bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of arsenic, cobalt, copper and manganese in biological Samples of Steel mill workers by electrothermal atomic absorption Spectrometry
Authors: Afridi HI , Kazi TG , Kazi NG , Jamali MK , Arain MB , Sirajuddin  , Kandhro GA , Shah AQ , Baig JA 
Published: March 2009

The determination of trace and toxic elements in biological samples (blood, urine and scalp hair samples) of human beings is an important clinical test. The aim of our present study was to determine the concentration of arsenic (As), copper (Cu), cobalt (Co) and manganese (Mn), in biological samples of male production workers (PW) and quality control workers (QW) of steel mill, with aged 25–55 years, to assess the possible influence of environmental exposure. For comparison purpose, the same biological samples of unexposed healthy males of same age group were collected as control subjects. The determination of all elements in biological samples was carried out by electrothermal atomic absorption spectrometry, prior to microwave assisted acid digestion. The accuracy of the As, Cu, Co and Mn measurements was tested by simultaneously analyzing certified reference materials (CRMs) and for comparative purposes conventional wet acid digestion method was used on the same CRMs. No significant differences were observed between the analytical results and the certified values, using both methods (paired t-test at P > 0.05). The results indicate that concentrations of As, Cu, Co and Mn in all three biological samples of the exposed workers (QW and PW) were significantly higher than those of the controls. The possible correlation of these elements with the etiology of different physiological disorders is discussed. The results were also demonstrated the need of attention for improvements in workplace, ventilation and industrial hygiene practices.
Concentration of antibodies to extractable nuclear antigens and disease activity in systemic lupus erythematosus
Authors: Agarwal S , Harper J , Kiely PDW 
Published: March 2009

A hallmark of systemic lupus erythematosus (SLE) is the production of autoantibodies directed against intracellular antigens. Antibodies to double stranded DNA (dsDNA) are most closely associated with the clinical manifestations of the condition and appear to have a direct role in pathogenesis. On the contrary, the relationship between disease activity in SLE and anti-extractable nuclear antigen (ENA) antibodies has not been well demonstrated. Despite this, commercial assays for the quantification of anti-ENA antibodies are now widely available, although their usefulness in clinical practice is not known. The aim of this study was to investigate whether there is an association between disease activity in SLE and concentrations of individual anti-ENA antibodies. A prospective 2-year study of 45 patients with SLE, known to be positive for at least one anti-ENA antibody, was performed. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Anti-ENA antibodies were quantified using a commercial antibody detection system. A total of 45 patients were studied over a 2-year period (median number of assessments 5, range 2–9). Of them 29 patients were positive for Ro, 8 for La, 9 for Sm and 27 for RNP antibodies. In the population as a whole, there was a weak relationship between peak SLEDAI score and anti-Sm concentration ( r = 0.57, NS), but no relation with the other anti-ENA antibodies. In a small number of patients, there appeared to be either a positive (Ro, Sm) or negative (La, Sm, RNP) association between ENA antibody concentration and disease activity over time; however, this was not apparent for the majority of individuals. These results show that in SLE, clinically significant changes in disease activity do not correlate well with concentrations of anti-ENA antibodies, either within the population as a whole or on an individual basis. Repeated quantitative measurement of anti-ENA antibodies does not therefore appear to provide useful additional information in assessing disease activity in SLE. The widespread application of commercial quantitative assays to routine clinical practice is not recommended.
Induction of autoimmunity in Brown Norway rats by oral and parenteral administration of sodium silicate
Authors: Al-Mogairen SM , Al-Arfaj AS , Meo SA ,   M Adam, Al-Hammad A , Gad El Rab MO 
Published: March 2009

