Expression profile of CREB knockdown in myeloid leukemia cells.

BackgroundThe cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not affect long-term hematopoietic reconstitution.MethodsTo understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line transduced with CREB shRNA.ResultsBy combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA.ConclusionWe have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle

Aboriginal Languages in Quebec: Fighting Linguicide with Bilingual Education

Aboriginal peoples in Quebec are fighting for the survival of their language and culture. An essential component of Aboriginal decolonization and empowerment is the protection and enhancement of the Aboriginal heritage language. In this article, we review twenty years of research in Arctic Quebec (Nunavik) involving Inuit students educated in Inuktitut as well as in French and English. Our research reveals that children not only learn better in their own heritage language as opposed to one of the societally dominant languages, but also develop a more positive view of themselves, and a healthier view of Inuit as a group. Bilingual Education is shown to be of crucial importance for the vitality of Inuit language and culture.Les peuples autochtones du Québec luttent afin de préserver la survie de leur langue et de leur culture. Un élément essentiel de la décolonisation et de l’autonomisation autochtone est la protection et l’enrichissement de la langue ancestrale autochtone. Dans cet article, nous effectuons une analyse de vingt années de recherche dans le Nord du Québec (Nunavik) impliquant des élèves inuits scolarisés en français et en anglais. Nos recherches ont révélé que ces enfants non seulement apprennent mieux dans leur propre langue ancestrale plutôt que dans une des langues dominantes de la société, mais aussi qu’ils développent une image d’eux-mêmes plus positive, et une représentation plus saine des Inuits en tant que groupe. Il est démontré que l’enseignement bilingue est d’une importance cruciale, contribuant à la vitalité de la langue et de la culture inuites

A snapshot of the student experience: Exploring student satisfaction through the use of photographic-elicitation

Student satisfaction is both an important and yet controversial issue within the higher education sector, which is typically measured through policy-driven metrics such as the National Student Survey. However, less is understood about the qualities of a satisfying student experience ‘as lived’ from the perspective of the student, thus questioning the adequacy of such measures. In response to this, the current study used student-driven photographic elicitation as a means of more adequately capturing the holistic student experience. This entailed nine final-year undergraduate psychology students who each gathered a series of photos, which formed the basis for discussion in an interview. Thematic analysis of the narratives of the interview discussions revealed several main themes surrounding their experiences. These were: ‘Learning Environment’, ‘Work–Life Balance’ and ‘Wider University Community’. Findings are discussed with reference to the implications of student satisfaction, and national metrics used for measuring it, for institutional policies of recruitment and retention

Effects of 30-, 60-, and 90-Day Bed Rest on Postural Control in Men and Women

INTRODUCTION Head-down-tilt bed rest (HDT) has been used as a safe gr ound-based analog to mimic and develop countermeasures for the physiological effects of spaceflight, including decrements in postural stability. The purpose of this investigation was to characterize the effects of 30-, 60-, and 90-day bed rest on postural control in men and women. METHODS Twenty-nine subjects (18M,11F) underwent 13 days of ambula tory acclimatization and were placed in 6? HDT for 30 (n=12), 60 (n=8), or 90 (n=9) days, followed by 14 days of ambulatory recovery. Computerized dynamic posturography (CDP) was used to assess changes in sensory and motor components of postural control, and recovery after HDT. Sensory Organization Tests (SOTs) objectively evaluate one?s ability to effectively use or suppress visual, vestibular, and proprioceptive information for postural control. Stability during the SOTs was assessed using peak-to-peak sway and convergence toward stability limits to derive an equilibrium score. Motor Control Tests (MCTs) evaluate one?s ability to recover from unexpected support surface perturbations, with performance determined by center-of-pressure path length. Whole-body kinematic data were collected to determine body-sway strategy used to maintain stability during each condition. Baselines were determined pre-HDT. Recovery was tracked post-HDT on days 0, 1, 2, and 4. RESULTS Immediately after HDT, subjects showed decreased performance on most SOTs, primarily on sway-referenced support conditions, typically returning to baseline levels within 4 days. MCT performance was not significantly affected. There were no significant gender or duration differences in performance. Kinematic data revealed a tendency to use ankle strategy to maintain an upright stance during most SOT conditions. Interestingly, six subjects (2M,4F) experienced orthostatic intolerance and were unable to complete day 0 testing. CONCLUSION HDT mimics some un loading mechanisms of spaceflight and elicits orthostatic issues present post-spaceflight (contributing to instability); however, it does not sufficiently address the vestibular dysfunction which occurs post-spaceflight

Mixed methods study of clinicians' perspectives on barriers to implementation of treat to target in psoriatic arthritis

