bluuebunny/crossref_metadata_2025 huggingface dataset:
Esterification of Fatty Acids with Short-Chain Alcohols over Commercial Acid Clays in a Semi-Continuous Reactor
Authors: Bouguerra Neji Soumaya , Trabelsi Mahmoud , Frikha Mohamed H.
Published: November 2009

Production of fatty acid esters from stearic, oleic, and palmitic acids and short-chain alcohols (methanol, ethanol, propanol, and butanol) for the production of biodiesel was investigated in this work. A series of montmorillonite-based clays catalysts (KSF, KSF/0, KP10, and K10) were used as acidic catalysts. The influence of the specific surface area and the acidity of the catalysts on the esterification rate were investigated. The best catalytic activities were obtained with KSF/0 catalyst. The esterification reaction has been carried out efficiently in a semi-continuous reactor at 150°C temperature higher than the boiling points of water and alcohol. The reactor used enabled the continuous removal of water and esterification with hydrated alcohol (ethanol 95%) without affecting the original activity of the clay.
C18:1 Methyl Ester Metathesis in [bmim][X] Type Ionic Liquids
Authors: Thomas Priya A. , Marvey Bassie B.
Published: November 2009

The efficacyof [bmim][X] ionic liquids (ILs) (X = PF6–, BF4– and NTf2–) as reaction media for methyl oleate metathesis was compared with that of conventional organic solvents (PhCl, PhMe, DCM and DCE) using the well-defined first and second generation Grubbs precatalysts, RuCl2(PCy3)(L)(=CHPh) (L = PCy3 or H2IMes). Best catalytic performance, with excellent selectivity (>98%) at moderate reaction temperatures, was achieved in [bmim][X] ILs compared to conventional solvents. The effects of anion, reaction temperature, solvent polarity, solvent viscosity, and ligand-anion interaction on the reaction are also addressed.
The Use of Ceramics as Bone Substitutes in Revision Hip Arthroplasty
Authors: Whitehouse Michael R. , Blom Ashley W.
Published: November 2009

The number of grafting procedures, including those performed in primary and revision hip arthroplasty, continues to rise around the world. Demand for musculoskeletal donor tissue now outstrips supply. There is no single bone substitute that is ideal for all circumstances. Bone substitutes act as a scaffold and are usually osteoconductive. They are rarely osteoinductive; if they are, a molecular bond is formed between the graft and host bone, improving fixation and longevity. Bone graft substitutes are very rarely osteogenic. There is a growing body of clinical evidence supporting the use of bone graft substitutes in vivo for complex hip arthroplasty.
Marine Benthic Diatoms Contain Compounds Able to Induce Leukemia Cell Death and Modulate Blood Platelet Activity
Authors: Prestegard Siv Kristin , Oftedal Linn , Coyne Rosie Theresa , Nygaard Gyrid , Skjærven Kaja Helvik , Knutsen Gjert , Døskeland Stein Ove , Herfindal Lars
Published: November 2009

In spite of the high abundance and species diversity of diatoms, only a few bioactive compounds from them have been described. The present study reveals a high number of mammalian cell death inducing substances in biofilm-associated diatoms sampled from the intertidal zone. Extracts from the genera Melosira, Amphora, Phaeodactylum and Nitzschia were all found to induce leukemia cell death, with either classical apoptotic or autophagic features. Several extracts also contained inhibitors of thrombin-induced blood platelet activation. Some of this activity was caused by a high content of adenosine in the diatoms, ranging from 0.07 to 0.31 μg/mg dry weight. However, most of the bioactivity was adenosine deaminase-resistant. An adenosine deaminase-resistant active fraction from one of the extracts was partially purified and shown to induce apoptosis with a distinct phenotype. The results show that benthic diatoms typically found in the intertidal zone may represent a richer source of interesting bioactive compounds than hitherto recognized.
New Lipophilic Piceatannol Derivatives Exhibiting Antioxidant Activity Prepared by Aromatic Hydroxylation with 2-Iodoxybenzoic Acid (IBX)
Authors: Bernini Roberta , Barontini Maurizio , Spatafora Carmela
Published: November 2009

Piceatannol (E-3,5,3’,4’-tetrahydroxystilbene) is a phytoalexin synthesized in grapes in response to stress conditions. It exhibits strong antioxidant and antileukaemic activities due to the presence of the catechol moiety. To modify some physical properties like solubility, and miscibility in non-aqueous media some new previously unreported piceatannol derivatives having lipophilic chains on the A-ring were prepared in good yields by a simple and efficient procedure. The key step was a chemo- and regioselective aromatic hydroxylation with 2-iodoxybenzoic acid (IBX). The new compounds showed antioxidant activity and seemed promising for possible applications as multifunctional emulsifiers in food, cosmetic and pharmaceutical fields.
Steroidal Triterpenes: Design of Substrate-Based Inhibitors of Ergosterol and Sitosterol Synthesis
Authors: Liu Jialin , Nes William David
Published: November 2009

This article reviews the design and study, in our own laboratory and others, of new steroidal triterpenes with a modified lanosterol or cycloartenol frame. These compounds, along with a number of known analogs with the cholestane skeleton, have been evaluated as reversible or irreversible inhibitors of sterol C24-methyltransferase (SMT) from plants, fungi and protozoa. The SMT catalyzes the C24-methylation reaction involved with the introduction of the C24-methyl group of ergosterol and the C24-ethyl group of sitosterol, cholesterol surrogates that function as essential membrane inserts in many photosynthetic and non-photosynthetic eukaryotic organisms. Sterol side chains constructed with a nitrogen, sulfur, bromine or fluorine atom, altered to possess a methylene cyclopropane group, or elongated to include terminal double or triple bonds are shown to exhibit different in vitro activities toward the SMT which are mirrored in the inhibition potencies detected in the growth response of treated cultured human and plant cells or microbes. Several of the substrate-based analogs surveyed here appear to be taxaspecific compounds acting as mechanism-based inactivators of the SMT, a crucial enzyme not synthesized by animals. Possible mechanisms for the inactivation process and generation of novel products catalyzed by the variant SMTs are discussed.
NMR-Based Multi Parametric Quality Control of Fruit Juices: SGF Profiling
Authors: Spraul Manfred , Schütz Birk , Rinke Peter , Koswig Susanne , Humpfer Eberhard , Schäfer Hartmut , Mörtter Monika , Fang Fang , Marx Ute C. , Minoja Anna
Published: November 2009

With SGF Profiling™ we introduce an NMR-based screening method for the quality control of fruit juices. This method has been developed in a joint effort by Bruker BioSpin GmbH and SGF International e.V. The system is fully automated with respect to sample transfer, measurement, data analysis and reporting and is set up on an Avance 400 MHz flow-injection NMR spectrometer. For each fruit juice a multitude of parameters related to quality and authenticity are evaluated simultaneously from a single data set acquired within a few minutes. This multimarker/multi-aspect NMR screening approach features low cost-per-sample and is highly competitive with conventional and targeted fruit juice quality control methods.
Remote Sensing of Channels and Riparian Zones with a Narrow-Beam Aquatic-Terrestrial LIDAR
Authors: McKean Jim , Nagel Dave , Tonina Daniele , Bailey Philip , Wright Charles Wayne , Bohn Carolyn , Nayegandhi Amar
Published: November 2009

The high-resolution Experimental Advanced Airborne Research LIDAR (EAARL) is a new technology for cross-environment surveys of channels and floodplains. EAARL measurements of basic channel geometry, such as wetted cross-sectional area, are within a few percent of those from control field surveys. The largest channel mapping errors are along stream banks. The LIDAR data adequately support 1D and 2D computational fluid dynamics models and frequency domain analyses by wavelet transforms. Further work is needed to establish the stream monitoring capability of the EAARL and the range of water quality conditions in which this sensor will accurately map river bathymetry.
A Simple Method to Determine the Timing of Snow Melt by Remote Sensing with Application to the CO2 Balances of Northern Mire and Heath Ecosystems
Authors: Rinne Janne , Aurela Mika , Manninen Terhikki
Published: November 2009

The timing of the disappearance of the snow cover in spring, or snow melt day (SMD), is a key parameter controlling the carbon dioxide balance between the northern mire and heath ecosystems and the atmosphere. We present a simple method for the determination of the SMD using a satellite-based surface albedo product (SAL). The method is based on the local change of albedo from higher wintertime values towards the lower summertime values. The satellite SMD timing correlates well with the SMD determined from snow depth measurements at Finnish weather stations (r = 0.86, slope 1.05). In 50% of the cases the error was 3.4 days or less and bias less than half a day. This would lead to a moderate uncertainty in the annual CO2 balance of mire and heath ecosystems, if the published SMD—CO2 balance relations are valid. However, due to the limited data sets available a systematic validation is left for the future.
Microfabricated Formaldehyde Gas Sensors
Authors: Flueckiger Jonas , Ko Frank  K. , Cheung Karen  C.
Published: November 2009

Formaldehyde is a volatile organic compound that is widely used in textiles, paper, wood composites, and household materials. Formaldehyde will continuously outgas from manufactured wood products such as furniture, with adverse health effects resulting from prolonged low-level exposure. New, microfabricated sensors for formaldehyde have been developed to meet the need for portable, low-power gas detection. This paper reviews recent work including silicon microhotplates for metal oxide-based detection, enzyme-based electrochemical sensors, and nanowire-based sensors. This paper also investigates the promise of polymer-based sensors for low-temperature, low-power operation.
A CMOS Time-Resolved Fluorescence Lifetime Analysis Micro-System
Authors: Rae Bruce  R. , Muir Keith  R. , Gong Zheng , McKendry Jonathan , Girkin John  M. , Gu Erdan , Renshaw David , Dawson Martin  D. , Henderson Robert  K.
Published: November 2009

We describe a CMOS-based micro-system for time-resolved fluorescence lifetime analysis. It comprises a 16 × 4 array of single-photon avalanche diodes (SPADs) fabricated in 0.35 μm high-voltage CMOS technology with in-pixel time-gated photon counting circuitry and a second device incorporating an 8 × 8 AlInGaN blue micro-pixellated light-emitting diode (micro-LED) array bump-bonded to an equivalent array of LED drivers realized in a standard low-voltage 0.35 μm CMOS technology, capable of producing excitation pulses with a width of 777 ps (FWHM). This system replaces instrumentation based on lasers, photomultiplier tubes, bulk optics and discrete electronics with a PC-based micro-system. Demonstrator lifetime measurements of colloidal quantum dot and Rhodamine samples are presented.
The Development of a Portable Hard Disk Encryption/Decryption System with a MEMS Coded Lock
Authors: Zhang Weiping , Chen Wenyuan , Tang Jian , Xu Peng , Li Yibin , Li Shengyong
Published: November 2009

In this paper, a novel portable hard-disk encryption/decryption system with a MEMS coded lock is presented, which can authenticate the user and provide the key for the AES encryption/decryption module. The portable hard-disk encryption/decryption system is composed of the authentication module, the USB portable hard-disk interface card, the ATA protocol command decoder module, the data encryption/decryption module, the cipher key management module, the MEMS coded lock controlling circuit module, the MEMS coded lock and the hard disk. The ATA protocol circuit, the MEMS control circuit and AES encryption/decryption circuit are designed and realized by FPGA(Field Programmable Gate Array). The MEMS coded lock with two couplers and two groups of counter-meshing-gears (CMGs) are fabricated by a LIGA-like process and precision engineering method. The whole prototype was fabricated and tested. The test results show that the user’s password could be correctly discriminated by the MEMS coded lock, and the AES encryption module could get the key from the MEMS coded lock. Moreover, the data in the hard-disk could be encrypted or decrypted, and the read-write speed of the dataflow could reach 17 MB/s in Ultra DMA mode.
Therapeutic Approaches Using Host Defence Peptides to Tackle Herpes Virus Infections
Authors: Jenssen Håvard
Published: November 2009

One of the most common viral infections in humans is caused by herpes simplex virus (HSV). It can easily be treated with nucleoside analogues (e.g., acyclovir), but resistant strains are on the rise. Naturally occurring antimicrobial peptides have been demonstrated to possess antiviral activity against HSV. New evidence has also indicated that these host defence peptides are able to selectively stimulate the innate immune system to fight of infections. This review will focus on the anti-HSV activity of such peptides (both natural and synthetic), describe their mode of action and their clinical potential.
Cellular Players in the Herpes Simplex Virus Dependent Apoptosis Balancing Act
Authors: Nguyen Marie L. , Blaho John A.
Published: November 2009

Apoptosis is triggered as an intrinsic defense against numerous viral infections. Almost every virus encodes apoptotic modulators, and the herpes simplex viruses (HSV) are no exception. During HSV infection, there is an intricate balance between pro- and anti-apoptotic factors that delays apoptotic death until the virus has replicated. Perturbations in the apoptotic balance can cause premature cell death and have the potential to dramatically alter the outcome of infection. Recently, certain cellular genes have been shown to regulate sensitivity to HSV-dependent apoptosis. This review summarizes current knowledge of the cellular genes that impact the apoptotic balance during HSV infection.
Influence of Cell Treatment with PDGF-BB and Reperfusion on Cardiac Persistence of Mononuclear and Mesenchymal Bone Marrow Cells after Transplantation into Acute Myocardial Infarction in Rats
Authors: Krausgrill Benjamin , Vantler Marius , Burst Volker , Raths Martin , Halbach Marcel , Frank Konrad , Schynkowski Silke , Schenk Kerstin , Hescheler Jürgen , Rosenkranz Stephan , Müller-Ehmsen Jochen
Published: November 2009

Bone marrow cells are used for cell therapy after myocardial infarction (MI) with promising results. However, cardiac persistence of transplanted cells is rather low. Here, we investigated strategies to increase the survival and cardiac persistence of mononuclear (MNC) and mesenchymal (MSC) bone marrow cells transplanted into infarcted rat hearts. MNC and MSC (male Fischer 344 rats) were treated with different doses of PDGF-BB prior to intramyocardial injection into border zone of MI (syngeneic females, permanent LAD ligation) and hearts were harvested after 5 days and 3 weeks. In additional experiments, untreated MNC and MSC were injected immediately after permanent or temporary LAD ligation and hearts were harvested after 48 h, 5 days, 3 weeks, and 6 weeks. DNA of the hearts was isolated and the number of donor cells was determined by quantitative real-time PCR with Y chromosome-specific primers. There was a remarkable though not statistically significant ( p = 0.08) cell loss of ~46% between 5 days and 3 weeks in the control group, which was completely inhibited by treatment with high dose of PDGF-BB. Forty-eight hours after reperfusion only 10% of injected MSC or 1% for MNC were found in the heart, decreasing to 1% for MSC and 0.5% for MNC after 6 weeks. These numbers were lower than after permanent LAD ligation for both MNC and MSC at all time points studied. Treatment with PDGF-BB seems to prevent loss of transplanted bone marrow cells at later times presumably by inhibition of apoptosis, while reperfusion of the occluded artery enhances cell loss at early times putatively due to enhanced early wash-out. Further investigations are needed to substantially improve the persistence and survival of grafted bone marrow cells in infarcted rat hearts, in order to fully explore the therapeutic potential of this novel treatment modality for myocardial repair.
Small Agarose Microcapsules with Cell-Enclosing Hollow Core for Cell Therapy: Transplantation of Ifosfamide-Activating Cells to the Mice with Preestablished Subcutaneous Tumor
Authors: Sakai Shinji , Hashimoto Ichiro , Tanaka Shinji , Salmons Brian , Kawakami Koei
Published: November 2009

Cell transplantation after enclosing in microcapsules has been studied as an alternative approach for treatment of wide variety of diseases. In the present study, we examined the feasibility of using agarose microcapsules, having a cell-enclosing hollow core of 100–150 μm in diameter and agarose gel membrane of about 20 μm in thickness, as a device for the methodology. We enclosed cells that had been genetically engineered to express cytochrome P450 2B1, an enzyme that activates the anticancer prodrug ifosfamide. The enclosed cells were shown to express the enzymatic function in the microcapsules in that they suppressed the growth of tumor cells in medium containing ifosfamide. In addition, a more significant regression of preformed tumors was observed in the nude mice implanted with the cell-enclosing microcapsules compared with those implanted with empty capsules after administration of ifosfamide. Preformed tumors shrank by less than 40% in volume in 6 of the 10 recipients implanted with cell-enclosing microcapsules. In contrast, only 1 in 10 of the preformed tumors in the recipient implanted with empty microcapsules shrank by this amount. These results suggest that agarose microcapsules containing cytochrome P450 2B1 enzyme-expressing cells are feasible devices for improving the chemotherapy of tumors. Thus, agarose microcapsule having hollow cores are generally a good candidate as vehicles for cell-encapsulation approaches to cell therapy.
Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal Rats
Authors: Chang Yun Sil , Oh Wonil , Choi Soo Jin , Sung Dong Kyung , Kim Soo Yoon , Choi Eun Yang , Kang Saem , Jin Hye Jin , Yang Yoon Sun , Park Won Soon
Published: November 2009

