bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of neuroimmune semaphorins 4A and 4D and their receptors in the lung is enhanced by allergen and vascular endothelial growth factor
Authors: Smith Elizabeth P , Shanks Kathleen , Lipsky Michael M , DeTolla Louis J , Keegan Achsah D , Chapoval Svetlana P
Published: May 2011

Background

Semaphorins were originally identified as molecules regulatingafunctional activity of axons in the nervous system. Sema4A and Sema4D were the first semaphorins found to be expressed on immune cells and were termed "immune semaphorins". It is known that Sema4A and Sema4D bind Tim-2 and CD72 expressed on leukocytes and PlexinD1 and B1 present on non-immune cells. These neuroimmune semaphorins and their receptors have been shown to play critical roles in many physiological and pathological processes including neuronal development, immune response regulation, cancer, autoimmune, cardiovascular, renal, and infectious diseases. However, the expression and regulation of Sema4A, Sema4D, and their receptors in normal and allergic lungs is undefined.

Results

Allergen treatment and lung-specific vascular endothelial growth factor (VEGF) expression induced asthma-like pathologies in the murine lungs. These experimental models of allergic airway inflammation were used for the expression analysis of immune semaphorins and their receptors employing immunohistochemistry and flow cytometry techniques. We found that besides accessory-like cells, Sema4A was also detected on bronchial epithelial and smooth muscle cells, whereas Sema4D expression was high on immune cells such as T and B lymphocytes. Surprisingly, under inflammation various cell types including macrophages, lymphocytes, and granulocytes in the lung expressed Tim-2, a previously defined marker for Th2 cells. CD72 was found on lung immune, inflammatory, and epithelial cells. Bronchial epithelial cells were positive for both plexins, whereas some endothelial cells selectively expressed Plexin D1. Plexin B1 expression was also detected on lung DC. Both allergen and VEGF upregulated the expression of neuroimmune semaphorins and their receptors in the lung tissue. However, the lung tissue Sema4A-Tim2 expression was rather weak, whereas Sema4D-CD72 ligand-receptor pair was vastly upregulated by allergen. Soluble Sema4D protein was present in the lung lysates and a whole Sema4A protein plus its dimer were readily detected in the bronchoalveolar (BAL) fluids under inflammation.

Conclusions

This study clearly shows that neuroimmune semaphorins Sema4A and Sema4D and their receptors might serve as potential markers for the allergic airway inflammatory diseases. Our current findings pave the way for further investigations of the role of immune semaphorins in inflammation and their use as potential therapeutic targets for the inflammatory lung conditions.
Toxoplasma gondiidown modulates cadherin expression in skeletal muscle cells inhibiting myogenesis
Authors: Gomes Alessandra F , Guimarães Erick V , Carvalho Laís , Correa José R , Mendonça-Lima Leila , Barbosa Helene S
Published: May 2011

Background

Toxoplasma gondii belongs to a large and diverse group of obligate intracellular parasitic protozoa. Primary culture of mice skeletal muscle cells (SkMC) was employed as a model for experimental toxoplasmosis studies. The myogenesis of SkMC was reproduced in vitro and the ability of T. gondii tachyzoite forms to infect myoblasts and myotubes and its influence on SkMC myogenesis were analyzed.

Results

In this study we show that, after 24 h of interaction, myoblasts (61%) were more infected with T. gondii than myotubes (38%) and inhibition of myogenesis was about 75%. The role of adhesion molecules such as cadherin in this event was investigated. First, we demonstrate that cadherin localization was restricted to the contact areas between myocytes/myocytes and myocytes/myotubes during the myogenesis process. Immunofluorescence and immunoblotting analysis of parasite-host cell interaction showed a 54% reduction in cadherin expression at 24 h of infection. Concomitantly, a reduction in M-cadherin mRNA levels was observed after 3 and 24 h of T. gondii-host cell interaction.

Conclusions

These data suggest that T. gondii is able to down regulate M-cadherin expression, leading to molecular modifications in the host cell surface that interfere with membrane fusion and consequently affect the myogenesis process.
Identification of tissue-specific, abiotic stress-responsive gene expression patterns in wine grape (Vitis viniferaL.) based on curation and mining of large-scale EST data sets
Authors: Tillett Richard L , Ergül Ali , Albion Rebecca L , Schlauch Karen A , Cramer Grant R , Cushman John C
Published: May 2011

Background

Abiotic stresses, such as water deficit and soil salinity, result in changes in physiology, nutrient use, and vegetative growth in vines, and ultimately, yield and flavor in berries of wine grape,Vitis viniferaL. Large-scale expressed sequence tags (ESTs) were generated, curated, and analyzed to identify major genetic determinants responsible for stress-adaptive responses. Although roots serve as the first site of perception and/or injury for many types of abiotic stress, EST sequencing in root tissues of wine grape exposed to abiotic stresses has been extremely limited to date. To overcome this limitation, large-scale EST sequencing was conducted from root tissues exposed to multiple abiotic stresses.

Results

A total of 62,236 expressed sequence tags (ESTs) were generated from leaf, berry, and root tissues from vines subjected to abiotic stresses and compared with 32,286 ESTs sequenced from 20 public cDNA libraries. Curation to correct annotation errors, clustering and assembly of the berry and leaf ESTs with currently availableV. viniferafull-length transcripts and ESTs yielded a total of 13,278 unique sequences, with 2302 singletons and 10,976 mapped toV. viniferagene models. Of these, 739 transcripts were found to have significant differential expression in stressed leaves and berries including 250 genes not described previously as being abiotic stress responsive. In a second analysis of 16,452 ESTs from a normalized root cDNA library derived from roots exposed to multiple, short-term, abiotic stresses, 135 genes with root-enriched expression patterns were identified on the basis of their relative EST abundance in roots relative to other tissues.

