bluuebunny/crossref_metadata_2025 huggingface dataset:
Housing, the Welfare State, and the Global Financial Crisis
Authors: Schwartz Herman
Published: January 2012

Analyses of the global financial crisis that assign causality to the erosion of parts of the welfare state that protected individuals miss the importance of macro level regulation that protected firms and the financial system from itself. Post-Depression macro level regulation of finance prevented the emergence of mismatched maturities where deposits lacked state guarantees, and thus prevented runs on banks or near-banks. A balance sheet approach shows that macro regulation linked long duration liabilities in housing finance (mortgages) to long duration assets (pensions). Deregulation permitted the reemergence of mismatched maturities, providing both a necessary and sufficient condition for the current financial crisis.
The treatment views and recommendations of substance abusing women: A meta-synthesis
Authors: Hines Lisa
Published: January 2012

The purpose of this review is to synthesize qualitative data describing the substance abuse treatment views and recommendations of addicted mothers. The meta-synthesis approach is a systematic comparison of qualitative studies all asking the same or similar questions and seeks to result in a theory that cuts across all of the studies. Keyword searches of online databases Academic Search Premiere, PubMed, and Google Scholar were conducted using the keywords: perinatal substance abuse, women and substance abuse, parenting and substance abuse to locate qualitative studies. The author also searched references of qualitative studies to access additional articles. Studies were included if they were qualitative, included excerpts from participants who discussed issues about perinatal substance abuse treatment views and recommendations and were published between 1992 and 2010. There were 30 studies reviewed. Evidence suggests that social marketing of substance abuse services that emphasize comprehensive services provided by caring non-judgmental staff is central to motivating women to enter treatment. Positive client and staff interactions are significant to retaining women in treatment. Culturally competent staff can motivate women who are considering treatment. Gender specific substance abuse services are recommended.
Reversine suppresses oral squamous cell carcinoma via cell cycle arrest and concomitantly apoptosis and autophagy
Authors: Lee Ying-Ray , Wu Wei-Ching , Ji Wen-Tsai , Chen Jeff Yi-Fu , Cheng Ya-Ping , Chiang Ming-Ko , Chen Hau-Ren
Published: January 2012

Background

The effective therapies for oral cancer patients of stage III and IV are generally surgical excision and radiation combined with adjuvant chemotherapy using 5-Fu and Cisplatin. However, the five-year survival rate is still less than 30% in Taiwan. Therefore, evaluation of effective drugs for oral cancer treatment is an important issue. Many studies indicated that aurora kinases (A, B and C) were potential targets for cancer therapies. Reversine was proved to be a novel aurora kinases inhibitor with lower toxicity recently. In this study, the potentiality for reversine as an anticancer agent in oral squamous cell carcinoma (OSCC) was evaluated.

Methods

Effects of reversine on cell growth, cell cycle progress, apoptosis, and autophagy were evaluated mainly by cell counting, flow cytometry, immunoblot, and immunofluorescence.

Results

The results demonstrated that reversine significantly suppressed the proliferation of two OSCC cell lines (OC2 and OCSL) and markedly rendered cell cycle arrest at G2/M stage. Reversine also induced cell death via both caspase-dependent and -independent apoptosis. In addition, reversine could inhibit Akt/mTORC1 signaling pathway, accounting for its ability to induce autophagy.

Conclusions

Taken together, reversine suppresses growth of OSCC via multiple mechanisms, which may be a unique advantage for developing novel therapeutic regimens for treatment of oral cancer in the future.
Intermittent preventive treatment with sulfadoxine-pyrimethamine does not modify plasma cytokines and chemokines or intracellular cytokine responses to Plasmodium falciparum in Mozambican Children
Authors: Quelhas Diana , Puyol Laura , Quintó Llorenç , Nhampossa Tacilta , Serra-Casas Elisa , Macete Eusébio , Aide Pedro , Sanz Sergi , Aponte John J , Doolan Denise L , Alonso Pedro L , Menéndez Clara , Dobaño Carlota
Published: January 2012

Background

Cytokines and chemokines are key mediators of anti-malarial immunity. We evaluated whether Intermittent Preventive Treatment in infants with Sulfadoxine-Pyrimethamine (IPTi-SP) had an effect on the acquisition of these cellular immune responses in Mozambican children. Multiple cytokines and chemokines were quantified in plasma by luminex, and antigen-specific cytokine production in whole blood was determined by intracellular cytokine staining and flow cytometry, at ages 5, 9, 12 and 24 months.

Results

IPTi-SP did not significantly affect the proportion of CD3+ cells producing IFN-γ, IL-4 or IL-10. Overall, plasma cytokine or chemokine concentrations did not differ between treatment groups. Th1 and pro-inflammatory responses were higher than Th2 and anti-inflammatory responses, respectively, and IFN-γ:IL-4 ratios were higher for placebo than for SP recipients. Levels of cytokines and chemokines varied according to age, declining from 5 to 9 months. Plasma concentrations of IL-10, IL-12 and IL-13 were associated with current infection or prior malaria episodes. Higher frequencies of IFN-γ and IL-10 producing CD3+ cells and elevated IL-10, IFN-γ, MCP-1 and IL-13 in plasma were individually associated with increased malaria incidence, at different time points. When all markers were analyzed together, only higher IL-17 at 12 months was associated with lower incidence of malaria up to 24 months.