Recent evidence suggests mesenchymal stem cells (MSCs) can downmodulate bleomycin-induced lung injury, and umbilical cord blood (UCB) is a promising source for human MSCs. This study examined whether intratracheal or intraperitoneal transplantation of human UCB-derived MSCs can attenuate hyperoxia-induced lung injury in immunocompetent newborn rats. Wild-type Sprague-Dawley rats were randomly exposed to 95% oxygen or air from birth. In the transplantation groups, a single dose of PKH26-labeled human UCB-derived MSCs was administered either intratracheally (2 × 106cells) or intraperitoneally (5 × 105cells) at postnatal day (P) 5. At P14, the harvested lungs were examined for morphometric analyses of alveolarization and TUNEL staining, as well as the myeoloperoxidase activity, the level of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and transforming growth factor (TGF)-β mRNA, α-smooth muscle actin (SMA) protein, and collagen levels. Differentiation of MSCs to the respiratory epithelium was also evaluated both in vitro before transplantation and in vivo after transplantation. Despite one fourth dosage of MSCs, significantly more PKH26-labeled donor cells were recovered with intratracheal administration than with intraperitoneal administration both during normoxia and hyperoxia. The hyperoxia-induced increase in the number of TUNEL-positive cells, myeloperoixdase activity, and the level of IL-6 mRNA were significantly attenuated with both intratracheal and intraperitoneal MSCs transplantation. However, the hyperoxia-induced impaired alveolarization and increased the level of TNF-α and TGF-β mRNA, α-SMA protein, and collagen were significantly attenuated only with intratracheal MSCs transplantation. MSCs differentiated into respiratory epithelium in vitro and a few PKH26-positive donor cells were colocalized with pro surfactant protein C in the damaged lungs. In conclusion, intratracheal transplantation of human UCB-derived MSCs is more effective than intraperitoneal transplantation in attenuating the hyperoxia-induced lung injury in neonatal rats.
Amniotic Mesenchymal Tissue Cells Inhibit Dendritic Cell Differentiation of Peripheral Blood and Amnion Resident Monocytes
Authors: Magatti Marta , De Munari Silvia , Vertua Elsa , Nassauto Claudia , Albertini Alberto , Wengler Georg S. , Parolini Ornella
Published: November 2009

Cells derived from the amniotic membranes of human term placenta have drawn much interest for their characteristics of multipotency and low immunogenicity, supporting a variety of possible clinical applications in the field of cell transplantation and regenerative medicine. We have previously shown that cells derived from the mesenchymal region of human amnion (AMTC) can strongly inhibit T-lymphocyte proliferation. In this study, we demonstrate that AMTC can block differentiation and maturation of monocytes into dendritic cells (DC), preventing the expression of the DC marker CD1a and reducing the expression of HLA-DR, CD80, and CD83. The monocyte maturation block resulted in impaired allostimulatory ability of these cells on allogeneic T cells. In attempting to define the mechanisms responsible for these findings, we have observed that the presence of AMTC in differentiating DC cultures results in the arrest of the cells to the G0 phase and abolishes the production of inflammatory cytokines such as TNF-α, CXCL10, CXCL9, and CCL5. Finally, we also demonstrate that the monocytic cells present in the amniotic mesenchymal region fail to differentiate toward the DC lineage. Taken together, our data suggest that the mechanisms by which AMTC exert immumodulatory effects do not only relate directly to T cells, but also include inhibition of the generation and maturation of antigen-presenting cells. In this context, AMTC represent a very attractive source of multipotent allogeneic cells that promise to be remarkably valuable for cell transplantation approaches, not only due to their low immunogenicity, but also because of the added potential of modulating immune responses, which could be fundamental both for controlling graft rejection after transplantation and also for controlling diseases characterized by inflammatory processes.
Increased Arterial Stiffness in HIV-Infected Children: Risk Factors and Antiretroviral Therapy
Authors: Charakida Marietta , Loukogeorgakis Stavros P , Okorie Michael I , Masi Stefano , Halcox Julian P , Deanfield John E , Klein Nigel J
Published: November 2009

Background

Recent evidence suggests that both the HIV virus and antiretroviral therapy (ART) are associated with premature atherosclerosis in adults. Increased arterial stiffness as assessed by pulse wave velocity (PWV) has been associated with adverse cardiovascular outcome in adults. The relationship between HIV infection and treatment and arterial stiffness has not been evaluated in children.

Methods

We studied 83 HIV-infected children with a mean ±sd age of 11.0 ±3.1 years and 59 controls aged 12.2 ±2.8 years. Among the HIV-infected children, 48 were receiving ART (23 including a protease inhibitor). Arterial stiffness was assessed non-invasively by carotid–radial PWV. Disease severity was defined according to the CDC classification.

Results

PWV was significantly increased in HIV-infected children compared with controls ( P<0.05). A significant association between age and PWV was noted in HIV-infected children but not in controls. HIV-infected children receiving ART had significantly increased total cholesterol levels and PWV compared with non-treated children ( P<0.001 and P<0.05, respectively). CDC stage was greater in ART-treated compared with non-treated HIV- infected children ( P<0.001). No differences in other cardiovascular risk factors were noted in the two groups. After multivariable analysis, ART, systolic blood pressure, disease severity and total cholesterol remained independent predictors of PWV.

