bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4+CD25+ Regulatory T Cells Resist a Novel Form of CD28- and Fas-Dependent p53-Induced T Cell Apoptosis
Authors: Singh Nagendra , Yamamoto Mutsumi , Takami Mariko , Seki Yoichi , Takezaki Mayuko , Mellor Andrew L. , Iwashima Makio
Published: December 2009

Ag receptor stimulation of preactivated T cells causes rapid cell death in an IL-2– and Fas-dependent manner. This phenomenon, known as activation-induced cell death (AICD), plays a pivotal role in the removal of Ag-reactive T cells after initial expansion. In this study, we report a novel form of T cell apoptosis that is distinct from classic AICD. When peripheral T cells were activated with anti-CD3 and anti-CD28 Abs precoated onto plastic plates, CD4+CD25− and CD8 T cells initially expanded but underwent massive apoptosis after 4 d. Unlike classic AICD, this type of T cell apoptosis pathway requires engagement of CD28 and expression of p53, a tumor-suppressor gene. The most striking feature of this form of apoptosis was regulatory T cell resistance. Under the same stimulating conditions, CD4+CD25+ T cells grew continuously beyond 4 d. Consequently, when the entire CD4 population was cultured with plate-bound anti-CD3 plus anti-CD28 Ab, CD4+CD25+FoxP3+ regulatory T cells outgrew nonregulatory T cells and expanded >7000-fold after 11 d. The data presented herein demonstrate a novel process of Ag-induced T cell death by sustained TCR and CD28 engagement and represent a simple and efficient procedure for the expansion of regulatory T cells in vitro.
γδ T Lymphocytes Count Is Normal and Expandable in Peripheral Blood of Patients with Follicular Lymphoma, Whereas It Is Decreased in Tumor Lymph Nodes Compared with Inflammatory Lymph Nodes
Authors: Braza Mounia Sabrina , Caraux Anouk , Rousset Thérèse , Lafaye de Micheaux Sylvie , Sicard Hélène , Squiban Patrick , Costes Valérie , Klein Bernard , Rossi Jean-François
Published: December 2009

γδ T lymphocytes are attractive effector cells for immunotherapy. In vitro, they can be expanded and kill efficiently a variety of tumor cells. The frequency and distribution of γδ T lymphocytes were compared in tumor lymph nodes of 51 patients with follicular lymphoma lymph nodes (FL-LNs) and 28 patients with inflammatory lymph nodes (I-LNs). γδ and CD8 T lymphocytes were less abundant in FL-LNs than in I-LNs (p ≤ 10−7). These lymphocytes were localized in the perifollicular zone outside of the tumor follicles. Perifollicular γδ T lymphocytes expressed CCR7, in contrast to peripheral blood γδ T lymphocytes and both perifollicular and peripheral blood γδ T lymphocytes expressed CXCR4. The very low number of perifollicular γδ T lymphocytes in FL-LNs could be explained in part by migratory problems because of absence of CCL19 expression in FL-LNs compared with I-LNs. Conversely, CCL21 and CXCL12 were similarly expressed in both FL-LNs and I-LNs. CCL19 and CCL21 were expressed in high endothelial venules and lymphatic vessels, whereas CXCL12 was expressed by stromal cells surrounding high endothelial venules and lymphatic vessels. Peripheral γδ T lymphocytes from 34 patients with FL, expanded with Phosphostim and IL-2 in vitro, had the same expansion capacity as those from healthy individuals. Thus, γδ T lymphocytes can be an attractive source for adoptive immunotherapy in patients with FL, providing they may home in tumor LNs.
The Herpes Simplex Virus-1 Encoded Glycoprotein B Diverts HLA-DR into the Exosome Pathway
Authors: Temme Sebastian , Eis-Hübinger Anna M. , McLellan Alexander D. , Koch Norbert
Published: December 2009

Neutralizing Abs play an important role for immunity against HSV-1 infection. This branch of the immune response is initiated by MHC class II Ag presentation and activation of T cell help. In this study, we show that the HSV-1 encoded glycoprotein B (gB) manipulates the class II processing pathway by perturbing endosomal sorting and trafficking of HLA-DR (DR) molecules. Expression of gB in the human melanoma cell line Mel JuSo results in formation of enlarged DR+ intracellular vesicles. Costaining of the vesicles revealed the presence of DR, gB, and the late endosomal marker CD63. The lumen of these late endosomal membranes shows a variable content, containing either gB or CD63, or both CD63 and gB. gB targets DR molecules on their biosynthetic route, after the MHC class II invariant chain is released from the DR heterodimer. gB-DR complexes were detected in a post-Golgi compartment and in exosomes, but not on the cell surface. Interestingly, increasing expression of gB strongly elevated the amount of DR and CD63 released into the exosome pathway. In conclusion, this is a previously undescribed mode of viral immune evasion involving hijacking of DR from its normal transport route to the cell surface, followed by viral-mediated release of DR into the exosome pathway.
Trafficking, Persistence, and Activation State of Adoptively Transferred Allogeneic and Autologous Simian Immunodeficiency Virus-Specific CD8+ T Cell Clones during Acute and Chronic Infection of Rhesus Macaques
Authors: Bolton Diane L. , Minang Jacob T. , Trivett Matthew T. , Song Kaimei , Tuscher Jennifer J. , Li Yuan , Piatak Michael , O’Connor David , Lifson Jeffrey D. , Roederer Mario , Ohlen Claes
Published: December 2009

