The Effect of Glucagon-Like Peptide-2 Receptor Agonists on Colonic Anastomotic Wound Healing
Authors: Redstone Heather A. , Buie William D. , Hart David A. , Wallace Laurie , Hornby Pamela J. , Sague Sarah , Holst Jen J. , Sigalet David L.
Published: October 2010

Background. Glucagon-like peptide 2 (GLP-2) is an intestinal specific trophic hormone, with therapeutic potential; the effects on intestinal healing are unknown. We used a rat model of colonic healing, under normoxic, and stress (hypoxic) conditions to examine the effect of GLP-2 on intestinal healing.Methods. Following colonic transection and reanastomosis, animals were randomized to one of six groups (n=8/group): controls, native GLP-2, long-acting GLP-2 (GLP-2- MIMETIBODY, GLP-2-MMB), animals were housed under normoxic or hypoxic (11%  O2) conditions. Animals were studied five days post-operation for anastomotic strength and wound characteristics.Results. Anastomotic bursting pressure was unchanged by GLP-2 or GLP-2-MMB in normoxic or hypoxic animals; both treatments increased crypt cell proliferation. Wound IL-1βincreased with GLP-2; IFNγwith GLP-2 and GLP-2-MMB. IL-10 and TGF-βwere decreased; Type I collagen mRNA expression increased in hypoxic animals while Type III collagen was reduced with both GLP-2 agonists. GLP-2 MMB, but not native GLP-2 increased TIMP 1-3 mRNA levels in hypoxia.Conclusions. The effects on CCP, cytokines and wound healing were similar for both GLP-2 agonists under normoxic and hypoxic conditions; anastomotic strength was not affected. This suggests that GLP-2 (or agonists) could be safely used peri-operatively; direct studies will be required.
Telomere Attrition Occurs during Ex Vivo Expansion of Human Dental Pulp Stem Cells
Authors: Mokry Jaroslav , Soukup Tomas , Micuda Stanislav , Karbanova Jana , Visek Benjamin , Brcakova Eva , Suchanek Jakub , Bouchal Jan , Vokurkova Doris , Ivancakova Romana
Published: October 2010

We provide a detailed characteristic of stem cells isolated and expanded from the human dental pulp. Dental pulp stem cells express mesenchymal cell markers STRO-1, vimentin, CD29, CD44, CD73, CD90, CD166, and stem cell markers Sox2, nestin, and nucleostemin. They are multipotent as shown by their osteogenic and chondrogenic potential. We measured relative telomere length in 11 dental pulp stem cell lines at different passages by quantitative real-time PCR. Despite their large proliferative capacity, stable viability, phenotype, and genotype over prolonged cultivation, human dental pulp stem cells suffer from progressive telomere shortening over time they replicate in vitro. Relative telomere length (T/S) was inversely correlated with cumulative doubling time. Our findings indicate that excessive ex vivo expansion of adult stem cells should be reduced at minimum to avoid detrimental effects on telomere maintenance and measurement of telomere length should become a standard when certificating the status and replicative age of stem cells prior therapeutic applications.
Effects of the PPARαAgonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism
Authors: Cunningham Michael L. , Collins Bradley J. , Hejtmancik Milton R. , Herbert Ronald A. , Travlos Gregory S. , Vallant Molly K. , Stout Matthew D.
Published: October 2010

Gemfibrozil is a widely prescribed hypolipidemic agent in humans and a peroxisome proliferator and liver carcinogen in rats. Three-month feed studies of gemfibrozil were conducted by the National Toxicology Program (NTP) in male Harlan Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters, primarily to examine mechanisms of hepatocarcinogenicity. There was morphologic evidence of peroxisome proliferation in rats and mice. Increased hepatocyte proliferation was observed in rats, primarily at the earliest time point. Increases in peroxisomal enzyme activities were greatest in rats, intermediate in mice, and least in hamsters. These studies demonstrate that rats are most responsive while hamsters are least responsive. These events are causally related to hepatotoxicity and hepatocarcinogenicity of gemfibrozil in rodents via peroxisome proliferator activated receptor-α(PPARα) activation; however, there is widespread evidence that activation of PPARαin humans results in expression of genes involved in lipid metabolism, but not in hepatocellular proliferation.
Overview of Cellular Immunotherapy for Patients with Glioblastoma
Authors: Vauleon Elodie , Avril Tony , Collet Brigitte , Mosser Jean , Quillien Véronique
Published: October 2010

