Search

The production of D* and D mesons in inelastic scattering of 160 GeV/c muons off a ^6LiD target has been investigated with the COMPASS spectrometer at CERN for 0.003 (GeV/c)^2 < Q^2 < 10 (GeV/c)^2 and 3x10^-5< x_Bj < 0.1. The study is based on 8100 events where a D^0 or anti D^0 is detected subsequently to a D*+ or D*- decay, and on 34000 events, where only a D^0 or anti D^0 is detected. Kinematic distributions of D*, D and K*_2 are given as a function of their energy E, transverse momentum p_T, energy fraction z, and of the virtual photon variables nu, Q^2 and x_Bj. Semi-inclusive differential D* production cross-sections are compared with theoretical predictions for D* production via photon-gluon fusion into open charm. The total observed production cross-section for D*+/- mesons with laboratory energies between 22 and 86 GeV is 1.9 nb. Significant cross-section asymmetries are observed between D*+ and D*- production for nu0.6., 22 pages, 12 figures and 2 tables

A self-assembled pseudopolyrotaxane consisting of lactoside-displaying cyclodextrin (CD) "beads" threaded onto a linear polyviologen "string" was investigated for its ability to inhibit galectin-1-mediated T-cell agglutination. The CDs of the pseudopolyrotaxane are able to spin around the axis of the polymer chain as well as to move back and forth along its backbone to alter the presentation of its ligand. This supramolecular superstructure incorporates all the advantages of polymeric structures, such as the ability to span large distances, along with a distinctively dynamic presentation of its lactoside ligands to afford a neoglycoconjugate that can adjust to the relative stereochemistries of the lectin's binding sites. The pseudopolyrotaxane exhibited a valency-corrected 10-fold enhancement over native lactose in the agglutination assay, which was greater than the enhancements observed for lactoside-bearing trivalent glycoclusters and a lactoside-bearing chitosan polymer tested using the same assay. The experimental results indicate that supramolecular architectures, such as the pseudopolyrotaxane, provide tools for investigating protein-carbohydrate interactions.

Galectin-1, a mammalian lectin expressed in many tissues, induces death of diverse cell types, including lymphocytes and tumor cells. The galectin-1 T cell death pathway is novel and distinct from other death pathways, including those initiated by Fas and corticosteroids. We have found that galectin-1 binding to human T cell lines triggered rapid translocation of endonuclease G from mitochondria to nuclei. However, endonuclease G nuclear translocation occurred without cytochrome c release from mitochondria, without nuclear translocation of apoptosis inducing factor, and prior to loss of mitochondrial membrane potential. Galectin-1 treatment did not result in caspase activation, nor was death blocked by caspase inhibitors. However, galectin-1 cell death was inhibited by intracellular expression of galectin-3, and galectin-3 expression inhibited the eventual loss of mitochondrial membrane potential. Galectin-1 induced cell death proceeds via a caspase-independent pathway that involves a unique pattern of mitochondrial events, and different galectin family members can coordinately regulate susceptibility to cell death.

Apoptotic elimination of T cells at sites of inflammation or infiltration into tumors limits an effective immune response. T cell apoptosis can be initiated by a variety of triggers, including galectin-1, a soluble, secreted lectin that binds to oligosaccharide ligands on cell surface glycoproteins, or to oligosaccharide ligands on extracellular matrix glycoproteins in tissue stroma. Although galectin-1 has no transmembrane domain and is secreted from cells that make it, it is not clear if galectin-1 functions as a soluble death trigger in vivo. We examined the ability of stromal cells secreting galectin-1 to kill T cells. Although the stromal cells synthesized abundant galectin-1, the majority of the galectin-1 remained bound to the cell surface, and stromal cell-associated galectin-1 killed bound T cells. In contrast, insufficient amounts of functional galectin-1 were released from the stromal cells into the media to kill T cells in the absence of contact with stromal cells. However, when stromal cells were grown on Matrigel, a mixture of extracellular matrix proteins, or on permeable membranes above Matrigel, secreted galectin-1 bound to Matrigel and killed T cells without stromal cell contact. Ten-fold less galectin-1 on Matrigel was sufficient to kill adherent T cells compared with soluble galectin-1. These results demonstrate that galectin-1 in extracellular matrix is able to directly kill susceptible T cells. Because increased galectin-1 deposition in tumor stroma occurs with tumor progression in various types of cancer, galectin-1 in stroma may act locally in the apoptotic elimination of infiltrating T cells during an immune response.

International audience; RICH-1 is a large size RICH detector in operation at the COMPASS experiment since 2001 and recently upgraded implementing a new photon detection system with increased performance.A dedicated software package has been developed to perform RICH-1 data reduction, pattern recognition and particle identification as well as a number of accessory tasks for detector studies.The software package, the algorithms implemented and the detector characterisation and performance are reported in detail.

The concept of “oncofetal antigens” (i.e., biomarkers that are expressed both on normal developing fetal tissue and on human cancer cells) was proposed in the 1960s, before we knew very much about cancer cell heterogeneity or had even conceptualized the cancer stem cell. It is now clear that tumors are indeed composed of very different, genetically distinct subpopulations of cancer cells and that a tiny fraction of those cells, the cancer stem cells, are endowed with the ability to self-renew and to persist and thus can establish new tumors. In PNAS, Cheung et al. (1) identify a specific glycolipid antigen, stage-specific embryonic antigen-3 (SSEA-3), that is preferentially expressed on a small fraction of cultured breast cancer cells that fulfill the definition of cancer stem cells. Importantly, this paper also identifies a single gene product, the β-1,3-galactosyltransferase 5 (β3GalT5) enzyme, that creates a critical domain of this glycolipid antigen (see figure S3 in ref. 1 for the glycolipid structures and the enzymes that create them). Thus, this work demonstrates that this oncofetal antigen is not merely a marker of breast cancer stem cells (BCSCs) but is also critical for survival of these cells.