Conclusions

The large-scale analysis of relative EST frequency counts among a diverse collection of 23 different cDNA libraries from leaf, berry, and root tissues of wine grape exposed to a variety of abiotic stress conditions revealed distinct, tissue-specific expression patterns, previously unrecognized stress-induced genes, and many novel genes with root-enriched mRNA expression for improving our understanding of root biology and manipulation of rootstock traits in wine grape. mRNA abundance estimates based on EST library-enriched expression patterns showed only modest correlations between microarray and quantitative, real-time reverse transcription-polymerase chain reaction (qRT-PCR) methods highlighting the need for deep-sequencing expression profiling methods.
Transcriptome analysis by GeneTrail revealed regulation of functional categories in response to alterations of iron homeostasis in Arabidopsis thaliana
Authors: Schuler Mara , Keller Andreas , Backes Christina , Philippar Katrin , Lenhof Hans-Peter , Bauer Petra
Published: May 2011

Background

High-throughput technologies have opened new avenues to study biological processes and pathways. The interpretation of the immense amount of data sets generated nowadays needs to be facilitated in order to enable biologists to identify complex gene networks and functional pathways. To cope with this task multiple computer-based programs have been developed. GeneTrail is a freely available online tool that screens comparative transcriptomic data for differentially regulated functional categories and biological pathways extracted from common data bases like KEGG, Gene Ontology (GO), TRANSPATH and TRANSFAC. Additionally, GeneTrail offers a feature that allows screening of individually defined biological categories that are relevant for the respective research topic.

Results

We have set up GeneTrail for the use of Arabidopsis thaliana. To test the functionality of this tool for plant analysis, we generated transcriptome data of root and leaf responses to Fe deficiency and the Arabidopsis metal homeostasis mutant nas4x-1. We performed Gene Set Enrichment Analysis (GSEA) with eight meaningful pairwise comparisons of transcriptome data sets. We were able to uncover several functional pathways including metal homeostasis that were affected in our experimental situations. Representation of the differentially regulated functional categories in Venn diagrams uncovered regulatory networks at the level of whole functional pathways. Over-Representation Analysis (ORA) of differentially regulated genes identified in pairwise comparisons revealed specific functional plant physiological categories as major targets upon Fe deficiency and in nas4x-1.

Conclusion

Here, we obtained supporting evidence, that the nas4x-1 mutant was defective in metal homeostasis. It was confirmed that nas4x-1 showed Fe deficiency in roots and signs of Fe deficiency and Fe sufficiency in leaves. Besides metal homeostasis, biotic stress, root carbohydrate, leaf photosystem and specific cell biological categories were discovered as main targets for regulated changes in response to - Fe and nas4x-1. Among 258 differentially expressed genes in response to - Fe and nas4x-1 five functional categories were enriched covering metal homeostasis, redox regulation, cell division and histone acetylation. We proved that GeneTrail offers a flexible and user-adapted way to identify functional categories in large-scale plant transcriptome data sets. The distinguished feature that allowed analysis of individually assembled functional categories facilitated the study of the Arabidopsis thaliana transcriptome.
WRKY Transcription Factors Involved in Activation of SA Biosynthesis Genes
Authors: van Verk Marcel C , Bol John F , Linthorst Huub JM
Published: May 2011

Background

Increased defense against a variety of pathogens in plants is achieved through activation of a mechanism known as systemic acquired resistance (SAR). The broad-spectrum resistance brought about by SAR is mediated through salicylic acid (SA). An important step in SA biosynthesis in Arabidopsis is the conversion of chorismate to isochorismate through the action of isochorismate synthase, encoded by the ICS1 gene. Also AVR

PPHB

SUSCEPTIBLE 3 (PBS3) plays an important role in SA metabolism, as pbs3 mutants accumulate drastically reduced levels of SA-glucoside, a putative storage form of SA. Bioinformatics analysis previously performed by us identified WRKY28 and WRKY46 as possible regulators of ICS1 and PBS3.

Results

Expression studies with ICS1 promoter::β-glucuronidase (GUS) genes in Arabidopsis thaliana protoplasts cotransfected with 35S::WRKY28 showed that over expression of WRKY28 resulted in a strong increase in GUS expression. Moreover, qRT-PCR analyses indicated that the endogenous ICS1 and PBS3 genes were highly expressed in protoplasts overexpressing WRKY28 or WRKY46, respectively. Electrophoretic mobility shift assays indentified potential WRKY28 binding sites in the ICS1 promoter, positioned -445 and -460 base pairs upstream of the transcription start site. Mutation of these sites in protoplast transactivation assays showed that these binding sites are functionally important for activation of the ICS1 promoter. Chromatin immunoprecipitation assays with haemagglutinin-epitope-tagged WRKY28 showed that the region of the ICS1 promoter containing the binding sites at -445 and -460 was highly enriched in the immunoprecipitated DNA.