Conclusions

Our work has confirmed that IPTi-SP does not negatively affect the development of cellular immune response during early childhood. This study has also provided new insights as to how these cytokine responses are acquired upon age and exposure toP. falciparum, as well as their associations with malaria susceptibility.

Trial Registration

ClinicalTrials.gov:NCT00209795
Molecular characterization of a mosaic locus in the genome of 'CandidatusLiberibacter asiaticus'
Authors: Wang Xuefeng , Zhou Changyong , Deng Xiaoling , Su Huanan , Chen Jianchi
Published: January 2012

Background

Huanglongbing (HLB) is a highly destructive disease of citrus production worldwide. 'Candidatus Liberibacter asiaticus', an unculturable alpha proteobacterium, is a putative pathogen of HLB. Information about the biology and strain diversity of 'Ca. L. asiaticus' is currently limited, inhibiting the scope of HLB research and control.

Results

A genomic region (CLIBASIA_05640 to CLIBASIA_05650) of 'Ca. L. asiaticus' showing hyper-sequence variation or locus mosaicism was identified and investigated using 262 bacterial strains (188 from China and 74 from Florida). Based on the characteristic electrophoretic profiles of PCR amplicons generated by a specific primer set, eight electrophoretic types (E-types) were identified, six E-types (A, B, C, D, E, and F) in China and four E-types (A, C, G, and H) in Florida. The 'Ca. L. asiaticus' strains from China consisted predominately of E-type A (71.3%) and E-type B (19.7%). In contrast, the 'Ca. L. asiaticus' strains from Florida was predominated by E-type G (82.4%). Diversity of 'Ca. L. asiaticus' in China was also evidenced. Strains from the high altitude Yunnan Province consisted of five E-types with E-type B being the majority (62.8%), whereas strains from the low altitude coastal Guangdong Province consisted of only two E-types with E-type A as the majority (97.0%). Sequence analyses revealed that variation of DNA amplicons was due to insertion/deletion events at CLIBASIA_05650 and the downstream intergenic region.

Conclusions

This study demonstrated the genomic mosaicism of 'Ca. L. asiaticus' resulted from active DNA insertion/deletion activities. Analyses of strain variation depicted the significant inter- and intra-continent diversity of 'Ca. L. asiaticus'.
The role of the Arabidopsis FUSCA3transcription factor during inhibition of seed germination at high temperature
Authors: Chiu Rex S , Nahal Hardeep , Provart Nicholas J , Gazzarrini Sonia
Published: January 2012

Background

Imbibed seeds integrate environmental and endogenous signals to break dormancy and initiate growth under optimal conditions. Seed maturation plays an important role in determining the survival of germinating seeds, for example one of the roles of dormancy is to stagger germination to prevent mass growth under suboptimal conditions. The B3-domain transcription factor FUSCA3 (FUS3) is a master regulator of seed development and an important node in hormonal interaction networks inArabidopsis thaliana. Its function has been mainly characterized during embryonic development, whereFUS3is highly expressed to promote seed maturation and dormancy by regulating ABA/GA levels.

Results

In this study, we present evidence for a role ofFUS3in delaying seed germination at supraoptimal temperatures that would be lethal for the developing seedlings. During seed imbibition at supraoptimal temperature, theFUS3promoter is reactivated and inducesde novosynthesis ofFUS3mRNA, followed by FUS3 protein accumulation. Genetic analysis shows thatFUS3contributes to the delay of seed germination at high temperature. Unlike WT, seeds overexpressingFUS3(ML1:FUS3-GFP) during imbibition are hypersensitive to high temperature and do not germinate, however, they can fully germinate after recovery at control temperature reaching 90% seedling survival.ML1:FUS3-GFPhypersensitivity to high temperature can be partly recovered in the presence of fluridone, an inhibitor of ABA biosynthesis, suggesting this hypersensitivity is due in part to higher ABA level in this mutant. Transcriptomic analysis shows that WT seeds imbibed at supraoptimal temperature activate seed-specific genes and ABA biosynthetic and signaling genes, while inhibiting genes that promote germination and growth, such as GA biosynthetic and signaling genes.

Conclusion

In this study, we have uncovered a novel function for the master regulator of seed maturation,FUS3, in delaying germination at supraoptimal temperature. Physiologically, this is important since delaying germination has a protective role at high temperature. Transcriptomic analysis of seeds imbibed at supraoptimal temperature reveal that a complex program is in place, which involves not only the regulation of heat and dehydration response genes to adjust cellular functions, but also the activation of seed-specific programs and the inhibition of germination-promoting programs to delay germination.
Hardship financing of healthcare among rural poor in Orissa, India
Authors: Binnendijk Erika , Koren Ruth , Dror David M
Published: January 2012

Background

This study examines health-related "hardship financing" in order to get better insights on how poor households finance their out-of-pocket healthcare costs. We define hardship financing as having to borrow money with interest or to sell assets to pay out-of-pocket healthcare costs.

