bluuebunny/crossref_metadata_2025 huggingface dataset:
Locating MIA: ‘Race’, commodification and the politics of production
Authors: Saha Anamik
Published: November 2012

MIA (real name: Mathangi ‘Maya’ Arulpragasam) is one of the few British South Asian music artists who have crossed into the mainstream of western pop. The way in which she has attained this while foregrounding an explicit anti-racist and anti-imperialist message in her songs can be seen as a significant musical-political intervention, although the particular contestation of her work that has followed also highlights the challenges that Asian artists continue to face in gaining recognition within western popular culture. However, what is truly significant about MIA’s career is how she has managed to express a disavowed Asian identity without becoming trapped in the marginal space through which Asian culture is excluded. This has been the outcome of particular industry practice that has harnessed successfully the enabling features of commodification. In this way MIA represents an effective cultural politics of difference, the success of which is absolutely contingent upon an equally effective politics of production.
‘Twin transformations’: The Salvation Army’s charity shops and the recreating of material and social value
Authors: Podkalicka Aneta , Meese James
Published: November 2012

This article uses an empirically grounded historical case study of The Salvation Army’s charity shops in Melbourne, Australia to review recent debates around the position and function of ‘cultural intermediaries’ beyond its traditional meaning and application to aesthetic sectors within cultural industries. Drawing on archival research, cultural observation and interviews with staff members, the article focuses on the stores’ specific cultural identity engendered by the organization’s history of remaking the value of discarded objects, alongside its development of individual human agency and context-based community links. Secondhand ‘Salvos Stores’ form a network of hybrid commercial and social enterprises that serves as a basis for developing a wider conceptualization of the notion ‘cultural intermediary’. Following Cronin, Howells and McFall, we argue for an understanding which emphasizes their embedded, contextually reliant qualities, informed by the discourses, practices and networks of sociality.
Morrigan Rising: Exploring female-targeted propaganda on hate group websites
Authors: Castle Tammy
Published: November 2012

The role of racist women in hate groups remains an underdeveloped area of research, although scholars have suggested that female participation in such groups may vary among the different ideologies of the organizations. One method for exploring this research question involves examining the hate groups’ propaganda. The internet has become an increasingly popular method for distributing propaganda, thus the purpose of this exploratory study was to examine the propaganda targeted towards women on hate group websites. A content analysis was conducted on the websites of hate groups identified by the Southern Poverty Law Center. The results indicate that of 19 websites containing propaganda targeted towards women, almost all of them highlighted traditional gender roles, primarily the woman’s role in educating and raising an Aryan family, as their primary contribution to the movement. Some groups emphasized secondary roles and the implications of the propaganda push are discussed.
Reduction Effect of Toxic Substances for Apartment Buildings with an Ecofriendly Pre-cast Composite Structural System
Authors: Ko Hyo-Jin , Hong Won-Kee , Park Seon-Chee , Lim Gyun-Taek , Kim Ji-Hun , Kim Jeong Tai
Published: November 2012

Concrete, one of the construction materials used for apartment buildings, emits some toxic substances including CO2 and chromium VI that are detrimental to occupants. This paper presents pre-cast composite beams with T-type steels at each end to reduce the use of concrete. The new structural system is developed to replace the bearing walls of conventional apartment buildings. The pre-cast composite beams of the new concept (which can be used for apartment buildings) provide similar floor depth while minimizing the use of concrete materials. The CO2 and chromium VI emissions estimated from apartment buildings constructed with bearing walls are compared with those from buildings designed with the proposed composite beams. The data obtained from the previous study of Hong et al. [Hong WK, Kim JM, Park SC, Lee SG, Kim SI, Yoon KJ, Kim HC, Kim JT: A new apartment construction technology with effective CO2 emission reduction capabilities: Energy Int J 2010;35(6):2639–2646; Hong WK, Park SC, Kim JM, Kim SI, Lee SG, Yune DY, Yoon TH, Ryoo BY: Development of structural composite hybrid systems and their application with regard to the reduction of CO2 emissions: Indoor Built Environ 2010;19(1):151–162] for the amount of concrete material in the apartment buildings was used to estimate the amounts of CO2 and chromium VI emissions. The pre-cast composite beams of the new concept are believed to be an effective structural system to reduce the use of concrete material, which in turn reduces the amounts of the noxious materials, CO2 and chromium VI. The new healthy structural frame system introduced in this paper shows the potential to enhance the health of occupants.
Subjective Responses to Changes in Spectral Power Distributions of LED Light
Authors: Yun Geun Young , Kim Hyoin , Kim Jeong Tai
Published: November 2012

