bluuebunny/crossref_metadata_2025 huggingface dataset:
Demonstration of diet-induced decoupling of fatty acid and cholesterol synthesis by combining gene expression array and2H2O quantification
Authors: Jensen Kristian K. , Previs Stephen F. , Zhu Lei , Herath Kithsiri , Wang Sheng-Ping , Bhat Gowri , Hu Guanghui , Miller Paul L. , McLaren David G. , Shin Myung K. , Vogt Thomas F. , Wang Liangsu , Wong Kenny K. , Roddy Thomas P. , Johns Douglas G. , Hubbard Brian K.
Published: November 2011

The liver is a crossroad for metabolism of lipid and carbohydrates, with acetyl-CoA serving as an important metabolic intermediate and a precursor for fatty acid and cholesterol biosynthesis pathways. A better understanding of the regulation of these pathways requires an experimental approach that provides both quantitative metabolic flux measurements and mechanistic insight. Under conditions of high carbohydrate availability, excess carbon is converted into free fatty acids and triglyceride for storage, but it is not clear how excessive carbohydrate availability affects cholesterol biosynthesis. To address this, C57BL/6J mice were fed either a low-fat, high-carbohydrate diet or a high-fat, carbohydrate-free diet. At the end of the dietary intervention, the two groups received2H2O to trace de novo fatty acid and cholesterol synthesis, and livers were collected for gene expression analysis. Expression of lipid and glucose metabolism genes was determined using a custom-designed pathway focused PCR-based gene expression array. The expression analysis showed downregulation of cholesterol biosynthesis genes and upregulation of fatty acid synthesis genes in mice receiving the high-carbohydrate diet compared with the carbohydrate-free diet. In support of these findings,2H2O tracer data showed that fatty acid synthesis was increased 10-fold and cholesterol synthesis was reduced by 1.6-fold in mice fed the respective diets. In conclusion, by applying gene expression analysis and tracer methodology, we show that fatty acid and cholesterol synthesis are differentially regulated when the carbohydrate intake in mice is altered.
Endometrial gene expression during early pregnancy differs between fertile and subfertile dairy cow strains
Authors: Walker Caroline G. , Littlejohn Mathew D. , Mitchell Murray D. , Roche John R. , Meier Susanne
Published: November 2011

A receptive uterine environment is a key component in determining a successful reproductive outcome. We tested the hypothesis that endometrial gene expression patterns differ in fertile and subfertile dairy cow strains. Twelve lactating dairy cattle of strains characterized as having fertile ( n = 6) and subfertile ( n = 6) phenotypes underwent embryo transfer on day 7 of the reproductive cycle. Caruncular and intercaruncular endometrial tissue was obtained at day 17 of pregnancy, and microarrays used to characterize transcriptional profiles. Statistical analysis of microarray data at day 17 of pregnancy revealed 482 and 1,021 differentially expressed transcripts ( P value < 0.05) between fertile and subfertile dairy cow strains in intercaruncular and caruncular tissue, respectively. Functional analysis revealed enrichment for several pathways involved in key reproductive processes, including the immune response to pregnancy, luteolysis, and support of embryo growth and development, and in particular, regulation of histotroph composition. Genes implicated in the process of immune tolerance to the embryo were downregulated in subfertile cows, as were genes involved in preventing luteolysis and genes that promote embryo growth and development. This study provides strong evidence that the endometrial gene expression profile may contribute to the inferior reproductive performance of the subfertile dairy cow strain.
Gastric Antral Vascular Ectasia in Systemic Sclerosis
Authors: Johnson Jill , Derk Chris T.
Published: November 2011

Gastric antral vascular ectasia is a not so well-understood, and more rare, gastrointestinal manifestation of Systemic Sclerosis which can lead to chronic anemia. A high suspicion and better understanding of this rare manifestation is needed for early detection and treatment. Therapeutic regiments include iron supplementation with acid suppressive therapy, while endoscopic intervention has been shown to be successful in most cases, with gastrectomy or antrectomy rarely needed.
Brain Magnetic Resonance Imaging Findings in Developmentally Delayed Children
Authors: Momen Ali Akbar , Jelodar Gholamreza , Dehdashti Hamid
Published: November 2011

Background. Developmental disorders are failure or inability to acquire various age-specific skills at expected maturational age, which affects about 5–10% of preschool children. One of the most important methods for evaluation of developmentally delayed children is neuroimaging, especially, brain magnetic resonance imaging (MRI) that provides useful information regarding brain tissue structures and anomalies.Method and Material. In this study, hospital records of 580 developmentally delayed children (aged 2 months to 15 years) who admitted in pediatric ward of Golestan Hospital from 1997 to 2009 were selected. Information such as age, MRI findings were collected in the questionnaire and statistically analyzed.Results. Total, 580 children including 333 males (57.4%) and 247 females (42.6%) were studied. Abnormal brain MRI was observed in 340 (58.6%) cases (204 Males, 136 females). The finding includes nonspecific in 38 (6.6%), congenital and developmental anomalies of brain in 39 (6.7%), recognizable syndromes in 3 (0.5%), neurovascular diseases or trauma in 218 (37.6%), and metabolic or neurodegenerative diseases in 42 (7.2%) cases.Conclusion. Because 60% of all study groups showed abnormal brain MRI, using this method could be effective in diagnosis, management, and almost prognosis determination processes.
Application of Polyethylene Glycol to Promote Cellular Biocompatibility of Polyhydroxybutyrate Films
Authors: Chan Rodman T. H. , Marçal Helder , Russell Robert A. , Holden Peter J. , Foster L. John R.
Published: November 2011

Polyhydroxybutyrate (PHB) is a biomaterial with potential for applications in biomedical and tissue engineering; however, its brittle nature and high crystallinity limit its potential. Blending PHB with a variety of PEGs produced natural-synthetic composite films composed of FDA-approved polymers with significant reductions in crystallinity, from 70.1% for PHB films to 41.5% for its composite with a 30% (w/w) loading of PEG2000. Blending also enabled manipulation of the material properties, increasing film flexibility with an extension to break of2.49±1.01%for PHB films and8.32±1.06%for films containing 30% (w/w) PEG106. Significant changes in the film surface properties, as measured by porosity, contact angles, and water uptake, were also determined as a consequence of the blending process, and these supported greater adhesion and proliferation of neural-associated olfactory ensheathing cells (OECs). A growth rate of7.2×105cells per day for PHB films with 30% (w/w) PEG2000 loading compared to2.5×105for PHB films was observed. Furthermore, while cytotoxicity of the films as measured by lactate dehydrogenase release was unaffected, biocompatibility, as measured by mitochondrial activity, was found to increase. It is anticipated that fine control of PEG composition in PHB-based composite biomaterials can be utilised to support their applications in medicinal and tissue engineering applications.
Spatiality of Derivations of Operator Algebras in Banach Spaces
Authors: Chen Quanyuan , Fang Xiaochun
Published: November 2011

Suppose that 𝒜 is a transitive subalgebra of B(X) and its norm closure contains a nonzero minimal left ideal ℐ. It is shown that if δ is a bounded reflexive transitive derivation from 𝒜 into B(X), then δ is spatial and implemented uniquely; that is, there exists T ∈ B(X) such that δ(A) = TA − AT for each A ∈ 𝒜, and the implementation T of δ is unique only up to an additive constant. This extends a result of E. Kissin that “if contains the ideal C(H) of all compact operators in B(H), then a bounded reflexive transitive derivation from 𝒜 into B(H) is spatial and implemented uniquely.” in an algebraic direction and provides an alternative proof of it. It is also
shown that a bounded reflexive transitive derivation from 𝒜 into B(X) is spatial and implemented uniquely, if X is a reflexive Banach space and contains a nonzero minimal right ideal ℐ.
Smouldering Malignant Melanoma and Metastatic Dormancy: An Update and Review
Authors: Piérard Gérald E. , Piérard-Franchimont Claudine , Reginster Marie-Annick , Quatresooz Pascale
Published: November 2011

The fund of knowledge regarding the versatility of presentation of MM metastases is still quite incomplete. The recent literature pertaining to the current understanding of the mechanisms underlying two special features of MM metastasis is reviewed. On the one hand, a long disease-free interval (MM dormancy) may occur before the surge of overt metastases. On the other hand, the so-called MM smouldering phenomenon refers to the condition where regional metastases wax and wane for long periods of time on restricted skin regions. It is important to emphasize that local micrometastases often predict sentinel lymph node involvement but may not reflect progression of the primary MM to full-blown visceral metastatic competence. It is likely that a combination of factors impacts the versatile MM metastasic progression. Among the main factors, one has to mention the phenotypic heterogeneity and variability in the phenotype of MM cells, the presence of MM stem cells and MM cells engaged in an amplification proliferation pool, as well as the host immune response, and possibly the induction of a particular stromal structure and vascularity.
Genetic Variants Associated with the Risk of Chronic Obstructive Pulmonary Disease with and without Lung Cancer
Authors: de Andrade Mariza , Li Yan , Marks Randolph S. , Deschamps Claude , Scanlon Paul D. , Olswold Curtis L. , Jiang Ruoxiang , Swensen Stephen J. , Sun Zhifu , Cunningham Julie M. , Wampfler Jason A. , Limper Andrew H. , Midthun David E. , Yang Ping
Published: November 2011

Chronic obstructive pulmonary disease (COPD) is a strong risk factor for lung cancer. Published studies about variations of genes encoding glutathione metabolism, DNA repair, and inflammatory response pathways in susceptibility to COPD were inconclusive. We evaluated 470 single-nucleotide polymorphisms (SNP) from 56 genes of these three pathways in 620 cases and 893 controls to identify susceptibility markers for COPD risk, using existing resources. We assessed SNP- and gene-level effects adjusting for sex, age, and smoking status. Differential genetic effects on disease risk with and without lung cancer were also assessed; cumulative risk models were established. Twenty-one SNPs were found to be significantly associated with risk of COPD (P < 0.01); gene-based analyses confirmed two genes (GCLC and GSS) and identified three additional genes (GSTO2, ERCC1, and RRM1). Carrying 12 high-risk alleles may increase risk by 2.7-fold; eight SNPs altered COPD risk without lung cancer by 3.1-fold and 4 SNPs altered the risk with lung cancer by 2.3-fold. Our findings indicate that multiple genetic variations in the three selected pathways contribute to COPD risk through GCLC, GSS, GSTO2, ERCC1, and RRM1 genes. Functional studies are needed to elucidate the mechanisms of these genes in the development of COPD, lung cancer, or both. Cancer Prev Res; 5(3); 365–73. ©2011 AACR.
Comprehensive risk reduction in patients with atrial fibrillation: Emerging diagnostic and therapeutic options
Authors: Lip Gregory , Van Gelder Isabelle , Bax Jeroen , Hylek Elaine , Kääb Stefan , Schotten Ulrich , Wegscheider Karl , Boriani Giuseppe , Ezekowitz Michael , Diener Hans , Heidbuchel Hein , Lane Deirdre , Mont Luis , Willems Stephan , Dorian Paul , Vardas Panos , Breithardt Günter , John Camm A. , Kirchhof Paulus
Published: November 2011

There are exciting new developments in several areas of atrial fibrillation (AF) management that carry the hope of improving outcomes in AF patients. This paper is an executive summary that summarises the proceedings from the 3rd AFNET/EHRA consensus conference on atrial fibrillation, held in Sophia Antipolis from November 7th to 9th 2010, shortly after the release of the new ESC guidelines on AF. The conference was jointly organised by the German Atrial Fibrillation competence NETwork (AFNET) and the European Heart Rhythm Association (EHRA). This executive summary report covers four sections: 1. Risk factors and risk markers for AF, 2. Pathophysiological classification of AF, 3. Relevance of monitored AF duration for AF-related outcomes, and 4. Perspectives and needs for implementing better antithrombotic therapy.
Adaptation of small capacity natural gas engine for producer gas operation
Authors: Dasappa S , Sridhar G , Paul P J
Published: November 2011

This article addresses the adaptation of a low-power natural gas engine for using producer gas as a fuel. The 5.9 L natural gas engine with a compression ratio of 10.5:1, rated at 55 kW shaft power, delivered 30 kW using producer gas as fuel in the naturally aspirated mode. Optimal ignition timing for peak power was found to be 20° before top dead centre. Air-to-fuel ratio (A/F) was found to be 1.2 ± 0.1 over a range of loads. Critical evaluation of the energy flows in the engine resulted in identifying losses and optimizing the engine cooling. The specific fuel consumption was found to be 1.2 ± 0.1 kg of biomass per kilowatt hour. A reduction of 40 per cent in brake mean effective pressure was observed compared with natural gas operation. Governor response to load variations has been studied with respect to frequency recovery time. The study also attempts to adopt a turbocharger for higher power output. Preliminary results suggest a possibility of about 30 per cent increase in the output.
Fair-Weather or Foul-Weather Friends? Group Identification and Children’s Responses to Bullying
Authors: Jones Siân E. , Manstead Antony S. R. , Livingstone Andrew G.
Published: November 2011

Research with adults shows that negative ingroup behavior can affect identification with the group, but also that the way in which members respond to negative events is moderated by prior levels of identification. Research with children shows that how strongly they identify with a group influences how they react to group-level bullying. The authors integrate these findings by examining how a bullying incident affects children’s group identification. Children aged 7–8 and 10–11 years were randomly assigned to either a perpetrator group or a target group. They read a scenario describing a target group member being bullied by members of the perpetrator group. The perpetrator group had a norm of behaving either kindly or unkindly to other children. How strongly children in the perpetrator group identified with their group was influenced by group norm and by initial in-group identification. Identification was higher when the group was normatively kind rather than unkind, but only among children whose initial identification was high.
Ribosomal protein gene deletions in Diamond-Blackfan anemia
Authors: Farrar Jason E. , Vlachos Adrianna , Atsidaftos Eva , Carlson-Donohoe Hannah , Markello Thomas C. , Arceci Robert J. , Ellis Steven R. , Lipton Jeffrey M. , Bodine David M.
Published: November 2011

Diamond-Blackfan anemia (DBA) is a congenital BM failure syndrome characterized by hypoproliferative anemia, associated physical abnormalities, and a predisposition to cancer. Perturbations of the ribosome appear to be critically important in DBA; alterations in 9 different ribosomal protein genes have been identified in multiple unrelated families, along with rarer abnormalities of additional ribosomal proteins. However, at present, only 50% to 60% of patients have an identifiable genetic lesion by ribosomal protein gene sequencing. Using genome-wide single-nucleotide polymorphism array to evaluate for regions of recurrent copy variation, we identified deletions at known DBA-related ribosomal protein gene loci in 17% (9 of 51) of patients without an identifiable mutation, including RPS19, RPS17, RPS26, and RPL35A. No recurrent regions of copy variation at novel loci were identified. Because RPS17 is a duplicated gene with 4 copies in a diploid genome, we demonstrate haploinsufficient RPS17 expression and a small subunit ribosomal RNA processing abnormality in patients harboring RPS17 deletions. Finally, we report the novel identification of variable mosaic loss involving known DBA gene regions in 3 patients from 2 kindreds. These data suggest that ribosomal protein gene deletion is more common than previously suspected and should be considered a component of the initial genetic evaluation in cases of suspected DBA.
Control of Plasmodium falciparum erythrocytic cycle: γδ T cells target the red blood cell–invasive merozoites
Authors: Costa Giulia , Loizon Séverine , Guenot Marianne , Mocan Iulia , Halary Franck , de Saint-Basile Geneviève , Pitard Vincent , Déchanet-Merville Julie , Moreau Jean-François , Troye-Blomberg Marita , Mercereau-Puijalon Odile , Behr Charlotte
Published: November 2011

The control of Plasmodium falciparum erythrocytic parasite density is essential for protection against malaria, because it prevents pathogenesis and progression toward severe disease. P falciparum blood-stage parasite cultures are inhibited by human Vγ9Vδ2 γδ T cells, but the underlying mechanism remains poorly understood. Here, we show that both intraerythrocytic parasites and the extracellular red blood cell–invasive merozoites specifically activate Vγ9Vδ2 T cells in a γδ T cell receptor–dependent manner and trigger their degranulation. In contrast, the γδ T cell–mediated antiparasitic activity only targets the extracellular merozoites. Using perforin-deficient and granulysin-silenced T-cell lines, we demonstrate that granulysin is essential for the in vitro antiplasmodial process, whereas perforin is dispensable. Patients infected with P falciparum exhibited elevated granulysin plasma levels associated with high levels of granulysin-expressing Vδ2+ T cells endowed with parasite-specific degranulation capacity. This indicates in vivo activation of Vγ9Vδ2 T cells along with granulysin triggering and discharge during primary acute falciparum malaria. Altogether, this work identifies Vγ9Vδ2 T cells as unconventional immune effectors targeting the red blood cell–invasive extracellular P falciparum merozoites and opens novel perspectives for immune interventions harnessing the antiparasitic activity of Vγ9Vδ2 T cells to control parasite density in malaria patients.
The grapevine guard cell-related VvMYB60 transcription factor is involved in the regulation of stomatal activity and is differentially expressed in response to ABA and osmotic stress
Authors: Galbiati Massimo , Matus José Tomás , Francia Priscilla , Rusconi Fabio , Cañón Paola , Medina Consuelo , Conti Lucio , Cominelli Eleonora , Tonelli Chiara , Arce-Johnson Patricio
Published: November 2011

Background

Under drought, plants accumulate the signaling hormone abscisic acid (ABA), which induces the rapid closure of stomatal pores to prevent water loss. This event is trigged by a series of signals produced inside guard cells which finally reduce their turgor. Many of these events are tightly regulated at the transcriptional level, including the control exerted by MYB proteins. In a previous study, while identifying the grapevine R2R3 MYB family, two closely related genes,VvMYB30andVvMYB60were found with high similarity toAtMYB60, an Arabidopsis guard cell-related drought responsive gene.

Results

Promoter-GUS transcriptional fusion assays showed that expression ofVvMYB60was restricted to stomatal guard cells and was attenuated in response to ABA. UnlikeVvMYB30,VvMYB60was able to complement the loss-of-functionatmyb60-1mutant, indicating thatVvMYB60is the only true ortholog ofAtMYB60in the grape genome. In addition,VvMYB60was differentially regulated during development of grape organs and in response to ABA and drought-related stress conditions.

Conclusions

These results show that VvMYB60 modulates physiological responses in guard cells, leading to the possibility of engineering stomatal conductance in grapevine, reducing water loss and helping this species to tolerate drought under extreme climatic conditions.
General practitioners' views and experiences of counselling for physical activity through the New Zealand Green Prescription program
Authors: Patel Asmita , Schofield Grant M , Kolt Gregory S , Keogh Justin WL
Published: November 2011

Background

Regular physical activity is beneficial in both the prevention and management of chronic health conditions. A large proportion of adult New Zealanders, however, are insufficiently active. To help increase population levels of physical activity in New Zealand the Green Prescription, a primary care physical activity scripting program, was developed. The primary aim of this study was to identify why general practitioners (GPs) counsel for physical activity and administer Green Prescriptions. A secondary aim was to examine GPs' views and experiences of Green Prescription counselling for the management of depression.

Methods

Individual face-to-face interviews were conducted with 15 GPs. All interviews were audio-taped and transcribed. Data were analysed using an inductive thematic approach.

Results

Several themes and sub-themes emerged from the data. Notably, GPs counselled for physical activity and prescribed Green Prescriptions for both primary preventive (e.g., weight control) and secondary management (e.g., diabetes management) purposes. GPs reported the benefits of the Green Prescription centred around two main themes: (i) a non-medication approach to a healthier lifestyle and (ii) the support benefits of physical activity. Time constraints within the consultation was the only main theme that emerged regarding the barriers GPs perceived to Green Prescription use. Physical activity in general, and physical activity prescribed through the Green Prescription, were also viewed by GPs as beneficial for the management of depression.

Conclusions

The results of this study suggest that New Zealand GPs view the Green Prescription program as beneficial for their patients with pre-existing conditions and/or weight problems. While this is encouraging, the Green Prescription may also be used to promote physical activity in currently healthy but low-active and sedentary individuals. Such individuals are currently disease free, but are at risk for future health-related problems because of their inactive lifestyle. It is recommended that time constraints of the consultation in regard to administering Green Prescriptions could be dealt with by delegating the more time consuming tasks to the patient support counsellors that support the Green Prescription program, and having practice nurses assist in the administration of Green Prescriptions. Green Prescription counselling in conjunction with antidepressant medication may be beneficial for the management of depression and warrants further research.
Factors associated with paradoxical immune response to antiretroviral therapy in HIV infected patients: a case control study
Authors: Casotti Janaina AS , Passos Luciana N , Oliveira Fabiano JP , Cerutti Crispim
Published: November 2011

Background

A paradoxical immunologic response (PIR) to Highly Active Antiretroviral Therapy (HAART), defined as viral suppression without CD4 cell-count improvement, has been reported in the literature as 8 to 42%, around 15% in most instances. The present study aims to determine, in a cohort of HIV infected patients in Brazil, what factors were independently associated with such a discordant response to HAART.

Methods

A case-control study (1:4) matched by gender was conducted among 934 HIV infected patients on HAART in Brazil. Cases: patients with PIR, defined as CD4 < 350 cells/mm3(hazard ratio for AIDS or death of at least 8.5) and undetectable HIV viral load on HAART for at least one year. Controls: similar to cases, but with CD4 counts ≥ 350 cells/mm3. Eligibility criteria were applied. Data were collected from medical records using a standardized form. Variables were introduced in a hierarchical logistic regression model if a p-value < 0.1 was determined in a bivariate analysis.

Results

Among 934 patients, 39 cases and 160 controls were consecutively selected. Factors associated with PIR in the logistic regression model were: total time in use of HAART (OR 0.981; CI 95%: 0.96-0.99), nadir CD4-count (OR 0.985; CI 95%: 0.97-0.99), and time of undetectable HIV viral load (OR 0.969; CI 95%: 0.94-0.99).

Conclusions

PIR seems to be related to a delay in the management of immunodeficient patients, as shown by its negative association with nadir CD4-count. Strategies should be implemented to avoid such a delay and improve the adherence to HAART as a way to implement concordant responses.
High Resolution Melt analysis for mutation screening in PKD1 and PKD2
Authors: Bataille Stanislas , Berland Yvon , Fontes Michel , Burtey Stéphane
Published: November 2011

Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder. It is characterized by focal development and progressive enlargement of renal cysts leading to end-stage renal disease. PKD1 and PKD2 have been implicated in ADPKD pathogenesis but genetic features and the size of PKD1 make genetic diagnosis tedious.

Methods

We aim to prove that high resolution melt analysis (HRM), a recent technique in molecular biology, can facilitate molecular diagnosis of ADPKD. We screened for mutations in PKD1 and PKD2 with HRM in 37 unrelated patients with ADPKD.

Results

We identified 440 sequence variants in the 37 patients. One hundred and thirty eight were different. We found 28 pathogenic mutations (25 in PKD1 and 3 in PKD2 ) within 28 different patients, which is a diagnosis rate of 75% consistent with literature mean direct sequencing diagnosis rate. We describe 52 new sequence variants in PKD1 and two in PKD2.

Conclusion

HRM analysis is a sensitive and specific method for molecular diagnosis of ADPKD. HRM analysis is also costless and time sparing. Thus, this method is efficient and might be used for mutation pre-screening in ADPKD genes.
Does quality of care for hypertension in primary care vary with postcode area deprivation? An observational study
Authors: Hammouche Salah , Holland Richard , Steel Nicholas
Published: November 2011

Background

Hypertension is a common major risk factor for stroke and coronary heart disease. Little is known about how achievement of financially incentivised and non-incentivised indicators of quality of care varies with deprivation, or about the effect of financial incentives on health inequalities in hypertension. General practices in the UK have received financial incentives for high quality care since 2004. This study set out to assess the variations in achievement of incentivised and non-incentivised quality indicators for hypertension by patient area deprivation, before and after the introduction of financial incentives.

Methods

Achievement of 14 quality indicators for hypertension in 304 patient participants in 18 general practices in Norfolk, England was assessed one year before (2003) and one year after (2005) the introduction of financial incentives. Four indicators were incentivised and 10 were non-incentivised. Each participant's postcode was linked to an index of multiple deprivation score.

Results

The range of achievement of incentivised quality indicators was 65-94% in the least deprived third of participants, and 77-94% in the most deprived third in 2003 and 2005 combined. For non-incentivised indicators, the range was 7-85% in the least deprived and 24-93% in the most deprived third.

Achievement of incentivised quality indicators in 2003 and 2005 combined did not vary significantly by area deprivation. Achievement of three of 10 non-incentivised indicators was higher in participants from more deprived postcode areas: providing lifestyle advice (odds ratio 1.34, 95% confidence interval 1.00-1.79), assessment of peripheral vascular disease (1.54, 1.02-2.35) and electrocardiography (1.38, 1.04-1.82).

Conclusions

Participants from more deprived areas received at least the same, and sometimes better, quality of care than those from less deprived areas. Quality of care for hypertension in general practice may not follow the inequitable distribution seen with some other conditions.
Loop-mediated isothermal amplification for detection of porcine circovirus type 2
Authors: Zhou Shun , Han Si , Shi Jianli , Wu Jiaqiang , Yuan Xiaoyuan , Cong Xiaoyan , Xu Shaojian , Wu Xiaoyan , Li Jun , Wang Jinbao
Published: November 2011

Background

Porcine circovirus type 2 (PCV2) is the primary causative agent of the emerging swine disease known as postweaning multisystemic wasting syndrome (PMWS). Nowadays, polymerase chain reaction (PCR) is still the most widespread technique in pathogen detection. Loop-mediated isothermal amplification (LAMP), a novel nucleic acid amplification method developed in 2000, will possibly replace PCR in the field of detection. To establish a LAMP method for rapid detection of PCV2, two pairs of primers were designed specially from the open reading frame 2 (ORF2) sequences of PCV2. A LAMP method for rapid detection of PCV2 was established. To compare with PCR, sensitivity and specificity of LAMP were evaluated using the optimized reaction system. The LAMP products could be determined by agarose gel electrophoresis or adding SYBR Green I dye.

Results

The amplification of LAMP could be obtained at 63°C for 60 min. The detection limit was nearly 1 copy of DNA plasmid, more sensitive than PCR. There was no cross-reaction with porcine circovirus type 1 (PCV1), porcine pseudorabies virus (PRV) and porcine parvovirus (PPV) under the same conditions.

Conclusions

LAMP is an useful rapid detection method with high sensitivity and specificity for PCV2.
Aberrant DNA methylation of cancer-related genes in giant breast fibroadenoma: a case report
Authors: Marzese Diego M , Gago Francisco E , Orozco Javier I , Tello Olga M , Roqué María , Vargas-Roig Laura M
Published: November 2011

Introduction

Giant fibroadenoma is an uncommon variant of benign breast lesions. Aberrant methylation of CpG islands in promoter regions is known to be involved in the silencing of genes (for example, tumor-suppressor genes) and appears to be an early event in the etiology of breast carcinogenesis. Only hypermethylation of p16INK4a has been reported in non-giant breast fibroadenoma. In this particular case, there are no previously published data on epigenetic alterations in giant fibroadenomas. Our previous results, based on the analysis of 49 cancer-related CpG islands have confirmed that the aberrant methylation is specific to malignant breast tumors and that it is completely absent in normal breast tissue and breast fibroadenomas.

Case presentation

A 13-year-old Hispanic girl was referred after she had noted a progressive development of a mass in her left breast. On physical examination, a 10 × 10 cm lump was detected and axillary lymph nodes were not enlarged. After surgical removal the lump was diagnosed as a giant fibroadenoma. Because of the high growth rate of this benign tumor, we decided to analyze the methylation status of 49 CpG islands related to cell growth control. We have identified the methylation of five cancer-related CpG islands in the giant fibroadenoma tissue: ESR1, MGMT, WT-1, BRCA2 and CD44.

Conclusion

In this case report we show for the first time the methylation analysis of a giant fibroadenoma. The detection of methylation of these five cancer-related regions indicates substantial epigenomic differences with non-giant fibroadenomas. Epigenetic alterations could explain the higher growth rate of this tumor. Our data contribute to the growing knowledge of aberrant methylation in breast diseases. In this particular case, there exist no previous data regarding the role of methylation in giant fibroadenomas, considered by definition as a benign breast lesion.
A patient with amyotrophic lateral sclerosis and atypical clinical and electrodiagnostic features: a case report
Authors: Venizelos Alexander , Park Youngsook , Fisher Morris A
Published: November 2011

Introduction

Amyotrophic lateral sclerosis is a rapidly progressive, fatal neurodegenerative disorder for which there is no effective treatment. The diagnosis is dependent on the clinical presentation and consistent electrodiagnostic studies. Typically, there is a combination of upper and lower motor neuron signs as well as electrodiagnostic studies indicative of diffuse motor axonal injury. The presentation of amyotrophic lateral sclerosis, however, may be variable. At the same time, the diagnosis is essential for patient prognosis and management. It is therefore important to appreciate the range of possible presentations of amyotrophic lateral sclerosis.

Case presentation

We present the case of a 57-year-old Caucasian man with pathological findings on postmortem examination consistent with amyotrophic lateral sclerosis but atypical clinical and electrodiagnostic features. He died after a rapid course of progressive weakness. The patient did not respond to immunosuppressive therapy.

Conclusion

Amyotrophic lateral sclerosis should be considered in patients with a rapidly progressive, unexplained neuropathic process. This should be true even if there are atypical clinical and electrodiagnostic findings. Absence of response to therapy and the development of upper motor neuron signs should reinforce the possibility that amyotrophic lateral sclerosis may be present. Since amyotrophic lateral sclerosis is a fatal illness, however, the possibility of this disease in patients with atypical clinical features should not diminish the need for a thorough diagnostic evaluation and treatment trials.
The protective effects of plasma gelsolin on stroke outcome in rats
Authors: Le Huong T , Hirko Aaron C , Thinschmidt Jeffrey S , Grant Maria , Li Zhimin , Peris Joanna , King Michael A , Hughes Jeffrey A , Song Sihong
Published: November 2011

Background

To date, recombinant tissue plasminogen activator (rtPA) is the only approved drug for ischemic stroke. It is intravenously administered functioning as a thrombolytic agent and is used to obtain reperfusion of the affected area of the brain. Excitotoxicity, inflammation and apoptosis are all involved in delayed neuronal death following stroke and offer multiple opportunities to intervene with neuroprotective agents. Gelsolin (GSN) is an actin- and calcium-binding protein mediating the disassembly of actin filaments and activity of calcium channels. It also functions as a regulator of apoptosis and inflammatory responses. This study tests the hypothesis that increasing the concentration of the form of GSN known as plasma GSN (pGSN) near an infarct will provide neuroprotection following ischemic stroke.

Methods

We induced middle cerebral artery occlusion (MCAO) in male rats via intracranial injection of endothelin-1 (ET-1), a potent vasoconstrictor, and then treated with local delivery of pGSN. Whole brain laser Doppler perfusion imaging was performed through the skull to assess MCAO effectiveness. Cylinder and vibrissae tests evaluated sensorimotor function before and 72 h after MCAO. Infarct volumes were examined 72 h after MCAO via 2, 3, 5-triphenyltetrazolium chloride (TTC) assay.

Results

Estimates of relative cerebral perfusion were significantly decreased in all groups receiving MCAO with no differences detected between treatments. Despite equivalent initial strokes, the infarct volume of the pGSN treatment group was significantly reduced compared with the untreated MCAO rats at 72 h. ET-1 induced significant deficits in both cylinder and vibrissae tests while pGSN significantly limited these deficits.

Conclusion

Gelsolin could be a promising drug for protection against neurodegeneration following ischemic stroke.
Transcriptional activation of theIL31gene by NFAT and STAT6
Authors: Park Keunhee , Park Joo-Hong , Yang Wook-Jin , Lee Jong-Joo , Song Min-Ji , Kim Hyoung-Pyo
Published: November 2011

IL-31, a newly identified member of the IL-6 cytokine family, is involved in many pathological conditions, including atopic dermatitis and pruritis. In this study, we investigated how expression of IL-31 is regulated in T cells and mast cells. We observed that expression of IL-31 required a calcium signal and was dependent on the calcineurin-NFAT signaling pathway. Moreover, we found that IL-31 promoter contains a positive regulatory region that mediates calcium- and IL-4-dependent induction of the IL-31 gene and demonstrated that a change into an open chromatin conformation occurs in this region after stimulation with calcium and IL-4. Whereas IL-4 responsiveness required STAT6 binding sites, calcium responsiveness of IL-31 promoter required NFAT binding sites that bind NFATc1 and NFATc2 in vitro and in vivo. The induction of IL-31 promoter activity was impaired when these sites were mutated but was enhanced by CA-NFATc1 or STAT6 proteins and further increased synergistically by combinations of both proteins. Furthermore, the importance of STAT6 proteins was indicated by impaired, IL-4-mediated induction of IL-31 in STAT6-diminished Jurkat cells. Thus, our data demonstrate that calcium and IL-4 signals are required to mediate induction of IL-31 in Th2 cells and mast cells and that this induction appears to result from specific binding of NFAT and STAT6 proteins.
Natural killer cell-produced IFN-γ and TNF-α induce target cell cytolysis through up-regulation of ICAM-1
Authors: Wang Ruipeng , Jaw Jessica J , Stutzman Nicole C , Zou Zhongcheng , Sun Peter D
Published: November 2011

NK cells control tumor and virus-infected cells through releasing cytotoxic granules and proinflammatory cytokines. IFN-γ and TNF-α secretions and cytotoxicity are regarded as two distinct functions of NK cells with little synergy in between as results of early association of the two functions with distinct subsets of NK populations and of the studies showing target cells developing NK resistance upon IFN-γ treatment. Here, we show that IFN-γ and TNF-α synergistically enhance NK cell cytotoxicity through NF-κB-dependent up-regulation of ICAM-1 expression in target cells, thereby promoting their conjugate formation with NK cells. Neutralizing IFN-γ and TNF-α during cytolysis significantly impaired NK cell lysis of the target cells. Further, tumor cells exhibiting IFN-γ-inducible lysis are generally less-sensitive NK target cells but express inducible levels of ICAM-1. In contrast, sensitive NK targets tend to express higher but less-inducible ICAM-1. Their preferential induction in the lysis of insensitive NK target cells suggests that IFN-γ and TNF-α are functionally linked to and should be regarded as an integral part of NK cytolytic function.
An Irradiation-Altered Bone Marrow Microenvironment Impacts Anabolic Actions of PTH
Authors: Koh A. J. , Novince C. M. , Li X. , Wang T. , Taichman R. S. , McCauley Laurie K.
Published: November 2011

PTH stimulates bone formation and increases hematopoietic stem cells through mechanisms as yet uncertain. The purpose of this study was to identify mechanisms by which PTH links actions on cells of hematopoietic origin with osteoblast-mediated bone formation. C57B6 mice (10 d) were nonlethally irradiated and then administered PTH for 5–20 d. Irradiation reduced bone marrow cellularity with retention of cells lining trabeculae. PTH anabolic activity was greater in irradiated vs. nonirradiated mice, which could not be accounted for by altered osteoblasts directly or osteoclasts but instead via an altered bone marrow microenvironment. Irradiation increased fibroblast growth factor 2, TGFβ, and IL-6 mRNA levels in the bone marrow in vivo. Irradiation decreased B220 cell numbers, whereas the percent of Lin−Sca-1+c-kit+ (LSK), CD11b+, CD68+, CD41+, Lin−CD29+Sca-1+ cells, and proliferating CD45−Nestin+ cells was increased. Megakaryocyte numbers were reduced with irradiation and located more closely to trabecular surfaces with irradiation and PTH. Bone marrow TGFβ was increased in irradiated PTH-treated mice, and inhibition of TGFβ blocked the PTH augmentation of bone in irradiated mice. In conclusion, irradiation created a permissive environment for anabolic actions of PTH that was TGFβ dependent but osteoclast independent and suggests that a nonosteoclast source of TGFβ drives mesenchymal stem cell recruitment to support PTH anabolic actions.
Bartonella henselae engages inside-out and outside-in signaling by integrin β1 and talin1 during invasome-mediated bacterial uptake
Authors: Truttmann Matthias C. , Misselwitz Benjamin , Huser Sonja , Hardt Wolf-Dietrich , Critchley David R. , Dehio Christoph
Published: November 2011

