bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Alternative Pathway Is Critical for Pathogenic Complement Activation in Endotoxin- and Diet-Induced Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient Mice
Authors: Malik Talat H. , Cortini Andrea , Carassiti Daniele , Boyle Joseph J. , Haskard Dorian O. , Botto Marina 
Published: October 2010

Background—

The early components of the classical and lectin complement pathways have been shown to protect low-density lipoprotein receptor–deficient mice (
Ldlr
−/−
) from early atherogenesis. However, the role of the alternative pathway remained unknown, and that was investigated in this study.

Methods and Results—

Mice lacking factor B (
Bf
−/−
), the initiator of the alternative pathway, were crossed with
Ldlr
−/−
mice and studied under different proatherogenic conditions. There was no statistically significant difference in lipid profiles or atherosclerotic lesion development between
Bf
−/−
/
Ldlr
−/−
and
Ldlr
−/−
mice fed a low-fat diet. However, in these groups, administration of bacterial lipopolysaccharide led to a significant increase in atherosclerosis only in
Ldlr
−/−
and not in
Bf
−/−
/
Ldlr
−/−
mice, indicating that the alternative pathway is necessary for endotoxin-mediated atherogenesis.
Bf
−/−
/
Ldlr
−/−
mice also had significantly decreased cross-sectional aortic root lesion fraction area and reduced lesion complexity compared with
Ldlr
−/−
animals after a 12-week period of high-fat diet, although this was also accompanied by reduced levels of serum cholesterol. Under both experimental conditions, the atherosclerotic changes in the
Bf
−/−
/
Ldlr
−/−
mice were accompanied by a marked reduction in complement activation in the circulation and in atherosclerotic plaques, with no statistically significant differences in immunoglobulin G deposition or in the serum antibody response to oxidized low-density lipoprotein.

Conclusions—
These data demonstrate that amplification of complement activation by the alternative pathway in response to lipopolysaccharide or high-fat diet plays a proatherogenic role.
Gender: Still a Useful Category of Analysis?
Authors: Scott Joan Wallach 
Published: October 2010

AbstractThis paper traces the history of uses of the word “gender”. It suggests that though “gender” has been recuperated and become commonplace, many issues persist around the way “women” and “men”, and the power relations between them, are defined and are evolving. Provided it still allows us to question the meanings attached to the sexes, how they are established and in what contexts, gender remains a useful, because critical, analytical category.
Gender Studies and Film Studies in France: Steps Forward and Back
Authors: Sellier Geneviève 
Published: October 2010

AbstractFifteen years after the first translations of Anglo-American feminist film theories, this gender approach is finding it hard to gain acceptance in France. The main reason is the elitist view of cinema d’auteur that is still prevalent in academic circles, where the art is seen as a genius's creation outside social determinations in general and gender relations in particular.However, under the influence of historians and sociologists, who dominate gender research in France, French work on film privileges a historical and sociocultural approach, whereas American research is dominated by psychoanalytical approaches. French gender analyses privilege the expression of dominant relations but also of contradictions at work in the films, whether popular or by an auteur-e, as well as in the stars’ image or in tv fiction. Finally some research explores the changes brought about by the emergence of female film-makers on the French scene.
Post-Queer: In Defense of a ‘Trans-Gender Approach’ or Trans-Gender as an Analytical Category
Authors: Cardon Patrick 
Published: October 2010

AbstractThe notion of gender, introduced into France by queens and drags in the late 20th century (the glorious period of the “drag-queens”) and revitalized by American “queer”, follows a traditionally feminist path where homosexual and particularly male issues are once again being hidden away. Having played a big part in popularizing that first version, Patrick Cardon proposes, in order to avoid any misunderstanding and escape once for all from any attempts at reification, to use the term and the universal notion of transgender, which would cover the deconstructivist notions of queer, post-colonial and cultural studies, in order to give a place intelligently to ALL diversities beyond any binarism and with a foresight of future hybridity.
Recent Feminist Outlooks on Intersectionality
Authors: Bilge Sirma 
Published: October 2010

AbstractWith its recognition of the combined effects of the social categories of race, class and gender intersectionality has risen to the rank of feminism's most important contribution to date. Though the first intersectional research (American and British) gave visibility to the social locus of women who self-identified as “black” or “of colour”, current research goes beyond the confines of the English-speaking world and aims increasingly to develop an intersectional instrument to deal with discrimination. This project gives rise to two kinds of debate: one related to producing intersectional information and to ways of carrying out research in this area, the other to do with the use of this information in the political struggle for equality. The current paper, which is confined to the first debate, attempts to bring out the main tension points in present theorizations of intersectionality. Its objective is twofold: to demonstrate certain limits to the explanatory power of intersectionality, and to suggest ways forward in the light of discussions already in train. In order to do so four points are tackled: intersectionality as a research paradigm, the issue of levels of analysis, the theoretical difference of opinion on the ontological status of categories of difference and the issue of widening the theoretical scope of intersectionality.
The immunostimulatory effect of lenalidomide on NK-cell function is profoundly inhibited by concurrent dexamethasone therapy
Authors: Hsu Andy K. , Quach Hang , Tai Tsin , Prince H. Miles , Harrison Simon J. , Trapani Joseph A. , Smyth Mark J. , Neeson Paul , Ritchie David S. 
Published: October 2010