Lighting is an indispensable element in buildings, which influences visual comfort, health, well-being, work performance and building energy consumption. Light emitting diode (LED) technologies for illumination have made rapid advancements. Commercially available LED lightings have high luminous efficacies ranging from 60 to 75 lumen per watt and their spectral power distributions (SPD) are easily controllable. This study aims to reveal the potential effects of spectral power distributions of LED lighting on subjective responses including the evaluation on likeness, comfort, preference, clarity, brightness, glare, skin colour, lighting colour, overall satisfaction and work performance. Wavelength controllable LED lighting system that can render the 4324 different SPDs has been developed in this study in order to achieve the aim and 26 people participated in the experiment. The experimental results indicate that the subjective evaluation on lighting changes would depend on different SPDs under the same illuminance. The participants would tend to prefer the red-colour emphasizing SPDs with a peak wavelength of 636 nm to the blue-colour emphasizing SPDs with a peak wavelength of 453 nm. This study should contribute to reducing carbon dioxide emissions from buildings without sacrificing visual comfort and satisfaction of occupants by encouraging a wider application of LED lighting in buildings.
Cognitive Processing Therapy With a Prelingually Deaf Patient Suffering From Posttraumatic Stress Disorder
Authors: König Julia
Published: November 2012

This case study describes the treatment of a prelingually deaf patient suffering from posttraumatic stress disorder (PTSD) using cognitive processing therapy (CPT). A 42-year-old woman who had experienced a severe accident several years earlier presented with moderate PTSD symptoms. She was treated with CPT by a therapist experienced in working with PTSD patients but not with deaf patients. A sign language interpreter aided treatment. After 20 sessions, the patient chose to end treatment because she felt she had sufficiently profited from it. The case study shows that, with the help of a professional sign language interpreter, a structured cognitive-behavioral treatment such as CPT can be successfully implemented with a deaf patient.
Queer Asian mobility and homonational modernity: Marriage equality, Indian students in Australia and Malaysian transgender refugees in the media
Authors: Yue Audrey
Published: November 2012

In recent years, the regulation of mobility has seen marriage equality emerge as a homonational discourse of progressive gay and lesbian politics championed on the erasure of homophobia to end systemic discrimination. While homonational modernity promotes the superiority of a nation through sexual openness, it also mobilizes the fear of homophobia to marginalize racialized and sexualized minorities through sexual quarantine. Using media case studies on Indian student migrants and Malaysian transgender refugees from the Asian Australian diaspora, this article examines how homonational modernity regulates the queer mobility of diasporic Asian subjects. The article uses these case studies to interrogate homonational modernity and, in doing so, hopes to create a critical platform for a politics of queer Asian mobility. Critically illustrating how ‘Asia’ (e.g. Malaysia and India) and the Asian diaspora (e.g. Asian refugees and queer migrants in Australia) have been made present in Australian’s homonational modern imagination as sites of inclusion and exclusion, this article provides a critical approach to the regulation of mobility that allows for the intervention of and accounting for the uneven distribution of race, sex and gender that conditions personal mobility, revealing the institutional constraints and privileges that shape queer liberalism and homonormativity.
Knowledge, attitudes, and practices of parents/guardians regarding pediculosis in the Umm el-Jimal district of Jordan
Authors: ALBashtawy Mohammed
Published: November 2012

The aim of this study is to assess the prevalence of pediculosis capitis in one district in Jordan, and to determine the knowledge, attitudes and practices of parents/guardians regarding head lice. The study was performed in Jordan’s Umm el-Jimal district from February 2010 to May 2010, and involved the surveying of 105 randomly selected households containing a total of 213 children. The households’ parents were interviewed for their knowledge, attitudes and practices regarding pediculosis, and afterward their children’s hair was checked for head lice via a 5-min visual scalp examination. Chi-square testing was used to analyse the data, with statistical significance assumed at p < 0.05. The prevalence rate of pediculosis among the 213 children was found to be 14.6%. Parental knowledge of head lice was found to be very limited; only 35.2% of the parents/guardians correctly answered 10 of the 20 questions (50%), and only 17.1% correctly answered 14 questions (70%). More than 94% of the parents reported feeling shame upon learning that their children were infested with pediculosis, and nearly 90% felt too ashamed to ask for help from a healthcare provider. Many parents used traditional/local techniques that they believed to be effective in managing pediculosis; 61% of the parents applied kerosene to the scalps of infested individuals, 39.9% used medical shampoo and 37.6% used special combs. There is a clear deficiency in Jordanian parents’ knowledge of, and practices concerning, pediculosis capitis. It is recommended that the Jordanian Ministry of Health and local health departments work together to ensure the dissemination of accurate and consistent head lice information to families.
Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis
Authors: Oba Yuji , Lone Nazir A.
Published: November 2012

Background:

Roflumilast, a phosphodiesterase 4 inhibitor, has been shown to improve lung function and reduce exacerbation rates, but is associated with adverse events (AEs). The purpose of this study was to systematically review the clinical effectiveness and safety of roflumilast.

Methods:

A systematic search was made of MEDLINE, Cochrane trials database, DARE and CINAHL. Randomized, controlled trials of more than 12 weeks’ duration comparing roflumilast with placebo were reviewed. Studies were pooled to yield relative risk (RR), incident rate difference or weighted mean differences with 95% confidence intervals (CIs).

