bluuebunny/crossref_metadata_2025 huggingface dataset:
Time course gene expression profiling of yeast spore germination reveals a network of transcription factors orchestrating the global response
Authors: Geijer Cecilia , Pirkov Ivan , Vongsangnak Wanwipa , Ericsson Abraham , Nielsen Jens , Krantz Marcus , Hohmann Stefan
Published: October 2012

Background

Spore germination of the yeastSaccharomyces cerevisiaeis a multi-step developmental path on which dormant spores re-enter the mitotic cell cycle and resume vegetative growth. Upon addition of a fermentable carbon source and nutrients, the outer layers of the protective spore wall are locally degraded, the tightly packed spore gains volume and an elongated shape, and eventually the germinating spore re-enters the cell cycle. The regulatory pathways driving this process are still largely unknown. Here we characterize the global gene expression profiles of germinating spores and identify potential transcriptional regulators of this process with the aim to increase our understanding of the mechanisms that control the transition from cellular dormancy to proliferation.

Results

Employing detailed gene expression time course data we have analysed the reprogramming of dormant spores during the transition to proliferation stimulated by a rich growth medium or pure glucose. Exit from dormancy results in rapid and global changes consisting of different sequential gene expression subprograms. The regulated genes reflect the transition towards glucose metabolism, the resumption of growth and the release of stress, similar to cells exiting a stationary growth phase. High resolution time course analysis during the onset of germination allowed us to identify a transient up-regulation of genes involved in protein folding and transport. We also identified a network of transcription factors that may be regulating the global response. While the expression outputs following stimulation by rich glucose medium or by glucose alone are qualitatively similar, the response to rich medium is stronger. Moreover, spores sense and react to amino acid starvation within the first 30 min after germination initiation, and this response can be linked to specific transcription factors.

Conclusions

Resumption of growth in germinating spores is characterized by a highly synchronized temporal organisation of up- and down-regulated genes which reflects the metabolic reshaping of the quickening spores.
Automated bolus advisor control and usability study (ABACUS): does use of an insulin bolus advisor improve glycaemic control in patients failing multiple daily insulin injection (MDI) therapy? [NCT01460446]
Authors: Cavan David A , Ziegler Ralph , Cranston Iain , Barnard Katharine , Ryder Jacqueline , Vogel Claudia , Parkin Christopher G , Koehler Walter , Vesper Iris , Petersen Bettina , Wagner Robin S
Published: October 2012

Background

People with T1DM and insulin-treated T2DM often do not follow and/or adjust their insulin regimens as needed. Key contributors to treatment non-adherence are fear of hypoglycaemia, difficulty and lack of self-efficacy associated with insulin dose determination. Because manual calculation of insulin boluses is both complex and time consuming, people may rely on empirical estimates, which can result in persistent hypoglycaemia and/or hyperglycaemia. Use of automated bolus advisors (BA) has been shown to help insulin pump users to more accurately meet prandial insulin dosage requirements, improve postprandial glycaemic excursions, and achieve optimal glycaemic control with an increased time within optimal range. Use of a BA containing an early algorithm based on sliding scales for insulin dosing has also been shown to improve HbA1c levels in people treated with multiple daily insulin injections (MDI). We designed a study to determine if use of an automated BA can improve clinical and psychosocial outcomes in people treated with MDI.

Methods/design

The Automated Bolus Advisor Control and Usability Study (ABACUS) is a 6-month, prospective, randomised, multi-centre, multi-national trial to determine if automated BA use improves glycaemic control as measured by a change in HbA1c in people using MDI with elevated HbA1c levels (#62;7.5%). A total of 226 T1DM and T2DM participants will be recruited. Anticipated attrition of 20% will yield a sample size of 90 participants, which will provide #62;80% power to detect a mean difference of 0.5%, with SD of 0.9%, using a one-sided 5% t-test, with 5% significance level. Other measures of glycaemic control, self-care behaviours and psychosocial issues will also be assessed.

Discussion

It is critical that healthcare providers utilise available technologies that both facilitate effective glucose management and address concerns about safety and lifestyle. Automated BAs may help people using MDI to manage their diabetes more effectively and minimise the risk of long-term diabetes related complications. Findings from a recent study suggest that BA use positively addresses both safety and lifestyle concerns; however, randomised trials are needed to confirm these perceptions and determine whether bolus advisor use improves clinical outcomes. Our study is designed to make these assessments.

Trial registration

NCT01460446
Characteristics of progressive multifocal leukoencephalopathy clarified through internet-assisted laboratory surveillance in Japan
Authors: Nakamichi Kazuo , Mizusawa Hidehiro , Yamada Masahito , Kishida Shuji , Miura Yoshiharu , Shimokawa Toshio , Takasaki Tomohiko , Lim Chang-Kweng , Kurane Ichiro , Saijo Masayuki
Published: October 2012

Background

Progressive multifocal leukoencephalopathy (PML), a rare but fatal demyelinating disease caused by JC virus (JCV), occurs mainly in immunocompromised patients. As PML develops in individuals with various underlying disorders sporadically and infrequently, a nationwide survey of PML is difficult. This study was conducted to elucidate the characteristics of PML in Japan through an internet-assisted laboratory surveillance program.

Methods

A diagnostic support system for PML was established using a real-time PCR assay of JCV DNA in cerebrospinal fluid (CSF), and requests for testing were received from clinicians via specialized websites. Medical histories of patients were collected through standardized questionnaires, and a database of CSF JCV loads and clinical information was created and analyzed.

Results

For 4 years from April 2007 to March 2011, CSF specimens from 419 patients were tested. Forty-eight individuals were found positive for JCV DNA in their CSF and were diagnosed with PML. PML primarily occurred not only in HIV-positive patients (33.3%) but also in patients with hematologic disorders after receiving stem cell transplantation, chemotherapy, and/or immunosuppressive treatment (39.6%). The frequencies of PML cases among the subjects in these two categories were 20.3% and 23.5%, respectively. Although no significant features were observed with respect to CSF JCV loads in PML patients with an HIV infection or hematologic disorder, males were predominant in both groups (100% and 89.5%, respectively). The proportion of PML cases with autoimmune disorders (6.3%) or solid-organ transplants (2.1%) was smaller than those with HIV infection or hematologic disorders, probably due to the limited availability of therapeutic monoclonal antibodies and transplantation from brain dead donors.

Conclusions

The results suggest that the internet-assisted laboratory surveillance program might be a useful strategy for collecting precise real-time information on PML on a national level. The current database provides important background information for the diagnosis and treatment of patients with risk factors for PML.
Application of the Western-based adjuvant online model to Korean colon cancer patients; a single institution experience
Authors: Jung Minkyu , Kim Geon Woo , Jung Inkyung , Ahn Joong Bae , Roh Jae Kyung , Rha Sun Young , Chung Hyun Cheol , Kim Nam Kyu , Kim Tae Il , Shin Sang Joon
Published: October 2012

Background

Adjuvant Online (AOL) is web-accessible risk-assessment model that predicts the mortality and the benefits of adjuvant therapy (http://www.newadjuvantonline.com). AOL has never been validated for Asian colon cancer patients.

Methods

Using the Yonsei Tumor Registry database, patients who were treated within the Yonsei University Health System between 1990 and 2005 for T1-4, N0-2, and M0 colon cancer were included in the calculations for survival. Observed and predicted 5-year overall survival was compared for each patient.

Results

The median age of the study population of 1431 patients was 60 years (range, 15–87 years), and the median follow-up duration was 7.9 years (range, 0.06–19.8 years). The predicted 5-year overall survival rate (77.7%) and observed survival (79.5%) was not statistically different (95% Confidential interval, 76.3–81.5) in all patients. Predicted outcomes were within 95% confidential interval of observed survival in both stage II and III disease, including most demographic and pathologic subgroups. Moreover, AOL more accurately predicted OS for patients with stage II than stage III.

Conclusions

AOL tended to offer reliable prediction for 5-year overall survival and could be used as a decision making tool for adjuvant treatment in Korean colon cancer patients whose prognosis is similar to other Asian patients.
Population-based study of breast cancer in older women: prognostic factors of relative survival and predictors of treatment
Authors: Dialla Pegdwende Olivia , Dabakuyo Tienhan Sandrine , Marilier Sophie , Gentil Julie , Roignot Patrick , Darut-Jouve Ariane , Poillot Marie-Laure , Quipourt Valérie , Arveux Patrick
Published: October 2012

Background

A large proportion of women with breast cancer (BC) are elderly. However, there is a lack of information regarding BC prognostic factors and care in this population. The aims of this study were to assess the prognostic factors of relative survival (RS) among women with BC aged ≥ 75 years old and to identify the predictive factors of treatments administered to this population.

Methods

A population-based study was performed using data from the Cote d’Or breast and gynaecological cancer registry. Women aged 75 years and older with primary invasive BC and resident in Cote d’Or at the time of diagnosis made between January 1998 and December 2008 were retrospectively selected. Prognostic factors of RS were estimated in a generalized linear model with a Poisson error structure. RS rate for the whole population was given at 5 years. Logistic regression models were used to identify the predictors of the treatments administered.

Results

Six hundred and eighty-one women were included. Median age at diagnosis was 80. Comorbidities (p=0.02), pT stage (p=0.04), metastases (p=<0.001), having a family doctor (p=0.03) and hormone-receptor status (p=0.006) were independent prognostic factors of RS. The RS rate at 5 years for the whole population was 78.2%, 95%CI = [72.2-83.0]. Age, pT stage, metastases, histoprognostic SBR grade, hormone receptor status and comorbidities were frequently found to be predictors of treatment with surgery alone, hormone therapy alone, breast conserving surgery plus adjuvant therapy and mastectomy plus adjuvant therapy.

Conclusions

Comorbid conditions adversely affect survival in older women with breast cancer. Moreover the results of this study showed that there are numerous predictors of the type of treatment administered, and that the most important were age and comorbidities.
Adherence evaluation of endocrine treatment in breast cancer: methodological aspects
Authors: Oberguggenberger Anne S , Sztankay Monika , Beer Beate , Schubert Birthe , Meraner Verena , Oberacher Herbert , Kemmler Georg , Giesinger Johannes , Gamper Eva , Sperner-Unterweger Barbara , Marth Christian , Holzner Bernhard , Hubalek Michael
Published: October 2012

Background

Current studies on adherence to endocrine therapy in breast cancer patients suffer from methodological limitations due to a lack of well-validated methods for assessing adherence. There is no gold standard for measuring adherence. The aim of our study was to compare four different approaches for evaluating adherence to anastrozole therapy for breast cancer with regard to concordance between methods.

Methods

Outpatients with early breast cancer treated with anastrozole completed the multi-method assessment of adherence. We implemented a self-report scale (the Simplified Medication Adherence Questionnaire), physician- ratings, refill records and determination of anastrozole serum concentration.

Results

Comparison of the four approaches using Spearman rank correlation revealed poor concordance across all methods reflecting weak correlations of 0.2-0.4. Considering this data incomparability across methods, we still observed high adherence rates of 78%-98% across measures.

Conclusion

Our findings contribute to the growing body of knowledge on the impact that methodological aspects exert on the results of adherence measurement in breast cancer patients receiving endocrine treatment. Our findings suggest that the development and validation of instruments specific to patients receiving endocrine agents is imperative in order to arrive at a more accurate assessment and to subsequently obtain more precise estimates of adherence rates in this patient population.
Histopathological changes in anatomical distribution of inflammatory bowel disease in children: a retrospective cohort study
Authors: Tsang Jessica , Sikora Sheena , Spady Donald , El-Matary Wael
Published: October 2012

Background

Anatomical progression of pediatric inflammatory bowel disease is under-reported. The aim of this work was to examine possible changes in the anatomical distribution of IBD in pediatric patients at diagnosis and at follow up.

Methods

In a retrospective cohort study, the medical records of children with inflammatory bowel disease were examined. Patients who had at least 2 endoscopic/colonoscopic examinations were included. Primary outcome was histopathological progression based on histopathological examination of biopsies taken during endoscopic and colonoscopic bowel examination. Factors predictive of disease progression were also examined.

Results

A total of 98 patients fulfilled inclusion criteria (49 female, 54 with ulcerative colitis, range 2 – 17 years, mean age at diagnosis was 10.6 years, SD ± 3.67), the mean duration of follow up was 32.9 months (range 0.1 – 60 months, SD ± 8.54). In the ulcerative colitis group, 41% had disease progression and none of the examined variables (age, gender, laboratory markers, growth and disease activity at diagnosis) appeared to effect disease progression. In the Crohn’s disease group, 75% had disease progression. Girls (OR = 0.13, 95% CI 0.02 – 0.79) and patients with high erythrocytic sedimentation rate (OR=0.942, 95% CI 0.894 – 0.99) were predictive for disease progression.

Conclusions

Despite maximum therapy, the majority of children with Crohn’s disease appeared to have histopathological disease progression. Female sex and high erythrocytic sedimentation rate seemed to be predictive for disease progression. None of the factors analyzed seemed predictive of disease progression in ulcerative colitis.
Immunogenicity when utilizing adenovirus serotype 4 and 5 vaccines expressing circumsporozoite protein in naïve and Adenovirus (Ad5) immune mice
Authors: Schuldt Nathaniel J , Aldhamen Yasser A , Godbehere-Roosa Sarah , Seregin Sergey S , Kousa Youssef A , Amalfitano Andrea
Published: October 2012

Background

Induction of potent long lasting effector T cell responses against liver stage malaria antigens strongly correlates with protection from malaria. While Adenovirus serotype 5 (Ad5) based malaria vaccine platforms have the ability to induce potent effector T cell responses against transgenes, high rates of pre-existing Ad5 immunity in malaria endemic regions has prompted study of alternative Ad serotype based malaria vaccines as replacements for Ad5 based malaria vaccines. The research described in this article examines the utility of alternative serotype adenovirus serotype 4 (Ad4) expressing a sporozoite surface protein (circumsporozoite protein (CSP)) (Ad4-CSP) to induce immune responses against CSP. The immunogenicity of Ad4-CSP was also tested in homologous and heterologous prime boost vaccinations in both Ad5 naïve and Ad5 immune backgrounds as compared to use of Ad5-CSP.

Results

In Ad5 naïve animals, use of Ad4-CSP priming vaccinations followed by boosting with Ad5-CSP (Ad4-CSP/Ad5-CSP) maximally increased the numbers of CSP specific cytokine secreting cytotoxic T cells relative to repeated use of Ad5-CSP. The Ad4-CSP/Ad5-CSP regimen also induced equivalent levels of CSP specific cell killing as did homologous prime-boost vaccinations with Ad5-CSP, despite stimulating lower numbers of CSP specific cytotoxic T cells. Priming with Ad4-CSP followed by a homologous boost resulted in significantly less CSP specific humoral responses than any other vaccination regimen tested in Ad naïve animals. In Ad5 immune animals, addition of Ad4-CSP in homologous or heterologous prime boost resulted in inductions of higher CSP specific responses than animals repeatedly vaccinated with Ad5-CSP alone. However, the observed responses were well below those observed in similarly treated Ad naïve mice.

Conclusions

While the Ad4-CSP/Ad5-CSP and Ad5-CSP/Ad5-CSP vaccination regimens resulted in equivalent CSP specific killing in Ad naïve animals, Ad4-CSP/Ad5-CSP achieved this result with a lower percentage of CSP specific CD8+T cells and a higher number of IFNγ secreting cells, suggesting that the Ad4-CSP/Ad5-CSP vaccination regimen elicits more efficient cytotoxic T cells. In Ad5 immune animals use of Ad4-CSP improved CSP specific immune responses as compared to repeated use of Ad5-CSP, but could not achieve the levels of immunogenicity observed when the same vaccine regimens were used in Ad naïve animals. These data indicate the existence of some level of immunological cross-reactivity between these two adenovirus subgroups. Based on these results, it is suggested that future studies should undertake similarly stringent analyses of alternative Ad serotypes to establish their effectiveness as replacements for Ad5.
Weight status and perception of body image in children: the effect of maternal immigrant status
Authors: Gualdi-Russo Emanuela , Manzon Vanessa Samantha , Masotti Sabrina , Toselli Stefania , Albertini Augusta , Celenza Francesca , Zaccagni Luciana
Published: October 2012

Background

Recent studies have shown that body image perception is an important factor in weight control and may be influenced by culture and ethnicity. The aim of the present study was to assess the relationship between immigrant status of the mother and weight status and body image perception of the child.

Methods

In total, 2706 schoolchildren (1405 boys and 1301 girls) aged 8–9 years and their mothers participated in a cross-sectional survey in Emilia-Romagna region (northern Italy). Weight and height of the children were measured and Body Mass Index (BMI) was calculated. Actual and ideal body image perception by the children and by the mothers with respect to their children was evaluated according to Collins’ body image silhouettes.

Results

The BMI values were significantly lower in children of immigrants than in children of Italian mothers (F:17.27 vs 17.99 kg/m2; M:17.77 vs 18.13 kg/m2). The prevalence of overweight/obesity was lower, and the prevalence of underweight higher, in children of immigrant mothers than in those of Italian mothers (overweight- F:21.3 vs 29.1%; M. 28.3 vs 31.4%; underweight- F:5.16 vs 3.84%; M:6.63 vs 2.82%). The children's body image perception was consistent with the differing pattern of nutritional status. In the comparison between actual and ideal figures, the Feel-Ideal Difference Index (FID) scores resulted different between the subsample with foreign-born mother in comparison to the native one (significantly lower in daughters of immigrants) (FID- F: 0.31 vs 0.57; M: 0.35 vs 0.32). There were significant differences in the choice of the ideal figure of the child between immigrant mothers and Italian mothers (FID- F: -0.05 vs 0.19; M: -0.35 vs −0.03): the ideal figure values were higher in the immigrant mothers of male children and lower in the Italian mothers of female children.

Conclusion

Our results suggest that cultural and behavioral factors linked to ethnicity play an important role in the nutritional status of children and in the perceived and ideal body image.
Socioeconomic determinants of geographic disparities in campylobacteriosis risk: a comparison of global and local modeling approaches
Authors: Weisent Jennifer , Rohrbach Barton , Dunn John R , Odoi Agricola
Published: October 2012

Background

Socioeconomic factors play a complex role in determining the risk of campylobacteriosis. Understanding the spatial interplay between these factors and disease risk can guide disease control programs. Historically, Poisson and negative binomial models have been used to investigate determinants of geographic disparities in risk. Spatial regression models, which allow modeling of spatial effects, have been used to improve these modeling efforts. Geographically weighted regression (GWR) takes this a step further by estimating local regression coefficients, thereby allowing estimations of associations that vary in space. These recent approaches increase our understanding of how geography influences the associations between determinants and disease. Therefore the objectives of this study were to: (i) identify socioeconomic determinants of the geographic disparities of campylobacteriosis risk (ii) investigate if regression coefficients for the associations between socioeconomic factors and campylobacteriosis risk demonstrate spatial variability and (iii) compare the performance of four modeling approaches: negative binomial, spatial lag, global and local Poisson GWR.

Methods

Negative binomial, spatial lag, global and local Poisson GWR modeling techniques were used to investigate associations between socioeconomic factors and geographic disparities in campylobacteriosis risk. The best fitting models were identified and compared.

Results

Two competing four variable models (Models 1 & 2) were identified. Significant variables included race, unemployment rate, education attainment, urbanicity, and divorce rate. Local Poisson GWR had the best fit and showed evidence of spatially varying regression coefficients.

Conclusions

The international significance of this work is that it highlights the inadequacy of global regression strategies that estimate one parameter per independent variable, and therefore mask the true relationships between dependent and independent variables. Since local GWR estimate a regression coefficient for each location, it reveals the geographic differences in the associations. This implies that a factor may be an important determinant in some locations and not others. Incorporating this into health planning ensures that a needs-based, rather than a “one-size-fits-all”, approach is used. Thus, adding local GWR to the epidemiologists’ toolbox would allow them to assess how the impacts of different determinants vary by geography. This knowledge is critical for resource allocation in disease control programs.
Optical properties of Ni and Cu nanowire arrays and Ni/Cu superlattice nanowire arrays
Authors: Zhang Yaya , Xu Wen , Xu Shaohui , Fei Guangtao , Xiao Yiming , Hu Jiaguang
Published: October 2012

In this study, Ni and Cu nanowire arrays and Ni/Cu superlattice nanowire arrays are fabricated using standard techniques such as electrochemical deposition of metals into porous anodic alumina oxide templates having pore diameters of about 50 nm. We perform optical measurements on these nanowire array structures. Optical reflectance (OR) of the as-prepared samples is recorded using an imaging spectrometer in the wavelength range from 400 to 2,000 nm (i.e., from visible to near-infrared bandwidth). The measurements are carried out at temperatures set to be 4.2, 70, 150, and 200 K and at room temperature. We find that the intensity of the OR spectrum for nanowire arrays depends strongly on the temperature. The strongest OR can be observed at about T = 200 K for all samples in visible regime. The OR spectra for these samples show different features in the visible and near-infrared bandwidths. We discuss the physical mechanisms responsible for these interesting experimental findings. This study is relevant to the application of metal nanowire arrays as optical and optoelectronic devices.
A divergent variant of Grapevine leafroll-associated virus 3is present in California
Authors: Seah Yee Mey , Sharma Abhineet M , Zhang Siming , Almeida Rodrigo PP , Duffy Siobain
Published: October 2012

Background

Grapevine leafroll-associated viruses are a problem for grape production globally. Symptoms are caused by a number of distinct viral species. During a survey of Napa Valley vineyards (California, USA), we found evidence of a new variant of Grapevine leafroll-associated virus 3 (GLRaV-3). We isolated its genome from a symptomatic greenhouse-raised plant and fully sequenced it.

Findings

In a maximum likelihood analysis of representative GLRaV-3 gene sequences, the isolate grouped most closely with a recently sequenced variant from South Africa and a partial sequence from New Zealand. These highly divergent GLRaV-3 variants have predicted proteins that are more than 10% divergent from other GLRaV-3 variants, and appear to be missing an open reading frame for the p6 protein.

Conclusions

This divergent GLRaV-3 phylogroup is already present in grape-growing regions worldwide and is capable of causing symptoms of leafroll disease without the p6 protein.
Serological evidence of ebolavirus infection in bats, China
Authors: Yuan Junfa , Zhang Yuji , Li Jialu , Zhang Yunzhi , Wang Lin-Fa , Shi Zhengli
Published: October 2012

Background

The genus Ebolavirus of the family Filoviridae currently consists of five species. All species, with the exception of Reston ebolavirus, have been found in Africa and caused severe human diseases. Bats have been implicated as reservoirs for ebolavirus. Reston ebolavirus, discovered in the Philippines, is the only ebolavirus species identified in Asia to date. Whether this virus is prevalent in China is unknown.

Findings

In this study, we developed an enzyme linked immunosorbent assay (ELISA) for ebolavirus using the recombinant nucleocapsid protein and performed sero-surveillance for the virus among Chinese bat populations. Our results revealed the presence of antibodies to ebolavirus in 32 of 843 bat sera samples and 10 of 16 were further confirmed by western blot analysis.

Conclusion

To our knowledge, this is the first report of any filovirus infection in China.
The Intrahepatic Expression and Distribution of BTLA and its Ligand HVEM in patients with HBV-related acute-on-chronic liver failure
Authors: Xu Huan , Cao Dayan , Guo Guoning , Ruan Zhihua , Wu Yuzhang , Chen Yongwen
Published: October 2012

Objective

It has been demonstrated that signals from the inhibitory receptor B and T lymphocyte attenuator (BTLA) are involved in regulating the pathogenesis of infectious diseases. However, the expression and anatomical distribution of BTLA and its ligand, the herpes virus entry mediator (HVEM), have not yet been determined in cases of HBV-related acute-on-chronic liver failure (HBV-ACLF) patients.

Methods

In this study, the expression of BTLA and HVEM in liver tissues from HBV-ACLF, chronic hepatitis B (CHB) patients and healthy individuals was analyzed by immunohistochemistry.

Results

The results of this analysis demonstrated that both molecules were observed in the HBV-ACLF samples and that their expression was chiefly in the infiltrating inflammatory cells and the damaged bile ducts. However, they were absent in liver sections from CHB patients and healthy controls. Immunofluorescence double-staining indicated that BTLA was found on CK-18+ epithelial cells, CD31+ endothelial cells, CD68+ macrophages, CD56+ NK cells, CD16+ monocytes, CD3+ , CD8+ T cells, and Foxp3+ regulatory T cells (Treg). By contrast, HVEM expression was restricted to CK18+ epithelial cells and CD68+ macrophages. Moreover, the expression of several members of the B7 superfamily, including PD-L1, PD-L2, B7-H3 and B7-H4, was also detected in these liver tissues, and these proteins were co-expressed with HVEM. Interestingly, the expression of fibrinogen-like protein 2 (FGL2), a virus-induced procoagulant molecule, was also found in liver sections from HBV-ACLF, this molecule also co-expresses with BTLA and HVEM.

Conclusions

These results suggest that BTLA-HVEM signaling is likely to affect the pathogenesis of HBV-ACLF, a clear understanding of the functional roles of these proteins should further elucidate the disease process.

Virtual slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/8080806838149123
Behavioural response of the malaria vector Anopheles gambiae to host plant volatiles and synthetic blends
Authors: Nyasembe Vincent O , Teal Peter EA , Mukabana Wolfgang R , Tumlinson James H , Torto Baldwyn
Published: October 2012

Background

Sugar feeding is critical for survival of malaria vectors and, although discriminative plant feeding previously has been shown to occur inAnopheles gambiae s.s., little is known about the cues mediating attraction to these plants. In this study, we investigated the role of olfaction inAn. gambiaediscriminative feeding behaviour.

Methods

Dual choice olfactometer assays were used to study odour discrimination byAn. gambiaeto three suspected host plants:Parthenium hysterophorus(Asteraceae),Bidens pilosa(Asteraceae) andRicinus communis(Euphorbiaceae). Sugar content of the three plant species was determined by analysis of their trimethylsilyl derivatives by coupled gas chromatography–mass spectrometry (GC-MS) and confirmed with authentic standards. Volatiles from intact plants of the three species were collected on Super Q and analyzed by coupled GC-electroantennographic detection (GC-EAD) and GC-MS to identify electrophysiologically-active components whose identities were also confirmed with authentic standards. Active compounds and blends were formulated using dose–response olfactory bioassays. Responses of females were converted into preference indices and analyzed by chi-square tests. The amounts of common behaviourally-active components released by the three host plants were compared with one-way ANOVA.

Results

Overall, the sugar contents were similar in the two Asteraceae plants,P. hysterophorusandB. pilosa,but richer inR. communis. Odours released byP. hysterophoruswere the most attractive, with those fromB. pilosabeing the least attractive to females in the olfactometer assays. Six EAD-active components identified were consistently detected by the antennae of adult females. The amounts of common antennally-active components released varied with the host plant, with the highest amounts released byP. hysterophorus. In dose–response assays, single compounds and blends of these components were attractive to females but to varying levels, with one of the blends recording a significantly attractive response from females when compared to volatiles released by either the most preferred plant,P. hysterophorus(χ2 = 5.23, df = 1,P < 0.05) or as a synthetic blend mimicking that released byP. hysterophorus.

Conclusions

Our results demonstrate that (a) a specific group of plant odours attract femaleAn. gambiae(b) females use both qualitative and quantitative differences in volatile composition to associate and discriminate between different host plants, and (c) altering concentrations of individual EAD-active components in a blend provides a practical direction for developing effective plant-based lures for malaria vector management.
Versatile inhibitory effects of the flavonoid‐derived PI3K/Akt inhibitor, LY294002, on ATP‐binding cassette transporters that characterize stem cells
Authors: Imai Yasuo , Yamagishi Hidetsugu , Ono Yuko , Ueda Yoshihiko
Published: October 2012

Stem cells are undifferentiated cells capable of proliferation, self‐renewal, and production of a large number of differentiated progeny. Stem cells exist even in malignancies. They are called cancer stem cells, which may represent the origin of these tumors and may be one of the reasons of chemoresistance. The phosphatidylinositol‐3‐kinase (PI3K)/Akt pathway is important for the maintenance of pluripotency in stem cells. Flow cytometry assay for identifying stem cells defines a side population of cells that displays low fluorescent dye and is highly enriched for stem cells. The dye efflux is attributed to expression of ATP‐binding cassette transporters such as P‐glycoprotein and breast cancer resistance protein (BCRP)/ABCG2, which also transport a variety of anticancer drugs. The PI3K/Akt pathway can modulate functions of ABC transporters through various mechanisms. Reportedly, inhibition of the PI3K/Akt pathway caused BCRP translocation in hematopoietic stem cells and glioma stem‐like cells. On the other hand, a PI3K inhibitor, LY294002, reversed multidrug resistance in cancer cells that overexpress BCRP not by affecting BCRP translocation but putatively as a competitive inhibitor. Other PI3K inhibitors, wortmannin and PI‐103, did not reverse BCRP‐mediated drug resistance. Since LY294002 is a derivative of quercetin that is a naturally occurring flavonoid, its chemical structure is similar to those of a group of flavonoids but those of wortmannin and PI‐103 are quite different. It is known that many flavonoids are inhibitors of BCRP and PI3K. LY294002 has also been reported to exert inhibitory effects on multidrug resistance‐associated protein 1 (MRP1) function via dual mechanisms, competitive block of substrate transport and modulation of expression. Furthermore, LY294002 has been found to antagonize transport activity of P‐glycoprotein without influencing its expression. Taken together, LY294002 can inhibit all BCRP, P‐glycoprotein, and MRP1, which are three major ABC transporters that are highly expressed in stem cells and cause multidrug resistance. Due to its versatile effects, LY294002 could be a lead compound for developing more effective and tolerable reagents for cancer treatment.
Optimization of the basal medium for improving production and secretion of taxanes from suspension cell culture of Taxus baccata L
Authors: Kajani Abolghasem Abbasi , Moghim Sharareh , Mofid Mohammad Reza
Published: October 2012

Background and purpose of the study

Taxol is one of the most effective anticancer drugs that isolated from Taxus sp. due to the slow growth of Taxus trees and low concentration of Taxol in the tissues, the biotechnological approaches especially plant cell culture have been considered to produce Taxol in commercial scale.

Methods

We investigated the effects of basal medium type used in culture media on production of Taxol and other taxane compounds from cell suspension culture of T. baccata L. Briefly, five commonly basal media including Gamborg, Murashige and Skoog, Woody Plant, Schenk and Hildebrandt, and Driver and Kuniyuki medium were used for preparing separate suspension culture media. The intra- and extra-cellular yields of taxanes were analyzed by using HPLC after 21 days period of culturing.

Results

The yields of taxanes were significantly different for the cultures prepared by different basal media. Moreover, the effects of basal medium on the yield of products differed for varius taxane compounds. Maximum yields of Baccatin III (10.03 mgl-1) and 10-deacetyl baccatin III (4.2 mgl-1) were achieved from the DKW basal media, but the yield of Taxol was maximum (16.58 mgl-1) in the WPM basal media. Furthermore, the secretion of taxanes from the cells into medium was also considerably affected by the type of basal medium. The maximum extra-cellular yield of Taxol (7.81 mgl-1), Baccatin III (5.0 mgl-1), and 10-deacetyl baccatin III (1.45 mgl-1) were also obtained by using DKW basal medium that were significantly higher than those obtained from other culture media.
Effect of chicory seed extract on glucose tolerance test (GTT) and metabolic profile in early and late stage diabetic rats
Authors: Ghamarian Abdolreza , Abdollahi Mohammad , Su Xiaogang , Amiri Azita , Ahadi Ali , Nowrouzi Azin
Published: October 2012

Background and purpose of the study

The goal was to evaluate and compare the effects of aqueous extract of the seeds of chicory, Cichorium intybus L., on glucose tolerance test (GTT) and blood biochemical indices of experimentally-induced hyperglycemic rats.

Methods

Late stage and early stage of Type 2 diabetes mellitus (T2DM) were induced in rats by streptozotocin (STZ) and a combination of STZ and niacinamide (NIA/STZ), respectively. Within each group, one subgroup received daily i. p. injections of chicory extract (125 mg/kg body weight, for 28 days). Body weight and fasting blood sugar (FBS) were measured weekly. Blood was analyzed for glycosylated hemoglobin (HbA1c) and sera for alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO), triacylglycerol (TG), total cholesterol (TC), total protein, and insulin on days 10 and 28 after treatment. Intraperitoneal glucose tolerance test (IPGTT) along with insulin determination was performed on a different set of rats in which the chicory-treated groups received the extract for 10 days.

Results

During 4 weeks of treatment, chicory prevented body-weight loss and decreased FBS. ALT activities and levels of TG, TC and HbA1c decreased, and concentration of NO increased in the chicory treated groups (p < 0.05). Unlike late-stage diabetes, fasting serum insulin concentrations were higher and GTT pattern approximated to normal in chicory-treated early-stage diabetic rats.

Conclusions

Chicory appeared to have short-term (about 2 hours, as far as GTT is concerned) and long-term (28 days, in this study) effects on diabetes. Chicory may be useful as a natural dietary supplement for slowing down the pace of diabetes progress, and delaying the development of its complications.
IP Multimedia subsystem authentication protocol in LTE-heterogeneous networks
Authors: Sharma Madhu J , Leung Victor CM
Published: October 2012

IP Multimedia Subsystem (IMS) introduces important advantages for users of LTE-femtocell heterogeneous access networks. In order to access services hosted in the IMS layer, the user has to undergo authentication procedure with the access network, followed by an authentication procedure with the IMS layer. This multi-pass authentication procedure is essential for securing IMS from malicious users, resulting in added overhead and possible quality of service degradations. The problem is further compounded when the user moves from one femtocell domain into another, which requires the authentication procedure to be repeated. To mitigate this problem, we present a lightweight, robust, and architecture-compatible IMS authentication protocol that implements a one-pass IMS procedure by promoting efficient key re-use for a mobile user. We make use of Home Node B femtocells to perform the role of IMS proxy. To verify the feasibility of using our protocol in mobile networks, an abstract model of our protocol is derived. The abstract model is emulated using Asterisk server and virtualization techniques. We also analyze the authentication delay of our proposed scheme. Numerical results reveal a reduction in user authentication delay of more than 50 percent compared to the existing authentication procedure.
Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation
Authors: Shekar Kiran , Roberts Jason A , Mcdonald Charles I , Fisquet Stephanie , Barnett Adrian G , Mullany Daniel V , Ghassabian Sussan , Wallis Steven C , Fung Yoke L , Smith Maree T , Fraser John F
Published: October 2012

Introduction

Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, with its success dependent on effective drug therapy that reverses the pathology and/or normalizes physiology. However, the circuit that sustains life can also sequester life-saving drugs, thereby compromising the role of ECMO as a temporary support device. This ex vivo study was designed to determine the degree of sequestration of commonly used antibiotics, sedatives and analgesics in ECMO circuits.

Methods

Four identical ECMO circuits were set up as per the standard protocol for adult patients on ECMO. The circuits were primed with crystalloid and albumin, followed by fresh human whole blood, and were maintained at a physiological pH and temperature for 24 hours. After baseline sampling, fentanyl, morphine, midazolam, meropenem and vancomycin were injected into the circuit at therapeutic concentrations. Equivalent doses of these drugs were also injected into four polyvinylchloride jars containing fresh human whole blood for drug stability testing. Serial blood samples were collected from the ECMO circuits and the controls over 24 hours and the concentrations of the study drugs were quantified using validated assays.

Results

Four hundred samples were analyzed. All study drugs, except meropenem, were chemically stable. The average drug recoveries from the ECMO circuits and the controls at 24 hours relative to baseline, respectively, were fentanyl 3% and 82%, morphine 103% and 97%, midazolam 13% and 100%, meropenem 20% and 42%, vancomycin 90% and 99%. There was a significant loss of fentanyl (p = 0.0005), midazolam (p = 0.01) and meropenem (p = 0.006) in the ECMO circuit at 24 hours. There was no significant circuit loss of vancomycin at 24 hours (p = 0.26).