Despite multiple lines of evidence suggesting their involvement, the precise role of CD8+ T cells in controlling HIV replication remains unclear. To determine whether CD8+ T cells can limit retroviral replication in the absence of other immune responses, we transferred 1–13 × 109 allogeneic in vitro expanded SIV-specific CD8+ T cell clones matched for the relevant restricting MHC-I allele into rhesus macaques near the time of i.v. SIV challenge. Additionally, in vitro expanded autologous SIV-specific CD8+ T cell clones were infused 4–9 mo postinfection. Infused cells did not appreciably impact acute or chronic viral replication. The partially MHC-matched allogeneic cells were not detected in the blood or most tissues after 3 d but persisted longer in the lungs as assessed by bronchoalveolar lavage (BAL). Autologous cells transferred i.v. or i.p. were found in BAL and blood samples for up to 8 wk postinfusion. Interestingly, despite having a nominally activated phenotype (CD69+HLA-DR+), many of these cells persisted in the BAL without dividing. This suggests that expression of such markers by T cells at mucosal sites may not reflect recent activation, but may instead identify stable resident memory T cells. The lack of impact following transfer of such a large number of functional Ag-specific CD8+ T cells on SIV replication may reflect the magnitude of the immune response required to contain the virus.
Stored Fas Ligand, a Mediator of Rapid CTL-Mediated Killing, Has a Lower Threshold for Response Than Degranulation or Newly Synthesized Fas Ligand
Authors: He Jin-Shu , Gong Dong-Er , Ostergaard Hanne L.
Published: December 2009

CTL lyse target cells through the release of cytolytic granule mediators and expression of the death receptor ligand Fas ligand (FasL). We previously demonstrated that FasL is stored in vesicles distinct from cytolytic granules and is translocated to the cell surface within 15 min of TCR stimulation, followed by a later wave of newly synthesized FasL cell surface expression at 2 h poststimulation. Initial studies suggested that the two FasL responses had different signaling thresholds. To test this possibility directly, we titrated Ag presented to murine CTL to measure FasL and degranulation response thresholds. Stored FasL translocation to the cell surface required substantially lower concentrations of peptide than was required for de novo expression of FasL and degranulation. Furthermore, a low-affinity agonist peptide stimulated strong stored FasL translocation but only limited de novo FasL expression and degranulation. These data imply that the two FasL populations may have distinct functions. We examined bystander killing and found that the rapidly expressed FasL triggered highly specific lysis of target cells, as did degranulation. In contrast, the newly synthesized later wave of FasL mediated extensive Fas-dependent bystander killing. Our data indicate that stored FasL is mobilized in response to low concentrations of Ag to mediate rapid, highly specific lysis of target cells, whereas the later, newly synthesized FasL requires higher concentrations of Ag and mediates indiscriminate lysis. These findings suggest that early and late FasL and degranulation represent nonredundant lytic mechanisms that have been selected for distinct situations, possibly for optimal pathogen clearance.
Diesel Exhaust Particles Stimulate Adaptive Immunity by Acting on Pulmonary Dendritic Cells
Authors: Provoost Sharen , Maes Tania , Willart Monique A. M. , Joos Guy F. , Lambrecht Bart N. , Tournoy Kurt G.
Published: December 2009

Particulate matter, such as diesel exhaust particles (DEPs), modulate adaptive immune responses in the lung; however, their mechanism of action remains largely unclear. Pulmonary dendritic cells (DCs) are crucial mediators in regulating immune responses. We hypothesized that the immunomodulatory effects of DEPs are caused by alteration of DC function. To test this, we instilled mice with DEPs and examined the pulmonary DC recruitment and maturation, their migration to the mediastinal lymph node (MLN), and the subsequent T cell response. We demonstrated that exposure to DEPs increased DC numbers in the bronchoalveolar lavage and the lungs and that DEPs increased the maturation status of these DCs. DEP exposure also enhanced the DC migration to the MLN. Moreover, we showed that DEPs themselves were transported to the MLN in a CCR7- and DC-dependent manner. This resulted in an enhanced T cell recruitment and effector differentiation in the MLN. These data suggest that DEP inhalation modulates immune responses in the lung via stimulation of DC function.
Murine IgG1 and IgG3 Isotype Switch Variants Promote Phagocytosis of Cryptococcus neoformans through Different Receptors
Authors: Saylor Carolyn A. , Dadachova Ekaterina , Casadevall Arturo
Published: December 2009

Almost 3 decades ago, murine IgG3 was proposed to interact with a different receptor than the other IgG subclasses, but the issue remains unresolved. The question of whether a specific receptor exists for IgG3 is critically important for understanding Ab-mediated immunity against Cryptococcus neoformans, where the different isotypes manifest profound differences in protective efficacy. In this study, we revisited this question by analyzing IgG1- and IgG3-mediated phagocytosis with variable region-identical mAbs using mouse macrophages deficient in various receptors and in conditions of FcγR and complement receptor blockage with specific Abs. IgG3 was an efficient opsonin for C. neoformans in FcγR- and CD18-deficient cells and in the presence of blocking Abs to FcγR and complement receptor. Like IgG1, IgG3-mediated phagocytosis was associated with fungal residence in a mature phagosome that was followed by intracellular replication and exocytosis events. We conclude that a specific receptor for IgG3 exists in mice that is structurally different from the known FcγRs.
The relationship between Early Holocene climate change and Neolithic settlement in central Anatolia, Turkey: current issues and prospects for future research
Authors: Asouti Eleni
Published: December 2009

Episodes of global climate change have traditionally been invoked as explanations for settlement re-organisation and socio-economic transformation in the prehistory of the Middle East (e.g., the Neolithic period). By focusing on the 8.2K event, this paper presents a theoretical and methodological argument against the assumption of unilinear, passive responses by prehistoric societies to global climate change, using as a case study datasets recently obtained from the Konya Plain in Central Anatolia, Turkey.
Risks associated with tendinitis: effects from demographic, socioeconomic, and psychological status among Brazilian workers
Authors: Frazão Paulo , Costa Carla Maria , de Almeida Márcia Furquim
Published: November 2009

Background

Self‐reported tendinitis/tenosynovitis was evaluated by gender, age group, skin color, family income, and educational and psychological status.

