bluuebunny/crossref_metadata_2025 huggingface dataset:
BAGE Hypomethylation Is an Early Event in Colon Transformation and Is Frequent in Histologically Advanced Adenomas
Authors: Lana Erica , Brun Marie-Elisabeth , Rivals Isabelle , Selves Janick , Kirzin Sylvain , Lutsyk Andriy P. , Gordiyuk Vasily V. , Bibeau Frédéric , Rynditch Alla , De Sario Albertina
Published: November 2009

We showed earlier that BAGE (B melanoma antigen) loci are hypermethylated in normal tissues and hypomethylated in 98% of human cancers. More recently, we provided evidence that hypomethylation of BAGE loci represents an informative marker for colon cancer detection. In this study, we show that hypomethylation of BAGE loci was an early event that occurred in 43% of colorectal adenomas. Interestingly, hypomethylation of BAGE loci was frequent (50%) in tubulo-villous and villous adenomas, these adenomas having a high probability of being transformed into colorectal cancers.
Two Distinct Training Methods for a Doctrine of Life with Healthy Heart in a Low Socioeconomic Society Model
Authors: Metintas Selma , Kalyoncu Cemalettin , Arıkan İnci
Published: November 2009

This study was conducted in three stages in a semi-rural region of Eskisehir, Turkey. In the first stage, individuals selected by random sampling were evaluated for cardiovascular disease risk factors. In the second stage, Group I and Group II training materials were randomly distributed. In the third stage, the subjects were screened one year later to assess and determine if there had been any changes in their attitudes towards the dangers of cardiovascular diseases. The number of active smokers significantly decreased after the training in the both groups. The percentage of people with regulated blood pressure exhibited an increase in Group II more than Group I.
Methylation of Dietary Flavones Increases Their Metabolic Stability and Chemopreventive Effects
Authors: Walle Thomas
Published: November 2009

Dietary flavones have promising chemoprotective properties, in particular with regard to cancer, but problems with low oral bioavailability and sometimes unacceptable toxicity have made their use as protective additives to normal diets questionable. However, methylation of free phenolic hydroxyl groups leads to derivatives not susceptible to glucuronic acid or sulfate conjugation, resulting in increased metabolic stability. Methylation also leads to greatly improved transport through biological membranes, such as in intestinal absorption, and much increased oral bioavailability. Recent studies also indicate that methylation results in derivatives with increasing potency to kill cancer cells. They also show high potency towards inhibition of hormone-regulating enzymes, e.g., aromatase, important in the causation of breast cancer. Methylation of the flavones may also result in derivatives with diminished toxic side-effects and improved aqueous solubility. In conclusion, it appears that methylation of dietary flavones as well as of other food products may produce derivatives with much improved health effects.
Dendronized Polyimides Bearing Long-Chain Alkyl Groups and Their Application for Vertically Aligned Nematic Liquid Crystal Displays
Authors: Tsuda Yusuke , OH Jae Min , Kuwahara Renpei
Published: November 2009

Polyimides having dendritic side chains were investigated. The terphenylene diamine monomer having a first-generation monodendron, 3,4,5-tris(n-dodecyloxy)-benzoate and the monomer having a second-generation monodendron, 3,4,5-tris[-3’,4’,5’-tri(n-dodecyloxy)benzyloxy]benzoate were successfully synthesized and the corresponding soluble dendritic polyimides were obtained by polycondensation with conventional tetracarboxylic dianhydride monomers such as benzophenone tertracarboxylic dianhydride (BTDA). The two-step polymerizations in NMP that is a general method for the synthesis of soluble polyimides is difficult; however, the expected dendritic polyimides can be obtained in aromatic polar solvents such as m-cresol and pyridine. The solubility of these dendoronized polyimides is characteristic; soluble in common organic solvents such as dichloromethane, chloroform, toluene and THF. These dendronized polyimides exhibited high glass transition temperatures and good thermal stability in both air and under nitrogen. Their application as alignment layers for LCDs was investigated, and it was found that these polyimides having dendritic side chains were applicable for the vertically aligned nematic liquid crystal displays (VAN-LCDs).
The Effect of Evolving Damage on the Finite Strain Response of Inelastic and Viscoelastic Composites
Authors: Aboudi Jacob
Published: November 2009

A ﬁnite strain micromechanical model is generalized in order to incorporate the effect of evolving damage in the metallic and polymeric phases of unidirectional compostes. As a result, it is possible to predict the response of composites with ductile and brittle phases undergoing large coupled inelastic-damage and viscoelastic-damage deformations, respectively. For inelastic composites, both ﬁnite strain elastoplastic (time-independent) and viscoplastic (time-dependent) behaviors are considered. The ductile phase exhibits initially a hyperelastic behavior which is followed by an inelastic one, and its analysis is based on the multiplicative split of its deformation gradient into elastic and inelastic parts. The embedded damage mechanisms and their evolutions are based on Gurson’s (which is suitable for the modeling of porous materials) and Lemaitre’s ﬁnite strain models. Similarly, the polymeric phase exhibits large viscoelastic deformations in which the damage evolves according to a suitable evolution law that depends on the amount of accumulated deformation. Evolving damage in hyperelastic materials can be analyzed as a special case by neglecting the viscous effects. The micromechanical analysis is based on the homogenization technique for periodic multiphase materials, which establishes the strong form of the Lagrangian equilibrium equations. These equations are implemented together with the interfacial and periodic boundary conditions, in conjunction with the current tangent tensor of the phase. As a result, the instantaneous strain concentration tensor that relates the local deformation gradient of the phase to the externally applied deformation gradient is established. This provides also the instantaneous effective stiffness tangent tensor of the composite as well as its current response. Results are given that exhibit the effect of damage on the initial yield surfaces, response and possible failure of the composite.
Cellulose/Gold Nanocrystal Hybrids via an Ionic Liquid/Aqueous Precipitation Route
Authors: Li Zhonghao , Taubert Andreas
Published: November 2009