Conclusions

Sequestration of drugs in the circuit has implications on both the choice and dosing of some drugs prescribed during ECMO. Sequestration of lipophilic drugs such as fentanyl and midazolam appears significant and may in part explain the increased dosing requirements of these drugs during ECMO. Meropenem sequestration is also problematic and these data support a more frequent administration during ECMO.
Myeloperoxidase: a front-line defender against phagocytosed microorganisms
Authors: Klebanoff Seymour J , Kettle Anthony J , Rosen Henry , Winterbourn Christine C , Nauseef William M
Published: October 2012

Review of myeloperoxidase supporting optimal microbicidal activity in the phagosomes of human neutrophils.

Successful immune defense requires integration of multiple effector systems to match the diverse virulence properties that members of the microbial world might express as they initiate and promote infection. Human neutrophils—the first cellular responders to invading microbes—exert most of their antimicrobial activity in phagosomes, specialized membrane-bound intracellular compartments formed by ingestion of microorganisms. The toxins generated de novo by the phagocyte NADPH oxidase and delivered by fusion of neutrophil granules with nascent phagosomes create conditions that kill and degrade ingested microbes. Antimicrobial activity reflects multiple and complex synergies among the phagosomal contents, and optimal action relies on oxidants generated in the presence of MPO. The absence of life-threatening infectious complications in individuals with MPO deficiency is frequently offered as evidence that the MPO oxidant system is ancillary rather than essential for neutrophil-mediated antimicrobial activity. However, that argument fails to consider observations from humans and KO mice that demonstrate that microbial killing by MPO-deficient cells is less efficient than that of normal neutrophils. We present evidence in support of MPO as a major arm of oxidative killing by neutrophils and propose that the essential contribution of MPO to normal innate host defense is manifest only when exposure to pathogens overwhelms the capacity of other host defense mechanisms.
The p400/Brd8 Chromatin Remodeling Complex Promotes Adipogenesis by Incorporating Histone Variant H2A.Z at PPARγ Target Genes
Authors: Couture Jean-Philippe , Nolet Guylaine , Beaulieu Elaine , Blouin Richard , Gévry Nicolas
Published: October 2012

Adipogenesis, the biological process by which preadipocytes differentiate into mature fat cells, is coordinated by a tightly regulated gene expression program. Indeed, it has been reported that a large number of genetic events, from fat cell-specific transcription factors expression, such as the master regulator of fat cell differentiation peroxisome proliferator-activated receptor (PPAR)γ2 to epigenetic modifications, govern the acquisition of a mature adipocyte phenotype. Here, we provide evidence that the E1A-binding protein p400 (p400) complex subunit bromo-containing protein 8 (Brd8) plays an important role in the regulation of PPARγ target genes during adipogenesis by targeting and incorporating the histone variant H2A.Z in transcriptional regulatory regions. The results reported here indicate that expression of both Brd8 and p400 increases during fat cell differentiation. In addition, small hairpin RNA-mediated knockdown of Brd8 or H2A.Z completely abrogated the ability of 3T3-L1 preadipocyte to differentiate into mature adipocyte, as evidenced by a lack of lipid accumulation. Chromatin immunoprecipitation experiments also revealed that the knockdown of Brd8 blocked the accumulation of PPARγ, p400, and RNA polymerase II and prevented the incorporation of H2A.Z at two PPARγ target genes. Taken together, these results indicate that the incorporation of the histone variant H2A.Z at the promoter regions of PPARγ target genes by p400/Brd8 is essential to allow fat cell differentiation.
Thyroid Peroxidase Gene Expression Is Induced by Lipopolysaccharide Involving Nuclear Factor (NF)-κB p65 Subunit Phosphorylation
Authors: Nazar Magalí , Nicola Juan Pablo , Vélez María Laura , Pellizas Claudia Gabriela , Masini-Repiso Ana María
Published: October 2012

Thyroid peroxidase (TPO), a tissue-specific enzyme expressed in differentiated thyroid follicular cells, is a major antigen that has been linked to autoimmune thyroid disease. We have previously reported the functional expression of the lipopolysaccharide (LPS) receptor Toll-like receptor 4 on thyroid follicular cells. Here we investigated the effect of LPS in TPO expression and analyzed the mechanisms involved. We found a dose-dependent enhancement of TSH-induced TPO expression in response to LPS stimulation. EMSAs demonstrated that LPS treatment increased thyroid transcription factor-1 and -2 binding to the B and Z regions of TPO promoter, respectively. Moreover, LPS increased TSH-stimulated TPO promoter activity. Using bioinformatic analysis, we identified a conserved binding site for transcription nuclear factor-κB (NF-κB) in the TPO promoter. Chemical inhibition of NF-κB signaling and site-directed mutagenesis of the identified κB-cis-acting element abolished LPS stimulation. Furthermore, chromatin immunoprecipitation assays confirmed that TPO constitutes a novel NF-κB p65 subunit target gene in response to LPS. Additionally, our results indicate that p65 phosphorylation of serine 536 constitutes an essential step in the p65-dependent, LPS-induced transcriptional expression of TPO. In conclusion, here we demonstrated that LPS increases TPO expression, suggesting a novel mechanism involved in the regulation of a major thyroid autoantigen. Our results provide new insights into the potential effects of infectious processes on thyroid homeostasis.