Conclusions

HIV-infected children have increased arterial stiffness compared with healthy children. These changes were more pronounced with increasing age in HIV-infected children particularly in those who were receiving ART.
Systematic Review and Metaanalysis of Patient Self-Report versus Trained Assessor Joint Counts in Rheumatoid Arthritis
Authors: BARTON JENNIFER L. , CRISWELL LINDSEY A. , KAISER RACHEL , CHEN YEA-HUNG , SCHILLINGER DEAN
Published: November 2009

Objective.

Patient self-report outcomes and physician-performed joint counts are important measures of disease activity and treatment response. This metaanalysis examines the degree of concordance in joint counts between trained assessors and patients with rheumatoid arthritis (RA).

Methods.

Studies eligible for inclusion met the following criteria: English language; compared patient with trained assessor joint counts; peer-reviewed; and RA diagnosis determined by board-certified or board-eligible specialist or met 1987 American College of Rheumatology criteria. We searched PubMed and Embase to identify articles between 1966 and January 1, 2008. We compared measures of correlation between patients and assessors for either tender/painful or swollen joint counts. We used metaanalysis methods to calculate summary correlation estimates.

Results.

We retrieved 462 articles and 18 were included. Self-report joint counts were obtained by a text and/or mannequin (picture) format. The summary estimates for the Pearson correlation coefficients for tender joint counts were 0.61 (0.47 lower, 0.75 upper) and for swollen joint counts 0.44 (0.15, 0.73). Summary results for the Spearman correlation coefficients were 0.60 (0.30, 0.90) for tender joint counts and 0.54 (0.35, 0.73) for swollen joint counts.

Conclusion.

A self-report tender joint count has moderate to marked correlation with those performed by a trained assessor. In contrast, swollen joint counts demonstrate lower levels of correlation. Future research should explore whether integrating self-report tender joint counts into routine care can improve efficiency and quality of care, while directly involving patients in assessment of RA disease activity.
Influence of the NAO on the northwestern Mediterranean wave climate
Authors: Cañellas Bartomeu , Orfila Alejandro , Méndez Fernando , Álvarez Alberto , Tintoré Joaquín
Published: November 2009

This study examines teleconnections between the North Atlantic Oscillation (NAO) and the wave climate of the northwestern Mediterranean Sea (NWM), defined by the monthly mean significant wave height (SWH) and the 95th percentile significant wave height (95th percentile SWH), in the period ranging from 1958 to 2001. The data analyzed comes from the multidecadal hindcast over Europe carried out during the HIPOCAS project. In order to avoid fictitious cross-correlations, data were prewhitened by fitting a p-order autoregressive model. To split the temporal and spatial variability, an EOF encoding technique was applied to residuals before searching for teleconnections. We found the northwestern Mediterranean wave climate to be influenced by the North Atlantic Oscillation (NAO) with an instantaneous response. When the NAO is in its positive phase, positive anomalies in the SWH and the 95th percentile SWH appear in the area between the Balearic Islands, the Gulf of Lions and the Catalonian coast.
Neutrophils and Macrophages Cooperate in Host Resistance againstLeishmania braziliensisInfection
Authors: Novais Fernanda O. , Santiago Rômulo C. , Báfica André , Khouri Ricardo , Afonso Lilian , Borges Valéria M. , Brodskyn Cláudia , Barral-Netto Manoel , Barral Aldina , de Oliveira Camila I.
Published: November 2009

Neutrophils play an active role in the control of infections caused by intracellular pathogens such as Leishmania. In the present study, we investigated the effect of neutrophil depletion at the time of Leishmania braziliensis infection of BALB/c mice and how neutrophils interact with the infected macrophage to promote parasite elimination. The in vivo depletion of neutrophils led to a significant increase in parasite load and enhanced the Th1-Th2 immune response in this experimental model of infection. BALB/c mice coinoculated with both parasites and live neutrophils displayed lower parasite burdens at the site of infection and in the draining lymph nodes. In vitro, we observed that live neutrophils significantly reduced the parasite load in L. braziliensis-infected murine macrophages, an effect not observed with Leishmania major. L. braziliensis elimination was dependent on the interaction between neutrophils and macrophages and was associated with TNF-α as well as superoxide production. Furthermore, cooperation between neutrophils and macrophages toward parasite elimination was also observed in experiments performed with L. braziliensis-infected human cells and, importantly, with two other New World Leishmania species. These results indicate that neutrophils play an important and previously unappreciated role in L. braziliensis infection, favoring the induction of a protective immune response.
Cutting Edge: Normal Regional Lymph Node Enrichment of Antigen-Specific Regulatory T Cells with Autoimmune Disease-Suppressive Capacity
Authors: Wheeler Karen M. , Samy Eileen T. , Tung Kenneth S. K.
Published: November 2009

Natural CD4+CD25+Foxp3+ regulatory T cells (Treg) effectively prevent autoimmune disease development, but their role in maintaining physiological tolerance against self-Ag of internal organs is not yet defined. In this study, we quantified disease-specific Treg (DS-Treg) as Treg that preferentially suppress one autoimmune disease over another in day 3 thymectomized recipients. A striking difference was found among individual lymph nodes (LN) of normal mice; Treg from draining LN were 15–50 times more efficient than those of nondraining LN at suppressing autoimmune diseases of ovary, prostate, and lacrimal glands. The difference disappeared upon auto-Ag ablation and returned upon auto-Ag re-expression. In contrast, the CD4+CD25− effector T cells from different individual LN induced multiorgan inflammation with comparable organ distribution. We propose that peripheral tolerance for internal organs relies on the control of autoreactive effector T cells by strategic enrichment of Ag-specific Treg in the regional LN.
IFN-γ Expressed by T Cells Regulates the Persistence of Antigen Presentation by Limiting the Survival of Dendritic Cells
Authors: Russell Marsha S. , Dudani Renu , Krishnan Lakshmi , Sad Subash
Published: November 2009