Graft versus host disease is a significant cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Galectin-1, a mammalian lectin that modulates T cell function and apoptosis, has been shown to be immunomodulatory in animal models of autoimmune disease. We investigated the efficacy of galectin-1 in a murine model of graft versus host disease and found that 68% of galectin-1-treated mice survived, compared to 3% of vehicle-treated mice. Galectin-1-treated animals also had reduced inflammatory infiltrates in tissues compared to animals treated with vehicle alone. Galectin-1 did not affect engraftment of donor hematopoietic cells. However, galectin-1-treated animals demonstrated increased cellularity in bone marrow and spleen with increased numbers of splenic B cells and CD4 T cells compared to those animals treated with vehicle alone. Galectin-1 treatment also significantly improved reconstitution of normal splenic architecture following transplant. Production of type I cytokines interleukin-2 (IL-2) and interferon-gamma was reduced in splenocytes derived from galectin-1-treated transplanted mice when compared to animals treated with vehicle alone, while production of the type II cytokines, IL-4 and IL-10, was similar between the two groups of animals. Although splenocytes from galectin-1-treated transplanted animals responded to both third party antigens and leukemic challenge, host alloreactivity was significantly reduced when compared to cells from vehicle-treated animals. These results demonstrate that galectin-1 therapy is capable of increasing survival and suppressing the graft versus host immune response without compromising engraftment or immune reconstitution following allogeneic hematopoietic stem cell transplant.

COMPASS RICH-1 is a large size gaseous Imaging Cherenkov Detector providing hadron identification in the range from 3 to 55 GeV/c, in the wide acceptance spectrometer of the COMPASS Experiment at CERN SPS. It uses a 3 m long C(4)F(10) radiator, a 21 m(2) large VUV mirror surface and two kinds of photon detectors: MAPMTs and MWPCs with CsI photocathodes, covering a total of 5.5 m(2). It is in operation since 2002 and its performance has increased in time thanks to progressive optimization and mostly to a major upgrade which was implemented in 2006. The main characteristics of COMPASS RICH-1 components are described and some specific aspects related to the radiator gas system, the mirror alignment, the MWPC electrical stability and the readout electronics are discussed. Some key features of the event reconstruction and the PID analysis are presented together with results from the COMPASS RICH-1 performance characterization study. (C) 2010 Elsevier B.V. All rights reserved.

Control of cell death is critical in eukaryotic development, immune system homeostasis, and control of tumorigenesis. The galectin family of lectins is implicated in all of these processes. Other families of molecules function as death receptors or death effectors, but galectins are uniquely capable of acting both extracellularly and intracellularly to control cell death. Extracellularly, galectins cross-link glycan ligands to transduce signals that lead directly to death or that influence other signals regulating cell fate. Intracellular expression of galectins can modulate other signals controlling cell viability. Individual galectins can act on multiple cell types, and multiple galectins can act on the same cell. Understanding how galectins regulate cell viability and function will broaden our knowledge of the roles of galectins in basic biological processes and facilitate development of therapeutic applications for galectins in autoimmunity, transplant-related disease, and cancer.

We have cloned and characterized the first galectin to be identified in Drosophila melanogaster. The amino acid sequence of Drosophila galectin showed striking sequence similarity to invertebrate and vertebrate galectins and contained amino acids that are crucial for binding β-galactoside sugars. Confirming its identity as a galectin family member, the Drosophila galectin bound β-galactoside sugars. Structurally, the Drosophila galectin was a tandem repeat galectin containing two carbohydrate recognition domains connected by a unique peptide link. This divalent structure suggests that like mammalian galectins, Drosophila galectin may mediate cell-cell communication or facilitate cross-linking of receptors to trigger signal transduction events. The Drosophilagalectin was very abundant in embryonic, larval, and adult Drosophila. During embryogenesis, Drosophilagalectin had a unique and specific tissue distribution.Drosophila galectin expression was concentrated in somatic and visceral musculature and in the central nervous system. Similar to other insect lectins, Drosophila galectin may function in both embryogenesis and in host defense. Drosophila galectin was expressed by hemocytes, circulating phagocytic cells, suggesting a role for Drosophila galectin in the innate immune system.

Lymphocytes are covered with sugars. Some of the oligosaccharides on lymphocytes may be recognized by specific lectins such as the selectins, but what other functions do all of these oligosaccharides serve? Two recent papers in Cell (Moody et al., 2001) and Immunity (Daniels et al., 2001) describe a novel role for glycosylation in the thymus—regulating the interaction of MHC class I molecules with CD8 during thymocyte maturation.