Methods

Using survey data of 5,383 low-income households in Orissa, one of the poorest states of India, we investigate factors influencing the risk of hardship financing with the use of a logistic regression.

Results

Overall, about 25% of the households (that had any healthcare cost) reported hardship financing during the year preceding the survey. Among households that experienced a hospitalization, this percentage was nearly 40%, but even among households with outpatient or maternity-related care around 25% experienced hardship financing.

Hardship financing is explained not merely by the wealth of the household (measured by assets) or how much is spent out-of-pocket on healthcare costs, but also by when the payment occurs, its frequency and its duration (e.g. more severe in cases of chronic illnesses). The location where a household resides remains a major predictor of the likelihood to have hardship financing despite all other household features included in the model.

Conclusions

Rural poor households are subjected to considerable and protracted financial hardship due to the indirect and longer-term deleterious effects of how they cope with out-of-pocket healthcare costs. The social network that households can access influences exposure to hardship financing. Our findings point to the need to develop a policy solution that would limit that exposure both in quantum and in time. We therefore conclude that policy interventions aiming to ensure health-related financial protection would have to demonstrate that they have reduced the frequency and the volume of hardship financing.
Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin
Authors: Yun Seong-Jo , Naidansuren Purevjargal , Sim Bo-Woong , Park Jong-Ju , Park Cha-Won , Nanjidsuren Tseeleema , Kang Myung-Hwa , Hwang Sue-Yun , Yoon Jong-Taek , Min Kwan-Sik
Published: January 2012

Background

Dimeric human erythropoietin (dHuEPO) peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg) mice expressing dHuEPO and to investigate the characteristics of these mice.

Methods

A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile), was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice.

Results

A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47) of tg mice expressing thedHuEPOgene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11). We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females) were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764). Reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative real-time PCR (qRT-PCR) were used for validating the results of the microarray analysis of mRNA expression.

Conclusions

In conclusion, dHuEPO tg mice caused excessive erythrocytosis that led to abnormal blood composition, short lifespan, and abnormal splenomegaly. Further, we identified 2,672 genes associated with splenomegaly by microarray analysis. These results could be useful in the development of dHuEPO-producing tg animals.
Strain specific transcriptional response in Mycobacterium tuberculosis infected macrophages
Authors: Koo Mi-Sun , Subbian Selvakumar , Kaplan Gilla
Published: January 2012

Background

Tuberculosis (TB), a bacterial infection caused byMycobacterium tuberculosis(Mtb)remains a significant health problem worldwide with a third of the world population infected and nearly nine million new cases claiming 1.1 million deaths every year. The outcome following infection byMtbis determined by a complex and dynamic host-pathogen interaction in which the phenotype of the pathogen and the immune status of the host play a role. However, the molecular mechanism by whichMtbstrains induce different responses during intracellular infection of the host macrophage is not fully understood. To explore the early molecular events triggered uponMtbinfection of macrophages, we studied the transcriptional responses of murine bone marrow-derived macrophages (BMM) to infection with two clinicalMtbstrains, CDC1551 and HN878. These strains have previously been shown to differ in their virulence/immunogenicity in the mouse and rabbit models of pulmonary TB.

Results

In spite of similar intracellular growth rates, we observed that compared to HN878, infection by CDC1551 of BMM was associated with an increased global transcriptome, up-regulation of a specific early (6 hours) immune response network and significantly elevated nitric oxide production. In contrast, at 24 hours post-infection of BMM by HN878, more host genes involved in lipid metabolism, including cholesterol metabolism and prostaglandin synthesis were up-regulated, compared to infection with CDC1551.

In association with the differences in the macrophage responses to infection with the 2Mtbstrains, intracellular CDC1551 expressed higher levels of stress response genes than did HN878.

Conclusions

In association with the early and more robust macrophage activation, intracellular CDC1551 cells were exposed to a higher level of stress leading to increased up-regulation of the bacterial stress response genes. In contrast, sub-optimal activation of macrophages and induction of a dysregulated host cell lipid metabolism favored a less stressful intracellular environment for HN878. Our findings suggest that the ability of CDC1551 and HN878 to differentially activate macrophages during infection probably determines their ability to either resist host cell immunity and progress to active disease or to succumb to the host protective responses and be driven into a non-replicating latent state in rabbit lungs.
Bone marrow stromal cell antigen 2 (BST-2) restricts mouse mammary tumor virus (MMTV) replication in vivo
Authors: Jones Philip H , Mehta Harshini V , Maric Martina , Roller Richard J , Okeoma Chioma M
Published: January 2012

Background

Bone marrow stromal cell antigen 2 (BST-2) is a cellular factor that restricts the egress of viruses such as human immunodeficiency virus (HIV-1) from the surface of infected cells, preventing infection of new cells. BST-2 is variably expressed in most cell types, and its expression is enhanced by cytokines such as type I interferon alpha (IFN-α). In this present study, we used the beta-retrovirus, mouse mammary tumor virus (MMTV) as a model to examine the role of mouse BST-2 in host infectionin vivo.

