bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial Dextran-Hydrolyzing Enzymes: Fundamentals and Applications
Authors: Khalikova Elvira , Susi Petri , Korpela Timo 
Published: June 2005

SUMMARYDextran is a chemically and physically complex polymer, breakdown of which is carried out by a variety of endo- and exodextranases. Enzymes in many groups can be classified as dextranases according to function: such enzymes include dextranhydrolases, glucodextranases, exoisomaltohydrolases, exoisomaltotriohydrases, and branched-dextran exo-1,2-α-glucosidases. Cycloisomalto-oligosaccharide glucanotransferase does not formally belong to the dextranases even though its side reaction produces hydrolyzed dextrans. A new classification system for glycosylhydrolases and glycosyltransferases, which is based on amino acid sequence similarities, divides the dextranases into five families. However, this classification is still incomplete since sequence information is missing for many of the enzymes that have been biochemically characterized as dextranases. Dextran-degrading enzymes have been isolated from a wide range of microorganisms. The major characteristics of these enzymes, the methods for analyzing their activities and biological roles, analysis of primary sequence data, and three-dimensional structures of dextranases have been dealt with in this review. Dextranases are promising for future use in various scientific and biotechnological applications.
Enteric Viruses of Humans and Animals in Aquatic Environments: Health Risks, Detection, and Potential Water Quality Assessment Tools
Authors: Fong Theng-Theng , Lipp Erin K. 
Published: June 2005

SUMMARYWaterborne enteric viruses threaten both human and animal health. These pathogens are host specific and cause a wide range of diseases and symptoms in humans or other animals. While considerable research has documented the risk of enteric viruses to human health from contact with contaminated water, the current bacterial indicator-based methods for evaluation of water quality are often ineffectual proxies for pathogenic viruses. Additionally, relatively little work has specifically investigated the risk of waterborne viruses to animal health, and this risk currently is not addressed by routine water quality assessments. Nonetheless, because of their host specificity, enteric viruses can fulfill a unique role both for assessing health risks and as measures of contamination source in a watershed, yet the use of animal, as well as human, host-specific viruses in determining sources of fecal pollution has received little attention. With improved molecular detection assays, viruses from key host groups can be targeted directly using PCR amplification or hybridization with a high level of sensitivity and specificity. A multispecies viral analysis would provide needed information for controlling pollution by source, determining human health risks based on assessments of human virus loading and exposure, and determining potential risks to production animal health and could indicate the potential for the presence of other zoonotic pathogens. While there is a need to better understand the prevalence and environmental distribution of nonhuman enteric viruses, the development of improved methods for specific and sensitive detection will facilitate the use of these microbes for library-independent source tracking and water quality assessment tools.
A MODEL PROBLEM FOR THE INITIAL-BOUNDARY VALUE FORMULATION OF EINSTEIN'S FIELD EQUATIONS
Authors: REULA OSCAR , SARBACH OLIVIER 
Published: June 2005

In many numerical implementations of the Cauchy formulation of Einstein's field equations one encounters artificial boundaries which raises the issue of specifying boundary conditions. Such conditions have to be chosen carefully. In particular, they should be compatible with the constraints, yield a well posed initial-boundary value formulation and incorporate some physically desirable properties like, for instance, minimizing reflections of gravitational radiation. Motivated by the problem in General Relativity, we analyze a model problem, consisting of a formulation of Maxwell's equations on a spatially compact region of space–time with timelike boundaries. The form in which the equations are written is such that their structure is very similar to the Einstein–Christoffel symmetric hyperbolic formulations of Einstein's field equations. For this model problem, we specify a family of Sommerfeld-type constraint-preserving boundary conditions and show that the resulting initial-boundary value formulations are well posed. We expect that these results can be generalized to the Einstein–Christoffel formulations of General Relativity, at least in the case of linearizations about a stationary background.
Are Remnant-Like Particles Independent Predictors of Coronary Heart Disease Incidence?
Authors: Imke Claudia , Rodriguez Beatriz L. , Grove John S. , McNamara Judith R. , Waslien Carol , Katz Alan R. , Willcox Bradley , Yano Katsuhiko , Curb J. David 
Published: June 2005

