bluuebunny/crossref_metadata_2025 huggingface dataset:
Systems Thinking Tools as Applied to Community-Based Participatory Research
Authors: BeLue Rhonda , Carmack Chakema , Myers Kyle R. , Weinreb-Welch Laurie , Lengerich Eugene J.
Published: March 2012

Community-based participatory research (CBPR) is being used increasingly to address health disparities and complex health issues. The authors propose that CBPR can benefit from a systems science framework to represent the complex and dynamic characteristics of a community and identify intervention points and potential “tipping points.” Systems science refers to a field of study that posits a holistic framework that is focused on component parts of a system in the context of relationships with each other and with other systems. Systems thinking tools can assist in intervention planning by allowing all CBPR stakeholders to visualize how community factors are interrelated and by potentially identifying the most salient intervention points. To demonstrate the potential utility of systems science tools in CBPR, the authors show the use of causal loop diagrams by a community coalition engaged in CBPR activities regarding youth drinking reduction and prevention.
Employer-Provided Health Insurance and the Adverse Selection Problem
Authors: Castaneda Marco A. , Marton James
Published: March 2012

The role of employers in the health insurance market in the United States is substantial, but there is little formal analysis investigating how the introduction of employers affects the structure of equilibrium contracts in the health insurance market. In this article, the authors present and analyze a model of employer-provided health insurance and show that if the labor market is competitive, the equilibrium must be a separating equilibrium, as in the standard model. The key to this result is that insurance companies and employers have similar incentives because health insurance is an important component of total compensation. In addition, the authors show that if workers bargain collectively for employment contracts, the equilibrium can be a separating or a pooling equilibrium, but in any equilibrium, the low risks obtain more insurance than in the standard model and subsidize the insurance premiums of the high risks.
Prevalence of intestinal parasites in private-household cats in Japan
Authors: Itoh Naoyuki , Ikegami Hiroshi , Takagi Masahiro , Ito Yoichi , Kanai Kazutaka , Chikazawa Seishiro , Hori Yasutomo , Hoshi Fumio , Higuchi Seiichi
Published: March 2012

The present study is the first national investigation of intestinal parasites in private-household cats in Japan. A total of 942 faecal samples were collected from private-household cats. Giardia species was assessed using an enzyme-linked immunosorbent assay kit and other intestinal parasites were identified microscopically. The overall prevalence of intestinal parasites was 10.1%; two protozoan parasites ( Giardia species and Cystoisospora species) and five helminths ( Toxocara cati, Toxascaris leonina, Ancylostoma tubaeforme, Taenia species and Spirometra erinacei) were detected. The total prevalence of intestinal parasite infection was significantly higher in cats aged ≤6 months old than in cats older than 6 months because of a significantly higher prevalence of Cystoisospora species and T cati. The total infection prevalence was higher among outdoor cats as a result of the significantly higher prevalence of T cati and S erinacei. Sex and faecal condition were not related to intestinal parasite infections. Regional differences were observed in Cystoisospora species and A tubaeforme.
3D GRASE arterial spin labelling reveals an inverse correlation of cortical perfusion with the white matter lesion volume in MS
Authors: Amann Michael , Achtnichts Lutz , Hirsch Jochen G , Naegelin Yvonne , Gregori Johannes , Weier Katrin , Thöni Alain , Mueller-Lenke Nicole , Radue Ernst-Wilhelm , Günther Matthias , Kappos Ludwig , Gass Achim
Published: March 2012

Background:

We hypothesized that in multiple sclerosis (MS) patients, reduced cortical perfusion is associated with chronic white matter injury.

Objective:

To investigate the influence of different clinical and magnetic resonance imaging characteristics on cortical perfusion.

Methods:

Cerebral blood flow (CBF) was assessed by applying a pulsed arterial spin labelling (ASL) technique combined with single-shot 3D-GRASE (gradient-spin echo) in a cohort of 165 MS patients with a relapsing–remitting ( n=123) or secondary progressive disease course ( n=42). Mean age was 45.4 years (20–68 years), mean disease duration was 14.2 years (1–48 years).

Results:

Mean cortical CBF was 45.6 ml/100g per min (SD: 7.8 ml/100g per min). Stepwise multiple linear regression models were calculated to investigate the relationship between different factor sets and mean CBF. The model with the highest adjusted coefficient of determination included T2 lesion load, age, gender and disease duration as significant factors. Post-hoc Spearman rank correlation revealed significant correlation of adjusted CBF with T2 lesion load (t=−0.35, p=1*10–6), with age (t =−0.34, p=4*10–6), and with disease duration (t=0.16, p=0.03), while Expanded Disability Status Scale (EDSS) did not reach significance in either model.