Conclusions

The results obtained here confirm results from our multiple microarray co-expression analyses indicating that WRKY28 and WRKY46 are transcriptional activators of ICS1 and PBS3, respectively, and support this in silico screening as a powerful tool for identifying new components of stress signaling pathways.
A rice calcium-dependent protein kinase is expressed in cortical root cells during the presymbiotic phase of the arbuscular mycorrhizal symbiosis
Authors: Campos-Soriano Lidia , Gómez-Ariza Jorge , Bonfante Paola , San Segundo Blanca
Published: May 2011

Background

The arbuscular mycorrhizal (AM) symbiosis consists of a mutualistic relationship between soil fungi and roots of most plant species. This association provides the arbuscular mycorrhizal fungus with sugars while the fungus improves the uptake of water and mineral nutrients in the host plant. Then, the establishment of the arbuscular mycorrhizal (AM) symbiosis requires the fine tuning of host gene expression for recognition and accommodation of the fungal symbiont. In plants, calcium plays a key role as second messenger during developmental processes and responses to environmental stimuli. Even though calcium transients are known to occur in host cells during the AM symbiosis, the decoding of the calcium signal and the molecular events downstream are only poorly understood.

Results

The expression of seventeen Calcium-dependent Protein Kinase (CPK) genes representative of the four distinct phylogenetic groups of rice CPKs was monitored during the presymbiotic phase of the AM symbiosis. Among them, OsCPK18 and OsCPK4, were found to be transcriptionally activated in response to inoculation with the AM fungus Glomus intraradices.
OsCPK18 and OsCPK4 gene expression was also up-regulated by fungal-produced diffusible molecules. Laser microdissection revealed expression of OsCPK18 in cortical cells, and not in epidermal cells of G. intraradices-inoculated rice roots, suggesting a preferential role of this gene in the root cortex. Moreover, a plasma membrane localization of OsCPK18 was observed by transient expression assays of green fluorescent protein-tagged OsCPK18 in onion epidermal cells. We also show that the myristoylation site of the OsCPK18 N-terminus is required for plasma membrane targeting.

Conclusion

The rapid activation of OsCPK18 expression in response to AM inoculation, its expression being also induced by fungal-secreted signals, together with the observed plasma membrane localization of OsCPK18, points to a role for OsCPK18 in perception of the AM fungus. The OsCPK18 gene might be considered as a marker for the presymbiotic phase of the symbiotic process. These findings provide a better understanding of the signaling mechanisms operating during the AM symbiosis and will greatly facilitate their molecular dissection.
Agrobacterium-mediated genetic transformation of Coffea arabica (L.) is greatly enhanced by using established embryogenic callus cultures
Authors: Ribas Alessandra F , Dechamp Eveline , Champion Anthony , Bertrand Benoît , Combes Marie-Christine , Verdeil Jean-Luc , Lapeyre Fabienne , Lashermes Philippe , Etienne Hervé
Published: May 2011

Background

Following genome sequencing of crop plants, one of the main challenges today is determining the function of all the predicted genes. When gene validation approaches are used for woody species, the main obstacle is the low recovery rate of transgenic plants from elite or commercial cultivars. Embryogenic calli have frequently been the target tissue for transformation, but the difficulty in producing or maintaining embryogenic tissues is one of the main problems encountered in genetic transformation of many woody plants, includingCoffea arabica.

Results

We identified the conditions required for successful long-term proliferation of embryogenic cultures inC. arabicaand designed a highly efficient and reliableAgrobacterium tumefaciens-mediated transformation method based on these conditions. The transformation protocol with LBA1119 harboring pBin 35S GFP was established by evaluating the effect of different parameters on transformation efficiency by GFP detection. Using embryogenic callus cultures, co-cultivation with LBA1119 OD600= 0.6 for five days at 20 °C enabled reproducible transformation. The maintenance conditions for the embryogenic callus cultures, particularly a high auxin to cytokinin ratio, the age of the culture (optimum for 7-10 months of proliferation) and the use of a yellow callus phenotype, were the most important factors for achieving highly efficient transformation (> 90%). At the histological level, successful transformation was related to the number of proembryogenic masses present. All the selected plants were proved to be transformed by PCR and Southern blot hybridization.

Conclusion

Most progress in increasing transformation efficiency in coffee has been achieved by optimizing the production conditions of embryogenic cultures used as target tissues for transformation. This is the first time that a strong positive effect of the age of the culture on transformation efficiency was demonstrated. Our results makeAgrobacterium-mediated transformation of embryogenic cultures a viable and useful tool both for coffee breeding and for the functional analysis of agronomically important genes.
Clinicopathologic characteristics and treatment outcomes of hepatoid adenocarcinoma of the stomach, a rare but unique subtype of gastric cancer
Authors: Baek Sun Kyung , Han Sae-Won , Oh Do-Youn , Im Seock-Ah , Kim Tae-You , Bang Yung-Jue
Published: May 2011

Background

Gastric hepatoid adenocarcinoma (HAC) is a special type of gastric cancer that morphologically mimics hepatocellular carcinoma. In this study, we performed an evaluation of clinicopathologic characteristics, treatment outcome, and prognosis in patients with gastric HAC.

Methods

We consecutively enrolled patients with pathologically proven gastric HAC at Seoul National University Hospital between January 1996 and December 2008 and conducted a retrospective review. Among 15,253 patients with gastric cancer, 26 patients (0.17%) were diagnosed as gastric HAC.

Results

Among 26 patients, 22 were male and the median age was 63. Stage at diagnosis was stage IB in 3 patients, stage II in 6 patients, stage III in 7 patients, and stage IV in 10 patients. Eight patients out of 18 patients with stage IB, II, III, and IV relapsed after curative surgery. Relapse-free survival for these patients was 16.67 months. The most common metastatic site was intraabdominal lymph nodes (n = 9), followed by the liver (n = 8). Thirteen patients received palliative chemotherapy. The most commonly used regimen was a combination of fluoropyrimidine and platinum. Partial response was observed in one patient and stable disease in 5 patients. Median overall survival and progression free survival of these patients were 8.03 (95% CI: 6.59-9.47) and 3.47 months (95% CI: 0.65-6.29), respectively.

