bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity of pneumococcal surface protein A (PspA) among prevalent clones in Spain
Authors: Rolo Dora , Ardanuy Carmen , Fleites Ana , Martín Rogelio , Liñares Josefina 
Published: May 2009

Abstract

Background
PspA is recognized as a major pneumococcal virulence factor and a possible vaccine candidate. The aim of this study was to analyze the PspA family and clade distribution among 112 Spanish pneumococci representatives of dominant clones among patients with invasive disease (n = 66) and nasopharyngeal healthy carriage in children (n = 46).

Results
PspA family 2 was predominant among invasive (63.6%) and carriage (54.3%) pneumococcal isolates. No PspA family 3 isolates were detected and only one strain was PspA negative. Although four clonal complexes contained strains of different clades, a clear association between clade and multi locus sequence typing results was found. Clades 1, 3 and 4 were associated with a wide variety of sequence types (ST) related to multiresistant and antibiotic-susceptible worldwide-disseminated clones. Clade 1 was associated with Spain6B-ST90, Spain14-ST18, Colombia5-ST289, Sweden1-ST306, Denmark14-ST230 and Sweden1-ST304 clones. Clade 3 was associated with Spain23F-ST81, Spain9V-ST156, Tennessee14-ST67, Netherlands3-ST180 and Netherlands7F-ST191 clones. Clade 4 was related to Sweden15A-ST63, Netherlands18C-ST113 and Greece21-ST193 clones. In contrast, PspA clade was not related to serotype, age or clinical origin of the isolates.

Conclusion
PspA clades were associated with genotypes. PspA family 2 and family 1 were dominant among major Spanish pneumococcal clones isolated from patients with invasive disease and nasopharyngeal carriage in children.
No effect of running and laboratory housing on adult hippocampal neurogenesis in wild caught long-tailed wood mouse
Authors: Hauser Thomas , Klaus Fabienne , Lipp Hans-Peter , Amrein Irmgard 
Published: May 2009

Abstract

Background
Studies of adult hippocampal neurogenesis (AHN) in laboratory rodents have raised hopes for therapeutic interventions in neurodegenerative diseases and mood disorders, as AHN can be modulated by physical exercise, stress and environmental changes in these animals. Since it is not known whether cell proliferation and neurogenesis in wild living mice can be experimentally changed, this study investigates the responsiveness of AHN to voluntary running and to environmental change in wild caught long-tailed wood mice (Apodemus sylvaticus).

Results
Statistical analyses show that running had no impact on cell proliferation (p = 0.44), neurogenesis (p = 0.94) or survival of newly born neurons (p = 0.58). Likewise, housing in the laboratory has no effect on AHN. In addition, interindividual differences in the level of neurogenesis are not related to interindividual differences of running wheel performance (rs = -0.09, p = 0.79). There is a correlation between the number of proliferating cells and the number of cells of neuronal lineage (rs = 0.63, p < 0.001) and the number of pyknotic cells (rs = 0.5, p = 0.009), respectively.

Conclusion
Plasticity of adult neurogenesis is an established feature in strains of house mice and brown rats. Here, we demonstrate that voluntary running and environmental changes which are effective in house mice and brown rats cannot influence AHN in long-tailed wood mice. This indicates that in wild long-tailed wood mice different regulatory mechanisms act on cell proliferation and neurogenesis. If this difference reflects a species-specific adaptation or a broader adaptive strategy to a natural vs. domestic environment is unknown.
A Schistosoma japonicumchimeric protein with a novel adjuvant induced a polarized Th1 immune response and protection against liver egg burdens
Authors: Xu Xindong , Zhang Dongmei , Sun Wei , Zhang Qingfeng , Zhang Jingjing , Xue Xiangyang , Shen Luhui , Pan Weiqing 
Published: May 2009

