bluuebunny/crossref_metadata_2025 huggingface dataset:
Duchenne Muscular Dystrophy - Family in a Crisis
Authors: Amin M Robed , Borua Chowdhury Chironjib , Alam Kaji Shafiqul , Chowdhury Fazle Rabbi , Sarkar Rabiul Jahan , Khandaker Md Abul Kashem , Faiz MA
Published: February 2009

Progressive muscular weakness with deformity leading to crippled states develop due to musculoskeletal and neurological disorders. Sometimes it is difficult to differentiate between primary muscle disease and neurological disease. But there is some classical presentation of muscle diseases which have its own entity and thus can be clinically differentiated from neurological disorder especially spinal cord and motor neuron diseases. Muscular dystrophy is one of those disorder with distinct clinical features. Muscular dystrophy refers to a group of genetic, hereditary muscle diseases that cause progressive muscle weakness. Most types of MD are multi-system disorders with manifestations in body systems including skeletal system, the heart, gastrointestinal and nervous systems, endocrine glands, skin, eyes and other organs. Duchenne muscular dystrophy (DMD), is inherited in an X-linked recessive pattern, meaning that the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes, and is thus considered sex-linked. Males are therefore affected by X-linked recessive disorders much more often than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Duchenne muscular dystrophy and Backers muscular dystrophy are caused by mutations of the gene for the dystrophin protein and lead to an overabundance of the enzyme creatine kinase. The dystrophin gene is the largest gene in humans. In this case series a family with three brothers suffering from Duchenne muscular dystrophy is described and review with literature was done. Â  doi:10.3329/jom.v10i3.2015 J Medicine 2009; 10 (Supplement 1): 36-39
Taking genre into account when analysing conceptual relation patterns
Authors: Condamines Anne
Published: February 2009

This paper uses a corpus study to investigate the influence of text genre on the frequency and semantic interpretation of certain pattern/concept relations. In linking pattern/concept relations to text genre, this study identifies three types of dependency: weak dependency, where the relation appears in almost any kind of text; complete dependency, where it is strongly linked to a particular text or group of related texts; and dependency in terms of text genre. The particular examples that form the basis of the study are meronymic chez, which is found to have a significant dependency in didactic texts in the natural sciences; comme as a marker of hypernymy and co-hyponymy, which has a weaker, but observable dependency in technical and didactic genres; nominal anaphora involving hypernyms, where no consistent conclusions can be reached; and meronymic avec, where the significant factor is shown to be communicative objective rather than domain (subject matter). I discuss the relevance of such studies to Natural Language Processing, and indicate the potential for further research.
Postprandial Oxidative Stress in Exercise Trained and Sedentary Cigarette Smokers
Authors: Bloomer Richard J. , Fisher-Wellman Kelsey H.
Published: February 2009

Cigarette smokers experience an exaggerated triglyceride (TAG) and oxidative stress response to high fat feeding. Exercise training may serve to attenuate the rise in these variables, by improving TAG clearance and antioxidant defense. We compared blood TAG, antioxidant capacity, and oxidative stress biomarkers in exercise trained (>2 hrs per wk) and untrained smokers matched for age, in response to a high fat test meal. We report here that low volume exercise training can attenuate postprandial lipid peroxidation, but has little impact on blood TAG and other markers of oxidative stress. Higher volumes of exercise may be needed to allow for clinically meaningful adaptations in postprandial lipemia and oxidative stress.
Prodrugs of Thyrotropin-Releasing Hormone and Related Peptides as Central Nervous System Agents
Authors: Prokai-Tatrai Katalin , Prokai Laszlo
Published: February 2009

Prodrug design for brain delivery of small- and medium-sized neuropeptides was reviewed, focusing on thyrotropin-releasing hormone and structurally related peptides as examples. We have summarized our most important advances in methodology, as well as assessed the benefits and limitations of bioreversible chemical manipulation techniques to achieve targeting of the parent molecules into the central nervous system. The value of prodrug-amenable analogues as potential drug-like central nervous systems agents was highlighted.
Local Type I IFN Receptor Signaling Protects against Virus Spread within the Central Nervous System
Authors: Detje Claudia N. , Meyer Thomas , Schmidt Hauke , Kreuz Dorothea , Rose John K. , Bechmann Ingo , Prinz Marco , Kalinke Ulrich
Published: February 2009

Several neurotropic viruses such as vesicular stomatitis virus (VSV) induce peripheral neutralizing Ab responses and still can infect cells within the CNS. To address whether local type I IFN receptor (IFNAR) triggering plays a role in controlling virus replication within the brain, we generated mice with a cell type-specific IFNAR deletion in neuroectodermal cells of the CNS (NesCre+/−IFNARflox/flox). Intranasal VSV infection with 103 PFU was well tolerated by wild-type mice, whereas conventional IFNAR−/− mice died within 2–3 days. In contrast, brain-specific NesCre+/−IFNARflox/flox mice survived until day 5–6 and then became hemiplegic and died. Terminally ill NesCre+/−IFNARflox/flox mice showed 10- to 100-fold higher virus loads in the brain than IFNAR−/− mice, whereas little or no virus was found in other organs. In wild-type animals, virus could be reisolated only from the olfactory bulb until day 6 where also STAT1 activation as a measure of IFNAR triggering was detected. Virus infection was found exclusively in glomerular structures of the olfactory bulb, whereas surrounding cells that showed STAT1 phosphorylation as a measure of IFNAR trigging were free of virus. Our data indicate that upon intranasal VSV instillation, early and localized IFNAR triggering in the glomerular layer of the olfactory bulb is critically required to prevent viral spread over the entire CNS and thus confers survival.
Critical Role of Apoptotic Speck Protein Containing a Caspase Recruitment Domain (ASC) and NLRP3 in Causing Necrosis and ASC Speck Formation Induced by Porphyromonas gingivalis in Human Cells
Authors: Huang Max Tze-Han , Taxman Debra J. , Holley-Guthrie Elizabeth A. , Moore Chris B. , Willingham Stephen B. , Madden Victoria , Parsons Rebecca Keyser , Featherstone Gerald L. , Arnold Roland R. , O'Connor Brian P. , Ting Jenny Pan-Yun
Published: February 2009