Conclusions

Gastric HAC is a very rare but unique type of stomach cancer. Early detection of this type of cancer is of critical importance to patient prognosis. Additional studies to reveal the biology of this tumor are warranted.
Low bone mass in microscopic colitis
Authors: Lőrinczy Katalin , Lakatos Gábor , Müllner Katalin , Hritz István , Lakatos Péter László , Tulassay Zsolt , Miheller Pál
Published: May 2011

Background

Microscopic colitis presents with similar symptoms to classic inflammatory bowel diseases. Osteoporosis is a common complication of Crohn's disease but there are no data concerning bone metabolism in microscopic colitis.

Aims

The aim of the present study was to evaluate bone density and metabolism in patients with microscopic colitis.

Methods

Fourteen patients microscopic colitis were included in the study, and 28 healthy persons and 28 age and gender matched Crohn's disease patients were enrolled as controls. Bone mineral density was measured using dual x-ray absorptiometry at the lumbar spine, femoral neck and the radius. Serum bone formation and bone resorption markers (osteocalcin and beta-crosslaps, respectively) were measured using immunoassays.

Results

Low bone mass was measured in 57.14% patients with microscopic colitis. Bone mineral density at the femoral neck in patients suffering from microscopic colitis and Crohn's disease was lower than in healthy controls (0.852 ± 0.165 and 0.807 ± 0.136 vs. 1.056 ± 0.126 g/cm2; p < 0.01). Bone mineral density at the non-dominant radius was decreased in microscopic colitis patients (0.565 ± 0.093 vs. 0.667 ± 0.072 g/cm2; p < 0.05) but unaffected in Crohn's disease patients (0.672 ± 0.056 g/cm2). Mean beta-crosslaps concentration was higher in microscopic colitis and Crohn's disease patients than controls (417.714 ± 250.37 and 466.071 ± 249.96 vs. 264.75 ± 138.65 pg/ml; p < 0.05). A negative correlation between beta-crosslaps concentration and the femoral and radius t-scores was evident in microscopic colitis patients.

Conclusions

Low bone mass is frequent in microscopic colitis, and alterations to bone metabolism are similar to those present in Crohn's disease. Therefore, microscopic colitis-associated osteopenia could be a significant problem in such patients.
Chronic diarrhea associated with persistent norovirus excretion in patients with chronic lymphocytic leukemia: report of two cases
Authors: Capizzi Todd , Makari-Judson Grace , Steingart Richard , Mertens Wilson C
Published: May 2011

Background

Chronic diarrhea in patients treated with immunosuppressive agents or suffering from immunosuppressive disease can represent a diagnostic and therapeutic challenge to the clinician. Norovirus infection, a major cause of acute epidemic diarrhea, has been described as a cause of chronic diarrhea in patients who are immunosuppressed, including transplant recipients and the very young.

Case presentations

We describe two patients, a 64 year-old man and a 59 year-old woman, both suffering from chronic lymphocytic leukemia and hypogammaglobulinemia, who developed chronic diarrhea resistant to therapy. In both cases, after months of symptoms, persistent norovirus infection--documented by repeatedly-positive high-sensitivity stool enzyme immunoassay--was found to be the cause. Both patients died with active diarrheal symptoms.

Conclusions

We describe the first cases of advanced chronic lymphocytic leukemia to suffer from chronic symptomatic norovirus infection. Clinicians caring for such patients, particularly those with concomitant hypogammaglobulinema, who have chronic unexplained diarrhea, should consider norovirus infection in the differential diagnosis.
Clinical characteristics and therapeutic outcomes of nosocomial super-infection in adult bacterial meningitis
Authors: Huang Chi-Ren , Chen Shu-Fang , Lu Cheng-Hsien , Chuang Yao-Chung , Tsai Nai-Wen , Chang Chiung-Chih , Wang Hung-Chen , Chien Chun-Chih , Chang Wen-Neng
Published: May 2011

Background

Super-infection in adult bacterial meningitis (ABM) is a condition wherein the cerebrospinal fluid (CSF) grows new pathogen(s) during the therapeutic course of meningitis. It is an uncommon but clinically important condition rarely examined in literature.

Methods

Twenty-seven episodes of super-infection states in 21 ABM patients collected in a 9.5-year study period (January 2001 to June 2010) were evaluated. The clinical characteristics, implicated pathogens, results of antimicrobial susceptibility tests, and therapeutic outcomes were analyzed.

Results

Twenty-one patients (13 men, 8 women) aged 25-73 years (median, 45 years) had post-neurosurgical state as the preceding event and nosocomial infection. The post-neurosurgical states included spontaneous intracranial hemorrhage (ICH) with craniectomy or craniotomy with extra-ventricular drainage (EVD) or ventriculo-peritoneal shunt (VPS) in 10 patients, traumatic ICH with craniectomy or craniotomy with EVD or VPS in 6 patients, hydrocephalus s/p VPS in 2 patients, and one patient each with cerebral infarct s/p craniectomy with EVD, meningeal metastasis s/p Omaya implant, and head injury. All 21 patients had EVD and/or VP shunt and/or Omaya implant during the whole course of ABM. Recurrent fever was the most common presentation and the implicated bacterial pathogens were protean, many of which were antibiotic resistant. Most patients required adjustment of antibiotics after the pathogens were identified but even with antimicrobial therapy, 33.3% (7/21) died. Morbidity was also high among survivors.

