bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activities of Several Classes of Acyclic Nucleoside Phosphonates against Camelpox Virus Replication in Different Cell Culture Models
Authors: Duraffour Sophie , Snoeck Robert , Krečmerová Marcela , van Den Oord Joost , De Vos Rita , Holý Antonín , Crance Jean-Marc , Garin Daniel , De Clercq Erik , Andrei Graciela 
Published: September 2007

ABSTRACT

Camelpox virus (CMLV) is the closest known virus to variola virus. Here we report on the anti-CMLV activities of several acyclic nucleoside phosphonates (ANPs) related to cidofovir [(
S
)-1-(3-hydroxy-2-phosphonomethoxypropyl)cytosine (HPMPC; Vistide)] against two CMLV strains, CML1 and CML14. Cytopathic effect (CPE) reduction assays performed with human embryonic lung fibroblast monolayers revealed the selectivities of the first two classes of ANPs (cHPMPA, HPMPDAP, and HPMPO-DAPy) and of the hexadecyloxyethyl ester of 1-{[(5
S
)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-5-azacytosine (HDE-cHPMP-5-azaC), belonging to the newly synthesized ANPs, which are HPMP derivatives containing a 5-azacytosine moiety. The inhibitory activities of ANPs against both strains were also confirmed with primary human keratinocyte (PHK) monolayers, despite the higher toxicity of those molecules on growing PHKs. Virus yield assays confirmed the anti-CML1 and anti-CML14 efficacies of the compounds selected for the highest potencies in CPE reduction experiments. Ex vivo studies were performed with a 3-dimensional model of human skin, i.e., organotypic epithelial raft cultures of PHKs. It was ascertained by histological evaluation, as well as by virus yield assays, that CMLV replicated in the human skin equivalent. HPMPC and the newly synthesized ANPs proved to be effective at protecting the epithelial cells against CMLV-induced CPE. Moreover, in contrast to the toxicity on PHK monolayers, signs of toxicity in the differentiated epithelium were seen only at high ANP concentrations. Our results demonstrate that compounds belonging to the newly synthesized ANPs, in addition to cidofovir, represent promising candidates for the treatment of poxvirus infections.
The
Streptococcus pyogenes
Serotype M49 Nra-Ralp3 Transcriptional Regulatory Network and Its Control of Virulence Factor Expression from the Novel
eno ralp3 epf sagA
Pathogenicity Region
Authors: Kreikemeyer Bernd , Nakata Masanobu , Köller Thomas , Hildisch Hendrikje , Kourakos Vassilios , Standar Kerstin , Kawabata Shigetada , Glocker Michael O. , Podbielski Andreas 
Published: September 2007

ABSTRACT

Many
Streptococcus pyogenes
(group A streptococcus [GAS]) virulence factor- and transcriptional regulator-encoding genes cluster together in discrete genomic regions. Nra is a central regulator of the FCT region. Previous studies exclusively described Nra as a transcriptional repressor of adhesin and toxin genes. Here transcriptome and proteome analysis of a serotype M49 GAS strain and an isogenic Nra mutant of this strain revealed the complete Nra regulon profile. Nra is active in all growth phases tested, with the largest regulon in the transition phase. Almost exclusively, virulence factor-encoding genes are repressed by Nra; these genes include the GAS pilus operon, the capsule synthesis operon, the cytolysin-mediated translocation system genes, all Mga region core virulence genes, and genes encoding other regulators, like the Ihk/Irr system, Rgg, and two additional RofA-like protein family regulators. Surprisingly, our experiments revealed that Nra additionally acts as a positive regulator, mostly for genes encoding proteins and enzymes with metabolic functions. Epidemiological investigations revealed strong genetic linkage of one particular Nra-repressed regulator, Ralp3 (SPy0735), with a gene encoding Epf (extracellular protein factor from
Streptococcus suis
). In a serotype-specific fashion, this
ralp3 epf
gene block is integrated, most likely via transposition, into the
eno sagA
virulence gene block, which is present in all GAS serotypes. In GAS serotypes M1, M4, M12, M28, and M49 this novel discrete genetic region is therefore designated the
eno ralp3 epf sagA
(ERES) pathogenicity region. Functional experiments showed that Epf is a novel GAS plasminogen-binding protein and revealed that Ralp3 activity counteracts Nra and MsmR regulatory activity. In addition to the Mga and FCT regions, the ERES region is the third discrete chromosomal pathogenicity region. All of these regions are transcriptionally linked, adding another level of complexity to the known GAS growth phase-dependent regulatory network.
Coinfection with Antigenically and Genetically Distinct Virulent Strains of
Babesia bovis
Is Maintained through All Phases of the Parasite Life Cycle
Authors: Berens Shawn J. , Brayton Kelly A. , McElwain Terry F. 
Published: September 2007

ABSTRACT

Antigenic polymorphism is a defining characteristic of the
Babesia bovis
variable merozoite surface antigen (VMSA) family. Sequence analysis strongly suggests that recombination between virulent strains contributes to VMSA diversity. While meiosis during the aneuploid stage of the parasite's life cycle in the tick vector
Rhipicephalus
(
Boophilus
)
microplus
is the most probable source of interstrain recombination, there is no definitive evidence that coinfection of the mammalian host or
R. microplus
ticks with more than one virulent strain occurs. Using allele-specific real-time quantitative PCR, we tested the hypotheses that cattle could support coinfection of two antigenically variant virulent tick-transmissible strains of
B. bovis
and that
R. microplus
ticks could acquire and transmit these two divergent strains. The results indicate that both calves and ticks can support virulent
B. bovis
coinfection through all phases of the hemoparasite's life cycle. Neither strain dominated in either the mammalian or invertebrate host, and larval tick progeny, which could be coinfected individually, were also able to transmit both strains, resulting in virulent babesiosis in recipients. While coinfection of the tick vector provides the context in which allelic antigenic diversity can be generated, recombination of VMSA genes could not be confirmed, suggesting that VMSA allelic changes are slow to accumulate.
Comparison of Tissue-Selective Proinflammatory Gene Induction in Mice Infected with Wild-Type, DNA Adenine Methylase-Deficient, and Flagellin-DeficientSalmonella enterica
Authors: Simon Raphael , Heithoff Douglas M. , Mahan Michael J. , Samuel Charles E. 
Published: September 2007

ABSTRACTMutants ofSalmonella entericaserovar Typhimurium deficient in DNA adenine methylase (Dam) are attenuated for virulence in mice and confer heightened immunity in vaccinated animals. In contrast, infection of mice with wild-type (WT) strains or flagellin-deficient mutants ofSalmonellacauses typhoid fever. Here we examined the bacterial load and spatiotemporal kinetics of expression of several classes of host genes in Peyer's patches, the liver, and the spleen following oral infection of mice with WT,dammutant, or flagellin-deficient (flhC)Salmonella. The genes evaluated included inflammatory (interleukin-1β [IL-1β], tumor necrosis factor alpha), chemokine (macrophage inflammatory protein 2), Th1/Th2 indicator (IL-12p40, IL-4), and interferon system (beta interferon [IFN-β], IFN-γ, protein Mx1 GTPase, RNA-dependent protein kinase, inducible nitric oxide synthase, suppressor of cytokine signaling 1) beacons. We showed that maximal interferon system and proinflammatory gene induction occurred by 5 days after infection and that the levels were comparable for the WT andflhCstrains but were significantly lower for thedammutant. Additionally, host gene expression in systemic tissues of individual animals was dependent on the bacterial load in the Peyer's patches for mice infected with WT,dammutant, orflhCmutantSalmonellaas early as 8 h after infection. Moreover, a bacterial load threshold in the Peyer's patches was necessary to stimulate the host gene induction in the liver and spleen. Taken together, these results suggest that bacterial load and the accompanying strain-specific cytokine signature are important determinants of the host innate immune response and associated disease manifestations observed indammutantSalmonella-infected animals compared to the immune response and disease manifestations observed in WT andflhCmutantSalmonella-infected animals.
Multilocus structure in thePinus contorta – Pinus banksianacomplex
Authors: Yang Rong-Cai , Yeh Francis C. , Ye Terrance Z. 
Published: September 2007

Natural hybridization between lodgepole pine ( Pinus contorta Dougl. ex Loud.) and jack pine ( Pinus banksiana Lamb.) in western Canada provides a distinct opportunity to infer evolutionary and demographic determinants of nonrandom associations of the alleles at different loci occurring in this Pinus contorta – Pinus banksiana complex (PCBC). Here, we investigated multilocus associations among and within 40 PCBC populations sampled from central and northwestern Alberta, using 39 random amplified polymorphic DNA (RAPD) markers. For each of the 40 PCBC populations, we examined distributions of 741 pairs of linkage (gametic) disequilibria (LD) between the 39 RAPDs and measured the “average” multilocus associations using the summary statistics that allow for packaging of individual LD in each population. We then partitioned the variance of LD in the total population to assess the causes of multilocus population structure. The results showed that (i) LD were more prominent in hybrid populations than in parental populations; (ii) multilocus Wahlund effect was a much more important determinant of population structure than its single-locus counterpart, particularly in hybrid populations; and (iii) considerable mutlilocus associations across the populations within each taxa group was due to the presence of different multilocus haplotypes in different populations. Such results are best explained by the fact that PCBC populations are geographically and ecologically marginal and are produced at the balance between mixing of two distinct gene pools creating new recombinants and selection in favor of parental gametes, but against the recombinants.
Extending the Path-Planning Horizon
Authors: Nabbe Bart , Hebert Martial 
Published: September 2007

The mobility sensors on a typical mobile robot vehicle have limited range. Therefore a navigation system has no knowledge about the world beyond this sensing horizon. As a result, path planners that rely only on this knowledge to compute paths are unable to anticipate obstacles sufficiently early and have no choice but to resort to an inefficient local obstacle avoidance behavior. To alleviate this problem, we present an opportunistic navigation and view planning strategy that incorporates look-ahead sensing of possible obstacle configurations. This planning strategy is based on a “what-if” analysis of hypothetical future configurations of the environment. Candidate sensing positions are evaluated based on their ability to observe anticipated obstacles. These sensing positions identified by this forward-simulation framework are used by the planner as intermediate waypoints. The validity of the strategy is supported by results from simulations as well as field experiments with a real robotic platform. These results show that significant reduction in path length can be achieved by using this framework.
Translocation of the novel cytokine HMGB1 to the cytoplasm and extracellular space coincides with the peak of clinical activity in experimentally UV-induced lesions of cutaneous lupus erythematosus
Authors: Barkauskaite V. , Ek M. , Popovic K. , Harris H.E. , Wahren-Herlenius M. , Nyberg F. 
Published: September 2007

HMGB1 is a pro-inflammatory cytokine that together with TNF-α and IL-1β is involved in the pathogenesis of spontaneously occurring skin lesions in lupus erythematosus. The purpose of the present study was to explore the sequence of events in HMGB1, TNF-α and IL-1β expression under development and resolution of experimentally induced CLE lesions. The study involved investigation of 38 serial skin biopsies acquired from photoprovoked skin lesions of nine CLE patients, using immunohistochemical staining of tissue sections. In biopsies from the clinically most active phase of skin involvement extracellular, secreted HMGB1 and increased cytoplasmic HMGB1 were found, as compared with the late and fading lesions or non-lesional skin. Besides HMGB1, increased expression of TNF-α and IL-1β was observed in dermal infiltrates of the induced CLE lesions. These cytokines were however not upregulated in all lesions, and increased expression of IL-1β was seen predominantly in late biopsies. In conclusion, extracellular and cytoplasmic HMGB1 coincides with the clinically most active phase of photoinduced lesions of cutaneous lupus, and suggests that HMGB1 is an important factor in the inflammatory autoimmune process of CLE. HMGB1 can induce expression of TNF-α and IL-1β, and formation of a pro-inflammatory loop between HMGB1, TNF-α, and IL-1β may be responsible for the prolonged and sustained inflammation in CLE. Lupus (2007) 16, 794—802.
Validity of a French version of the fatigue impact scale in multiple sclerosis
Authors: Debouverie M. , Pittion-Vouyovitch S. , Louis S. , Guillemin F. 
Published: September 2007

Purpose Fatigue is a frequent and common symptom of multiple sclerosis (MS) that can interfere with patients' everyday activities. There is no objective scale for assessing fatigue in French MS patients. The objective of this study was to adapt an English language scale for use with French patients. Methods The Fatigue Impact Scale was translated and culturally adapted into French by a committee of medical and linguistic specialists. The psychometric properties of this new instrument, called EMIF-SEP were assessed. Results EMIF-SEP is composed of 40 items. Four dimensions of this scale (cognitive, physical, social role and psychological) were identified by factor analysis. Each dimension had a high internal consistency (Cronbach's alpha >0.80). The test-retest reproducibility was very satisfactory; intra-class correlation coefficients were all above 0.70. Conclusion EMIF-SEP is the first scale for assessing MS-related fatigue which has been adapted to French-speaking patients. It is useful for clinical practice and MS-related research. Multiple Sclerosis 2007; 13: 1026—1032. http://msj.sagepub.com
Sexual habits before multiple sclerosis: a National case—control study
Authors: Lidegaard Øjvind , Svendsen Anne Louise 
Published: September 2007

The trigging off agent for multiple sclerosis (MS) is despite intensive epidemiological and biomedical research still unknown. The disease is typically diagnosed in reproductive age and recent findings have suggested that MS could be a sexually transmitted disease. Aim To assess the influence of different sexual practices in young age on the risk of developing MS, and specifically to explore the possible impact of oral sex and oral sperm exposure on this risk. Design National case—control study. Methods Inclusion: Danish women with a first time MS discharge diagnosis from a neurological department at most 40 years old during the period 1998—2005, and an age and geographically matched control group. The response rate to our postal questionnaires was 75% for cases and 61% for controls. A total of 604/619 completed case/control questionnaires were included in the analysis. Data underwent logistic regression analysis. Results We found no difference between women with and without MS for years of schooling, oral herpes infections, genital herpes, blood transfusions, age at sexual debut, age at coital debut, number of sexual partners before and after age 20 years, anal sex, condyloma attack or chlamydia infections. Family disposition with an affected father, mother or sibling, increased the risk of MS 9.1, 6.9 and 4.1 times, respectively. A total of 68% of cases and of 72% of controls had oral sex sometimes or often before their 20th year. Among women entertaining oral sex, 53%, respectively, 54% had experienced oral sperm exposure. Also oral sex after 20 years was similar in women with and without MS. Conclusion Neither oral sex in early reproductive age, oral sperm exposure, oral sex after 20 years, sexual debut, nor number of sexual partners had any association to the risk of later developing MS. This study does not support the hypothesis that MS is a sexually transmitted or acquired disease. Multiple Sclerosis 2008; 14: 67—72. http://msj.sagepub.com
Superficial and deep sternal wound infection after more than 9000 coronary artery bypass graft (CABG): incidence, risk factors and mortality
Authors: Salehi Omran Abbas , Karimi Abbasali , Ahmadi S Hossein , Davoodi Setareh , Marzban Mehrab , Movahedi Namvar , Abbasi Kyomars , Boroumand Mohammad Ali , Davoodi Saeed , Moshtaghi Naghmeh 
Published: September 2007

Abstract

Background
Sternal wound infection (SWI) is an uncommon but potentially life-threatening complication of cardiac surgery. Predisposing factors for SWI are multiple with varied frequencies in different studies. The purpose of this study was to assess the incidence, risk factors, and mortality of SWI after coronary artery bypass grafting (CABG) at Tehran Heart Center.

Methods
This study prospectively evaluated multiple risk factors for SWI in 9201 patients who underwent CABG at Tehran Heart Center between January 2002 and February 2006. Cases of SWI were confirmed based on the criteria of the Centers for Disease Control and Prevention. Deep SWI (bone and mediastinitis) was categorized according to the Oakley classification.

Results
In the study period, 9201 CABGs were performed with a total SWI rate of 0.47 percent (44 cases) and deep SWI of 0.22 percent (21 cases). Perioperative (in-hospital) mortality was 9.1% for total SWI and about 14% for deep SWI versus 1.1% for non-SWI CABG patients. Female gender, preoperative hypertension, high functional class, diabetes mellitus, obesity, prolonged intubation time (more than 48 h), and re-exploration for bleeding were significant risk factors for developing SWI (p = 0.05) in univariate analysis. In multivariate analysis, hypertension (OR = 10.7), re-exploration (OR = 13.4), and female gender (OR = 2.7) were identified as significant predictors of SWI (p < 0.05 for all). The rate of SWI was relatively similar in 3 groups of prophylactic antibiotic regimen (Cefazolin, Cefazolin + Gentamycin and Cefazolin + Amikacin: 0.5%, 0.5%, and 0.34% respectively).