Periodontal disease is a chronic inflammatory disorder that leads to the destruction of tooth-supporting tissue and affects 10–20 million people in the U.S. alone. The oral pathogen Porphyromonas gingivalis causes inflammatory host response leading to periodontal and other secondary inflammatory diseases. To identify molecular components that control host response to P. gingivalis in humans, roles for the NLR (NBD-LRR) protein, NLRP3 (cryopyrin, NALP3), and its adaptor apoptotic speck protein containing a C-terminal caspase recruitment domain (ASC) were studied. P. gingivalis strain A7436 induces cell death in THP1 monocytic cells and in human primary peripheral blood macrophages. This process is ASC and NLRP3 dependent and can be replicated by P. gingivalis LPS and Escherichia coli. P. gingivalis-induced cell death is caspase and IL-1 independent and exhibits morphological features consistent with necrosis including loss of membrane integrity and release of cellular content. Intriguingly, P. gingivalis-induced cell death is accompanied by the formation of ASC aggregation specks, a process not previously described during microbial infection. ASC specks are observed in P. gingivalis-infected primary human mononuclear cells and are dependent on NLRP3. This work shows that P. gingivalis causes ASC- and NLRP3-dependent necrosis, accompanied by ASC speck formation.
Cutting Edge: Phenotypic Characterization and Differentiation of Human CD8+ T Cells Producing IL-17
Authors: Kondo Takaaki , Takata Hiroshi , Matsuki Fumichika , Takiguchi Masafumi
Published: February 2009

Although IL-17-producing CD8+ T cells (Tc17 cells) have recently been identified, the detailed information about these cells still remains unclear. In this article we describe a study investigating the phenotype and differentiation of human Tc17 cells. Human Tc17 cells were detected in a minor population of CD8+ T cells and were predominantly found in CD27−/+CD28+CD45RA− memory subsets. They also expressed CCR6 and a high level of CCR5. Though most Tc17 cells produced IFN-γ, a small part of the Tc17 cell population was IFN-γ negative in some individuals. Analysis of the in vitro induction of Tc17 cells showed that these cells were induced from the CD27+CD28+CD45RA+ naive subset and that they expressed the CD27−CD28+CD45RA− and CCR6+ phenotype. These results together indicate that Tc17 cells have a unique phenotype and suggest that they differentiate from the same precursors that differentiate into IFN-γ-producing CD8+ T cells.
Bacterial Endotoxin Induces the Release of High Mobility Group Box 1 via the IFN-β Signaling Pathway
Authors: Kim Ju-Hyun , Kim Seon-Ju , Lee Im-Soon , Lee Myung-Shik , Uematsu Satoshi , Akira Shizuo , Oh Kwon Ik
Published: February 2009

Sepsis is a devastating condition characterized by a systemic inflammatory response. Recently, high mobility group box 1 (HMGB1) was identified as a necessary and sufficient mediator of the lethal systemic inflammation caused by sepsis. However, despite its clinical importance, the mechanism of HMGB1 release has remained to be elusive. In this study, we demonstrate that the IFN-β-mediated JAK/STAT pathway is essential for LPS or Escherichia coli-induced HMGB1 release, which is dependent on Toll/IL-1R domain-containing adapter-inducing IFN-β adaptor. Additionally, we show that NO acts as a downstream molecule of the IFN-β signaling. Furthermore, the JAK inhibitor treatment as well as the STAT-1 or IFN-β receptor deficiency reduced HMGB1 release in a murine model of endotoxemia. Our results suggest that HMGB1 release in sepsis is dependent on the IFN-β signaling axis; thus, therapeutic agents that selectively inhibit IFN-β signaling could be beneficial in the treatment of sepsis.
The Ubiquitin Ligase c-Cbl Down-Regulates FcγRIIa Activation in Human Neutrophils
Authors: Marois Louis , Vaillancourt Myriam , Marois Sébastien , Proulx Sophie , Paré Guillaume , Rollet-Labelle Emmanuelle , Naccache Paul H.
Published: February 2009

Little is known about the mechanisms that arrest FcγRIIa signaling in human neutrophils once engaged by immune complexes or opsonized pathogens. In our previous studies, we observed a loss of immunoreactivity of Abs directed against FcγRIIa following its cross-linking. In this study, we report on the mechanisms involved in this event. A stimulated internalization of FcγRIIa leading to the down-regulation of its surface expression was observed by flow cytometry and confocal microscopy. Immunoprecipitation of the receptor showed that FcγRIIa is ubiquitinated after stimulation. MG132 and clasto-lactacystin β-lactone inhibited the loss of immunoreactivity of FcγRIIa, suggesting that this receptor was down-regulated via the proteasomal pathway. The E3 ubiquitin ligase c-Cbl was found to translocate from the cytosol to the plasma membrane following receptor cross-linking. Furthermore, c-Cbl was recruited to the same subset of high-density, detergent-resistant membrane fractions as stimulated FcγRIIa itself. Silencing the expression of c-Cbl by small interfering RNA decreased FcγRIIa ubiquitination and prevented its degradation without affecting the internalisation process. It also prolonged the stimulation of the tyrosine phosphorylation response to the cross-linking of the receptor. We conclude that c-Cbl mediates the ubiquitination of stimulated FcγRIIa and thereby contributes to the termination of FcγRIIa signaling via its proteasomal degradation, thus leading to the down-regulation of neutrophil signalisation and function (phagocytosis) through this receptor.
CD8+ T Cell Responses to a Viral Escape Mutant Epitope: Active Suppression via Altered SHP-1 Activity
Authors: Schnell Frederick J. , Alberts-Grill Noah , Evavold Brian D.
Published: February 2009

