bluuebunny/crossref_metadata_2025 huggingface dataset:
Neither Truth nor Justice
Authors: Quezada Sergio Aguayo , Rangel Javier Treviño
Published: February 2006

All countries that travel the path to democracy eventually have to decide what to do about the atrocities and excesses of their predecessors. During Mexico’s own interminable transition to democracy, opinion was divided about what to do about the human rights violations committed during the long authoritarian rule of the Partido Revolucionario Institucional. The government of Vicente Fox sided, both verbally and in some of its early decisions, in favor of truth and justice. Meanwhile, however, the president was proposing and/or approving political, administrative, and legal decisions which in practice granted de facto amnesty to the perpetrators of state crimes under the old regime. Some consequences are evident. The culture of impunity remains intact, and it has continued to erode and trivialize the culture of human right and justice, which, in Mexico, have become abused rhetorical concepts gradually emptied of political meaning.
Images of the Dirty TV-War
Authors: Navarro Luis Hernández
Published: February 2006

Since the 1980s, the concept of “civil society” has served as a self-identification for nonpartisan actors confronting Mexico’s authoritarian state. Propelled by the left, this civil society called for the construction of an enlarged citizenry and a new kind of participation based on public involvement in government. Lately, however, the concept of civil society has been co-opted by corporate and partisan interests acting through Mexico’s television networks. Through constant transmission of violent images, they have managed to fill the public with dread, providing a propitious environment for the iron-fisted policies of the political right. At the same time, they have waged a teleguerra sucia (dirty TV-war) against the left, selectively exposing the corruption of leftist political parties and striving in particular to discredit the presidential candidate Andrés Manuel López Obrador. Although López Obrador has so far survived their attacks, the media enter the political campaign of 2006 convinced of their ability to influence the outcome by manipulating information and maintaining a climate of fear and insecurity.
What Is Left of the Mexican Left?
Authors: Semo Enrique
Published: February 2006

As Mexico approaches the 2006 elections, the candidate for president closest to the left is Andrés Manuel López Obrador, supported by the Partido de la Revolución Democrática and other left and center organizations. All the polls place him well ahead of the candidates of the other two parties, presenting a unique possibility of a pendulum swing of Mexican politics to the left of center.
The State, the Bourgeoisie, and the Unions
Authors: Roman Richard , Arregui Edur Velasco
Published: February 2006

Mexico’s unions combine features of a state institution, a party machine, and an employment service with those of corrupt and authoritarian unions. These hybrid institutions have been partners with the state and the bourgeoisie in disciplining the working class both in the workplace and politically. A number of features of union organization and perspective contribute to this controlling role. The state and the bourgeoisie have again enlisted labor officialdom to contain working-class discontent in the face of the crisis of the Mexican regime and of the neoliberal project. This recycling of the system of labor control is fully compatible with the interests of this hybrid and opportunist set of labor leaders, interests that are far from those of their membership and the vast masses of unorganized workers. Rank-and-file workers and the left have not yet been able to launch an effective challenge to this system of control.
The Indigenous Movement in Mexico
Authors: Castillo Rosalva Aída Hernández
Published: February 2006

Taking as its starting point the response of indigenous organizations to the Zapatistas’ so-called Otra Campaña (Other Campaign), this article reflects on the cultural politics of Mexico’s indigenous movement and the tensions between local forms of resistance and the national strategies proposed by the Ejército Zapatista de Liberación Nacional.
Selective increases in the cytokine, TNFα, in the prefrontal cortex of PCP-treated rats and human schizophrenic subjects: influence of antipsychotic drugs
Authors: Paterson G. J. , Ohashi Y. , Reynolds G. P. , Pratt J. A. , Morris B. J.
Published: February 2006

The psychotomimetic drug phencyclidine (PCP) induces symptoms closely related to those of schizophrenia in humans. In order to test the hypothesis that cytokines may be involved in the aetiology and treatment of schizophrenia, this study investigated the levels of cytokine mRNAs in rat brain after acute and chronic administration of PCP, in the presence and absence of antipsychotic drugs. The levels of the mRNAs encoding TNF, IL-2, IL-6, TGF 1, 2, 3, IL-3 and GM-CSF were measured in the prefrontal cortex, cortex, hippocampus, ventral and dorsal striatum regions of male hooded Long Evans rats after acute drug administration. Antipsychotic drugs and PCP significantly reduced the levels of TNF in the prefrontal cortex compared to vehicle-treated animals, whilst other cytokines remained unchanged. In addition, significant reductions in the levels of TNF mRNA in the prefrontal cortex still occurred 24h after acute PCP administration. However, levels of TNF mRNA were restored to control values after chronic PCP treatment, whereas increased expression was detected in animals co-administered with haloperidol. Levels of TNF mRNA were also found to be significantly increased in the prefrontal cortex of schizophrenic subjects. The relationship between TNF levels and schizophrenia are discussed.
The impact of experimental design on assessing mechanism-based inactivation of CYP2D6 by MDMA (Ecstasy)
Authors: Van Linh M. , Heydari Amir , Yang Jiansong , Hargreaves Judith , Rowland-Yeo Karen , Lennard Martin S. , Tucker Geoffrey T. , Rostami-Hodjegan Amin
Published: February 2006

MDMA (3-4-methylenedioxymethamphetamine, commonly known as Ecstasy) is a potent mechanism-based inhibitor (MBI) of cytochrome P450 2D6 (CYP2D6), causing quasi-irreversible inhibition of the enzyme in vitro. An evaluation of the in vivo implications of this phenomenon depends on the accuracy of the estimates of the parameters that define the inhibition in vitro, namely kinact (the maximal inhibition rate) and KI (the inactivation constant). These values are determined in two steps, pre-incubation of the enzyme with the inhibitor (enzyme inactivation), followed by dilution and further incubation to measure residual enzyme activity with a probe substrate. The aim of this study was to assess the impact of different dilutions and probe substrate concentrations on the estimates of kinact and KI using recombinantly expressed CYP2D6. Enzyme activity was measured by the conversion of dextromethorphan (DEX) to dextrorphan (DOR). Dilution factors of 1.25, 2, 5, 10, 25 and 50 (DEX at 30µM) gave mean (±SE) values of kinact (min 1) of 0.20±0.06, 0.21±0.05, 0.31±0.06, 0.37±0.11, 0.51±0.10 and 0.58±0.08, respectively, and KI (µM) values (after correction for non-specific microsomal binding) of 2.22±1.90, 2.80±1.34, 5.78±2.07, 6.36±2.93, 3.99±1.57 and 4.86±1.37, respectively. Accordingly, high (e.g. 50 fold) and low (e.g. 1.25 fold) dilutions were associated with statistically significant differences in kinetic values ( p <0.05). Varying DEX concentration (10–100µM) was not associated with significant changes in kinact and K values when a five-fold dilution was used (with the exception of a lower KI at 10µM DEX). High dilution was also shown to reduce non-specific microsomal binding of MDMA. The changes in the two kinetic parameters were dependent on the experimental procedure and shown to be unlikely to have a material influence on the maximum inhibition of CYP2D6 expected in vivo after typical recreational doses of MDMA (50–100mg), since the potency of inhibition was high. The different values of the kinetic parameters were predicted to have a marginal influence on the time for recovery of enzyme activity following re-synthesis of CYP2D6.
Elastoplastic Stress Analysis and Residual Stresses in Metal-matrix-laminated Plates under In-plane and Transverse Loading
Authors: Küçük Mümin
Published: February 2006

Fiber-reinforced metal-matrix composites provide high strength, ductility, specific stiffness, yield point, and a good temperature performance. In this study, steel fiber-reinforced aluminum metal-matrix composite-laminated plates are loaded under in-plane and transverse forces. The finite element method is used for obtaining the solution. The Tsai-Hill theory is used as a yield criterion. The laminated plates are oriented symmetrically and antisymmetrically. The orientation angles are chosen as (0/90)2, (15/15)2, (30/30)2, (45/45)2, (60/60)2, (75/75)2, (0/15)2,(0/30)2,(0/45)2,(0/60)2, and (0/75)2 for the in-plane loading. The stress components are calculated for 500 and 700 load steps. The in-plane force is increased 0.08 (N/mm) per step. The transverse loading is carried out on symmetric and antisymmetric (0/90)2, (30/30)2, (45/45)2, and (60/60)2 laminated plates. The expansion of the plastic region is carried out for 100, 300, and 500 load steps. The magnitude of the residual stress components at the midpoint of the plates for different orientation angles are calculated.
Loss of Mechanical Properties by Water Absorption of Vinyl-ester Reinforced with Glass Fiber
Authors: De La Osa O. , Alvarez V. A. , Fraga A. N. , Mammone E. Martínez , Vázquez A.
Published: February 2006

The effect of water absorption on the mechanical properties of the composites has been studied. The matrix used was vinyl-ester. Different arrangements of glass fibers were used to reinforce vinyl-ester matrix: mat, unidirectional, and bidirectional cloth. The samples were immersed in distillated water at 80 C. The flexural modulus was measured as a function of immersion time. The decrease in the glass transition temperature, Tg, was correlated with the water absorption and flexural modulus. The composite flexural modulus was fitted by means of a modified rule of mixture, which included an interfacial coefficient. The relationship between the directionality of the fiber in the composite material and the water absorption was also analyzed.
Release of Polyanions from Polyelectrolyte Complexes by Selective Degradation of the Polycation
Authors: Etrych T. , Boustta M. , Leclercq L. , Vert M.
Published: February 2006

One of the major problems associated with analyzing polyelectrolyte complexes is the separation of strongly bound oppositely charged polymeric components. As part of a work aimed at better understanding the factors that affect polyelectrolyte complex formation and stability, an investigation of the possibility to release and analyze the polyanion, after hydrolytic or enzymatic degradation of the partner polycation, was made. Mixtures of poly(acrylic acid) or poly(L-lysine citramide) polyanions with poly(L-lysine) or poly(amino serinate) polycations were investigated. For each polycation-polyanion couple, four complex fractions were obtained by adding the polycation to the polyanion according to a titration protocol. The selective degradation of the polycation within the different complex fractions was investigated after the complex was disrupted with a NaCl solution. The molecular weights of the recovered polyanionic macromolecules were assessed by both static light scattering and size exclusion chromatography. The data supported previous findings that complexation was selective according to the molecular weight of the polyanion for a given polycation. The lower the degree of neutralization of the polyanion negative charges by the polycation positive charges, the greater the molecular weight of the complexed polyanionic macromolecules.
Plasminogen inhibits TNFα-induced apoptosis in monocytes
Authors: Mitchell Jennifer W. , Baik Nagyung , Castellino Francis J. , Miles Lindsey A.
Published: February 2006

Monocytes are major mediators of inflammation, and apoptosis provides a mechanism for regulating the inflammatory response by eliminating activated macrophages. Furthermore, as a consequence of apoptosis, plasminogen binding is markedly increased on monocytoid cells. Therefore, we investigated the ability of plasminogen to modulate monocyte apoptosis. Apoptosis of monocytoid cells (human monocytes and U937 cells) was induced with either TNFα or cycloheximide. When apoptosis was induced in the presence of increasing concentrations of plasminogen, apoptosis was inhibited in a dose-dependent manner with full inhibition achieved at 2 μM plasminogen. Plasminogen treatment also markedly reduced internucleosomal DNA fragmentation and reduced levels of active caspase 3, caspase 8, and caspase 9 induced by TNFα or by cycloheximide. We examined the requirement for plasmin proteolytic activity in the cytoprotective function of plasminogen. A plasminogen active site mutant, [D(646)E]-Plg, failed to recapitulate the cytoprotective effect of wild-type plasminogen. Furthermore, antibodies against PAR1 blocked the antiapoptotic effect of plasminogen. Our results suggest that plasminogen inhibits monocyte apoptosis. The cytoprotective effect of plasminogen requires plasmin proteolytic activity and requires PAR1. Because apoptosis of monocytes plays a key role in inflammation and atherosclerosis, these results provide insight into a novel role of plasminogen in these processes.
Phenotypic correction of von Willebrand disease type 3 blood-derived endothelial cells with lentiviral vectors expressing von Willebrand factor
Authors: De Meyer Simon F. , Vanhoorelbeke Karen , Chuah Marinee K. , Pareyn Inge , Gillijns Veerle , Hebbel Robert P. , Collen Désiré , Deckmyn Hans , VandenDriessche Thierry
Published: February 2006

Von Willebrand disease (VWD) is an inherited bleeding disorder, caused by quantitative (type 1 and 3) or qualitative (type 2) defects in von Willebrand factor (VWF). Gene therapy is an appealing strategy for treatment of VWD because it is caused by a single gene defect and because VWF is secreted into the circulation, obviating the need for targeting specific organs or tissues. However, development of gene therapy for VWD has been hampered by the considerable length of the VWF cDNA (8.4 kb [kilobase]) and the inherent complexity of the VWF protein that requires extensive posttranslational processing. In this study, a gene-based approach for VWD was developed using lentiviral transduction of blood-outgrowth endothelial cells (BOECs) to express functional VWF. A lentiviral vector encoding complete human VWF was used to transduce BOECs isolated from type 3 VWD dogs resulting in high-transduction efficiencies (95.6% ± 2.2%). Transduced VWD BOECs efficiently expressed functional vector-encoded VWF (4.6 ± 0.4 U/24 hour per 106 cells), with normal binding to GPIbα and collagen and synthesis of a broad range of multimers resulting in phenotypic correction of these cells. These results indicate for the first time that gene therapy of type 3 VWD is feasible and that BOECs are attractive target cells for this purpose.
Allogeneic T cells induce rapid CD34+ cell differentiation into CD11c+CD86+ cells with direct and indirect antigen-presenting function
Authors: Abbasian Javaneh , Mahmud Dolores , Mahmud Nadim , Chunduri Sandeep , Araki Hiroto , Reddy Pavan , Hoffman Ronald , Arpinati Mario , Ferrara James L. M. , Rondelli Damiano
Published: February 2006

Dendritic cells (DCs) derive from CD34+ cells or monocytes and stimulate alloimmune responses in transplantation. We hypothesized that the interaction between CD34+ cells and allogeneic T cells would influence the function of hematopoietic stem cells (HSCs). Cord blood (CB) CD34+ cells proliferated briskly in response to allogeneic, but not autologous, T cells when mixed with irradiated T cells for 6 days in vitro. This proliferation was significantly inhibited by an anti-HLA class II monoclonal antibody (mAb), by an anti-TNFα mAb, or by CTLA4-Ig. Allogeneic T cells induced the differentiation of CD34+ progenitors into cells with the morphology of dendritic monocytic precursors and characterized by the expression of HLA-DR, CD86, CD40, CD14, and CD11c, due to an endogenous release of TNFα. Cotransplantation of CD34+ cells with allogeneic T cells into nonobese diabetic-severe combined immunodeficiency (NOD/SCID) mice resulted in a greater engraftment of myeloid CD1c+ dendritic cells compared with cotransplantation with autologous T cells. In vitro, CD34+ cell-derived antigen-presenting cells (APCs) were functionally capable of both direct and indirect presentation of alloantigens. Based on these findings, we hypothesize that in HSC transplantation the initial cross talk between allogeneic T cells and CD34+ cells may result in the increased generation of APCs that can present host alloantigens and possibly contribute to the development of graft-versus-host disease. (Blood. 2006;108:203-208)
Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE)
Authors: Persidsky Yuri , Heilman David , Haorah James , Zelivyanskaya Marina , Persidsky Raisa , Weber Gregory A. , Shimokawa Hiroaki , Kaibuchi Kozo , Ikezu Tsuneya
Published: February 2006

The blood-brain barrier (BBB) is compromised during progressive HIV-1 infection, but how this occurs is incompletely understood. We studied the integrity of tight junctions (TJs) of brain microvascular endothelial cells (BMVECs) in an in vitro BBB system and in human brain tissues with HIV-1 encephalitis (HIVE). A downregulation of TJ proteins, claudin-5 and occludin, paralleled monocyte migration into the brain during HIVE. Because small G proteins (such as Rho) can play a role in BMVEC TJ assembly, an artificial BBB system explored the relationship among TJs, Rho/Rho kinase (RhoK) activation, and transendothelial monocyte migration. Coculture of monocytes with endothelial cells led to Rho activation and phosphorylation of TJ proteins. Rho and RhoK inhibitors blocked migration of infected and uninfected monocytes. The RhoK inhibitor protected BBB integrity and reversed occludin/claudin-5 phosphorylation associated with monocyte migration. BMVEC transfection with a constitutively active mutant of RhoK led to dislocation of occludin from the membrane and loss of BMVEC cell contacts. When dominant-negative RhoK-transfected BMVECs were used in BBB constructs, monocyte migration was reduced by 84%. Thus, loss of TJ integrity was associated with Rho activation caused by monocyte brain migration, suggesting that Rho/RhoK activation in BMVECs could be an underlying cause of BBB impairment during HIVE.
Regulation of phagocyte lifespan in the lung during bacterial infection
Authors: Dockrell David H , Whyte Moira K B
Published: February 2006

The innate-immune response to infection is critically dependent on the antimicrobial actions of macrophages and neutrophils. Host and pathogen have evolved strategies to regulate immune-cell antimicrobial functions via alterations in cell death. Modulation of phagocyte death by bacteria is an important pathogenic mechanism. Host benefits of phagocyte apoptosis also exist, and understanding the mechanisms and consequences of apoptosis is essential before we can devise strategies to modulate this element of the innate-immune response to the host's benefit. This is of particular importance in an organ such as the lung, in which the balance between the need to recruit phagocytes to maintain bacterial sterility and the requirement to clear recruited cells from the alveolar units to preserve physiologic gas exchange must be finely tuned to ensure survival during bacterial infection. Apoptosis clearly plays a critical role in reconciling these physiological requirements.
Chemokines, chemokine receptors, and cancer metastasis
Authors: Kakinuma Takashi , Hwang Sam T
Published: February 2006

It is clear from large clinical studies that selected chemokine receptors are often up-regulated in a large number of common human cancers, including those of the breast, lung, prostate, colon, and melanoma. Chemokine receptors and their corresponding chemokine ligands have been demonstrated to play a number of nonredundant roles in cancer metastasis to vital organs as well as regional lymph nodes, the most frequent site of cancer metastasis. Chemokine receptors may potentially facilitate tumor dissemination at several key steps of metastasis, including adherence of tumor cells to endothelium, extravasation from blood vessels, metastatic colonization, angiogenesis, proliferation, and protection from the host response via activation of key survival pathways such as phosphatidylinositol-3 kinase and Akt. It is interesting that many of these roles are reminiscent of their functions in leukocyte and stem cell trafficking. Lastly, we discuss therapeutic applications for chemokine receptor antagonists in cancer therapy.
Violence Against Women in Turkey and the Role of Women Physicians
Authors: Büken Nüket Örnek , Sahinoglu Serap
Published: February 2006

Violence against women is a serious problem in Turkey. The Women and Ethics Commission of the Turkish Physicians’ Association (Ankara Physicians’ Chamber) has undertaken significant work to counteract this. This article gives some indications of the sources of violence and discusses its social and health care implications. The Commission is pivotal in the education of women physicians and in heightening awareness of the situation. An outline is given of this work and recommendations are made on how violence against women can be tackled and eliminated.
New Perspectives on Rickettsial Evolution from New Genome Sequences of Rickettsia, particularly R. canadensis, and Orientia tsutsugamushi
Authors: EREMEEVA MARINA E. , MADAN ANUP , SHAW CHRIS D. , TANG KEVIN , DASCH GREGORY A.
Published: February 2006

Abstract: The complete genome sequences available for eight species of Rickettsia and information for other near relatives in the Rickettsiales including Orientia and species of Anaplasmataceae are a rich resource for comparative analyses of the evolution of these obligate intracellular bacteria. Differences in these organisms have permitted them to colonize varied intracellular compartments, arthropod vectors, and vertebrate reservoirs in both pathogenic and symbiotic relationships. We summarize some comparative aspects of the genomes of these organisms, paying particular attention to the recently completed sequence for R. canadensis McKiel strain and an estimated two‐thirds of the genome sequence for a Thailand patient isolate of Orientia tsutsugamushi. The Rickettsia genomes exhibit a high degree of synteny punctuated by distinctive chromosome inversions and consistent phylogenetic relationships regardless of whether protein coding sequences or RNA genes, concatenated open reading frames or gene regions, or whole genomes are used to construct phylogenetic trees. The aggregate characteristics (number, length, composition, repeat identity) of tandem repeat sequences of Rickettsia, which often exhibit recent and rapid divergence between closely related strains and species of bacteria, are also very conserved in Rickettsia but differed significantly in Orientia. O. tsutsugamushi shared no significant synteny to species of Rickettsia or Anaplasmataceae, supporting its placement in a unique genus. Like Rickettsia felis, Orientia has many transposases and ankyrin and tetratricopeptide repeat domains. Orientia shares the important ATP/ADP translocase and proline‐betaine transporter multigene families with Rickettsia, but has more gene families that may be involved in regulatory and transporter responses to environmental stimuli.
Preliminary Assessment of Genome Differences between the Reference Nine Mile Isolate and Two Human Endocarditis Isolates of Coxiella burnetii
Authors: BEARE PAUL A. , PORCELLA STEPHEN F. , SESHADRI REKHA , SAMUEL JAMES E. , HEINZEN ROBERT A.
Published: February 2006

Abstract: This study investigates the complete genome sequences of the Nine Mile, K, and G isolates to improve our understanding of the unique virulence properties of C. burnetii and to provide important insight into the genome architecture and genetic diversity of this pathogen.
A Minimal Set of DNA Repair Genes Is Sufficient for Survival of Coxiella burnetii under Oxidative Stress
Authors: MERTENS K , LANTSHEER L , SAMUEL J E
Published: February 2006

Abstract: This paper studies the functional and regulatory role of RecA, but further investigations are necessary to clarify the control mechanism of the SOS response gene expression in C. burnetii.
Phylogenic Analysis of Rickettsial Patatin‐like Protein with Conserved Phospholipase A2 Active Sites
Authors: BLANC GUILLAUME , RENESTO PATRICIA , RAOULT DIDIER
Published: February 2006

Abstract: Genome analysis of Rickettsia felis highlighted the presence of three patatin‐like protein (PLP) genes (pat1, pat2A, and pat2B), whereas only one PLP gene (pat1) is found in the other sequenced rickettsial genomes. Here, we aligned the rickettsial PLPs with characterized patatins from plants and found that they possess all the conserved amino acid residues identified as important for phospholipase A2 activity. We also carried out a phylogenic analysis of the rickettsial PLPs together with bacterial and eukaryotic homologs. The phylogeny of the rickettsial Pat1 proteins is in conflict with the currently recognized Rickettsia phylogeny. Possible scenarios that might explain this incongruence are discussed and involve either gene conversion or gene duplication events.
Growth of Typhus Group and Spotted Fever Group Rickettsiae in Insect Cells
Authors: UCHIYAMA TSUNEO
Published: February 2006

Abstract: To analyze the host dependency of rickettsial growth, NIAS‐AeAl‐2 insect cells (AeAl2) derived from mosquito were first used in this study. It was demonstrated that typhus group rickettsiae (TGR) grew well in AeAl2 cells, but spotted fever group rickettsiae (SFGR) failed. To elucidate the inhibitory process of the growth of SFGR in AeAl2 cells, the adherence and invasion were first analyzed. SFGR possessed abilities to adhere to and invade AeAl2 cells as well as TGR in contrast to their inability of the growth in the cells. Morphologically, generation of microvilli could not be observed on AeAl2 cells inoculated with either group of rickettsiae. On the contrary, Vero cells inoculated with rickettsiae generated a great number of microvilli that adhered to rickettsiae and engulfed them into the cells. The roles of rickettsial major outer membrane protein A and B (rOmpA and rOmpB) were later investigated using E. coli expressing either rOmpA or rOmpB on their surface. Bacteria expressing either one of the major outer membrane proteins of rickettsiae as well as bacteria not expressing these proteins showed adherence to and invasion of AeAl2 cells. Thus, it is yet to be elucidated whether these major outer membrane proteins have any roles in these steps.
Activity of Telithromycin against Thirteen New Isolates of C. burnetii Including Three Resistant to Doxycycline
Authors: ROLAIN JEAN‐MARC , LAMBERT FRÉDÉRIC , RAOULT DIDIER
Published: February 2006

Abstract: In this study we have evaluated the in vitro activity of antibiotics against 13 new isolates of Coxiella burnetii using a real‐time quantitative PCR assay. MICs against doxycycline ranged from 1 to 8 μg/mL, telithromycin from 0.5 to 2 μg/mL, and all strains had MICs ≥ 8 μg/mL for erythromycin. We report that strains resistant to doxycycline exist either in humans or animals.
Structural Features of Lipopolysaccharide from Rickettsia Typhi: The Causative Agent of Endemic Typhus
Authors: FODOROVA MARCELA , VADOVIC PAVOL , SKULTETY LUDOVIT , SLABA KATARINA , TOMAN RUDOLF
Published: February 2006

Abstract: Rickettsia typhi causes endemic typhus, a relatively mild, acute febrile illness characterized by headache and macular rash. It is maintained in rodents and transmitted to humans by flea Xenopsylla cheopis. R. typhi contains a lipopolysaccharide thought to display a noticeable antigenic activity. We examined its structural features and it appears that the O‐specific chain of the R. typhi LPS is composed mainly of the alternating Glc and QuiNAc residues linked by 1→4 bonds.
Phylogenetic Analysis of a Novel Molecular Isolate of Spotted Fever Group Rickettsiae from Northern Peru: Candidatus Rickettsia andeanae
Authors: JIANG JU , BLAIR PATRICK J. , FELICES VIDAL , MORON CECILIA , CESPEDES MANUEL , ANAYA ELIZABETH , SCHOELER GEORGE B. , SUMNER JOHN W. , OLSON JAMES G. , RICHARDS ALLEN L.
Published: February 2006

Abstract: Phylogenetic analysis of five rickettsial genes (17‐kDa gene, gltA, ompB, ompA, and sca4) from two molecular isolates of Candidatus Rickettsia andeanae from two ticks (Amblyomma maculatum and Ixodes boliviensis) collected from two domestic horses living in two separate locations in northern Peru (Coletas and Naranjo) was conducted to more clearly characterize this recently reported novel spotted fever group (SFG) rickettsia. Following nested polymerase chain reaction (PCR) amplification of the17‐kDa gene, gltA, ompB, ompA, and sca4, amplicons were purified, sequenced, and compared to those downloaded from GenBank. Phylogenetic analyses of the Candidatus Rickettsia andeanae sequences generated from17‐kDa gene (483 bp), gltA (1185 bp), ompA (1598 bp), ompB (4839 bp), and sca4 (2634 bp) demonstrated that they aligned strongly with those of SFG rickettsiae. Moreover, the sequences of these five genes most closely aligned with the following rickettsiae: ompA: Rickettsia sp RpA4 (98.03%), R. sp DnS28 (97.90%), and R. rhipicephali and R. massiliae (97.11%); ompB: R. aeschlimannii (97.22%), R. rhipicephali (97.20%), and R. sp Bar 29 (97.10%); and sca4: R. massiliae (97.8%), R. rhipicephali, and R. slovaca (97.7%). These results from the additional phylogenetic analyses of Candidatus Rickettsia andeanae confirm its inclusion within, and distance and uniqueness from, other known SFG rickettsiae.
Molecular and Biological Characterization of a Novel Coxiella‐like Agent from Carios capensis
Authors: REEVES WILL K. , LOFTIS AMANDA D. , PRIESTLEY RACHAEL A. , WILLS WILLIAM , SANDERS FELICIA , DASCH GREGORY A.
Published: February 2006

Abstract: The genus Coxiella is currently defined by a single monotypic species, Coxiella burnetii. Novel Coxiella spp. have been detected in ticks throughout the world. These bacteria have not been cultured or named, and their evolutionary relationships to C. burnetii are poorly known. A novel Coxiella‐like agent was detected by PCR amplification and sequencing of DNA extracted from 64 pelican ticks, Carios capensis, from Devoux Bank, South Carolina, USA. PCR was used to amplify and characterize genes from the new bacterium. Sequences from some metabolic and housekeeping genes shared a 92–98% similarity to C. burnetii, but other genes such as the IS1111 transposon, com1, and 5S and 16S rRNA genes were not amplified by conventional PCR. Transovarial and transtadial transmission and environmental shedding of the agent were detected by PCR.
Balancing Protective Immunity and Immunopathology: A Unifying Model of Monocytotropic Ehrlichiosis
Authors: ISMAIL NAHED , WALKER DAVID H.
Published: February 2006

Abstract: Interactions among pathogens, antigen‐presenting cells (APCs) and lymphocytes are critical in maintaining balance in the daily challenges to the immune system. Monocytotropic ehrlichiosis, caused by Ehrlichia chaffeensis, is a multisystem inflammatory ailment. A complex interaction between Ehrlichia and the immune systems of a number of mammalian hosts, in human disease and animal models, has been described. The presence of an overwhelming ehrlichial infection in immunocompromised individuals suggests that severe tissue damage is most likely due to direct bacterial effect. However, clinical and experimental observations indicate that this is an oversimplified concept. First, immunocompetent patients with severe ehrlichiosis have a low bacterial burden. Second, severe and fatal murine ehrlichiosis in immunocompetent animals, which mimics human disease, is associated with a low bacterial burden in different organs and late systemic and local overproduction of TNF‐α by T cells. In order to counterbalance overshooting immune responses, T cells and APCs secrete anti‐inflammatory cytokines that are key for maintaining a healthy balance between protection and immunopathology. CD4+ T cell‐mediated immunity and antibody responses of a Th1 phenotype play critical roles in protection against Ehrlichia. Of particular importance for the generation of protective immunity is the induction of activation programs in APCs directly by pathogens or by T cell‐derived factors. In this study, we consider the roles of innate and adaptive immune responses in terms of protection from severe ehrlichiosis and their potential roles in immunopathology.
Susceptibility and Resistance to Monocytic Ehrlichiosis in the Mouse
Authors: WINSLOW GARY M. , BITSAKTSIS CONSTANTINE , YAGER ERIC
Published: February 2006

Abstract: To address the role of cellular immunity during ehrlichia infection, we have utilized a model of monocytic ehrlichiosis that results from infection of mice by Ixodes ovatus ehrlichia (IOE). Although ehrlichiosis in humans is largely a disease of immunocompromised individuals, the use of the IOE model has allowed us to identify factors required for host defense in normal mice. Using a low‐dose infection C57BL/6 mouse model, we have demonstrated that host defense requires immune mechanisms involving CD4 T cell‐mediated, TNF‐α‐, IL‐12‐, and IFN‐γ‐dependent, macrophage activation. We have also provided formal evidence that IFN‐γ produced by CD4 Th1 cells is sufficient for protective immunity. Our recent studies have demonstrated, in addition, an essential role for IL‐10, which is probably important in inhibiting immunopathological responses, and for inducible nitric oxide synthase. The latter observation establishes an important role for reactive nitrogen intermediates in bacterial elimination in vivo. In contrast, evaluation of mice carrying wild‐type and mutant alleles of Nramp1 revealed at most a modest role for this gene in resistance to fatal IOE infection. Other studies in low‐dose infected mice have indicated that the generation of immunological memory may be impaired during low‐dose IOE infection, possibly due to bacterial immune subversion. These studies highlight the utility of the IOE mouse model in identifying important parameters of the immune response during ehrlichiosis.
Platelet Dysfunction after Association withAnaplasma phagocytophilum in Vitro
Authors: BORJESSON DORI L. , BRAZZELL JENNIFER L. , FEFERMAN REGINA
Published: February 2006