Conclusion:

This study suggests that the amount of white matter lesions indicates a reduced metabolic demand and reduced perfusion at a cortical level.
Predicting resistance to health education messages for cannabis use: The role of rebelliousness, autic mastery, health value and ethnicity
Authors: Boddington Ellen L , McDermott Mark R
Published: March 2012

The prevalent use of cannabis by adolescents and young adults, combined with the common misconception that smoking cannabis is relatively harmless, warrants the exploration of factors influencing resistance to health education messages about cannabis use. This investigation did so within a Reversal Theory framework. One hundred and thirteen undergraduate students responded to an informative leaflet detailing the health effects of smoking cannabis. The most significant independent predictor of message resistance was frequency of cannabis use, followed by proactive rebelliousness, autic mastery, health value and ethnicity. These findings have implications for the development, design and targeting of cannabis health education programmes.
Deterioration of endothelial function and carotid intima-media thickness in Tibetan male adolescents exposed to second-hand smoke
Authors: Yang Bo , Li Min , Chen Bin , Xu Yong , Li Tian-De
Published: March 2012

Introduction:

It has been commonly accepted that second-hand smoke (SHS) is associated with atherosclerosis and endothelial dysfunction. There is growing evidence that the changes might begin in childhood. Unfortunately, no study has focused on the early atherosclerosis of Tibetan adolescents exposed to SHS.

Aims:

We aimed to investigate the endothelial function and carotid atherosclerosis in healthy school-aged Tibetan male adolescents.

Materials and methods:

All passive smoking participants (SHS) were students were 16 years old and male, and were recruited through middle schools in Lhasa city. In total 624 subjects were accepted after excluding subjects who actively smoked. The adolescents were divided into three groups according to serum cotinine level: high cotinine group (High Group) with 205 boys, intermediate cotinine group (Intermediate Group) with 210 boys, and low cotinine group (Low Group) with 209 boys. Venous blood was sampled for the measurement of cotinine concentration, lipid profile and endothelin-1 (ET-1) quantitation. High-resolution B-mode ultrasonography was performed to evaluate carotid intima-media thickness (cIMT) and intima smoothness. The invasive vascular endothelial function was evaluated through the measurement of flow-mediated dilation (FMD) with B-mode ultrasound and ankle-brachial index (ABI) by using a blood pressure cuff and a Doppler instrument.

Results:

No statistical significance was found between groups in total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, ApoA-I, systolic blood pressure, diastolic blood pressure, and heart rate ( p>0.05). In the lipid profile, only apolipoprotein B (ApoB) values were different between groups: ApoB in the High Group was higher than in the Low Group ( p=0.0164). Plasma ET-1 concentrations in the High Group were also much higher than in the Intermediate and Low Groups ( p=0.0112, p<0.001). The cIMT and intima smoothness had deteriorated in the High Group compared with the Low Group ( p<0.001 and p<0.05 respectively). FMD and ABI, which indicate vascular endothelial function, was decreased in the High Group compared with the Intermediate and Low Groups (FMD, p<0.001; ABI, p<0.001).

Conclusions:

SHS was associated with sub-clinical carotid atherosclerosis and endothelial dysfunction in Tibetan school-aged male adolescents. Considering the widespread exposure to SHS and the clinical relevance of early atherosclerosis, this result is of public health importance in Tibet, where health education is not satisfactory. Data from our study emphasize the importance of endorsing smoke-free environments for adolescents.
Interactive analysis of time intervals in a two-dimensional space
Authors: Qiang Yi , Delafontaine Matthias , Versichele Mathias , De Maeyer Philippe , Van de Weghe Nico
Published: March 2012

Time intervals are conventionally represented as linear segments in a one-dimensional space. An alternative representation of time intervals is the triangular model (TM), which represents time intervals as points in a two-dimensional space. In this paper, the use of TM in visualising and analysing time intervals is investigated. Not only does this model offer a compact visualisation of the distribution of intervals, it also supports an innovative temporal query mechanism that relies on geometries in the two-dimensional space. This query mechanism has the potential to simplify queries that are difficult to specify using traditional linear temporal query devices. Moreover, a software prototype that implements TM in a geographical information system (GIS) is introduced. This prototype has been applied in a real scenario to analyse time intervals that were detected by a Bluetooth tracking system. This application shows that TM has the potential to support a traditional GIS to analyse interval-based geographical data.
An Assessment of Community Capacity to Prevent Adolescent Alcohol Consumption
Authors: Williams Rebecca J. , Kittinger Daniela Spoto , Ta Van M. , Nihoa Wendy K. , Payne Christine , Nigg Claudio R.
Published: March 2012

To effectively address the issue of youth alcohol use, communities need to have sufficient infrastructure and capacity in place to operate effective prevention programs. This study evaluates community capacity in the state of Hawai’i, using the Capacity Assessment Survey administered to stakeholders in the youth alcohol prevention system. Capacity is quantified with gap scores, which measure the discrepancy between an agency’s performance of an attribute and the attribute’s relative importance. Six assessment areas, termed capacity domains, are defined. Results are given for each county and the state overall. Based on these results, communities need to prioritize capacity-building efforts specifically in the domains of effectiveness, funding/resource availability, and sustainability. Organization, workforce skills/knowledge, and cultural competency were categorized as relative strengths in comparison, but gap scores are nevertheless significantly greater than 0 (“ideal”; p < .001), indicating these areas need improvement as well. Suggestions for improvement in each capacity domain are given. This assessment is the first step in a five-step planning process to implement youth alcohol prevention programs in communities in Hawai’i.
Interview With Dr. Omar Khan, Noted Global Health Specialist
Authors: Simmons Rob , Khubchandani Jagdish
Published: March 2012

Dr. Khan has had a distinguished career in global health. He has served as a faculty member at the University of Vermont College of Medicine and Johns Hopkins University School of Public Health. He is currently a family medicine physician at Christiana Care Health System in Newark, Delaware, and is President of the Delaware Academy of Family Physicians. Dr. Khan has authored more than 55 peer-reviewed journal articles and book chapters and has conducted research and lead primary care and public health initiatives in numerous countries. Last year, Dr. Khan also coedited a book titled Megacities and Global Health sponsored by the American Public Health Association with Dr. Gregory Pappas, Deputy Health Commissioner for Washington, DC.
Community-Based Participatory Evaluation
Authors: Braithwaite Ronald L. , McKenzie Robetta D. , Pruitt Vikki , Holden Kisha B. , Aaron Katrina , Hollimon Chavone
Published: March 2012

The use of community-based participatory research has gained momentum as a viable approach to academic and community engagement for research over the past 20 years. This article discusses an approach for extending the process with an emphasis on evaluation of a community partnership–driven initiative and thus advances the concept of conducting community-based participatory evaluation (CBPE) through a model used by the Healthy Start project of the Augusta Partnership for Children, Inc., in Augusta, Georgia. Application of the CBPE approach advances the importance of bilateral engagements with consumers and academic evaluators. The CBPE model shows promise as a reliable and credible evaluation approach for community-level assessment of health promotion programs.
Feminist Approaches to Triangulation
Authors: Hesse-Biber Sharlene
Published: March 2012

This article explores the deployment of triangulation in the service of uncovering subjugated knowledge and promoting social change for women and other oppressed groups. Feminist approaches to mixed methods praxis create a tight link between the research problem and the research design. An analysis of selected case studies of feminist praxis explores the specific reasons feminist researchers employ triangulation, and the strengths and weaknesses they encountered in the process of implementing a mixed methods design.
Safety, pharmacokinetics and pharmacodynamics of four-hour intravenous infusions of eritoran in healthy Japanese and Caucasian men
Authors: Aikawa Naoki , Okubo Yoshio , Lynn Melvyn , Rossignol Daniel P , Wong Y Nancy , Schuck Edgar , Kitahara Yasumi , Nakano Tomohisa , Sivak Olena , Wasan Kishor M , Nagy Christa , Yen Mark
Published: March 2012

Eritoran, a synthetic analogue of lipid A, has been shown to bind to TLR4/MD-2 complex and thereby block the interaction of endotoxins with TLR4. We report here the results of a study conducted to assess the single-dose safety and tolerability, as well as the pharmacokinetics and pharmacodynamics, of eritoran infusion in Japanese and Caucasian healthy adult men. Sixty-four men (aged 20–45 years; body mass index 18–30 kg/m2) were randomized into four groups: 4-mg total dose (six Japanese and six Caucasian men); 12-mg total dose (12 Japanese and 12 Caucasian men); 28-mg total dose (six Japanese and six Caucasian men); and placebo (eight Japanese and eight Caucasian men). Eritoran in single doses up to 28 mg over 4 h was well tolerated, with no apparent ethnic differences noted. Plasma concentrations were slightly higher in Japanese versus Caucasian men; these differences were not significant after adjustment for differences in body mass (clearance: approximately 1.2 ml/h/kg; volume of distribution at steady state: approximately 0.07 l/kg). The ex vivo endotoxin inhibitory activity of eritoran was similar in Japanese and Caucasian men. The data do not indicate any need for clinical dose adjustment for possible ethnic-based differences in drug distribution or metabolism.
Interferon-inducible transmembrane proteins of the innate immune response act as membrane organizers by influencing clathrin and v-ATPase localization and function
Authors: Wee Yin Shen , Roundy Kirstin M , Weis Janis J , Weis John H
Published: March 2012

The innate response interferon-inducible transmembrane (Ifitm) proteins have been characterized as influencing proliferation, signaling complexes and restricting virus infections. Treatment of cells lacking these proteins ( IfitmDel) with IFN-β resulted in the loss of clathrin from membrane compartments and the inhibition of clathrin-mediated phagocytosis, suggesting a molecular interaction between clathrin and Ifitm proteins. The pH of endosomes of IfitmDel cells, with or without IFN activation, was neutralized, suggesting the function of the vacular ATPase proton pumps in such cells was compromised. Co-immunoprecipitation of Ifitm3 with Atp6v0b demonstrated a direct interaction between the Ifitm proteins and the v-ATPase. These data suggest that the Ifitm proteins help stabilize v-ATPase complexes in cellular membranes which, in turn, facilitates the appropriate subcellular localization of clathrin.
Neurostimulation for chronic cluster headache
Authors: Wolter Tilman , Kaube Holger
Published: March 2012

Neurostimulation techniques for the treatment of primary headache syndromes, particularly of chronic cluster headache, have received much interest in recent years. Occipital nerve stimulation (ONS) has yielded favourable clinical results and, despite the limited numbers of published cases, is becoming a routine treatment for refractory chronic cluster headache in specialized centres. Meanwhile, other promising techniques such as spinal cord stimulation (SCS) or sphenopalate ganglion stimulation have emerged. In this article the current state of clinical research for neurostimulation techniques for chronic cluster headache is reviewed.
Bone disease in primary hyperparathyrodism
Authors: Marcocci Claudio , Cianferotti Luisella , Cetani Filomena
Published: March 2012

Nowadays, primary hyperparathyroidism (PHPT) is mostly a mild disease. Overt skeletal manifestations are rare but decreased bone mineral density (BMD) can still be demonstrated. Even in mild cases, excess parathyroid hormone (PTH) increases bone turnover leading to bone loss particularly at cortical sites. Conversely, a relative preservation of cancellous bone has been shown by histomorphometric analyses and advanced imaging techniques. An increased fracture rate has been demonstrated in untreated patients with PHPT at peripheral sites and in the spine. Parathyroidectomy (PTx) is the definitive cure for PHPT. With the restoration of normal PTH, bone resorption is quickly tapered down, while bone formation proceeds at the level of bone multicellular units, which were activated prior to PTx. The rapid refilling of the enlarged remodeling space and the subsequent matrix mineralization will result in an increase in BMD at sites rich in trabecular bone, such as lumbar spine and hip, which mainly occurs during the first 6–12 months after PTx. Cortical bone is less responsive to PTX because of the low rate of bone turnover, but sensible increases in BMD at the distal third of the radius can be observed in the long term. PTx seems to decrease the risk of fractures but more data are needed before a definitive conclusion on this important matter can be reached. Treatment with bisphosphonates can be considered for patients with low BMD who do not undergo PTx. Two-year treatment with alendronate has been shown to decrease bone turnover markers and increase BMD at the lumbar spine and hip, but not at the distal radius. Cinacalcet stably decreased serum calcium levels across a broad range of PHPT severity, but no change in BMD occurred in patients treated for up to 5.5 years.
Eltrombopag, a thrombopoietin- receptor agonist in the treatment of adult chronic immune thrombocytopenia: a review of the efficacy and safety profile
Authors: Cheng Gregory
Published: March 2012

Chronic immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a low platelet count that has persisted for more than 12 months. Patients may be asymptomatic but those with severe disease may have significant morbidity and require treatment. Corticosteroids and intravenous immunoglobulin are recommended as first-line treatments. Recently, two thrombopoietin-receptor agonists, romiplostim and eltrombopag have been licensed for the treatment of chronic ITP. The current indications for thrombopoietin-receptor agonists are for splenectomized adult patients with chronic ITP who are refractory to other treatments and adult nonsplenectomized patients in whom splenectomy is contraindicated. This article reviews data on the pharmacology, clinical efficacy and safety profile of eltrombopag in the treatment of ITP.
Categorization of 77 dystrophinexons into 5 groups by a decision tree using indexes of splicing regulatory factors as decision markers
Authors: Malueka Rusdy Ghazali , Takaoka Yutaka , Yagi Mariko , Awano Hiroyuki , Lee Tomoko , Dwianingsih Ery Kus , Nishida Atsushi , Takeshima Yasuhiro , Matsuo Masafumi
Published: March 2012

Background

Duchenne muscular dystrophy, a fatal muscle-wasting disease, is characterized by dystrophin deficiency caused by mutations in the dystrophin gene. Skipping of a target dystrophin exon during splicing with antisense oligonucleotides is attracting much attention as the most plausible way to express dystrophin in DMD. Antisense oligonucleotides have been designed against splicing regulatory sequences such as splicing enhancer sequences of target exons. Recently, we reported that a chemical kinase inhibitor specifically enhances the skipping of mutated dystrophin exon 31, indicating the existence of exon-specific splicing regulatory systems. However, the basis for such individual regulatory systems is largely unknown. Here, we categorized the dystrophin exons in terms of their splicing regulatory factors.

Results

Using a computer-based machine learning system, we first constructed a decision tree separating 77 authentic from 14 known cryptic exons using 25 indexes of splicing regulatory factors as decision markers. We evaluated the classification accuracy of a novel cryptic exon (exon 11a) identified in this study. However, the tree mislabeled exon 11a as a true exon. Therefore, we re-constructed the decision tree to separate all 15 cryptic exons. The revised decision tree categorized the 77 authentic exons into five groups. Furthermore, all nine disease-associated novel exons were successfully categorized as exons, validating the decision tree. One group, consisting of 30 exons, was characterized by a high density of exonic splicing enhancer sequences. This suggests that AOs targeting splicing enhancer sequences would efficiently induce skipping of exons belonging to this group.

Conclusions

The decision tree categorized the 77 authentic exons into five groups. Our classification may help to establish the strategy for exon skipping therapy for Duchenne muscular dystrophy.
De novo sequencing and characterization of Picrorhiza kurrooa transcriptome at two temperatures showed major transcriptome adjustments
Authors: Gahlan Parul , Singh Heikham Russiachand , Shankar Ravi , Sharma Niharika , Kumari Anita , Chawla Vandna , Ahuja Paramvir Singh , Kumar Sanjay
Published: March 2012

Background

Picrorhiza kurrooa Royle ex Benth. is an endangered plant species of medicinal importance. The medicinal property is attributed to monoterpenoids picroside I and II, which are modulated by temperature. The transcriptome information of this species is limited with the availability of few hundreds of expressed sequence tags (ESTs) in the public databases. In order to gain insight into temperature mediated molecular changes, high throughput de novo transcriptome sequencing and analyses were carried out at 15°C and 25°C, the temperatures known to modulate picrosides content.

Results

Using paired-end (PE) Illumina sequencing technology, a total of 20,593,412 and 44,229,272 PE reads were obtained after quality filtering for 15°C and 25°C, respectively. Available (e.g., De-Bruijn/Eulerian graph) and in-house developed bioinformatics tools were used for assembly and annotation of transcriptome. A total of 74,336 assembled transcript sequences were obtained, with an average coverage of 76.6 and average length of 439.5. Guanine-cytosine (GC) content was observed to be 44.6%, while the transcriptome exhibited abundance of trinucleotide simple sequence repeat (SSR; 45.63%) markers.

Large scale expression profiling through "read per exon kilobase per million (RPKM)", showed changes in several biological processes and metabolic pathways including cytochrome P450s (CYPs), UDP-glycosyltransferases (UGTs) and those associated with picrosides biosynthesis. RPKM data were validated by reverse transcriptase-polymerase chain reaction using a set of 19 genes, wherein 11 genes behaved in accordance with the two expression methods.

Conclusions

Study generated transcriptome of P. kurrooa at two different temperatures. Large scale expression profiling through RPKM showed major transcriptome changes in response to temperature reflecting alterations in major biological processes and metabolic pathways, and provided insight of GC content and SSR markers. Analysis also identified putative CYPs and UGTs that could help in discovering the hitherto unknown genes associated with picrosides biosynthesis.
Computational models for in-vitro anti-tubercular activity of molecules based on high-throughput chemical biology screening datasets
Authors: Periwal Vinita , Kishtapuram Shireesha ,   Open Source Drug Discovery Consortium, Scaria Vinod
Published: March 2012

Background

The emergence of Multi-drug resistant tuberculosis in pandemic proportions throughout the world and the paucity of novel therapeutics for tuberculosis have re-iterated the need to accelerate the discovery of novel molecules with anti-tubercular activity. Though high-throughput screens for anti-tubercular activity are available, they are expensive, tedious and time-consuming to be performed on large scales. Thus, there remains an unmet need to prioritize the molecules that are taken up for biological screens to save on cost and time. Computational methods including Machine Learning have been widely employed to build classifiers for high-throughput virtual screens to prioritize molecules for further analysis. The availability of datasets based on high-throughput biological screens or assays in public domain makes computational methods a plausible proposition for building predictive models. In addition, this approach would save significantly on the cost, effort and time required to run high throughput screens.

Results

We show that by using four supervised state-of-the-art classifiers (SMO, Random Forest, Naive Bayes and J48) we are able to generate in-silico predictive models on an extremely imbalanced (minority class ratio: 0.6%) large dataset of anti-tubercular molecules with reasonable AROC (0.6-0.75) and BCR (60-66%) values. Moreover, these models are able to provide 3-4 fold enrichment over random selection.

Conclusions

In the present study, we have used the data from in-vitro screens for anti-tubercular activity from a high-throughput screen available in public domain to build highly accurate classifiers based on molecular descriptors of the molecules. We show that Machine Learning tools can be used to build highly effective predictive models for virtual high-throughput screens to prioritize molecules from large molecular libraries.
Suicidal expressions among young people in Nicaragua and Cambodia: a cross-cultural study
Authors: Medina Claudia Obando , Jegannathan Bhoomikumar , Dahlblom Kjerstin , Kullgren Gunnar
Published: March 2012

Background

Whereas prevalence of suicidal expressions among young people is fairly similar in different countries, less is known about associated risk factors. This study compares young people in Nicaragua and Cambodia to examine if the pattern of association between mental health problems and suicidal expressions differs.

Methods

368 and 316 secondary school students, from each country respectively, participated. Self-reported suicidal expressions, exposure to suicidal behavior in significant others and mental health problems among the students were measured using Attitude Towards Suicide (ATTS) and the Youth Self-Report (YSR) questionnaires.

Results

Prevalence of serious suicidal expressions (plans and attempts) during recent year, did not differ between countries. Cambodian young people scored significantly higher on all eight YSR-syndromes, except for withdrawn/depressed. In Nicaragua, all YSR-syndromes were significantly associated with serious suicidal expressions in both genders compared to Cambodia where only one syndrome showed an association in each gender; Withdrawn/depressed among girls and Somatic complaints among boys. Associations between being exposed to suicide among significant others and serious suicidal expressions also differed between Cambodia and Nicaragua.

Conclusions

While the magnitude of serious suicidal expressions is similar between these structurally similar but culturally different countries, determinants behave differently. Qualitative studies are warranted to further explore cultural specific determinants for suicidal expressions among young people.
Improved negative selection protocol for Plasmodium berghei in the rodent malarial model
Authors: Orr Rachael Y , Philip Nisha , Waters Andrew P
Published: March 2012

An improved methodology is presented here for transgenic Plasmodium berghei lines that express the negative selectable marker yFCU (a bifunctional protein that combines yeast cytosine deaminase and uridyl phosphoribosyl transferase (UPRT)) and substitutes delivery of selection drug 5-fluorocytosine (5FC) by intraperitoneal injection for administration via the drinking water of the mice. The improved methodology is shown to be as effective, less labour-intensive, reduces animal handling and animal numbers required for successful selection thereby contributing to two of the "three Rs" of animal experimentation, namely refinement and reduction.
Comparative proteomic analysis of early salt stress-responsive proteins in roots of SnRK2 transgenic rice
Authors: Nam Myung Hee , Huh Sun Mi , Kim Kyung Mi , Park Woong Woong , Seo Jong Bok , Cho Kun , Kim Dool Yi , Kim Beom Gi , Yoon In In
Published: March 2012

Background

The rice roots are highly salt-sensitive organ and primary root growth is rapidly suppressed by salt stress. Sucrose nonfermenting 1-related protein kinase2 (SnRK2) family is one of the key regulator of hyper-osmotic stress signalling in various plant cells. To understand early salt response of rice roots and identify SnRK2 signaling components, proteome changes of transgenic rice roots over-expressing OSRK1, a rice SnRK2 kinase were investigated.

Results

Proteomes were analyzed by two-dimensional electrophoresis and protein spots were identified by LC-MS/MS from wild type and OSRK1 transgenic rice roots exposed to 150 mM NaCl for either 3 h or 7 h. Fifty two early salt -responsive protein spots were identified from wild type rice roots. The major up-regulated proteins were enzymes related to energy regulation, amino acid metabolism, methylglyoxal detoxification, redox regulation and protein turnover. It is noted that enzymes known to be involved in GA-induced root growth such as fructose bisphosphate aldolase and methylmalonate semialdehyde dehydrogenase were clearly down-regulated. In contrast to wild type rice roots, only a few proteins were changed by salt stress in OSRK1 transgenic rice roots. A comparative quantitative analysis of the proteome level indicated that forty three early salt-responsive proteins were magnified in transgenic rice roots at unstressed condition. These proteins contain single or multiple potential SnRK2 recognition motives. In vitro kinase assay revealed that one of the identified proteome, calreticulin is a good substrate of OSRK1.

Conclusions

Our present data implicate that rice roots rapidly changed broad spectrum of energy metabolism upon challenging salt stress, and suppression of GA signaling by salt stress may be responsible for the rapid arrest of root growth and development. The broad spectrum of functional categories of proteins affected by over-expression of OSRK1 indicates that OSRK1 is an upstream regulator of stress signaling in rice roots. Enzymes involved in glycolysis, branched amino acid catabolism, dnaK-type molecular chaperone, calcium binding protein, Sal T and glyoxalase are potential targets of OSRK1 in rice roots under salt stress that need to be further investigated.
Prognostic value of RKIP and p-ERK in gastric cancer
Authors: Fujimori Yoshitaka , Inokuchi Mikito , Takagi Yoko , Kato Keiji , Kojima Kazuyuki , Sugihara Kenichi
Published: March 2012

Background

The mitogen-activated protein kinase (MAPK) signaling pathway participates in several steps of tumour development and is considered a prominent therapeutic target for the design of chemotherapeutic agents. We evaluated the expressions of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MEK), an upstream regulator of ERK, and Raf kinase inhibitor protein (RKIP), and investigated correlations of these expressions with clinicopathological features and outcomes in gastric cancer.

Methods

Tumour samples were obtained from 105 patients with gastric adenocarcinomas who underwent radical gastrectomy. The expressions of phosphorylated ERK (p-ERK), phosphorylated MEK (p-MEK), and RKIP were analysed by immunohistochemical staining.

Results

Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively. RKIP expression negatively correlated with the depth of invasion (p < 0.001), lymph node involvement (p = 0.028), and Union for International Cancer Control (UICC) stage (p = 0.007). RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79). Patients with p-ERK expression had slightly, but not significantly shorter RFS than those without such expression (p = 0.054). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001). The combination of RKIP and p-ERK expression was an independent prognostic factor (hazard ratio, 2.4; 95% confidence interval, 1.3 - 4.6; p = 0.008).

Conclusions

Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival. Negative RKIP expression combined with positive p-ERK expression was an independent predictor of poor outcomes in patients with gastric cancer.
BlyS is up-regulated by hypoxia and promotes migration of human breast cancer cells
Authors: Zhu Jing , Sun Li , Lin Sensen , Zhao Renping , Zhou Liqiang , Fang Dongdong , Chen Liang , Liu Jin , Shi Wenting , Zhang Luyong , Yuan Shengtao
Published: March 2012

Background

The role of B Lymphocyte Stimulator (BLyS) in the survival of malignant B cells and the maintenance of normal B cell development and homeostasis has been intensively studied in the literature. However, the influence of BLyS on breast cancer progression remains unclear. The study aimed to investigate the effect of hypoxia on BLyS regulation, cell migratory response to BLyS and the possible molecular mechanisms.

Methods

In this study, we examined the role of BLyS in the migration of human breast cancer cells by transwell assay. We also explored whether BLyS and its receptors expressed in human breast cancer cell lines by immunofluorescence and Western Blotting. Then we detected the expression level of BLyS in both normoxic and hypoxic conditions by real time-PCR and Western Blotting. Pathways involved were confirmed by Western Blotting, immunofluorescence, transwell assay and luciferase assay.

Results

According to our study, the expression level of BlyS was increased in human breast cancer cell lines in hypoxic conditions. Up-regulation of this protein led to activation and nuclear translocation of NF-kappa B p65. We also found that the number of migrated cells was increased in the presence of BLyS and inhibition of phosphorylation of Akt attenuated the enhanced migratory response.