Results:

Eight trials (8698 patients) met the inclusion criteria. Roflumilast significantly reduced moderate to severe exacerbations (RR 0.85; 95% CI 0.80−0.91) compared with placebo, but not severe exacerbations (RR 0.83; 95% CI 0.68–1.01) or mortality (RR 0.90; 95% CI 0.63–1.28). Roflumilast significantly improved lung function relative to placebo, but not quality of life measures. AEs (RR 1.11; 95% CI 1.03–1.19) and discontinuations of treatment due to AEs (RR 1.63; 95% CI 1.45–1.84) were significantly more frequent with roflumilast than placebo. In the chronic obstructive pulmonary disease (COPD) Safety Pool (12,054 patients), the overall incidence of serious AEs did not differ between groups. However, atrial fibrillation (0.4% versus 0.2%; p = 0.02) and suicidality (0.08% versus 0%) were more frequent with roflumilast than placebo.

Conclusions:

The efficacy of roflumilast appears modest compared with other available therapies for COPD. Further studies are needed to investigate the risk–benefit ratio and long-term safety of roflumilast before its wider use.
Correlation of symptoms with total IgE and specific IgE levels in patients presenting with allergic rhinitis
Authors: Karli Rifat , Balbaloglu Evrim , Uzun Lokman , Çınar Fikret , Uğur Mehmet Birol
Published: November 2012

Objective:

The objective of this study was to investigate the correlation of symptoms in patients with presumed allergic rhinitis on the basis of their medical history and physical examination with the levels of total immunoglobulin E (IgE) and specific IgE, and to question the necessity of these tests in diagnosis.

Methods:

The records of 295 patients, who had at least two complaints of nasal itching, nasal obstruction, runny discharge and sneezing, and/or presumed as allergic rhinitis on physical examination findings were retrospectively screened. The correlation between the levels of IgE, specific inhalant IgE, and food-specific serum IgE were evaluated in these patients.

Results:

A total of 70 cases (23.7%) were determined to have a total value of IgE under 20 U/ml, 113 cases (38.3%) with IgE values between 20 U/ml and 100 U/ml, and 100 cases with IgE values above 100 U/ml. Results of total IgE could not be obtained in 12 (4.06%) patients. Dermatophagoides farinae was the most common allergy in this group with 74 (68.5%) cases.

Conclusions:

The determination of IgE in allergic rhinitis is a supportive method. However, it cannot be recommended for routine use because of the time loss and high cost.
The Balance Error Scoring System Learned Response Among Young Adults
Authors: Mulligan Ivan J. , Boland Mark A. , McIlhenny Carol V.
Published: November 2012

Background:

Concussion management practices are important for athlete safety. Baseline testing provides a benchmark to which post-injury assessments are compared. Yet few neurophysical concussion assessment studies have examined learned response. The Balance Error Scoring System (BESS) measures postural stability through 6 conditions by counting the errors committed during each condition. In a study examining the performance of high school–aged athletes on the BESS, the learned response extinguished in 3 weeks. However, this phenomenon has not been studied in the college-aged population.

Hypothesis:

College-aged adults performing the BESS will have a learned response at 1 and 2 weeks but would have no change from baseline at or after 3 weeks, as found previously in high school–aged subjects.

Study Design:

Randomized controlled clinical trial.

Methods:

Three groups of college-aged adults ages 18 to 26 years were tested using the BESS at scheduled intervals. Each subject was randomly assigned into 1 of 3 groups to determine learned response at weeks 1, 2, and 4. Changes in pretest and posttest BESS scores were compared using the paired t test for each group at week 4 and other intervals. Differences among groups were compared using analysis of variance for means or the chi-square test for proportions.

Results:

After 4 weeks, participants exhibited a mean (95% confidence interval) change from pretest baseline of −2.30 (−4.75, 0.16) in the control group ( P = 0.065), −3.13 (−4.84, −1.41) in Group 1 ( P = 0.001), and −2.57 (−5.28, 0.15) in Group 2 ( P = 0.063). There were no statistically significant differences between the 3 groups for week 4 BESS score ( P = 0.291) or changes from baseline to week 4 BESS scores ( P = 0.868). Overall, participant score changes from baseline to the 4-week follow-up still showed a statistically significant or close to significant reduction across the 3 groups, indicating the learned response did not extinguish after 4 weeks.

Conclusion:

Repeated BESS testing results in a learned effect in college-aged adults did not extinguish after 4 weeks. These results question the ability of the BESS to assess an athlete’s balance deficits following a concussion.

Clinical Relevance:

Given learned response did not extinguish in this sample and the BESS has a minimal detectable change/reliable change index of 7 or greater, the effectiveness of the BESS to assess balance may be limited.
Asenapine in bipolar I disorder: evidence and place in patient management
Authors: Samalin Ludovic , Charpeaud Thomas , Llorca Pierre-Michel
Published: November 2012

Asenapine is a new second-generation antipsychotic approved in September 2010 by the European Medicines Agency for the treatment of bipolar disorder. It demonstrated significant efficacy compared with placebo in acute mania or mixed episodes as monotherapy or adjunctive therapy to mood stabilizers (lithium or valproate). Early improvement was noted at day 2 and was strongly associated with response and remission at week 3. Asenapine also appeared effective in treating acute mania in older patients with bipolar disorder. Post hoc analyses of asenapine showed efficacy in treating depressive symptoms during manic or mixed episodes compared with placebo. The efficacy of asenapine in patients with acute mania appeared to remain constant during maintenance treatment. Asenapine was reasonably well tolerated, especially with regard to metabolic effects. There were minimal signs of glucose elevation or lipid changes and the risk of weight gain appeared limited. The prolactin elevation was smaller than other antipsychotic comparators. Only oral hypoesthesia occurred as a new adverse event compared with other second-generation antipsychotics. Asenapine presents several advantages over other second-generation antipsychotics, such as sublingual formulation, early efficacy and good metabolic tolerability. This tolerability profile confirms the heterogeneity of the second-generation antipsychotic class and supports the view of some authors for the need to re-evaluate the boundaries of this group.
iASeq: integrative analysis of allele-specificity of protein-DNA interactions in multiple ChIP-seq datasets
Authors: Wei Yingying , Li Xia , Wang Qian-fei , Ji Hongkai
Published: November 2012

Background

ChIP-seq provides new opportunities to study allele-specific protein-DNA binding (ASB). However, detecting allelic imbalance from a single ChIP-seq dataset often has low statistical power since only sequence reads mapped to heterozygote SNPs are informative for discriminating two alleles.

Results

We develop a new method iASeq to address this issue by jointly analyzing multiple ChIP-seq datasets. iASeq uses a Bayesian hierarchical mixture model to learn correlation patterns of allele-specificity among multiple proteins. Using the discovered correlation patterns, the model allows one to borrow information across datasets to improve detection of allelic imbalance. Application of iASeq to 77 ChIP-seq samples from 40 ENCODE datasets and 1 genomic DNA sample in GM12878 cells reveals that allele-specificity of multiple proteins are highly correlated, and demonstrates the ability of iASeq to improve allelic inference compared to analyzing each individual dataset separately.

Conclusions

iASeq illustrates the value of integrating multiple datasets in the allele-specificity inference and offers a new tool to better analyze ASB.
Curcumin and synthetic analogs induce reactive oxygen species and decreases specificity protein (Sp) transcription factors by targeting microRNAs
Authors: Gandhy Shruti U , Kim KyoungHyun , Larsen Lesley , Rosengren Rhonda J , Safe Stephen
Published: November 2012

Background

Curcumin inhibits growth of several cancer cell lines, and studies in this laboratory in bladder and pancreatic cancer cells show that curcumin downregulates specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and pro-oncogenic Sp-regulated genes. In this study, we investigated the anticancer activity of curcumin and several synthetic cyclohexanone and piperidine analogs in colon cancer cells.

Methods

The effects of curcumin and synthetic analogs on colon cancer cell proliferation and apoptosis were determined using standardized assays. The changes in Sp proteins and Sp-regulated gene products were analysed by western blots, and real time PCR was used to determine microRNA-27a (miR-27a), miR-20a, miR-17-5p and ZBTB10 and ZBTB4 mRNA expression.

Results

The IC50 (half-maximal) values for growth inhibition (24 hr) of colon cancer cells by curcumin and synthetic cyclohexanone and piperidine analogs of curcumin varied from 10 μM for curcumin to 0.7 μM for the most active synthetic piperidine analog RL197, which was used along with curcumin as model agents in this study. Curcumin and RL197 inhibited RKO and SW480 colon cancer cell growth and induced apoptosis, and this was accompanied by downregulation of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4 and Sp-regulated genes including the epidermal growth factor receptor (EGFR), hepatocyte growth factor receptor (c-MET), survivin, bcl-2, cyclin D1 and NFκB (p65 and p50). Curcumin and RL197 also induced reactive oxygen species (ROS), and cotreatment with the antioxidant glutathione significantly attenuated curcumin- and RL197-induced growth inhibition and downregulation of Sp1, Sp3, Sp4 and Sp-regulated genes. The mechanism of curcumin-/RL197-induced repression of Sp transcription factors was ROS-dependent and due to induction of the Sp repressors ZBTB10 and ZBTB4 and downregulation of microRNAs (miR)-27a, miR-20a and miR-17-5p that regulate these repressors.

Conclusions

These results identify a new and highly potent curcumin derivative and demonstrate that in cells where curcumin and RL197 induce ROS, an important underlying mechanism of action involves perturbation of miR-ZBTB10/ZBTB4, resulting in the induction of these repressors which downregulate Sp transcription factors and Sp-regulated genes.
Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995–2012) in South China
Authors: Wang Yu-hong , Lin Yuan , Xue Ling , Wang Jin-hui , Chen Min-hu , Chen Jie
Published: November 2012

Background

Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine tumors accounting for 65–75% of neuroendocrine neoplasms (NENs). Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China.

Methods

Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively.

Results

Pancreas was found the most common site of involvement (34.8%). 149 patients (83.7%) presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%); carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA) and synaptophysin (Syn) immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5%) had G1 tumors, 31(18.3%) G2 tumors and 51 (30.2%) G3 tumors. Neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4%) patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors.