Background—Remnant-like particles have been proposed as a new risk factor for coronary heart disease (CHD). This is the first long-term prospective investigation of the relationship between remnant-like particles and a cardiovascular disease outcome in healthy men.Methods and Results—A cohort of 1156 Japanese-American men aged 60 to 82 from the Honolulu Heart Program was followed for 17 years. During that period 164 incident cases of CHD were identified. In multivariate Cox regression analyses, baseline remnant-like particle cholesterol (RLP-C) and triglyceride (RLP-TG) levels were significantly related to CHD incidence independently of nonlipid cardiovascular risk factors and of total cholesterol or high-density and low-density lipoprotein cholesterol levels. Total triglyceride levels were an independent predictor of CHD incidence. However, in models including RLP and triglyceride level simultaneously, neither variable was significant when adjusted for the other. This finding can be attributed to the strong correlation between RLP-C and RLP-TG levels and total triglycerides. When individuals with normal triglyceride levels (n=894) were separated from those with elevated triglycerides (n=260), the association between RLPs and CHD relative risk was only significant for the group with elevated triglyceride levels.Conclusions—RLP levels predicted CHD incidence independently of nonlipid risk factors and of total cholesterol or high-density and low-density lipoprotein cholesterol levels. However, RLP levels did not provide additional information about CHD incidence over and above total triglyceride levels. Therefore, this study does not support the need for testing of remnants in men if measures of fasting triglycerides are available.
The expression and the regulatory role of OX40 and 4-1BB heterodimer in activated human T cells
Authors: Ma Bruce Y. , Mikolajczak Sebastian A. , Danesh Ali , Hosiawa Karoline A. , Cameron Cheryl M. , Takaori-Kondo Akifumi , Uchiyama Takashi , Kelvin David J. , Ochi Atsuo 
Published: June 2005

AbstractOX40 and 4-1BB are members of the tumor necrosis factor (TNF) family of costimulatory receptors whose signaling is important for differential immune responses mediated by CD4+ or CD8+ T cells. Although activated T cells may acquire OX40/4-1BB double-positive phenotype and signaling from each receptor is expected to influence cell functions, the relevance between OX40 and 4-1BB has never been investigated before. While we were investigating the expression of OX40 and 4-1BB on activated human T cells, we found that they colocalize. The study of receptor gene–transfected cells showed that both receptors coendocytose and the complex of OX40 and 4-1BB was detected by specific ligands or antibodies (Abs). The heterodimer of OX40 and 4-1BB was identified by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) under nonreduced conditions and was associated with the tumor receptor–associated factor (TRAF) family proteins in a unique manner. Furthermore, the stimulation of OX40/4-1BB rendered cells sensitive to apoptosis induced by TNF-α that accompanied reduced activation of nuclear factor-κB (NF-κB). Finally, the OX40/4-1BB stimulation repressed the mitogen response in activated CD25+CD4+ T cells and preactivated CD8+ T cells. Thus, the OX40/4-1BB heterodimer appears to represent a unique regulatory receptor in activated T cells.
Impact of tumor Epstein-Barr virus status on presenting features and outcome in age-defined subgroups of patients with classic Hodgkin lymphoma: a population-based study
Authors: Jarrett Ruth F. , Stark Gail L. , White Jo , Angus Brian , Alexander Freda E. , Krajewski Andrew S. , Freeland June , Taylor G. Malcolm , Taylor Penelope R. A. ,   for the Scotland and Newcastle Epidemiology of Hodgkin Disease Study Group
Published: June 2005