Methods

!The study was carried out in a representative sample of formally contracted Brazilian workers from a household survey. A total of 54,660 participants were included. Occupations were stratified according to estimated prevalences of self‐reported injuries. Non‐conditional logistic regression was performed, and all variables were analyzed in two occupational groups.

Results

The overall prevalence rate of tendinitis/tenosynovitis was 3.1%: 5.5% in high‐prevalence occupations (n = 10,726); and 2.5% in low‐prevalence occupations (n = 43,934). White female workers between the ages of 45 and 64 years and at a higher socioeconomic level were more likely to report tendinitis/tenosynovitis regardless of their occupational category. An adjusted OR = 3.59 [95% CI: 3.15‐‐4.09] was found between tendinitis/tenosynovitis and psychological status.

Conclusion

Among formally contracted Brazilian workers, higher income can imply greater physical and psychological demands that, regardless of occupational stratum, increase the risk of tendinitis/tenosynovitis. Am. J. Ind. Med. 53:72–79, 2010. © 2009 Wiley‐Liss, Inc.
Back problems among emergency medical services professionals: The LEADS health and wellness follow‐up study
Authors: Studnek Jonathan R. , Crawford J. Mac , Wilkins J.R. , Pennell Michael L.
Published: November 2009

Objective

Describe work‐life and demographic characteristics associated with reporting recent back pain, and estimate back pain severity among Emergency Medical Services (EMS) professionals.

Methods

A 58‐item postal questionnaire was used to collect relevant health and wellness information from a national sample of EMS professionals. The outcome variables were self‐reported pain in the back or legs, and severity of recent back pain as indicated by the Aberdeen Back Pain Scale (ABPS).

Results

There were 470/930 (50.5%) participants who reported one or more days of pain in the back or legs over a 2‐week period. The variables most strongly associated with recent back pain and pain severity were prior back problems, self‐reported health, and job satisfaction.

Conclusion

This study indicated that work‐life, health, and demographic characteristics of EMS professionals were associated with reporting recent back pain. Am. J. Ind. Med. 53:12–22, 2010. © 2009 Wiley‐Liss, Inc.
South Africa's export trade in asbestos: Demise of an industry
Authors: Harington John S. , McGlashan Neil D. , Chelkowska Elzbieta Z.
Published: November 2009

Background

South Africa's export of each of its three types of asbestos, crocidolite, amosite, and chrysotile, and the total amounts to 84 countries in metric tonnes is examined over a 24‐year period, 1980–2003.

Methods

For convenience, the countries are divided into nine world regional groups, Europe, Eastern Europe, North America with the Caribbean, South America, Africa, Middle East, Far East, South Asia, and Oceania.

Results

The three greatest importing countries of total asbestos in metric tonnes were all in the Far East region, ranging from Japan, South Korea to Thailand, and followed by USA and Italy. All exports to all countries diminished steadily as the South African trade came virtually to an end by 2003, due to ever increasing international pressure.

Conclusion

The export trade has changed significantly since 1960 from being dominantly to European countries to being directed in recent years to the Far East, with serious implications for asbestos‐related ill‐health in those countries. Am. J. Ind. Med. 53:524–534, 2010. © 2010 Wiley‐Liss, Inc.
Enantioselective addition of diethylzinc to aldehydes catalyzed by β‐amino alcohols derived from (1R,2S)‐norephedrine
Authors: Tasgin Dilek Isik , Unaleroglu Canan
Published: November 2009

β‐Amino alcohols derived from (1R,2S)‐norephedrine were synthesized and used as ligands in the catalytic enantioselective diethylzinc addition to benzaldehydes. N‐alkylated (1R,2S)‐norephedrine‐based derivative 3a gave the highest enantioselectivity. The effects of different parameters on the enantioselectivity of the product were investigated. Copyright © 2009 John Wiley & Sons, Ltd.
Molecular‐selective adsorption property of chemically surface modified nanoporous alumina membrane by di(1‐naphthyl)silanediol to anthracenes
Authors: Kakiage Kenji , Kyomen Toru , Unno Masafumi , Hanaya Minoru
Published: November 2009

Nano‐porous alumina membrane (NPAM) formed by the anodic oxidation of aluminum is an attractive composite as the base material for a functional filter, because of its honeycombed ordered structure with large surface area per weight and also high shape stability. In this work, we investigated the adsorption properties of the NPAM possessing π‐electron systems on the surface, which were produced through chemical surface modification by di(1‐naphthyl)silanediol, to aromatic compounds using anthracenes as typical aromatic compounds. The chemically surface‐modified NPAM exhibited strong affinity to anthracene molecules and the affinity was observed to be weakened remarkably with the introduction of methyl and phenyl substituents to anthracene, indicating a molecular‐selective adsorption property of the NPAM. Copyright © 2009 John Wiley & Sons, Ltd.
Design, synthesis, characterization and antibacterial properties of copper(II) complexes with chromone‐derived compounds
Authors: Chohan Zahid H. , Iqbal Mohammad S. , Aftab Syed K.
Published: November 2009

A new series of six chromone‐derived compounds and their Cu(II) complexes was synthesized and characterized by their physical, spectral and analytical data The elemental analysis data of the complexes agree well with the proposed composition of the compounds, which were found to be dimeric in nature with two hydrazine molecules bridging the two copper atoms through coordination. The ligands and their Cu(II) complexes were screened for their in‐vitro antibacterial activity against four Gram‐negative (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri) and two Gram‐positive (Bacillus subtilis, Staphylococcus aureus) bacterial strains by the agar‐well diffusion method. The ligands were found to exhibit either no or low to moderate activities against one or more of the bacterial species, whereas all the metal complexes exhibited moderate to high activities against different bacterial species. The ligands which were inactive before complexation turned active and less active ones became more active upon coordination with copper ions. Overall, the complexes 7–12 showed comparatively much higher activities than the ligands. Copyright © 2009 John Wiley & Sons, Ltd.
In Vivo Morphological Changes in Animal Models of Amyotrophic Lateral Sclerosis and Alzheimer's‐Like Disease: MRI Approach
Authors: Andjus Pavle R. , Schäfer Karl‐Herbert , Mitrečić Dinko
Published: November 2009

Adapted composite picture of images taken from different contributions to this Neurodegeneration and Neuroplasticity special issue (see Andjus et al., on page 1871; Schäfer et al., on page 1929; and Mitrečić et al., on page 1951).
Signaling by Neuronal Tyrosine Kinase Receptors: Relevance for Development and Regeneration
Authors: Hausott Barbara , Kurnaz Isil , Gajovic Srecko , Klimaschewski Lars
Published: November 2009

Receptor tyrosine kinase activation by binding of neurotrophic factors determines neuronal morphology and identity, migration of neurons to appropriate destinations, and integration into functional neural circuits as well as synapse formation with appropriate targets at the right time and at the right place. This review summarizes the most important aspects of intraneuronal signaling mechanisms and induced gene expression changes that underlie morphological and neurochemical consequences of receptor tyrosine kinase activation in central and peripheral neurons. Anat Rec, 292:1976–1985, 2009. © 2009 Wiley‐Liss, Inc.
A Preliminary Study of Solid Embryonic Cerebellar Graft Survival in Adult B6CBA Lurcher Mutant and Wild Type Mice
Authors: Cendelín Jan , Korelusová Ivana , Vožeh František
Published: November 2009

Lurcher mutant mice represent a model of olivocerebellar degeneration. They suffer from complete loss of Purkinje cells and a reduction of granule cells and inferior olive neurons. Their wild type littermates serve as healthy controls. The aim of the work was to compare solid embryonic cerebellar graft survival within a period of 9 weeks after their transplantation in adult Lurcher mutant and wild type mice of the B6CBA strain. The solid grafts were injected through a hole in the occipital bone. Host mice were sacrificed 3, 6, or 9 weeks after the transplantation and their cerebella and brain‐stems were examined histologically to assess graft presence and structure. We did not find significant differences in graft survival rates between Lurcher mutant and wild type mice. The frequency of graft presence did not differ between mice examined 3, 6, and 9 weeks after the transplantation, neither in Lurchers nor in wild type mice. The grafts were of various sizes. In some cases, only small residua of the grafts were found. Nerve fiber sprouting and cell migration from the graft to the host tissue were observed more often in wild type mice than in Lurchers when examined 6 weeks after surgery. In the period 3–9 weeks after transplantation, massive dying out of the grafts was not observed despite regressive processes in some of the grafts. The degenerative changes in the Lurcher mutant cerebellum do not have strong impact on the fate of the solid cerebellar graft. Anat Rec, 292:1986–1992, 2009. © 2009 Wiley‐Liss, Inc.
From Genes to Proteins in Mendelian Parkinson's Disease: An Overview
Authors: Pirkevi Caroline , Lesage Suzanne , Brice Alexis , Nazli Başak A.
Published: November 2009

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. A progressive movement disorder typified by the production of bradykinesia, tremor, rigidity, and impairment of postural reflexes, PD is characterized by a depletion of dopamine in the striatum. For the last decade, several Mendelian forms of PD have been identified. Mutations in these genes potentially lead to autosomal dominant (α‐synuclein and LRRK2), or autosomal recessive PD (Parkin, PINK1, DJ1, and ATP13A2). This article will spotlight these six distinct genes unambiguously associated with Mendelian PD and the function of their encoded proteins. Anat Rec, 292:1893–1901, 2009. © 2009 Wiley‐Liss, Inc.
Structural Features of Ischemic Damage in the Hippocampus
Authors: Nikonenko Alexander G. , Radenovic Lidija , Andjus Pavle R. , Skibo Galyna G.
Published: November 2009

Cerebral ischemic injury resulting from either focal or global circulatory arrests in the brain is one of the major causes of death and disability in the adult population. The hippocampus, playing important roles in learning and memory, is selectively vulnerable to ischemic insults. Distinct populations of hippocampal neurons are targeted by ischemia and multiple factors, including excitotoxicity, oxidative stress, and inflammation, are responsible for their damage and death. Modifications of synapses occur very early after ischemia, reflecting related changes in synaptic transmission. These modifications structurally relate to spatial patterns formed by synaptic vesicles, geometry of postsynaptic density, and so forth. Ischemia‐induced changes of synaptic contacts can be implicated in the mechanisms leading to delayed neuronal death. In this review, we summarize the available data on the structural aspects of ischemic injury of the hippocampus obtained in tissue culture and animal models and discuss pathways of neurodegeneration common for cerebral ischemia and various neurodegenerative disorders. Anat Rec, 292:1914–1921, 2009. © 2009 Wiley‐Liss, Inc.
Guanosine‐Induced Synaptogenesis in the Adult Brain In Vivo
Authors: Gerrikagoitia Inmaculada , Martínez‐Millán Luis
Published: November 2009

Astrocytes release factors like cholesterol, apoE, and pleiotropic molecules that influence synaptogenesis in the central nervous system. In vitro studies have shown that guanosine elicits the production and further release of these synaptogenic factors. To demonstrate that such astrocytic factors are synaptogenic in vivo, osmotic pumps were implanted in primary visual cortex (VC) of Sprague‐Dawley rats to deliver guanosine. Simultaneous injection of dextran amine as an anterograde tracer at the same site where the osmotic pumps were implanted enabled the morphology of the fibers emerging from the VC to be visualized as well. The guanosine‐treated efferent connections from these animals showed a significant increase in the number and size of synaptic boutons along the efferent fibers when compared with controls. A similar increase in the number and size of synaptic boutons was also detected when the cortico–cortical connection to the lateral secondary visual area was studied in more detail. The ensuing morphological changes to the synapses did not show a clear preference for any particular type or site of the axonal branches that integrates this cortical connection. Moreover, the distribution of boutons along the fibers was clearly stochastic according to their size. Thus, guanosine administration appears to open up the possibility of manipulating connections to compensate for total or partial denervation. Anat Rec, 292:1968–1975, 2009. © 2009 Wiley‐Liss, Inc.
Alzheimer's Mechanisms in Ischemic Brain Degeneration
Authors: Pluta Ryszard , Ułamek Marzena , Jabłoński Mirosław
Published: November 2009

There is increasing evidence for influence of Alzheimer's proteins and neuropathology on ischemic brain injury. This review investigates the relationships between β‐amyloid peptide, apolipoproteins, presenilins, tau protein, α‐synuclein, inflammation factors, and neuronal survival/death decisions in brain following ischemic episode. The interactions of these molecules and influence on β‐amyloid peptide synthesis and contribution to ischemic brain degeneration and finally to dementia are reviewed. Generation and deposition of β‐amyloid peptide and tau protein pathology are important key players involved in mechanisms in ischemic neurodegeneration as well as in Alzheimer's disease. Current evidence suggests that inflammatory process represents next component, which significantly contribute to degeneration progression. Although inflammation was initially thought to arise secondary to ischemic neurodegeneration, recent studies present that inflammatory mediators may stimulate amyloid precursor protein metabolism by upregulation of β‐secretase and therefore are able to establish a vicious cycle. Functional brain recovery after ischemic lesion was delayed and incomplete by an injury‐related increase in the amount of the neurotoxic C‐terminal of amyloid precursor protein and β‐amyloid peptide. Moreover, ischemic neurodegeneration is strongly accelerated with aging, too. New therapeutic alternatives targeting these proteins and repairing related neuronal changes are under development for the treatment of ischemic brain consequences including memory loss prevention. Anat Rec, 292:1863–1881, 2009. © 2009 Wiley‐Liss, Inc.
MAPK Signal Transduction Underlying Brain Inflammation and Gliosis as Therapeutic Target
Authors: Kaminska Bozena , Gozdz Agata , Zawadzka Malgorzata , Ellert‐Miklaszewska Aleksandra , Lipko Maciej
Published: November 2009

A majority, if not all, acute and progressive neurodegenerative diseases are accompanied by local microglia‐mediated inflammation, astrogliosis, infiltration of immune cells, and activation of the adaptive immunity. These processes progress by the expression of cytokines, adhesion molecules, proteases, and other inflammation mediators. In response to brain injury or infection, intracellular signaling pathways are activated in microglia, which turn on inflammatory and antigen‐presenting cell functions. Different extrinsic signals shape microglial activation toward neuroprotective or neurotoxic phenotype under pathological conditions. This review discusses recent advances regarding molecular mechanisms of inflammatory signal transduction in neurological disorders and inin vitromodels of inflammation/gliosis. Mitogen‐activated protein kinases (MAPKs) are a family of serine/threonine protein kinases responsible for most cellular responses to cytokines and external stress signals and crucial for regulation of the production of inflammation mediators. Increased activity of MAPKs in activated microglia and astrocytes, and their regulatory role in the synthesis of inflammatory cytokines mediators, make them potential targets for novel therapeutics. MAPK inhibitors emerge as attractive anti‐inflammatory drugs, because they are capable of reducing both the synthesis of inflammation mediators at multiple levels and are effective in blocking inflammatory cytokine signaling. Small molecule inhibitors targeting of p38 MAPK and JNK pathways have been developed and offer a great potential as potent modulators of brain inflammation and gliosis in neurological disorders, where cytokine overproduction contributes to disease progression. Many of the pharmacological MAPK inhibitors can be administered orally and initial results show therapeutic benefits in preclinical animal models. Anat Rec, 292:1902–1913, 2009. © 2009 Wiley‐Liss, Inc.
The novel ruthenium—γ‐linolenic complex [Ru2(aGLA)4Cl] inhibits C6 rat glioma cell proliferation and induces changes in mitochondrial membrane potential, increased reactive oxygen species generation and apoptosisin vitro
Authors: Ribeiro Geise , Benadiba Marcel , de Oliveira Silva Denise , Colquhoun Alison
Published: November 2009