Conclusions

Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.
Quantitative proteomics for identifying biomarkers for tuberculous meningitis
Authors: Kumar Ghantasala S Sameer , Venugopal Abhilash K , Mahadevan Anita , Renuse Santosh , Harsha H C , Sahasrabuddhe Nandini A , Pawar Harsh , Sharma Rakesh , Kumar Praveen , Rajagopalan Sudha , Waddell Keith , Ramachandra Yarappa L , Satishchandra Parthasarathy , Chaerkady Raghothama , Prasad T S Keshava , Shankar K , Pandey Akhilesh
Published: November 2012

Introduction

Tuberculous meningitis is a frequent extrapulmonary disease caused by Mycobacterium tuberculosis and is associated with high mortality rates and severe neurological sequelae. In an earlier study employing DNA microarrays, we had identified genes that were differentially expressed at the transcript level in human brain tissue from cases of tuberculous meningitis. In the current study, we used a quantitative proteomics approach to discover protein biomarkers for tuberculous meningitis.

Methods

To compare brain tissues from confirmed cased of tuberculous meningitis with uninfected brain tissue, we carried out quantitative protein expression profiling using iTRAQ labeling and LC-MS/MS analysis of SCX fractionated peptides on Agilent’s accurate mass QTOF mass spectrometer.

Results and conclusions

Through this approach, we identified both known and novel differentially regulated molecules. Those described previously included signal-regulatory protein alpha (SIRPA) and protein disulfide isomerase family A, member 6 (PDIA6), which have been shown to be overexpressed at the mRNA level in tuberculous meningitis. The novel overexpressed proteins identified in our study included amphiphysin (AMPH) and neurofascin (NFASC) while ferritin light chain (FTL) was found to be downregulated in TBM. We validated amphiphysin, neurofascin and ferritin light chain using immunohistochemistry which confirmed their differential expression in tuberculous meningitis. Overall, our data provides insights into the host response in tuberculous meningitis at the molecular level in addition to providing candidate diagnostic biomarkers for tuberculous meningitis.
Silencer-delimited transgenesis: NRSE/RE1 sequences promote neural-specific transgene expression in a NRSF/REST-dependent manner
Authors: Xie Xiayang , Mathias Jonathan R , Smith Marie-Ange , Walker Steven L , Teng Yong , Distel Martin , Köster Reinhard W , Sirotkin Howard I , Saxena Meera T , Mumm Jeff S
Published: November 2012

Background

We have investigated a simple strategy for enhancing transgene expression specificity by leveraging genetic silencer elements. The approach serves to restrict transgene expression to a tissue of interest - the nervous system in the example provided here - thereby promoting specific/exclusive targeting of discrete cellular subtypes. Recent innovations are bringing us closer to understanding how the brain is organized, how neural circuits function, and how neurons can be regenerated. Fluorescent proteins enable mapping of the 'connectome', optogenetic tools allow excitable cells to be short-circuited or hyperactivated, and targeted ablation of neuronal subtypes facilitates investigations of circuit function and neuronal regeneration. Optimally, such toolsets need to be expressed solely within the cell types of interest as off-site expression makes establishing causal relationships difficult. To address this, we have exploited a gene 'silencing' system that promotes neuronal specificity by repressing expression in non-neural tissues. This methodology solves non-specific background issues that plague large-scale enhancer trap efforts and may provide a means of leveraging promoters/enhancers that otherwise express too broadly to be of value for in vivo manipulations.

Results

We show that a conserved neuron-restrictive silencer element (NRSE) can function to restrict transgene expression to the nervous system. The neuron-restrictive silencing factor/repressor element 1 silencing transcription factor (NRSF/REST) transcriptional repressor binds NRSE/repressor element 1 (RE1) sites and silences gene expression in non-neuronal cells. Inserting NRSE sites into transgenes strongly biased expression to neural tissues. NRSE sequences were effective in restricting expression of bipartite Gal4-based 'driver' transgenes within the context of an enhancer trap and when associated with a defined promoter and enhancer. However, NRSE sequences did not serve to restrict expression of an upstream activating sequence (UAS)-based reporter/effector transgene when associated solely with the UAS element. Morpholino knockdown assays showed that NRSF/REST expression is required for NRSE-based transgene silencing.

Conclusions

Our findings demonstrate that the addition of NRSE sequences to transgenes can provide useful new tools for functional studies of the nervous system. However, the general approach may be more broadly applicable; tissue-specific silencer elements are operable in tissues other than the nervous system, suggesting this approach can be similarly applied to other paradigms. Thus, creating synthetic associations between endogenous regulatory elements and tissue-specific silencers may facilitate targeting of cellular subtypes for which defined promoters/enhancers are lacking.
Actomyosin-based Self-organization of cell internalization during C. elegans gastrulation
Authors: Pohl Christian , Tiongson Michael , Moore Julia L , Santella Anthony , Bao Zhirong
Published: November 2012

Background

Gastrulation is a key transition in embryogenesis; it requires self-organized cellular coordination, which has to be both robust to allow efficient development and plastic to provide adaptability. Despite the conservation of gastrulation as a key event in Metazoan embryogenesis, the morphogenetic mechanisms of self-organization (how global order or coordination can arise from local interactions) are poorly understood.