The VirB/D4 type IV secretion system (T4SS) of the bacterial pathogen Bartonella henselae (Bhe) translocates seven effector proteins (BepA–BepG) into human cells that subvert host cellular functions. Two redundant pathways dependent on BepG or the combination of BepC and BepF trigger the formation of a bacterial uptake structure termed the invasome. Invasome formation is a multi-step process consisting of bacterial adherence, effector translocation, aggregation of bacteria on the cell surface and engulfment, and eventually, complete internalization of the bacterial aggregate occurs in an F-actin-dependent manner. In the present study, we show that Bhe-triggered invasome formation depends on integrin-β1-mediated signaling cascades that enable assembly of the F-actin invasome structure. We demonstrate that Bhe interacts with integrin β1 in a fibronectin- and VirB/D4 T4SS-independent manner and that activated integrin β1 is essential for both effector translocation and the actin rearrangements leading to invasome formation. Furthermore, we show that talin1, but not talin2, is required for inside-out activation of integrin β1 during invasome formation. Finally, integrin-β1-mediated outside-in signaling by FAK, Src, paxillin and vinculin is necessary for invasome formation. This is the first example of a bacterial entry process that fully exploits the bi-directional signaling capacity of integrin receptors in a talin1-specific manner.
Effects of phosphorylation and neuronal activity on the control of synapse formation by synapsin I
Authors: Perlini Laura E. , Botti Francesca , Fornasiero Eugenio F. , Giannandrea Maila , Bonanomi Dario , Amendola Mario , Naldini Luigi , Benfenati Fabio , Valtorta Flavia
Published: November 2011

Synapsins are synaptic vesicle (SV)-associated proteins that regulate synaptic transmission and neuronal differentiation. At early stages, Syn I and II phosphorylation at Ser9 by cAMP-dependent protein kinase (PKA) and Ca2+/calmodulin-dependent protein kinase I/IV modulates axon elongation and SV-precursor dynamics. We evaluated the requirement of Syn I for synapse formation by siRNA-mediated knockdown as well as by overexpression of either its wild-type (WT) form or its phosphorylation mutants. Syn1 knockdown at 14 days in vitro caused a decrease in the number of synapses, accompanied by a reduction of SV recycling. Although overexpression of WT Syn I was ineffective, overexpression of its phosphorylation mutants resulted in a complex temporal regulation of synapse density. At early stages of synaptogenesis, phosphomimetic Syn I S9E significantly increased the number of synapses. Conversely, dephosphomimetic Syn I S9A decreased synapse number at more advanced stages. Overexpression of either WT Syn I or its phosphomimetic S9E mutant rescued the decrease in synapse number caused by chronic treatment with tetrodotoxin at early stages, suggesting that Syn I participates in an alternative PKA-dependent mechanism that can compensate for the impairment of the activity-dependent synaptogenic pathway. Altogether these results indicate that Syn I is an important regulator of synapse formation, which adjusts synapse number in response to extracellular signals.
The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer's Disease
Authors: McManus Meagan J. , Murphy Michael P. , Franklin James L.
Published: November 2011

Considerable evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the progression of Alzheimer's disease (AD). We examined the ability of the novel mitochondria-targeted antioxidant MitoQ (mitoquinone mesylate: [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cycloheexadienl-yl) decyl triphenylphosphonium methanesulfonate]) to prevent AD-like pathology in mouse cortical neurons in cell culture and in a triple transgenic mouse model of AD (3xTg-AD). MitoQ attenuated β-amyloid (Aβ)-induced neurotoxicity in cortical neurons and also prevented increased production of reactive species and loss of mitochondrial membrane potential (Δψm) in them. To determine whether the mitochondrial protection conferred by MitoQ was sufficient to prevent the emergence of AD-like neuropathologyin vivo, we treated young female 3xTg-AD mice with MitoQ for 5 months and analyzed the effect on the progression of AD-like pathologies. Our results show that MitoQ prevented cognitive decline in these mice as well as oxidative stress, Aβ accumulation, astrogliosis, synaptic loss, and caspase activation in their brains. The work presented herein suggests a central role for mitochondria in neurodegeneration and provides evidence supporting the use of mitochondria-targeted therapeutics in diseases involving oxidative stress and metabolic failure, namely AD.
The Laminar and Temporal Structure of Stimulus Information in the Phase of Field Potentials of Auditory Cortex
Authors: Szymanski Francois D. , Rabinowitz Neil C. , Magri Cesare , Panzeri Stefano , Schnupp Jan W. H.
Published: November 2011

Recent studies have shown that the phase of low-frequency local field potentials (LFPs) in sensory cortices carries a significant amount of information about complex naturalistic stimuli, yet the laminar circuit mechanisms and the aspects of stimulus dynamics responsible for generating this phase information remain essentially unknown. Here we investigated these issues by means of an information theoretic analysis of LFPs and current source densities (CSDs) recorded with laminar multi-electrode arrays in the primary auditory area of anesthetized rats during complex acoustic stimulation (music and broadband 1/fstimuli). We found that most LFP phase information originated from discrete “CSD events” consisting of granular–superficial layer dipoles of short duration and large amplitude, which we hypothesize to be triggered by transient thalamocortical activation. These CSD events occurred at rates of 2–4 Hz during both stimulation with complex sounds and silence. During stimulation with complex sounds, these events reliably reset the LFP phases at specific times during the stimulation history. These facts suggest that the informativeness of LFP phase in rat auditory cortex is the result of transient, large-amplitude events, of the “evoked” or “driving” type, reflecting strong depolarization in thalamo-recipient layers of cortex. Finally, the CSD events were characterized by a small number of discrete types of infragranular activation. The extent to which infragranular regions were activated was stimulus dependent. These patterns of infragranular activations may reflect a categorical evaluation of stimulus episodes by the local circuit to determine whether to pass on stimulus information through the output layers.