bluuebunny/crossref_metadata_2025 huggingface dataset:
A Virus Essential for Insect Host-Parasite Interactions Encodes Cystatins
Authors: Espagne E. , Douris V. , Lalmanach G. , Provost B. , Cattolico L. , Lesobre J. , Kurata S. , Iatrou K. , Drezen J.-M. , Huguet E.
Published: July 2005

Cotesia congregata
is a parasitoid wasp that injects its eggs in the host caterpillar
Manduca sexta
. In this host-parasite interaction, successful parasitism is ensured by a third partner: a bracovirus. The relationship between parasitic wasps and bracoviruses constitutes one of the few known mutualisms between viruses and eukaryotes. The
C. congregata
bracovirus (CcBV) is injected at the same time as the wasp eggs in the host hemolymph. Expression of viral genes alters the caterpillar's immune defense responses and developmental program, resulting in the creation of a favorable environment for the survival and emergence of adult parasitoid wasps. Here, we describe the characterization of a CcBV multigene family which is highly expressed during parasitism and which encodes three proteins with homology to members of the cystatin superfamily. Cystatins are tightly binding, reversible inhibitors of cysteine proteases. Other cysteine protease inhibitors have been described for lepidopteran viruses; however, this is the first description of the presence of cystatins in a viral genome. The expression and purification of a recombinant form of one of the CcBV cystatins, cystatin 1, revealed that this viral cystatin is functional having potent inhibitory activity towards the cysteine proteases papain, human cathepsins L and B and
Sarcophaga
cathepsin B in assays in vitro. CcBV cystatins are, therefore, likely to play a role in host caterpillar physiological deregulation by inhibiting host target proteases in the course of the host-parasite interaction.
Mapping of the Hepatitis B Virus Pre-S1 Domain Involved in Receptor Recognition
Authors: Barrera Azeneth , Guerra Bernadette , Notvall Lena , Lanford Robert E.
Published: July 2005

Hepatitis B virus (HBV) and woolly monkey hepatitis B virus (WMHBV) are primate hepadnaviruses that display restricted tissue and host tropisms. Hepatitis D virus (HDV) particles pseudotyped with HBV and WMHBV envelopes (HBV-HDV and WM-HDV) preferentially infect human and spider monkey hepatocytes, respectively, thereby confirming host range bias in vitro. The analysis of chimeric HBV and WMHBV large (L) envelope proteins suggests that the pre-S1 domain may comprise two regions that affect infectivity: one within the amino-terminal 40 amino acids of pre-S1 and one downstream of this region. In the present study, we further characterized the role of the amino terminus of pre-S1 in infectivity by examining the ability of synthetic peptides to competitively block HDV infection of primary human and spider monkey hepatocytes. A synthetic peptide representing the first 45 residues of the pre-S1 domain of the HBV L protein blocked infectivity of HBV-HDV and WM-HDV, with a requirement for myristylation of the amino terminal residue. Competition studies with truncated peptides suggested that pre-S1 residues 5 to 20 represent the minimal domain for inhibition of HDV infection and, thus, presumably represent the residues involved in virus-host receptor interaction. Recombinant pre-S1 proteins expressed in insect cells blocked infection with HBV-HDV and WM-HDV at a concentration of 1 nanomolar. The ability of short pre-S1 peptides to efficiently inhibit HDV infection suggests that they represent suitable ligands for identification of the HBV receptor and that a pre-S1 mimetic may represent a rational therapy for the treatment of HBV infection.
Age-Dependent Role for CCR5 in Antiviral Host Defense against Herpes Simplex Virus Type 2
Authors: Ank Nina , Petersen Klavs , Malmgaard Lene , Mogensen Søren C. , Paludan Søren R.
Published: July 2005

Elimination of viral infections is dependent on rapid recruitment and activation of leukocytes with antiviral activities to infected areas. Chemokines constitute a class of cytokines that have regulatory effects on leukocyte migration and activity. In this study we have studied the role of CC chemokine receptor 1 (CCR1) and CCR5 in host defense during a generalized herpes simplex virus type 2 (HSV-2) infection. Whereas both 4- and 8-week-old CCR1−/−mice resembled wild-type mice (C57BL/6) with respect to defense against the infection, significantly higher virus titers were seen in the livers and brains of 4-week-old CCR5−/−mice. At the age of 8 weeks, CCR5−/−were indistinguishable from wild-type mice and cleared the infection from liver and spleen. Although 4-week-old CCR5−/−mice were able to recruit natural killer (NK) cells to the site of infection, these cells had reduced cytotoxic activity compared to NK cells from wild-type mice. This was not due to lower production of alpha/beta interferon or interleukin-12, two well-described activators of cytotoxic activity in NK cells. We also noted that the spleens of young CCR5−/−mice did not increase in size during infection as did the spleens of wild-type and CCR1−/−mice. This observation was accompanied by impaired proliferation of CCR5−/−splenocytes (SCs) ex vivo. Moreover, migration of CD8+T cells to the liver in response to infection was impaired in CCR5−/−mice, and adoptive transfer of SCs from CCR5−/−mice infected for 6 days into newly infected wild-type mice did not improve antiviral activity in the liver, in contrast to what was seen in mice receiving immune SCs from wild-type mice. Altogether, this study shows that CCR5 plays an age-dependent role in host defense against HSV-2 by supporting both the innate and adaptive immune response.
Murine Coronavirus Requires Lipid Rafts for Virus Entry and Cell-Cell Fusion but Not for Virus Release
Authors: Choi Keum S. , Aizaki Hideki , Lai Michael M. C.
Published: July 2005

Thorp and Gallagher first reported that depletion of cholesterol inhibited virus entry and cell-cell fusion of mouse hepatitis virus (MHV), suggesting the importance of lipid rafts in MHV replication (E. B. Thorp and T. M. Gallagher, J. Virol.
78:
2682-2692, 2004). However, the MHV receptor is not present in lipid rafts, and anchoring of the MHV receptor to lipid rafts did not enhance MHV infection; thus, the mechanism of lipid rafts involvement is not clear. In this study, we defined the mechanism and extent of lipid raft involvement in MHV replication. We showed that cholesterol depletion by methyl β-cyclodextrin or filipin did not affect virus binding but reduced virus entry. Furthermore, MHV spike protein bound to nonraftraft membrane at 4°C but shifted to lipid rafts at 37°C, indicating a redistribution of membrane following virus binding. Thus, the lipid raft involvement in MHV entry occurs at a step following virus binding. We also found that the viral spike protein in the plasma membrane of the infected cells was associated with lipid rafts, whereas that in the Golgi membrane, where MHV matures, was not. Moreover, the buoyant density of the virion was not changed when MHV was produced from the cholesterol-depleted cells, suggesting that MHV does not incorporate lipid rafts into the virion. These results indicate that MHV release does not involve lipid rafts. However, MHV spike protein has an inherent ability to associate with lipid rafts. Correspondingly, cell-cell fusion induced by MHV was retarded by cholesterol depletion, consistent with the association of the spike protein with lipid rafts in the plasma membrane. These findings suggest that MHV entry requires specific interactions between the spike protein and lipid rafts, probably during the virus internalization step.
Genetic Analysis of the Polyomavirus DnaJ Domain
Authors: Whalen Kerry A. , de Jesus Rowena , Kean Jennifer A. , Schaffhausen Brian S.
Published: July 2005

Polyomavirus T antigens share a common N-terminal sequence that comprises a DnaJ domain. DnaJ domains activate DnaK molecular chaperones. The functions of J domains have primarily been tested by mutation of their conserved HPD residues. Here, we report detailed mutagenesis of the polyomavirus J domain in both large T (63 mutants) and middle T (51 mutants) backgrounds. As expected, some J mutants were defective in binding DnaK (Hsc70); other mutants retained the ability to bind Hsc70 but were defective in stimulating its ATPase activity. Moreover, the J domain behaves differently in large T and middle T. A given mutation was twice as likely to render large T unstable as it was to affect middle T stability. This apparently arose from middle T's ability to bind stabilizing proteins such as protein phosphatase 2A (PP2A), since introduction of a second mutation preventing PP2A binding rendered some middle T J-domain mutants unstable. In large T, the HPD residues are critical for Rb-dependent effects on the host cell. Residues Q32, A33, Y34, H49, M52, and N56 within helix 2 and helix 3 of the large T J domain were also found to be required for Rb-dependent transactivation. Cyclin A promoter assays showed that J domain function also contributes to large T transactivation that is independent of Rb. Single point mutations in middle T were generally without effect. However, residue Q37 is critical for middle T's ability to form active signaling complexes. The Q37A middle T mutant was defective in association with pp60
c-src
and in transformation.
SU(2)×U(1) NONANTICOMMUTATIVE N = 2 SUPERSYMMETRIC GAUGE THEORY
Authors: KETOV SERGEI V. , SASAKI SHIN
Published: July 2005

We derive the master function governing the component action of the four-dimensional nonanticommutative (NAC) and fully N = 2 supersymmetric gauge field theory with a nonsimple gauge group U (2) = SU (2) × U (1). The new NAC master function is a nontrivial generalization of the known master functions in the NAC, N = 2 supersymmetric gauge theories with the U(1) and SU(2) gauge groups. We use a Lorentz-singlet NAC-deformation parameter and an N = 2 supersymmetric star (Moyal) product, which do not break any of the fundamental symmetries of the undeformed N = 2 gauge theory. The scalar potential in the NAC-deformed theory is calculated. We also propose the non-Abelian BPS-type equations in the case of the NAC-deformed N = 2 gauge theory with the SU(2) gauge group, and comment on the SU(3) case too. The NAC-deformed field theories can be thought of as the effective (nonperturbative) N = 2 gauge field theories in a certain (scalar only) N = 2 supergravity background.
Bc AND HEAVY MESON SPECTROSCOPY IN THE LOCAL APPROXIMATION OF THE SCHRÖDINGER EQUATION WITH RELATIVISTIC KINEMATICS
Authors: IKHDAIR SAMEER M. , SEVER RAMAZAN
Published: July 2005

We present bound state masses of the self-conjugate and non-self-conjugate mesons in the context of the Schrödinger equation taking into account the relativistic kinematics and the quark spins. We apply the usual interaction by adding the spin dependent correction. The hyperfine splittings for the 2S charmonium and 1S bottomonium are calculated. The pseudoscalar and vector decay constants of the Bc meson and the unperturbed radial wave function at the origin are also calculated. We have obtained a local equation with a complete relativistic corrections to a class of three attractive static interaction potentials of the general form V(r) = -Ar-β+κrβ+V0, with β = 1, 1/2, 3/4 which can also be decomposed into scalar and vector parts in the form VV(r) = -Ar-β+(1-∊)κrβ and VS(r) = ∊κrβ+V0; where 0≤∊≤1. The energy eigenvalues are carried out up to the third order approximation using the shifted large-N-expansion technique.
CONFORMAL MODULI AND b-c PICTURES FOR NSR STRINGS
Authors: POLYAKOV DIMITRI
Published: July 2005

We explore the geometry of superconformal moduli of the NSR superstring theory in order to construct the consistent sigma-model for NSR strings, free of picture-changing complications. The sigma-model generating functional is constructed by the integration over the bosonic and fermionic moduli, corresponding to insertions of the vertex operators in scattering amplitudes. While the integration over the supermoduli leads to the standard picture-changing insertions, the integration over the bosonic moduli results in the appearance of picture-changing operators for the b-c fermionic ghosts with the ghost number -1. Important example of the b-c ghost pictures involves the vertex operators in integrated and unintegrated forms. We obtain the BRST-invariant expressions for the b-c picture-changing operators for open and closed strings and study some of their properties. We also show that the superconformal moduli spaces of the NSR theory contain the global singularities, leading to the phenomenon of ghost-matter mixing and the appearance of nonperturbative D-brane creation operators.
Delayed-rectifier (KV2.1) regulation of pancreatic β-cell calcium responses to glucose: inhibitor specificity and modeling
Authors: Tamarina Natalia A. , Kuznetsov Andrey , Fridlyand Leonid E. , Philipson Louis H.
Published: July 2005

The delayed-rectifier (voltage-activated) K+conductance (KV) in pancreatic islet β-cells has been proposed to regulate plasma membrane repolarization during responses to glucose, thereby determining bursting and Ca2+oscillations. Here, we verified the expression of KV2.1 channel protein in mouse and human islets of Langerhans. We then probed the function of KV2.1 channels in islet glucose responses by comparing the effect of hanatoxin (HaTx), a specific blocker of KV2.1 channels, with a nonspecific K+channel blocker, tetraethylammonium (TEA). Application of HaTx (1 μM) blocked delayed-rectifier currents in mouse β-cells, resulting in a 40-mV rightward shift in threshold of activation of the voltage-dependent outward current. In the presence of HaTx, there was negligible voltage-activated outward current below 0 mV, suggesting that KV2.1 channels form the predominant part of this current in the physiologically relevant range. We then employed HaTx to study the role of KV2.1 in the β-cell Ca2+responses to elevated glucose in comparison with TEA. Only HaTx was able to induce slow intracellular Ca2+concentration ([Ca2+]i) oscillations in cells stimulated with 20 mM glucose, whereas TEA induced an immediate rise in [Ca2+]ifollowed by rapid oscillations. In human islets, HaTx acted in a similar fashion. The data were analyzed using a detailed mathematical model of ionic flux and Ca2+regulation in β-cells. The results can be explained by a specific HaTx effect on the KVcurrent, whereas TEA affects multiple K+conductances. The results underscore the importance of KV2.1 channel in repolarization of the pancreatic β-cell plasma membrane and its role in regulating insulin secretion.
Endurance training increases skeletal muscle LKB1 and PGC-1α protein abundance: effects of time and intensity
Authors: Taylor Eric B. , Lamb Jeremy D. , Hurst Richard W. , Chesser David G. , Ellingson William J. , Greenwood Lyle J. , Porter Brian B. , Herway Seth T. , Winder William W.
Published: July 2005

Recent research suggests that LKB1 is the major AMP-activated protein kinase kinase (AMPKK). Peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master coordinator of mitochondrial biogenesis. Previously we reported that skeletal muscle LKB1 protein increases with endurance training. The purpose of this study was to determine whether training-induced increases in skeletal muscle LKB1 and PGC-1α protein exhibit a time course and intensity-dependent response similar to that of citrate synthase. Male Sprague-Dawley rats completed endurance- and interval-training protocols. For endurance training, rats trained for 4, 11, 25, or 53 days. Interval-training rats trained identically to endurance-trained rats, except that after 25 days interval training was combined with endurance training. Time course data were collected from endurance-trained red quadriceps (RQ) after each time point. Interval training data were collected from soleus, RQ, and white quadriceps (WQ) muscle after 53 days only. Mouse protein 25 (MO25) and PGC-1α protein increased significantly after 4 days. Increased citrate synthase activity, increased LKB1 protein, and decreased AMPKK activity were found after 11 days. Maximal increases occurred after 4 days for hexokinase II, 25 days for MO25, and 53 days for citrate synthase, LKB1, and PGC-1α. In WQ, but not RQ or soleus, interval training had an additive effect to endurance training and induced significant increases in all proteins measured. These results demonstrate that LKB1 and PGC-1α protein abundances increase with endurance and interval training similarly to citrate synthase. The increase in LKB1 and PGC-1α with endurance and interval training may function to maintain the training-induced increases in mitochondrial mass.
Endothelial dysfunction occurs in peripheral circulation patients with acute and stable coronary artery disease
Authors: Thanyasiri Panuratn , Celermajer David S. , Adams Mark R.
Published: July 2005

Atherosclerosis is a diffuse, systemic process. In addition, acute coronary syndromes (ACS) are associated with inflammatory marker elevations that are hypothesized to affect the function of nonculprit coronary as well as peripheral vessels. We investigated whether femoral vascular reactivity and/or fibrinolytic capacity are impaired in ACS patients over and above any dysfunction associated with stable coronary artery disease. Patients undergoing diagnostic coronary angiography ( n = 42 total, 14 patients/group) were recruited into three groups as follows: 1) stable coronary syndromes (SAP group), 2) ACS as defined by rest angina with ECG changes and troponin rise (ACS group), and 3) angiographically normal coronary arteries (control group). After diagnostic coronary angiography, femoral artery endothelial and smooth muscle function were assessed by infusing acetylcholine (ACh) and nitroglycerin (GTN), and tissue-type plasminogen activator (t-PA) release across the femoral circulation was measured as the difference between arterial and venous concentrations before and after ACh and GTN stimulation. There were no significant differences between groups in relevant baseline characteristics apart from significantly higher C-reactive protein levels and reduced net t-PA release in the ACS group at baseline ( P < 0.05). The ACS and SAP groups had equivalent angiographic severity of coronary artery disease. Endothelium-dependent dilatation was significantly higher in control individuals (14.9 ± 9.1%; P < 0.001) compared with either stable patients (2.3 ± 8.1%) or those with unstable syndromes (2.6 ± 8.9%, who were similar to each other; P = not significant). Although baseline t-PA release was impaired in the ACS patients (0.09 ± 0.06 compared with 0.39 ± 0.33 and 0.49 ± 0.56 ng/ml; P = 0.03), stimulation of t-PA release by ACh and GTN occurred only in the control subjects and not in the ACS or SAP patients. Coronary artery disease is associated with impaired endothelium-dependent dilatation and impaired stimulation of t-PA release in the systemic circulation. These aspects of endothelial dysfunction, however, were equally severe in acute and chronic coronary syndrome patients.
CytochromeP-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus
Authors: Sarkis Albert , Ito Osamu , Mori Takefumi , Kohzuki Masahiro , Ito Sadayoshi , Verbalis Joseph , Cowley Allen W. , Roman Richard J.
Published: July 2005

This study compared the renal metabolism of arachidonic acid in Brattleboro (BB) (vasopressin deficient) and Long-Evans (LE) control rats and the effects of a cytochrome P-450 (CYP) inhibitor 1-aminobenzotriazole (ABT) on renal function in these animals. The production of 20-hydroxyeicosatetraenoic acid (20-HETE) by renal cortical and outer medullary microsomes was significantly greater in BB than in LE rats (155 ± 16 vs. 92 ± 13 and 59 ± 7 vs. 33 ± 3 pmol·min−1·mg protein−1). Renal cortical epoxygenase activity was not different in these strains. The expression of CYP4A proteins was 58 and 78% higher in the renal cortex and outer medulla of BB than in LE rats. Chronic treatment of BB rats with a vasopressin type 2 receptor agonist for 1 wk normalized the renal production of 20-HETE. Chronic blockade of the formation of 20-HETE and EETs with ABT had little effect on renal function in LE rats. However, urine flow increased by 54% and urine osmolarity decreased by 33% in BB rats treated with ABT. Plasma levels of oxytocin fell significantly from 7.2 ± 1.3 to 3.9 ± 1.0 pg/ml. The effects of ABT in BB rats were attenuated by chronic infusion of oxytocin (0.7 ng·min−1·100 g−1) to maintain fixed high plasma levels of this hormone. These results indicate that the expression of CYP4A protein and the renal formation of 20-HETE are elevated in the kidney of BB rats due to a lack of vasopressin and that chronic blockade of the formation of 20-HETE and EETs with ABT promotes water excretion in vasopressin-deficient BB rats by reducing the circulating levels of oxytocin, which is a weak vasopressin agonist.
Dialectics and Crisis Theory: A Response to Tony Smith
Authors: Fine Ben , Milonakis Dimitris , Lapavitsas Costas
Published: July 2005

Brenner's ‘The Economics of Global Turbulence’ has induced a flood of responses, the vast majority of them critical, especially on grounds of (divergence from Marx's) method and theory. Tony Smith1 is an exception in seeking to defend Brenner, mostly by pushing his arguments further and by attacking his critics, including ourselves. In part, Smith interprets Brenner and credits him with positions that he can either defend for himself or, as we suspect, reject. Our concern in this reply is not to address issues through the prism of Brenner but to assess Smith's own contribution critically on its own terms and merits.
Vygotsky on Language and Social Consciousness: Underpinning the Use of Voloshinov in the Study of Popular Protest
Authors: Collins Chik
Published: July 2005

The term ‘Bakhtin Circle’ is used to refer to a group of Russian thinkers centred around Mikhail Bakhtin in the years following the 1917 Revolution. The group's prime concern was with the importance of questions of language-use in social life, and with the way in which language-use registered conflicts between social groups and classes. Prominent members, as well as Bakhtin himself, included P.N. Medvedev and V.N. Voloshinov. Between 1929, when a number of members were arrested, and his death in 1975, Bakhtin continued to work on the issues which had occupied the group.
Family of "Civilized" States and Japan: A Story of Humiliation, Assimilation, Defiance and Confrontation
Authors:   Anand
Published: July 2005

No Abstract
The Concept of Money
Authors:   Vakhitov,   Vakhitov
Published: July 2005

The authors of this article—a lawyer and economist—describe modern developments in the forms and functions of money and examine the question of whether the current legal regulation (in the Russian Federation) adequately reflects such developments. The authors suggest that the rule applicable to non-cash money be applied to cash money since the distinction in legal regulation is based more on traditions than it is on actual differences in substance.
Russia's "Dictatorship of Law" and the European Court of Human Rights
Authors:   Kahn
Published: July 2005

This article is an adaptation of a lecture given at St. Antony's College, Oxford on 5 July 2003 in honor of the fiftieth anniversary of the Centre for Russian and East European Studies at Oxford University. The author evaluates the effect of the European Convention on Human Rights on Russian law and politics. Russia has been a signatory to the Convention for five years. The author argues that the full power of the Convention as a force for reform in Russia was unanticipated at the time of Russia's accession. Nevertheless, the Convention has been the catalyst for substantial reforms, especially in the criminal justice system. The author examines these reforms as well as the increasing number of cases in which Russia is a respondent before the European Court of Human Rights in Strasbourg. Drawing on interviews, the Court's statistics and his own experience training Russian human rights lawyers, the author charts the rapid growth in Russia of interest in the Strasbourg process.
Mutations in the ATM gene lead to impaired overall and treatment-free survival that is independent of IGVH mutation status in patients with B-CLL
Authors: Austen Belinda , Powell Judith E. , Alvi Azra , Edwards Ian , Hooper Laura , Starczynski Jane , Taylor A. Malcolm R. , Fegan Christopher , Moss Paul , Stankovic Tatjana
Published: July 2005

The ataxia telangiectasia mutated (ATM) protein is the principal activator of the p53 protein in the response to DNA double-strand breaks. Mutations in the ATM gene have been previously found in B-cell chronic lymphocytic leukemias (B-CLLs) but their clinical significance is unknown. We analyzed 155 CLL tumors and found 12% with ATM mutations and 4% with TP53 mutations; 2 tumors contained mutations in both genes. Retrospective analysis on selected samples indicated that the ATM mutations were usually present at diagnosis. Compared with patients with wild-type ATM/TP53 genes, patients with ATM mutations had statistically significantly reduced overall and treatment-free survival. Although present in both IGVH mutation subgroups, ATM mutations were associated with unmutated IGVH genes and they provided independent prognostic information on multivariate analysis. Mutations in the ATM gene resulted in impaired in vitro DNA damage responses. Tumors with ATM mutations only partially correlated with tumors with loss of an ATM allele through an 11q deletion and, interestingly, those 11q-deleted tumors with a second wild-type ATM allele had a preserved DNA damage response. The majority of patients with ATM mutations were refractory to DNA damaging chemotherapeutic drugs and as such might benefit from therapies that bypass the ATM/p53 pathway.
Loss of EBNA1-specific memory CD4+ and CD8+ T cells in HIV-infected patients progressing to AIDS-related non-Hodgkin lymphoma
Authors: Piriou Erwan , van Dort Karel , Nanlohy Nening M. , van Oers Marinus H. J. , Miedema Frank , van Baarle Debbie
Published: July 2005

We previously observed a loss of Epstein-Barr virus (EBV)–specific CD8+ T cells in subjects progressing to EBV-related non-Hodgkin lymphoma (NHL), correlating with loss of CD4+ T cells. The aim of the present study was to determine the role of EBV-specific CD4+ T cells in the development of NHL during chronic HIV infection. To this end, CD4+ and CD8+ memory T cells, capable of both proliferation and subsequent interferon γ (IFNγ) production, directed against a latent (Epstein-Barr virus nuclear antigen 1 [EBNA1]) and a lytic (BamH fragment Z left frame 1 [BZLF1]) EBV antigen were studied longitudinally in 9 progressors to NHL, 4 progressors to non–EBV-related AIDS, and 4 slow progressors to AIDS. In all 3 groups we observed a decline of EBV-specific memory CD4+ and CD8+ T-cell responses during HIV infection. However, whereas latent antigen EBNA1-specific CD4+ T cells were lost well before diagnosis in all subjects who developed an AIDS-related NHL (and EBNA1-specific CD8+ T cells were significantly lower compared with the other groups), these cells were better preserved in progressors to non–EBV-related disease and slow progressors. Loss of EBNA1-specific T-cell immunity thus might be important for progression to NHL. Interestingly, BZLF1-specific T cells were not lost in all progressors to NHL, suggesting a different function of these cells in the surveillance of EBV-infected B cells.
Transduction of CLL cells by CD40 ligand enhances an antigen-specific immune recognition by autologous T cells
Authors: Mayr Christine , Kofler David M. , Büning Hildegard , Bund Dagmar , Hallek Michael , Wendtner Clemens-Martin
Published: July 2005

Several features of chronic lymphocytic leukemia (CLL) suggest that immune-based strategies may have therapeutic potential. A promising approach is provided by the transduction of CLL cells with CD40 ligand (CD40L) by viral vectors to enhance their immunogenicity. We compared the antigen-presenting capacity of CD40L-transduced CLL cells with mock-transduced or CD40L-stimulated CLL cells (CD40-CLL). A significantly higher number of T cells could be expanded using CD40L-transduced CLL cells as antigen-presenting cells (APCs) compared with the control group (P = .008). Using 5 different CLL-associated tumor antigens, including fibromodulin, MDM2 (murine double minute 2), survivin, p53, and KW-13, we show in interferon-γ (IFN-γ) enzyme-linked immunospot (ELISPOT) assays after 35 days of in vitro culture that the number of antigen-specific autologous T cells was also significantly higher when CD40L-transduced CLL cells were used as APCs (P < .001). Thus, CD40L-transduced CLL cells are able to induce an antigen-specific T-cell response and might be superior to CD40-CLL cells for immune-based therapeutic strategies in CLL.
SeqX: a tool to detect, analyze and visualize residue co-locations in protein and nucleic acid structures
Authors: Biro Jan C , Fördös Gergely
Published: July 2005

Background

The interacting residues of protein and nucleic acid sequences are close to each other – they are co-located. Structure databases (like Protein Data Bank, PDB and Nucleic Acid Data Bank, NDB) contain all information about these co-locations; however it is not an easy task to penetrate this complex information. We developed a JAVA tool, called SeqX for this purpose.

Results

SeqX tool is useful to detect, analyze and visualize residue co-locations in protein and nucleic acid structures. The user

a. selects a structure from PDB;

b. chooses an atom that is commonly present in every residues of the nucleic acid and/or protein structure(s)

c. defines a distance from these atoms (3–15 Å). The SeqX tool detects every residue that is located within the defined distances from the defined "backbone" atom(s); provides a DotPlot-like visualization (Residues Contact Map), and calculates the frequency of every possible residue pairs (Residue Contact Table) in the observed structure. It is possible to exclude +/- 1 to 10 neighbor residues in the same polymeric chain from detection, which greatly improves the specificity of detections (up to 60% when tested on dsDNA). Results obtained on protein structures showed highly significant correlations with results obtained from literature (p < 0.0001, n = 210, four different subsets). The co-location frequency of physico-chemically compatible amino acids is significantly higher than is calculated and expected in random protein sequences (p < 0.0001, n = 80).

Conclusion

The tool is simple and easy to use and provides a quick and reliable visualization and analyses of residue co-locations in protein and nucleic acid structures.

Availability and requirements

http://janbiro.com/Downloads.html SeqX, Java J2SE Runtime Environment 5.0 (available from [see Additional file 1] http://www.sun.com) and at least a 1 GHz processor and with a minimum 256 Mb RAM. Source codes are available from the authors.
Systematic determination of the mosaic structure of bacterial genomes: species backbone versus strain-specific loops
Authors: Chiapello H , Bourgait I , Sourivong F , Heuclin G , Gendrault-Jacquemard A , Petit M-A , El Karoui M
Published: July 2005

Background

Public databases now contain multitude of complete bacterial genomes, including several genomes of the same species. The available data offers new opportunities to address questions about bacterial genome evolution, a task that requires reliable fine comparison data of closely related genomes. Recent analyses have shown, using pairwise whole genome alignments, that it is possible to segment bacterial genomes into a common conserved backbone and strain-specific sequences called loops.

Results

Here, we generalize this approach and propose a strategy that allows systematic and non-biased genome segmentation based on multiple genome alignments. Segmentation analyses, as applied to 13 different bacterial species, confirmed the feasibility of our approach to discern the 'mosaic' organization of bacterial genomes. Segmentation results are available through a Web interface permitting functional analysis, extraction and visualization of the backbone/loops structure of documented genomes. To illustrate the potential of this approach, we performed a precise analysis of the mosaic organization of three E. coli strains and functional characterization of the loops.

Conclusion

The segmentation results including the backbone/loops structure of 13 bacterial species genomes are new and available for use by the scientific community at the URL: http://genome.jouy.inra.fr/mosaic.
Protein subcellular localization prediction for Gram-negative bacteria using amino acid subalphabets and a combination of multiple support vector machines
Authors: Wang Jiren , Sung Wing-Kin , Krishnan Arun , Li Kuo-Bin
Published: July 2005

Background

Predicting the subcellular localization of proteins is important for determining the function of proteins. Previous works focused on predicting protein localization in Gram-negative bacteria obtained good results. However, these methods had relatively low accuracies for the localization of extracellular proteins. This paper studies ways to improve the accuracy for predicting extracellular localization in Gram-negative bacteria.

Results

We have developed a system for predicting the subcellular localization of proteins for Gram-negative bacteria based on amino acid subalphabets and a combination of multiple support vector machines. The recall of the extracellular site and overall recall of our predictor reach 86.0% and 89.8%, respectively, in 5-fold cross-validation. To the best of our knowledge, these are the most accurate results for predicting subcellular localization in Gram-negative bacteria.

Conclusion

Clustering 20 amino acids into a few groups by the proposed greedy algorithm provides a new way to extract features from protein sequences to cover more adjacent amino acids and hence reduce the dimensionality of the input vector of protein features. It was observed that a good amino acid grouping leads to an increase in prediction performance. Furthermore, a proper choice of a subset of complementary support vector machines constructed by different features of proteins maximizes the prediction accuracy.
Muscle regeneration in dystrophin-deficient mdx mice studied by gene expression profiling
Authors: Turk R , Sterrenburg E , de Meijer EJ , van Ommen G-JB , den Dunnen JT , 't Hoen PAC
Published: July 2005

Background

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is lethal. In contrast, dystrophin-deficient mdx mice recover due to effective regeneration of affected muscle tissue. To characterize the molecular processes associated with regeneration, we compared gene expression levels in hindlimb muscle tissue of mdx and control mice at 9 timepoints, ranging from 1–20 weeks of age.

Results

Out of 7776 genes, 1735 were differentially expressed between mdx and control muscle at at least one timepoint (p < 0.05 after Bonferroni correction). We found that genes coding for components of the dystrophin-associated glycoprotein complex are generally downregulated in the mdx mouse. Based on functional characteristics such as membrane localization, signal transduction, and transcriptional activation, 166 differentially expressed genes with possible functions in regeneration were analyzed in more detail. The majority of these genes peak at the age of 8 weeks, where the regeneration activity is maximal. The following pathways are activated, as shown by upregulation of multiple members per signalling pathway: the Notch-Delta pathway that plays a role in the activation of satellite cells, and the Bmp15 and Neuregulin 3 signalling pathways that may regulate proliferation and differentiation of satellite cells. In DMD patients, only few of the identified regeneration-associated genes were found activated, indicating less efficient regeneration processes in humans.

Conclusion

Based on the observed expression profiles, we describe a model for muscle regeneration in mdx mice, which may provide new leads for development of DMD therapies based on the improvement of muscle regeneration efficacy.
Estren promotes androgen phenotypes in primary lymphoid organs and submandibular glands
Authors: Islander Ulrika , Hasséus Bengt , Erlandsson Malin C , Jochems Caroline , Skrtic Sofia Movérare , Lindberg Marie , Gustafsson Jan-Åke , Ohlsson Claes , Carlsten Hans
Published: July 2005

Background

Estrogens and androgens have extensive effects on the immune system, for example they suppress both T and B lymphopoiesis in thymus and bone marrow. Submandibular glands are sexually dimorphic in rodents, resulting in larger granular convoluted tubules in males compared to females. The aim of the present experiments was to investigate the estrogenic and androgenic effects of 4-estren-3α,17β-diol (estren) on thymus, bone marrow and submandibular glands, and compare the effects to those of 17β-estradiol (E2) and 5α-dihydrotestosterone (DHT), respectively. Estrogen receptors (ERs) were blocked by treatment of mice with the ER-antagonist ICI 182,780; also, knock-out mice lacking one or both ERs were used.

Results

As expected, the presence of functional ERs was mandatory for all the effects of E2. Similar to DHT-treatment, estren-treatment resulted in decreased thymus weight, as well as decreased frequency of bone marrow B cells. Treatment with estren or DHT also resulted in a shift in submandibular glands towards an androgen phenotype. All the effects of estren and DHT were independent of ERs.

Conclusion

Our study is the first to show that estren has similar effects as the androgen DHT on lymphopoiesis in thymus and bone marrow, and on submandibular glands, and that these effects are independent of estrogen receptors. This supports the hypothesis of estren being able to signal through the androgen receptor.
The development and implementation of a regional network of physiotherapists for exercise therapy in patients with peripheral arterial disease, a preliminary report
Authors: Willigendael EM , Bendermacher BLW , van der Berg C , Welten RJThJ , Prins MH , Bie de RA , Teijink JAW
Published: July 2005

Background

Exercise therapy (ET) is the main conservative and proven effective treatment of patients with intermittent claudication. Currently, the most frequent exercise prescription is a single 'go home and walk' advise, without supervision or follow-up. There is no evidence to support the efficacy of this advise and compliance is known to be low. Therefore, a systematic approach was used to guarantee quality and standardisation of treatment, optimal guideline adherence and improved of inter-professional communication between vascular surgeons and physiotherapists. In this preliminary report we would like to outline the steps taken for the development and implementation of the Network Exercise Therapy Parkstad

Methods

In October 2003 all 59 regional physiotherapy practices were invited to attend a symposium regarding ET in a physiotherapeutic setting. Attending physiotherapists interested in providing ET and willing to follow a certified course on ET, were asked to register. Three tastkgroups were formed to accomplish the set targets: Exercise therapy education, Exercise therapy implementation and continuity, and Inter-professional communication in the Parkstad region.