Results

We report a modular structure of cell internalization in Caenorhabditis elegans gastrulation that reveals mechanisms of self-organization. Cells that internalize during gastrulation show apical contractile flows, which are correlated with centripetal extensions from surrounding cells. These extensions converge to seal over the internalizing cells in the form of rosettes. This process represents a distinct mode of monolayer remodeling, with gradual extrusion of the internalizing cells and simultaneous tissue closure without an actin purse-string. We further report that this self-organizing module can adapt to severe topological alterations, providing evidence of scalability and plasticity of actomyosin-based patterning. Finally, we show that globally, the surface cell layer undergoes coplanar division to thin out and spread over the internalizing mass, which resembles epiboly.

Conclusions

The combination of coplanar division-based spreading and recurrent local modules for piecemeal internalization constitutes a system-level solution of gradual volume rearrangement under spatial constraint. Our results suggest that the mode of C. elegans gastrulation can be unified with the general notions of monolayer remodeling and with distinct cellular mechanisms of actomyosin-based morphogenesis.
LoxP-FRT Trap (LOFT): a simple and flexible system for conventional and reversible gene targeting
Authors: Chaiyachati Barbara H , Kaundal Ravinder K , Zhao Jiugang , Wu Jie , Flavell Richard , Chi Tian
Published: November 2012

Background

Conditional gene knockout (cKO) mediated by the Cre/LoxP system is indispensable for exploring gene functions in mice. However, a major limitation of this method is that gene KO is not reversible. A number of methods have been developed to overcome this, but each method has its own limitations.

Results

We describe a simple method we have named LOFT [LoxP-flippase (FLP) recognition target (FRT) Trap], which is capable of reversible cKO and free of the limitations associated with existing techniques. This method involves two alleles of a target gene: a standard floxed allele, and a multi-functional allele bearing an FRT-flanked gene-trap cassette, which inactivates the target gene while reporting its expression with green fluorescent protein (GFP); the trapped allele is thus a null and GFP reporter by default, but is convertible into a wild-type allele. The floxed and trapped alleles can typically be generated using a single construct bearing a gene-trap cassette doubly flanked by LoxP and FRT sites, and can be used independently to achieve conditional and constitutive gene KO, respectively. More importantly, in mice bearing both alleles and also expressing the Cre and FLP recombinases, sequential function of the two enzymes should lead to deletion of the target gene, followed by restoration of its expression, thus achieving reversible cKO. LOFT should be generally applicable to mouse genes, including the growing numbers of genes already floxed; in the latter case, only the trapped alleles need to be generated to confer reversibility to the pre-existing cKO models. LOFT has other applications, including the creation and reversal of hypomorphic mutations. In this study we proved the principle of LOFT in the context of T-cell development, at a hypomorphic allele of Baf57/Smarce1 encoding a subunit of the chromatin-remodeling Brg/Brahma-associated factor (BAF) complex. Interestingly, the FLP used in the current work caused efficient reversal in peripheral T cells but not thymocytes, which is advantageous for studying developmental epigenetic programming of T-cell functions, a fundamental issue in immunology.

Conclusions

LOFT combines well-established basic genetic methods into a simple and reliable method for reversible gene targeting, with the flexibility of achieving traditional constitutive and conditional KO.
Atrophic dermatofibrosarcoma protuberans: report of a case demonstrated by detecting COL1A1-PDGFB rearrangement
Authors: Qiao Jianjun , Patel Kayuri U , López-Terrada Dolores , Fang Hong
Published: November 2012

Dermatofibrosarcoma protuberans is a locally aggressive mesenchymal neoplasm. It usually presents as an indurated plaque that protrudes above the surface of the skin. Some patients have clinically persistent plaques that might be atrophic. The atrophic variant of dermatofibrosarcoma protuberans may be confused with some common skin diseases with atrophic appearance. We reported a 40-year-old woman who had a 10-year history of an atrophic dermatofibrosarcoma protuberans. Molecular analysis showed a fusion between COL1A1 exon 31 to exon 2 of PDGFB. The lesion was totally excised, with negative margins of the resection demonstrated by CD34 immunostaining. To our knowledge, this is the second case of atrophic dermatofibrosarcoma protuberans confirmed by detection of COL1A1-PDGFB fusion gene. This appears to be the first report of a fusion between COL1A1 exon 31 to exon 2 of PDGFB in atrophic dermatofibrosarcoma protuberans.

Virtual slides

The virtual slides for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1249657688795311
Co-administration of avian influenza virus H5 plasmid DNA with chicken IL-15 and IL-18 enhanced chickens immune responses
Authors: Lim Kian-Lam , Jazayeri Seyed Davoud , Yeap Swee Keong , Alitheen Noorjahan Banu Mohamed , Bejo Mohd Hair , Ideris Aini , Omar Abdul Rahman
Published: November 2012

Background

DNA vaccines offer several advantages over conventional vaccines in the development of effective vaccines against avian influenza virus (AIV). However, one of the limitations of the DNA vaccine in poultry is that it induces poor immune responses. In this study, chicken interleukin (IL) -15 and IL-18 were used as genetic adjuvants to improve the immune responses induced from the H5 DNA vaccination in chickens. The immunogenicity of the recombinant plasmid DNA was analyzed based on the antibody production, T cell responses and cytokine production, following inoculation in 1-day-old (Trial 1) and 14-day-old (Trial 2) specific-pathogen-free chickens. Hence, the purpose of the present study was to explore the role of chicken IL-15 and IL-18 as adjuvants following the vaccination of chickens with the H5 DNA vaccine.