High grade gliomas (HGG) including glioblastomas (GBM) are the most common and devastating primary brain tumours. Despite important progresses in GBM treatment that currently includes surgery combined to radio‐ and chemotherapy, GBM patients′ prognosis remains very poor. Immunotherapy is one of the new promising therapeutic approaches that can specifically target tumour cells. Such an approach could also maintain long term antitumour responses without inducing neurologic defects. Since the past 25 years, adoptive and active immunotherapies using lymphokine‐activated killer cells, cytotoxic T cells, tumour‐infiltrating lymphocytes, autologous tumour cells, and dendritic cells have been tested in phase I/II clinical trials with HGG patients. This paper inventories these cellular immunotherapeutic strategies and discusses their efficacy, limits, and future perspectives for optimizing the treatment to achieve clinical benefits for GBM patients.
Single Nucleotide Polymorphism Detection Using Au-Decorated Single-Walled Carbon Nanotube Field Effect Transistors
Authors: Lee Keum-Ju , So Hye-Mi , Kim Byoung-Kye , Kim Do Won , Jang Jee-Hwan , Kong Ki-Jeong , Chang Hyunju , Lee Jeong-O
Published: October 2010

We demonstrate that Au-cluster-decorated single-walled carbon nanotubes (SWNTs) may be used to discriminate single nucleotide polymorphism (SNP). Nanoscale Au clusters were formed on the side walls of carbon nanotubes in a transistor geometry using electrochemical deposition. The effect of Au cluster decoration appeared as hole doping when electrical transport characteristics were examined. Thiolated single-stranded probe peptide nucleic acid (PNA) was successfully immobilized on Au clusters decorating single-walled carbon nanotube field-effect transistors (SWNT-FETs), resulting in a conductance decrease that could be explained by a decrease in Au work function upon adsorption of thiolated PNA. Although a target single-stranded DNA (ssDNA) with a single mismatch did not cause any change in electrical conductance, a clear decrease in conductance was observed with matched ssDNA, thereby showing the possibility of SNP (single nucleotide polymorphism) detection using Au-cluster-decorated SWNT-FETs. However, a power to discriminate SNP target is lost in high ionic environment. We can conclude that observed SNP discrimination in low ionic environment is due to the hampered binding of SNP target on nanoscale surfaces in low ionic conditions.
Role of PIR‐B in Autoimmune Glomerulonephritis
Authors: Takai Toshiyuki , Nakamura Akira , Endo Shota
Published: October 2010

PIR‐B, an inhibitory receptor expressed on murine B cells and myeloid cells, regulates humoral and cellular immune responses via its constitutive binding to the ligand, MHC class I molecules, on the same cells (cis) or on different cells (trans). Although it has been speculated that PIR‐B is important for maintaining peripheral tolerance, PIR‐B single deficiency does not cause overt autoimmune diseases. Recently, however, the combination of its deficiency with the Fas lpr mutation was found to result in augmented production of autoantibodies such as IgG rheumatoid factor and anti‐DNA IgG, leading to glomerulonephritis in mice. Although the precise molecular mechanism for the overall scenario is unclear, PIR‐B was found to suppress TLR9‐mediated production of naturally autoreactive antibodies by innate B cells or B‐1 cells by inhibiting the activation of Bruton′s tyrosine kinase. Thus, PIR‐B is an important regulator of innate immunity mediated by TLR9 in B‐1 cells, which can otherwise provoke autoimmunity when overactivated.
Future Perspectives: Therapeutic Targeting of Notch Signalling May Become a Strategy in Patients Receiving Stem Cell Transplantation for Hematologic Malignancies
Authors: Ersvaer Elisabeth , Hatfield Kimberley J. , Reikvam Håkon , Bruserud Øystein
Published: October 2010

The human Notch system consists of 5 ligands and 4 membrane receptors with promiscuous ligand binding, and Notch-initiated signalling interacts with a wide range of other intracellular pathways. The receptor signalling seems important for regulation of normal and malignant hematopoiesis, development of the cellular immune system, and regulation of immune responses. Several Notch-targeting agents are now being developed, including natural receptor ligands, agonistic and antagonistic antibodies, and inhibitors of intracellular Notch-initiated signalling. Some of these agents are in clinical trials, and several therapeutic strategies seem possible in stem cell recipients: (i) agonists may be used for stem cell expansion and possibly to enhance posttransplant lymphoid reconstitution; (ii) receptor-specific agonists or antagonists can be used for immunomodulation; (iii) Notch targeting may have direct anticancer effects. Although the effects of therapeutic targeting are difficult to predict due to promiscuous ligand binding, targeting of this system may represent an opportunity to achieve combined effects with earlier posttransplant reconstitution, immunomodulation, or direct anticancer effects.
Review: Magnetic Resonance Spectroscopy Studies of Pediatric Major Depressive Disorder
Authors: Kondo Douglas G. , Hellem Tracy L. , Sung Young-Hoon , Kim Namkug , Jeong Eun-Kee , DelMastro Kristen K. , Shi Xianfeng , Renshaw Perry F.
Published: October 2010