Injection of a mixture of HAuCl4 and cellulose dissolved in the ionic liquid (IL) 1-butyl-3-methylimidazolium chloride [Bmim]Cl into aqueous NaBH4 leads to colloidal gold nanoparticle/cellulose hybrid precipitates. This process is a model example for a very simple and generic approach towards (noble) metal/cellulose hybrids, which could find applications in sensing, sterile filtration, or as biomaterials.
Chemosystematic Value of the Essential Oil Composition of Thuja species Cultivated in Poland—Antimicrobial Activity
Authors: Tsiri Dimitroula , Graikou Konstantia , Pobłocka-Olech Loretta , Krauze-Baranowska Miroslawa , Spyropoulos Caroline , Chinou Ioanna
Published: November 2009

In the framework of the correlation between chemotaxonomy and chemical analysis studies, the chemical composition of the essential oils of four varieties of Thuja species cultivated in Poland − T. occidentalis ‘globosa’, T. occidentalis ‘aurea’, T. plicata and T. plicata ‘gracialis’ − were investigated by GC and GC-MS. Thirty-one compounds were identified from T. occidentalis ‘globosa’, representing 96.92% of the total oil; twenty-seven from T. occidentalis ‘aurea’ (94.34%); thirty-one from T. plicata (94.75%); and thirty compounds from T. plicata ‘gracialis’ (96.36%). The main constituents in all samples were the monoterpene ketones α- and β-thujone, fenchone and sabinene, as well as the diterpenes beyerene and rimuene.The chemosystematic value of the total ketone content of all samples (which varied from 54.30–69.18%) has been discussed and investigated. The constituents, beyerene and the mixture of α- and β-thujone, were isolated from the oils and tested against six Gram-positive and -negative bacteria and three pathogenic fungi. The oils of the two T. plicata species exhibited significant antimicrobial activity, while the mixture of α- and β-thujone showed very strong activity as well.
Chemical Composition and Phytotoxic Effects of Essential Oils of Salvia hierosolymitana Boiss. and Salvia multicaulis Vahl. var. simplicifolia Boiss. Growing Wild in Lebanon
Authors: Mancini Emilia , Arnold Nelly Apostolides , De Martino Laura , De Feo Vincenzo , Formisano Carmen , Rigano Daniela , Senatore Felice
Published: November 2009

The chemical composition of the essential oils of S. hierosolymitana Boiss. and S. multicaulis Vahl. var. simplicifolia Boiss. collected in Lebanon was studied by means of GC and GC-MS analysis. In all 115 compounds were identified: 82 for S hierosolymitana and 72 for S. multicaulis var. simplicifolia. The presence of carbonylic compounds (17%) characterizes the oil from S. hierosolymitana,while S. multicaulis var. simplicifolia oil is rich of monoterpenes (34.5%) and sesquiterpenes (46.9%). The effects of the essential oils on germination and initial radical elongation of Raphanus sativus L. (radish) and Lepidium sativum L. (garden cress) were studied, indicating in a different activity against radical elongation of the species tested.
Evaluating the Effects of Environmental Changes on the Gross Primary Production of Italian Forests
Authors: Maselli Fabio , Moriondo Marco , Chiesi Marta , Chirici Gherardo , Puletti Nicola , Barbati Anna , Corona Piermaria
Published: November 2009

A ten-year data-set descriptive of Italian forest gross primary production (GPP) has been recently constructed by the application of Modified C-Fix, a parametric model driven by remote sensing and ancillary data. That data-set is currently being used to develop multivariate regression models which link the inter-year GPP variations of five forest types (white fir, beech, chestnut, deciduous and evergreen oaks) to seasonal values of temperature and precipitation. The five models obtained, which explain from 52% to 88% of the inter-year GPP variability, are then applied to predict the effects of expected environmental changes (+2 °C and increased CO2 concentration). The results show a variable response of forest GPP to the simulated climate change, depending on the main ecosystem features. In contrast, the effects of increasing CO2 concentration are always positive and similar to those given by a combination of the two environmental factors. These findings are analyzed with reference to previous studies on the subject, particularly concerning Mediterranean environments. The analysis confirms the plausibility of the scenarios obtained, which can cast light on the important issue of forest carbon pool variations under expected global changes.
An Immunity-Based Anomaly Detection System with Sensor Agents
Authors: Okamoto Takeshi , Ishida Yoshiteru
Published: November 2009

This paper proposes an immunity-based anomaly detection system with sensor agents based on the specificity and diversity of the immune system. Each agent is specialized to react to the behavior of a specific user. Multiple diverse agents decide whether the behavior is normal or abnormal. Conventional systems have used only a single sensor to detect anomalies, while the immunity-based system makes use of multiple sensors, which leads to improvements in detection accuracy. In addition, we propose an evaluation framework for the anomaly detection system, which is capable of evaluating the differences in detection accuracy between internal and external anomalies. This paper focuses on anomaly detection in user’s command sequences on UNIX-like systems. In experiments, the immunity-based system outperformed some of the best conventional systems.
Thin Magnetically Soft Wires for Magnetic Microsensors
Authors: Zhukova Valentina , Ipatov Mihail , Zhukov Arcady
Published: November 2009

