HBP1 (HMG-box transcription factor 1)

Review on HBP1 (HMG-box transcription factor 1), with data on DNA, on the protein encoded, and where the gene is implicated

Which game narratives do adolescents of different gameplay and sociodemographic backgrounds prefer? a mixed-methods analysis

OBJECTIVE: The aim of this study was to investigate which narrative elements of digital game narratives are preferred by the general adolescent population, and to examine associations with gender, socioeconomic status (SES), and gameplay frequency. Further, the study aims to discuss how results can be translated to serious digital games. MATERIALS AND METHODS: Adolescents were recruited through school to complete a survey on narrative preferences in digital games. The survey included questions on sociodemographic information, frequency of gameplay, and an open-ended question on what could be an appealing narrative for them. Data were analyzed in a mixed-methods approach, using thematic analysis and chi-square analyses to determine narrative preferences and the associations between game narrative elements and player characteristics (gender, SES, and frequency of gameplay). RESULTS: The sample consisted of 446 adolescents (12-15 years old) who described 30 narrative subthemes. Preferences included human characters as protagonists; nonhuman characters only as antagonists; realistic settings, such as public places or cities; and a strong conflict surrounding crime, catastrophe, or war. Girls more often than boys defined characters by their age, included avatars, located the narrative in private places, developed profession-related skills, and included a positive atmosphere. Adolescents of nonacademic education more often than adolescents of academic education defined characters by criminal actions. Infrequent players more often included human characters defined by their age than frequent players. After performing a Bonferroni correction, narrative preferences for several gender differences remained. CONCLUSION: Different narrative elements related to subgroups of adolescents by gender, SES, and frequency of gameplay. Customization of narratives in serious digital health games should be warranted for boys and girls; yet, further research is needed to specify how to address girls in particular

P193 USEFUL I: musculoskeletal ultrasound to identify patients with lupus arthritis with better response to therapy

Background In SLE, musculoskeletal manifestations have an impact on quality of life, disability and clinical trial outcomes, but are harder to assess than in RA and PsA. We previously showed that joint swelling lacks sensitivity, specificity and responsiveness compared to ultrasound. USEFUL was a multicentre longitudinal study to determine clinical features predicting ultrasound synovitis and whether patients with ultrasound synovitis respond better to therapy. Methods SLE patients were recruited if the referring physician deemed they had inflammatory pain warranting treatment. Swollen joints were not required. At baseline, physicians recorded the features that led them to diagnose inflammatory pain and features of concurrent fibromyalgia and osteoarthritis. Stable doses of prednisolone (≤5 mg/day), antimalarials or immunosuppressants were allowed. Participants received depomedrone 120 mg IM then were assessed at 0, 2 and 6 weeks for 66/68 swollen and tender joint counts, BILAG-2004, SLEDAI-2K, physician global and MSK-VAS, inflammatory markers, patient pain and disease activity-VAS, HAQ-DI, LupusQoL, ultrasound of hands and wrists (blinded to patient and clinical assessor). An internal pilot determined the primary endpoint: EMS-VAS at 2 weeks (adjusted for baseline) between patients with ultrasound-synovitis vs. normal ultrasound at baseline. Sensitivity analyses adjusted for prednisolone and immunosuppressants. Results 122/133 patients recruited completed all visits. There was significant disagreement between clinical examination and ultrasound. 78/133 had ultrasound synovitis; 68% of these had ≥1 swollen joint. Of 66/133 patients with ≥ 1 swollen joint, 20% had normal ultrasound. Ultrasound-synovitis was more likely with joint swelling, a symmetrical small joint distribution and active serology. Physician-determined EMS, other lupus features or prior response to therapy were not associated. Fibromyalgia or osteoarthritis did not reduce the probability of ultrasound synovitis. In the full analysis set (n=133) there was no difference in EMS VAS at 2 weeks according to ultrasound synovial status as baseline (difference -8 mm, 95% CI -19, 4 mm, p=0.178). 32 patients had fibromyalgia. After excluding these patients, we found a statistically and clinically significantly better clinical response to depomedrone in patients with ultrasound-synovitis at baseline (baseline-adjusted EMS VAS at 2 weeks -12 mm, 95% CI -24, 0 mm, p=0.049). This difference was greater in the treatment-adjusted sensitivity analysis (-12.8 (95% CI -22, -3 mm), p=0.007) and the per-protocol-adjusted sensitivity analysis (-14.8 mm (95% CI -20.8, -8.8 mm), p<0.001). Patient with ultrasound synovitis had higher rates of improvement in the musculoskeletal BILAG-2004 (56% vs. 26%, p=0.09) and SLEDAI-2K (37% vs. 15%, p=0.03). Conclusions In lupus arthritis distribution and serology, but not other features, help identify ultrasound-synovitis. Ultrasound-synovitis was independent of features of fibromyalgia, but fibromyalgia confounded assessment of response. Excluding fibromyalgia, response to therapy was better in patients with abnormal ultrasound compared to normal. Ultrasound should be used to select patients for therapy and clinical trials, especially when there are inflammatory symptoms without swollen joints

Boundary Conditions and Unitarity: the Maxwell-Chern-Simons System in AdS_3/CFT_2

We consider the holography of the Abelian Maxwell-Chern-Simons (MCS) system in Lorentzian three-dimensional asymptotically-AdS spacetimes, and discuss a broad class of boundary conditions consistent with conservation of the symplectic structure. As is well-known, the MCS theory contains a massive sector dual to a vector operator in the boundary theory, and a topological sector consisting of flat connections dual to U(1) chiral currents; the boundary conditions we examine include double-trace deformations in these two sectors, as well as a class of boundary conditions that mix the vector operators with the chiral currents. We carefully study the symplectic product of bulk modes and show that almost all such boundary conditions induce instabilities and/or ghost excitations, consistent with violations of unitarity bounds in the dual theory.Comment: 50+1 pages, 6 figures, PDFLaTeX; v2: added references, corrected typo

An Experimental Field Study of Delayed Density Dependence in Natural Populations of Aedes albopictus

Aedes albopictus, a species known to transmit dengue and chikungunya viruses, is primarily a container-inhabiting mosquito. The potential for pathogen transmission by Ae. albopictus has increased our need to understand its ecology and population dynamics. Two parameters that we know little about are the impact of direct density-dependence and delayed density-dependence in the larval stage. The present study uses a manipulative experimental design, under field conditions, to understand the impact of delayed density dependence in a natural population of Ae. albopictus in Raleigh, North Carolina. Twenty liter buckets, divided in half prior to experimentation, placed in the field accumulated rainwater and detritus, providing oviposition and larval production sites for natural populations of Ae. albopictus. Two treatments, a larvae present and larvae absent treatment, were produced in each bucket. After five weeks all larvae were removed from both treatments and the buckets were covered with fine mesh cloth. Equal numbers of first instars were added to both treatments in every bucket. Pupae were collected daily and adults were frozen as they emerged. We found a significant impact of delayed density-dependence on larval survival, development time and adult body size in containers with high larval densities. Our results indicate that delayed density-dependence will have negative impacts on the mosquito population when larval densities are high enough to deplete accessible nutrients faster than the rate of natural food accumulation

NBC update: The addition of viral and fungal databases to the Naïve Bayes classification tool

<p>Abstract</p> <p>Background</p> <p>Classifying the fungal and viral content of a sample is an important component of analyzing microbial communities in environmental media. Therefore, a method to classify any fragment from these organisms' DNA should be implemented.</p> <p>Results</p> <p>We update the näive Bayes classification (NBC) tool to classify reads originating from viral and fungal organisms. NBC classifies a fungal dataset similarly to Basic Local Alignment Search Tool (BLAST) and the Ribosomal Database Project (RDP) classifier. We also show NBC's similarities and differences to RDP on a fungal large subunit (LSU) ribosomal DNA dataset. For viruses in the training database, strain classification accuracy is 98%, while for those reads originating from sequences not in the database, the order-level accuracy is 78%, where order indicates the taxonomic level in the tree of life.</p> <p>Conclusions</p> <p>In addition to being competitive to other classifiers available, NBC has the potential to handle reads originating from any location in the genome. We recommend using the Bacteria/Archaea, Fungal, and Virus databases separately due to algorithmic biases towards long genomes. The tool is publicly available at: <url>http://nbc.ece.drexel.edu</url>.</p