Conclusion
Rarely reported previously, the two risk factors of hypertension and the female gender were significant risk factors in our study. Conversely, some other risk factors such as cigarette smoking and age mentioned as significant in other reports were not significant in our study. Further studies are needed for better documentation.
Crystal structure of Leishmania tarentolae hypoxanthine-guanine phosphoribosyltransferase
Authors: Monzani Paulo S , Trapani Stefano , Thiemann Otavio H , Oliva Glaucius 
Published: September 2007

Abstract

Background
Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) (EC 2.4.2.8) is a central enzyme in the purine recycling pathway. Parasitic protozoa of the order Kinetoplastida cannot synthesize purines de novo and use the salvage pathway to synthesize purine bases, making this an attractive target for antiparasitic drug design.

Results
The glycosomal HGPRT from Leishmania tarentolae in a catalytically active form purified and co-crystallized with a guanosine monophosphate (GMP) in the active site. The dimeric structure of HGPRT has been solved by molecular replacement and refined against data extending to 2.1 Å resolution. The structure reveals the contacts of the active site residues with GMP.

Conclusion
Comparative analysis of the active sites of Leishmania and human HGPRT revealed subtle differences in the position of the ligand and its interaction with the active site residues, which could be responsible for the different reactivities of the enzymes to allopurinol reported in the literature. The solution and analysis of the structure of Leishmania HGPRT may contribute to further investigations leading to a full understanding of this important enzyme family in protozoan parasites.
An experimental evaluation of the antidiabetic and antilipidemic properties of a standardized Momordica charantia fruit extract
Authors: Fernandes Nafisa PC , Lagishetty Chakradhar V , Panda Vandana S , Naik Suresh R 
Published: September 2007

Abstract

Background
The MCE, Momordica charantia fruit extract Linn. (Cucurbitaceae) have been documented to elicit hypoglycemic activity on various occasions. However, due to lack of standardization of these extracts, their efficacy remains questionable. The present study was undertaken by selecting a well standardised MCE. This study reports hypoglycemic and antilipidemic activities of MCE employing relevant animal models and in vitro methods.

Methods
Diabetes was induced in Wistar rats by a s.c., subcutaneous injection of alloxan monohydrate (100 mg/kg) in acetate buffer (pH 4.5). MCE and glibenclamide were administered orally to alloxan diabetic rats at doses of 150 mg/kg, 300 mg/kg & 600 mg/kg, and 4 mg/kg respectively for 30 days, blood was withdrawn for glucose determination on 0, 7, 14, 21 and 30th days. On the 31st day, overnight fasted rats were sacrificed and blood was collected for various biochemical estimations including glycosylated haemoglobin, mean blood glucose, serum insulin, cholesterol, triglcerides, protein and glycogen content of liver. The hemidiaphragms and livers were also isolated, carefully excised and placed immediately in ice cooled perfusion solution and processed to study the glucose uptake/transfer processes. Hypolipidemic activity in old obese rats was evaluated by treating two groups with MCE (150 mg/kg & 300 mg/kg) orally for 30 days and determining total cholesterol, triglyceride and HDL-CH, LDL-CH and VLDL-CH levels from serum samples.

Results
Subchronic study of MCE in alloxan induced diabetic rats showed significant antihyperglycemic activity by lowering blood glucose and GHb%, percent glycosylated haemoglobin. Pattern of glucose tolerance curve was also altered significantly. MCE treatment enhanced uptake of glucose by hemidiaphragm and inhibited glycogenolysis in liver slices in vitro. A significant reduction in the serum cholesterol and glyceride levels of obese rats following MCE treatment was also observed.

Conclusion
Our experimental findings with respect to the mechanism of action of MCE in alloxan diabetic rats suggest that it enhances insulin secretion by the islets of Langerhans, reduces glycogenesis in liver tissue, enhances peripheral glucose utilisation and increases serum protein levels. Furthermore, MCE treatment restores the altered histological architecture of the islets of Langerhans. Hence, the biochemical, pharmacological and histopathological profiles of MCE clearly indicate its potential antidiabetic activity and other beneficial effects in amelioration of diabetes associated complications. Further, an evaluation of its antilipidemic activity in old obese rats demonstrated significant lowering of cholesterol and triglyceride levels while elevating HDL-cholesterol levels. Also, the extract lowered serum lipids in alloxan diabetic rats, suggesting its usefulness in controlling metabolic alterations associated with diabetes.