Introduction. This paper focuses on the application of Magnetic Resonance Spectroscopy (MRS) to the study of Major Depressive Disorder (MDD) in children and adolescents.Method. A literature search using the National Institutes of Health's PubMed database was conducted to identify indexed peer-reviewed MRS studies in pediatric patients with MDD.Results. The literature search yielded 18 articles reporting original MRS data in pediatric MDD. Neurochemical alterations in Choline, Glutamate, and N-Acetyl Aspartate are associated with pediatric MDD, suggesting pathophysiologic continuity with adult MDD.Conclusions. The MRS literature in pediatric MDD is modest but growing. In studies that are methodologically comparable, the results have been consistent. Because it offers a noninvasive and repeatable measurement of relevantin vivobrain chemistry, MRS has the potential to provide insights into the pathophysiology of MDD as well as the mediators and moderators of treatment response.
Ventilator-Associated Lung Injury Superposed to Oleic Acid Infusion or Surfactant Depletion: Histopathological Characteristics of Two Porcine Models of Acute Lung Injury
Authors: Wang H.M. , Bodenstein M. , Duenges B. , Ganatti S. , Boehme S. , Ning Y. , Roehrig B. , Markstaller K.
Published: October 2010

Background: The pathophysiological concept of acute lung injury (ALI) in combination with ventilator-associated lung injury (VALI) is still unclear. We characterized the histopathological features of intravenous injection of oleic acid (OAI) and lung lavage (LAV) combined with VALI. Methods: Pigs were randomized to the control, LAV or OAI group and ventilated by pressure-controlled ventilation. Measurements included: haemodynamics, spirometry, blood gas analysis, lung wet-to-dry weight ratio (W/D), total protein content in broncho-alveolar lavage fluid (BALF), and lung pathological description and scoring. Results: Five hours after lung injury induction, gas exchange was significantly impaired in both the OAI and the LAV groups. Compared to controls, we found an increase in W/D and histopathological total injury scores in both the LAV and OAI groups and an increase in BALF total protein content in the OAI group. In contrast to the LAV group, the OAI group showed septal necrosis and alveolar oedema. Both groups exhibited dorsal and caudal atelectasis and interstitial oedema. In addition, the OAI group demonstrated a propensity to dorsal necrosis and congestion whereas the LAV group tended to develop ventral overdistension and barotrauma. Conclusions: This study presents a comparison of porcine OAI and LAV models combined with VALI, providing information for study design in research on ALI.
A Simple and Computationally Efficient Sampling Approach to Covariate Adjustment for Multifactor Dimensionality Reduction Analysis of Epistasis
Authors: Gui Jiang , Andrew Angeline S. , Andrews Peter , Nelson Heather M. , Kelsey Karl T. , Karagas Margaret R. , Moore Jason H.
Published: October 2010

Epistasis or gene-gene interaction is a fundamental component of the genetic architecture of complex traits such as disease susceptibility. Multifactor dimensionality reduction (MDR) was developed as a nonparametric and model-free method to detect epistasis when there are no significant marginal genetic effects. However, in many studies of complex disease, other covariates like age of onset and smoking status could have a strong main effect and may potentially interfere with MDR’s ability to achieve its goal. In this paper, we present a simple and computationally efficient sampling method to adjust for covariate effects in MDR. We use simulation to show that after adjustment, MDR has sufficient power to detect true gene-gene interactions. We also compare our method with the state-of-art technique in covariate adjustment. The results suggest that our proposed method performs similarly, but is more computationally efficient. We then apply this new method to an analysis of a population-based bladder cancer study in New Hampshire.
Biomarkers of Acute Kidney Injury in Different Clinical Settings: A Time to Change the Paradigm?
Authors: Malyszko Jolanta
Published: October 2010