AbstractBackgroundSchitosomiasis japonica is still a significant public health problem in China. A protective vaccine for human or animal use represents an important strategy for long-term control of this disease. Due to the complex life cycle of schistosomes, different vaccine design approaches may be necessary, including polyvalent subunit vaccines. In this study, we constructed four chimeric proteins (designated SjGP-1~4) via fusion of Sj26GST and four individual paramyosin fragments. We tested these four proteins as vaccine candidates, and investigated the effect of deviating immune response on protection roles in mice.MethodsThe immunogencity and protection efficacy of chimeric proteins were evaluated in mice. Next, the chimeric protein SjGP-3 was selected and formulated in various adjuvants, including CFA, ISA 206, IMS 1312 and ISA 70M. The titers of antigen-specific IgG, IgE and IgG subclass were measured. The effect of adjuvant on cytokine production and percentages of CD3+CD8-IFN-γ+cells and CD3+CD8-IL-4+cells were analyzed at different time points. Worm burdens and liver egg counts in different adjuvant groups were counted to evaluate the protection efficacy against cercarial challenge.ResultsImmunization of mice with chimeric proteins provided various levels of protection. Among the four proteins, SjGP-3 induced the highest level of protection, and showed enhanced protective efficacy compared with its individual component Sj26GST. Because of this, SjGP-3 was further formulated in various adjuvants to investigate the effect of adjuvant on immune deviation. The results revealed that SjGP-3 formulated in veterinary adjuvant ISA 70M induced a lasting polarized Th1 immune response, whereas the other adjuvants, including CFA, ISA 206 and IMS 1312, generated a moderate mixed Th1/Th2 response after immunization but all except for IMS 1312 shifted to Th2 response after onset of eggs. More importantly, the SjGP-3/70M formulation induced a significant reduction in liver egg deposition at 47.0–50.3% and the number of liver eggs per female at 34.5–37.2% but less effect on worm burdens at only 17.3–23.1%, whereas no effect of the formulations with other adjuvants on the number of liver eggs per female was observed.ConclusionConstruction of polyvalent subunit vaccine was capable to enhance immunogenicity and protection efficacy against schistosomiasis. There was correlation of the polarized Th1 response with reduction of liver egg burdens, supporting the immune deviation strategy for schistosomiasis japonica vaccine development.
Diagnosis of growth hormone (GH) deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency
Authors: Louvel Murielle , Marcu Mariana , Trivin Christine , Souberbielle Jean-Claude , Brauner Raja 
Published: May 2009

AbstractBackgroundMost patients with childhood non-organic growth hormone (GH) deficiency (GHD) produce a normal GH peak as young adults. Our objectives were to better define this transient GHD and evaluate the factors influencing the growth response of patients with pituitary stalk interruption syndrome (PSIS).MethodsWe studied 72 prepubertal patients with a GH peak < 6.7 ng/ml after 2 stimulation tests, treated with 0.2 mg GH/kg/w for at least 3 years. Group 1 (n = 53, 4.7 ± 4.0 years) had PSIS and Group 2 (n = 19, 9.2 ± 3.0 years) had transient GHD and normal pituitary.ResultsAt diagnosis, 64% of Group 1 and one Group 2 were < 5 years old. The growth rate of 59% Group 1 and two Group 2 patients was ≤ -2 SDS. The GH peak of 64% Group 1 patients and no Group 2 patients was < 3 ng/ml. The plasma insulin-like growth factor-1 of all Group 1 and all but one Group 2 patients was ≤ -2 z scores.During the first year of GH treatment, the growth rate was ≥ 2 SDS in 81% Group 1 and 37% Group 2 patients. In Group 1, it was negatively correlated with the GH peak before treatment (P < 0.03), and with the difference between the target and adult heights (P < 0.01).The height gain SDSs between diagnosis and adult height were 1.7 ± 1.2 in Group 1 (n = 30) and 1.08 ± 0.8 in Group 2 (n = 12, P = 0.05).ConclusionThe factors of the growth response to GH treatment should be analysed separately for each population: with and without PSIS or other markers.
Disease modifying and antiangiogenic activity of 2-Methoxyestradiol in a murine model of rheumatoid arthritis
Authors: Plum Stacy M , Park Eun J , Strawn Steve J , Moore Elizabeth G , Sidor Carolyn F , Fogler William E 
Published: May 2009