Conclusions

It suggested that better understanding of BLyS, an immunopotentiator, may offer a potential therapeutic target for the treatment of human breast cancers. In addition, BLyS promoted breast cancer cells migration, underscoring the necessity of appropriate applications of immunopotentiators to cancer treatment.
The Fox and the Grapes: Is Real Reform Beyond Reach in the United States?
Authors: Brown Lawrence D.
Published: March 2012

As the challenges of maintaining (or, in the US case, attaining) affordable universal coverage multiply, the debate about what constitutes “real” reform intensifies in Western health care systems. The reality of reform, however, lies in the eyes of myriad beholders who variously enshrine consumer responsibility, changes in payment systems, reorganization, and other strategies — or some encompassing combination of all of the above — as the essential ingredient(s). This debate, increasingly informed by the agendas of health services researchers and health policy analysts, arguably serves as much or more to becloud as to clarify the practical options policy makers face and remains severely imbalanced with respect to the institutional sectors on which it concentrates, the fields of knowledge on which it draws, and the roles it envisions for markets and the state.
Real Reform Begins Within: An Organizational Approach to Health Care Reform
Authors: Denis Jean-Louis , Forest Pierre-Gerlier
Published: March 2012

Health care systems are under pressure to control their increasing costs, to better adapt to evolving demands, to improve the quality and safety of care, and ultimately to ameliorate the health of their populations. This article looks at a battery of organizational options aimed at transforming health care systems and argues that more attention must be paid to reforming the delivery mechanisms that are so crucial for health care systems' overall performance. To support improvement, policies can rely on organizational assets in two ways. First, reforms can promote the creation of new organizational forms; second, they can employ organizational levers (e.g., capacity development, team-based organizations, evidence-informed practices) to achieve specific policy goals. In both cases organizational assets are mobilized with a view to creating complete health care organizations — that is to say, organizations that have the capacity to function as high-performing systems. The challenges confronting the development of more complete health care organizations are significant. Real health care system reforms may likewise require implementing ecologies of complex innovation at the clinical, organizational, and policy levels. Policies play a determining role in shaping these new spaces for action so that day-to-day practices may change.
Markets and Targets in the English National Health Service: Is There a Role for Behavioral Economics?
Authors: Oliver Adam
Published: March 2012

Over the past twenty years, the emphasis of reform attempts to improve efficiency within the English National Health Service (NHS) has oscillated between markets and targets. Both strategies are informed by standard economic theory but thus far have achieved varying degrees of success. Behavioral economics is currently in vogue and offers an alternative (or, in some cases, a complement) to standard economic theory on what motivates human behavior. There are many aspects to behavioral economics, but space constraints allow just three to be considered here: identity, loss aversion, and hyperbolic discounting. An attempt is made in this article to speculate on the extent to which these three concepts can explain the success or otherwise of the NHS market and target policies of the last two decades, and some suggestions are offered as to how policies might be usefully designed in the future. Arguably the key points are that people are more likely to be motivated if they identify with the ethos of the policy; the threat of losses will often provoke more of a response than the promise of gains; and the “immediate moment” matters enormously to individuals, so policies that require human action should be designed to make that moment as enjoyable (or as pain free) as possible.
A Conversation with Donald Berwick on Implementing National Health Reform
Authors: Birnbaum Michael
Published: March 2012

Michael Birnbaum interviews Donald Berwick shortly after his departure from the Centers for Medicare and Medicaid Services about the national health care landscape. Berwick discusses the strategic vision, policy levers, operational challenges, and political significance of federal health care reform. He rejects the notion that the Affordable Care Act represents a government takeover of health care financing or service delivery but says the law's Medicaid expansion and its creation of health benefit exchanges present a “watershed moment for American federalism.” Berwick argues that the solution to Medicare's cost-containment challenge lies in quality improvement. He is optimistic that accountable care organizations can deliver savings and suggests that shifting risk downstream to providers throws the health insurance model into question. Finally, looking to the future, Berwick sees a race against time to make American health care more affordable.
Radixin regulates cell migration and cell-cell adhesion through Rac1
Authors: Valderrama Ferran , Thevapala Subangi , Ridley Anne J.
Published: March 2012

The ERM proteins ezrin, radixin and moesin are adaptor proteins that link plasma membrane receptors to the actin cytoskeleton. Ezrin and moesin have been implicated in cell polarization and cell migration, but little is known about the involvement of radixin in these processes. Here we show that radixin is required for migration of PC3 prostate cancer cells, and that radixin, but not ezrin or moesin, depletion by RNAi increases cell spread area and cell-cell adhesion mediated by adherens junctions. Radixin depletion also alters actin organization and distribution of active phosphorylated ezrin and moesin. Similar effects were observed in MDA-MB-231 breast cancer cells. The phenotype of radixin-depleted cells is similar to that induced by constitutively active Rac1, and Rac1 is required for the radixin knockdown phenotype. Radixin depletion also increases the activity of Rac1 but not Cdc42 or RhoA. Analysis of Rac guanine nucleotide exchange factors (GEFs) suggests that radixin affects the activity of Vav GEFs. Indeed, Vav GEF depletion reverts the phenotype of radixin knockdown and reduces the effect of radixin knockdown on Rac1 activity. Our results indicate that radixin plays an important role in promoting cell migration by regulating Rac1-mediated epithelial polarity and formation of adherens junctions through Vav GEFs.
Dental Pulp of the Third Molar: A New Source of Pluripotent-like Stem Cells
Authors: Atari M. , Gil-Recio C. , Fabregat M. , García-Fernández D. A. , Barajas M. , Carrasco M. , Jung Han-Sung , Hernández-Alfaro F. , Casals N. , Prosper F. , Ferrés Padró E. , Giner L.
Published: March 2012