Acute kidney injury (AKI) is diagnosed in 5% of all hospitalized patients and in up to 50% of all ICU patients. In the last years a dramatic rise in the prevalence of AKI has been observed with virtually no change in mortality, reaching up to 50–80% in all dialyzed ICU patients. AKI may progress to end-stage renal disease, and even subclinical episodes of AKI, which are common, may also progress to end-stage renal disease. The early detection of AKI may enable timely intervention and prevention of progression; however, in animal models and in human studies the ‘window of therapeutic intervention’ is narrow. Different urinary and serum proteins have been intensively investigated as possible biomarkers for the early diagnosis of AKI. There are promising candidate biomarkers with the ability to detect an early and graded increase in tubular epithelial cell injury and distinguish pre-renal disease from acute tubular necrosis. In this review, new emerging biomarkers of AKI are presented and described in some clinical settings, such as cardiac surgery, contrast-induced nephropathy, delayed graft function and ICU/emergency departments, where biomarkers are urgently needed to diagnose, make prognoses and differentiate.
Lipschütz Genital Ulceration Associated with Mumps
Authors: Chanal Johan , Carlotti Agnès , Laude Hélène , Wallet-Faber Nadège , Avril Marie-Françoise , Dupin Nicolas
Published: October 2010

Lipschütz ulcers are characterised by a first flare of non-sexually related acute genital ulcers (AGU) occurring in adolescent girls. Epstein-Barr primary infection is the most frequently reported aetiology but other infectious agents are probably implicated. We report the first case of mumps associated with an AGU in a 21-year-old girl. She presented a bilateral parotitis with genital ulcers, and serology confirmed she had mumps. As in our case, most Lipschütz ulcers heal spontaneously within a couple of weeks and the diagnosis should be reconsidered in case of recurrence.
Prevalence of Chronic Pruritus in Germany: Results of a Cross-Sectional Study in a Sample Working Population of 11,730
Authors: Ständer S. , Schäfer I. , Phan N.Q. , Blome C. , Herberger K. , Heigel H. , Augustin M.
Published: October 2010

Background: Pruritus is a frequent symptom in many diseases; its prevalence in German adults is unknown. Objective: Our purpose was to assess the prevalence, severity and health care of chronic pruritus in the German working population. Methods: A cross-sectional observational study was conducted in employees of 144 German companies. Pruritus-specific data were obtained by standardized questions. Results: 11,730 people (53.2% male, 16–70 years, mean = 43.7 years) were suitable for analysis. The point prevalence of chronic pruritus (at least 6 weeks prior to data collection) was 16.8%. The prevalence increased with age from 12.3% (16–30 years) to 20.3% (61–70 years). A quarter of the affected persons had suffered from pruritus for >5 years, 47% had never sought medical advice, and 94% had not undergone any treatment. Conclusions: Chronic pruritus is a prevalent symptom in the working age population. A high proportion of people affected are not medically treated.
Early Cyst Growth Is Associated with the Increased Nuclear Expression of Cyclin D1/Rb Protein in an Autosomal-Recessive Polycystic Kidney Disease Rat Model
Authors: Schwensen Kristina G. , Burgess Jane S. , Graf Nicole S. , Alexander Stephen I. , Harris David C. , Phillips Jacqueline K. , Rangan Gopala K.
Published: October 2010

Background: In this study we hypothesised that proliferation, and the increased expression of G1-phase cyclins (D1, E) and phosphorylated retinoblastoma protein (p-Rb) is restricted to the early period of synchronized cyst growth in autosomal-recessive polycystic kidney disease (ARPKD). Methods: Lewis polycystic kidney disease (lpk) rats (model of ARPKD; postnatal weeks 1, 3, 6, 12 and 24; n = 6 each) as well as human juvenile cystic renal disease tissue (n = 2) were examined. Results: Between weeks 1 and 3, the percentage cyst area increased 6-fold in lpk rats, followed by a more progressive rise (1.5-fold increase) until week 24. The number of Ki-67-, cyclin D1- and p-Rb-positive cells increased in lpk rats and peaked at week 3, declining thereafter. By serial sections, cysts co-expressed Ki-67, cyclin D1 and p-Rb. The expression of cyclin E was variable, and peaked at week 24. In human tissue, small cysts had a higher expression of p-Rb. Conclusion: Proliferation and the increased nuclear expression of cyclin D1 and p-Rb coincide with the early phase of cyst growth in rats and humans, suggesting that there might be a therapeutic window in which cyclin-dependent kinase inhibitors are most effective in preventing kidney enlargement in ARPKD.