As evidenced by the reviews in this special issue of Glycoconjugate Journal, much research is focused on determining functions for mammalian galectins. However, the identification of precise functions for mammalian galectins may be complicated by redundancy in tissue expression and in target cell recognition of the many mammalian galectins. Therefore, lower organisms may be useful in deciphering precise functions for galectins. Unfortunately, some genetically manipulable model systems such as Caenorhabditis elegans may have more galectins than mammals. Recently, galectins were identified in two well-studied insect systems, Drosophila melanogaster and Anopheles gambiae. In addition to the powerful genetic manipulation available in these insect models, there is a sophisticated understanding of many biological processes in these organisms that can be directly compared and applied to mammalian systems. Understanding the roles of galectins in insects may provide insight into precise functions of galectins in mammals.

Leukocyte migration from the bloodstream into tissues, and from tissues to lymph nodes, depends on expression of specific adhesion and signaling molecules by vascular endothelial cells and lymphatic endothelial cells. Tissue damage and microbial infection induce vascular endothelial cells to up-regulate expression of adhesion molecules to facilitate entry of several leukocyte populations from blood into tissues. Many of these cells then leave inflamed tissue and migrate to regional lymph nodes. A critical population that emigrates from inflamed tissue is dendritic cells. Dendritic cells in tissue have to migrate through extracellular matrix and across a layer of lymphatic endothelial cells to enter the lymphatic vasculature. Little is known about the adhesion molecules expressed by lymphatic endothelial cells or the processes required for the critical step of dendritic cell exit from tissues, specifically migration through the extracellular matrix and basal-to-apical migration across the lymphatic endothelial cell layer into lymphatic vasculature.Members of the galectin family of carbohydrate binding proteins are expressed in both vascular and lymphatic endothelial cells. Dynamic changes in galectin expression during inflammation are known to regulate leukocyte tissue entry during inflammation. However, the roles of galectin family members expressed by lymphatic endothelial cells in leukocyte tissue exit remain to be explored.Here, we describe an in vitro transmigration assay that mimics dendritic cell tissue exit in the presence and absence of galectin protein. Fluorescently labeled human dendritic cell migration through extracellular matrix and across human lymphatic endothelial cells is examined in the presence and absence of recombinant human galectin protein.

Leukocyte migration from the bloodstream into tissues, and from tissues to lymph nodes, depends on expression of specific adhesion and signaling molecules by vascular endothelial cells and lymphatic endothelial cells. Tissue damage and microbial infection induce vascular endothelial cells to up-regulate expression of adhesion molecules to facilitate entry of several leukocyte populations from blood into tissues. Many of these cells then leave inflamed tissue and migrate to regional lymph nodes. A critical population that emigrates from inflamed tissue is dendritic cells. Dendritic cells in tissue have to migrate through extracellular matrix and across a layer of lymphatic endothelial cells to enter the lymphatic vasculature. Little is known about the adhesion molecules expressed by lymphatic endothelial cells or the processes required for the critical step of dendritic cell exit from tissues, specifically migration through the extracellular matrix and basal-to-apical migration across the lymphatic endothelial cell layer into lymphatic vasculature.Members of the galectin family of carbohydrate binding proteins are expressed in both vascular and lymphatic endothelial cells. Dynamic changes in galectin expression during inflammation are known to regulate leukocyte tissue entry during inflammation. However, the roles of galectin family members expressed by lymphatic endothelial cells in leukocyte tissue exit remain to be explored.Here, we describe an in vitro transmigration assay that mimics dendritic cell tissue exit in the presence and absence of galectin protein. Fluorescently labeled human dendritic cell migration through extracellular matrix and across human lymphatic endothelial cells is examined in the presence and absence of recombinant human galectin protein.

Microbe–host interactions are complex processes that are directly and indirectly regulated by a variety of factors, including microbe presentation of specific molecular signatures on the microbial surface, as well as host cell presentation of receptors that recognize these pathogen signatures. Cell surface glycans are one important class of microbial signatures that are recognized by a variety of host cell lectins. Host cell lectins that recognize microbial glycans include members of the galectin family of lectins that recognize specific glycan ligands on viruses, bacteria, fungi, and parasites. In this review, we will discuss the ways that the interactions of microbial glycans with host cell galectins positively and negatively regulate pathogen attachment, invasion, and survival, as well as regulate host responses that mitigate microbial pathogenesis.

The COMPASS Collaboration at CERN has investigated the reaction $\pi^- \gamma \rightarrow \pi^-\pi^-\pi^+$ embedded in the Primakoff reaction of $190~\textrm{GeV}$ pions scattering in the Coulomb field of a lead target, $\pi^- \text{Pb} \rightarrow \pi^-\pi^-\pi^+ \text{Pb}$. Exchange of quasi-real photons is selected by isolating the sharp Coulomb peak observed at momentum transfer below $0.001~(\text{GeV}/c)^2$. Using a partial-wave analysis the amplitudes and relative phases of the $a_2(1320)$ and $\pi_2(1670)$ mesons have been extracted, and the Coulomb and the diffractive contributions have been disentangled. Measuring absolute production cross sections we have determined the radiative width of the $a_2(1320)$ to be $\Gamma_0(a_2(1320) \rightarrow \pi\gamma) = (358 \pm 6_{\textrm{stat}} \pm 42_{\textrm{syst}})~\textrm{keV}$. As the first measurement, $\Gamma_0(\pi_2(1670) \rightarrow \pi\gamma) = (181 \pm 11_{\textrm{stat}} \pm 27_{\textrm{syst}})~\textrm{keV} \cdot (\textrm{BR}^{\textrm{PDG}}_{f_2 \pi}/\textrm{BR}_{f_2 \pi})$ is obtained for the radiative width of the $\pi_2(1670)$, where in this analysis the branching ratio $\textrm{BR}^{\textrm{PDG}}_{f_2 \pi}=0.56$ has been used. We compare these values to previous measurements and theoretical predictions., Comment: 27 pages, 12 figures and 3 tables

Galectin-1, an endogenous lectin expressed in lymphoid organs and immune-privileged sites, induces death of human and murine thymocytes and T cells. Galectin-1 binds to several glycoproteins on the T cell surface, including CD7. However, the T cell surface glycoprotein receptors responsible for delivering the galectin-1 death signal have not been identified. We show that CD7 is required for galectin-1-mediated death. This demonstrates a novel function for CD7 as a death trigger and identifies galectin-1/CD7 as a new biologic death signaling pair.