Recent advances in technology involving magnetic materials require development of novel advanced magnetic materials with improved magnetic and magneto-transport properties and with reduced dimensionality. Therefore magnetic materials with outstanding magnetic characteristics and reduced dimensionality have recently gained much attention. Among these magnetic materials a family of thin wires with reduced geometrical dimensions (of order of 1–30 μm in diameter) have gained importance within the last few years. These thin wires combine excellent soft magnetic properties (with coercivities up to 4 A/m) with attractive magneto-transport properties (Giant Magneto-impedance effect, GMI, Giant Magneto-resistance effect, GMR) and an unusual re-magnetization process in positive magnetostriction compositions exhibiting quite fast domain wall propagation. In this paper we overview the magnetic and magneto-transport properties of these microwires that make them suitable for microsensor applications.
Trial of Multidisciplinary Observation at an Expandable Sub-Marine Cabled Station “Off-Hatsushima Island Observatory” in Sagami Bay, Japan
Authors: Kasaya Takafumi , Mitsuzawa Kyohiko , Goto Tada-nori , Iwase Ryoichi , Sayanagi Keizo , Araki Eiichiro , Asakawa Kenichi , Mikada Hitoshi , Watanabe Tomoki , Takahashi Ichiro , Nagao Toshiyasu
Published: November 2009

Sagami Bay is an active tectonic area in Japan. In 1993, a real-time deep sea floor observatory was deployed at 1,175 m depth about 7 km off Hatsushima Island, Sagami Bay to monitor seismic activities and other geophysical phenomena. Video cameras monitored biological activities associated with tectonic activities. The observation system was renovated completely in 2000. An ocean bottom electromagnetic meter (OBEM), an ocean bottom differential pressure gauge (DPG) system, and an ocean bottom gravity meter (OBG) were installed January 2005; operations began in February of that year. An earthquake (M5.4) in April 2006, generated a submarine landslide that reached the Hatsushima Observatory, moving some sensors. The video camera took movies of mudflows; OBEM and other sensors detected distinctive changes occurring with the mudflow. Although the DPG and OBG were recovered in January 2008, the OBEM continues to obtain data.
Tiny Medicine: Nanomaterial-Based Biosensors
Authors: Yun Yeo-Heung , Eteshola Edward , Bhattacharya Amit , Dong Zhongyun , Shim Joon-Sub , Conforti Laura , Kim Dogyoon , Schulz Mark J. , Ahn Chong H. , Watts Nelson
Published: November 2009

Tiny medicine refers to the development of small easy to use devices that can help in the early diagnosis and treatment of disease. Early diagnosis is the key to successfully treating many diseases. Nanomaterial-based biosensors utilize the unique properties of biological and physical nanomaterials to recognize a target molecule and effect transduction of an electronic signal. In general, the advantages of nanomaterial-based biosensors are fast response, small size, high sensitivity, and portability compared to existing large electrodes and sensors. Systems integration is the core technology that enables tiny medicine. Integration of nanomaterials, microfluidics, automatic samplers, and transduction devices on a single chip provides many advantages for point of care devices such as biosensors. Biosensors are also being used as new analytical tools to study medicine. Thus this paper reviews how nanomaterials can be used to build biosensors and how these biosensors can help now and in the future to detect disease and monitor therapies.
Synthesis and Characterization of Anti-HER2 Antibody Conjugated CdSe/CdZnS Quantum Dots for Fluorescence Imaging of Breast Cancer Cells
Authors: Tiwari Dhermendra K. , Tanaka Shin-Ichi , Inouye Yasushi , Yoshizawa Keiko , Watanabe Tomonobu M. , Jin Takashi
Published: November 2009

The early detection of HER2 (human epidermal growth factor receptor 2) status in breast cancer patients is very important for the effective implementation of anti-HER2 antibody therapy. Recently, HER2 detections using antibody conjugated quantum dots (QDs) have attracted much attention. QDs are a new class of fluorescent materials that have superior properties such as high brightness, high resistance to photo-bleaching, and multi-colored emission by a single-light source excitation. In this study, we synthesized three types of anti-HER2 antibody conjugated QDs (HER2Ab-QDs) using different coupling agents (EDC/sulfo-NHS, iminothiolane/sulfo-SMCC, and sulfo-SMCC). As water-soluble QDs for the conjugation of antibody, we used glutathione coated CdSe/CdZnS QDs (GSH-QDs) with fluorescence quantum yields of 0.23~0.39 in aqueous solution. Dispersibility, hydrodynamic size, and apparent molecular weights of the GSH-QDs and HER2Ab-QDs were characterized by using dynamic light scattering, fluorescence correlation spectroscopy, atomic force microscope, and size-exclusion HPLC. Fluorescence imaging of HER2 overexpressing cells (KPL-4 human breast cancer cell line) was performed by using HER2Ab-QDs as fluorescent probes. We found that the HER2Ab-QD prepared by using SMCC coupling with partially reduced antibody is a most effective probe for the detection of HER2 expression in KPL-4 cells. We have also studied the size dependency of HER2Ab-QDs (with green, orange, and red emission) on the fluorescence image of KPL-4 cells.
Innate and Adaptive Immune Responses to Herpes Simplex Virus
Authors: Chew Tracy , Taylor Kathryne E. , Mossman Karen L.
Published: November 2009