One mechanism viruses use to subvert immune surveillance is through mutation of MHC contact residues of antigenic epitopes that weaken T cell recognition to the point that the immune system is ignorant of the infection. However, in contrast to ignorance, results presented herein demonstrate that intracellular signaling does occur upon stimulation with a lymphocytic choriomeningitis virus-derived escape mutant as demonstrated by the sustained activation of Src homology 2 domain-containing protein tyrosine phosphatase (SHP-1). In addition to the increased SHP-1 activity, we found that the mutated epitope failed to induce oxidation of SHP-1, further enhancing enzymatic activity. Sustained activation of SHP-1 in a reduced form correlated with ERK and early growth response gene 1 activation and failure of T cells to commit to the effector lineage. Thus, instead of immune ignorance, these studies demonstrate the activation of a negative signaling pathway that actively suppresses T cell responses and limits recognition of viral escape mutants.
Coronin 1 Is Essential for IgM-Mediated Ca2+ Mobilization in B Cells but Dispensable for the Generation of Immune Responses In Vivo
Authors: Combaluzier Benoit , Mueller Philipp , Massner Jan , Finke Daniela , Pieters Jean
Published: February 2009

Coronin 1 is a leukocyte specific regulator of Ca2+-dependent signaling and is essential for the survival of peripheral T lymphocytes, but its role in B cells is unknown. In this study, we show that coronin 1 is essential for intracellular Ca2+ mobilization and proliferation upon triggering of the BCR. However, the presence of costimulatory signals rendered coronin 1 dispensable for B cell signaling, consistent with the generation of normal immune responses against a variety of Ags in coronin 1-deficient mice. We conclude that coronin 1, while being essential for T cell function and survival, is dispensable for B cell function in vivo.
Human IgA-Inducing Protein from Dendritic Cells Induces IgA Production by Naive IgD+ B Cells
Authors: Endsley Mark A. , Njongmeta Leo M. , Shell Elisabeth , Ryan Matthew W. , Indrikovs Alexander J. , Ulualp Seckin , Goldblum Randall M. , Mwangi Waithaka , Estes D. Mark
Published: February 2009

Over the last several years, there has been a great deal of progress in characterizing the role of dendritic cells (DCs) in the activation and modulation of B cells. DC-secreted chemokines can induce B cell trafficking to the lymph nodes. DC-produced survival factors such as B cell-activating factor of the TNF family and a proliferation-inducing ligand have been shown to be essential for B cell maturation, but have also been implicated in class-switch recombination and B cell lymphoma survival. Recently added to this list of DC-derived factors effecting B cells is IgA-inducing protein (IGIP). In this study, we characterize production of IGIP by human DCs, and examine its capacity to induce IgA class switching and differentiation of naive B cells in vitro. Monocyte-derived DCs were cultured in vitro with TLR agonists (TLR3, 4, 5, and 9) and other factors, including CD40 ligand, GM-CSF, and IL-4 as well as the neuropeptide vasoactive intestinal peptide. Under in vitro stimulation with vasoactive intestinal peptide and CD40L, IGIP mRNA expression could be up-regulated as much as 35-fold above nonstimulated samples within 12–48 h. Naive B cells cultured with exogenous recombinant human IGIP produced IgA in greater quantities than nonstimulated controls. Finally, we demonstrate that IGIP stimulation drives the production of μ-α switch circles from IgM+IgD+ naive human B cells, indicating its role as an IgA switch factor.
Lactate Boosts TLR4 Signaling and NF-κB Pathway-Mediated Gene Transcription in Macrophages via Monocarboxylate Transporters and MD-2 Up-Regulation
Authors: Samuvel Devadoss J. , Sundararaj Kamala P. , Nareika Alena , Lopes-Virella Maria F. , Huang Yan
Published: February 2009

It has been shown that lactate induces insulin resistance. However, the underlying mechanisms have not been well understood. Based on our observation that lactate augments LPS-stimulated inflammatory gene expression, we proposed that lactate may enhance TLR4 signaling in macrophages, which has been shown to play an important role in insulin resistance in adipocytes. In this study, we demonstrated that lactate stimulated MD-2, a coreceptor for TLR4 signaling activation, NF-κB transcriptional activity, and the expression of inflammatory genes in human U937 histiocytes (resident macrophages). Similar enhancement of the inflammatory gene expression by lactate was also observed in human monocyte-derived macrophages. The essential role of MD-2 in lactate-augmented TLR4 signaling was confirmed by observation that the suppression of MD-2 expression by small interfering RNA led to significant inhibition of inflammatory gene expression. To further elucidate how lactate treatment enhances TLR4 activation, we showed that the augmentation of inflammatory gene expression by lactate was abrogated by antioxidant treatment, suggesting a critical role of reactive oxygen species in the enhancement of TLR4 activation by lactate. Finally, we showed that α-cyano-4-hydroxycinnamic acid, a classic inhibitor for monocarboxylate transporters, blocked lactate-augmented inflammatory gene expression and nuclear NF-κB activity, indicating that lactate transport through monocarboxylate transporters is required for lactate-enhanced TLR4 activation. Collectively, this study documents that lactate boosts TLR4 activation and NF-κB-dependent inflammatory gene expression via monocarboxylate transporters and MD-2 up-regulation.
Regulatory T Cells: A Role in the Control of Helminth-Driven Intestinal Pathology and Worm Survival
Authors: D'Elia Riccardo , Behnke Jerzy M. , Bradley Janette E. , Else Kathryn J.
Published: February 2009

The chronic nature of intestinal nematode infections suggests that these parasites have evolved sophisticated immunomodulatory strategies. The induction of regulatory responses during chronic helminth infections could be advantageous to the host by minimizing damage incurred by these organisms. Regulation of the host immune response to infection could however be exploited by parasites as a survival strategy. We have explored both these aspects using the murine model of whipworm infection, Trichuris muris. Of the three laboratory isolates of T. muris in use, two (the E (Edinburgh) and J (Japan, subcultured from E)) are readily expelled by C57BL/6 mice, whereas the third, the S isolate (Sobreda, isolated from wild mice in Portugal) survives for much longer. The existence of the T. muris isolates thus presents a powerful tool to explore the mechanisms underlying chronic infection in a single strain of mouse. In this study, we show that S isolate-infected mice have increased numbers of Foxp3+ T cells in the gut compared with mice infected with the E isolate. Treatment of mice infected with the S isolate with either anti-CD25 or anti-glucocorticoid-induced TNFR exacerbated intestinal pathology, and, in addition, mice treated with anti-glucocorticoid-induced TNFR were able to expel worms more rapidly, implying the release of local effector mechanisms from a regulatory influence. Thus, our data show for the first time that T regulatory cells protect the host from worm-driven intestinal pathology. In addition, our data reveal a subversion of this damage-limiting response by the S isolate to facilitate its own survival.
Dendritic Cells and Monocyte/Macrophages That Create the IL-6/APRIL-Rich Lymph Node Microenvironments Where Plasmablasts Mature
Authors: Mohr Elodie , Serre Karine , Manz Rudolf A. , Cunningham Adam F. , Khan Mahmood , Hardie Deborah L. , Bird Roger , MacLennan Ian C. M.
Published: February 2009

IL-6 and APRIL influence the growth, differentiation, and survival of normal and neoplastic Ab-forming cells (AFC). In this study, we identify two subsets of myeloid cells that associate with the AFC and are the main producers of these factors during a T-dependent Ab response to alum-precipitated protein in mouse lymph nodes. First CD11c+CD8α− dendritic cells located in the perivascular area of the T zone provide about half of the IL-6 mRNA produced in the node together with significant amounts of APRIL mRNA. The number of these cells increases during the response, at least in part due to local proliferation. The second subset comprises Gr1+CD11b+F4/80+ monocyte/macrophages. These colonize the medullary cords during the response and are the other main IL-6 mRNA producers and the greatest source of APRIL mRNA. This medullary cord monocyte/macrophage subset results in local increase of APRIL mRNA that mirrors the polarity of CXCL12 expression in the node. The distribution of these myeloid cell subsets correlates with a gradient of AFC maturation assessed by progressive loss of Ki67 as AFC pass from the B cell follicle along the perivascular areas to the medullary cords.
IL-21: An Executor of B Cell Fate
Authors: Konforte Danijela , Simard Nathalie , Paige Christopher J.
Published: February 2009

IL-21 is a type I cytokine that shares the common receptor γ-chain with IL-2, IL-4, IL-7, IL-9, and IL-15. B cells are one of the lymphoid cell types whose development and function are regulated by IL-21. Depending on the interplay with costimulatory signals and on the developmental stage of a B cell, IL-21 can induce proliferation, differentiation into Ig-producing plasma cells, or apoptosis in both mice and humans. Alone and in combination with Th cell-derived cytokines IL-21 can regulate class switch recombination to IgG, IgA, or IgE isotypes, indicating its important role in shaping the effector function of B cells. This review highlights the role of IL-21 in B cell development, function, and disease and provides some perspectives on the future studies in this area.
γδ T Lymphocyte Homeostasis Is Negatively Regulated by β2-Microglobulin
Authors: French Jena D. , Roark Christina L. , Born Willi K. , O'Brien Rebecca L.
Published: February 2009

