bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural Features of Proteins Responsible for Resistance of Tryptophan Residues to Nitrosylation
Authors: Suntsova Tatiana P. , Beda Nataliya V. , Nedospasov Andrei A. 
Published: September 2003

AbstractIt is known that potentially reactive groups of the protein molecule may be most efficiently nitros(yl)ated only when located within hydrophobic globules or built into the membrane. N 1 ‐nitrosotryptophan (NOW) is a stable product of nitrosation in vitro. However, the NOW fraction in proteins is small in ordinary proteins. It suggests the existence of unknown mechanisms preventing the accumulation of NOW. Here we show that these mechanisms are underlain by the protein structure. Analysis of protein structure databases to explore the atomic surroundings of tryptophan residues revealed preferential selection of certain surroundings. N(E) atoms of tryptophan residues, which are the targets for nitrosation, have usually polar and nucleophilic groups in their environment. Residues of Asp, Glu, Cys, His, and Met act as catalysts of denitrosation (internal denitrosilase). We found that short peptides with the same residues possessed denitrosilase activity even in solution. This selection might explain both the resistance of tryptophan residues in proteins to nitrosation and the mechanisms of chemical communication by means of reversible nitrosation of proteins.
The Energetics of Ion Distribution: The Origin of the Resting Electric Potential of Cells
Authors: Veech Richard L. , Kashiwaya Yoshihiro , Gates Denise N. , King M. Todd , Clarke Kieran 
Published: September 2003

AbstractThe relation between the energies of ion movement and ATP hydrolysis is unknown in tissues with widely varying electric potentials. Consequently, we measured the concentration of the nine major inorganic ions in the extra‐ and intracellular phases in heart, liver, and red cells with resting electrical potentials, E N, of ‐86, ‐28, and ‐6 mV, respectively, under six different physiological conditions. We calculated the Nernst electric potential and the energy of ion movement between the phases. We found that the energy of ATP hydrolysis was essentially constant, between ‐54 and ‐58 kJ/mol, in all tissues and conditions. In contrast, as E N decreased, the energies of the Na + and K + gradients decreased, with slopes approximating their valence. The difference between the energies of Na + and K + gradients remained constant at 17 kJ/mol, which is approximately one third of the energy of ATP hydrolysis, demonstrating near‐equilibrium of the Na +/K + ATPase in all tissues under all conditions. All cations, except K +, were pumped out of cells and all anions, except Cl ‐ in liver and red cell, were pumped into cells. We conclude that the energy of ATP was expressed in Na +/K + ATPase and its linked inorganic ion transporters to create a Gibbs‐Donnan near‐equilibrium system, an inherent part of which was the electric potential.
Effects of Epidermal Growth Factor and Linoleic Acid on Lipid Contents in Human Intestinal C2BBe1 Cells
Authors: Liang Chiu‐Fang , Chao Jane C. ‐J. , Hwang Shiaw‐Min , Tsai Ya‐Hui 
Published: September 2003

AbstractEpidermal growth factor (EGF) was reported to regulate triacyl glycerol synthesis in various cells. Linoleic acid and its metabolites were thought to modulate the signal transduction of growth factors. This study determined whether linoleic acid regulated the effect of EGF on lipid contents in human intestinal C2BBe1 cells. Confluent cells were incubated with serum‐free medium (control), EGF (45 ng/mL), linoleic acid (42 μg/mL), or combined EGF (45 ng/mL) and linoleic acid (42 μg/mL) for 48 h. The results showed EGF and linoleic acid significantly increased intracellular cholesterol and triglyceride levels compared with the control and combined groups. EGF was a more potent stimulator for triacyl glycerol synthesis in C2BBe1 cells than linoleic acid. However, intracellular cholesterol and triglyceride levels did not differ between the control and combined groups. The secretion of cholesterol and triglyceride into the medium by C2BBe1 cells did not differ among four groups. Both EGF and linoleic acid strongly stimulated the expression of EGF receptor mRNA in C2BBe1 cells at 48 h compared with the control and combined groups. Therefore, EGF and linoleic acid increased triacyl glycerol synthesis in C2BBe1 cells through stimulating the expression of EGF receptor mRNA. The effect of EGF and linoleic acid on this lipogenesis was reversed in the presence of both EGF and linoleic acid by downregulating the expression of EGF receptor mRNA.
RNA‐Binding Proteins That Target the Androgen Receptor mRNA
Authors: Wilce Jackie A. , Leedman Peter J. , Wilce Matthew C. J. 
Published: September 2003

AbstractRecent efforts to elucidate mechanisms of posttranscriptional gene regulation have resulted in the description of both cis ‐ and trans ‐acting factors which affect the stability and translational efficiency of specific mRNAs. Here we summarise some of the concepts in this field, with particular attention to recently discovered protein/RNA interactions involving the human androgen receptor mRNA. Such systems are of interest for their potential as targets for the modulation of protein production.
Degradation of mRNA in Escherichia coli
Authors: Jain Chaitanya 
Published: September 2003

AbstractDegradation of messenger RNAs (mRNAs) is a universal process that occurs in every cell and has important implications for nucleotide metabolism and gene expression. One organism in which mRNA degradation has been thoroughly studied is the bacterium Escherichia coli ( E. coli ). In this review I describe what is presently known about the different processes involved in the conversion of mRNAs from high molecular weight species to mononucleotides in E. coli . The ribonucleases and accessory factors involved in mRNA degradation, and features on mRNAs that make them resistant or sensitive to degradation will also be described. At the conclusion of this review, some of the anticipated directions of future research on this topic will be discussed.
Insect Inhibitors of Metalloproteinases
Authors: Vilcinskas Andreas , Wedde Marianne 
Published: September 2003

AbstractTwo types of peptidic metalloproteinase inhibitors have recently been identified in insects. A homologue of vertebrate tissue inhibitors of metalloproteinases (TIMPs) was found in the fruitfly Drosophila melanogaster which may contributes to regulation of a corresponding matrix metalloproteinase (MMP). The first member of MMPs from insects which shares similarity with vertebrate MMPs has also been cloned and characterized from Drosophila, suggesting conserved evolution of both MMPs and TIMPs. The first insect inhibitor of metalloproteinases (IMPI), which was identified in larvae of the greater wax moth, Galleria mellonella, shares no sequence similarity with known vertebrate or invertebrate proteins and represents the first non‐TIMP‐like inhibitor of metalloproteinases reported to date. In contrast to TIMPs, the IMPI is not active against MMPs but inhibits microbial metalloproteinases such as bacterial thermolysin. Insects may recognize such toxic metalloproteinases associated with invading pathogens by particular peptidic fragments that result from their nonregulated activity within the hemolymph. Metalloproteinases induce expression of the IMPI along with other antimicrobial proteins in course of humoral immune response of G. mellonella, thereby mediating regulation of metalloproteinase activity released within the hemolymph and inhibition of pathogen development as well.
The Geometry of Singular Quaternionic Kähler Quotients
Authors: Dancer Andrew , Swann Andrew 
Published: September 2003

Two descriptions of quaternionic Kähler quotients by proper group actions are given: the first as a union of smooth manifolds, some of which come equipped with quaternionic Kähler or locally Kähler structures; the second as a union of quaternionic Kähler orbifolds. In particular the quotient always has an open set which is a smooth quaternionic Kähler manifold. When the original manifold and the group are compact, we describe a length space structure on the quotient. Similar descriptions of singular hyperKähler and 3-Sasakian quotients are given.
INVARIANT KINEMATICS ON A ONE-DIMENSIONAL LATTICE IN NONCOMMUTATIVE GEOMETRY
Authors: ATZMON E. 
Published: September 2003

In a one-dimensional lattice, the induced metric (from a noncommutative geometry calculation) breaks translation invariance. This leads to some inconsistencies among different spectator frames, in the observation of the hoppings of a test particle between lattice sites. To resolve the inconsistencies between the different spectator frames, we replace the test particle's bare mass by an effective locally dependent mass. This effective mass also depends on the lattice constant — i.e. it a scale dependent variable (a "running" mass). We also develop an alternative approach based on a compensating potential. The induced potential between a spectator frame and the test particle is attractive on the average. We then show that the entire formalism holds for a quantum particle represented by a wave function, just as it applies to the mechanics of a classical point particle.
SPECTRAL GEOMETRY AND CAUSALITY
Authors: KOPF TOMÁŠ 
Published: September 2003