Immune responses against HSV-1 and HSV-2 are complex and involve a delicate interplay between innate signaling pathways and adaptive immune responses. The innate response to HSV involves the induction of type I IFN, whose role in protection against disease is well characterized in vitro and in vivo. Cell types such as NK cells and pDCs contribute to innate anti-HSV responses in vivo. Finally, the adaptive response includes both humoral and cellular components that play important roles in antiviral control and latency. This review summarizes the innate and adaptive effectors that contribute to susceptibility, immune control and pathogenesis of HSV, and highlights the delicate interplay between these two important arms of immunity.
Copper Modulates the Differentiation of Mouse Hematopoietic Progenitor Cells in Culture
Authors: Huang Xiaosong , Pierce L. Jeanne , Cobine Paul A. , Winge Dennis R. , Spangrude Gerald J.
Published: November 2009

Copper chelation has been shown to favor the expansion of human hematopoietic stem/progenitor cells in vitro. To further understand the effects of copper modulation on defined subsets of stem cells versus progenitor cells, we extended the studies in a mouse system. We isolated mouse hematopoietic stem cells (HSCs) or hematopoietic progenitor cells (HPCs) and cultured them with or without the copper chelator tetraethylenepentamine (TEPA) or CuCl2. Cytokine-stimulated HPC cultures treated with TEPA for 7 days generated about two to three times more total and erythroid colony-forming cells (CFCs) compared to control cultures. In contrast, CuCl2treatment decreased the CFC numbers. Similar results were seen with HSC after 14, but not 7, days of culture. Transplant studies showed that HPCs cultured for 7 days in TEPA had about twofold higher short-term erythroid repopulation potential compared to control cultures, while CuCl2decreased the erythroid potential of cultured HPCs compared to control cultures. HSCs cultured with TEPA for 7 days did not exhibit significantly higher repopulation potential in either leukocyte or erythrocyte lineages compared to control cultures in short-term or long-term assays. Based on JC-1 staining, the mitochondrial membrane potential of HPCs cultured with TEPA was lower relative to control cultures. Our data suggest that decreasing the cellular copper content with TEPA results in preferential expansion or maintenance of HPC that are biased for erythroid differentiation in vivo, but does not enhance the maintenance of HSC activity in culture.
Effects of Mechanical Stretch on Collagen and Cross-Linking in Engineered Blood Vessels
Authors: Solan Amy , Dahl Shannon L. M. , Niklason Laura E.
Published: November 2009

It has been shown that mechanical stimulation affects the physical properties of multiple types of engineered tissues. However, the optimum regimen for applying cyclic radial stretch to engineered arteries is not well understood. To this end, the effect of mechanical stretch on the development of engineered blood vessels was analyzed in constructs grown from porcine vascular smooth muscle cells. Cyclic radial distension was applied during vessel culture at three rates: 0 beats per minute (bpm), 90 bpm, and 165 bpm. At the end of the 7-week culture period, harvested vessels were analyzed with respect to physical characteristics. Importantly, mechanical stretch at 165 bpm resulted in a significant increase in rupture strength in engineered constructs over nonstretched controls. Stress–strain data and maximal elastic moduli from vessels grown at the three stretch rates indicate enhanced physical properties with increasing pulse rate. In order to investigate the role of collagen cross-linking in the improved mechanical characteristics, collagen cross-link density was quantified by HPLC. Vessels grown with mechanical stretch had somewhat more collagen and higher burst pressures than nonpulsed control vessels. Pulsation did not increase collagen cross-link density. Thus, increased wall thickness and somewhat elevated collagen concentrations, but not collagen cross-link density, appeared to be responsible for increased burst strength.
Autologous Umbilical Cord Blood Mononuclear Cell Transplantation Preserves Right Ventricular Function in a Novel Model of Chronic Right Ventricular Volume Overload
Authors: Yerebakan Can , Sandica Eugen , Prietz Stephanie , Klopsch Christian , Ugurlucan Murat , Kaminski Alexander , Abdija Sefer , Lorenzen Björn , Boltze Johannes , Nitzsche Björn , Egger Dietmar , Barten Malte , Furlani Dario , Ma Nan , Vollmar Brigitte , Liebold Andreas , Steinhoff Gustav
Published: November 2009