Successful application of γδ T cells in adoptive cell therapies depends upon our ability to maintain these cells in vivo. Using an adoptive transfer model to study lymphopenia-induced homeostatic expansion, we show that CD8+ and NK1.1+ γδ T cell subsets are differentially regulated. While CD8+ γδ T cells have an early and sustained advantage following transfer into TCRβ−/−/δ−/− mice, NK1.1+ γδ T cells proliferate slowly and are maintained at low numbers. The advantage of the CD8+ subset could not be explained by increased bcl-2 or cytokine receptor expression but did correlate with Vγ4+ and Vδ5+ expression. Despite the role of CD8 in MHC class I recognition by αβ T cells, β2-microglobulin (β2m)-associated MHC class I molecules were not required for CD8+ γδ T cell homeostatic expansion. Surprisingly, all γδ T cells, including the CD8+ subset, exhibited enhanced proliferation following adoptive transfer into Rag1−/−/β2m−/− compared with Rag1−/− recipients. This effect was most notable for the NK1.1+ subset, which expresses high levels of NKG2A/CD94 and Ly49. Although expression of these inhibitory receptors correlated with poor homeostatic expansion in the presence of β2m, γδ T cell homeostatic proliferation in TCRβ−/−/δ−/− mice was not altered in the presence of Ly49C/I- and NKG2-blocking Abs. While the mechanism by which β2m negatively regulates γδ T cell homeostasis remains to be determined, this observation is unique to γδ T cells and confirms that multiple mechanisms are in place to maintain strict regulation of both the size and the composition of the γδ T cell pool.
Cutting Edge: The Y Chromosome Controls the Age-Dependent Experimental Allergic Encephalomyelitis Sexual Dimorphism in SJL/J Mice
Authors: Spach Karen M. , Blake Melissa , Bunn Janice Y. , McElvany Ben , Noubade Rajkumar , Blankenhorn Elizabeth P. , Teuscher Cory
Published: February 2009

Multiple sclerosis is a sexually dimorphic, demyelinating disease of the CNS, and experimental allergic encephalomyelitis (EAE) is its principal autoimmune model. Young male SJL/J mice are relatively resistant to EAE whereas older males and SJL/J females of any age are susceptible. By comparing a wide age range of proteolipid protein peptide 139–151 immunized mice, we found that female disease severity remains constant with age. In contrast, EAE disease severity increases with age in SJL/J males, with young males having significantly less severe disease and older males having significantly more disease than equivalently aged females. To determine whether the Y chromosome contributes to this sexual dimorphism, EAE was induced in consomic SJL/J mice carrying a B10.S Y chromosome (SJL.YB10.S). EAE was significantly more severe in young male SJL.YB10.S mice compared with young male SJL/J mice. These studies show that a Y chromosome-linked polymorphism controls the age-dependent EAE sexual dimorphism observed in SJL/J mice.
Specific Targeting of the EBV Lytic Phase Protein BNLF2a to the Transporter Associated with Antigen Processing Results in Impairment of HLA Class I-Restricted Antigen Presentation
Authors: Horst Daniëlle , van Leeuwen Daphne , Croft Nathan P. , Garstka Malgorzata A. , Hislop Andrew D. , Kremmer Elisabeth , Rickinson Alan B. , Wiertz Emmanuel J. H. J. , Ressing Maaike E.
Published: February 2009

EBV persists for life in the human host while facing vigorous antiviral responses that are induced upon primary infection. This persistence supports the idea that herpesviruses have acquired dedicated functions to avoid immune elimination. The recently identified EBV gene product BNLF2a blocks TAP. As a result, reduced amounts of peptides are transported by TAP from the cytoplasm into the endoplasmic reticulum (ER) lumen for binding to newly synthesized HLA class I molecules. Thus, BNLF2a perturbs detection by cytotoxic T cells. The 60-aa-long BNLF2a protein prevents the binding of both peptides and ATP to TAP, yet further mechanistic insight is, to date, lacking. In this study, we report that EBV BNLF2a represents a membrane-associated protein that colocalizes with its target TAP in subcellular compartments, primarily the ER. In cells devoid of TAP, expression levels of BNLF2a protein are greatly diminished, while ER localization of the remaining BNLF2a is retained. For interactions of BNLF2a with the HLA class I peptide-loading complex, the presence of TAP2 is essential, whereas tapasin is dispensible. Importantly, we now show that in B cells supporting EBV lytic replication, the BNLF2a protein is expressed early in infection, colocalizing and associating with the peptide-loading complex. These results imply that, during productive EBV infection, BNLF2a contributes to TAP inhibition and surface HLA class I down-regulation. In this way, EBV BNLF2a-mediated evasion from HLA class I-restricted T cell immunity contributes to creating a window for undetected virus production.
Human Liver Dendritic Cells Promote T Cell Hyporesponsiveness
Authors: Bamboat Zubin M. , Stableford Jennifer A. , Plitas George , Burt Bryan M. , Nguyen Hoang M. , Welles Alexander P. , Gonen Mithat , Young James W. , DeMatteo Ronald P.
Published: February 2009

The liver is believed to promote tolerance, which may be beneficial due to its constant exposure to foreign Ags from the portal circulation. Although dendritic cells (DCs) are critical mediators of immune responses, little is known about human liver DCs. We compared freshly purified liver DCs from surgical specimens with autologous blood DCs. Liver and blood DCs were equally immature, but had distinct subset compositions. BDCA-1+ DCs represented the most prevalent liver DC subset, whereas the majority of peripheral blood DCs were CD16+. Upon TLR4 ligation, blood DCs secreted multiple proinflammatory cytokines, whereas liver DCs produced substantial amounts of IL-10. Liver DCs induced less proliferation of allogeneic T cells both in a primary MLR and after restimulation. Similarly, Ag-specific CD4+ T cells were less responsive to restimulation when initially stimulated by autologous liver DCs rather than blood DCs. In addition, liver DCs generated more suppressive CD4+CD25+FoxP3+ T regulatory cells and IL-4-producing Th2 cells via an IL-10-dependent mechanism. Our findings are critical to understanding hepatic immunity and demonstrate that human liver DCs promote immunologic hyporesponsiveness that may contribute to hepatic tolerance.
Transglutaminase 2 Is Needed for the Formation of an Efficient Phagocyte Portal in Macrophages Engulfing Apoptotic Cells
Authors: Tóth Beáta , Garabuczi Éva , Sarang Zsolt , Vereb György , Vámosi György , Aeschlimann Daniel , Blaskó Bernadett , Bécsi Bálint , Erdõdi Ferenc , Lacy-Hulbert Adam , Zhang Ailiang , Falasca Laura , Birge Raymond B. , Balajthy Zoltán , Melino Gerry , Fésüs László , Szondy Zsuzsa
Published: February 2009