AbstractBackgroundA critical component of disease progression in rheumatoid arthritis (RA) involves neovascularization associated with pannus formation. 2-methoxyestradiol (2ME2) is a naturally occurring molecule with no known physiologic function, although at pharmacologic concentrations it has antiproliferative and antiangiogenic activities. We investigated the impact of orally administered 2ME2 on the initiation and development of proliferative synovitis using the anti-collagen monoclonal antibodies (CAIA) model.MethodsSevere polyarticular arthritis was induced in Balb/c female mice by administration of 2 mg of a monoclonal antibody cocktail intravenously into the tail vein of mice. Twenty-four hours following monoclonal antibody administration, mice were injected with 25 μg of LPS (E. colistrain 0111:B4) via the intraperitoneal route. Treatment with 2ME2 (100, 75, 50, 25, 10, 1 mg/kg, p.o., daily), or vehicle control began 24 hrs following LPS challenge and continued to day 21. Hind limbs were harvested, sectioned and evaluated for DMARD activity and general histopathology by histomorphometric analysis and immunohistochemistry (vWF staining). In a separate study, different dosing regimens of 2ME2 (100 mg/kg; q.d.vsq.w.vsq.w. × 2) were evaluated. The effect of treatment with 2ME2 on gene expression of inflammatory cytokines and angiogenic growth factors in the joint space was evaluated 5 and 14 days after the induction of arthritis.ResultsMice treated with 2ME2 beginning 24 hours post anti-collagen monoclonal antibody injection, showed a dose-dependent inhibition in mean arthritic scores. At study termination (day 21), blinded histomorphometric assessments of sectioned hind limbs demonstrated decreases in synovial inflammation, articular cartilage degradation, pannus formation, osteoclast activity and bone resorption. At the maximal efficacious dosing regimen (100 mg/kg/day), administration of 2ME2 resulted in total inhibition of the study parameters and prevented neovascularization into the joint. Examination of gene expression on dissected hind limbs from mice treated for 5 or 14 days with 2ME2 showed inhibition of inflammatory cytokine message for IL-1β, TNF-α, IL-6 and IL-17, as well as the angiogenic cytokines, VEGF and FGF-2.ConclusionThese data demonstrate that in the CAIA mouse model of RA, 2ME2 has disease modifying activity that is at least partially attributable to the inhibition of neovascular development. Further, the data suggests new mechanistic points of intervention for 2ME2 in RA, specifically inhibition of inflammatory mediators and osteoclast activity.
PTools: an opensource molecular docking library
Authors: Saladin Adrien , Fiorucci Sébastien , Poulain Pierre , Prévost Chantal , Zacharias Martin 
Published: May 2009

Abstract

Background
Macromolecular docking is a challenging field of bioinformatics. Developing new algorithms is a slow process generally involving routine tasks that should be found in a robust library and not programmed from scratch for every new software application.

Results
We present an object-oriented Python/C++ library to help the development of new docking methods. This library contains low-level routines like PDB-format manipulation functions as well as high-level tools for docking and analyzing results. We also illustrate the ease of use of this library with the detailed implementation of a 3-body docking procedure.

Conclusion
The PTools library can handle molecules at coarse-grained or atomic resolution and allows users to rapidly develop new software. The library is already in use for protein-protein and protein-DNA docking with the ATTRACT program and for simulation analysis. This library is freely available under the GNU GPL license, together with detailed documentation.
Structural insights into chondroitin sulphate A binding Duffy-binding-like domains from Plasmodium falciparum: implications for intervention strategies against placental malaria
Authors: Gill Jasmita , Chitnis Chetan E , Sharma Amit 
Published: May 2009

Abstract

Background
Placental malaria is typified by selective clustering of Plasmodium falciparum in the intervillous blood spaces of the placenta. Sequestration of malaria parasite in the human placenta is mediated by interactions between chondroitin sulphate A (CSA) on the syncytiotrophoblasts and proteins expressed on the surface of infected human erythrocytes. Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) encoded by the var2CSA gene is believed to be the main parasite ligand for CSA-mediated placental binding.

Methods
Extensive sequence and structure comparisons of the various CSA-binding and non-binding DBL domains from the var2CSA gene from A4 and 3D7 strains of P. falciparum were performed. Three-dimensional structural models of various DBL domains were built and analysed with a view to assessing conservation of CSA interaction sites across various DBL domains.

Results
Each of the six DBL domains from var2CSA are likely to retain the disulfide linkages evident from previously published DBL domain crystal structures. The number of disulfide linkages between the various DBL domains analysed varies from three to seven, of which two are conserved across all DBL domains. The conserved disulfide linkages are distributed within the respective three sub-domains and only one linkage is shared by sub-domains I and II. Major differences between CSA-binding DBL domains are in the loop regions, which tie the alpha helices together, and in variable length terminal extensions. Intriguingly, a crucial loop from A4 DBL 3X which provides the important Gly and Lys residues that chelate the bound sulphate is missing or significantly altered in all other DBL domains that interact with CSA. Further analysis of the proposed sulphate and predicted CSA-binding site indicates either none or very low level of conservation among the critical interacting residues.