Results

By using RNA interference, we show that loss of BST-2 enhances MMTV replication in cultured mammary tumor cells andin vivo. In cultured cells, BST-2 inhibits virus accumulation in the culture medium, and co-localizes at the cell surface with virus structural proteins. Furthermore, both scanning electron micrograph (SEM) and transmission electron micrograph (TEM) show that MMTV accumulates on the surface of IFNα-stimulated cells.

Conclusions

Our data provide evidence that BST-2 restricts MMTV release from naturally infected cells and that BST-2 is an antiviral factorin vivo.
The occurrence of Chlamydiaspp. in pigs with and without clinical disease
Authors: Englund Stina , Hård af Segerstad Carl , Arnlund Frida , Westergren Eva , Jacobson Magdalena
Published: January 2012

Background

Within the generaChlamydia, the development of refined diagnostic techniques has allowed the identification of four species that are capable of infecting pigs. The epidemiology, clinical, and zoonotic impacts of these species are however largely unknown. The study aimed to investigate the presence ofChlamydiaspp. in the intestines of growing pigs and in conjunctival swabs from finisher pigs, and relate the findings to clinical signs.

Results

By histology, 20 of 48 pigs had intestinal lesions that may be consistent with chlamydial infection. By PCR, forty-six of the pigs were positive whereas two samples were inhibited. Sequencing of 19 DNA extracts identified these asChlamydia suis. By immunohistochemistry, 32 of 44 samples were positive and a significant relationship was detected between macroscopically visible intestinal lesions and a high degree of infection. By real-time PCR, a significant difference was detected between pigs with and without conjunctivitis when a Ct value of 36 was employed but not when a Ct value of 38 was employed.

Conclusions

Chlamydia suiswas demonstrated in most samples and overall, no correlation to clinical signs was detected. However, a correlation was noted between samples with a high degree of infection and the presence of clinical signs. It is possible, that the intensive pig production systems studied might predispose for the transmission and maintenance of the infection thus increasing the infectious load and the risk for disease in the pig.
A cluster randomised controlled trial of the clinical and cost-effectiveness of a 'whole systems' model of self-management support for the management of long- term conditions in primary care: trial protocol
Authors: Bower Peter , Kennedy Anne , Reeves David , Rogers Anne , Blakeman Tom , Chew-Graham Carolyn , Bowen Robert , Eden Martin , Gardner Caroline , Hann Mark , Lee Victoria , Morris Rebecca , Protheroe Joanne , Richardson Gerry , Sanders Caroline , Swallow Angela , Thompson David
Published: January 2012

Background

Patients with long-term conditions are increasingly the focus of quality improvement activities in health services to reduce the impact of these conditions on quality of life and to reduce the burden on care utilisation. There is significant interest in the potential for self-management support to improve health and reduce utilisation in these patient populations, but little consensus concerning the optimal model that would best provide such support. We describe the implementation and evaluation of self-management support through an evidence-based 'whole systems' model involving patient support, training for primary care teams, and service re-organisation, all integrated into routine delivery within primary care.

Methods

The evaluation involves a large-scale, multi-site study of the implementation, effectiveness, and cost-effectiveness of this model of self-management support using a cluster randomised controlled trial in patients with three long-term conditions of diabetes, chronic obstructive pulmonary disease (COPD), and irritable bowel syndrome (IBS). The outcome measures include healthcare utilisation and quality of life. We describe the methods of the cluster randomised trial.

Discussion

If the 'whole systems' model proves effective and cost-effective, it will provide decision-makers with a model for the delivery of self-management support for populations with long-term conditions that can be implemented widely to maximise 'reach' across the wider patient population.

Trial registration number

ISRCTN:ISRCTN90940049
Prenatal diagnosis of a trisomy 7/trisomy 13 mosaicism
Authors: Huijsdens-van Amsterdam Karin , Barge-Schaapveld Daniela QCM , Mathijssen Inge B , Alders Mariëlle , Pajkrt Eva , Knegt Alida C
Published: January 2012

Double aneuploidy mosaicism of two different aneuploidy cell lines is rare. We describe for the first time a double trisomy mosaicism, involving chromosomes 7 and 13 in a fetus presenting with multiple congenital anomalies. No evidence for chimerism was found by DNA genotyping. The origin of both trisomies are consistent with isodisomy of maternal origin. Therefore, it is most likely that the double trisomy mosaicism arose from two independent events very early in embryonic development. The trisomy 7 and 13 cells were shown to be of maternal origin.
Rapid multiplex high resolution melting method to analyze inflammatory related SNPs in preterm birth
Authors: Pereyra Silvana , Velazquez Tatiana , Bertoni Bernardo , Sapiro Rossana
Published: January 2012

