Speech Analysis

Contains research objectives and reports on one research project.National Science Foundatio

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell–like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2–containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia

Effect of a major ice storm on understory light conditions in an old-growth Acer-Fagus forest: Pattern of recovery over seven years

We evaluated the effects of a major ice storm on understory light conditions (%PPFD, photosynthetic photon flux density) in an old-growth Acer-Fagus forest in Quebec, based on pre- and post-disturbance light measurements taken until the seventh growing season after the event (which occurred in January 1998). Before the ice storm, most microsites received between 2 and 4%PPFD. Following the ice storm, the stand-level mean %PPFD increased four- to five-fold, ranging from 13.8 to 20.5%PPFD, from 0.3 to 4 m aboveground. Despite its magnitude, the post-ice storm increase in light transmission was short-lived. By 1999 (2-year+), the mean light levels had decreased by half, and recovery to pre-storm conditions occurred within 3-7 years, depending on height. The decrease in light transmission during the post-disturbance years followed an inverse J-shape trend, indicating more dynamic changes early after disturbance. By 2004 (7-year+), light levels at ≤2 m had become slightly but significantly lower than before the ice storm, with most microsites receiving <2%PPFD. The ice storm led to a synchronized increase of the light levels at almost all understory locations, which might allow a high proportion of the advanced regeneration to experience a release. However, due to the rapid recovery of the light conditions to levels similar or lower than before the ice storm, this disturbance should be more advantageous to shade-tolerant species

Assessment of Cytomegalovirus-Specific Cell-Mediated Immunity for the Prediction of Cytomegalovirus Disease in High-Risk Solid-Organ Transplant Recipients: A Multicenter Cohort Study

In high-risk solid-organ transplant recipients receiving antiviral prophylaxis, the measurement of specific cell-mediated immunity using the Quantiferon assay appropriately stratified the individual risk of developing subsequent cytomegalovirus diseas

Identification of a Phosphorylation Site for Calcium/Calmodulindependent Protein Kinase II in the NR2B Subunit of the N-Methyl-D-aspartate Receptor

The N-methyl-D-aspartate (NMDA) subtype of excitatory glutamate receptors plays critical roles in embryonic and adult synaptic plasticity in the central nervous system. The receptor is a heteromultimer of core subunits, NR1, and one or more regulatory subunits, NR2A-D. Protein phosphorylation can regulate NMDA receptor function (Lieberman, D. N., and Mody, I. (1994) Nature 369, 235-239; Wang, Y. T., and Salter, M. W. (1994) Nature 369, 233-235; Wang, L.-Y., Orser, B. A., Brautigan, D. L., and MacDonald, J. F. (1994) Nature 369, 230-232). Here we identify a major phosphorylation site on subunit NR2B that is phosphorylated by Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), an abundant protein kinase located at postsynaptic sites in glutamatergic synapses. For the initial identification of the site, we constructed a recombinant fusion protein containing 334 amino acids of the C terminus of the NR2B subunit and phosphorylated it with CaM kinase II in vitro. By peptide mapping, automated sequencing, and mass spectrometry, we identified the major site of phosphorylation on the fusion protein as Ser-383, corresponding to Ser-1303 of full-length NR2B. The Km for phosphorylation of this site in the fusion protein was ~50 nM, much lower than that of other known substrates for CaM kinase II, suggesting that the receptor is a high affinity substrate. We show that serine 1303 in the full-length NR2B and/or the cognate site in NR2A is a major site of phosphorylation of the receptor both in the postsynaptic density fraction and in living hippocampal neurons

Remix as Professional Learning: Educators’ Iterative Literacy Practice in CLMOOC

The Connected Learning Massive Open Online Collaboration (CLMOOC) is an online professional development experience designed as an openly networked, production-centered, participatory learning collaboration for educators. Addressing the paucity of research that investigates learning processes in MOOC experiences, this paper examines the situated literacy practices that emerged as educators in CLMOOC composed, collaborated, and distributed multimediated artifacts. Using a collaborative, interactive visual mapping tool as participant-researchers, we analyzed relationships between publically available artifacts and posts generated in one week through a transliteracies framework. Culled data included posts on Twitter (n = 678), a Google+ Community (n = 105), a Facebook Group (n = 19), a blog feed (n = 5), and a “make� repository (n = 21). Remix was found to be a primary form of interaction and mediator of learning. Participants not only iterated on each others’ artifacts, but on social processes and shared practices as well. Our analysis illuminated four distinct remix mobilities and relational tendencies—bursting, drifting, leveraging, and turning. Bursting and drifting characterize the paces and proximities of remixing while leveraging and turning are activities more obviously disruptive of social processes and power hierarchies. These mobilities and tendencies revealed remix as an emergent, iterative, collaborative, critical practice with transformative possibilities for openly networked web-mediated professional learning.ECU Open Access Publishing Support Fun

Passive heat exposure alters perception and executive function

Findings regarding the influence of passive heat exposure on cognitive function remain equivocal due to a number of methodological issues including variation in the domains of cognition examined. In a randomized crossover design, forty-one male participants completed a battery of cognitive function tests [Visual Search, Stroop, Corsi Blocks and Rapid Visual Information Processing (RVIP) tests] prior to and following 1 h of passive rest in either hot (39.6 ± 0.4°C, 50.8 ± 2.3% Rh) or moderate (21.2 ± 1.8°C, 41.9 ± 11.4% Rh) conditions. Subjective feelings of heat exposure, arousal and feeling were assessed alongside physiological measures including core temperature, skin temperature and heart rate, at baseline and throughout the protocol. Response times were slower in the hot trial on the simple (main effect of trial, P 0.05). Subjective feelings of thermal sensation and felt arousal were higher, feeling was lower in the hot trial, whilst skin temperature, core temperature and heart rate were higher (main effects of trial, all P < 0.001). The findings of the present study suggest that response times for perception and executive function tasks are worse in the heat. An improvement in accuracy on perceptual tasks may suggest a compensatory speed-accuracy trade-off effect occurring within this domain, further highlighting the task dependant nature of heat exposure on cognition

Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc −, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives: Our goal was to determine whether increased system xc − activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc −, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system xc − inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc − activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc − activity. Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc −. Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system xc − independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine