bluuebunny/crossref_metadata_2025 huggingface dataset:
Do the Institute of Medicine’s (IOM’s) dimensions of quality capture the current meaning of quality in health care? – An integrative review
Authors: Beattie Michelle , Shepherd Ashley , Howieson Brian
Published: April 2012

Aims:

The aim of this study was to determine whether the widely adopted Institute of Medicine’s dimensions of quality capture the current meaning of quality in health care literature.

Design:

An integrative review was utilised as there has been a multitude of published papers defining quality in relation to health care, therefore collective analysis may provide new insight and understanding.

Method:

Papers offering a definition or conceptual understanding of quality in relation to health care were identified by searching relevant databases. Papers were excluded according to predefined criteria. An integrative review was conducted and the Institute of Medicine’s dimensions were used as a framework for data extraction and analysis.

Findings:

The review identified two important additional dimensions of quality; namely caring and navigating the health care system and argues that they require recognition as dimensions in their own right.

Conclusion:

In the current climate of constrained finances there is a risk that the allocation of resources is directed to current explicit dimensions to the detriment of others. The result may be a reduction in health care quality, rather than improvement.
The application of simulation to the understanding of football flight
Authors: Tuplin Simon , Passmore Martin , Rogers David , Harland Andy R , Lucas Tim , Holmes Chris
Published: April 2012

This paper demonstrates the value of using a flight model in the analysis of the flight of a football, and explores the complexity of the model required to produce useful results. Two specific aspects of the simulation are addressed: the need to include a model of spin decay and the requirement to include a full aerodynamic drag profile as a function of Reynolds number rather than a single indicative value. Both are aspects of the ball performance that are experimentally intensive to obtain.

The simulated flights show that the inclusion of spin degradation is important if flight validation is the objective, but that it may be unnecessary in a comparative study. The simple analytical model of spin degradation is shown to over-estimate the reduction in lateral deviation when compared to experimentally acquired data. Therefore, the experimental method is preferred.

The analysis of the shape of the drag profile (drag coefficient against Reynolds number) is explored, and it is shown from the simulated flights that post-critical coefficients of drag have the greatest effect on trajectories, and an average drag value is sufficient for most modelled scenarios.
The Indian Corporate Structure and the ‘Theory’ of Emerging Market Business Groups
Authors: Mazumdar Surajit
Published: April 2012

This article critically evaluates the value of the contemporary analysis of the ‘emerging market’ business group found in international literature for studying the institution in India. It argues that this value is limited by the top-down and ahistorical approach most of that analysis tends to adopt. The article shows that while business groups have been a common feature of the Indian corporate scene, they do not conform to the static conceptions of the business group found in the current literature. The article also presents a critical review of the influential functional explanation of developing country business groups as responses to ‘institutional voids’. It argues that this theory neither explains the institution of the group nor does it really shed light on the phenomenon of concentration expressed through that institution.
Rationalising Bt Technology: Creating a Biopolitical Space Around Bt Cotton
Authors: Raina Sunita
Published: April 2012

Sociologists have long recognised rationalisation as a process through which a universally applicable technical code crystallises as technological rationality of a modern society. This article challenges such essentialist theories that offer deter-ministic and universal generalisations about such abstract categories as technical rationality. Rather it suggests that technical rationality in itself is constructed by a network of actors in a specific context. This article analyses the historical moment of the introduction of Bt cotton in India, in 2002, in order to explore how the technical rationality guiding the introduction of Bt technology was itself constructed by a network of neoliberal actors. In doing so, the article reveals the political economy of this technology at both the discursive and institutional levels. Here, rationalisation is defined as a biopolitical process whereby a host of neoliberal actors used discursive framings and institutional strategies in order to create a hospitable environment for an imported Bt technology. The article argues that a hegemonic capitalist rationale guided the adoption of Bt cotton through the 2002 policy decision. The construction of this context-specific rationale led to the emergence of a global agbiotech industry at the local level, which, in turn, further strengthened the state-biotechnology-market nexus.
A critical role for endoglin in the emergence of blood during embryonic development
Authors: Borges Luciene , Iacovino Michelina , Mayerhofer Timothy , Koyano-Nakagawa Naoko , Baik June , Garry Daniel J. , Kyba Michael , Letarte Michelle , Perlingeiro Rita C. R.
Published: April 2012