Conclusions

Super-infection in ABM is usually seen in patients with preceding neurosurgical event, especially insertion of an external drainage device. Repeat CSF culture is mandatory for diagnostic confirmation because most of the implicated bacterial strains are non-susceptible to common antibiotics used. Unusual pathogens like anaerobic bacteria and fungi may also appear. Despite antimicrobial therapy, prognosis remains poor.
Association of PGC-1alphapolymorphisms with age of onset and risk of Parkinson's disease
Authors: Clark Joanne , Reddy Sonika , Zheng Kangni , Betensky Rebecca A , Simon David K
Published: May 2011

Background

Peroxisome proliferator-activated receptor-γ co-activator (PGC)-1α is a transcriptional co-activator of antioxidant genes and a master regulator of mitochondrial biogenesis. Parkinson's disease (PD) is associated with oxidative stress and mitochondrial dysfunction and recent work suggests a role for PGC-1α. We hypothesized that the rs8192678 PGC-1α single nucleotide polymorphism (SNP) may influence risk or age of onset of PD. The A10398G mitochondrial SNP has been inversely associated with risk of PD in some studies. In the current study we analyzed whether rs8192678 or other PGC-1α SNPs affect PD risk or age of onset, singularly or in association with the A10398G SNP.

Methods

Genomic DNA samples from 378 PD patients and 173 age-matched controls were analyzed by multiplexed probe sequencing, followed by statistical analyses of the association of each SNP, alone or in combination, with risk or age of onset of PD. Adjustments were made for age of onset being less than the age of sampling, and for the observed dependence between these two ages. The PD samples were obtained as two separate cohorts, therefore statistical methods accounted for different sampling methods between the two cohorts, and data were analyzed using Cox regression adjusted for sampling in the risk set definition and in the model.

Results

The rs8192678 PGC-1α SNP was not associated with the risk of PD. However, an association of the PGC-1α rs8192678 GG variant with longevity was seen in control subjects (p = 0.019). Exploratory studies indicated that the CC variant of rs6821591 was associated with risk of early onset PD (p = 0.029), with PD age of onset (p = 0.047), and with longevity (p = 0.022). The rs2970848 GG allele was associated with risk of late onset PD (p = 0.027).

Conclusions

These data reveal possible associations of the PGC-1α SNPs rs6821591 and rs2970848 with risk or age of onset of PD, and of the PGC-1α rs8192678 GG and the rs6821591 CC variants with longevity. If replicated in other datasets, these findings may have important implications regarding the role of PGC-1α in PD and longevity.
HGF/c-met/Stat3 signaling during skin tumor cell invasion: indications for a positive feedback loop
Authors: Syed Zanobia A , Yin Weihong , Hughes Kendall , Gill Jennifer N , Shi Runhua , Clifford John L
Published: May 2011

Background

Stat3 is a cytokine- and growth factor-inducible transcription factor that regulates cell motility, migration, and invasion under normal and pathological situations, making it a promising target for cancer therapeutics. The hepatocyte growth factor (HGF)/c-met receptor tyrosine kinase signaling pathway is responsible for stimulation of cell motility and invasion, and Stat3 is responsible for at least part of the c-met signal.

Methods

We have stably transfected a human squamous cell carcinoma (SCC) cell line (SRB12-p9) to force the expression of a dominant negative form of Stat3 (S3DN), which we have previously shown to suppress Stat3 activity. The in vitro and in vivo malignant behavior of the S3DN cells was compared to parental and vector transfected controls.

Results

Suppression of Stat3 activity impaired the ability of the S3DN cells to scatter upon stimulation with HGF (c-met ligand), enhanced their adhesion, and diminished their capacity to invade in vitro and in vivo. Surprisingly, S3DN cells also showed suppressed HGF-induced activation of c-met, and had nearly undetectable basal c-met activity, as revealed by a phospho-specific c-met antibody. In addition, we showed that there is a strong membrane specific localization of phospho-Stat3 in the wild type (WT) and vector transfected control (NEO4) SRB12-p9 cells, which is lost in the S3DN cells. Finally, co-immunoprecipitation experiments revealed that S3DN interfered with Stat3/c-met interaction.

Conclusion

These studies are the first confirm that interference with the HGF/c-met/Stat3 signaling pathway can block tumor cell invasion in an in vivo model. We also provide novel evidence for a possible positive feedback loop whereby Stat3 can activate c-met, and we correlate membrane localization of phospho-Stat3 with invasion in vivo.
Married women's decision making power on modern contraceptive use in urban and rural southern Ethiopia
Authors: Bogale Binyam , Wondafrash Mekitie , Tilahun Tizta , Girma Eshetu
Published: May 2011

Background

Women in developing countries are either under collective decision making with their partners or completely rely on the male partner's decision on issues that affect their reproductive live. Identifying the major barriers of married women's decision making power on contraceptive use has significant relevance for planning contextually appropriate family planning interventions. The objective of this study was to determine current modern contraceptive practices and decision making power among married women in Tercha Town and surrounding rural areas of Dawro zone, Southern Ethiopia.

Methods

Community based comparative cross-sectional design with both quantitative and Qualitative study has been employed in March and April 2010. The respondents were 699 married women of child bearing age from urban and rural parts of Dawro zone. After conducting census, we took the sample using simple random sampling technique.

Results

Current modern contraceptive use among married women in the urban was 293 (87.5%) and 243 (72.8%) in rural. Married women who reside in urban area were more likely to decide on the use of modern contraceptive method than rural women. Having better knowledge about modern contraceptive methods, gender equitable attitude, better involvement in decisions related to children, socio-cultural and family relations were statistically significant factors for decision making power of women on the use of modern contraceptive methods in the urban setting. Better knowledge, fear of partner's opposition or negligence, involvement in decisions about child and economic affairs were statistically significant factors for better decision making power of women on the use of modern contraceptive methods in the rural part.