Silica and silicate may disturb immune function such as autoimmunity and tumour immunity. The main objective of this study was to examine the relation between sodium silicate and induction of autoimmunity in genetically susceptible rats. In this study, thirty Brown Norway rats were randomised into four treatment groups, the first and second group receiving 3 mg of sodium silicate (NaSiO4) (equivalent to 2 mg silica) in 0.2 mL of normal saline either per oral or subcutaneously, and the third and fourth group (control) receiving 0.2 mL of normal saline (0.9%) through the same corresponding route. A significant number of rats (80%) ( P < 0.05) which received sodium silicate by the subcutaneous route showed a high level of serum ANA compared with controls. In the oral, sodium silicate group showed high serum ANA in an insignificant number of rats. Other autoantibodies in both groups (anti-dsDNA, anti-Smith, anti-SSA, anti-SSB) showed gradual increased post exposure, but the numbers of rats with positive titres post exposure was statistically not significant. Silica exposure in rats appears to induce the development of autoimmunity. A longer duration post exposure to silicate seems to be associated with greater risks.
Mitral valve prolapse in young healthy individuals. An early index of autoimmunity?
Authors: Evangelopoulos ME , Toumanidis S , Sotou D , Evangelopoulos C , Mavrikakis M , Alevizaki M , Dimopoulos MA 
Published: March 2009

Mitral valve prolapse (MVP) is a benign valvular abnormality. However, an increased prevalence of MVP is reported in patients with systemic lupus erythematosus and autoimmune thyroid disease. Our aim was to evaluate whether the presence of MVP in healthy individuals might indicate a premature index of subclinical autoimmune disorder. A total of 75 individuals with MVP and 44 individuals without MVP were identified by echocardiography. Serum samples were examined for various organ and non-organ specific autoantibodies. In all, 35 of the 75 individuals with MVP had at least one autoantibody. ANA were detected in 17/75 in MVP(+) versus 1/44 in the MVP(−), ( P < 0.05), and anti-ENA in 6/75 in the MVP(+) versus 0/44 in the control group, P = ns. In the MVP(+) group, thyroid autoantibodies, IgA and IgG RF were found at a statistically significant higher incidence, 16/75, 11/75 and 10/75 versus 1/44, 0/44 and 0/44 in the MVP(−)group, respectively ( P < 0.05). The levels of IgG anticardiolipin antibodies were significantly higher in the MVP(+) group, P < 0.05. The presence of organ and non-organ specific autoantibodies in young healthy MVP(+) individuals insinuate the presence of subclinical autoimmunity and might suggest that autoimmune mechanisms might be involved in its pathogenesis. A follow-up of these individuals might elucidate whether MVP constitutes an early index of autoimmunity.
Mycophenolate mofetil in patients with systemic lupus erythematosus: a prospective pharmacokinetic study
Authors: Roland M , Barbet C , Paintaud G , Magdelaine-Beuzelin C , Diot E , Halimi JM , Lebranchu Y , Nivet H , Büchler M 
Published: March 2009

Few studies have assessed the pharmacokinetics of mycophenolic acid (MPA) in non-transplanted patients treated with mycophenolate mofetil (MMF), and little information is available concerning a concentration-effect relationship between the MPA area under the curve (AUC) and the immunological parameters in patients treated for systemic lupus erythematosus (SLE). We evaluated the variations in pharmacokinetics for MPA in patients with SLE and the relationship between MPA-AUC and markers of disease activity. MPA blood concentrations were measured through enzyme-multiplied immunotechnique (T0, T30’, T1h, T2h, T3h and T4h) to determine the MPA AUC0–4h in patients treated with MMF since at least 4 weeks for SLE. Clinical examination, biochemical analyses and immunological analyses were performed on the same day. The relationship between MPA exposure and disease activity markers was assessed. A total of 20 patients were included in the study. The diagnosis of SLE had been made 87 ± 72 months before and patients had been treated with MMF for 31 ± 30 months. Mean dose of MMF on the day of the study was 1600 ± 447 mg/day. Mean MPA AUC0–4h was 28.4 ± 13.6 mg h/L, mean dose-normalised AUC0–4h was 35.5 ± 13.8 mg h/L and mean MPA C0 was 3.1 ± 2.2 mg/L. There was a high correlation between MPA AUC0–4h and MPA C0, ( r = 0.80; P < 0.001). AUC0–4h tended to be lower in patients who had low complement C3 concentration (<0.67 g/L) and low complement C4 concentration (<0.14 g/L). Moreover, there was a significant relationship between MPA trough levels and complement C4 concentrations ( P = 0.043). We confirmed high inter-individual variability of MPA AUC in patients treated with MMF for SLE. This suggests that MPA exposure may be unpredictable with a fixed MMF dose. There was a concentration-effect relationship between MPA exposure (C0) and immunological disease activity parameters.
Evolution of MIR168 paralogs in Brassicaceae
Authors: Gazzani Silvia , Li Mingai , Maistri Silvia , Scarponi Eliana , Graziola Michele , Barbaro Enrico , Wunder Jörg , Furini Antonella , Saedler Heinz , Varotto Claudio 
Published: March 2009