Results

The overall HI antibody titer in chickens immunized with pDis/H5 + pDis/IL-15 was higher compared to chickens immunized with pDis/H5 (p < 0.05). The findings revealed that the inoculation of the 14-day-old chickens exhibited a shorter time to achieve the highest HI titer in comparison to the inoculation of the 1-day-old chickens. The cellular immunity was assessed by the flow cytometry analysis to enumerate CD4+ and CD8 + T cells in the peripheral blood. The chickens inoculated with pDis/H5 + pDis/IL-15 demonstrated the highest increase in CD4+ T cells population relative to the control chickens. However, this study revealed that pDis/H5 + pDis/IL-15 was not significant (P > 0.05) in inducing CD8+ T cells. Meanwhile, with the exception of Trial 1, the flow cytometry results for Trial 2 demonstrated that the pDis/H5 + pDis/IL-18 inoculated group was able to trigger a higher increase in CD4+ T cells than the pDis/H5 group (P < 0.05). On the other hand, the pDis/H5 + pDis/IL-18 group was not significant (P > 0.05) in modulating CD8+ T cells population in both trials. The pDis/H5 + pDis/IL-15 inoculated group showed the highest IL-15 gene expression in both trials compared to other inoculated groups (P < 0.05). Similar results were obtained for the IL-18 expression where the pDis/H5 + pDis/IL-18 groups in both trials (Table 8) were significantly higher compared to the control group (P < 0.05). However, the expressions of other cytokines remained low or undetected by GeXP assay.

Conclusions

This study shows the diverse immunogenicity of pDis/H5 co-administered with chicken IL-15 and IL-18,with pDis/H5 + pDis/IL-15 being a better vaccine candidate compared to other groups.
18F-fluoro-deoxyglucose positron emission tomography/computed tomography scan findings in Rosai-Dorfman disease with IgG4-positive plasma cell infiltration mimicking breast malignancy: a case report and literature review
Authors: Fu Liping , Liu Mei , Song Zhigang , Xu Baixuan , Tian Jiahe
Published: November 2012

Introduction

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, is a rare benign disorder characterized histologically by lymphatic sinus dilatation due to histiocyte proliferation. Rosai-Dorfman disease accompanied by IgG4+ plasma cell infiltration is an even rarer situation. To the best of our knowledge, no imaging report of fluoro-deoxyglucose positron emission tomography/computed tomography findings of Rosai-Dorfman disease with IgG4+ plasma cell infiltration has been published, although a series of pathological research has focused on this phenomenon.

Case presentation

We reviewed the 18F-fluoro-deoxyglucose positron emission tomography/computed tomography scan of a 78-year-old Chinese woman with a solid mass that was found in her right breast during a health checkup. 18F-fluoro-deoxyglucose positron emission tomography/computed tomography showed a hypermetabolic nodule in her right breast and slightly heterogeneous increased fluoro-deoxyglucose uptake of the pulmonary nodules, which were histologically proven to be mammary Rosai-Dorfman disease with IgG4+ plasma cell infiltration and pulmonary amyloidosis, respectively. A literature review was performed to gather information on this rare disease process.

Conclusions

Although distinguishing benign lymphoplasmacytic proliferation from malignancy may be difficult with 18F-fluoro-deoxyglucose positron emission tomography/computed tomography in light of the pattern and intensity of fluoro-deoxyglucose uptake, our case highlights that whole-body positron emission tomography/computed tomography imaging not only can display the extent of the disease to help complete staging but also can provide functional information about disease activity to guide biopsy.
Pneumonitis and pulmonary fibrosis in a patient receiving adjuvant docetaxel and cyclophosphamide for stage 3 breast cancer: a case report and literature review
Authors: Ochoa Roberto , Bejarano Pablo A , Glück Stefan , Montero Alberto J
Published: November 2012

Introduction

Pulmonary toxicities associated with chemotherapeutic agents utilized as adjuvant therapy in patients with breast cancer are distinctly uncommon. The chemotherapy regimen of docetaxel/cyclophosphamide has a more favorable therapeutic index compared to anthracycline-based regimens due to a significantly lower incidence of heart failure and leukemia. Consequently, docetaxel/cyclophosphamide is the preferred adjuvant chemotherapy of choice in older women or in women where anthracyclines may be contraindicated. Pulmonary complications in patients with breast cancer receiving taxane-based adjuvant chemotherapy in the absence of radiation are distinctly uncommon. Here, we report the case of a patient receiving adjuvant docetaxel/cyclophosphamide who developed rapid-onset, biopsy-proven interstitial pneumonitis.