For a physical interpretation of a theory of quantum gravity, it is necessary to recover classical space–time, at least approximately. However, quantum gravity may eventually provide classical space–times by giving spectral data similar to those appearing in noncommutative geometry, rather than by giving directly a space–time manifold. It is shown that a globally hyperbolic Lorentzian manifold can be given by spectral data. A new phenomenon in the context of spectral geometry is observed: causal relationships. The employment of the causal relationships of spectral data is shown to lead to a highly efficient description of Lorentzian manifolds, indicating the possible usefulness of this approach. Connections to free quantum field theory are discussed for both motivation and physical interpretation. It is conjectured that the necessary spectral data can be generically obtained from an effective field theory having the fundamental structures of generalized quantum mechanics: a decoherence functional and a choice of histories.
Magnitude of HDL Cholesterol Variation After High-Dose Atorvastatin Is Genetically Determined at the LDL Receptor Locus in Patients With Homozygous Familial Hypercholesterolemia
Authors: Sposito Andrei C. , Gonbert Sophie , Bruckert Eric , Atassi Marielle , Beucler Isabel , Amsellem Sabine , Khallouf Oumayma , Benlian Pascale , Turpin Gerard 
Published: September 2003

Objective—The combination of LDL apheresis with high doses of a potent hepatic hydroxymethylglutaryl coenzyme A reductase inhibitor, such as atorvastatin, has been the best therapy available for the prevention of cardiovascular disease in patients with homozygous familial hypercholesterolemia (HFH). However, some concerns have been made about the effect of atorvastatin on HDL cholesterol levels in these patients.Methods and Results—HDL cholesterol levels were determined bimonthly over the course of 2 years of treatment with high-dose atorvastatin in genotypically defined HFH patients either receptor-defective (n=6) or receptor-negative (n=6) under long-term treatment with LDL apheresis. We additionally stratified the atorvastatin effect on HDL cholesterol according to the genotype as an indicator of residual in vivo LDL receptor activity. Our findings indicate that (1) an early and transitory reduction of plasma HDL cholesterol levels occurs during the first 4 weeks of atorvastatin treatment; (2) the degree of the transient HDL reduction is higher in receptor-negative than in receptor-defective patients (−21±11 versus −10±4%;P=0.01); and (3) after long-term treatment, HDL cholesterol concentration remains higher in receptor-defective than receptor-negative patients (P=0.026).Conclusions—The present study reveals that HDL cholesterol reduction after high-dose atorvastatin is an early and transient event in HFH patients which magnitude depends on the presence of a residual LDL-R activity.
IL-13 production by donor T cells is prognostic of acute graft-versus-host disease following unrelated donor stem cell transplantation
Authors: Jordan William J. , Brookes Paul A. , Szydlo Richard M. , Goldman John M. , Lechler Robert I. , Ritter Mary A. 
Published: September 2003

AbstractDespite the success of human leukocyte antigen (HLA) typing in allogeneic stem cell transplantation (SCT) it is rare to find an unrelated donor that is perfectly matched, making identification of “permissive” mismatches of paramount importance. Here, we describe novel associations between donor T-cell cytokine production during donor-antipatient mixed lymphocyte reactions (MLRs) and acute graft-versus-host disease (aGVHD). The data reveal positive correlations between both Th1-type and Th2-type cytokine production and GVHD and the assay established could potentially represent a useful tool for identification of permissible unrelated SCT donors. Associations between interleukin 13 (IL-13) levels and aGVHD were by far the strongest predictor of a GVHD (P = .0002). All patients suffering severe (grade III) aGVHD following SCT had donors who produced very high pretransplantation IL-13 responses, while those developing little or no aGVHD (grades 0-I) produced no IL-13 at all. IL-13 levels were independent of all other cytokines measured as well as cytotoxic T-lymphocyte precursor (CTLp) frequencies. The cytokines IL-5, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) also predicted development of aGVHD (P &lt; .05 for all 3), appearing to be coproduced in the assay and correlating with estimated CTLp frequencies. The data challenge the notion that aGVHD is purely a Th1-type cytokine-driven response, high-lighting a novel and highly significant link between the Th2-type cytokine IL-13 and aGVHD.
Graft-versus-host-reactive donor CD4 cells can induce T cell-mediated rejection of the donor marrow in mixed allogeneic chimeras prepared with nonmyeloablative conditioning
Authors: Kim Yong-Mi , Mapara Markus Y. , Down Julian D. , Johnson Kevin W. , Boisgerault Florence , Akiyama Yoshinobu , Benichou Gilles , Pelot Michele , Zhao Guiling , Sykes Megan 
Published: September 2003