We aimed to evaluate the feasibility and efficacy of autologous umbilical cord blood mononuclear cell (UCMNC) transplantation on right ventricular (RV) function in a novel model of chronic RV volume overload. Four-month-old sheep ( n = 20) were randomized into cell ( n = 10) and control groups ( n = 10). After assessment of baseline RV function by the conductance catheter method, a transannular patch (TAP) was sutured to the right ventricular outflow tract (RVOT). Following infundibulotomy the ring of the pulmonary valve was transected without cardiopulmonary bypass. UCMNC implantation (8.22 ± 6.28 × 107) in the cell group and medium injection in the control group were performed into the RV myocardium around the TAP. UCMNCs were cultured for 2 weeks after fluorescence-activated cell sorting (FACS) analysis for CD34 antigen. Transthoracic echocardiography (TTE) and computed tomography were performed after 6 weeks and 3 months, respectively. RV function was assessed 3 months postoperatively before the hearts were excised for immunohistological examinations. FACS analysis revealed 1.2 ± 0.22% CD34+ cells within the isolated UCMNCs from which AcLDL+ endothelial cells were cultured in vitro. All animals survived surgery. TTE revealed grade II–III pulmonary regurgitation in both groups. Pressure-volume loops under dobutamine stress showed significantly improved RV diastolic function in the cell group (dP/dtmin: p = 0.043; Eed: p = 0.009). CD31 staining indicated a significantly enhanced number of microvessels in the region of UCMNC implantation in the cell group ( p < 0.001). No adverse tissue changes were observed. TAP augmentation and pulmonary annulus distortion without cardiopulmonary bypass constitutes a valid large animal model mimicking the surgical repair of tetralogy of Fallot. Our results indicate that the chronically volume-overloaded RV profits from autologous UCMNC implantation by enhanced diastolic properties with a probable underlying mechanism of increased angiogenesis.
Different Effects of FK506, Rapamycin, and Mycophenolate Mofetil on Glucose-Stimulated Insulin Release and Apoptosis in Human Islets
Authors: Johnson James D. , Ao Ziliang , Ao Peter , Li Hong , Dai Long-Jun , He Zehua , Tee May , Potter Kathryn J. , Klimek Agnieszka M. , Meloche R. Mark , Thompson David M. , Verchere C. Bruce , Warnock Garth L.
Published: November 2009

Pancreatic islet transplantation has the potential to be an effective treatment for type 1 diabetes mellitus. While recent improvements have improved 1-year outcomes, follow-up studies show a persistent loss of graft function/survival over 5 years. One possible cause of islet transplant failure is the immunosuppressant regimen required to prevent alloimmune graft rejection. Although there is evidence from separate studies, mostly in rodents and cell lines, that FK506 (tacrolimus), rapamycin (sirolimus), and mycophenolate mofetil (MMF; CellCept) can damage pancreatic β-cells, there have been few side-by-side, multiparameter comparisons of the effects of these drugs on human islets. In the present study, we show that 24-h exposure to FK506 or MMF impairs glucose-stimulated insulin secretion in human islets. FK506 had acute and direct effects on insulin exocytosis, whereas MMF did not. FK506, but not MMF, impaired human islet graft function in diabetic NOD.scid mice. All of the immunosuppressants tested in vitro increased caspase-3 cleavage and caspase-3 activity, whereas MMF induced ER-stress to the greatest degree. Treating human islets with the GLP-1 agonist exenatide ameliorated the immunosuppressant-induced defects in glucose-stimulated insulin release. Together, our results demonstrate that immunosuppressants impair human β-cell function and survival, and that these defects can be circumvented to a certain extent with exenatide treatment.
Experience of Microbiological Screening of Human Hepatocytes for Clinical Transplantation
Authors: Lehec Sharon C. , Hughes Robin D. , Mitry Ragai R. , Graver Michelle A. , Verma Anita , Wade Jim J. , Dhawan Anil
Published: November 2009

Hepatocyte transplantation is being used in patients with liver-based metabolic disorders and acute liver failure. Hepatocytes are isolated from unused donor liver tissue under GMP conditions. Cells must be free of microbiological contamination to be safe for human use. The experience of microbiological screening during 72 hepatocyte isolation procedures at one center is reported. Samples were taken at different stages of the process and tested using a blood culture bottle system and Gram stain. Bacterial contamination was detected in 37.5% of the UW organ preservative solutions used to transport the liver tissue to the Cell Isolation Unit. After tissue processing the contamination was reduced to 7% overall in the final hepatocyte product, irrespective of the presence of initial contamination of the transport solution. The most common organisms recovered were coagulase-negative staphylococci, a skin commensal. A total of 41 preparations of fresh or cryopreserved hepatocytes were used for cell transplantation in children with liver-based metabolic disorders without any evidence of sepsis due to infusion of hepatocytes. In conclusion, the incidence of bacterial contamination of the final product was low, confirming the suitability of the organs used, hepatocyte isolation procedure, and the environmental conditions of the clean room.
Laser Capture Microdissection as a New Tool to Assess Graft-Infiltrating Lymphocytes Gene Profile in Islet Transplantation
Authors: Vergani A. , Clissi B. , Sanvito F. , Doglioni C. , Fiorina P. , Pardi R.
Published: November 2009

Innovative tolerogenic protocols in transplantation would take advantage of the development of new tools capable of evaluating the impact of these treatments on the immune system. These assays have potential for clinical application. Currently, many of these studies are based on the analysis of peripheral lymph nodes and blood-derived cells, where the percentage of alloantigen-specific cells can be low or even unpredictable. We combined a laser capture microdissection (LCM) technique with real-time PCR (RT-PCR) to evaluate gene profile of islet-infiltrating lymphocytes. Donor Lewis rats islets were transplanted under the kidney capsule in diabetic Brown Norway rats. Administration of anti-LFA1 mAb or anti-CD28 F(Ab)′ was able to prolong islet survival, while the combined treatment resulted in indefinite survival. The analysis of gene expression profile for IL-2, IFN-γ, and IL-10 production of graft-infiltrating cells revealed high IL-2, IFN-γ, and IL-10 in untreated rats; on the contrary, the combined treatment selectively abrogated IL-2- and IFN-γ-producing cells infiltrate. The comparison between cytokine profile in periphery (even during an allogenic extra stimulus) and in the graft revealed the dichotomy between graft and peripheral cytokine assessment. We thus propose that direct analysis of graft-infiltrating cells should be used whenever possible to evaluate the effects of a new immunomodulatory protocol.
Can we measure catalyst efficiency in asymmetric chemical reactions? A theoretical approach
Authors: El-Fayyoumy Shaimaa , Todd Matthew H , Richards Christopher J
Published: November 2009