The present study reports the synthesis of a novel compound with the formula [Ru2(aGLA)4Cl] according to elemental analyses data, referred to as Ru2GLA. The electronic spectra of Ru2GLA is typical of a mixed valent diruthenium(II,III) carboxylate. Ru2GLA was synthesized with the aim of combining and possibly improving the anti‐tumour properties of the two active components ruthenium andγ‐linolenic acid (GLA). The properties of Ru2GLA were tested in C6 rat glioma cells by analysing cell number, viability, lipid droplet formation, apoptosis, cell cycle distribution, mitochondrial membrane potential and reactive oxygen species. Ru2GLA inhibited cell proliferation in a time and concentration dependent manner. Nile Red staining suggested that Ru2GLA enters the cells and ICP‐AES elemental analysis found an increase in ruthenium from <0.02 to 425 mg/Kg in treated cells. The sub‐G1 apoptotic cell population was increased by Ru2GLA (22 ± 5.2%) when analysed by FACS and this was confirmed by Hoechst staining of nuclei. Mitochondrial membrane potential was decreased in the presence of Ru2GLA (44 ± 2.3%). In contrast, the cells which maintained a high mitochondrial membrane potential had an increase (18 ± 1.5%) in reactive oxygen species generation. Both decreased mitochondrial membrane potential and increased reactive oxygen species generation may be involved in triggering apoptosis in Ru2GLA exposed cells. The EC50for Ru2GLA decreased with increasing time of exposure from 285 µM at 24 h, 211 µM at 48 h to 81 µM at 72 h. In conclusion, Ru2GLA is a novel drug with antiproliferative properties in C6 glioma cells and is a potential candidate for novel therapies in gliomas. Copyright © 2009 John Wiley & Sons, Ltd.
Catalytic Ammonia Synthesis over Mo Nitride/ZSM‐5
Authors: Liu Na , Nie Lei , Xue Nianhua , Dong Houhuan , Peng Luming , Guo Xuefeng , Ding Weiping
Published: November 2009

Molybdenum nitride species in HZSM‐5 are prepared by the reaction of ammonia with MoOx, which is pre‐exchanged into the channel of HZSM‐5. Both the processes of solid exchange of molybdenum oxide with the zeolite and the ammonia reaction are monitored by mass spectrometry. The Mo/N ratio of the MoNx species in the Mo nitride/HZSM‐5 is close to 2, as measured by temperature‐programmed oxidation. The MoNx species are more stable than bulk Mo2N against oxidation, due to the interaction between the molybdenum nitride species and the charged zeolite framework. The MoNx species, of which the dispersion is found to be greater than 90 %, are very active in ammonia synthesis and the catalytic activity is much more stable than that of bulk Mo2N. The reaction pressure is much more favorable to ammonia formation on the MoNx/ZSM‐5 catalyst than on bulk Mo2N. The interaction of nitrogen molecules with the inner electric field of the zeolite, at an equivalent pressure, enhances the reaction of ammonia synthesis.
Volcano Relation for the Deacon Process over Transition‐Metal Oxides
Authors: Studt Felix , Abild‐Pedersen Frank , Hansen Heine A. , Man Isabela C. , Rossmeisl Jan , Bligaard Thomas
Published: November 2009

We establish an activity relation for the heterogeneous catalytic oxidation of HCl (the Deacon Process) over rutile transition‐metal oxide catalysts by combining density functional theory calculations (DFT) with microkinetic modeling. Linear energy relations for the elementary reaction steps are obtained from the DFT calculations and used to establish a one‐dimensional descriptor for the catalytic activity. The descriptor employed here is the dissociative chemisorption energy of oxygen. It is found that the commonly employed RuO2 catalyst is close to optimal, but that there could still be room for improvements. The analysis suggests that oxide surfaces which offer slightly weaker bonding of oxygen should exhibit a superior activity to that of RuO2.
Ion‐Exchange Temperature Effect on Cu/HMS Catalysts for the Hydrogenation of Dimethyl Oxalate to Ethylene Glycol
Authors: Yin Anyuan , Guo Xiuying , Fan Kangnian , Dai Wei‐Lin
Published: November 2009

A series of Cu/HMS (HMS=hexagonal mesoporous silica) catalysts, synthesized by ion exchange at temperatures from 303 to 363 K, are extensively investigated as catalysts for the hydrogenation of dimethyl oxalate to ethylene glycol. The physicochemical properties and catalytic activity are compared with those of a catalyst prepared by the conventional impregnation method. Characterization of the Cu/HMS catalysts shows that the surface and textural structure of the HMS support as well as the dispersion and nature of copper species depend strongly on the ion‐exchange temperature. Temperature‐programmed reduction patterns reveal the presence of three types of copper species. N2O titration experiments show that the catalyst prepared by ion‐exchange treatment at 333 K has the highest metallic copper surface area. A 98 % ethylene glycol yield is attained over the catalyst ion‐exchanged at 333 K, illustrating that an optimum ion‐exchange temperature is beneficial for the generation of copper catalysts with enhanced activity.
The Protonation of HSO3F: Preparation and Characterization of Fluorodihydroxyoxosulfonium Hexafluoroantimonate [H2SO3F]+[SbF6]−
Authors: Seelbinder Raphael , Goetz Nadine R. , Weber Johannes , Minkwitz Rolf , Kornath Andreas J.
Published: November 2009