Much remains unknown about the signals that induce early mesoderm to initiate hematopoietic differentiation. Here, we show that endoglin (Eng), a receptor for the TGFβ superfamily, identifies all cells with hematopoietic fate in the early embryo. These arise in an Eng+Flk1+ mesodermal precursor population at embryonic day 7.5 (E7.5), a cell fraction also endowed with endothelial potential. In Eng-knockout embryos, hematopoietic colony activity and numbers of CD71+Ter119+ erythroid progenitors were severely reduced. This coincided with severely reduced expression of embryonic globin and key bone morphogenic protein (BMP) target genes, including the hematopoietic regulators Scl, Gata1, Gata2, and Msx-1. To interrogate molecular pathways active in the earliest hematopoietic progenitors, we applied transcriptional profiling to sorted cells from E7.5 embryos. Eng+Flk-1+ progenitors coexpressed TGFβ and BMP receptors and target genes. Furthermore, Eng+Flk-1+ cells presented high levels of phospho-SMAD1/5, indicating active TGFβ and/or BMP signaling. Remarkably, under hematopoietic serum-free culture conditions, hematopoietic outgrowth of Eng-expressing cells was dependent on the TGFβ superfamily ligands BMP4, BMP2, or TGF-β1. These data demonstrate that the E+F+ fraction at E7.5 represents mesodermal cells competent to respond to TGFβ1, BMP4, or BMP2, shaping their hematopoietic development, and that Eng acts as a critical regulator in this process by modulating TGF/BMP signaling.
Genome-wide identification of endothelial cell–enriched genes in the mouse embryo
Authors: Takase Haruka , Matsumoto Ken , Yamadera Rie , Kubota Yoshiaki , Otsu Ayaka , Suzuki Rumiko , Ishitobi Hiroyuki , Mochizuki Hiromi , Kojima Takahiro , Takano Shingo , Uchida Kazuhiko , Takahashi Satoru , Ema Masatsugu
Published: April 2012

The early blood vessels of the embryo and yolk sac in mammals develop by aggregation of de novo–forming angioblasts into a primitive vascular plexus, which then undergoes a complex remodeling process. Angiogenesis is also important for disease progression in the adult. However, the precise molecular mechanism of vascular development remains unclear. It is therefore of great interest to determine which genes are specifically expressed in developing endothelial cells (ECs). Here, we used Flk1-deficient mouse embryos, which lack ECs, to perform a genome-wide survey for genes related to vascular development. We identified 184 genes that are highly enriched in developing ECs. The human orthologs of most of these genes were also expressed in HUVECs, and small interfering RNA knockdown experiments on 22 human orthologs showed that 6 of these genes play a role in tube formation by HUVECs. In addition, we created Arhgef15 knockout and RhoJ knockout mice by a gene-targeting method and found that Arhgef15 and RhoJ were important for neonatal retinal vascularization. Thus, the genes identified in our survey show high expression in ECs; further analysis of these genes should facilitate our understanding of the molecular mechanisms of vascular development in the mouse.
Myeloma as a model for the process of metastasis: implications for therapy
Authors: Ghobrial Irene M.
Published: April 2012

Multiple myeloma (MM) is a plasma cell dyscrasia characterized by the presence of multiple myelomatous “omas” throughout the skeleton, indicating that there is continuous trafficking of tumor cells to multiple areas in the bone marrow niches. MM may therefore represent one of the best models to study cell trafficking or cell metastasis. The process of cell metastasis is described as a multistep process, the invasion-metastasis cascade. This involves cell invasion, intravasation into nearby blood vessels, passage into the circulation, followed by homing into predetermined distant tissues, the formation of new foci of micrometastases, and finally the growth of micrometastasis into macroscopic tumors. This review discusses the significant advances that have been discovered in the complex process of invasion-metastasis in epithelial carcinomas and cell trafficking in hematopoietic stem cells and how this process relates to progression in MM. This progression is mediated by clonal intrinsic factors that mediate tumor invasiveness as well as factors present in the tumor microenvironment that are permissive to oncogenic proliferation. Therapeutic agents that target the different steps of cell dissemination and progression are discussed. Despite the significant advances in the treatment of MM, better therapeutic agents that target this metastatic cascade are urgently needed.
CBDB: The codon bias database
Authors: Hilterbrand Adam , Saelens Joseph , Putonti Catherine
Published: April 2012

Background

In many genomes, a clear preference in the usage of particular codons exists. The mechanisms that induce codon biases remain an open question; studies have attributed codon usage to translational selection, mutational bias and drift. Furthermore, correlations between codon usage within host genomes and their viral pathogens have been observed for a myriad of host-virus systems. As such, numerous studies have investigated codon usage and codon bias in an effort to better understand how species evolve. Numerous metrics have been developed to identify biases in codon usage. In addition, a few data repositories of codon bias data are available, differing in the metrics reported as well as the number and taxonomy of strains examined.

Description

We have created a new web resource called the Codon Bias Database (CBDB) which provides information regarding the codon bias within the set of highly expressed genes for 300+ bacterial genomes. CBDB was developed to provide a resource for researchers investigating codon bias in bacteria, facilitating comparisons between strains and species. Furthermore, the site was created to serve those studying adaptation in phage; the genera selected for this first release of CBDB all have sequenced, annotated bacteriophages. The annotations and sequences for the highly expressed gene set are available for each strain in addition to the strain’s codon bias measurements.

Conclusions

Comparing species and strains provides a comprehensive look at how codon usage has been shaped over evolutionary time and can elucidate the putative mechanisms behind it. The Codon Bias Database provides a centralized repository of look-up tables and codon usage bias measures for a wide variety of genera, species and strains. Through our analysis of the variation in codon usage within the strains presently available, we find that most members of a genus have a codon composition most similar to other members of its genus, although not necessarily other members of its species.
The stable traits of melanoma genetics: an alternate approach to target discovery
Authors: Spivey Tara L , De Giorgi Valeria , Zhao Yingdong , Bedognetti Davide , Pos Zoltan , Liu Qiuzhen , Tomei Sara , Ascierto Maria Libera , Uccellini Lorenzo , Reinboth Jennifer , Chouchane Lotfi , Stroncek David F , Wang Ena , Marincola Francesco M
Published: April 2012

Background

The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number.

Results

Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis.

Conclusions

This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy.
Role of CD40 ligation in dendritic cell semimaturation
Authors: Gerlach Anna-Maria , Steimle Alexander , Krampen Lea , Wittmann Alexandra , Gronbach Kerstin , Geisel Julia , Autenrieth Ingo B , Frick Julia-Stefanie
Published: April 2012

Background

DC are among the first antigen presenting cells encountering bacteria at mucosal surfaces, and play an important role in maintenance of regular homeostasis in the intestine. Upon stimulation DC undergo activation and maturation and as initiators of T cell responses they have the capacity to stimulate naïve T cells. However, stimulation of naïve murine DC withB. vulgatusor LPS at low concentration drives DC to a semimature (sm) state with low surface expression of activation-markers and a reduced capacity to activate T-cells. Additionally, semimature DC are nonresponsive to subsequent TLR stimulation in terms of maturation, TNF-α but not IL-6 production. Ligation of CD40 is an important mechanism in enhancing DC maturation, function and capacity to activate T-cells. We investigated whether the DC semimaturation can be overcome by CD40 ligation.

Results

Upon CD40 ligation smDC secreted IL-12p40 but not the bioactive heterodimer IL-12p70. Additionally, CD40 ligation of smDC resulted in an increased production of IL-6 but not in an increased expression of CD40. Analysis of the phosphorylation pattern of MAP kinases showed that in smDC the p38 phosphorylation induced by CD40 ligation is inhibited. In contrast, phosphorylation of ERK upon CD40 ligation was independent of the DC maturation state.

Conclusion

Our data show that the semimature differentiation state of DC can not be overcome by CD40 ligation. We suggest that the inability of CD40 ligation in overcoming DC semimaturation might contribute to the tolerogenic phenotype of semimature DC and at least partially account for maintenance of intestinal immune homeostasis.
Inhibitory effect of Bifidobacterium infantis-mediated sKDR prokaryotic expression system on angiogenesis and growth of Lewis lung cancer in mice
Authors: Li Zhao-Jun , Zhu Hong , Ma Bu-Yun , Zhao Fen , Mao Shu-Hua , Liu Tai-Guo , He Jian-Ping , Deng Li-Cong , Yi Cheng , Huang Ying
Published: April 2012

Background

To construct the Bifidobacterium infantis-mediated soluble kinase insert domain receptor (sKDR) prokaryotic expression system and to observe its inhibitory effect on growth of human umbilicus vessel endothelial cells (HUVECs) in vitro and Lewis lung cancer (LLC) on mice in vivo.

Methods

The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed through electroporation and subsequently identified through PCR and Western blot analysis. HUVECs were added to the products of this system to evaluate the anti-angiogenesis effect through MTT assay in vitro. The LLC mice models were divided into three groups: one group treated with saline (group a); one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT plasmid group (group b); and one group treated with recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid group (group c). The quality of life and survival of mice were recorded. Tumor volume, tumor weight, inhibitive rate, and necrosis rate of tumor were also evaluated. Necrosis of tumor and signals of blood flow in tumors were detected through color Doppler ultrasound. In addition, microvessel density (MVD) of the tumor tissues was assessed through CD31 immunohistochemical analysis.

Results

The positively transformed Bifidobacterium infantis with recombinant pTRKH2-PsT/sKDR plasmid was established, and was able to express sKDR at gene and protein levels. The proliferation of HUVECs cultivated with the extract of positively transformed bacteria was inhibited significantly compared with other groups (P < 0. 05). The quality of life of mice in group c was better than in group a and b. The recombinant Bifidobacterium infantis containing pTRKH2-PsT/sKDR plasmid enhanced the efficacy of tumor growth suppression and prolongation of survival, increased the necrosis rate of tumor significantly, and could obviously decrease MVD and the signals of blood flow in tumors.

Conclusion

The Bifidobacterium infantis-mediated sKDR prokaryotic expression system was constructed successfully. This system could express sKDR at gene and protein levels and significantly inhibit the growth of HUVECs induced by VEGF in vitro. Moreover, it could inhibit tumor growth and safely prolong the survival time of LLC C57BL/6 mice.
The use of complementary and alternative medicine by people with cardiovascular disease: a systematic review
Authors: Grant Suzanne J , Bin Yu Sun , Kiat Hosen , Chang Dennis Hsu-Tung
Published: April 2012

Background

Complementary and alternative medicine (CAM) may offer benefits as well as risks to people with cardiovascular disease. Understanding the prevalence and the nature of CAM use will encourage beneficial CAM therapies, prevent potential herb-drug interactions and foster communication between patients and physicians.

Methods

A systematic search of eight bibliographic databases was conducted for studies that investigated CAM use in patients with cardiovascular diseases. Two independent reviewers selected relevant abstracts and evaluated the quality of included studies.

Results

Twenty-seven studies were included. Prevalence of CAM use in cardiac patients ranged from 4% - 61%. Biologically-based therapies usage ranged from 22% to 68%. Herbal medicines were used by between 2% and 46%. A large proportion of patients did not inform medical practitioners about their CAM use and up to 90% of treating physicians did not discuss CAM use with their patients.

Conclusions

CAM use in patients with cardiovascular disease appears common. The findings suggest that the effects of CAM on medical management of cardiovascular disease may be overlooked and that patient-physician communication need to be strengthened.
Reliability and validity of the Korean standard pattern identification for stroke (K-SPI-Stroke) questionnaire
Authors: Kang Byoung-Kab , Park Tae-Yong , Lee Ju Ah , Moon Tae-Woong , Ko Mi Mi , Choi Jiae , Lee Myeong Soo
Published: April 2012

Background

The present study was conducted to examine the reliability and validity of the ‘Korean Standard Pattern Identification for Stroke (K-SPI-Stroke)’, which was developed and evaluated within the context of traditional Korean medicine (TKM).

Methods

Between September 2006 and December 2010, 2,905 patients from 11 Korean medical hospitals were asked to complete the K-SPI-Stroke questionnaire as a part of project ' Fundamental study for the standardization and objectification of pattern identification in traditional Korean medicine for stroke (SOPI-Stroke). Each patient was independently diagnosed by two TKM physicians from the same site according to one of four patterns, as suggested by the Korea Institute of Oriental Medicine: 1) a Qi deficiency pattern, 2) a Dampness-phlegm pattern, 3) a Yin deficiency pattern, or 4) a Fire-heat pattern. We estimated the internal consistency using Cronbach’s α coefficient, the discriminant validity using the means score of patterns, and the predictive validity using the classification accuracy of the K-SPI-Stroke questionnaire.

Results

The K-SPI-Stroke questionnaire had satisfactory internal consistency (α = 0.700) and validity, with significant differences in the mean of scores among the four patterns. The overall classification accuracy of this questionnaire was 65.2 %.

Conclusion

These results suggest that the K-SPI-Stroke questionnaire is a reliable and valid instrument for estimating the severity of the four patterns.
Using routine data to monitor inequalities in an acute trust: a retrospective study
Authors: Langford Katharine M , Bottle Alex , Aylin Paul P , Ward Helen
Published: April 2012

Background

Reducing inequalities is one of the priorities of the National Health Service. However, there is no standard system for monitoring inequalities in the care provided by acute trusts. We explore the feasibility of monitoring inequalities within an acute trust using routine data.

Methods

A retrospective study of hospital episode statistics from one acute trust in London over three years (2007 to 2010). Waiting times, length of stay and readmission rates were described for seven common surgical procedures. Inequalities by age, sex, ethnicity and social deprivation were examined using multiple logistic regression, adjusting for the other socio-demographic variables and comorbidities. Sample size calculations were computed to estimate how many years of data would be ideal for this analysis.

Results

This study found that even in a large acute trust, there was not enough power to detect differences between subgroups. There was little evidence of inequalities for the outcome and process measures examined, statistically significant differences by age, sex, ethnicity or deprivation were only found in 11 out of 80 analyses. Bariatric surgery patients who were black African or Caribbean were more likely than white patients to experience a prolonged wait (longer than 64 days, aOR = 2.47, 95% CI: 1.36-4.49). Following a coronary angioplasty, patients from more deprived areas were more likely to have had a prolonged length of stay (aOR = 1.66, 95% CI: 1.25-2.20).

Conclusions

This study found difficulties in using routine data to identify inequalities on a trust level. Little evidence of inequalities in waiting time, length of stay or readmission rates by sex, ethnicity or social deprivation were identified although some differences were identified which warrant further investigation. Even with three years of data from a large trust there was little power to detect inequalities by procedure. Data will therefore need to be pooled from multiple trusts to detect inequalities.
Central obesity is important but not essential component of the metabolic syndrome for predicting diabetes mellitus in a hypertensive family-based cohort. Results from the Stanford Asia-pacific program for hypertension and insulin resistance (SAPPHIRe) Taiwan follow-up study
Authors: Lee I-Te , Chiu Yen-Feng , Hwu Chii-Min , He Chih-Tsueng , Chiang Fu-Tien , Lin Yu-Chun , Assimes Themistocles , Curb J David , Sheu Wayne H-H
Published: April 2012

Background

Metabolic abnormalities have a cumulative effect on development of diabetes, but only central obesity has been defined as the essential criterion of metabolic syndrome (MetS) by the International Diabetes Federation. We hypothesized that central obesity contributes to a higher risk of new-onset diabetes than other metabolic abnormalities in the hypertensive families.

Methods

Non-diabetic Chinese were enrolled and MetS components were assessed to establish baseline data in a hypertensive family-based cohort study. Based on medical records and glucose tolerance test (OGTT), the cumulative incidence of diabetes was analyzed in this five-year study by Cox regression models. Contribution of central obesity to development of new-onset diabetes was assessed in subjects with the same number of positive MetS components.

Results

Among the total of 595 subjects who completed the assessment, 125 (21.0%) developed diabetes. Incidence of diabetes increased in direct proportion to the number of positive MetS components (P ≪ 0.001). Although subjects with central obesity had a higher incidence of diabetes than those without (55.7 vs. 30.0 events/1000 person-years, P ≪ 0.001), the difference became non-significant after adjusting of the number of positive MetS components (hazard ratio = 0.72, 95%CI: 0.45-1.13). Furthermore, in all participants with three positive MetS components, there was no difference in the incidence of diabetes between subjects with and without central obesity (hazard ratio = 1.04, 95%CI: 0.50-2.16).

Conclusion

In Chinese hypertensive families, the incidence of diabetes in subjects without central obesity was similar to that in subjects with central obesity when they also had the same number of positive MetS components. We suggest that central obesity is very important, but not the essential component of the metabolic syndrome for predicting of new-onset diabetes. (Trial registration: NCT00260910, ClinicalTrials.gov).
Molecular mechanism implicated in Pemetrexed-induced apoptosis in human melanoma cells
Authors: Buqué Aitziber , Muhialdin Jangi Sh , Muñoz Alberto , Calvo Begoña , Carrera Sergio , Aresti Unai , Sancho Aintzane , Rubio Itziar , López-Vivanco Guillermo
Published: April 2012

Background

Metastatic melanoma is a lethal skin cancer and its incidence is rising every year. It represents a challenge for oncologist, as the current treatment options are non-curative in the majority of cases; therefore, the effort to find and/or develop novel compounds is mandatory. Pemetrexed (Alimta®, MTA) is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. It is currently used in the treatment of mesothelioma and non-small cell lung cancer (NSCLC), and has shown clinical activity in other tumors such as breast, colorectal, bladder, cervical, gastric and pancreatic cancer. However, its effect in human melanoma has not been studied yet.

Results

In the current work we studied the effect of MTA on four human melanoma cell lines A375, Hs294T, HT144 and MeWo and in two NSCLC cell lines H1299 and Calu-3. We have found that MTA induces DNA damage, S-phase cell cycle arrest, and caspase- dependent and –independent apoptosis. We show that an increment of the intracellular reactive oxygen species (ROS) and p53 is required for MTA-induced cytotoxicity by utilizing N-Acetyl-L-Cysteine (NAC) to blockage of ROS and p53-defective H1299 NSCLC cell line. Pretreatment of melanoma cells with NAC significantly decreased the DNA damage, p53 up-regulation and cytotoxic effect of MTA. MTA was able to induce p53 expression leading to up-regulation of p53-dependent genes Mcl-1 and PIDD, followed by a postranscriptional regulation of Mcl-1 improving apoptosis.

Conclusions

We found that MTA induced DNA damage and mitochondrial-mediated apoptosis in human melanoma cells in vitro and that the associated apoptosis was both caspase-dependent and –independent and p53-mediated. Our data suggest that MTA may be of therapeutic relevance for the future treatment of human malignant melanoma.
Runx2 mediates epigenetic silencing of the bone morphogenetic protein-3B (BMP-3B/GDF10) in lung cancer cells
Authors: Tandon Manish , Gokul Karthiga , Ali Syed A , Chen Zujian , Lian Jane , Stein Gary S , Pratap Jitesh
Published: April 2012

Background

The Runt-related transcription factor Runx2 is essential for bone development but is also implicated in progression of several cancers of breast, prostate and bone, where it activates cancer-related genes and promotes invasive properties. The transforming growth factor β (TGF-β) family member bone morphogenetic protein-3B (BMP-3B/GDF10) is regarded as a tumor growth inhibitor and a gene silenced in lung cancers; however the regulatory mechanisms leading to its silencing have not been identified.

Results

Here we show that Runx2 is highly expressed in lung cancer cells and downregulates BMP-3B. This inverse relationship between Runx2 and BMP-3B expression is further supported by increased expression of BMP-3B in mesenchymal cells from Runx2 deficient mice. The ectopic expression of Runx2, but not DNA binding mutant Runx2, in normal lung fibroblast cells and lung cancer cells resulted in suppression of BMP-3B levels. The chromatin immunoprecipitation studies identified that the mechanism of Runx2-mediated suppression of BMP-3B is due to the recruitment of Runx2 and histone H3K9-specific methyltransferase Suv39h1 to BMP-3B proximal promoter and a concomitant increase in histone methylation (H3K9) status. The knockdown of Runx2 in H1299 cells resulted in decreased histone H3K9 methylation on BMP-3B promoter and increased BMP-3B expression levels. Furthermore, co-immunoprecipitation studies showed a direct interaction of Runx2 and Suv39h1 proteins. Phenotypically, Runx2 overexpression in H1299 cells increased wound healing response to TGFβ treatment.

Conclusions

Our studies identified BMP-3B as a new Runx2 target gene and revealed a novel function of Runx2 in silencing of BMP-3B in lung cancers. Our results suggest that Runx2 is a potential therapeutic target to block tumor suppressor gene silencing in lung cancer cells.
Nuclear overexpression of metastasis-associated protein 1 correlates significantly with poor survival in nasopharyngeal carcinoma
Authors: Li Wen-Fei , Liu Na , Cui Rui-Xue , He Qing-Mei , Chen Mo , Jiang Ning , Sun Ying , Zeng Jing , Liu Li-Zhi , Ma Jun
Published: April 2012

Background

Metastasis-associated protein 1 (MTA1) has been associated with poor prognosis in several malignant carcinomas. The purpose of this study was to investigate the expression and prognostic value of MTA1 in nasopharyngeal carcinoma (NPC).

Methods

MTA1 expression was assessed using immunohistochemistry in paraffin-embedded tumor specimens from 208 untreated NPC patients. Cox regression analysis was used to calculate the hazard ratio (HR), 95% confidence interval (CI) and identify independent prognostic factors, and recursive partitioning analysis was used to create a decision tree.

Results

Nuclear overexpression of MTA1 was observed in 48.6% (101/208) of the NPC tissues. Nuclear overexpression of MTA1 correlated positively with N classification (P= 0.02), clinical stage (P= 0.04), distant metastasis (P< 0.01) and death (P= 0.01). Additionally, nuclear overexpression of MTA1 correlated significantly with poorer distant metastasis-free survival (DMFS;P<0.01) and poorer overall survival (OS;P< 0.01). MTA1 had prognostic significance in NPC patients with stage II disease, but not stage III or IV disease. Multivariate analysis demonstrated that nuclear overexpression of MTA1 was independently associated with poorer DMFS (HR, 2.05; 95% CI, 1.13–3.72;P= 0.02) and poorer OS (HR, 1.98; 95% CI, 1.09–3.59;P= 0.03). Using recursive partitioning analysis, the NPC patients could be classified with a low, intermediate or high risk of distant metastasis and death, on the basis of clinical stage, age and MTA1 expression.

Conclusion

The results of this study suggest that nuclear overexpression of MTA1 correlates significantly with poorer DMFS and poorer OS in NPC. MTA1 has potential as a novel prognostic biomarker in NPC.
Carbon-modified TiO2 for photocatalysis
Authors: Wojtoniszak Malgorzata , Dolat Diana , Morawski Antoni , Mijowska Ewa
Published: April 2012

Here we present a method to produce TiO2 nanocrystals coated by thin layer of graphitic carbon. The coating process was prepared via chemical vapor deposition (CVD) with acetylene used as a carbon feedstock with TiO2 used as a substrate. Different temperatures (400°C and 500°C) and times (10, 20, and 60 s) of reaction were explored. The prepared nanocomposites were investigated by means of transmission electron microscopy, Raman spectroscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy/diffuse reflectance spectroscopy and ultraviolet-vis (UV-vis)/diffuse reflectance spectroscopy. Furthermore, photocatalytic activity of the materials was investigated under visible and UV-vis light irradiation in the process of phenol decomposition. It was found that TiO2 modification with carbon resulted in a significant increase of photoactivity under visible irradiation and decrease under UV-vis light irradiation. Interestingly, a shorter CVD time and higher process temperature resulted in the preparation of the samples exhibiting higher activity in the photocatalytic process under visible light irradiation.
Face recognition using nonparametric-weighted Fisherfaces
Authors: Li Dong-Lin , Prasad Mukesh , Hsu Sheng-Chih , Hong Chao-Ting , Lin Chin-Teng
Published: April 2012

This study presents an appearance-based face recognition scheme called the nonparametric-weighted Fisherfaces (NW-Fisherfaces). Pixels in a facial image are considered as coordinates in a high-dimensional space and are transformed into a face subspace for analysis by using nonparametric-weighted feature extraction (NWFE). According to previous studies of hyperspectral image classification, NWFE is a powerful tool for extracting hyperspectral image features. The Fisherfaces method maximizes the ratio of between-class scatter to that of within-class scatter. In this study, the proposed NW-Fisherfaces weighted the between-class scatter to emphasize the boundary structure of the transformed face subspace and, therefore, enhances the separability for different persons' face. The proposed NW-Fisherfaces was compared with Orthogonal Laplacianfaces, Eigenfaces, Fisherfaces, direct linear discriminant analysis, and null space linear discriminant analysis methods for tests on five facial databases. Experimental results showed that the proposed approach outperforms other feature extraction methods for most databases.
Immunoadsorption therapy in patients with multiple sclerosis with steroid-refractory optical neuritis
Authors: Koziolek Michael J , Tampe Desiree , Bähr Matthias , Dihazi Hassan , Jung Klaus , Fitzner Dirk , Klingel Reinhard , Müller Gerhard A , Kitze Bernd
Published: April 2012

Background

In multiple sclerosis relapses refractory to intravenous corticosteroid therapy, plasma exchange is recommended. Immunoadsorption (IA) is regarded as an alternative therapy, but its efficacy and putative mechanism of action still needs to be established.

Methods

We prospectively treated 11 patients with multiple sclerosis who had optical neuritis and fulfilled the indications for apheresis therapy (Trial registration DE/CA25/00007080-00). In total, five IA treatments were performed using tryptophan-IA. Clinical activity (visual acuity, Expanded Disability Status Scale, Incapacity Status Scale), laboratory values and visual evoked potentials were measured before, during and after IA, with a follow-up of six months. Moreover, proteomic analyses were performed to analyze column-bound proteins as well as corresponding changes in patients’ sera.

Results

After the third IA, we detected an improvement of vision in eight of eleven patients, whom we termed responders. Amongst these, the mean visual acuity improved from 0.15 ± 0.12 at baseline to 0.47 ± 0.32 after the third IA (P = 0.0252) up to 0.89 ± 0.15 (P < 0.0001) at day 180 ± 10 after IA. Soluble interleukin-2 receptor decreased in responders (P = 0.03), whereas in non-responders it did not. Proteomic analyses of proteins adsorbed to IA columns revealed that several significant immunological proteins as well as central nervous system protein fragments, including myelin basic protein, had been removed by IA.

Conclusions

IA was effective in the treatment of corticosteroid-refractory optic neuritis. IA influenced the humoral immune response. Strikingly, however, we found strong evidence that demyelination products and immunological mediators were also cleared from plasma by IA.
Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function
Authors: Meuwissen Pieter J , Stolp Bettina , Iannucci Veronica , Vermeire Jolien , Naessens Evelien , Saksela Kalle , Geyer Matthias , Vanham Guido , Arien Kevin K , Fackler Oliver T , Verhasselt Bruno
Published: April 2012

Background

The Nef protein of HIV facilitates virus replication and disease progression in infected patients. This role as pathogenesis factor depends on several genetically separable Nef functions that are mediated by interactions of highly conserved protein-protein interaction motifs with different host cell proteins. By studying the functionality of a series of nef alleles from clinical isolates, we identified a dysfunctional HIV group O Nef in which a highly conserved valine-glycine-phenylalanine (VGF) region, which links a preceding acidic cluster with the following proline-rich motif into an amphipathic surface was deleted. In this study, we aimed to study the functional importance of this VGF region.

Results

The dysfunctional HIV group O8 nef allele was restored to the consensus sequence, and mutants of canonical (NL4.3, NA-7, SF2) and non-canonical (B2 and C1422) HIV-1 group M nef alleles were generated in which the amino acids of the VGF region were changed into alanines (VGF→AAA) and tested for their capacity to interfere with surface receptor trafficking, signal transduction and enhancement of viral replication and infectivity. We found the VGF motif, and each individual amino acid of this motif, to be critical for downregulation of MHC-I and CXCR4. Moreover, Nef’s association with the cellular p21-activated kinase 2 (PAK2), the resulting deregulation of cofilin and inhibition of host cell actin remodeling, and targeting of Lck kinase to the trans-golgi-network (TGN) were affected as well. Of particular interest, VGF integrity was essential for Nef-mediated enhancement of HIV virion infectivity and HIV replication in peripheral blood lymphocytes. For targeting of Lck kinase to the TGN and viral infectivity, especially the phenylalanine of the triplet was essential. At the molecular level, the VGF motif was required for the physical interaction of the adjacent proline-rich motif with Hck.

Conclusion

Based on these findings, we propose that this highly conserved three amino acid VGF motif together with the acidic cluster and the proline-rich motif form a previously unrecognized amphipathic surface on Nef. This surface appears to be essential for the majority of Nef functions and thus represents a prime target for the pharmacological inhibition of Nef.
Distinct Degree of Radiculopathy at Different Levels of Peripheral Nerve Injury
Authors: Takiguchi Noboru , Yoshida Munehito , Taniguchi Wataru , Hashizume Hiroshi , Yamada Hiroshi , Miyazaki Nobuyuki , Nishio Naoko , Nakatsuka Terumasa
Published: April 2012

Background:

Lumbar radiculopathy is a common clinical problem, characterized by dorsal root ganglion (DRG) injury and neural hyperactivity causing intense pain. However, the mechanisms involved in DRG injury have not been fully elucidated. Furthermore, little is known about the degree of radiculopathy at the various levels of nerve injury. The purpose of this study is to compare the degree of radiculopathy injury at the DRG and radiculopathy injury proximal or distal to the DRG.