Small molecule asymmetric catalysts are often described as being “good” or “bad” but to date there has been no way of comparing catalyst efficiency quantitatively. We define a simple formula, Asymmetric Catalyst Efficiency (ACE), that allows for such a comparison. We propose that a catalyst is more efficient if fewer atoms are utilised to give a product in a required enantiomeric excess. We illustrate this concept by analysing several well-known asymmetric catalytic chemical reactions carried out in academic laboratories, and compare small molecule catalysts with enzymes. We conclude that ACE is a useful descriptor for the comparison of diverse catalytic systems. It is also noteworthy that, despite the relatively short period of investigation into small molecule catalysts, they are competitive with enzymes with regards to this measure of catalytic efficiency.
Body morphometrics, swimming diversity and niche in demersal sharks: a comparative case study from the Mediterranean Sea
Authors: Scacco Umberto , La Mesa Gabriele , Vacchi Marino
Published: November 2009

Seven demersal shark species belonging to six families, obtained from the southern Mediterranean Sea, were selected as representative of different putative swimming modes, inhabited depths and trophic levels. Caudal fin morphometrics (caudal fin span, area and aspect ratio), hepatosomatic index and muscular-skeletal amount per unit length were estimated and compared within and among species by means of both parametric and non-parametric multivariate and univariate statistical procedures. Intra-specific variation was related to size and, for one species only, also to sex. Two inter-specific patterns of variation were observed: the first pattern was interpreted as a swimming ability gradient between slow benthic and more pelagic species, as a function of caudal morphometry and body characteristics; the second pattern is related to the depth the species inhabit and/or their trophic level. These two hypotheses were tested with the current data and literature information, and discussed in the context of shark swimming modes, habit and environment. Based on observed differences in caudal fin morphometrics, liver and muscular masses, this paper is the first to provide a quantitative and comparative dataset for demersal sharks as a group, and attempts to describe sample variability as a function of expected swimming ability and occupied niche (depth inhabited and/or trophic level).
Role of CX3CL1/Fractalkine in Osteoclast Differentiation and Bone Resorption
Authors: Koizumi Keiichi , Saitoh Yurika , Minami Takayuki , Takeno Nobuhiro , Tsuneyama Koichi , Miyahara Tatsuro , Nakayama Takashi , Sakurai Hiroaki , Takano Yasuo , Nishimura Miyuki , Imai Toshio , Yoshie Osamu , Saiki Ikuo
Published: November 2009

The recruitment of osteoclast precursors toward osteoblasts and subsequent cell-cell interactions are critical for osteoclast differentiation. Chemokines are known to regulate cell migration and adhesion. CX3CL1 (also called fractalkine) is a unique membrane-bound chemokine that has dual functions for cells expressing its receptor CX3CR1: a potent chemotactic factor in its soluble form and a type of efficient cell adhesion molecule in its membrane-bound form. In this paper, we demonstrate a novel role of CX3CL1 in osteoblast-induced osteoclast differentiation. We found that osteoclast precursors selectively expressed CX3CR1, whereas CX3CL1 is expressed by osteoblasts. We confirmed that soluble CX3CL1 induced migration of bone marrow cells containing osteoclast precursors, whereas immobilized CX3CL1 mediated firm adhesion of osteoclast precursors. Furthermore, a blocking mAb against CX3CL1 efficiently inhibited osteoclast differentiation in mouse bone marrow cells cocultured with osteoblasts. Anti-CX3CL1 also significantly suppressed bone resorption in neonatal mice by reducing the number of bone-resorbing mature osteoclasts. Collectively, CX3CL1 expressed by osteoblasts plays an important role in osteoclast differentiation, possibly through its dual functions as a chemotactic factor and adhesion molecule for osteoclast precursors expressing CX3CR1. The CX3CL1-CX3CR1 axis may be a novel target for the therapeutic intervention of bone resorbing diseases such as rheumatoid arthritis, osteoporosis, and cancer bone metastasis.
Infection with Arginase-DeficientLeishmania majorReveals a Parasite Number-Dependent and Cytokine-Independent Regulation of Host Cellular Arginase Activity and Disease Pathogenesis
Authors: Muleme Helen M. , Reguera Rosa M. , Berard Alicia , Azinwi Richard , Jia Ping , Okwor Ifeoma B. , Beverley Stephen , Uzonna Jude E.
Published: November 2009