Ag presentation to T cells orchestrates the development of acquired immune response. Although it is considered that Ag presentation may persist at high levels during chronic infections, we have previously reported that in mice infected with bacillus Calmette-Guérin, Ag presentation gets drastically curtailed during the chronic stage of infection despite antigenic persistence. In this report we evaluated the mechanism of this curtailment. Ag presentation declined precipitously as the T cell response developed, and Ag presentation was not curtailed in mice that were deficient in CD8+ T cells or MHC class II, suggesting that T cells regulate Ag presentation. Curtailment of Ag presentation was reduced in IFN-γ-deficient mice, but not in mice with a deficiency/mutation in inducible NOS2, perforin, or Fas ligand. In hosts with no T cells (Rag1−/−), Ag presentation was not curtailed during the chronic stage of infection. However, adoptive transfer of wild-type, but not IFN-γ−/−, CD4+ and CD8+ T cells into Rag1-deficient hosts strongly curtailed Ag presentation. Increased persistence of Ag presentation in IFN-γ-deficient hosts correlated to increased survival of dendritic cells, but not of macrophages, and was not due to increased stimulatory capacity of IFN-γ-deficient dendritic cells. These results reveal a novel mechanism indicating how IFN-γ prevents the persistence of Ag presentation, thereby preventing memory T cells from going into exhaustion.
What Role Does the Route of Immunization Play in the Generation of Protective Immunity against Mucosal Pathogens?
Authors: Belyakov Igor M. , Ahlers Jeffrey D.
Published: November 2009

The route of vaccination is important in influencing immune responses at the initial site of pathogen invasion where protection is most effective. Immune responses required for mucosal protection can differ vastly depending on the individual pathogen. For some mucosal pathogens, including acute self-limiting infections, high-titer neutralizing Abs that enter tissue parenchyma or transude into the mucosal lumen are sufficient for clearing cell-free virus. However, for pathogens causing chronic infections such as HIV, hepatitis C virus, herpes viruses, mycobacteria, and fungal and parasitic infections, a single arm of the immune response generated by systemic vaccination may be insufficient for protection. Induction of the mucosal innate and adaptive immune systems, including CD4+ T help, Th17, high avidity CD8+ CTL, and secretory IgA and IgG1 neutralizing Abs, at the site of pathogen entry may be required for effective protection against highly invasive pathogens that lead to chronic infection and may be generated predominantly by mucosal vaccination.
IL-23 Is Required for Protection against Systemic Infection withListeria monocytogenes
Authors: Meeks Karen D. , Sieve Amy N. , Kolls Jay K. , Ghilardi Nico , Berg Rance E.
Published: November 2009

Listeria monocytogenes (LM) is a Gram-positive, intracellular bacterium that can induce spontaneous abortion, septicemia, and meningitis. Although it is known that neutrophils are required for elimination of the bacteria and for survival of the host, the mechanisms governing the recruitment of neutrophils to LM-infected tissues are not fully understood. We demonstrate here that IL-23 and the IL-17 receptor A (IL-17RA), which mediates both IL-17A and IL-17F signaling, are necessary for resistance against systemic LM infection. LM-infected IL-23p19 knockout (KO) mice have decreased production of IL-17A and IL-17F, while IFN-γ production is not altered by the lack of IL-23. LM induces the production of IL-17A from γδ T cells, but not CD4, CD8, or NK cells. Furthermore, a lack of efficient neutrophil recruitment to the liver is evident in both IL-23p19 KO and IL-17RA KO mice during LM infection. Immunocytochemical analysis of infected livers revealed that neutrophils were able to localize with LM in IL-23p19 KO and IL-17RA KO mice, indicating that IL-23 and IL-17RA do not regulate the precise localization of neutrophils with LM. The importance of IL-23-induced IL-17A was demonstrated by injecting IL-23p19 KO mice with recombinant IL-17A. These mice had reduced LM bacterial burdens compared with IL-23p19 KO mice that did not receive IL-17A. These results indicate that during LM infection, IL-23 regulates the production of IL-17A and IL-17F from γδ T cells, resulting in optimal liver neutrophil recruitment and enhanced bacterial clearance.
Cutting Edge: Inhibitory Effects of CD4 and CD8 on T Cell Activation Induced by High-Affinity Noncognate Ligands
Authors: Chervin Adam S. , Stone Jennifer D. , Bowerman Natalie A. , Kranz David M.
Published: November 2009

It has been proposed that MHC restriction during thymocyte selection is controlled by coreceptor (CD4 or CD8) sequestration of the signaling molecule Lck. We explored this model as a mechanism for preventing peripheral T cell activation due to non-MHC ligand cross-reactivities of TCRs. TCRs that have a range of affinities for a class I MHC ligand were transduced into a T cell hybridoma in the absence or presence of coreceptors. High and intermediate affinity TCRs (KD = 17 and 540 nM) did not require CD8 for T cell activity, but CD4 acted as a potent inhibitor of the intermediate affinity TCR. These and other findings support the view that even high-affinity TCR:ligand interactions can be influenced by coreceptor sequestration of Lck. Thus, CD4 and CD8 act as “coreceptor inhibitors” to maintain appropriate TCR-mediated MHC restriction in peripheral T cell activity.
Matrix Metalloproteinase (MMP)-1 and MMP-3 Induce Macrophage MMP-9: Evidence for the Role of TNF-α and Cyclooxygenase-2
Authors: Steenport Michel , Khan K. M. Faisal , Du Baoheng , Barnhard Sarah E. , Dannenberg Andrew J. , Falcone Domenick J.
Published: November 2009