Galectin-1 induces apoptosis of immature thymocytes and activated T cells, suggesting that galectin-1 regulates cell death in the thymus during selection and in the periphery following an immune response. Although it is known that galectin-1 recognizes lactosamine (Gal-GlcNAc) as a minimal ligand, this disaccharide is ubiquitously expressed on a variety of cell surface glycoproteins. Thus, susceptibility to galectin-1 may be regulated by the presentation of lactosamine on specific oligosaccharide structures created by specific glycosyltransferase enzymes. The core 2 beta-1, 6-N-acetylglucosaminyltransferase (core 2 GnT) creates a branched structure on O-glycans that can be elongated to present multiple lactosamine sequences. In the thymus, the core 2 GnT is expressed in galectin-1-sensitive thymocyte subsets. In the periphery, an oligosaccharide epitope created by the core 2 GnT is expressed on galectin-1-sensitive activated T-cells. In this report, we demonstrate that expression of the core 2 GnT was necessary and sufficient for galectin-1-induced death of murine T cell lines. In addition, overexpression of the core 2 GnT in mice increased the susceptibility of double positive thymocytes to galectin-1. These data demonstrate that expression of a specific glycosyltransferase can control susceptibility to galectin-1, suggesting that developmentally regulated glycosyltransferase expression may be a mechanism to modulate cell death during T cell development and function.

A broad range of disorders can cause inflammation of the thyroid gland. True thyroid infections are rare and can result from a variety of microorganisms, of which bacteria are the most common. Other rarer pathogens include fungi, parasites, and viruses. Gram-positive bacteria, especially staphylococci, predominate as causative agents in adults and children. In immunocompromised patients, opportunistic pathogens have been isolated. Most infections in adults occur as a result of hematogenous or lymphatic seeding of the thyroid gland. In children, congenital anomalies can lead to thyroid infection and require surgical correction to prevent recurrence. Fine-needle aspiration of the thyroid is usually required to identify the infecting agent, and prolonged antimicrobial therapy with or without surgical drainage is the cornerstone of management. This review outlines the pathogenesis, microbiology, diagnosis, and management of infectious thyroiditis in adults and children and compares this disorder with other, more common causes of thyroid inflammation.

Background : the BARRIERS to research utilization scale was developed in the US almost a decade ago (Funk et al. 1991). Since then it has been used in several countries with different, relatively small groups of nurses in different settings. The work reported here is a sub-section of a larger survey of more than 2000 nurses working in acute and community settings in Yorkshire. Results for the hospital-based nurses only are presented here. Aim : the aim of the study was to produce a general picture of the main barriers to the implementation of research findings as reported by hospital nurses and to explore sub-samples in order to identify similarities and differences between them. Method : a census survey of nurses from two hospital trusts was undertaken. The BARRIERS questionnaire was sent by mail to 1984 nurses, with a response rate of 36% ( n =712). Results : the greatest area of concern focused on resources. This included time and facilities for implementation and cooperation from colleagues, in particular medical colleagues. Inadequate authority to make changes and incomprehensible statistical analyses were also major barriers. Night nurses and older nurses reported greater difficulties with the accessibility of research and had more negative views of the benefits of research for practice. Conclusions : the provision of time, facilities and peer support appeared to be needed, in keeping with other UK-based studies of hospital nurses using the BARRIERS scale. Nurses needed authority to make changes to practice. Furthermore, there was a need for training to improve nurses’ understanding of statistics, as well as statistics being presented more clearly and with greater explanation. The current drive for evidence-based practice makes the use of an instrument such as the BARRIERS scale to measure the progress of nurses with research implementation highly desirable.

Galectin-1 induces apoptosis of human thymocytes and activated T cells by an unknown mechanism. Apoptosis is a novel function for a mammalian lectin; moreover, given the ubiquitous distribution of the oligosaccharide ligand recognized by galectin-1, it is not clear how susceptibility to and signaling by galectin-1 is regulated. We have determined that galectin-1 binds to a restricted set of T cell surface glycoproteins, and that only CD45, CD43, and CD7 appear to directly participate in galectin-1-induced apoptosis. To determine whether these specific glycoproteins interact cooperatively or independently to deliver the galectin-1 death signal, we examined the cell surface localization of CD45, CD43, CD7, and CD3 after galectin-1 binding to human T cell lines and human thymocytes. We found that galectin-1 binding resulted in a dramatic redistribution of these glycoproteins into segregated membrane microdomains on the cell surface. CD45 and CD3 colocalized on large islands on apoptotic blebs protruding from the cell surface. These islands also included externalized phosphatidylserine. In addition, the exposure of phosphatidylserine on the surface of galectin-1-treated cells occurred very rapidly. CD7 and CD43 colocalized in small patches away from the membrane blebs, which excluded externalized phosphatidylserine. Receptor segregation was not seen on cells that did not die in response to galectin-1, including mature thymocytes, suggesting that spatial redistribution of receptors into specific microdomains is required for triggering apoptosis.