The balance between the products of l-arginine metabolism in macrophages regulates the outcome of Leishmania major infection. l-arginine can be oxidized by host inducible NO synthase to produce NO, which contributes to parasite killing. In contrast, l-arginine hydrolysis by host arginase blocks NO generation and provides polyamines, which can support parasite proliferation. Additionally, Leishmania encode their own arginase which has considerable potential to modulate infectivity and disease pathogenesis. In this study, we compared the infectivity and impact on host cellular immune response in vitro and in vivo of wild-type (WT) L. major with that of a parasite arginase null mutant (arg−) L. major. We found that arg− L. major are impaired in their macrophage infectivity in vitro independent of host inducible NO synthase activities. As with in vitro results, the proliferation of arg− L. major in animal infections was also significantly impaired in vivo, resulting in delayed onset of lesion development, attenuated pathology, and low parasite burden. Despite this attenuated pathology, the production of cytokines by cells from the draining lymph node of mice infected with WT and arg− L. major was similar at all times tested. Interestingly, in vitro and in vivo arginase levels were significantly lower in arg− than in WT-infected cases and were directly correlated with parasite numbers inside infected cells. These results suggest that Leishmania-encoded arginase enhances disease pathogenesis by augmenting host cellular arginase activities and that contrary to previous in vitro studies, the host cytokine response does not influence host arginase activity.
Enhanced Susceptibility toLeishmaniaInfection in Resistant Mice in the Absence of Immediate Early Response Gene X-1
Authors: Akilov Oleg E. , Ustyugova Irina V. , Zhi Liang , Hasan Tayyaba , Wu Mei X.
Published: November 2009

Immediate early response gene X-1 (IEX-1) is a stress-inducible gene abundantly expressed in macrophages and T cells following various stimuli. To explore a potential role for IEX-1 in control of the susceptibility to Leishmania major infection, the inflammatory response during cutaneous leishmaniasis was evaluated in 129Sv/C57BL/6-resistant mice in the presence or absence of IEX-1. Null mutation of IEX-1 enhanced the susceptibility of the mice to L. major infection, and aggravated inflammatory responses in comparison with wild-type control mice. The excessive inflammation was not ascribed to a Th2-biased immune response or a defect in Th1 polarization, but rather to an elevated level of IL-17 production by both γδ T and CD4+ cells, concomitant with an increase of the neutrophil recruitment early in the infection. The lack of IEX-1 also suppressed TNF-α production in both macrophages and T cells, resulting in a high intralesional load of parasites and delayed healing of the lesion, both of which were reversed by TNF-α treatment. These findings indicate the crucial role of IL-17 and TNF-α in determining the outcome of L. major infection beyond a balance between Th1- and Th2-mediated immune responses.
Signaling Crosstalk during Sequential TLR4 and TLR9 Activation Amplifies the Inflammatory Response of Mouse Macrophages
Authors: De Nardo Dominic , De Nardo Christine M. , Nguyen Thao , Hamilton John A. , Scholz Glen M.
Published: November 2009

The TLR family of pattern recognition receptors is largely responsible for meditating the activation of macrophages by pathogens. Because macrophages may encounter multiple TLR ligands during an infection, signaling crosstalk between TLR pathways is likely to be important for the tailoring of inflammatory reactions to pathogens. Here, we show that rather than inducing tolerance, LPS pretreatment primed the inflammatory response (e.g., TNF production) of mouse bone marrow-derived macrophages (BMM) to the TLR9 ligand, CpG DNA. The priming effects of LPS, which correlated with enhanced Erk1/2, JNK, and p38 MAPK activation, appeared to be mediated via both c-Fms-dependent and -independent mechanisms. LPS pretreatment and inhibition of the M-CSF receptor, c-Fms, with GW2580 had comparable effects on CpG DNA-induced Erk1/2 and p38 MAPK activation. However, c-Fms inhibition did not enhance CpG DNA-induced JNK activation; also, the levels of TNF produced were significantly lower than those from LPS-primed BMM. Thus, the priming effects of LPS on TLR9 responses appear to be largely mediated via the c-Fms-independent potentiation of JNK activity. Indeed, inhibition of JNK abrogated the enhanced production of TNF by LPS-pretreated BMM. The c-Fms-dependent priming effects of LPS are unlikely to be a consequence of the inhibitory constraints of M-CSF signaling on TLR9 expression being relieved by LPS; instead, LPS may exert its priming effects via signaling molecules downstream of TLR9. In summary, our findings highlight the importance of signaling crosstalk between TLRs, as well as between TLRs and c-Fms, in regulating the inflammatory reaction to pathogens.
Brain-Derived Neurotrophic Factor Induces Sustained Elevation of Intracellular Ca2+ in Rodent Microglia
Authors: Mizoguchi Yoshito , Monji Akira , Kato Takahiro , Seki Yoshihiro , Gotoh Leo , Horikawa Hideki , Suzuki Satoshi O. , Iwaki Toru , Yonaha Miyuki , Hashioka Sadayuki , Kanba Shigenobu
Published: November 2009

Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, NO, and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca2+ concentration ([Ca2+]i) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we observed that BDNF induced a sustained increase in [Ca2+]i through binding with the truncated tropomyosin-related kinase B receptor, resulting in activation of the PLC pathway and store-operated calcium entry in rodent microglial cells. RT-PCR and immunocytochemical techniques revealed that truncated tropomyosin-related kinase B-T1 receptors were highly expressed in rodent microglial cells. Sustained activation of store-operated calcium entry occurred after brief BDNF application and contributed to the maintenance of sustained [Ca2+]i elevation. Pretreatment with BDNF significantly suppressed the release of NO from activated microglia. Additionally, pretreatment of BDNF suppressed the IFN-γ-induced increase in [Ca2+]i, along with a rise in basal levels of [Ca2+]i in rodent microglial cells. We show direct evidence that rodent microglial cells are able to respond to BDNF, which may be important for the regulation of inflammatory responses, and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders.
CCR7 Modulates Pulmonary and Lymph Node Inflammatory Responses in Cigarette Smoke-Exposed Mice
Authors: Demoor Tine , Bracke Ken R. , Vermaelen Karim Y. , Dupont Lisa , Joos Guy F. , Brusselle Guy G.
Published: November 2009