Results

In total 27 physiotherapists, from 22 different practices followed the educational program and are now trained and accredited to provide ET according to the guideline of the Royal Dutch Society for Physiotherapy. A web-based database wasdesigned to contain information on disease specific items provided by the vascular surgery department, and aspects with respect to ET registered by the physiotherapist. The information is regularly updated and available online. Access tothe database is restricted to vascular surgeons and physiotherapists in the network. The secondary purpose of the database is to register essential benchmark data for future analysis of ET in a physiotherapeutic setting in the Netherlands and to enable physiotherapists continuous feedback on patient performance. A triage system was developed to detect patients with a compromised cardiac history. This group receives ET at the in-hospital department of revalidation with the possibility of immediate consultation of a cardiologist in case of cardiac complications or even CPR.

Conclusion

The Network Exercise Therapy Parkstad of supervised ET is the first initiative in the Netherlands to provide ET close to the patient's home environment. With the implementation of supervised ET in an outpatient physiotherapeutic setting for all eligible patients with symptomatic PAD, the access to care has been improved. A web-based communication system provides physiotherapists and vascular surgeons with all the necessary and continues updated patient information. Future research, currently in progress, will investigate the therapeutic benefits and cost-effectiveness of exercise therapy in a physiotherapeutic setting.
Pharmacy-based needle exchange in New Zealand: a review of services
Authors: Sheridan Janie , Henderson Charles , Greenhill Nicola , Smith Andrew
Published: July 2005

Background

New Zealand has been offering needle exchange services since 1987. Over 170 community pharmacies are involved in the provision of this service. However, no recent detailed review of New Zealand's pharmacy-based needle exchange has been published. This study aimed to explore service provision, identify problems faced by pharmacists, and look for improvements to services.

Methods

The study used a cross-sectional survey of all needle exchange pharmacies. Postal questionnaires were used with postal and telephone follow-up.

Results

A response rate of 88% was obtained overall. Pharmacists had been providing the service for a mean of 6 years. Pharmacies had given out an average of 130 injecting units, in a mean of 62 transactions to a mean of 17 clients in the 4 weeks prior to completing the questionnaire. The majority had not incurred problems such as violence or intoxicated clients in the last 12 months, although almost one third had experienced shoplifting which they associated with service provision. Training and improving return rates were identified as potential areas for further development.

Conclusion

New Zealand needle exchange pharmacies are providing services to a number of clients. The majority of service providers had been involved for a number of years, indicating the problems incurred had not caused them to withdraw their services – findings which echo those from the UK. Further training and support, including an exploration of improving return rates may be needed in the future.
Ku protein as a potential human T-cell leukemia virus type 1 (HTLV-1) Tax target in clastogenic chromosomal instability of mammalian cells
Authors: Majone Franca , Luisetto Roberto , Zamboni Daniela , Iwanaga Yoichi , Jeang Kuan-Teh
Published: July 2005

The HTLV-1 Tax oncoprotein rapidly induces cytogenetic damage which can be measured by a significant increase in the number of micronuclei (MN) in cells. Tax is thought to have both aneuploidogenic and clastogenic effects. To examine the cellular target for Tax which might mechanistically explain the clastogenic phenomenon, we tested the ability of Tax to induce MN in rodents cells genetically defective for either the Ku80 protein or the catalytic subunit of DNA protein kinase (DNAPKcs). We found that cells genetically mutated in Ku80 were refractory to Tax's induction of MN while cells knocked-out for DNAPKcs showed increased number of Tax-induced MN. Using a cytogenetic method termed FISHI (Fluorescent In Situ Hybridization and Incorporation) which measures the number of DNA-breaks in cells that contained unprotected 3'-OH ends, we observed that Tax increased the prevalence of unprotected DNA breaks in Ku80-intact cells, but not in Ku80-mutated cells. Taken together, our findings suggest Ku80 as a cellular factor targeted by Tax in engendering clastogenic DNA damage.
Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides
Authors: Bonaci-Nikolic Branka , Nikolic Milos M , Andrejevic Sladjana , Zoric Svetlana , Bukilica Mirjana
Published: July 2005

Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (α1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low α1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease.
Anatomic Analysis of the Transforaminal Ligament in the Lumbar Intervertebral Foramen
Authors: Min Jun-Hong , Kang Shin-Hyuk , Lee Jang-Bo , Cho Tai-Hyoung , Suh Jung-Guen
Published: July 2005

OBJECTIVE:

The objective of this study was to evaluate the clinical significance of the transforaminal ligaments (TFLs) in relation to the area of the lumbar intervertebral foramen (IVF) by analyzing cadaveric spines.

METHODS:

One hundred ninety-eight cadaveric lumbar IVFs were studied, and the existence and type of TFLs were identified. All IVFs were photographed, and the images were saved. The areas of the IVFs and TFLs were measured with the Scion Image for Windows image analysis program.

RESULTS:

TFLs were found in 82.8% of the IVFs. The oblique inferior transforaminal ligament was the most common. The mean area of the IVFs was 155.8 ± 51.1 mm2, and the mean area occupied by the TFLs was 46.3 ± 37.6 mm2. The mean percentage of the IVF area occupied by the TFLs was 28.5 ± 18.8%.

CONCLUSION:

TFLs are common structures in the IVF and may reduce the space available for the spinal nerve root within the IVF. In this circumstance, any compromise of the IVF may impinge on the nerve root.