Galectin-1 is an endogenous lectin expressed by thymic and lymph node stromal cells at sites of Ag presentation and T cell death during normal development. It is known to have immunomodulatory activity in vivo and can induce apoptosis in thymocytes and activated T cells (1–3). Here we demonstrate that galectin-1 stimulation cooperates with TCR engagement to induce apoptosis, but antagonizes TCR-induced IL-2 production and proliferation in a murine T cell hybridoma and freshly isolated mouse thymocytes, respectively. Although CD4+CD8+ double positive cells are the primary thymic subpopulation susceptible to galectin-1 treatment alone, concomitant CD3 engagement and galectin-1 stimulation broaden susceptible thymocyte subpopulations to include a subset of each CD4−CD8−, CD4+CD8+, CD4−CD8+, and CD4+CD8− subpopulations. Furthermore, CD3 engagement cooperates with suboptimal galectin-1 stimulation to enhance cell death in the CD4+CD8+ subpopulation. Galectin-1 stimulation is shown to synergize with TCR engagement to dramatically and specifically enhance extracellular signal-regulated kinase-2 (ERK-2) activation, though it does not uniformly enhance TCR-induced tyrosine phosphorylation. Unlike TCR-induced IL-2 production, TCR/galectin-1-induced apoptosis is not modulated by the expression of kinase inactive or constitutively activated Lck. These data support a role for galectin-1 as a potent modulator of TCR signals and functions and indicate that individual TCR-induced signals can be independently modulated to specifically affect distinct TCR functions.

Thyroid hormone stimulates renal proximal tubule NaCl and NaHCO3absorption in part by activating the apical membrane Na/H exchanger NHE3. We used a renal epithelial cell line, the opossum kidney (OK) cell, to define the mechanism by which 3,5,3′-triiodothyronine (T3) increases NHE3 activity. T3stimulated NHE3 activity, an effect that was blocked by inhibition of cellular transcription or translation. The increase in activity was associated with increases in steady-state cell surface and total cellular NHE3 protein and NHE3 transcript abundance. T3stimulated transcription of the NHE3 gene and had no effect on NHE3 transcript stability. The transcriptional activity of the 5′-flanking region of the rat NHE3 gene was stimulated by T3when expressed in OK cells. When heterologously expressed rat NHE3 transcript levels were clamped constant with a constitutive promoter in OK cells, T3has no effect on rat NHE3 protein abundance, suggesting the absence of regulation of NHE3 protein stability or translation. These studies demonstrate that T3stimulates NHE3 activity by activating NHE3 gene transcription and increasing NHE3 transcript and protein abundance.

The 2006 Annual Meeting of the Society for Glycobiology was held in Los Angeles, California, November 15–19, 2006. The meeting attracted over 450 participants from North and South America, Europe, ...

Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics. Here we demonstrate a structural basis for this hypothesis. Cell surface receptors for both human and avian influenza viruses were identified in the pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Surprisingly, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility of their direct transmission to human populations. These findings help to explain the emergence of pandemic influenza viruses and support the need for continued surveillance of swine for viruses carrying avian virus genes.

Lectins, or carbohydrate binding proteins, recognize specific oligosaccharide structures on glycoproteins and glycolipids. Several families of animal lectins have been identified; for some of these lectins, functions such as leukocyte adhesion and microbial opsonization have been described. The galectins are a family of lectins found in species ranging from sponges and nematodes to humans. Members of the galectin family have been proposed to mediate cell adhesion, to regulate cell growth, and to trigger or inhibit apoptosis. The expression pattern of different galectins changes during development, and this pattern is also altered at sites of inflammation and in breast, colon, prostate, and thyroid carcinomas. In addition, the level of expression of some galectins by tumor cells has been shown to be correlated with metastatic potential. The mechanisms by which galectins exert these diverse effects remain largely unknown. Some glycoprotein counterreceptors recognized by certain galectins have been identified; this is an important first step in understanding the cell-type specific effects of different galectins. This review discusses the way in which the modulation of galectin activity may affect strategies for treatment of a variety of human diseases, including autoimmunity and cancer.

The characterization of invisible hydrocarbon micro-seepage intensities in surface sediments is used to evaluate subsurface hydrocarbon potential. A cost-effective multidisciplinary surface prospecting method, termed "BIG", is employed as a supplementary instrument to conventional exploration tools to assess the remaining prospectivity of a licence tract in the Dutch North Sea. Microbial investigations, molecular and isotopic gas characterization as well as UV fluorescence measurements are utilized for direct hydrocarbon detection in surface sediments. The definition and distribution of anomalous intensities is used as an index for the hydrocarbon potential in the deeper sub-surface. In combination with seismic information the BIG method can help to reduce exploration risk. It proves to be an effective instrument to determine the lateral extent of liquid hydrocarbon migration and to localize areas of prospective potential. This case history covers a successful application of the BIG method to investigate undetected hydrocarbon potential in an established producing province.