Insulin receptor substrate adaptor proteins mediate prognostic gene expression profiles in breast cancer

Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer

Spatial distribution of the risk of dengue fever in southeast Brazil, 2006-2007

Background: Many factors have been associated with circulation of the dengue fever virus and vector, although the dynamics of transmission are not yet fully understood. The aim of this work is to estimate the spatial distribution of the risk of dengue fever in an area of continuous dengue occurrence. Methods: This is a spatial population-based case-control study that analyzed 538 cases and 727 controls in one district of the municipality of Campinas, Sao Paulo, Brazil, from 2006-2007, considering socio-demographic, ecological, case severity, and household infestation variables. Information was collected by in-home interviews and inspection of living conditions in and around the homes studied. Cases were classified as mild or severe according to clinical data, and they were compared with controls through a multinomial logistic model. A generalized additive model was used in order to include space in a non-parametric fashion with cubic smoothing splines. Results: Variables associated with increased incidence of all dengue cases in the multiple binomial regression model were: higher larval density (odds ratio (OR) = 2.3 (95%CI: 2.0-2.7)), reports of mosquito bites during the day (OR = 1.8 (95%CI: 1.4-2.4)), the practice of water storage at home (OR = 2.5 (95%CI: 1.4, 4.3)), low frequency of garbage collection (OR = 2.6 (95%CI: 1.6-4.5)) and lack of basic sanitation (OR = 2.9 (95%CI: 1.8-4.9)). Staying at home during the day was protective against the disease (OR = 0.5 (95%CI: 0.3-0.6)). When cases were analyzed by categories (mild and severe) in the multinomial model, age and number of breeding sites more than 10 were significant only for the occurrence of severe cases (OR = 0.97, (95%CI: 0.96-0.99) and OR = 2.1 (95%CI: 1.2-3.5), respectively. Spatial distribution of risks of mild and severe dengue fever differed from each other in the 2006/2007 epidemic, in the study area. Conclusions: Age and presence of more than 10 breeding sites were significant only for severe cases. Other predictors of mild and severe cases were similar in the multiple models. The analyses of multinomial models and spatial distribution maps of dengue fever probabilities suggest an area-specific epidemic with varying clinical and demographic characteristics

PR1-Specific T Cells Are Associated with Unmaintained Cytogenetic Remission of Chronic Myelogenous Leukemia After Interferon Withdrawal

Interferon-alpha (IFN) induces complete cytogenetic remission (CCR) in 20-25% CML patients and in a small minority of patients; CCR persists after IFN is stopped. IFN induces CCR in part by increasing cytotoxic T lymphocytes (CTL) specific for PR1, the HLA-A2-restricted 9-mer peptide from proteinase 3 and neutrophil elastase, but it is unknown how CCR persists after IFN is stopped.We reasoned that PR1-CTL persist and mediate CML-specific immunity in patients that maintain CCR after IFN withdrawal. We found that PR1-CTL were increased in peripheral blood of 7/7 HLA-A2+ patients during unmaintained CCR from 3 to 88 months after IFN withdrawal, as compared to no detectable PR1-CTL in 2/2 IFN-treated CML patients not in CCR. Unprimed PR1-CTL secreted IFNgamma and were predominantly CD45RA+/-CD28+CCR7+CD57-, consistent with functional naïve and central memory (CM) T cells. Similarly, following stimulation, proliferation occurred predominantly in CM PR1-CTL, consistent with long-term immunity sustained by self-renewing CM T cells. PR1-CTL were functionally anergic in one patient 6 months prior to cytogenetic relapse at 26 months after IFN withdrawal, and in three relapsed patients PR1-CTL were undetectable but re-emerged 3-6 months after starting imatinib.These data support the hypothesis that IFN elicits CML-specific CM CTL that may contribute to continuous CCR after IFN withdrawal and suggest a role for T cell immune therapy with or without tyrosine kinase inhibitors as a strategy to prolong CR in CML