Abstract

Background
In plants, expression of ARGONAUTE1 (AGO1), the catalytic subunit of the RNA-Induced Silencing Complex responsible for post-transcriptional gene silencing, is controlled through a feedback loop involving the miR168 microRNA. This complex auto-regulatory loop, composed of miR168-guided AGO1-catalyzed cleavage of AGO1 mRNA and AGO1-mediated stabilization of miR168, was shown to ensure the maintenance of AGO1 homeostasis that is pivotal for the correct functioning of the miRNA pathway.

Results
We applied different approaches to studying the genomic organization and the structural and functional evolution of MIR168 homologs in Brassicaeae. A whole genome comparison of Arabidopsis and poplar, phylogenetic footprinting and phylogenetic reconstruction were used to date the duplication events originating MIR168 homologs in these genomes. While orthology was lacking between Arabidopsis and poplar MIR168 genes, we successfully isolated orthologs of both loci present in Arabidopsis (MIR168a and MIR168b) from all the Brassicaceae species analyzed, including the basal species Aethionema grandiflora, thus indicating that (1) independent duplication events took place in Arabidopsis and poplar lineages and (2) the origin of MIR168 paralogs predates both the Brassicaceae radiation and the Arabidopsis alpha polyploidization. Different phylogenetic footprints, corresponding to known functionally relevant regions (transcription starting site and double-stranded structures responsible for microRNA biogenesis and function) or for which functions could be proposed, were found to be highly conserved among MIR168 homologs. Comparative predictions of the identified microRNAs also indicate extreme conservation of secondary structure and thermodynamic stability.

Conclusion
We used a comparative phylogenetic footprinting approach to identify the structural and functional constraints that shaped MIR168 evolution in Brassicaceae. Although their duplication happened at least 40 million years ago, we found evidence that both MIR168 paralogs have been maintained throughout the evolution of Brassicaceae, most likely functionally as indicated by the extremely high conservation of functionally relevant regions, predicted secondary structure and thermodynamic profile. Interestingly, the expression patterns observed in Arabidopsis indicate that MIR168b underwent partial subfunctionalization as determined by the experimental characterization of its expression pattern provided in this study. We found further evolutionary evidence that pre-miR168 lower stem (the RNA-duplex structure adjacent to the miR-miR* stem) is significantly longer than animal lower stems and probably plays a relevant role in multi-step miR168 biogenesis.
Comparative transcriptomic characterization of aluminum, sodium chloride, cadmium and copper rhizotoxicities in Arabidopsis thaliana
Authors: Zhao Cheng-Ri , Ikka Takashi , Sawaki Yoshiharu , Kobayashi Yuriko , Suzuki Yuji , Hibino Takashi , Sato Shigeru , Sakurai Nozomu , Shibata Daisuke , Koyama Hiroyuki 
Published: March 2009

Abstract

Background
Rhizotoxic ions in problem soils inhibit nutrient and water acquisition by roots, which in turn leads to reduced crop yields. Previous studies on the effects of rhizotoxic ions on root growth and physiological functions suggested that some mechanisms were common to all rhizotoxins, while others were more specific. To understand this complex system, we performed comparative transcriptomic analysis with various rhizotoxic ions, followed by bioinformatics analysis, in the model plant Arabidopsis thaliana.