Background

Complex traits like cancer, diabetes, obesity or schizophrenia arise from an intricate interaction between genetic and environmental factors. Complex disorders often cluster in families without a clear-cut pattern of inheritance. Genomic wide association studies focus on the detection of tens or hundreds individual markers contributing to complex diseases. In order to test if a subset of single nucleotide polymorphisms (SNPs) from candidate genes are associated to a condition of interest in a particular individual or group of people, new techniques are needed. High-resolution melting (HRM) analysis is a new method in which polymerase chain reaction (PCR) and mutations scanning are carried out simultaneously in a closed tube, making the procedure fast, inexpensive and easy. Preterm birth (PTB) is considered a complex disease, where genetic and environmental factors interact to carry out the delivery of a newborn before 37 weeks of gestation. It is accepted that inflammation plays an important role in pregnancy and PTB.

Methods

Here, we used real time-PCR followed by HRM analysis to simultaneously identify several gene variations involved in inflammatory pathways on preterm labor. SNPs from TLR4, IL6, IL1 beta and IL12RB genes were analyzed in a case-control study. The results were confirmed either by sequencing or by PCR followed by restriction fragment length polymorphism.

Results

We were able to simultaneously recognize the variations of four genes with similar accuracy than other methods. In order to obtain non-overlapping melting temperatures, the key step in this strategy was primer design. Genotypic frequencies found for each SNP are in concordance with those previously described in similar populations. None of the studied SNPs were associated with PTB.

Conclusions

Several gene variations related to the same inflammatory pathway were screened through a new flexible, fast and non expensive method with the purpose of analyzing their association to PTB. It can easily be used for simultaneously analyze any set of SNPs, either as the first choice for new association studies or as a complement to large-scale genotyping analysis. Given that inflammatory pathway is in the base of several diseases, it is potentially useful to analyze a broad range of disorders.
Methodology optimizing SAGE library tag-to-gene mapping: application to Leishmania
Authors: Smandi Sondos , Guerfali Fatma Z , Farhat Mohamed , Ben-Aissa Khadija , Laouini Dhafer , Guizani-Tabbane Lamia , Dellagi Koussay , Benkahla Alia
Published: January 2012

Background

Leishmaniasis are widespread parasitic-diseases with an urgent need for more active and less toxic drugs and for effective vaccines. Understanding the biology of the parasite especially in the context of host parasite interaction is a crucial step towards such improvements in therapy and control. Several experimental approaches including SAGE (Serial analysis of gene expression) have been developed in order to investigate the parasite transcriptome organisation and plasticity. Usual SAGE tag-to-gene mapping techniques are inadequate because almost all tags are normally located in the 3'-UTR outside the CDS, whereas most information available forLeishmaniatranscripts is restricted to the CDS predictions. The aim of this work is to optimize a SAGE libraries tag-to-gene mapping technique and to show how this development improves the understanding ofLeishmaniatranscriptome.

Findings

The in silico method implemented herein was based on mapping the tags toLeishmaniagenome using BLAST then mapping the tags to their gene using a data-driven probability distribution. This optimized tag-to-gene mappings improved the knowledge ofLeishmaniagenome structure and transcription. It allowed analyzing the expression of a maximal number ofLeishmaniagenes, the delimitation of the 3' UTR of 478 genes and the identification of biological processes that are differentially modulated during the promastigote to amastigote differentiation.

Conclusion

The developed method optimizes the assignment of SAGE tags in trypanosomatidae genomes as well as in any genome having polycistronic transcription and small intergenic regions.
Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cells
Authors: Sharma Shikhar , Gerke Daniel S , Han Han F , Jeong Shinwu , Stallcup Michael R , Jones Peter A , Liang Gangning
Published: January 2012

Background

DNA methylation, histone modifications and nucleosome occupancy act in concert for regulation of gene expression patterns in mammalian cells. Recently, G9a, a H3K9 methyltransferase, has been shown to play a role in establishment of DNA methylation at embryonic gene targets in ES cells through recruitment of de novo DNMT3A/3B enzymes. However, whether G9a plays a similar role in maintenance of DNA methylation in somatic cells is still unclear.

Results

Here we show that G9a is not essential for maintenance of DNA methylation in somatic cells. Knockdown of G9a has no measurable effect on DNA methylation levels at G9a-target loci. DNMT3A/3B remain stably anchored to nucleosomes containing methylated DNA even in the absence of G9a, ensuring faithful propagation of methylated states in cooperation with DNMT1 through somatic divisions. Moreover, G9a also associates with nucleosomes in a DNMT3A/3B and DNA methylation-independent manner. However, G9a knockdown synergizes with pharmacologic inhibition of DNMTs resulting in increased hypomethylation and inhibition of cell proliferation.