Transglutaminase 2 (TG2), a protein cross-linking enzyme with many additional biological functions, acts as coreceptor for integrin β3. We have previously shown that TG2−/− mice develop an age-dependent autoimmunity due to defective in vivo clearance of apoptotic cells. Here we report that TG2 on the cell surface and in guanine nucleotide-bound form promotes phagocytosis. Besides being a binding partner for integrin β3, a receptor known to mediate the uptake of apoptotic cells via activating Rac1, we also show that TG2 binds MFG-E8 (milk fat globulin EGF factor 8), a protein known to bridge integrin β3 to apoptotic cells. Finally, we report that in wild-type macrophages one or two engulfing portals are formed during phagocytosis of apoptotic cells that are characterized by accumulation of integrin β3 and Rac1. In the absence of TG2, integrin β3 cannot properly recognize the apoptotic cells, is not accumulated in the phagocytic cup, and its signaling is impaired. As a result, the formation of the engulfing portals, as well as the portals formed, is much less efficient. We propose that TG2 has a novel function to stabilize efficient phagocytic portals.
The relationship of hyperuricemia and blood pressure in the Thai army population
Authors: Ouppatham S , Bancha S , Choovichian P
Published: February 2009

Background:

Previous studies have demonstrated a strong association of hypertension and renal disease with gout. Nevertheless, controversy remains concerning serum uric acid concentration as an independent factor of hypertension.

Aim:

To explore the relationship between systolic blood pressure (SBP) and diastolic blood pressure (DBP) with serum uric acid levels. Settings and Design: An observational study.

Materials and Methods:

A total of 5,564 subjects from the Armed Forces Research Institute of Medical Sciences were included in the study.

Statistical Analysis:

ANOVA tests, Chi-square test, correlation coefficients, and multiple regression analysis were performed.

Results:

Of the total subjects, 4,099 (73.7%) were male. Mean SBP and DBP were 128.73±17.06 and 81.62 ± 11.58 mm Hg, respectively. The mean serum uric acid level was 6.54 ± 1.71 mg/dL. A significant and positive correlation was found both between serum uric acid and SBP (r=0.186, P < 0.001) and between serum uric acid and DBP (r=0.255, P < 0.001). After multiple regression analysis of various clinical variables, serum uric acid levels were correlated with the severity of both SBP and DBP, increased age, increased body mass index, decreased glomerular filtration rate, increased serum cholesterol, and male gender.

Conclusions:

In this study, we suggest that serum uric acid be used to correlate with levels of blood pressure in the general population. Further investigation is required to establish the treatment for hyperuricemia in hypertensive patients.
Supramolecular Crystal Engineering at the Solid–Liquid Interface from First Principles: Toward Unraveling the Thermodynamics of 2D Self‐Assembly
Authors: Palma Carlos‐Andres , Bonini Massimo , Breiner Thomas , Samorì Paolo
Published: February 2009

The formation of highly ordered 2D supramolecular architectures self‐assembled at the solid–solution interfaces is subject to complex interactions between the analytes, the solvent, and the substrate. These forces have to be mastered in order to regard self‐assembly as an effective bottom‐up approach for functional‐device engineering. At such interfaces, prediction of the thermodynamics governing the formation of spatially ordered 2D arrangements is far from being fully understood, even for the physisorption of a single molecular component on the basal plane of a flat surface. Two recent contributions on controlled polymorphism and nanopattern formation render it possible to gain semi‐quantitative insight into the thermodynamics of physisorption at interfaces, paving the way towards 2D supramolecular crystal engineering. Although in these two works different systems have been chosen to tackle such a complex task, authors showed that the chemical design of molecular building blocks is not the only requirement to fulfill when trying to preprogram self‐assembled patterns at the solid–liquid interface.
Tandem Metal and Organocatalysis in Sequential Hydroformylation and Enantioselective Mannich Reactions
Authors: Chercheja Serghei , Rothenbücher Thomas , Eilbracht Peter
Published: February 2009

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Metal‐catalysed hydroformylation is successfully combined with an organocatalysed stereoselective Mannich reaction in a tandem reaction sequence. This novel type of “tandem catalysis” allows access to complex molecular systems with high levels of enantioselectivity, using simple starting materials and an amino acid as the chiral catalyst.
Cyclobutenes as Isolable Intermediates in the Gold(I)‐Catalysed Cycloisomerisation of 1,8‐Enynes
Authors: Odabachian Yann , Gagosz Fabien
Published: February 2009

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The gold(I)‐catalysed isomerisation of 1,8‐enynes allows the efficient synthesis of functionalised bicyclo[5.2.0]nonenes. Notably, these cyclobutenes derivatives can be isolated as reactive intermediates that could undergo subsequent gold(I)‐catalysed transformations such as isomerisation, fragmentation or ene reaction to furnish more structurally complex products. This study also provides useful information related to the mechanism leading to metathesis‐type derivatives, examples of which were shown to be produced, in the present case, by a gold(I)‐catalysed ring fragmentation of the cyclobutene moiety.
Hydrogenation of 2‐ethylanthraquinone under Taylor flow in single square channel monolith reactors
Authors: Liu Dingsheng , Zhang Jianguo , Li Defu , Kong Qingdan , Zhang Tong , Wang Shudong
Published: February 2009