AbstractThe association between tumor Epstein-Barr virus (EBV) status and clinical outcome in Hodgkin lymphoma (HL) is controversial. This population-based study assessed the impact of EBV status on survival in age-stratified cohorts of adults with classic HL (cHL). Data from 437 cases were analyzed with a median follow-up of 93 months. Overall survival (OS) was significantly better for EBV-negative compared with EBV-positive patients (P &lt; .001), with 5-year survival rates of 81% and 66%, respectively; disease-specific survival (DSS) was also greater for EBV-negative patients (P = .03). The impact of EBV status varied with age at diagnosis. In patients aged 16 to 34 years, EBV-associated cases had a survival advantage compared with EBV-negative cases, but differences were not statistically significant (P = .21). Among patients 50 years or older, EBV positivity was associated with a significantly poorer outcome (P = .003). Excess deaths occurred in EBV-positive patients with both early- and advanced-stage disease. In multivariate analysis of OS in the older patients, EBV status retained statistical significance after adjusting for the effects of sex, stage, and B symptoms (P = .01). Impaired immune status may contribute to the development of EBV-positive cHL in older patients, and strategies aimed at boosting the immune response should be investigated in the treatment of these patients. (Blood. 2005;106:2444-2451)
Novel pathway for megakaryocyte production after in vivo conditional eradication of integrin αIIb-expressing cells
Authors: Jacquelin Beatrice , Kortulewski Thierry , Vaigot Pierre , Pawlik Alexandre , Gruel Gaetan , Alibert Olivier , Soularue Pascal , Joubert Christophe , Gidrol Xavier , Roux Diana Tronik-Le 
Published: June 2005

Abstract
Our knowledge of the molecular mechanisms that regulate hematopoiesis in physiologic and pathologic conditions is limited. Using a molecular approach based on cDNA microarrays, we demonstrated the emergence of an alternative pathway for mature bone marrow cell recovery after the programmed and reversible eradication of CD41+ cells in transgenic mice expressing a conditional toxigene targeted by the platelet αIIb promoter. The expression profile of the newly produced CD41+ cells showed high levels of transcripts encoding Ezh2, TdT, Rag2, and various immunoglobulin (Ig) heavy chains. In this context, we identified and characterized a novel population of Lin-Sca-1hic-Kit- cells, with a lymphoid-like expression pattern, potentially involved in the reconstitution process. Our study revealed novel transcriptional cross talk between myeloid and lymphoid lineages and identified gene expression modifications that occur in vivo under these particular stress conditions, opening important prospects for therapeutic applications.
In vivo delivery of caspase-8 or Fas siRNA improves the survival of septic mice
Authors: Wesche-Soldato Doreen E. , Chung Chun-Shiang , Lomas-Neira Joanne , Doughty Lesley A. , Gregory Stephen H. , Ayala Alfred 
Published: June 2005

Abstract
Although studies have shown increased evidence of death receptor-driven apoptosis in intestinal lymphoid cells, splenocytes, and the liver following the onset of polymicrobial sepsis, little is known about the mediators controlling this process or their pathologic contribution. We therefore attempted to test the hypothesis that the hydrodynamic administration of small interfering RNA (siRNA) against the death receptor, Fas or caspase-8, should attenuate the onset of morbidity and mortality seen in sepsis, as produced by cecal ligation and puncture (CLP). We initially show that in vivo administration of green fluorescent protein (GFP) siRNA in GFP transgenic mice results in a decrease in GFP fluorescence in most tissues. Subsequently, we also found that treating septic nontransgenic mice with siRNA targeting Fas or caspase-8 but not GFP (used as a control here) decreased the mRNA, in a sustained fashion up to 10 days, and protein expression of Fas and caspase-8, respectively. In addition, transferase-mediated dUTP (deoxyuridine triphosphate) nick end labeling (TUNEL) and active caspase-3 analyses revealed a decrease in apoptosis in the liver and spleen but not the thymus following siRNA treatment. Indices of liver damage were also decreased. Finally, the injection of Fas or caspase-8 given not only 30 minutes but up to 12 hours after CLP significantly improved the survival of septic mice.
MHC class II/CD38/CD9: a lipid-raft–dependent signaling complex in human monocytes
Authors: Zilber Marie-Thérèse , Setterblad Niclas , Vasselon Thierry , Doliger Christelle , Charron Dominique , Mooney Nuala , Gelin Catherine 
Published: June 2005

AbstractDespite a lack of signaling motifs in their cytoplasmic domain, major histocompatibility complex (MHC) class II molecules trigger a variety of intracellular signals that regulate antigen-presenting cell function. They thus may use associated effector molecules as demonstrated on B cells and dendritic cells. The starting point of this study comes from our previous work, which demonstrated that the ecto-enzyme CD38 is functionally linked to MHC class II molecules. We report that CD38 and human leukocyte antigen-DR (HLA-DR) are functionally and physically associated in lipid rafts microdomains of cellsurface monocytes and that the integrity of these domains is necessary for the HLA-DR and CD38 signaling events. Moreover, we identified the tetraspanin CD9 molecule as a partner of the CD38/HLA-DR complex and demonstrated that HLA-DR, CD38, and CD9 share a common pathway of tyrosine kinase activation in human monocytes. The analysis of conjugate formation between monocytes presenting superantigen and T cells shows the active participation of CD9 and HLA-DR on the monocyte surface. Together, these observations demonstrate the presence of a CD38 and HLA-DR signaling complex within tetraspanin-containing lipid rafts and the functional impact of their molecular partner CD9 in antigen presentation.
B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model
Authors: Dunussi-Joannopoulos Kyri , Hancock Gerald E. , Kunz Arthur , Hegen Martin , Zhou Xiaochuan X. , Sheppard Barbara J. , Lamothe Jennifer , Li Evelyn , Ma Hak-Ling , Hamann Philip R. , Damle Nitin K. , Collins Mary 
Published: June 2005

AbstractWe report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.
Fas signal links innate and adaptive immunity by promoting dendritic-cell secretion of CC and CXC chemokines
Authors: Guo Zhenhong , Zhang Minghui , Tang Hua , Cao Xuetao 
Published: June 2005

AbstractDendritic cells (DCs) and chemokines are important in linking innate and adaptive immunity. We previously reported that Fas ligation induced interleukin 1β (IL-1β)–dependent maturation and IL-1β–independent survival of DCs, with extracellular signal–regulated kinase (ERK) and nuclear factor–κB (NF-κB) signaling pathways involved, respectively. We describe here that Fas ligation induced DCs to rapidly produce both CXC and CC chemokines, including macrophage inflammatory protein 2 (MIP-2), MIP-1α, MIP-1β, monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated on activation normal T cell expressed and secreted), and TARC (thymus and activation-regulated chemokine), resulting in enhanced chemoattraction of neutrophils and T cells by Fas-ligated DCs in vivo or by its supernatant in vitro. These chemokines work synergistically in chemoattraction of neutrophils and T cells with MIP-2 more important for neutrophils, MIP-1α and TARC more important for T cells. Moreover, Fas-ligated DCs increased endocytosis by neutrophils and activation and proliferation of antigen-specific naive T cells. Fas ligation-induced DC secretion of chemokines involves Ras/Raf/mitogen-activated protein kinase kinase (MEK)/ERK activation and is ERK, but not NF-κB, dependent. Activation of caspases, including caspase 1, but not IL-1 autocrine action, is involved in this process. These data indicate that Fas signaling provides a key link between innate response and adaptive immunity by promoting DC chemokine production.
Vav proteins regulate peripheral B-cell survival
Authors: Vigorito Elena , Gambardella Laure , Colucci Francesco , McAdam Simon , Turner Martin 
Published: June 2005