Sulfurtrioxide reacts with the superacidic solutions XF/SbF5 (X=H, D) to form the corresponding salts [X2SO3F]+[SbF6]−, which are the protonated forms of fluorosulfuric acid. The salts have been characterized by vibrational spectroscopy and a single‐crystal structure analysis. [H2SO3F]+[SbF6]− crystallizes in the monoclinic space group P21/n (no. 14) with four formula units in the unit cell. The crystal structure possesses a distorted tetrahedral O3SF skeleton of the cations, which are linked with two strong hydrogen bridges to [SbF6]− anions and forms a one‐dimensional chain. The crystal structure and the vibrational spectra are compared to the quantum‐chemical‐calculated free [H2SO3F]+ cation. Additionally, an [H2SO3F(HF)2]+ unit was calculated at the RHF/6‐311++G(d,p) level to simulate H⋅⋅⋅F hydrogen bridges found in the solid state.
Synthesis of (Z)‐Trisubstituted Olefins by Decarboxylative Grob‐Type Fragmentations: Epothilone D, Discodermolide, and Peloruside A
Authors: Prantz Kathrin , Mulzer Johann
Published: November 2009

Methyl‐branched (Z)‐trisubstituted olefins are found in many polyketides with interesting biological activity, such as epothilone D (1), discodermolide (3), and peloruside A (2). Despite the employment of numerous different strategies, this motif has often been the weak point in total synthesis. Thus, we present a novel hydroxide‐ induced Grob‐type fragmentation as an easy access to trisubstituted olefins. In our case, β‐mesyloxy δ‐lactones with three stereogenic centers were chosen whose fragmentation underlies a high stereoelectronic control. Major challenges in the syntheses were the installation of quaternary stereocenters, achieved by enzymatic desymmetrization of meso‐diesters and by aluminium‐promoted stereoselective rearrangement of chiral epoxides, respectively. Different aldol strategies were developed for the formation of the fragmentation precursors. Additionally a short survey about nucleophilic additions to aldehydes with quaternary α‐centers is presented.
A Selective, Nontoxic, OFF–ON Fluorescent Molecular Sensor Based on 8‐Hydroxyquinoline for Probing Cd2+ in Living Cells
Authors: Mameli Marta , Aragoni M. Carla , Arca Massimiliano , Caltagirone Claudia , Demartin Francesco , Farruggia Giovanna , De Filippo Greta , Devillanova Francesco A. , Garau Alessandra , Isaia Francesco , Lippolis Vito , Murgia Sergio , Prodi Luca , Pintus Anna , Zaccheroni Nelsi
Published: November 2009

In spite of the fact that cadmium(II) has been recognized as a highly toxic element and that excessive exposure to this metal ion has been reported to have many adverse effects on human health, very few selective and specific fluorescent probes are available for imaging Cd2+ in living cells. Herein, we report the spectroscopic and photochemical characterization of 5‐(5‐chloro‐8‐hydroxyquinolinylmethyl)‐2,8‐dithia‐5‐aza‐2,6‐pyridinophane (L) as a fluorescent sensor for the selective imaging of Cd2+ in living cells. In particular, the response of L to Cd2+ was first assessed in aqueous solutions, sodium dodecyl sulfate micelles, and liposomes, and subsequently in living cells by fluorescence microscopy techniques. Cytofluorimetric analyses of leukemic HL‐60 cells loaded with L also allowed evaluation of the toxicity of the probe and the selective analysis of its intracellular fluorescence in the presence of Cd2+. Furthermore, the 1:1 complex species [Cd(L)H2O]2+ responsible for the OFF–ON chelation enhancement of fluorescence (CHEF) effect on L was structurally characterized; time‐dependent DFT calculations allowed the prediction of theoretical excitations, which were comparable with the experimental ones.
Synthesis of a Monophosphoryl Derivative of Escherichia coli Lipid A and Its Efficient Coupling to a Tumor‐Associated Carbohydrate Antigen
Authors: Tang Shouchu , Wang Qianli , Guo Zhongwu
Published: November 2009

Monophosphoryl lipid A is a safe and potent immunostimulant and vaccine adjuvant, which is potentially useful for the development of effective carbohydrate‐based conjugate vaccines. This paper presents a convergent and efficient synthesis of a monophosphoryl derivative of E. coli lipid A that has an alkyne functionality at the reducing end, which is suitable for coupling with various molecules. The coupling of this derivative to an N‐modified analogue of tumor‐associated antigen GM3 through click chemistry is also presented.
Neuroprotective Effects of N‐Alkyl‐1,2,4‐oxadiazolidine‐3,5‐diones and Their Corresponding Synthetic Intermediates N‐Alkylhydroxylamines and N‐1‐Alkyl‐3‐carbonyl‐1‐hydroxyureas against in vitro Cerebral Ischemia
Authors: Biraboneye Alain Cesar , Madonna Sebastien , Maher Pamela , Kraus Jean‐Louis
Published: November 2009

Herein we report the synthesis and neuroprotective effects of new N‐alkyl‐1,2,4‐oxadiazolidine‐3,5‐diones and their corresponding synthetic intermediates, N‐alkylhydroxylamines and N‐1‐alkyl‐3‐carbonyl‐1‐hydroxyureas, in an in vitro model of ischemia. We found five analogues that protect HT22 cells from death in the concentration range of 1–5 μM. Because members of the MAP kinase family are known to be key players in nerve cell survival and death, we characterized the role of these kinases in the neuroprotective mechanisms of the newly synthesized analogues. The results indicate that these compounds provide neuroprotection through distinct mechanisms of action.
Functional Materials for Sustainable Energy Technologies: Four Case Studies
Authors: Kuznetsov V. L. , Edwards P. P.
Published: November 2009