Abstract
Lenalidomide combined with dexamethasone is an effective treatment for refractory/relapsed multiple myeloma (MM). Lenalidomide stimulates natural killer (NK) cells and enhances antitumor responses. We assessed NK cell number and function in 25 patients with MM participating in a clinical trial of lenalidomide and dexamethasone. NK cell numbers increased from a mean of 2.20 ± 0.05 × 105/mL (baseline) to a mean of 3.90 ± 0.03 × 105/mL (cycle 6; P = .05); however, in vitro NK-cell–mediated cytotoxicity decreased from 48.9% ± 6.8% to 27.6% ± 5.1% (P = .0028) and could not be rescued by lenalidomide retreatment. Lenalidomide increased normal donor NK-cell cytotoxicity in vitro from 38.5% to 53.3%, but this was completely abrogated by dexamethasone. Dexamethasone suppression of NK cell–mediated cytotoxicity was partially reversed by a 3-day washout, but these cells remained refractory to lenalidomide-induced enhanced function. Lymphocyte subset depletion experiments revealed that lenalidomide's enhancement of NK cell–mediated cytotoxicity was mediated by CD4+ T-cell production of interleukin 2 and that dexamethasone acted by suppressing interleukin-2 production. Similarly, the reduced ability of NK cells from patients with MM to respond to lenalidomide was also due to impaired CD4 T-cell function. Our findings indicate that lenalidomide immunostimulatory effects on patient NK cells are severely blunted by concurrent dexamethasone administration.
Confronting two-pair primer design for enzyme-free SNP genotyping based on a genetic algorithm
Authors: Yang Cheng-Hong , Cheng Yu-Huei , Chuang Li-Yeh , Chang Hsueh-Wei 
Published: October 2010

Abstract

Background
Polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method produces allele-specific DNA bands of different lengths by adding four designed primers and it achieves the single nucleotide polymorphism (SNP) genotyping by electrophoresis without further steps. It is a time- and cost-effective SNP genotyping method that has the advantage of simplicity. However, computation of feasible CTPP primers is still challenging.

Results
In this study, we propose a GA (genetic algorithm)-based method to design a feasible CTPP primer set to perform a reliable PCR experiment. The SLC6A4 gene was tested with 288 SNPs for dry dock experiments which indicated that the proposed algorithm provides CTPP primers satisfied most primer constraints. One SNP rs12449783 in the SLC6A4 gene was taken as an example for the genotyping experiments using electrophoresis which validated the GA-based design method as providing reliable CTPP primer sets for SNP genotyping.

Conclusions
The GA-based CTPP primer design method provides all forms of estimation for the common primer constraints of PCR-CTPP. The GA-CTPP program is implemented in JAVA and a user-friendly input interface is freely available at http://bio.kuas.edu.tw/ga-ctpp/.
House mouse colonization patterns on the sub-Antarctic Kerguelen Archipelago suggest singular primary invasions and resilience against re-invasion
Authors: Hardouin Emilie A , Chapuis Jean-Louis , Stevens Mark I , van Vuuren Jansen Bettine , Quillfeldt Petra , Scavetta Rick J , Teschke Meike , Tautz Diethard 
Published: October 2010