Case presentation

A 72-year-old Hispanic woman was diagnosed as having stage 3 hormone-receptor positive, human epidermal growth factor receptor 2/neu negative, invasive breast cancer. Due to the estimated 10-year risk of recurrence of approximately 80 percent, a decision was made to treat our patient with adjuvant chemotherapy. Due to her age and increased risk of cardiac toxicity with anthracycline-based chemotherapy regimens, our patient was treated with docetaxel/cyclophosphamide chemotherapy for a total of four planned cycles. However, approximately two weeks after receiving the third cycle of chemotherapy, our patient developed rapidly progressive dyspnea, and a non-productive cough and went to the emergency room at an outside medical facility. She was found to have mild hypoxemia, and new onset of peripheral, subpleural fibrotic changes not present on pre-treatment scans. A thorascopic-guided wedge biopsy of the lung tissue revealed subacute interstitial pneumonitis. Our patient made a rapid clinical recovery after treatment with corticosteroids.

Conclusions

Interstitial pneumonitis is a rare complication of docetaxel/cyclophosphamide chemotherapy that carries a high mortality rate. The only way to make a definitive diagnosis is with a wedge biopsy of the lung, which should be performed when feasible. Our patient’s case illustrates that no therapeutic intervention is without its intrinsic and unanticipated risks, and interstitial pneumonitis should be discussed as a potential side effect with all patients prior to administering docetaxel/cyclophosphamide chemotherapy.
Does use of the CONSORT Statement impact the completeness of reporting of randomised controlled trials published in medical journals? A Cochrane reviewa
Authors: Turner Lucy , Shamseer Larissa , Altman Douglas G , Schulz Kenneth F , Moher David
Published: November 2012

Background

The Consolidated Standards of Reporting Trials (CONSORT) Statement is intended to facilitate better reporting of randomised clinical trials (RCTs). A systematic review recently published in the Cochrane Library assesses whether journal endorsement of CONSORT impacts the completeness of reporting of RCTs; those findings are summarised here.

Methods

Evaluations assessing the completeness of reporting of RCTs based on any of 27 outcomes formulated based on the 1996 or 2001 CONSORT checklists were included; two primary comparisons were evaluated. The 27 outcomes were: the 22 items of the 2001 CONSORT checklist, four sub-items describing blinding and a ‘total summary score’ of aggregate items, as reported. Relative risks (RR) and 99% confidence intervals were calculated to determine effect estimates for each outcome across evaluations.

Results

Fifty-three reports describing 50 evaluations of 16,604 RCTs were assessed for adherence to at least one of 27 outcomes. Sixty-nine of 81 meta-analyses show relative benefit from CONSORT endorsement on completeness of reporting. Between endorsing and non-endorsing journals, 25 outcomes are improved with CONSORT endorsement, five of these significantly (α = 0.01). The number of evaluations per meta-analysis was often low with substantial heterogeneity; validity was assessed as low or unclear for many evaluations.

Conclusions

The results of this review suggest that journal endorsement of CONSORT may benefit the completeness of reporting of RCTs they publish. No evidence suggests that endorsement hinders the completeness of RCT reporting. However, despite relative improvements when CONSORT is endorsed by journals, the completeness of reporting of trials remains sub-optimal. Journals are not sending a clear message about endorsement to authors submitting manuscripts for publication. As such, fidelity of endorsement as an ‘intervention’ has been weak to date. Journals need to take further action regarding their endorsement and implementation of CONSORT to facilitate accurate, transparent and complete reporting of trials.
Predicting stem cell fate changes by differential cell cycle progression patterns
Authors: Roccio Marta , Schmitter Daniel , Knobloch Marlen , Okawa Yuya , Sage Daniel , Lutolf Matthias P.
Published: November 2012

Stem cell self-renewal, commitment and reprogramming rely on a poorly understood coordination of cell cycle progression and execution of cell fate choices. Using existing experimental paradigms, it has not been possible to probe this relationship systematically in live stem cells in vitro or in vivo. Alterations in stem cell cycle kinetics probably occur long before changes in phenotypic markers are apparent and could be used as predictive parameters to reveal changes in stem cell fate. To explore this intriguing concept, we developed a single-cell tracking approach that enables automatic detection of cell cycle phases in live (stem) cells expressing fluorescent ubiquitylation-based cell-cycle indicator (FUCCI) probes. Using this tool, we have identified distinctive changes in lengths and fluorescence intensities of G1 (red fluorescence) and S/G2-M (green) that are associated with self-renewal and differentiation of single murine neural stem/progenitor cells (NSCs) and embryonic stem cells (ESCs). We further exploited these distinctive features using fluorescence-activated cell sorting to select for desired stem cell fates in two challenging cell culture settings. First, as G1 length was found to nearly double during NSC differentiation, resulting in progressively increasing red fluorescence intensity, we successfully purified stem cells from heterogeneous cell populations by their lower fluorescence. Second, as ESCs are almost exclusively marked by the green (S/G2-M) FUCCI probe due to their very short G1, we substantially augmented the proportion of reprogramming cells by sorting green cells early on during reprogramming from a NSC to an induced pluripotent stem cell state. Taken together, our studies begin to shed light on the crucial relationship between cell cycle progression and fate choice, and we are convinced that the presented approach can be exploited to predict and manipulate cell fate in a wealth of other mammalian cell systems.