Results:

The lumbar radiculopathy rat model was created by ligating the L5 nerve root 2 mm proximal to the DRG or 2 mm distal to the DRG with 6.0 silk. We examined the degree of the radiculopathy using different points of mechanical sensitivity, immunohistochemistry and in vivo patch-clamp recordings, 7 days after surgery. The rats injured distal to the DRG were more sensitive than those rats injured proximal to the DRG in the behavioral study. The number of activated microglia in laminas I–II of the L5 segmental level was significantly increased in rats injured distal to the DRG when compared with rats injured proximal to the DRG. The amplitudes and frequencies of EPSC in the rats injured distal to the DRG were higher than those injured proximal to the DRG. The results indicated that there is a different degree of radiculopathy at the distal level of nerve injury.

Conclusions:

Our study examined the degree of radiculopathy at different levels of nerve injury. Severe radiculopathy occurred in rats injured distal to the DRG when compared with rats injured proximal to the DRG. This finding helps to correctly diagnose a radiculopathy.
Network Dynamics in Nociceptive Pathways Assessed by the Neuronal Avalanche Model
Authors: Wu José Jiun-Shian , Shih Hsi-Chien , Yen Chen-Tung , Shyu Bai-Chuang
Published: April 2012

Background:

Traditional electroencephalography provides a critical assessment of pain responses. The perception of pain, however, may involve a series of signal transmission pathways in higher cortical function. Recent studies have shown that a mathematical method, the neuronal avalanche model, may be applied to evaluate higher-order network dynamics. The neuronal avalanche is a cascade of neuronal activity, the size distribution of which can be approximated by a power law relationship manifested by the slope of a straight line (i.e., the α value). We investigated whether the neuronal avalanche could be a useful index for nociceptive assessment.

Findings:

Neuronal activity was recorded with a 4 × 8 multichannel electrode array in the primary somatosensory cortex (S1) and anterior cingulate cortex (ACC). Under light anesthesia, peripheral pinch stimulation increased the slope of the α value in both the ACC and S1, whereas brush stimulation increased the α value only in the S1. The increase in α values was blocked in both regions under deep anesthesia. The increase in α values in the ACC induced by peripheral pinch stimulation was blocked by medial thalamic lesion, but the increase in α values in the S1 induced by brush and pinch stimulation was not affected.

Conclusions:

The neuronal avalanche model shows a critical state in the cortical network for noxious-related signal processing. The α value may provide an index of brain network activity that distinguishes the responses to somatic stimuli from the control state. These network dynamics may be valuable for the evaluation of acute nociceptive processes and may be applied to chronic pathological pain conditions.
Associations between a neurophysiological marker of central cholinergic activity and cognitive functions in young and older adults
Authors: Young-Bernier Marielle , Kamil Yael , Tremblay François , Davidson Patrick S R
Published: April 2012

Background

The deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging.

Methods

We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31).

Results

We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions.

Conclusion

Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging.
Ubiquitous presence of piscidin-1 in Atlantic cod as evidenced by immunolocalisation
Authors: Ruangsri Jareeporn , Fernandes Jorge M O , Rombout Jan H W M , Brinchmann Monica F , Kiron Viswanath
Published: April 2012

Background

Antimicrobial peptides (AMPs), the natural antibiotics bestowed upon all forms of life, consist of small molecular weight proteins with a broad spectrum antimicrobial activity against a variety of pathogenic microorganisms. Piscidins are one of the AMP families that are imperative for the innate defence mechanisms of teleosts. Atlantic cod, a basal fish belonging to the superorder Paracanthopterygii also possesses multiple piscidin peptides. Two piscidin paralogues (pis1 and pis2) and a novel alternative splice variant of pis2 of this fish were previously described by us. To shed light on other potent roles of these molecules, now we have mapped the distribution of piscidin 1 (Pis1), in different tissues and organs of cod through immunohistochemistry (IHC) employing an affinity purified polyclonal antibody specific to Pis1.

Results

Various cell types and tissues of Atlantic cod including those from the immune organs of naïve fish are armed with Pis1 peptide. Different types of the blood leucocytes and phagocytic cells among the leucocytes examined gave a relatively strong indication of Pis1 immunopositivity. In addition, other cell types such as hematopoietic cells, epithelial cells and multi-granular cells located in the mucosal and hematopoietic tissues were also Pis1-immunoreactive. More interestingly, chondrocytes appear to produce Pis1 and this is the first report on the presence of an AMP in cartilage tissue of fish. Furthermore, Pis1 immunopositivity was detected in other tissues and organs of naïve fish including neural tissues, exocrine and endocrine glands, compound gland cells, excretory kidney, intestinal and respiratory epithelial cells, swim bladder, skin and hypodermis layer, myosepta, liver, heart, eye and oocytes.

Conclusions

Pis1 peptide is produced by various cell types located in different tissues and organs of Atlantic cod. It is present in all immune-related organs of naïve fish and the elevated peptide expression following phagocytosis strongly suggest their involvement in innate defence. Further, its widespread occurrence in non-immune tissues and organs of apparently healthy fish implies that piscidin may have other functions in addition to its role as an immune effector molecule.