AbstractMice lacking all 3 Vav proteins fail to produce significant numbers of recirculating follicular or marginal zone B cells. Those B cells that do mature have shortened lifespans. The constitutive nuclear factor-kappaB (NF-κB) activity of resting naive B cells required Vav function and expression of cellular reticuloendotheliosis (c-Rel). Rel-A was reduced in Vav-deficient B cells. Furthermore, expression of the NF-κB-regulated antiapoptotic genes A1 and Bcl-2 was reduced in mature Vav-deficient B cells. Overexpression of Bcl-2 restored the number of mature follicular B cells in the spleens of Vav-deficient mice. When activated by B-cell receptor (BCR) cross-linking, Vav-deficient B cells failed to activate NF-κB. Vav proteins thus regulate an NF-κB-dependent survival signal in naive B cells and are required for NF-κB function after BCR cross-linking.
Motility, proliferation, and egress to the circulation of human AML cells are elastase dependent in NOD/SCID chimeric mice
Authors: Tavor Sigal , Petit Isabelle , Porozov Svetlana , Goichberg Polina , Avigdor Abraham , Sagiv Sari , Nagler Arnon , Naparstek Elizabeth , Lapidot Tsvee 
Published: June 2005

AbstractThe role of the proteolytic enzyme elastase in motility and proliferation of leukemic human acute myeloblastic leukemia (AML) cells is currently unknown. We report a correlation between abnormally high levels of elastase in the blood of AML patients and the number of leukemic blast cells in the circulation. In AML cells, we observed expression of cell-surface elastase, which was regulated by the chemokine stromal cell-derived factor-1 (SDF-1). In vitro inhibition of elastase prevented SDF-1-induced cell polarization, podia formation, and reduced migration of human AML cells as well as their adhesion. Elastase inhibition also significantly impaired in vivo homing of most human AML cells to the bone marrow (BM) of nonobese diabetic-severe combined immunodeficient (NOD/SCID)/beta-2 microglobulin knock-out (B2mnull) mice that underwent transplantation. Moreover, in vitro proliferation of AML cells was elastase dependent. In contrast, treatment with elastase inhibitor enhanced the proliferation rate of human cord blood CD34+ cells, including primitive CD34+/CD38- cells, and their in vivo homing. Finally, NOD/SCID mice previously engrafted with human AML cells and treated with elastase inhibitor had significantly reduced egress of leukemic cells into the circulation. Taken together, our data demonstrate that human AML cells constitutively secrete and express SDF-1-dependent cell-surface elastase, which regulates their migration and proliferation. (Blood. 2005;106:2120-2127)
TGF-β in allogeneic stem cell transplantation: friend or foe?
Authors: Banovic Tatjana , MacDonald Kelli P. A. , Morris Edward S. , Rowe Vanessa , Kuns Rachel , Don Alistair , Kelly Jane , Ledbetter Steve , Clouston Andrew D. , Hill Geoffrey R. 
Published: June 2005

AbstractDonor treatment with granulocyte-colony-stimulating factor (G-CSF) attenuates the ability of donor T cells to induce acute graft-versus-host disease (aGVHD) but increases the severity of chronic GVHD (cGVHD). We investigated the role of the regulatory cytokine transforming growth factor β (TGF-β) in this paradox in well-established murine models of aGVHD and cGVHD wherein recipients undergo transplantation with splenocytes from donors treated with G-CSF. Neutralization of TGF-β after stem-cell transplantation (SCT) significantly increased the severity of aGVHD, and the concurrent prevention of interleukin-10 (IL-10) production further exaggerated this effect. Early after SCT, donor T cells were the predominant source of TGF-β and were able to attenuate aGVHD in a TGF-β-dependent fashion. Although the neutralization of TGF-β augmented the proliferation and expansion of donor T cells after SCT, it paradoxically impaired cellular cytotoxicity to host antigens and associated graft-versus-leukemia (GVL) effects. In cGVHD, neutralization of TGF-β from day 14 after SCT attenuated histologic abnormalities, and CD11b+ mononuclear cells infiltrating sclerodermatous skin produced 50-fold more TGF-β than corresponding T cells. Thus, though the production of TGF-β by donor T cells early after transplantation attenuates aGVHD and is required for optimal GVL, the production of TGF-β late after SCT is preferentially from mononuclear cells and mediates cGVHD. These data have important implications for the timing of therapeutic TGF-β neutralization to prevent cGVHD after allogeneic SCT. (Blood. 2005;106:2206-2214)