Objectives: In treat to target (T2T), the patient is treated to reach and maintain specified and sequentially measured goals, such as remission or low disease activity. T2T in psoriatic arthritis (PsA) has demonstrated improved clinical and patient-reported outcomes and is recommended in European guidelines. However, most clinicians do not use T2T in PsA. This study examined the barriers and enablers to implementation in practice. Methods: Sequential mixed methods comprising a qualitative design (interviews and focus group) to inform a quantitative design (survey). Qualitative data were analysed thematically, and quantitative statistics were analysed descriptively. Results: Nineteen rheumatology clinicians participated in telephone interviews or a face-to-face focus group. An overarching theme 'Complexity' (including 'PsA vs Rheumatoid Arthritis', 'Measurement' and 'Resources') and an underpinning theme 'Changes to current practice' (including 'Reluctance due to organisational factors' and 'Individual determination to make changes') were identified. 153 rheumatology clinicians responded to an online survey. Barriers included limited clinical appointment time to collect outcome data (54.5%) and lack of training in assessing skin disease (35%). Enablers included provision of a protocol (86.4%), a local implementation lead (80.9%), support in clinic to measure outcomes (83.3%) and training in T2T (69.8%). The importance of regular audit with feedback, specialist PsA clinics and a web-based electronic database linked to hospital/national information technology (IT) systems were also identified as enablers. Conclusions: Implementation of T2T in PsA requires an integrated approach to address the support, training and resource needs of individual clinicians, rheumatology teams, local IT systems and service providers to maximise success

A descriptive study of school discipline referrals in first grade

School discipline referrals (SDRs) may be useful in the early detection and monitoring of disruptive behavior problems to inform prevention efforts in the school setting, yet little is known about the nature and validity of SDRs in the early grades. For this descriptive study, SDR data were collected on a sample of first grade students who were at risk for developing disruptive behavior problems (n = 186) and a universal sample (n = 531) from 20 schools. Most SDRs were given for physical aggression and the predominant consequence was time out. As expected, boys and at-risk students were more likely to receive an SDR and to have more SDRs than were girls and the universal sample. A large difference between schools regarding the delivery of SDRs was found. A zero-inflated Poisson model clustered by school tested the prediction of school-level variables. Students in schools that had a systematic way of tracking SDRs were more likely to receive one. Also, schools with more low-income students and larger class sizes gave fewer SDRs. SDRs predicted teacher ratings, and to a lesser extent, parent ratings of disruptive behavior at the end of first grade. Practitioners and researchers must examine school-level influences whenever first grade discipline referrals are used to measure problem behavior for the purpose of planning and evaluating interventions

Histamine stimulates the proliferation of small and large cholangiocytes by activation of both IP3/Ca2+ and cAMP-dependent signaling mechanisms

Although large cholangiocytes exert their functions by activation of cyclic adenosine 3',5'-monophosphate (cAMP), Ca(2+)-dependent signaling regulates the function of small cholangiocytes. Histamine interacts with four receptors, H1-H4HRs. H1HR acts by Gαq activating IP(3)/Ca(2+), whereas H2HR activates Gα(s) stimulating cAMP. We hypothesize that histamine increases biliary growth by activating H1HR on small and H2HR on large cholangiocytes. The expression of H1-H4HRs was evaluated in liver sections, isolated and cultured (normal rat intrahepatic cholangiocyte culture (NRIC)) cholangiocytes. In vivo, normal rats were treated with histamine or H1-H4HR agonists for 1 week. We evaluated: (1) intrahepatic bile duct mass (IBDM); (2) the effects of histamine, H1HR or H2HR agonists on NRIC proliferation, IP(3) and cAMP levels and PKCα and protein kinase A (PKA) phosphorylation; and (3) PKCα silencing on H1HR-stimulated NRIC proliferation. Small and large cholangiocytes express H1-H4HRs. Histamine and the H1HR agonist increased small IBDM, whereas histamine and the H2HR agonist increased large IBDM. H1HR agonists stimulated IP(3) levels, as well as PKCα phosphorylation and NRIC proliferation, whereas H2HR agonists increased cAMP levels, as well as PKA phosphorylation and NRIC proliferation. The H1HR agonist did not increase proliferation in PKCα siRNA-transfected NRICs. The activation of differential signaling mechanisms targeting small and large cholangiocytes is important for repopulation of the biliary epithelium during pathologies affecting different-sized bile ducts

Threshold Dose for Shrimp: A Risk Characterization Based on Objective Reactions in Clinical Studies

A DBPCFC [double-blind, placebo-controlled food challenge] of shrimp-allergic adults was conducted to obtain individual threshold doses. Results of this study and published research were combined and a population threshold for shrimp was determined from dose-distribution modeling. The shrimp-allergic population seems to have a higher threshold compared to other populations for other food allergens. Additional shrimp challenges should be done to confirm these initial results