Conclusion
Structural comparisons of the three-dimensional structures of CSA-binding DBL domains indicates that the proposed CSA interaction site on A4 DBL 3X is unlikely to be conserved across the other CSA-binding DBL domains from var2CSA. Therefore, the 4 CSA-binding DBL domains encoded by var2CSA are unlikely to have common architectures to their CSA recognition sites. These structural insights have clear implications in using CSA-binding DBL domains for vaccines against placental malaria as it is proposed that the various CSA-binding DBL domains on var2CSA will recognize their CSA ligands differently.
Preliminary study of malaria incidence in Nouakchott, Mauritania
Authors: Lekweiry Khadijetou Mint , Abdallahi Mohamed Ould , Ba Hâmpaté , Arnathau Céline , Durand Patrick , Trape Jean-François , Salem Ali Ould Mohamed 
Published: May 2009

Abstract

Background
Malaria is one of the main motives for outpatient consultation and hospitalization in Mauritania. However, its incidence remains unclear because of diagnostic problems and insufficient epidemiological data.

Methods
Between April and August 2007, a study on malaria incidence was carried out in Nouakchott city. A total of 237 febrile outpatients, from all Nouakchott districts, attending the two main hospitals of the city were investigated. Finger prick and blood dried filter paper samples were performed to prepare thick and thin films and nested-PCR for malaria parasite species identification and density. The accuracy of diagnosis of 'presumptive malaria', assigned by clinicians and based on fever and other malaria suggestive symptoms, was assessed. Entomological investigations based on morphological and molecular characterization of Anopheline species were conducted in Dar Naïm district.

Results
Malaria prevalence rate was 25.7% (61/237), the majority of positive blood slides as well as nested-PCR products were due to Plasmodium vivax 70.5% (43/61) and Plasmodium ovale 24.6% (15/61). Two malaria patients, both with P. vivax, have never travelled out of Nouakchott and seem likely to have been autochthonous (3.3%). Of the 237 individuals included in the survey, 231(97.5%) were clinically diagnosed and treated as malaria cases. 26.4% of clinically diagnosed cases were positive for Plasmodium using microscopic examination and PCR. Thus, false positive cases constituted 73.6% (170/231) of the clinically diagnosed malaria cases. The search for mosquito vectors in Dar Naïm district allowed morphological and molecular identification of Anopheles arabiensis and Anopheles pharoensis.

Conclusion
This study demonstrates that, during the hot and dry season, Plasmodium species responsible of recurrent malaria (P. vivax and P. ovale) are the dominant species in Nouakchott city and autochthonous malaria cases exist but are rare. Clinical diagnosis of malaria has a very low positive predicted value. The systematic use of microscopy-based diagnosis and/or rapid diagnostic tests should be considered to appropriately manage malaria and non-malaria cases.
Cigarette smoke regulates the expression of TLR4 and IL-8 production by human macrophages
Authors: Sarir Hadi , Mortaz Esmaeil , Karimi Khalil , Kraneveld Aletta D , Rahman Irfan , Caldenhoven Eric , Nijkamp Frans P , Folkerts Gert 
Published: May 2009

AbstractBackgroundToll-like receptors (TLRs) are present on monocytes and alveolar macrophages that form the first line of defense against inhaled particles. The importance of those cells in the pathophysiology of chronic obstructive pulmonary disease (COPD) has well been documented. Cigarette smoke contains high concentration of oxidants which can stimulate immune cells to produce reactive oxygen species, cytokines and chemokines.MethodsIn this study, we evaluated the effects of cigarette smoke medium (CSM) on TLR4 expression and interleukin (IL)-8 production by human macrophages investigating the involvement of ROS.Results and DiscussionTLR4 surface expression was downregulated on short term exposure (1 h) of CSM. The downregulation could be explained by internalization of the TLR4 and the upregulation by an increase in TLR4 mRNA. IL-8 mRNA and protein were also increased by CSM. CSM stimulation increased intracellular ROS-production and decreased glutathione (GSH) levels. The modulation of TLR4 mRNA and surface receptors expression, IRAK activation, IκB-α degradation, IL-8 mRNA and protein, GSH depletion and ROS production were all prevented by antioxidants such as N-acetyl-L-cysteine (NAC).ConclusionTLR4 may be involved in the pathogenesis of lung emphysema and oxidative stress and seems to be a crucial contributor in lung inflammation.
Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial
Authors: Beran Jiri , Ambrozaitis Arvydas , Laiskonis Alvydas , Mickuviene Narseta , Bacart Patrick , Calozet Yvan , Demanet Etienne , Heijmans Stephane , Van Belle Paul , Weber Françoise , Salamand Camille 
Published: May 2009

Abstract

Background
Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine.