Peribronchial lymphoid follicles have recently been identified as one of the hallmark features of (severe) chronic obstructive pulmonary disease (COPD). However, little is known about the relative contribution of peribronchial lymphoid follicles vs mediastinal lymph nodes in inflammatory responses in COPD patients and animal models. In a murine model of COPD, we studied inflammatory responses in airways, lungs, and mediastinal lymph nodes of wild-type (WT) vs CCR7 knockout (CCR7−/−) mice upon subacute or chronic exposure to cigarette smoke (CS). Although crucial for the organization of the secondary lymphoid organs, CCR7 was not required for the development of chronic CS-induced pulmonary lymphoid follicles. Moreover, T cell numbers were significantly increased in airways and lungs of air-exposed CCR7−/− mice, and they continued to increase upon chronic CS exposure. Unexpectedly, subacute CS-induced inflammation in airways and lungs, including airway neutrophilia and the recruitment of inflammatory-type CD11b+ dendritic cells, depended greatly on CCR7. In the draining lymph nodes, chronic CS exposure induced CCR7-dependent recruitment of airway-derived dendritic cells, accompanied by increases in CD4+ and CD8+ T cells. Correspondingly, CS exposure up-regulated mRNA expression of CCR7 ligands CCL19 and CCL21-Ser in lymph nodes of WT mice, but not CCR7−/− mice. In the lungs of WT mice, chronic CS exposure significantly increased CCL19 mRNA and protein. Furthermore, double staining for CCL19 and pro-surfactant protein C showed that alveolar type II cells express high levels of CCL19. These data unveil a so far unappreciated role for CCR7 in modulating inflammatory responses in airways and lungs.
Langerin+CD8α+ Dendritic Cells Are Critical for Cross-Priming and IL-12 Production in Response to Systemic Antigens
Authors: Farrand Kathryn J. , Dickgreber Nina , Stoitzner Patrizia , Ronchese Franca , Petersen Troels R. , Hermans Ian F.
Published: November 2009

Distinct dendritic cell (DC) subsets differ with respect to pathways of Ag uptake and intracellular routing to MHC class I or MHC class II molecules. Murine studies suggest a specialized role for CD8α+ DC in cross-presentation, where exogenous Ags are presented on MHC class I molecules to CD8+ T cells, while CD8α− DC are more likely to present extracellular Ags on MHC class II molecules to CD4+ T cells. As a proportion of CD8α+ DC have been shown to express langerin (CD207), we investigated the role of langerin+CD8α+ DC in presenting Ag and priming T cell responses to soluble Ags. When splenic DC populations were sorted from animals administered protein i.v., the ability to cross-present Ag was restricted to the langerin+ compartment of the CD8α+ DC population. The langerin+CD8α+ DC population was also susceptible to depletion following administration of cytochrome c, which is known to trigger apoptosis if diverted to the cytosol. Cross-priming of CTL in the presence of the adjuvant activity of the TLR2 ligand N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-Cys-[S]-Serl-[S]-Lys4-trihydrochloride or the invariant NKT cell ligand α-galactosylceramide was severely impaired in animals selectively depleted of langerin+ cells in vivo. The production of IL-12p40 in response to these systemic activation stimuli was restricted to langerin+CD8α+ DC, and the release of IL-12p70 into the serum following invariant NKT cell activation was ablated in the absence of langerin+ cells. These data suggest a critical role for the langerin+ compartment of the CD8α+ DC population in cross-priming and IL-12 production.
(Re)discovering a missional-incarnational ethos
Authors: Kok Jacobus , Niemandt Cornelius J.P.
Published: November 2009

In this article, a few of the elements and dynamics of social movements will be explored. It will be argued that the traditional institutional church is in a critical period in the cycle of movements, where the need for the (re)discovery of our missional-incarnational ethos and the theology of restoration might energise the church to (re)activate the dynamics of movements. The narrative of Jesus and the Samaritan woman in John 4 will be investigated as an example of Jesus’s missionalincarnational ethos and of the relation to a theology of restoration. Finally, some challenges for the church with regard to ecclesiology, spirituality and leadership will be proposed.
Estimating the Maximum Attainable Efficiency in Dye‐Sensitized Solar Cells
Authors: Snaith Henry J.
Published: November 2009

For an ideal solar cell, a maximum solar‐to‐electrical power conversion efficiency of just over 30% is achievable by harvesting UV to near IR photons up to 1.1 eV. Dye‐sensitized solar cells (DSCs) are, however, not ideal. Here, the electrical and optical losses in the dye‐sensitized system are reviewed, and the main losses in potential from the conversion of an absorbed photon at the optical bandgap of the sensitizer to the open‐circuit voltage generated by the solar cell are specifically highlighted. In the first instance, the maximum power conversion efficiency attainable as a function of optical bandgap of the sensitizer and the “loss‐in‐potential” from the optical bandgap to the open‐circuit voltage is estimated. For the best performing DSCs with current technology, the loss‐in‐potential is ∼0.75 eV, which leads to a maximum power‐conversion efficiency of 13.4% with an optical bandgap of 1.48 eV (840 nm absorption onset). Means by which the loss‐in‐potential could be reduced to 0.4 eV are discussed; a maximum efficiency of 20.25% with an optical bandgap of 1.31 eV (940 nm) is possible if this is achieved.