AbstractBackgroundStarting from Western Europe, the house mouse (Mus musculus domesticus) has spread across the globe in historic times. However, most oceanic islands were colonized by mice only within the past 300 years. This makes them an excellent model for studying the evolutionary processes during early stages of new colonization. We have focused here on the Kerguelen Archipelago, located within the sub-Antarctic area and compare the patterns with samples from other Southern Ocean islands.ResultsWe have typed 18 autosomal and six Y-chromosomal microsatellite loci and obtained mitochondrial D-loop sequences for a total of 534 samples, mainly from the Kerguelen Archipelago, but also from the Falkland Islands, Marion Island, Amsterdam Island, Antipodes Island, Macquarie Island, Auckland Islands and one sample from South Georgia. We find that most of the mice on the Kerguelen Archipelago have the same mitochondrial haplotype and all share the same major Y-chromosomal haplotype. Two small islands (Cochons Island and Cimetière Island) within the archipelago show a different mitochondrial haplotype, are genetically distinct for autosomal loci, but share the major Y-chromosomal haplotype. In the mitochondrial D-loop sequences, we find several single step mutational derivatives of one of the major mitochondrial haplotypes, suggesting an unusually high mutation rate, or the occurrence of selective sweeps in mitochondria.ConclusionsAlthough there was heavy ship traffic for over a hundred years to the Kerguelen Archipelago, it appears that the mice that have arrived first have colonized the main island (Grande Terre) and most of the associated small islands. The second invasion that we see in our data has occurred on islands that are detached from Grande Terre and were likely to have had no resident mice prior to their arrival. The genetic data suggest that the mice of both primary invasions originated from related source populations. Our data suggest that an area colonized by mice is refractory to further introgression, possibly due to fast adaptations of the resident mice to local conditions.
Involvement of EupR, a response regulator of the NarL/FixJ family, in the control of the uptake of the compatible solutes ectoines by the halophilic bacterium Chromohalobacter salexigens
Authors: Rodríguez-Moya Javier , Argandoña Montserrat , Reina-Bueno Mercedes , Nieto Joaquín J , Iglesias-Guerra Fernando , Jebbar Mohamed , Vargas Carmen 
Published: October 2010

Abstract

Background
Osmosensing and associated signal transduction pathways have not yet been described in obligately halophilic bacteria. Chromohalobacter salexigens is a halophilic bacterium with a broad range of salt tolerance. In response to osmotic stress, it synthesizes and accumulates large amounts of the compatible solutes ectoine and hydroxyectoine. In a previous work, we showed that ectoines can be also accumulated upon transport from the external medium, and that they can be used as carbon sources at optimal, but not at low salinity. This was related to an insufficient ectoine(s) transport under these conditions.

Results
A C. salexigens Tn1732-induced mutant (CHR95) showed a delayed growth with glucose at low and optimal salinities, could not grow at high salinity, and was able to use ectoines as carbon sources at low salinity. CHR95 was affected in the transport and/or metabolism of glucose, and showed a deregulated ectoine uptake at any salinity, but it was not affected in ectoine metabolism. Transposon insertion in CHR95 caused deletion of three genes, Csal0865-Csal0867: acs, encoding an acetyl-CoA synthase, mntR, encoding a transcriptional regulator of the DtxR/MntR family, and eupR, encoding a putative two-component response regulator with a LuxR_C-like DNA-binding helix-turn-helix domain. A single mntR mutant was sensitive to manganese, suggesting that mntR encodes a manganese-dependent transcriptional regulator. Deletion of eupR led to salt-sensitivity and enabled the mutant strain to use ectoines as carbon source at low salinity. Domain analysis included EupR as a member of the NarL/FixJ family of two component response regulators. Finally, the protein encoded by Csal869, located three genes downstream of eupR was suggested to be the cognate histidine kinase of EupR. This protein was predicted to be a hybrid histidine kinase with one transmembrane and one cytoplasmic sensor domain.

Conclusions
This work represents the first example of the involvement of a two-component response regulator in the osmoadaptation of a true halophilic bacterium. Our results pave the way to the elucidation of the signal transduction pathway involved in the control of ectoine transport in C. salexigens.
Transplanted bone marrow stem cells relocate to infarct penumbra and co-express endogenous proliferative and immature neuronal markers in a mouse model of ischemic cerebral stroke
Authors: Zhang Xue-mei , Du Fang , Yang Dan , Yu Chun-jiang , Huang Xiang-nan , Liu Wei , Fu Jin 
Published: October 2010

Abstract

Background
Several studies demonstrate that neurogenesis may be induced or activated following vascular insults, which may be important for neuronal regeneration and functional recovery. Understanding the cellular mechanism underlying stroke-associated neurogenesis is of neurobiological as well as neurological/clinical relevance. The present study attempted to explore potential homing and early development of transplanted bone marrow stem cells in mouse forebrain after focal occlusion of the middle cerebral artery, an experimental model of ischemic stroke.

Results
Bone marrow stem cells isolated from donor mice were confirmed by analysis of surface antigen profile, and were pre-labeled with a lipophilic fluorescent dye PKH26, and subsequently transfused into recipient mice with middle cerebral artery coagulation. A large number of PKH26-labeled cells were detected surrounding the infarct site, most of which colocalized with immunolabelings for the proliferating cell nuclear antigen (PCNA) and some also colocalized with the immature neuronal marker doublecortin (DCX) during 1-2 weeks after the bone marrow cells transfusion.