The hydrogenation of 2‐ethylanthraquinone (EAQ) to 2‐ethylanthrahydroquinone (EAHQ) was carried out under Taylor flow in single square channel monolith reactors. The two opening ends of opaque reaction channel were connected with two circular transparent quartz‐glass capillaries, where Taylor flow hydrodynamics parameters were measured and further used to obtain practical flow state of reactants in square reaction channels. A carefully designed gas‐liquid inlet mixer was used to supply steady gas bubbles and liquid slugs with desired length. The effects of various operating parameters, involving superficial gas velocity, superficial liquid velocity, gas bubble length, liquid slug length, two‐phase velocity and temperature, on EAQ conversion were systematically researched. Based on EAQ conversion, experimental overall volumetric mass transfer coefficients were calculated, and also studied as functions of various parameters as mentioned earlier. The film model, penetration model, and existing semi‐empirical formula were used to predict gas‐solid, gas‐liquid, and liquid‐solid volumetric mass transfer coefficients in Taylor flow, respectively. The predicted overall volumetric mass transfer coefficients agreed well with the experimental ones. © 2009 American Institute of Chemical Engineers AIChE J, 2009
The influence of temporal cake moisture content on a discontinuous washing process in the centrifugal field
Authors: Ruslim Franky , Nirschl Hermann , Stahl Werner , Carvin Philippe
Published: February 2009

In solid/liquid separation processes, filter cake washing is an essential step in improving the quality of particulate products by elimination of impurities. During cake washing and dewatering, the cake saturation changes depending on the flow conditions and it cannot always be measured and controlled accurately. This article deals with investigations on the influence of the initial and temporal cake saturation on washing PVC and silica sand particles in the centrifugal field. It was found, that high initial saturation levels and high maximum saturations during the washing process had a positive impact in inducing a high hydrostatic pressure for advective flow and enabling a homogeneous distribution of the wash water inside the cake. This was achieved by increasing the wash water flux and/or decreasing the g‐factor. A good method to obtain low final impurity quantity is the combination of washing at a low g‐factor and dewatering at a high one. © 2009 American Institute of Chemical Engineers AIChE J, 2009
Occupational exposure to UV light and mortality from multiple sclerosis
Authors: Westberg M. , Feychting M. , Jonsson F. , Nise G. , Gustavsson P.
Published: February 2009

Background

The etiology of multiple sclerosis (MS) is largely unknown; low exposure to ultraviolet (UV) light has been a suggested risk factor. The aim of this study was to investigate whether occupational exposure to UV light reduces the risk of death from MS.

Methods

The cohort was based on all individuals in the Swedish census in 1980. All MS‐related deaths were identified in the national registry of causes of death. A job‐exposure matrix was developed to classify the occupational exposure to UV light.

Results

MS was recorded as a cause of the death for 839 individuals. The risk of MS‐related death decreased with increasing occupational exposure to UV light. The relative risk adjusted for age, sex, and socioeconomic status was 0.48 (95% CI 0.28–0.80) in the high‐exposure group and 0.88 (95% CI 0.73–1.06) in the intermediate‐exposure group.

Conclusions

Occupational exposure to UV light was associated with a reduced risk of MS. Our findings are corroborated by previous observations that UV light has a preventive role in the development of MS, although the possibility of reversed causality cannot be completely ruled out. Am. J. Ind. Med. 52:353–357, 2009. © 2009 Wiley‐Liss, Inc
Livestock‐handling injuries in agriculture: An analysis of Colorado workers' compensation data
Authors: Douphrate David I. , Rosecrance John C. , Stallones Lorann , Reynolds Stephen J. , Gilkey David P.
Published: February 2009

Background

Previous studies have reported that livestock‐handling injuries are among the most severe of agricultural injuries. This study identifies the costs, characteristics, and contributing factors associated with livestock‐handling injuries among Colorado dairy farmers, cattle/livestock raisers, and cattle dealers.

Methods

A 10‐year (1997–2006) history of Colorado's workers' compensation claims data was used for analysis. Descriptive analyses of livestock‐handling injury claims were performed. Claim cost analysis was also conducted. The agent–host–environment epidemiological model was used to analyze injury event descriptions.

Results

A total of 1,114 livestock‐handling claims were analyzed. Claims associated with milking parlor tasks represented nearly 50% of injuries among dairy workers. Claims associated with riding horseback, sorting/penning cattle, and livestock‐handling equipment represented high proportions of livestock‐handling injuries among cattle/livestock raisers and cattle dealers. Claims associated with livestock‐handling represented the highest percentage of high‐cost and high‐severity injuries in all three sectors.

Conclusions

Livestock‐handling injuries are a significant problem, more costly, and result in more time off work than other causes of agricultural injuries. There is a strong and compelling need to develop cost‐effective interventions to reduce the number of livestock‐handling injuries in agriculture. Am. J. Ind. Med. 52:391–407, 2009. © 2009 Wiley‐Liss, Inc.
Room‐Temperature Growth of Silicon Oxide Nanofilms: New Opportunities for Plastic Electronics
Authors: Hoffmann Helmuth
Published: February 2009

A new generation of plastic transistors consisting primarily of light and flexible organic materials requires new fabrication methods which combine low‐temperature, solution‐phase processing with precise control in the nanometer range over the component dimensions. Ultrathin silicon oxide films, which serve as gate dielectric layers in these transistors, were recently grown at room temperature from polymer precursor films by a novel layer‐by‐layer deposition/oxidation process.