Conclusions

High level of current modern contraceptive practice with reduced urban-rural difference was found as compared to regional and national figures. Urban women had better power to make decisions on modern contraceptive than rural women. Modern family planning interventions in the area should be promoted by considering empowering of women on modern contraceptive use decision making.
Childhood meat eating and inflammatory markers: The Guangzhou Biobank Cohort Study
Authors: Schooling CM , Jiang CQ , Lam TH , Zhang WS , Cheng KK , Leung GM
Published: May 2011

Background

We hypothesized that socio-economic development could, via nutritionally driven levels of pubertal sex-steroids, promote a pro-inflammatory state among men but not women in developing countries. We tested this hypothesis, using recalled childhood meat eating as a proxy for childhood nutrition, in southern China.

Methods

We used multivariable linear regression in the Guangzhou Biobank Cohort Study phase 3 (2006-8) to examine the adjusted associations of recalled childhood meat eating, <1/week (n = 5,023), about once per week (n = 3,592) and almost daily (n = 1,252), with white blood cell count and its differentials among older (≥50 years) men (n = 2,498) and women (n = 7,369).

Results

Adjusted for age, childhood socio-economic position, education and smoking, childhood meat eating had sex-specific associations with white blood cell count and lymphocyte count, but not granulocyte count. Men with childhood meat eating almost daily compared to <1/week had higher white blood cell count (0.33 109/L, 95% confidence interval (CI) 0.10 to 0.56) and higher lymphocyte count (0.16 109/L, 95% CI 0.07 to 0.25). Adjustment for obesity slightly attenuated these associations.

Conclusion

If confirmed, this hypothesis implies that economic development and the associated improvements in nutrition at puberty may be less beneficial among men than women; consistent with the widening sex differentials in life expectancy with economic development.
Impact of episiotomy on pelvic floor disorders and their influence on women's wellness after the sixth month postpartum: a retrospective study
Authors: Bertozzi Serena , Londero Ambrogio P , Fruscalzo Arrigo , Driul Lorenza , Delneri Cristina , Calcagno Angelo , Di Benedetto Paolo , Marchesoni Diego
Published: May 2011

Background

The role of episiotomy as a protective factor against pelvic floor disorders postpartum has been debated for many years, but its routine use has been hitherto discouraged in the literature. Comparisons between restrictive and routine use of episiotomy in existent literature, however, fail to include any consideration relating to quality of life. The aim of this study, therefore, is to state the role of episiotomy in preserving the perineum from damage, in order to prevent the influence of pelvic floor disorders on women's psycho-physical wellness after the sixth month postpartum.

Methods

A follow-up telephone interview was performed among 377 primiparous and secondiparous Caucasian women who had a child by spontaneous or operative vaginal delivery in 2006 using a self-created questionnaire and King's Health Questionnaire (KHQ).

Results

The mean age at delivery was 35.26 (±4.68) years and episiotomy was performed in 59.2% of women. Multivariate linear regression shows episiotomy associated to higher quality of life after the sixth month postpartum by correlating with inferior values of King's Health Questionnaire (p < 0.05).

Conclusions

Episiotomy appears to be a protective factor for women's wellness. Women who had episiotomy and who experienced perineal symptoms have a better psycho-physical health status in the 12.79 months (±3.3) follow-up.
Increased arterial stiffness in healthy subjects with high-normal glucose levels and in subjects with pre-diabetes
Authors: Shin Jin Young , Lee Hye Ree , Lee Duk Chul
Published: May 2011

Background

Increased fasting plasma glucose (FPG), which includes impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes, is a risk factor for arterial stiffness. While IFG is widely accepted as a cardiovascular risk factor, recent studies have argued that subjects with high-normal glucose level were characterized by a high incidence of cardiovascular disease. The purpose of this study is to investigate the relationship between FPG and arterial stiffness in non-diabetic healthy subjects.

Methods

We recruited 697 subjects who visited the health promotion center of a university hospital from May 2007 to August 2008. Age, sex, body mass index (BMI), resting heart rate, smoking habits, alcohol intake, exercise, blood pressure, medical history, FPG, lipid profile, high sensitivity C-reactive protein (hs-CRP), and Brachial-ankle pulse wave velocity (ba-PWV) were measured. We performed correlation and multiple linear regression analyses to divide the research subjects into quartiles: Q1(n = 172), 65 mg/dL ≤FPG < 84 mg/dL; Q2(n = 188), 84 mg/dL ≤FPG < 91 mg/dl; Q3(n = 199), 91 mg/dL ≤FPG < 100 mg/dL; Q4(n = 138), 100 mg/dL ≤FPG < 126 mg/dL.

Results

FPG has an independent, positive association with ba-PWV in non-diabetic subjects after correcting for confounding variables, including age, sex, BMI, blood pressure, resting heart rate, hs-CRP, lipid profile, and behavioral habits. The mean ba-PWV of the high-normal glucose group (Q3, 1384 cm/s) was higher than that of the low-normal glucose group (1303 ± 196 cm/s vs.1328 ± 167 cm/s, P < 0.05). The mean ba-PWV value in the IFG group (1469 ± 220 cm/s) was higher than that in the normoglycemic group (P < 0.05, respectively).