The muon-proton and muon-deuteron inclusive deep inelastic scattering cross sections were measured in the kinematic range 0.002 < x < 0.60 and 0.5 < Q(2) < 75 GeV2 at incident muon energies of 90, 120, 200 and 280 GeV. These results are based on the full data set collected by the New Muon Collaboration, including the data taken with a small angle trigger. The extracted values of the structure functions F-2(p) and F-2(d) are in good agreement with those from other experiments. The data cover a sufficient range of y to allow the determination of the ratio of the longitudinally to transversely polarised virtual photon absorption cross sections, R = sigma(L)/sigma(T), for 0.002 < x < 0.12. The values of R are compatible with a perturbative QCD prediction; they agree with earlier measurements and extend to smaller x.

ガレクチン-1は、β-ガラクトシド結合タンパク質がつくるガレクチン家系の一構成員で、多くの正常細胞や癌細胞で産生されている。ガレクチン-1は、たとえば細胞と細胞の相互作用の仲介、細胞増殖に対する影響など多くの機能を持つことが示されている。最近、我々はガレクチン-1の新たな機能として、T細胞のアポトーシスにおける伝達物質としての作用を明らかにした。アポトーシスは、胸腺における免疫適格 (immunocompetent) なT細胞の産生と、末梢リンパ系器官での免疫応答の終結になくてはならない重要な機構である。ガレクチン-1は免疫系の組織としてのヒト胸腺、リンパ節、脾臓に発現している。これらリンパ系器官内にガレクチン-1が存在すること、および胸腺細胞や活性化T細胞のアポトーシスを誘導することは、ガレクチン-1が中枢や末梢部位で自己抗原に対する免疫寛容の維持に重要な役割を果たしていることを示唆する。ガレクチン-1に対するT細胞の感受性は、ガレクチン-1のカウンターレセプターとなる細胞表層糖タンパク質の発現を制御することで調節されていると考えられる。CD45もそのようなカウンターレセプターのひとつで、ガレクチン-1が誘導するアポトーシスの不可欠な引き金になっているようだ。しかし、T細胞のガレクチン-1に対する感受性は、CD45の糖鎖付加の状態や、CD43のような他のカウンターレセプターの存在によっても調節されているらしい。またガレクチン-1は、非リンパ系器官における免疫系の制御でも重要な役割を持つと考えられる。ガレクチン-1は胎盤、前立腺、角膜など多くの免疫特権的 (immune priviledged) 部位や組織で発現されている。免疫特権部位、および組織というのは、たとえば角膜などのような重要な器官が、活性化T細胞による炎症反応で損傷されることのないように、免疫反応がやわらげられている生体内部位のことである。アポトーシスは免疫特権を維持するために不可欠な機構であることが示されている。免疫特権的組織でガレクチン-1が発現されることによって、侵入してくる活性化T細胞のアポトーシスが誘導され、その結果免疫特権が維持されると考えられる。我々は、上記リンパ系器官と免疫特権的部位でガレクチン-1が発現されているのは、免疫反応の調節を行う上で重要な役割を果たしているから、という仮説を提唱する。

Galectin-1, a β-galactoside binding protein, is produced by thymic epithelial cells and binds to human thymocytes. We have previously reported that galectin-1 induces the apoptosis of activated T lymphocytes. Because the majority of thymocytes die via apoptosis while still within the thymus, we tested whether galectin-1 could induce the apoptosis of these cells. We now report that in vitro exposure to galectin-1 induced apoptosis of two subsets of CD4lo CD8lo thymocytes. The phenotypes of susceptible thymocytes were consistent with that of both negatively selected and nonselected cells. Galectin-1–induced apoptosis was enhanced by preexposure of thymocytes to antibody to CD3, suggesting that galectin-1 may be a participant in T-cell– receptor mediated apoptosis. In contrast, pretreatment of thymocytes with dexamethasone had no effect on galectin-1 susceptibility. We noted that 71% of the cells undergoing apoptosis after galectin-1 treatment had a DNA content greater than 2N, indicating that proliferating thymocytes were most sensitive to galectin-1. We propose that galectin-1 plays a role in the apoptosis of both negatively selected and nonselected thymocytes, and that the susceptibility of thymocytes to galectin-1 is regulated, in part, by entry or exit from the cell cycle.

Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. Sarcospan facilitates interactions between the adhesion glycoprotein complexes, dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin, which protect the sarcolemma during muscle contraction. Over-expression of sarcospan ameliorates dystrophic pathology in mdx muscle by upregulating integrins and the utrophin-glycoprotein complex, Akt phosphorylation, and glycosylation of the dystroglycans. These mechanisms result in stabilization of the sarcolemmal membrane by restoring connections to laminin. © 2013 FEBS.

Aim:Accumulating evidence suggests that extracellular galectin-1 and galectin-3 promote angiogenesis. Increased expression of galectin-1 and/or galectin-3 has been reported to be associated with tumour progression. Thus, it is critical to identify their influence on angiogenesis.Methods:We examined the individual and combined effects of galectin-1 and galectin-3 on endothelial cell (EC) growth and tube formation using two EC lines, EA.hy926 and HUVEC. The activation of vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) was determined by ELISA and Western blots. We evaluated the VEGFR1 and VEGFR2 levels in endosomes by proximity ligation assay.Results:We observed different responses to exogenous galectins depending on the EC line. An enhanced effect on EA.hy926 cell growth and tube formation was observed when both galectins were added together. Focusing on this enhanced effect, we observed that together galectins induced the phosphorylation of both VEGFR1 and VEGFR2, whereas galectin-1 and -3 alone induced VEGFR2 phosphorylation only. In the same way, the addition of a blocking VEGFR1 antibody completely abolished the increase in tube formation induced by the combined addition of both galectins. In contrast, the addition of a blocking VEGFR2 antibody only partially inhibited this effect. Finally, the addition of both galectins induced a decrease in the VEGFR1 and VEGFR2 endocytic pools, with a significantly enhanced effect on the VEGFR1 endocytic pool. These results suggest that the combined action of galectin-1 and galectin-3 has an enhanced effect on angiogenesis via VEGFR1 activation, which could be related to a decrease in receptor endocytosis. © 2013 D'Haene et al., SCOPUS: ar.j, info:eu-repo/semantics/published