Conclusions

Taken together, these data suggest that G9a is not involved in maintenance of DNA methylation in somatic cells but might play a role in re-initiation of de novo methylation after treatment with hypomethylating drugs, thus serving as a potential target for combinatorial treatments strategies involving DNMTs inhibitors.
Local administration of glucocorticoids decreases synovial citrullination in rheumatoid arthritis
Authors: Makrygiannakis Dimitrios , Revu Shankar , Engström Marianne , af Klint Erik , Nicholas Anthony P , Pruijn Ger JM , Catrina Anca I
Published: January 2012

Introduction

Protein citrullination is present in the rheumatoid synovium, presumably contributing to the perpetuation of chronic inflammation, in the presence of specific autoimmunity. As a result, the present study examined the possibility that effective antirheumatic treatment will decrease the level of synovial citrullination.

Methods

Synovial biopsies were obtained from 11 rheumatoid arthritis (RA) patients before and after 8 weeks of treatment with 20 mg methotrexate weekly, 15 RA patients before and 2 weeks after an intraarticular glucocorticoid injection, and eight healthy volunteers. Synovial inflammation was assessed with double-blind semiquantitative analysis of lining thickness, cell infiltration, and vascularity by using a 4-point scale. Expression of citrullinated proteins (CPs) with the monoclonal antibody F95 and peptidylarginine deiminase (PAD) 2 and 4 was assessed immunohistochemically with double-blind semiquantitative analysis. In vitro synovial fluid (SF), peripheral blood (PB), mononuclear cells (MCs), and synovial explants obtained from RA patients were incubated with dexamethasone and analyzed with immunohistochemistry for expression of CP as well as PAD2 and PAD4 enzymes.

Results

The presence of synovial CP was almost exclusive in RA compared with healthy synovium and correlated with the degree of local inflammation. Treatment with glucocorticoids but not methotrexate alters expression of synovial CP and PAD enzymes, in parallel with a decrease of synovial inflammation. Ex vivo and in vitro studies suggest also a direct effect of glucocorticoids on citrullination, as demonstrated by the decrease in the level of citrullination and PAD expression after incubation of SFMC and synovial explants with dexamethasone.

Conclusion

Synovial citrullination and PAD expression are dependent on local inflammation and targeted by glucocorticoids.
A randomised controlled trial of a self-management education program for osteoarthritis of the knee delivered by health care professionals
Authors: Coleman Sophie , Briffa N Kathryn , Carroll Graeme , Inderjeeth Charles , Cook Nicola , McQuade Jean
Published: January 2012

Introduction

Our aim in the present study was to determine whether a disease-specific self-management program for primary care patients with osteoarthritis (OA) of the knee (the Osteoarthritis of the Knee Self-Management Program (OAK)) implemented by health care professionals would achieve and maintain clinically meaningful improvements in health-related outcomes compared with a control group.

Methods

Medical practitioners referred 146 primary care patients with OA of the knee. Volunteers with coexistent inflammatory joint disease or serious comorbidities were excluded. Randomisation was to either a control group or the OAK group. The OAK group completed a 6-week self-management program. The control group had a 6-month waiting period before entering the OAK program. Assessments were taken at baseline, 8 weeks and 6 months. The primary outcomes were the results measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain and Function subscales on the Short Form 36 version 1 questionnaire (SF-36) Secondary outcomes were Visual Analogue Scale (VAS) pain, Timed Up & Go Test (TUG), knee range of motion and quadriceps and hamstring strength-isometric contraction. Responses to treatment (responders) and minimal clinically important improvements (MCIIs) were determined.

Results

In the OAK group, VAS pain improved from baseline to week 8 from mean (SEM) 5.21 (0.30) to 3.65 (0.29) (P ≤ 0.001). During this period, improvements in the OAK group compared with the control group and responses to treatment were demonstrated according to the following outcomes: WOMAC Pain, Physical Function and Total dimensions, as well as SF-36 Physical Function, Role Physical, Body Pain, Vitality and Social Functioning domains. In addition, from baseline to week 8, the proportion of MCIIs was greater among the OAK group than the control group for all outcomes. For the period between baseline and month 6, WOMAC Pain, Physical Function and Total dimensions significantly improved in the OAK group compared to the control group, as did the SF-36 Physical Function, Role Physical, Body Pain, Vitality and Social Functioning domains, as well as hamstring strength in both legs. During the same period, the TUG Test, range of motion extension and left-knee flexion improved compared with the control group, although these improvements had little clinical relevance.

Conclusions

We recorded statistically significant improvements compared with a control group with regard to pain, quality of life and function for participants in the OAK program on the basis of WOMAC and SF-36 measures taken 8 weeks and 6 months from baseline.
Orbital Views on Electron-Transport Properties of Cyclophanes: Insight into Intermolecular Transport
Authors: Li Xinqian , Staykov Aleksandar , Yoshizawa Kazunari
Published: January 2012