Abstract:Granulocytic anaplasmosis is a tick‐borne, zoonotic disease caused by an obligate intracellular granulocytotropic bacterium,Anaplasma phagocytophilum.A. phagocytophilumand otherAnaplasmaandEhrlichiaspp. have been variably implicated with an associated hematologic alteration, platelet dysfunction, that can result in potentially serious clinical sequelae including hemorrhage. The objective of this work was to define anin vitromodel to assess alterations in platelet function associated withA. phagocytophilum.
Anaplasma phagocytophilum Infection Reduces Expression of Phagocytosis‐Related Receptors on Neutrophils
Authors: GARYU JUSTIN W. A. , DUMLER J STEPHEN
Published: February 2006

Abstract: Anaplasma phagocytophilum is a tick‐transmitted obligate intracellular bacterium of neutrophils that causes human granulocytic anaplasmosis. Previous data confirm that in vitro infection by A. phagocytophilum modifies neutrophil functions, including a 50% or greater reduction in phagocytosis and shedding of neutrophil cell surface adhesion molecule receptors. If these receptors are downregulated or shed from the surface of neutrophils with A. phagocytophilum infection, it may prevent neutrophils from effective phagocytosis. We hypothesized that diminished phagocytosis in neutrophils is partly associated with the loss of surface phagocytic receptors. To address this, we assayed the expression of these receptors after 24 h of A. phagocytophilum infection in human neutrophils.
Second Primary Cancers in Thyroid Cancer Patients: A Multinational Record Linkage Study
Authors: Sandeep Thekkepat C. , Strachan Mark W. J. , Reynolds Rebecca M. , Brewster David H. , Scélo Ghislaine , Pukkala Eero , Hemminki Kari , Anderson Aage , Tracey Elizabeth , Friis Søren , McBride Mary L. , Kee-Seng Chia , Pompe-Kirn Vera , Kliewer Erich V. , Tonita Jon M. , Jonasson Jon G. , Martos Carmen , Boffetta Paolo , Brennan Paul
Published: February 2006

Context: Increasing incidence and improved prognosis of thyroid cancer have led to concern about the development of second primary cancers, especially after radioiodine treatment. Thyroid cancer can also arise as a second primary neoplasm after other cancers.

Objective: The objective of the study was to assess the risk of second primary cancer after thyroid cancer and vice versa.

Design: This was a multinational record linkage study.

Setting: The study was conducted at 13 population-based cancer registries in Europe, Canada, Australia, and Singapore.

Patients or Other Participants: A cohort of 39,002 people (356,035 person-yr of follow-up) with primary thyroid cancer were followed up for SPN for up to 25 yr, and 1,990 cases of thyroid cancer were diagnosed after another primary cancer.

Main Outcome Measures: To assess any possible excess of second primary neoplasms after thyroid cancer, the observed numbers of neoplasms were compared with expected numbers derived from age-, sex-, and calendar period-specific cancer incidence rates from each of the cancer registries, yielding standardized incidence ratios (SIRs). The SIR of second primary thyroid cancer after various types of cancer was also calculated.

Results: During the observation period, there were 2821 second primary cancers (all sites combined) after initial diagnosis of thyroid cancer, SIR of 1.31 (95% confidence interval 1.26–1.36) with significantly elevated risks for many specific cancers. Significantly elevated risks of second primary thyroid cancer were also seen after many types of cancer.

Conclusion: Pooled data from 13 cancer registries show a 30% increased risk of second primary cancer after thyroid cancer and increased risks of thyroid cancer after various primary cancers. Although bias (detection, surveillance, misclassification) and chance may contribute to some of these observations, it seems likely that shared risk factors and treatment effects are implicated in many. When following up patients who have been treated for primary thyroid cancer, clinicians should maintain a high index of suspicion for second primary cancers.
Association of tracheal placodes with leg primordia inDrosophilaand implications for the origin of insect tracheal systems
Authors: Franch-Marro Xavier , Martín Nicolás , Averof Michalis , Casanova Jordi
Published: February 2006

Adaptation to diverse habitats has prompted the development of distinct organs in different animals to better exploit their living conditions. This is the case for the respiratory organs of arthropods, ranging from tracheae in terrestrial insects to gills in aquatic crustaceans. Although Drosophila tracheal development has been studied extensively, the origin of the tracheal system has been a long-standing mystery. Here, we show that tracheal placodes and leg primordia arise from a common pool of cells in Drosophila, with differences in their fate controlled by the activation state of the wingless signalling pathway. We have also been able to elucidate early events that trigger leg specification and to show that cryptic appendage primordia are associated with the tracheal placodes even in abdominal segments. The association between tracheal and appendage primordia in Drosophila is reminiscent of the association between gills and appendages in crustaceans. This similarity is strengthened by the finding that homologues of tracheal inducer genes are specifically expressed in the gills of crustaceans. We conclude that crustacean gills and insect tracheae share a number of features that raise the possibility of an evolutionary relationship between these structures. We propose an evolutionary scenario that accommodates the available data.
Somite-derived cells replace ventral aortic hemangioblasts and provide aortic smooth muscle cells of the trunk
Authors: Pouget Claire , Gautier Rodolphe , Teillet Marie-Aimee , Jaffredo Thierry
Published: February 2006