Conclusions

An increase in FPG, even within the normal range, was associated with aggravated arterial stiffness. Further research is needed to determine the glycemic target value for the prevention of arterial stiffness in clinical and public health settings.
A multiple antibiotic and serum resistant oligotrophic strain, Klebsiella pneumoniae MB45 having novel dfrA30, is sensitive to ZnO QDs
Authors: Kumar Arvind , Chakraborti Soumynanda , Joshi Prachi , Chakrabarti Pinak , Chakraborty Ranadhir
Published: May 2011

Background

The aim of this study was to describe a novel trimethoprim resistance gene cassette, designated dfrA30, within a class 1 integron in a facultatively oligotrophic, multiple antibiotic and human serum resistant test strain, MB45, in a population of oligotrophic bacteria isolated from the river Mahananda; and to test the efficiency of surface bound acetate on zinc oxide quantum dots (ZnO QDs) as bactericidal agent on MB45.

Methods

Diluted Luria broth/Agar (10-3) media was used to cultivate the oligotrophic bacteria from water sample. Multiple antibiotic resistant bacteria were selected by employing replica plate method. A rapid assay was performed to determine the sensitivity/resistance of the test strain to human serum. Variable region of class 1 integron was cloned, sequenced and the expression of gene coding for antibiotic resistance was done in Escherichia coli JM 109. Identity of culture was determined by biochemical phenotyping and 16S rRNA gene sequence analyses. A phylogenetic tree was constructed based on representative trimethoprim resistance-mediating DfrA proteins retrieved from GenBank. Growth kinetic studies for the strain MB45 were performed in presence of varied concentrations of ZnO QDs.

Results and conclusions

The facultatively oligotrophic strain, MB45, resistant to human serum and ten antibiotics trimethoprim, cotrimoxazole, ampicillin, gentamycin, netilmicin, tobramycin, chloramphenicol, cefotaxime, kanamycin and streptomycin, has been identified as a new strain of Klebsiella pneumoniae. A novel dfr gene, designated as dfrA30, found integrated in class 1 integron was responsible for resistance to trimethoprim in Klebsiella pneumoniae strain MB45. The growth of wild strain MB45 was 100% arrested at 500 mg/L concentration of ZnO QDs. To our knowledge this is the first report on application of ZnO quantum dots to kill multiple antibiotics and serum resistant K. pneumoniae strain.
Effects of 1α,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells
Authors: Wang Wei-Lin W , Chatterjee Namita , Chittur Sridar V , Welsh JoEllen , Tenniswood Martin P
Published: May 2011

Background

There is evidence from epidemiological and in vitro studies that the biological effects of testosterone (T) on cell cycle and survival are modulated by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in prostate cancer. To investigate the cross talk between androgen- and vitamin D-mediated intracellular signaling pathways, the individual and combined effects of T and 1,25(OH)2D3 on global gene expression in LNCaP prostate cancer cells were assessed.

Results

Stringent statistical analysis identifies a cohort of genes that lack one or both androgen response elements (AREs) or vitamin D response elements (VDREs) in their promoters, which are nevertheless differentially regulated by both steroids (either additively or synergistically). This suggests that mechanisms in addition to VDR- and AR-mediated transcription are responsible for the modulation of gene expression. Microarray analysis shows that fifteen miRNAs are also differentially regulated by 1,25(OH)2D3 and T. Among these miR-22, miR-29ab, miR-134, miR-1207-5p and miR-371-5p are up regulated, while miR-17 and miR-20a, members of the miR-17/92 cluster are down regulated. A number of genes implicated in cell cycle progression, lipid synthesis and accumulation and calcium homeostasis are among the mRNA targets of these miRNAs. Thus, in addition to their well characterized effects on transcription, mediated by either or both cognate nuclear receptors, 1,25(OH)2D3 and T regulate the steady state mRNA levels by modulating miRNA-mediated mRNA degradation, generating attenuation feedback loops that result in global changes in mRNA and protein levels. Changes in genes involved in calcium homeostasis may have specific clinical importance since the second messenger Ca2+ is known to modulate various cellular processes, including cell proliferation, cell death and cell motility, which affects prostate cancer tumor progression and responsiveness to therapy.

Conclusions

These data indicate that these two hormones combine to drive a differentiated phenotype, and reinforce the idea that the age dependent decline in both hormones results in the de-differentiation of prostate tumor cells, which results in increased proliferation, motility and invasion common to aggressive tumors. These studies also reinforce the potential importance of miRNAs in prostate cancer progression and therapeutic outcomes.
Targeting oncogenic miR-335 inhibits growth and invasion of malignant astrocytoma cells
Authors: Shu Minfeng , Zheng Xiaoke , Wu Sihan , Lu Huimin , Leng Tiandong , Zhu Wenbo , Zhou Yuehan , Ou Yanqiu , Lin Xi , Lin Yuan , Xu Dong , Zhou Yuxi , Yan Guangmei
Published: May 2011

Background

Astrocytomas are the most common and aggressive brain tumors characterized by their highly invasive growth. Gain of chromosome 7 with a hot spot at 7q32 appears to be the most prominent aberration in astrocytoma. Previously reports have shown that microRNA-335 (miR-335) resided on chromosome 7q32 is deregulated in many cancers; however, the biological function of miR-335 in astrocytoma has yet to be elucidated.