Methods
In a randomised, partially blinded, controlled study, healthy volunteers (1150 aged 18 to 57 years at enrolment) received three annual vaccinations of intradermal or intramuscular vaccine. In Year 1, subjects were randomised to one of three groups: 3 μg or 6 μg haemagglutinin/strain/dose of inactivated influenza vaccine intradermally, or a licensed inactivated influenza vaccine intramuscularly containing 15 μg/strain/dose. In Year 2 subjects were randomised again to one of two groups: 9 μg/strain/dose intradermally or 15 μg intramuscularly. In Year 3 subjects were randomised a third time to one of two groups: 9 μg intradermally or 15 μg intramuscularly. Randomisation lists in Year 1 were stratified for site. Randomisation lists in Years 2 and 3 were stratified for site and by vaccine received in previous years to ensure the inclusion of a comparable number of subjects in a vaccine group at each centre each year. Immunogenicity was assessed 21 days after each vaccination. Safety was assessed throughout the study.

Results
In Years 2 and 3, 9 μg intradermal was comparably immunogenic to 15 μg intramuscular for all strains, and both vaccines met European requirements for annual licensing of influenza vaccines. The 3 μg and 6 μg intradermal formulations were less immunogenic than intramuscular 15 μg. Safety of the intradermal and intramuscular vaccinations was comparable in each year of the study. Injection site erythema and swelling was more common with the intradermal route.

Conclusion
An influenza vaccine with 9 μg of haemagglutinin/strain given using an intradermal microinjection system showed comparable immunogenic and safety profiles to a licensed intramuscular vaccine, and presents a promising alternative to intramuscular vaccination for influenza for adults younger than 60 years.

Trial registration
Clinicaltrials.gov NCT00703651.
Activation of Cytosolic Phospholipase A2 in Dorsal Root Ganglion Neurons by Ca2+/Calmodulin-Dependent Protein Kinase II after Peripheral Nerve Injury
Authors: Hasegawa Shigeo , Kohro Yuta , Tsuda Makoto , Inoue Kazuhide 
Published: May 2009

Background Peripheral nerve injury leads to a persistent neuropathic pain state in which innocuous stimulation elicits pain behavior (tactile allodynia), but the underlying mechanisms have remained largely unknown. We have previously shown that spinal nerve injury induces the activation of cytosolic phospholipase A2 (cPLA2) in injured dorsal root ganglion (DRG) neurons that contribute to tactile allodynia. However, little is known about the signaling pathway that activates cPLA2 after nerve injury. In the present study, we sought to determine the mechanisms underlying cPLA2 activation in injured DRG neurons in an animal model of neuropathic pain, focusing on mitogen-activated protein kinases (MAPKs) and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Results Pharmacological inhibition of either p38 or extracellular signal-regulated kinase (ERK) in the injured DRG, which led to suppression of the development of tactile allodynia, did not affect cPLA2 phosphorylation and translocation after nerve injury. By contrast, a CaMKII inhibitor prevented the development and expression of nerve injury-induced tactile allodynia and reduced both the level of cPLA2 phosphorylation and the number of DRG neurons showing translocated cPLA2 in response to nerve injury. Applying ATP to cultured DRG neurons increased the level of both phosphorylated cPLA2 and CaMKII in the vicinity of the plasma membrane and caused physical association of these two proteins. In addition, ATP-stimulated cPLA2 and CaMKII phosphorylation were inhibited by both a selective P2X3R/P2X2+3R antagonist and a nonselective voltage-dependent Ca2+ channel (VDCC) blocker. Conclusion These results suggest that CaMKII, but not MAPKs, has an important role in cPLA2 activation following peripheral nerve injury, probably through P2X3R/P2X2+3R and VDCCs in primary afferent neurons.