We have previously shown that endothelial cells of the aortic floor give rise to hematopoietic cells, revealing the existence of an aortic hemangioblast. It has been proposed that the restriction of hematopoiesis to the aortic floor is based on the existence of two different and complementary endothelial lineages that form the vessel: one originating from the somite would contribute to the roof and sides, another from the splanchnopleura would contribute to the floor. Using quail/chick orthotopic transplantations of paraxial mesoderm, we have traced the distribution of somite-derived endothelial cells during aortic hematopoiesis. We show that the aortic endothelium undergoes two successive waves of remodeling by somitic cells: one when the aortae are still paired, during which the initial roof and sides of the vessels are renewed; and a second, associated to aortic hematopoiesis, in which the hemogenic floor is replaced by somite endothelial cells. This floor thus appears as a temporary structure, spent out and replaced. In addition,the somite contributes to smooth muscle cells of the aorta. In vivo lineage tracing experiments with non-replicative retroviral vectors showed that endothelial cells do not give rise to smooth muscle cells. However, in vitro,purified endothelial cells acquire smooth muscle cells characteristics. Taken together, these data point to the crucial role of the somite in shaping the aorta and also give an explanation for the short life of aortic hematopoiesis.
Semaphorin 3d guides laterality of retinal ganglion cell projections in zebrafish
Authors: Sakai Jill A. , Halloran Mary C.
Published: February 2006

The optic chiasm is an important choice point at which retinal ganglion cell (RGC) axons either cross the midline to innervate the contralateral brain or turn back to innervate the ipsilateral brain. Guidance cues that regulate this decision, particularly those directing the midline crossing of contralateral axons, are still not well understood. Here we show that Sema3d,a secreted semaphorin expressed at the midline, guides the crossing of RGC axons in zebrafish. Both Sema3d knockdown and ubiquitous overexpression induced aberrant ipsilateral projections, suggesting that Sema3d normally guides axons into the contralateral optic tract. Live imaging in vivo showed that RGC growth cones responded to ubiquitous Sema3d overexpression by pausing for extended periods and increasing their exploratory behavior at the midline,suggesting that Sema3d overexpression causes the midline environment to become less favorable for RGC axon extension. Interestingly, Sema3d overexpression did not affect growth cone behaviors before the midline, suggesting that RGC axons normally respond to Sema3d only upon reaching the midline. After Sema3d knockdown, growth cones grew across the midline but then paused or repeatedly retracted, impairing their ability to leave the midline region. Our results indicate that a proper balance of Sema3d is needed at the midline for the progression of RGC axons from the chiasm midline into the contralateral optic tract.
Sfrp1andSfrp2regulate anteroposterior axis elongation and somite segmentation during mouse embryogenesis
Authors: Satoh Wataru , Gotoh Takafumi , Tsunematsu Yasuhiko , Aizawa Shinichi , Shimono Akihiko
Published: February 2006

Regulation of Wnt signaling is essential for embryonic patterning. Sfrps are secreted Wnt antagonists that directly interact with the Wnt ligand to inhibit signaling. Here, we show that Sfrp1 and Sfrp2 are required for anteroposterior (AP) axis elongation and somitogenesis in the thoracic region during mouse embryogenesis. Double homozygous mutations in Sfrp1 and Sfrp2 lead to severe shortening of the thoracic region. By contrast, a homozygous mutation in one or the other exerts no effect on embryogenesis, indicating that Sfrp1 and Sfrp2 are functionally redundant. The defect of a shortened thoracic region appears to be the consequence of AP axis reduction and incomplete somite segmentation. The reduction in the AP axis is partially due to abnormalities in cell migration of pre-somitic mesoderm from the end of gastrulation. Aberrant somite segmentation is associated with altered oscillations of Notch signaling, as evidenced by abnormal Lfng and Hes7 expression during somitogenesis in the thoracic region. This study suggests that Wnt regulation by Sfrp1 and Sfrp2 is required for embryonic patterning.
Critical temperatures in the cephalopodSepia officinalisinvestigated usingin vivo31P NMR spectroscopy
Authors: Melzner Frank , Bock Christian , Pörtner Hans-O.
Published: February 2006

The present study was designed to test the hypothesis of an oxygen limitation defining thermal tolerance in the European cuttlefish (Sepia officinalis). Mantle muscle organ metabolic status and pHiwere monitored using in vivo31P NMR spectroscopy, while mantle muscle performance was determined by recording mantle cavity pressure oscillations during ventilation and spontaneous exercise.

Under control conditions (15°C), changes in muscle phospho-l-arginine (PLA) and inorganic phosphate (Pi)levels could be linearly related to frequently occurring, high-pressure mantle contractions with pressure amplitudes (MMPA) of >0.2 kPa. Accordingly,mainly MMPA of >2 kPa affected muscle PLA reserves, indicating that contractions with MMPA of <2 kPa only involve the thin layers of aerobic circular mantle musculature. On average, no more than 20% of muscle PLA was depleted during spontaneous exercise under control conditions.

Subjecting animals to acute thermal change at an average rate of 1 deg. h–1 led to significant Pi accumulation (equivalent to PLA breakdown) and decrements in the free energy of ATP hydrolysis(dG/dζ) at both ends of the temperature window, starting at mean critical temperatures (Tc) of 7.0 and 26.8°C,respectively. Frequent groups of high-pressure mantle contractions could not(in the warm) or only partially (in the cold) be related to net PLA breakdown in mantle muscle, indicating an oxygen limitation of routine metabolism rather than exercise-related phosphagen use. We hypothesize that it is mainly the constantly working radial mantle muscles that become progressively devoid of oxygen. Estimates of very low dG/dζ values (–44 kJ mol–1) in this compartment, along with correlated stagnating ventilation pressures in the warm, support this hypothesis. In conclusion, we found evidence for an oxygen limitation of thermal tolerance in the cuttlefish Sepia officinalis, as indicated by a progressive transition of routine mantle metabolism to an anaerobic mode of energy production.