AbstractMurine mixed hematopoietic chimerism can be achieved following nonmyeloablative conditioning with cyclophosphamide, T cell–depleting monoclonal antibodies, and thymic irradiation. Donor lymphocyte infusions (DLIs) 35 days after bone marrow transplantation (BMT) convert mixed to full donor chimerism and mediate graft-versus-lymphoma effects without graft-versus-host disease. We evaluated the role of T-cell subsets in DLIs in converting mixed to full donor chimerism in a fully major histocompatibility complex–mismatched strain combination. Whereas DLIs administered on day 35 converted 100% of mixed chimeras to full donor chimerism, conversion was less frequent when either CD4 or CD8 cells were depleted, indicating that both subsets contribute to the conversion. Surprisingly, administration of CD8-depleted DLIs led to complete loss of donor chimerism in a high proportion (54%) of recipients compared with CD4-plus CD8-depleted DLIs (15%) or CD4-depleted DLIs (0%) (P &lt; .05). DLIs administered at early time points after BMT (eg, day 21) also precipitated rejection of donor marrow by recipient αβ T cells, in association with donor CD4 cell expansion and high production of interleukin 2 (IL-2), IL-4, and interferon-γ. Thus, DLIs can paradoxically induce marrow rejection by residual host αβ T cells. These results have implications for the timing of and use of subset depletion of DLIs in recipients of nonmyeloablative transplants.
Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors
Authors: Miklos David B. , Kim Haesook T. , Zorn Emmanuel , Hochberg Ephraim P. , Guo Luxuan , Mattes-Ritz Alex , Viatte Sebastien , Soiffer Robert J. , Antin Joseph H. , Ritz Jerome 
Published: September 2003

AbstractMinor histocompatibility antigens (mHAs) recognized by donor T cells play a central role as immunologic targets of graft-versus-host disease (GVHD) and graft versus leukemia after allogeneic hematopoietic stem cell transplantation (HSCT). Men who have undergone sex-mismatched allogeneic HSCT are at high risk for GVHD because of immune responses directed against mHAs encoded by genes on the Y chromosome (termed H-Y antigens). We hypothesized that the immunogenicity of mHAs results in a coordinated response involving B cells as well as T cells. To test this, we measured antibody responses to a well-characterized H-Y antigen, dead box RNAhelicase Y (DBY), and its homolog, DBX, in 150 HSCT patients. Using Western blot and enzyme-linked immunosorbent assay (ELISA), we found that 50% of male patients who received stem cell grafts from female donors developed antibody responses to recombinant DBY protein. Antibodies to DBY were also detected in 17% of healthy women, but not in healthy men. Antibody responses were directed primarily against areas of amino acid disparity between DBY and DBX. These studies demonstrate that the immune response to mHA includes the generation of specific antibodies and suggests that the serologic response to these antigens may also be useful in the identification of new mHAs.
Granzyme B and perforin: constitutive expression in human polymorphonuclear neutrophils
Authors: Wagner Christof , Iking-Konert Christof , Denefleh Birgit , Stegmaier Sabine , Hug Friederike , Hänsch G. Maria 
Published: September 2003

AbstractPolymorphonuclear neutrophils (PMNs) produce an abundance of bactericidal and cytotoxic molecules consistent with their role as first-line defense against bacterial infection. PMNs, however, also cause efficient cellular cytotoxicity when targeted through Fc receptors to appropriate antibody-coated target cells. Although this so-called antibody-dependent cellular cytotoxicity (ADCC) was described many years ago, the mechanism of killing is still elusive. We now have found that PMNs contain perforin and granzyme B, the 2 molecules known as the cytotoxic entity of natural killer cells and of cytotoxic T lymphocytes as well. Lysates of PMNs were lytic for chicken erythrocytes in a time-, temperature-, and Ca2+-dependent manner. Moreover, apoptosis of Jurkat cells was induced, consistent with the observation that the PMN lysates contain enzymatically active granzyme B. Taken together, our data provide evidence for the presence of perforin and granzyme B within the cytotoxic arsenal of PMNs. (Blood. 2004;103:1099-1104)
Helper-dependent adenoviral vectors mediate therapeutic factor VIII expression for several months with minimal accompanying toxicity in a canine model of severe hemophilia A
Authors: Brown Brian D. , Shi Chang Xin , Powell Sandra , Hurlbut David , Graham Frank L. , Lillicrap David 
Published: September 2003