Matrix metalloproteinase (MMP)-9 (gelatinase B) participates in a variety of diverse physiologic and pathologic processes. We recently characterized a cyclooxygenase-2 (COX-2)→PGE2→EP4 receptor axis that regulates macrophage MMP-9 expression. In the present studies, we determined whether MMPs, commonly found in inflamed and neoplastic tissues, regulate this prostanoid-EP receptor axis leading to enhanced MMP-9 expression. Results demonstrate that exposure of murine peritoneal macrophages and RAW264.7 macrophages to MMP-1 (collagenase-1) or MMP-3 (stromelysin-1) lead to a marked increase in COX-2 expression, PGE2 secretion, and subsequent induction of MMP-9 expression. Proteinase-induced MMP-9 expression was blocked in macrophages preincubated with the selective COX-2 inhibitor celecoxib or transfected with COX-2 small interfering RNA (siRNA). Likewise, proteinase-induced MMP-9 was blocked in macrophages preincubated with the EP4 antagonist ONO-AE3-208 or transfected with EP4 siRNA. Exposure of macrophages to MMP-1 and MMP-3 triggered the rapid release of TNF-α, which was blocked by MMP inhibitors. Furthermore, both COX-2 and MMP-9 expression were inhibited in macrophages preincubated with anti-TNF-α IgG or transfected with TNF-α siRNA. Thus, proteinase-induced MMP-9 expression by macrophages is dependent on the release of TNF-α, induction of COX-2 expression, and PGE2 engagement of EP4. The ability of MMP-1 and MMP-3 to regulate macrophage secretion of PGE2 and expression of MMP-9 defines a nexus between MMPs and prostanoids that is likely to play a role in the pathogenesis of chronic inflammatory diseases and cancer. These data also suggest that this nexus is targetable utilizing anti-TNF-α therapies and/or selective EP4 antagonists.
Duality of Enhancer Functioning Mode Revealed in a Reduced TCRβ Gene Enhancer Knockin Mouse Model
Authors: Bonnet Marie , Huang Fang , Benoukraf Touati , Cabaud Olivier , Verthuy Christophe , Boucher Anaelle , Jaeger Sébastien , Ferrier Pierre , Spicuglia Salvatore
Published: November 2009

The TCRβ gene enhancer (Eβ) commands TCRβ gene expression through the lifespan of T lymphocytes. Genetic and molecular studies have implied that in early thymocytes, Eβ directs chromatin opening over the Dβ-Jβ-Cβ domains and triggers initial Dβ-Jβ recombination. In mature T cells, Eβ is required for expression of the assembled TCRβ gene. Whether these separate activities rely on distinct Eβ regulatory sequences and involve differing modes of activation is unclear. Using gene targeting in mouse embryonic stem cells, we replaced Eβ by a conserved core fragment (Eβ169). We found that Eβ169-carrying alleles were capable of sustaining β gene expression and the development of mature T cells in homozygous knockin mice. Surprisingly, these procedures and underlying molecular transactions were affected to a wide range of degrees depending on the developmental stage. Early thymocytes barely achieved Dβ-Jβ germline transcription and recombination. In contrast, T cells displayed substantial though heterogeneous levels of VDJ-rearranged TCRβ gene expression. Our results have implications regarding enhancer function in cells of the adaptive immune system and, potentially, TCRβ gene recombination and allelic exclusion.
Viruses within theFlaviviridaeDecrease CD4 Expression and Inhibit HIV Replication in Human CD4+ Cells
Authors: Xiang Jinhua , McLinden James H. , Rydze Robert A. , Chang Qing , Kaufman Thomas M. , Klinzman Donna , Stapleton Jack T.
Published: November 2009

Viral infections alter host cell homeostasis and this may lead to immune evasion and/or interfere with the replication of other microbes in coinfected hosts. Two flaviviruses are associated with a reduction in HIV replication or improved survival in HIV-infected people (dengue virus (DV) and GB virus type C (GBV-C)). GBV-C infection and expression of the GBV-C nonstructural protein 5A (NS5A) and the DV NS5 protein in CD4+ T cells inhibit HIV replication in vitro. To determine whether the inhibitory effect on HIV replication is conserved among other flaviviruses and to characterize mechanism(s) of HIV inhibition, the NS5 proteins of GBV-C, DV, hepatitis C virus, West Nile virus, and yellow fever virus (YFV; vaccine strain 17D) were expressed in CD4+ T cells. All NS5 proteins inhibited HIV replication. This correlated with decreased steady-state CD4 mRNA levels and reduced cell surface CD4 protein expression. Infection of CD4+ T cells and macrophages with YFV (17D vaccine strain) also inhibited HIV replication and decreased CD4 gene expression. In contrast, mumps virus was not inhibited by the expression of flavivirus NS5 protein or by YFV infection, and mumps infection did not alter CD4 mRNA or protein levels. In summary, CD4 gene expression is decreased by all human flavivirus NS5 proteins studied. CD4 regulation by flaviviruses may interfere with innate and adaptive immunity and contribute to in vitro HIV replication inhibition. Characterization of the mechanisms by which flaviviruses regulate CD4 expression may lead to novel therapeutic strategies for HIV and immunological diseases.
Activated CD8+ T-Effector/Memory Cells Eliminate CD4+ CD25+ Foxp3+ T-Suppressor Cells from Tumors via FasL Mediated Apoptosis
Authors: Kilinc Mehmet O. , Rowswell-Turner Rachael B. , Gu Tao , Virtuoso Lauren P. , Egilmez Nejat K.
Published: November 2009