Electron-transport properties of cyclophanes are investigated with qualitative Hückel molecular orbital analysis for better understanding of the intermolecular interaction in molecular devices. Charge and electron transfers often take place via through-space interactions, which are observed both in large biological molecules and in organic molecular crystals. Since the intermolecular electronic coupling in π-stacked structures plays an important role in total device performance, in this work [2,2]paracyclophane is studied to investigate the effect of the intermolecular interactions in aromatic hydrocarbons on its electron-transport properties. According to the orbital symmetry rule, the symmetry-allowed and symmetry-forbidden connections for electron transport between the benzene rings are predicted just from the phase and amplitude of the frontier orbitals. The meta connection is symmetry allowed for electron transport while the para and ortho connections are symmetry forbidden. The qualitative predictions made with the Hückel approximation are found consistent with the calculation results obtained with density functional theory. The qualitative but essential understanding in the orbital views would extend the application of the rule from a single molecule to a crystal structure for the development of high-performance molecular devices.
Rapid and Convenient Sample Preparation in a Single Tube Using Magnetic Beads for Fluorescence Detection of Single Nucleotide Variation Based on Oligonucleotide Ligation
Authors: Hashimoto Masahiko , Morimoto Chika , Hagihara Kenta , Tsukagoshi Kazuhiko
Published: January 2012

We here describe a rapid and convenient sample preparation in a single tube for detecting single nucleotide variation based on oligonucleotide ligation assay (OLA) using a biotinylated primer and a set of four different fluorophore-labeled primers. Only one of the fluorophore-labeled primers that was fully complementary to a DNA template was ligated with the biotin-primer by DNA ligase. We isolated the ligated fragments that carried a biotin at the 3′-end by capture with streptavidin-coated magnetic beads. The distinct fluorescence signature of each ligation product coded the single nucleotide differences.
Benzo[b]trithiophene Polymer Network Prepared by Electrochemical Polymerization with a Combination of Thermal Conversion
Authors: Nakae Takahiro , Mizobuchi Shingo , Yano Maki , Ukai Takuya , Sato Hisako , Shinmei Toru , Inoue Toru , Irifune Tetsuo , Sakaguchi Hiroshi
Published: January 2012

A two-step procedure of two-dimensional polymer constructed from benzo[b]trithiophene (BTT) was proposed by electrochemical polymerization and thermal conversion. Electropolymerized BTT oligomer on an electrode was thermally converted to conjugated polymer. Obtained conductive material is found to retain BTT structure by Raman spectra and to extend π conjugation by absorption spectra.
Highly Efficient and Selective Formation of Hydrogencarbonate in CO2 Absorption Process Using Piperidine and Piperazine Derivatives
Authors: Shin Man Sub , Park Yoon Kook , Nam Sung Chan , Hwang Kwang-Jin
Published: January 2012

This investigation demonstrated that bicarbonate ions were selectively formed over carbamate in a CO2 absorption process using piperidine and piperazine derivatives based on 13C NMR. Piperidines with methyl or hydroxymethyl substituent at 2 position (PiP-Me and PiP-MeOH) and 2,5-dimethylpiperazine (DM-PiZ) generated the bicarbonate ions as main adducts in reaction with CO2. The absorptions of CO2 by those aqueous amines (PiP-Me and DM-PiZ) were faster than those of MEA (2-aminoethanol).
Synthesis and Reactivity of a Platinum(II) Complex with Hydrosulfido Ligands Induced by a Chelated N-Heterocyclic Carbene Ligand
Authors: Maeda Yuri , Hashimoto Hideki , Nishioka Takanori
Published: January 2012

A bis(hydrosulfido)platinum(II) complex with a bidentate chelate N-heterocyclic carbene ligand was oxidized by O2 to give a linear tetrasulfide complex in the presence of excess hydrogen sulfide and a thiosulfato-bridged dinuclear complex without hydrogen sulfide.
The chopstick-noodle twist: an easy technique of percutaneous patellar fixation in minimally displaced patellar fractures
Authors: Muzaffar Nasir , Ahmad Nawaz , Ahmad Aejaz , Ahmad Nissar
Published: January 2012

We report six cases of minimally displaced two-part patellar fractures with skin injury over the patella that were treated with percutaneous K wire fixation and compression applied using stainless steel (SS) wire. This technique makes it possible to perform early operative treatment in cases where unhealthy skin is not amenable to conventional tension band wiring. The technique employs two K wires inserted through the two fracture fragments under local or regional anaesthesia. They are then compressed using simple SS wire knots at the two ends – making it look like noodles at the end of two chopsticks. The fixation is subsequently augmented with a cylindrical plaster-of-Paris cast. The technique is simple, cheap and does not cause soft tissue injury.
Prenatal Care and Subsequent Birth Intervals
Authors: Teitler Julien O. , Das Dhiman , Kruse Lakota , Reichman Nancy E.
Published: January 2012

CONTEXT:

Prenatal care generally includes contraceptive and health education that may help women to control their subsequent fertility. However, research has not examined whether receipt of prenatal care is associated with subsequent birthspacing.

METHODS:

Longitudinally linked birth records from 113,662 New Jersey women who had had a first birth in 1996–2000 were used to examine associations between the timing and adequacy of prenatal care prior to a woman’s first birth and the timing of her second birth. Multinomial logistic regression analyses adjusted for social and demographic characteristics, hospital and year of birth.

RESULTS:

Most women (85%) had initiated prenatal care during the first trimester. Women who had not obtained prenatal care until the second or third trimester, or at all, were more likely than those who had had first‐trimester care to have a second child within 18 months, rather than in 18–59 months (odds ratios, 1.2–1.6). Similarly, women whose care had been inadequate were more likely than those who had had adequate care to have a short subsequent birth interval (1.2). The associations were robust to alternative measures of prenatal care and birth intervals, and were strongest for mothers with less than 16 years of education.

CONCLUSIONS:

Providers should capitalize on their limited encounters with mothers who initiate prenatal care late or use it sporadically to ensure that these women receive information about family planning.
Relationships Between Flowering Time and Rainfall Gradients Across Mediterranean-Desert Transects
Authors: Kigel Jaime , Konsens Irit , Rosen Naomi , Rotem Gur , Kon Ari , Fragman-Sapir Ori
Published: January 2012

There is growing evidence for rapid adaptive evolution in response to climate change, including phenological transitions such as earlier flowering with climate warming. The consequences of these evolutionary changes for population dynamics and shifts in species ranges remain, however, quite unexplored. Here, we propose that inter-population differences in patterns of flowering across geographic precipitation gradients can be considered a proxy for changes in flowering time due to variation in rainfall resulting from climate change. To this end, we analyze trends of variation in flowering time across rainfall gradients in the eastern Mediterranean region in three main plant life-forms present in the local vegetation: winter annuals, geophytes, and perennial grasses. These life-forms cope with the hot and dry summer via a drought escape strategy. The analysis is based on published and unpublished data from common-garden experiments in which plants from populations sampled along rainfall gradients were grown under similar conditions, thus allowing detection of genetic differences in flowering time along the gradient. The data clearly indicate that decreasing rainfall across a Mediterranean-desert transect is associated with earlier flowering in winter annual species. In contrast, the limited available data shows no consistent trend of change in flowering time with decreasing rainfall in geophytes and perennial grasses. The phenological shift to early flowering in winter annuals coping with terminal drought appears to be a widespread method for adaptation to arid environments by stress avoidance, diminishing the risk of early death before seed production. However, changes in flowering time associated with the reduction in precipitation predicted by climate change models are relatively small, suggesting that additional traits are involved in the adaptation to increasing aridity. The hypothesis that low water availability is an environmental signal inducing earlier flowering of annual plants under drought conditions is not supported by experimental data.
Personas as a user-centred design tool for the built environment
Authors: Siddall Emma , Baibarac Corelia , Byrne Aimee , Byrne Niall , Deasy Ashling , Flood Nuala , Goulding Camille , O'Driscoll Shane , Rabbitt Niamh , Sweeney Angharad , Wang Yue , Dyer Mark
Published: January 2012

The physical structure of a city frequently defines how people interact with each other and their environment. This paper examines the use of personas as a user-centred design tool for the re-engineering of a city to promote sustainable behaviour and social inclusion of its citizens (the Eight Eyes of Dublin Project). The research was carried out through the adoption of personas and collaboration with design partners to identify barriers to sustainability, and resulted in recommendations for the future development of Dublin city, Ireland. These recommendations are then compared with the draft Dublin development plan 2011–17 to determine the effectiveness of personas as a design tool for identifying key issues for sustainability in the built environment. The results suggest that personas may be an appropriate tool for universal design and may act as a good diagnostic tool in the early stages of the re-engineering of urban areas towards sustainability. It is concluded that personas may work most effectively when used in combination with other user-centred design tools, such as participatory design.
Planning cycling networks: human factors and design processes
Authors: Deegan Brian , Parkin John
Published: January 2012

Developing a network for cycle traffic is a complex process, particularly in a dense and heavily motor trafficked city such as London. The London Cycle Network Plus has delivered cycle routes on strategic highways, and local cycling stakeholders have assisted in the design process through cycle route implementation and stakeholder plans. Stakeholders were trained in aspects of highway engineering and used the London cycling design standards as a reference tool. The paper summarises the lessons learnt, and concludes that knowledge from stakeholders is needed to help in the design process, and such intense involvement was novel in transport planning. The current proposals for cycle superhighways and other borough transport schemes seek to build on previous participative successes and also emphasise planning issues in the geographical neighbourhood of routes.
Sustainable development and professional practice
Authors: Laws David , Loeber Anne
Published: January 2012

This paper explores the implications of treating sustainable development as a feature of the design and implementation of concrete technical projects, rather than as an abstract line of thinking about possible futures. In such ventures, human dimensions of sustainability, like managing conflicting interpretations and coping with divergent plans and perspectives, become core questions for the professionals involved. The paper describes four common dilemmas that shape this process and discusses their persistent influence on professional practice. The paper argues that confronting these problems will lead engineers to approach technical projects as arenas for learning and problem-oriented negotiation. The conclusion reviews practical strategies that engineers and other professionals may employ to cope with the complexities of integrating sustainability into their practice.