Results
Roots of Arabidopsis were treated with the major rhizotoxic stressors, aluminum (Al) ions, cadmium (Cd) ions, copper (Cu) ions and sodium (NaCl) chloride, and the gene expression responses were analyzed by DNA array technology. The top 2.5% of genes whose expression was most increased by each stressor were compared with identify common and specific gene expression responses induced by these stressors. A number of genes encoding glutathione-S-transferases, peroxidases, Ca-binding proteins and a trehalose-synthesizing enzyme were induced by all stressors. In contrast, gene ontological categorization identified sets of genes uniquely induced by each stressor, with distinct patterns of biological processes and molecular function. These contained known resistance genes for each stressor, such as AtALMT1 (encoding Al-activated malate transporter) in the Al-specific group and DREB (encoding dehydration responsive element binding protein) in the NaCl-specific group. These gene groups are likely to reflect the common and differential cellular responses and the induction of defense systems in response to each ion. We also identified co-expressed gene groups specific to rhizotoxic ions, which might aid further detailed investigation of the response mechanisms.

Conclusion
In order to understand the complex responses of roots to rhizotoxic ions, we performed comparative transcriptomic analysis followed by bioinformatics characterization. Our analyses revealed that both general and specific genes were induced in Arabidopsis roots exposed to various rhizotoxic ions. Several defense systems, such as the production of reactive oxygen species and disturbance of Ca homeostasis, were triggered by all stressors, while specific defense genes were also induced by individual stressors. Similar studies in different plant species could help to clarify the resistance mechanisms at the molecular level to provide information that can be utilized for marker-assisted selection.
Plant origin and ploidy influence gene expression and life cycle characteristics in an invasive weed
Authors: Broz Amanda K , Manter Daniel K , Bowman Gillianne , Müller-Schärer Heinz , Vivanco Jorge M 
Published: March 2009

Abstract

Background
Ecological, evolutionary and physiological studies have thus far provided an incomplete picture of why some plants become invasive; therefore we used genomic resources to complement and advance this field. In order to gain insight into the invasive mechanism of Centaurea stoebe we compared plants of three geo-cytotypes, native Eurasian diploids, native Eurasian tetraploids and introduced North American tetraploids, grown in a common greenhouse environment. We monitored plant performance characteristics and life cycle habits and characterized the expression of genes related to constitutive defense and genome stability using quantitative PCR.

Results
Plant origin and ploidy were found to have a significant effect on both life cycle characteristics and gene expression, highlighting the importance of comparing appropriate taxonomic groups in studies of native and introduced plant species. We found that introduced populations of C. stoebe exhibit reduced expression of transcripts related to constitutive defense relative to their native tetraploid counterparts, as might be expected based on ideas of enemy release and rapid evolution. Measurements of several vegetative traits were similar for all geo-cytotypes; however, fecundity of tetraploids was significantly greater than diploids, due in part to their polycarpic nature. A simulation of seed production over time predicts that introduced tetraploids have the highest fecundity of the three geo-cytotypes.

Conclusion
Our results suggest that characterizing gene expression in an invasive species using populations from both its native and introduced range can provide insight into the biology of plant invasion that can complement traditional measurements of plant performance. In addition, these results highlight the importance of using appropriate taxonomic units in ecological genomics investigations.
Diabetic cardiomyopathy: effects of fenofibrate and metformin in an experimental model – the Zucker diabetic rat
Authors: Forcheron Fabien , Basset Alexandra , Abdallah Pauline , Del Carmine Peggy , Gadot Nicolas , Beylot Michel 
Published: March 2009

Abstract

Background
Diabetic cardiomyopathy (DCM) contributes to cardiac failure in diabetic patients. It is characterized by excessive lipids accumulation, with increased triacylglycerol (TAG) stores, and fibrosis in left ventricle (LV). The mechanisms responsible are incompletely known and no specific treatment is presently defined. We evaluated the possible usefulness of two molecules promoting lipid oxidation, fenofibrate and metformin, in an experimental model of DCM, the Zucker diabetic rat (ZDF).