Tumor-resident CD8+ T cells display a quiescent effector/memory phenotype that is maintained in part by infiltrating CD4+ CD25+ Foxp3+ T-suppressor cells. Intratumoral delivery of IL-12, in contrast, can restore cytotoxic function to tumor-associated CD8+ T cells and induce the apoptotic death of T-suppressor cells. Depletion of CD8+ T cells from tumors before IL-12 treatment resulted in the abrogation of treatment-mediated T-suppressor cell apoptosis revealing a link between CD8+ T cell activation and T-suppressor elimination. Furthermore, IL-12 failed to induce T-suppressor cell loss in IFN-γ- or FasL-deficient mice demonstrating a requirement for IFN-γ and FasL in this process. Adoptive transfer of wild-type CD8+ T cells to FasL-knockout mice restored posttherapy T-suppressor cell elimination from tumors establishing that expression of FasL on CD8+ T cells was sufficient to promote T-suppressor cell death. IL-12 failed to induce FasL on T-effectors in IFN-γ-knockout mice demonstrating a requirement for IFN-γ in FasL up-regulation. Adoptive transfer of wild-type CD8+ T cells induced T-suppressor cell death in IFN-γ-knockout mice confirming that autocrine IFN-γ was sufficient for CD8+ T cell FasL expression. These findings reveal a mechanism by which cytotoxic T cells can abrogate regulatory cell activity.
The Tpl2 Mutation Sluggish Impairs Type I IFN Production and Increases Susceptibility to Group B Streptococcal Disease
Authors: Xiao Nengming , Eidenschenk Celine , Krebs Philippe , Brandl Katharina , Blasius Amanda L. , Xia Yu , Khovananth Kevin , Smart Nora G. , Beutler Bruce
Published: November 2009

Sluggish was identified in a population of third generation mice descended from N-ethyl-N-nitrosourea-mutagenized sires. Macrophages from homozygotes exhibited impaired TNF-α production in response to all TLR ligands tested and displayed impaired type I IFN production in response to TLR7 and TLR9 stimulations. The phenotype was confined to a critical region on mouse chromosome 18 and then ascribed to a T to A transversion in the acceptor splice site of intron 4 at position 13346 of the Map3k8 gene, resulting in defective splicing. The Map3k8Sluggish mutation does not result in susceptibility to viral infections, but Sluggish mice displayed high susceptibility to group B streptococcus infection, with impaired TNF-α and type I IFN production in infected macrophages. Our data demonstrate that the encoded protein kinase Tpl2 plays an essential role in cell signaling in the immune response to certain pathogens.
Distinct Antiviral Roles for Human 2′,5′-Oligoadenylate Synthetase Family Members against Dengue Virus Infection
Authors: Lin Ren-Jye , Yu Han-Pang , Chang Bi-Lan , Tang Wei-Chun , Liao Ching-Len , Lin Yi-Ling
Published: November 2009

The 2′,5′-oligoadenylate synthetase (OAS) and its downstream effector RNase L play important roles in host defense against virus infection. Oas1b, one of the eight Oas1 genes in the mouse genome, has been identified as a murine flavivirus-resistance gene. Four genes, OAS1, OAS2, OAS3, and OAS-like (OASL), have been identified in the human OAS gene family, and 10 isoforms, including OAS1 (p42, p44, p46, p48, and p52), OAS2 (p69 and p71), OAS3 (p100), and OASL (p30 and p59) can be generated by alternative splicing. In this study, we determined the role of the human OAS/RNase L pathway in host defense against dengue virus (DEN) infection and assessed the antiviral potential of each isoform in the human OAS family. DEN replication was reduced by overexpression and enhanced by knockdown of RNase L expression, indicating a protective role for RNase L against DEN replication in human cells. The human OAS1 p42, OAS1 p46, and OAS3 p100, but not the other OAS isoforms, blocked DEN replication via an RNase L-dependent mechanism. Furthermore, the anti-DEN activities of these three OAS isoforms correlated with their ability to trigger RNase L activation in DEN-infected cells. Thus, OAS1 p42/p46 and OAS3 p100 are likely to contribute to host defense against DEN infection and play a role in determining the outcomes of DEN disease severity.
Acceleration of Functional Maturation and Differentiation of Neonatal Porcine Islet Cell Monolayers Shortly In Vitro Cocultured with Microencapsulated Sertoli Cells
Authors: Mancuso Francesca , Calvitti Mario , Luca Giovanni , Nastruzzi Claudio , Baroni Tiziano , Mazzitelli Stefania , Becchetti Ennio , Arato Iva , Boselli Carlo , Ngo Nselel Monique D. , Calafiore Riccardo
Published: November 2009

The limited availability of cadaveric human donor pancreata as well as the incomplete success of the Edmonton protocol for human islet allografts fasten search for new sources of insulin the producing cells for substitution cell therapy of insulin-dependent diabetes mellitus (T1DM). Starting from isolated neonatal porcine pancreatic islets (NPIs), we have obtained cell monolayers that were exposed to microencapsulated monolayered Sertoli cells (ESCs) for different time periods (7, 14, 21 days). To assess the development of the cocultured cell monolayers, we have studied either endocrine cell phenotype differentiation markers or c-kit, a hematopoietic stem cell marker, has recently been involved with growth and differentiation ofβ-cell subpopulations in human as well as rodent animal models. ESC which were found to either accelerate maturation and differentiation of the NPIsβ-cell phenotype or identify an islet cell subpopulation that was marked positively for c-kit. The insulin/c-kit positive cells might represent a new, still unknown functionally immatureβ-cell like element in the porcine pancreas. Acceleration of maturation and differentiation of our NPI cell monolayers might generate a potential new opportunity to develop insulin-producing cells that may suite experimental trials for cell therapy of T1DM.