Conclusions
The present study shows that transplanted bone morrow cells largely relocate to the infarct penumbra in ischemic mouse cerebrum. These transplanted bone marrow cells appear to undergo a process of in situ proliferation and develop into putative cortical interneurons during the early phase of experimental vascular injury.
IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma
Authors: White Colin D , Khurana Hema , Gnatenko Dmitri V , Li Zhigang , Odze Robert D , Sacks David B , Schmidt Valentina A 
Published: October 2010

AbstractBackgroundIQGAP1 and IQGAP2 are homologous members of the IQGAP family of scaffold proteins. Accumulating evidence implicates IQGAPs in tumorigenesis. We recently reported that IQGAP2 deficiency leads to the development of hepatocellular carcinoma (HCC) in mice. In the current study we extend these findings, and investigate IQGAP1 and IQGAP2 expression in human HCC.MethodsIQGAP1 and IQGAP2 protein expression was assessed by Western blotting and immunohistochemistry. IQGAP mRNA was measured by quantitative RT-PCR. The methylation status of theIqgap2promoter was determined by pyrosequencing of bisulfite-treated genomic DNA.ResultsIQGAP1 and IQGAP2 expression was reciprocally altered in 6/6 liver cancer cell lines. Similarly, immunohistochemical staining of 82 HCC samples showed that IQGAP2 protein expression was reduced in 64/82 (78.0%), while IQGAP1 was present in 69/82 (84.1%). No IQGAP1 staining was detected in 23/28 (82.1%) normal livers, 4/4 (100.0%) hepatic adenomas and 23/23 (100.0%) cirrhosis cases, while IQGAP2 was increased in 22/28 (78.6%), 4/4 (100.0%) and 23/23 (100.0%), respectively. Although theIqgap2promoter was not hypermethylated in HCC at any of the 25 CpG sites studied (N = 17), IQGAP2 mRNA levels were significantly lower in HCC specimens (N = 23) than normal livers (N = 6).ConclusionsWe conclude that increased IQGAP1 and/or decreased IQGAP2 contribute to the pathogenesis of human HCC. Furthermore, downregulation of IQGAP2 in HCC occurs independently of hypermethylation of theIqgap2promoter. Immunostaining of IQGAP1 and IQGAP2 may aid in the diagnosis of HCC, and their pharmacologic modulation may represent a novel therapeutic strategy for the treatment of liver cancer.
A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report
Authors: Rodríguez-Martínez Ana B , Garrido Joseba M , Zarranz Juan J , Arteagoitia Jose M , de Pancorbo Marian M , Atarés Begoña , Bilbao Miren J , Ferrer Isidro , Juste Ramón A 
Published: October 2010

Abstract

Background
Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion.

Case presentation
We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine.

Conclusions
A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.
Cardiovascular risk estimated after 13 years of follow-up in a low-incidence Mediterranean region with high-prevalence of cardiovascular risk factors
Authors: Huerta José M , Tormo María-José , Gavrila Diana , Navarro Carmen 
Published: October 2010

Abstract

Background
Murcia (south-east Spain) shows increased cardiovascular (CV) morbimortality as compared to other Spanish regions. Our objective was to assess the CV risk associated with major risk factors (RF) among adult population of Murcia.

Methods
A cohort of 2314 subjects (18-70 years) with full biochemical and questionnaire data was followed-up for 13 years. Incident cases of ischemic heart disease and stroke were identified by record linkage, individual questionnaires and revision of medical records. Relative risks were obtained by multivariate Cox regression stratified by age and sex, and ischemic risk attributable to CVRF was calculated.

Results
After more than 26276 person-years of follow-up, 57 incident ischemic events (77% men) and 37 stroke cases (62% men) were identified. Independent risk factors of ischemic heart disease (IHD) and all CV events combined, with RR ranging from 1.6 to 2.6, were total serum cholesterol ≥ 240 mg/dl (HR = 2.6, 95%CI:1.3-5.1), blood pressure levels ≥ 140/90 mmHg (HR = 2.6, 95%CI:1.4-4.8), ever tobacco smoking (HR = 2.2; 95%CI:1.1-4.5), and diabetes (HR = 2.0; 95%CI: 1.0-3.8). No increased CV risk was detected for known participants under treatment who showed cholesterol and blood pressure values below the clinical risk threshold. Smoking was significantly associated with stroke. For all events combined, the major risk factors were hypercholesterolemia, hypertension and ever use of tobacco. Despite its high prevalence, obesity was not associated to CV risk. Most of the IHD cases were attributable to smoking (44%), hypertension (38%) and hypercholesterolemia (26%).

Conclusions
In the Region of Murcia, smoking accounted for the largest proportion of cardiovascular risk, whereas hypertension displaced hypercholesterolemia as the second leading cause of CV disease. Our study deepens in our understanding of the cardiovascular epidemiology in Spanish areas of Mediterranean Europe with relatively high cardiovascular morbimortality, that are poorly represented by the available risk equations.