Results

We report that miR-335 acts as a tumor promoter in conferring tumorigenic features such as growth and invasion on malignant astrocytoma. The miR-335 level is highly elevated in C6 astrocytoma cells and human malignant astrocytomas. Ectopic expression of miR-335 in C6 cells dramatically enhances cell viability, colony-forming ability and invasiveness. Conversely, delivery of antagonist specific for miR-335 (antagomir-335) to C6 cells results in growth arrest, cell apoptosis, invasion repression and marked regression of astrocytoma xenografts. Further investigation reveals that miR-335 targets disheveled-associated activator of morphogenesis 1(Daam1) at posttranscriptional level. Moreover, silencing of endogenous Daam1 (siDaam1) could mimic the oncogenic effects of miR-335 and reverse the growth arrest, proapoptotic and invasion repression effects induced by antagomir-335. Notably, the oncogenic effects of miR-335 and siDAAM1 together with anti-tumor effects of antagomir-335 are also confirmed in human astrocytoma U87-MG cells.

Conclusion

These findings suggest an oncogenic role of miR-335 and shed new lights on the therapy of malignant astrocytomas by targeting miR-335.
Composition of fatty acids in plasma and erythrocytes and eicosanoids level in patients with metabolic syndrome
Authors: Novgorodtseva Tatyana P , Karaman Yulia K , Zhukova Natalia V , Lobanova Elena G , Antonyuk Marina V , Kantur Tatyana A
Published: May 2011

Background

Disturbances of the fatty acids composition in plasma and red blood cells and eicosanoid synthesis play an important role in the metabolic syndrome (MS) formation.

Methods

The observation group included 61 people with metabolic syndrome (30 patients with MS and normal levels of insulin, 31 people with MS and insulin resistance - IR). The parameters of carbohydrate and lipid metabolism in blood serum were examined. The composition of nonesterified fatty acids (NEFA), fatty acid (FA) of red blood cells lipids was analyzed by gas-liquid chromatography. Eicosanoids level in MS patients blood serum was studied by enzyme immunoassay.

Results

In MS patients in the absence of glucose-insulin homeostasis disturbances and in patients with IR the accumulation of polyunsaturated fatty acids (18:2 n6, 18:3 n3, 22:4 n6) and lower pool of saturated FA (12:0, 14:0, 16: 0, 17:0) in plasma were discovered. A deficit of polyunsaturated FA (18:3 n3, 20:4 n6) with a predominance of on-saturated FA (14:0, 18:0) in erythrocyte membranes was revealed. In MS patients regardless of the carbohydrate metabolism status high levels of leukotriene B4 and 6-keto-prostaglandin-F1α in serum were found. The development of IR in MS patients leads to increased synthesis of thromboxane A2.

Conclusion

The results revealed a disturbance in nonesterified fatty acids of plasma lipids and red blood cells, eicosanoid synthesis in MS patients. The breach of the plasma and cell membranes fatty acids compositions, synthesis of vasoactive and proinflammatory eicosanoids is an important pathogenetic part of the MS development.
Design and characterization of protein-quercetin bioactive nanoparticles
Authors: Fang Ru , Jing Hao , Chai Zhi , Zhao Guanghua , Stoll Serge , Ren Fazheng , Liu Fei , Leng Xiaojing
Published: May 2011

Background

The synthesis of bioactive nanoparticles with precise molecular level control is a major challenge in bionanotechnology. Understanding the nature of the interactions between the active components and transport biomaterials is thus essential for the rational formulation of bio-nanocarriers. The current study presents a single molecule of bovine serum albumin (BSA), lysozyme (Lys), or myoglobin (Mb) used to load hydrophobic drugs such as quercetin (Q) and other flavonoids.

Results

Induced by dimethyl sulfoxide (DMSO), BSA, Lys, and Mb formed spherical nanocarriers with sizes less than 70 nm. After loading Q, the size was further reduced by 30%. The adsorption of Q on protein is mainly hydrophobic, and is related to the synergy of Trp residues with the molecular environment of the proteins. Seven Q molecules could be entrapped by one Lys molecule, 9 by one Mb, and 11 by one BSA. The controlled releasing measurements indicate that these bioactive nanoparticles have long-term antioxidant protection effects on the activity of Q in both acidic and neutral conditions. The antioxidant activity evaluation indicates that the activity of Q is not hindered by the formation of protein nanoparticles. Other flavonoids, such as kaempferol and rutin, were also investigated.

Conclusions

BSA exhibits the most remarkable abilities of loading, controlled release, and antioxidant protection of active drugs, indicating that such type of bionanoparticles is very promising in the field of bionanotechnology.
Extracranial propagation of glioblastoma with extension to pterygomaxillar fossa
Authors: Tomac Damir , Chudy Darko , Lambaša Smiljka , Topić Iva , Grahovac Gordan , Zoric Arijana
Published: May 2011

Background

Glioblastoma multiforme is a highly malignant primary brain tumor that shows marked local aggressiveness, but extracranial spread is not a common occurrence. We present an unusual case of recurrent glioblastoma in 54-year old male that spread through the scull base to the ethmoid and sphenoid sinuses, to the orbita, pterygomaxillar fossa, and to the neck.

Methods

A 54-year old male underwent left temporal resection because of brain tumor of his left temporal lobe. Operation was followed by external beam radiation combined with temozolomide. The tumor recurred eight months after first surgery. The patient developed swelling of left temporal region, difficult swallowing and headache. MRI of head showed recurrent tumor, which invaded orbita, ethmoid and sphenoid sinuses, nasal cavity, pterygomaxillar fossa.

Results

The patient died ten months after initial diagnosis of glioblastoma multiforme, and two months after his second operation.

Conclusions

The aggressive surgical operation helped to downsize the tumor mass as much as possible, but did not prolonged significantly the life or improved the life quality of the patient. The current literature is reviewed, and the diagnostic approaches as well as therapeutic options are discussed.