Dental pulp is particularly interesting in regenerative medicine because of the accessibility and differentiation potential of the tissue. Dental pulp has an early developmental origin with multi-lineage differentiation potential due to its development during childhood and adolescence. However, no study has previously identified the presence of stem cell populations with embryonic-like phenotypes in human dental pulp from the third molar. In the present work, we describe a new population of pluripotent-like stem cells (DPPSCs) that were isolated from the dental pulp by culture in media containing LIF, EGF and PDGF. These cells are SSEA4+, OCT3/4+, NANOG+, SOX2+, LIN28+, CD13+, CD105+, CD34−, CD45−, CD90+, CD29+, CD73+, STRO1+ and CD146−, and they show genetic stability in vitro based on genomic analysis with a newly described CGH technique. Interestedly DPPSCs were able to form both embryoid bodies-like structutes (EBs) in vitro and teratom-like structures that contained tissues derived from all three embryonic germ layers when injected in nude mice. We examined the capacity of DPPSCs to differentiate in vitro into tissues that have similar characteristics to mesoderm, endoderm and ectoderm layers in both 2D and 3D cultures. We performed a comparative RT-PCR analysis of GATA4, GATA6, MIXL1, NANOG, OCT3/4, SOX1 and SOX2 to determine the degree of similarity between DPPSCs, EBs and human induced pluripotent stem cells (hIPSC). Our analysis revealed that DPPSCs, hIPSC and EBs have the same gene expression profile. Because DPPSCs can be derived from healthy human molars from patients of different sexes and ages, they represent an easily accessible source of stem cells, which opens a range of new possibilities for regenerative medicine.
The function of the M-line protein, obscurin, in controlling the symmetry of the sarcomere inDrosophilaflight muscle
Authors: Katzemich Anja , Kreisköther Nina , Alexandrovich Alexander , Elliott Christopher , Schöck Frieder , Leonard Kevin , Sparrow John , Bullard Belinda
Published: March 2012

Drosophila obscurin is a large modular protein in the muscle M-line, similar to nematode UNC-89. We find four isoforms in the muscles of adult flies: two in the indirect flight muscle (IFM), and two in other muscles; a fifth isoform is in the larva. The larger IFM isoform has all the domains predicted in the gene. Obscurin is in the M-line throughout development, in embryo, larva and adult. The effect of reducing obscurin expression on the structure of the sarcomere was studied in a P-element mutant and in RNAi knockdown flies. Embryo, larva and pupa developed normally. In the pupa, the IFM was affected; the H-zone was misaligned, but the Z-disc was normal. Adults were unable to fly and the structure of the IFM was irregular: M-lines were missing and H-zones misplaced or absent. Isolated thick filaments were asymmetrical, with bare zones shifted from the middle of the filaments. In the sarcomere, the length and polarity of thin filaments depended on the symmetry of adjacent thick filaments; shifted bare zones resulted in thin filaments that were abnormally long or short. Obscurin is needed in the IFM for the development of a symmetrical sarcomere.
The F-BAR domains from srGAP1, srGAP2, and srGAP3 differentially regulate membrane deformation
Authors: Coutinho-Budd Jaeda , Ghukasyan Vladimir , Zylka Mark J. , Polleux Franck
Published: March 2012

Coordination of membrane deformation and cytoskeletal dynamics lies at the heart of many biological processes critical for cell polarity, motility and morphogenesis. We recently showed that slit-robo GTPase-activating protein 2 (srGAP2) regulates neuronal morphogenesis through the ability of its F-BAR domain to regulate membrane deformation and induce filopodia formation. Here we demonstrate that the F-BAR domains of two closely related family members, srGAP1 and srGAP3 (F-BAR(1) and F-BAR(3), respectively) display significantly different membrane deformation properties in non-neuronal COS7 cells and in cortical neurons. F-BAR(3) induces filopodia in both cell types, though less potently than F-BAR(2), whereas F-BAR(1) prevents filopodia formation in cortical neurons and reduces plasma membrane dynamics. These three F-BAR domains can heterodimerize and act synergistically towards filopodia induction in COS7 cells. At the molecular level, F-BAR(2) displays faster molecular dynamics than F-BAR(3) and F-BAR(1) respectively at the plasma membrane which correlates well with its increased potency to induce filopodia. We also show that the molecular dynamic properties of F-BAR(2) at the membrane are partially dependent on F-Actin. Interestingly, acute phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) depletion in cells does not interfere with plasma membrane localization of F-BAR(2), which is compatible with our result showing that F-BAR(2) binds to a broad range of negatively-charged phospholipids present at the plasma membrane, including phosphatidylserine (PS). Overall, our results provide novel insights into the functional diversity of the membrane deformation properties of this subclass of F-BAR-domains required for cell morphogenesis.