The Q(2) dependence of the structure function ratio F-2(Sn)/F-2(C) for 0.01 < x < 0.75 and 1 < Q(2) < 140 GeV2 is reported. For x < 0.1 the size of shadowing decreases linearly with In Q(2) and the maximum rate is about 0.04 at x = 0.01. The rate decreases with x and is compatible with zero for x greater than or equal to 0.1. The difference R(Sn) - R(C), where R is the ratio of longitudinally to transversely polarised virtual photon absorption cross sections, is also given. No dependence on x is seen and the average value is 0.040 +/- 0.021 (stat.) +/- 0.026 (syst.) at a mean Q(2) of 10 GeV2.

Galectin-1, a member of a family of carbohydrate binding proteins, is synthesized by thymic epithelial cells in normal juvenile thymus, and mediates adhesion of immature T cells to thymic epithelium. Because cell adhesion molecules are proposed to play a role in the thymic hyperplasia and neoplasia seen in the autoimmune disease myasthenia gravis, we examined the expression of galectin-1 in myasthenic thymi. We detected abundant galectin-1 expression in thymic epithelial cells in 27 hyperplastic and neoplastic thymi from patients with myasthenia gravis. Primary cultures of neoplastic epithelial cells from a thymoma continued to express galectin-1, and bound immature T cells; T cell binding was inhibited by the addition of the beta-galactosides lactose and thiodigalactoside, suggesting that galectin-1 on the thymoma cells and a saccharide ligand on the T cells participated in cell-cell adhesion. Expression of galectin-1 by thymic epithelial cells may play a role in the thymic pathology seen in myasthenia gravis.

T cell surface sialylation changes during maturation in the thymus. We have previously demonstrated increased expression of mRNA encoding the Galβ1, 3GalNAc α2,3-sialyltransferase in mature medullary human thymocytes, compared with immature cortical thymocytes. For this enzyme, increased expression of transferase mRNA correlated with increased sialylation of O-glycans. We have now examined the pattern of expression in the human thymus of two additional sialyltransferases, the Galβ1,4GlcNAc α2,6-sialyltransferase (ST6N) and the Galβ1,3/4GlcNAc α2,3-sialyltransferase (ST3N). The patterns of mRNA expression were compared with the pattern of binding of two sialic acid-specific plant lectins, Sambucus nigra agglutinin and Maackia amurensis agglutinin, which preferentially recognize α2,6- and α2,3-linked sialic acids, respectively, on N-glycans. By in situ hybridization, mRNA encoding ST3N was detected uniformly throughout the thymus. All thymocytes bound M. amurensis agglutinin, demonstrating a direct correlation between the level of ST3N mRNA expression and cell-surface glycosylation. In contrast, mRNA encoding ST6N was also expressed uniformly throughout the thymus; however, only mature (CD3hi) medullary thymocytes bound S. nigra agglutinin. On mature thymocytes, S. nigra agglutinin appeared to bind primarily to the cell-surface glycoprotein CD45; since only the mature thymocytes expressed the CD45RA isoform, while both mature and immature populations expressed the CD45R0 isoform, CD45RA may be a preferred substrate for ST6N. These results demonstrate that glycoprotein sialylation is tightly regulated during T cell development and that the developmentally regulated expression of specific oligosaccharide structures on the cell surface may be influenced by expression of both the relevant glycosyltransferase and specific acceptor substrates.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and an aggressive malignancy. Galectin-3 (gal-3), the only antiapoptotic member of the galectin family, is overexpressed in DLBCL. While gal-3 can localize to intracellular sites, gal-3 is secreted by DLBCL cells and binds back to the cell surface in a carbohydrate-dependent manner. The major counterreceptor for gal-3 on DLBCL cells was identified as the transmembrane tyrosine phosphatase CD45. Removal of cell-surface gal-3 from CD45 with the polyvalent glycan inhibitor GCS-100 rendered DLBCL cells susceptible to chemotherapeutic agents. Binding of gal-3 to CD45 modulated tyrosine phosphatase activity; removal of endogenous cell-surface gal-3 from CD45 with GCS-100 increased phosphatase activity, while addition of exogenous gal-3 reduced phosphatase activity. Moreover, the increased susceptibility of DLBCL cells to chemotherapeutic agents after removal of gal-3 by GCS-100 required CD45 phosphatase activity. Gal-3 binding to a subset of highly glycosylated CD45 glycoforms was regulated by the C2GnT-1 glycosyltransferase, indicating that specific glycosylation of CD45 is important for regulation of gal-3–mediated signaling. These data identify a novel role for cell-surface gal-3 and CD45 in DLBCL survival and suggest novel therapeutic targets to sensitize DLBCL cells to death.