The critical topic of energy and the environment has rarely had such a high profile, nor have the associated materials challenges been more exciting. The subject of functional materials for sustainable energy technologies is demanding and recognized as a top priority in providing many of the key underpinning technological solutions for a sustainable energy future. Energy generation, consumption, storage, and supply security will continue to be major drivers for this subject. There exists, in particular, an urgent need for new functional materials for next‐generation energy conversion and storage systems. Many limitations on the performances and costs of these systems are mainly due to the materials′ intrinsic performance. We highlight four areas of activity where functional materials are already a significant element of world‐wide research efforts. These four areas are transparent conducting oxides, solar energy materials for converting solar radiation into electricity and chemical fuels, materials for thermoelectric energy conversion, and hydrogen storage materials. We outline recent advances in the development of these classes of energy materials, major factors limiting their intrinsic functional performance, and potential ways to overcome these limitations.
The influence of erythropoietin on levels of endothelin‐1 and nitric oxide in patients on hemodialysis
Authors: Tomić Monika , Galešić Krešimir , Markota Ivica , Markota Nina Pinjuh , Zelenika Anka
Published: November 2009

OBJECTIVE

Examine the influence of the chronic use of erythropoietin on the value of endothelin‐1 (ET‐1) and nitric oxide (NO), as well as on ET‐1/NO ratio in serum, before and after dialysis.

METHODS

A total of 30 patients on hemodialysis were included in the study. Different doses of erythropoietin were administered at least 3 weeks before study. All patients had stable blood pressure values, without changes in antihypertensive therapy in the last 3 months, and without significant intradialytic hypertension and hypotension. The concentration of ET‐1 and NO was measured before and after dialysis treatment. Blood pressure was measured before dialysis, each hour during dialysis, and after dialysis. The control group had 20, age and sex matched, healthy examinees.

RESULTS

Endothelin‐1 was increased in all patients treated with hemodialysis compared to healthy controls, but their values did not correlate with the weekly dosage of erythropoietin. The level of NO after dialysis was significantly lower in patients receiving hemodialysis compared to healthy controls. The ET‐1/NO ratio is increased in patients treated with dialysis compared to healthy controls, but this does not correlate with the weekly dosage of erythropoietin. The decrease of the value of ET‐1 and NO was noted at the end of dialysis compared to the values measured before dialysis.

DISCUSSION

Our results show that the chronic use of erythropoietin in patients treated with hemodialysis does not affect the levels of serum ET‐1 and NO as well as the ET‐1/NO ratio. A significant decrease of ET‐1 and NO is noted compared to the values before dialysis.
Prevention of gestational diabetes mellitus: a review of studies on weight management
Authors: Morisset Anne‐Sophie , St‐Yves Annie , Veillette Johanne , Weisnagel S. John , Tchernof André , Robitaille Julie
Published: November 2009

Entering pregnancy with overweight, obesity or gaining excessive gestational weight could increase the risk of gestational diabetes mellitus (GDM), which is associated with negative consequences for both the mother and the offspring. The objective of this article was to review scientific evidence regarding the association between obesity and GDM, and how weight management through nutritional prevention strategies could prove successful in reducing the risk for GDM. Studies published between January 1975 and January 2009 on the relationship between GDM, pre‐pregnancy body mass index (BMI), gestational weight gain and nutritional prevention strategies were included in this review. Results from these reports suggest that maternal obesity assessed by pre‐pregnancy BMI is associated with an increased risk of GDM. They also show an association between gestational weight gain and increased risk for GDM. Higher dietary fat and lower carbohydrate intakes during pregnancy appear to be associated with a higher risk for GDM, independent of pre‐pregnancy BMI. Some studies showed that restricting energy and carbohydrates could minimize gestational weight gain. However, a firm conclusion on the most effective nutritional intervention for the control of gestational weight gain and glycaemic responses could not be reached based on available studies. In light of the studies reviewed, we conclude that weight management through nutritional prevention strategies could be successful in reducing the risk of GDM. Further studies are required to identify the most effective diet composition to prevent GDM and excessive gestational weight gain. Copyright © 2009 John Wiley & Sons, Ltd.
Participatory futures methods: towards adaptability and resilience in climate‐vulnerable communities
Authors: Gidley Jennifer M. , Fien John , Smith Jodi‐Anne , Thomsen Dana C. , Smith Timothy F.
Published: November 2009

This paper points to the value of broadening the palette of approaches to climate change futures beyond the dominant methods of empiricist predictive trends and expert scenarios. The first half of the paper contextualizes the climate change discourse within the field of futures studies and explores potential points of dialogue between a number of futures approaches and the most prominent of the climate protection work. The second half of the paper introduces a case study of community based participatory approaches involving community scenario writing and community visioning, which enacts a collaborative engagement between futures researchers and climate‐vulnerable communities. However, any participatory futures method chosen to facilitate climate change adaptation must be context aware in both its design and implementation if it is to facilitate adaptability and resilience in climate‐vulnerable communities. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment.
Social learning for solving complex problems: a promising solution or wishful thinking? A case study of multi‐actor negotiation for the integrated management and sustainable use of the Drentsche Aa area in the Netherlands
Authors: Van Bommel S. , Röling N. , Aarts N. , Turnhout E.
Published: November 2009

Social learning has been championed as a promising approach to address complex resource problems. According to theory, social learning requires several pre‐conditions to be met, including (1) a divergence of interests, (2) mutual interdependence and (3) the ability to communicate. This article investigates what happened when social learning was put into practice in a multi‐actor negotiation platform in the Dutch Drentsche Aa area. Our findings show that, although the platform aimed for open dialogue and at first sight appeared to meet the conditions, social learning was not achieved and the negotiations stagnated because of disagreement, frustration and distrust. Further analysis shows that the process was characterized from the beginning by unequal power relations, which enabled a dominant coalition to impose its problem definition and limit possible solutions. The article concludes by discussing the implications of our findings for the theory and practice of social learning. Copyright © 2009 John Wiley & Sons, Ltd and ERP Environment.