Methods
ZDF and controls (C) rats were studied at 7, 14 and 21 weeks. After an initial study at 7 weeks, ZDF rats received no treatment, metformin or fenofibrate until final studies (at 14 or 21 weeks). C rats received no treatment. Each study comprised measurements of metabolic parameters (plasma glucose, TAG, insulin levels) and sampling of heart for histology and measurements of TAG content and relevant mRNA concentration.

Results
ZDF rats were insulin-resistant at 7 weeks, type 2 diabetic at 14 weeks and diabetic with insulin deficiency at 21 weeks. Their plasma TAG levels were increased. ZDF rats had at 7 weeks an increased LV TAG content with some fibrosis. LV TAG content increased in untreated ZDF rats at 14 and 21 weeks and was always higher than in C. Fibrosis increased also moderately in untreated ZDF rats. Metformin and fenofibrate decreased plasma TAG concentrations. LV TAG content was decreased by metformin (14 and 21 weeks) and by fenofibrate (14 weeks). Fibrosis was reduced by fenofibrate only and was increased by metformin. Among the mRNA measured, fenofibrate increased Acyl-CoA Oxidase mRNA level, metformin decreased Acyl-CoA Synthase and increased AdipoR1 and pro-inflammatory mRNA levels.

Conclusion
Fenofibrate had favourable actions on DCM. Metformin had beneficial effect on TAG content but not on fibrosis. PPARα agonists could be useful for the prevention and treatment of DCM.
Microbial factories for recombinant pharmaceuticals
Authors: Ferrer-Miralles Neus , Domingo-Espín Joan , Corchero José Luis , Vázquez Esther , Villaverde Antonio 
Published: March 2009

Abstract
Most of the hosts used to produce the 151 recombinant pharmaceuticals so far approved for human use by the Food and Drug Administration (FDA) and/or by the European Medicines Agency (EMEA) are microbial cells, either bacteria or yeast. This fact indicates that despite the diverse bottlenecks and obstacles that microbial systems pose to the efficient production of functional mammalian proteins, namely lack or unconventional post-translational modifications, proteolytic instability, poor solubility and activation of cell stress responses, among others, they represent convenient and powerful tools for recombinant protein production. The entering into the market of a progressively increasing number of protein drugs produced in non-microbial systems has not impaired the development of products obtained in microbial cells, proving the robustness of the microbial set of cellular systems (so far Escherichia coli and Saccharomyces cerevisae) developed for protein drug production. We summarize here the nature, properties and applications of all those pharmaceuticals and the relevant features of the current and potential producing hosts, in a comparative way.
Reduction in corpora lutea number in obese melanocortin-4-receptor-deficient mice
Authors: Sandrock Mara , Schulz Angela , Merkwitz Claudia , Schöneberg Torsten , Spanel-Borowski Katharina , Ricken Albert 
Published: March 2009

Abstract
Obese melanocortin-4-receptor-deficient (MC4R-/-) male mice are reported to have erectile dysfunction, while homozygous MC4R-/- female mice are apparently fertile. A recently established obese mouse strain, carrying an inactivating mutation in the MC4R gene, revealed difficulties in breeding for the homozygous female mice. This prompted us to determine the presence of follicles and corpora lutea (CL) in ovaries of MC4R-/- mice aged 3–6 months in comparison to wild type (MC4R+/+) littermates. Serial sections of formaldehyde-fixed ovaries of mice with vaginal signs of estrus and metestrus were assessed for the number of healthy and regressing follicles and CL. The number of CL, as an estimate for the ovulation rate, decreased to zero during aging in MC4R-/- mice. The number of small- (diameter 100–200 micrometer) and large-sized follicles namely antral follicles (diameter >200 micrometer) were slightly increased in MC4R-/- compared to MC4R+/+ mice. Greater differences were found in very large to cystic follicles, which were more numerous in MC4R-/- mice. The number of regressing antral follicles was higher in the MC4R-/- group compared to the MC4R+/+ group. This was associated with a wide range in the number of collapsed zonae pellucidae as the last remnants of regressed follicles. A conspicuous hypertrophy of the interstitial cells was noted in 6-month-old MC4R-/- mice. In conclusion, cystic follicles and the reduction in CL number point to a decreased ovulation rate in obese MC4R-/- mice.