AbstractTwo helper-dependent (HD) adenoviral vectors encoding a canine factor VIII B-domain–deleted transgene (cFVIII) were constructed and evaluated in 4 hemophilia A dogs. One vector was regulated by the cytomegalovirus (CMV) promoter (HD-CMV-cFVIII), while the other vector contained a tissue-restricted promoter comprised of the human FVIII proximal promoter with an upstream concatemer of 5 hepatocyte nuclear factor 1 binding sites (HD-HNF-cFVIII). We detected no toxicity at low dose (5 × 1011 vp/kg), but at higher vector doses (&gt; 1 × 1012 vp/kg) transient hepatotoxicity and thrombocytopenia were observed. Low-level increases in FVIII activity were detected in all 3 HD-HNF-cFVIII–treated dogs, which corresponded with decreased whole blood clotting times. None of the animals receiving the HD-HNF-cFVIII vector developed FVIII inhibitors, and in 1 of the 3 animals, FVIII activity was sustained for over 6 months after treatment. One animal, which received the HD-CMV-cFVIII vector, achieved peak levels of FVIII above 19 000 mU/mL, but FVIII activity disappeared within 1 week, coincident with the development of a potent anti–canine FVIII antibody response. This study supports previous demonstrations of improved safety using HD gene transfer and suggests that these vectors can provide transient FVIII expression with minimal, acute toxicity in the absence of inhibitor formation.
Recent insights into the mechanisms of myeloid leukemogenesis in Down syndrome
Authors: Gurbuxani Sandeep , Vyas Paresh , Crispino John D. 
Published: September 2003

AbstractGATA-1 is the founding member of a transcription factor family that regulates growth and maturation of a diverse set of tissues. GATA-1 is expressed primarily in hematopoietic cells and is essential for proper development of erythroid cells, megakaryocytes, eosinophils, and mast cells. Although loss of GATA-1 leads to differentiation arrest and apoptosis of erythroid progenitors, absence of GATA-1 promotes accumulation of immature megakaryocytes. Recently, we and others have reported that mutagenesis of GATA1 is an early event in Down syndrome (DS) leukemogenesis. Acquired mutations in GATA1 were detected in the vast majority of patients with acute megakaryoblastic leukemia (DS-AMKL) and in nearly every patient with transient myeloproliferative disorder (TMD), a “preleukemia” that may be present in as many as 10% of infants with DS. Although the precise pathway by which mutagenesis of GATA1 contributes to leukemia is unknown, these findings confirm that GATA1 plays an important role in both normal and malignant hematopoiesis. Future studies to define the mechanism that results in the high frequency of GATA1 mutations in DS and the role of altered GATA1 in TMD and DS-AMKL will shed light on the multistep pathway in human leukemia and may lead to an increased understanding of why children with DS are markedly predisposed to leukemia.
Overexpression of murine TSLP impairs lymphopoiesis and myelopoiesis
Authors: Osborn Mark J. , Ryan Patricia L. , Kirchhof Nicole , Panoskaltsis-Mortari Angela , Mortari Frank , Tudor Kim-Sue R. S. 
Published: September 2003

AbstractThe role of thymic stromal cell–derived lymphopoietin (TSLP) in regulating hematopoiesis is poorly characterized, so we investigated its regulatory effects in vivo using TSLP transgenic mice. Overexpression of TSLP disrupted hematopoietic homeostasis by causing imbalances in lymphopoiesis and myelopoiesis. Mice harboring a TSLP transgene had 5- to 700-fold fewer B and T precursors and no detectable pre-B lymphocyte colonyforming activity in the marrow or spleen. Conversely, TSLP transgenic mice possessed 15 to 20 times more splenic myeloid precursors than their littermates, and progenitor activity of the granulocyteerythrocyte-macrophage-megakaryocyte colony-forming units was significantly elevated. The arrest in lymphopoiesis and the expansion of myeloid progenitor cells in TSLP transgenic mice suggest that TSLP has negative and positive regulatory effects on lymphoid and myeloid development, respectively.