Galectin-1, a member of the family of beta-galactoside binding proteins, has growth regulatory and immunomodulatory activities. We report here that galectin-1, expressed by stromal cells in human thymus and lymph nodes, is present at sites of cell death by apoptosis during normal T-cell development and maturation. Galectin-1 induced apoptosis of activated human T cells and human T leukaemia cell lines. Resting T cells also bound galectin-1, but did not undergo apoptosis. Human endothelial cells that expressed galectin-1 induced apoptosis of bound T cells. Galectin-1-induced apoptosis required expression of CD45, and was decreased when N-glycan elongation was blocked by treatment of the cells by swainsonine, whereas inhibition of O-glycan elongation potentiated the apoptotic effect of galectin-1. Induction of apoptosis by an endogenous mammalian lectin represents a new mechanism for regulating the immune response.

We have carried out numerical simulations to investigate roughening on4He crystal surfaces. Algorithms were constructed for an h.c.p. crystal, incorporating van-der-Waals interatomic interactions. The Wulff plot was calculated at 0 K. Also, by sectioning the crystal in several symmetry directions, roughening temperatures, TR, have been calculated for these orientations using a lattice-gas model. In particular, these have been determined for thec, a ands facets, as well as for lower-symmetry facets which involve interactions between higher-than-nearest-neighbours. On one of these facets, we have observed the formation of anisotropic clusters below a certain critical temperature. The values for the high-symmetry facets are more precise but in broad agreement with those calculated by Touzani and Wortis1 and do not agree particularly well with the observed values. We are therefore investigating quantum corrections to the calculations.

We present a re-evaluation of the structure function ratios F2(He)/F2(D), F2(C)/F2(D) and F2(Ca)/F2(D) measured in deep inelastic muon-nucleus scattering at an incident muon momentum of 200 GeV. We also present the ratios F2(C)/F2(Li), F2(Ca)/F2(Li) and F2(Ca)/F2(C) measured at 90 GeV. The results are based on data already published by NMC; the main difference in the analysis is a correction for the masses of the deuterium targets and an improvement in the radiative corrections. The kinematic range covered is 0.0035 < x < 0.65, 0.5 < Q~2

The D-dimer assay is a rapid latex agglutination assay that detects specific cross-linked fibrin fragments resulting from plasmin-mediated fibrinolysis. When we introduced the D-dimer assay at our institution, clinicians began to order both D-dimer and conventional fibrin degradation products assays to evaluate patients with disseminated intravascular coagulation. Because this pattern of laboratory test use appeared to generate redundant clinical information, we instituted a test-ordering algorithm that uses the D-dimer assay as a screening test, and reserves the fibrin degradation products assay for specific cases. After establishing this policy, we examined test-ordering patterns during the next 6 months and found excellent clinician compliance with the policy. The use of a test-ordering algorithm increased laboratory efficiency, conserved laboratory resources, and eliminated redundant testing.

The pattern of expression of an endogenous lectin, galectin-1, was examined in human lymphoid tissue. Galectin-1 was detected in the endothelial cells lining specialized vessels, termed high endothelial venules, in activated lymphoid tissue, but not in a resting lymph node. Cultured endothelial cells (human aortic and umbilical vein endothelial cells (HAECs and HUVECs)) expressed galectin-1. Activation of the cultured endothelial cells increased the level of galectin-1 expression, as determined by ELISA. Northern blot analysis and high throughput cDNA sequencing. These results suggest that galectin-1 expressed by endothelial cells may bind to and affect the trafficking of cells emigrating from blood into tissues.

The COMPASS collaboration at CERN has investigated the \pi^- \gamma -> \pi^- \pi^- \pi^+ reaction at center-of-momentum energy below five pion masses, sqrt(s) < 5 m(\pi), embedded in the Primakoff reaction of 190 GeV pions impinging on a lead target. Exchange of quasi-real photons is selected by isolating the sharp Coulomb peak observed at smallest momentum transfers, t' < 0.001 (GeV/c)^2. Using partial-wave analysis techniques, the scattering intensity of Coulomb production described in terms of chiral dynamics and its dependence on the 3\pi-invariant mass m(3\pi) = sqrt(s) were extracted. The absolute cross section was determined in seven bins of $\sqrt{s}$ with an overall precision of 20%. At leading order, the result is found to be in good agreement with the prediction of chiral perturbation theory over the whole energy range investigated.

Exclusive ϱ 0 and φ muoproduction on deuterium, carbon and calcium has been studied in the kinematic range 2 Q 2 2 and 40 Q 2 dependence of the cross sections, the transverse momentum distributions for the vector mesons, the decay angular distributions and, in the case of the ϱ 0 , nuclear effects. The data for 0 production are compatible with a diffractive mechanism. The distinct features of φ production are a smaller cross section and less steep p t 2 distributions than those for the 0 mesons.

Quasielastic production of J / ψ mesons has been measured in muon interactions with hydrogen, deuterium, carbon and tin targets at incident muon energies of 200 and 280 GeV. The hydrogen and deuterium data were used to study the transverse momentum distribution of the J / ψ 's. These data have been analysed together with previously published ϱ 0 data in the framework of the vector meson dominance model. The radii of the Jψ and the ϱ 0 as well as the total J / ψ - N and ϱ 0 - N cross sections were deduced. From the tin and carbon data the ratio of the quasielastic J / ψ production cross sections, R qe (Sn/C), has been extracted and found to be less than unity. In the Glauber approach this suppression can be related to the J / ψ absorption probability in nuclei. The suppression is also compared to those predicted by various colour transparency models.