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Mechanism of Cyclic Carbonate Synthesis from Epoxides and CO2
Authors: North Michael , Pasquale Riccardo
Published: February 2009

Three interconnected catalytic cycles account for the title reaction catalyzed by a bimetallic aluminum(salen) complex and Bu4NBr. In the first, Bu4NBr acts as a nucleophile to activate the epoxide. In the second, Bu3N generated in situ serves to activate CO2. In the third, the aluminum(salen) complex brings the two activated species together so that the key bonds can be formed intramolecularly.

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LiCl‐Mediated Preparation of Functionalized Benzylic Indium(III) Halides and Highly Chemoselective Palladium‐Catalyzed Cross‐Coupling in a Protic Cosolvent
Authors: Chen Yi‐Hung , Sun Mai , Knochel Paul
Published: February 2009

Sensitive functional groups such as COR, CHO, or CH2OH can be present in benzylic indium reagents prepared by the direct insertion of indium in the presence of LiCl. These reagents undergo palladium‐catalyzed cross‐coupling reactions in the presence of a protic cosolvent after activation with iPrMgCl⋅LiCl (see scheme). Remarkable chemoselectivities are achieved by using various electrophiles containing NH or OH groups.

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Stereoselective Synthesis of Enantiomerically Pure Nupharamine Alkaloids from Castoreum
Authors: Stoye Alexander , Quandt Gabriele , Brunnhöfer Björn , Kapatsina Elissavet , Baron Julia , Fischer André , Weymann Markus , Kunz Horst
Published: February 2009

An animalic note: The first total synthesis of the all‐cis nupharamine 2, an alkaloid from beaver castoreum, is based on the stereoselective domino Mannich–Michael reaction of N‐galactosylfurylaldimine to give 1 (Piv=pivaloyl), subsequent conjugate cuprate addition, and stereoselective protonation of the enolate. These reactions are all controlled by the carbohydrate. Protonation of the enolate after cleavage of the auxiliary leads to epimer 3.

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Selective CF Bond Activation of Tetrafluorobenzenes by Nickel(0) with a Nitrogen Donor Analogous to N‐Heterocyclic Carbenes
Authors: Doster Meghan E. , Johnson Samuel A.
Published: February 2009

N, not NHC: A neutral, basic, strong σ‐donor nitrogen ancillary ligand with properties analogous to those of N‐heterocyclic carbenes (NHCs) was developed to aid in the oxidative additions of challenging substrates to late transition metals. Selective, room‐temperature CF bond activation was observed with hexa‐, penta‐, and all three isomers of tetrafluorobenzene using a nickel(0) source in the presence of this donor.

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The Proline‐Catalyzed Double Mannich Reaction of Acetaldehyde with N‐Boc Imines
Authors: Chandler Carley , Galzerano Patrizia , Michrowska Anna , List Benjamin
Published: February 2009

Double‐cross: Proline catalyzes the double Mannich reaction of acetaldehyde with N‐Boc imines in excellent yields (up to 99 %; Boc=tert‐butoxycarbonyl) and close to perfect diastereo‐ and enantioselectivities. Depending on the choice of catalysts, both the chiral, pseudo‐C2‐symmetric diastereomer and the corresponding meso compound can be prepared. Cross double Mannich reactions of acetaldehyde with two different imines are also demonstrated.

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Effect of dissolved carbon dioxide on the glass transition and crystallization of poly(lactic acid) as probed by ultrasonic measurements
Authors: Reignier J. , Tatibouët J. , Gendron R.
Published: February 2009

The effects of dissolved carbon dioxide (CO2) molecules on the glass‐transition temperature as well as the crystallization kinetics of poly(lactic acid) have been investigated with a novel device that combines ultrasonic and volumetric measurements. Ultrasonic parameters such as the sound velocity are very sensitive to crystallization and can be used to monitor the crystallization kinetics. The glass‐transition temperature has been found to decrease nonlinearly as the CO2 concentration increases. The maximum in the crystallization rate has been found to increase with the addition of CO2. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Unlubricated rolling wear of HNBR/FKM/MWCNT compounds against steel
Authors: Xu D. , Karger‐Kocsis J. , Major Z. , Thomann R.
Published: February 2009

The rolling friction and wear of the compounds of peroxide‐cured hydrogenated acrylonitrile/butadiene rubber (HNBR) and fluororubber (FKM) (HNBR‐FKM) with and without multiwalled carbon nanotube (MWCNT) contents were studied against steel in orbital rolling ball (steel)‐on‐plate (rubber) test rig (Orbital‐RBOP). The phase structure of the rubber compounds in the presence and absence of MWCNT was studied by dynamic mechanical thermal analysis (DMTA), transmission electron and atomic force microscopy (TEM and AFM, respectively). It was established that HNBR formed the matrix in which micron‐scaled FKM domains were dispersed. MWCNT was preferentially embedded in the HNBR. The network‐related and surface tension properties of the rubber compounds were derived from DMTA tests and contact angle measurements, respectively. The Martens hardness of the rubbers was also measured. The coefficient of friction (COF) and specific wear rate (Ws) were determined in Orbital‐RBOP. Blending of HNBR with FKM increased the COF slightly and decreased the specific wear rate prominently when compared with pure HNBR. Additional MWCNT reinforcement (10 parts per hundred part rubber, phr) of the HNBR and HNBR‐FKM further increased the COF and at the same time improved the wear resistance. The wear mechanisms were concluded by inspecting the worn surfaces in scanning electron microscope (SEM) and discussed as a function of FKM and MWCNT modifications. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009