Effect of Instruction Method on Competency and Perception of Proloquo2Go

This study investigated three approaches to learning the basics of Proloquo2Go in order to assess the effectiveness of the instructional method and its effect on the participants’ attitude toward AAC.With the establishment of the Individuals with Disabilities Education Act (IDEA), more children with severe communication disorders are being educated in public school general education classrooms. Augmentative and alternative communication (AAC) devices are often the primary means of communication for nonverbal students and have been shown to improve the communication, language, and literacy skills of children with such deficits.Teacher’s attitudes toward the use and effectiveness of AAC has been found to be negative. Does instructional method affect the speed at which novel users demonstrate competency in Proloquo2Go? Does the type of training influence the attitude of novel users toward AAC

Using the Voice of the Student to Evaluate Learning Management Systems

A learning management system is an educational tool employed in higher education to organize, document, track, report, and deliver courses. Selecting the appropriate learning management system is a critical decision for a university. This study explores the usability of two leading systems, Blackboard and Canvas, from the students’ perspective. The goal is to gather and analyze user preferences in order to select an appropriate learning management system. Data was collected through surveys of student’s experience with the two learning management systems. The survey evaluated the ease of the following tasks: finding course documents, viewing grades, ease of navigation, intuitiveness, and communicating with professors. A usability study was also conducted on both learning management systems. The information was combined to provide an overall ranking of the learning management systems

BAK Alters Neuronal Excitability and Can Switch from Anti- to Pro-Death Function during Postnatal Development

AbstractBAK is a pro-apoptotic BCL-2 family protein that localizes to mitochondria. Here we evaluate the function of BAK in several mouse models of neuronal injury including neuronotropic Sindbis virus infection, Parkinson's disease, ischemia/stroke, and seizure. BAK promotes or inhibits neuronal death depending on the specific death stimulus, neuron subtype, and stage of postnatal development. BAK protects neurons from excitotoxicity and virus infection in the hippocampus. As mice mature, BAK is converted from anti- to pro-death function in virus-infected spinal cord neurons. In addition to regulating cell death, BAK also protects mice from kainate-induced seizures, suggesting a possible role in regulating synaptic activity. BAK can alter neurotransmitter release in a direction consistent with its protective effects on neurons and mice. These findings suggest that BAK inhibits cell death by modifying neuronal excitability

Intra-oropharyngeal food transport and swallowing in white-spotted bamboo sharks

Despite the importance of intraoral food transport and swallowing, relatively few studies have examined the biomechanics of these behaviors in non-tetrapods, which lack a muscular tongue. Studies show that elasmobranch and teleost fishes generate water currents as a 'hydrodynamic tongue' that presumably transports food towards and into the esophagus. However, it remains largely unknown how specific musculoskeletal motions during transport correspond to food motion. Previous studies of white-spotted bamboo sharks (Chiloscyllium plagiosum) hypothesized that motions of the hyoid, branchial arches and pectoral girdle, generate caudal motion of the food through the long oropharynx of modern sharks. To test these hypotheses, we measured food and cartilage motion with XROMM during intra-oropharyngeal transport and swallowing (N=3 individuals, 2-3 trials per individual). After entering the mouth, food does not move smoothly toward the esophagus, but rather moves in distinct steps with relatively little retrograde motion. Caudal food motion coincides with hyoid elevation and a closed mouth, supporting earlier studies showing that hyoid motion contributes to intra-oropharyngeal food transport by creating caudally directed water currents. Little correspondence between pectoral girdle and food motion was found, indicating minimal contribution of pectoral girdle motion. Transport speed was fast as food entered the mouth, slower and step-wise through the pharyngeal region and then fast again as it entered the esophagus. The food's static periods in the step-wise motion and its high velocity during swallowing could not be explained by hyoid or girdle motion, suggesting these sharks may also use the branchial arches for intra-oropharyngeal transport and swallowing

Bcl-xL regulates mitochondrial energetics by stabilizing the inner membrane potential

To promote cell survival, the antiapoptotic factor Bcl-xL both inhibits Bax-induced mitochondrial outer membrane permeabilization and stabilizes mitochondrial inner membrane ion flux and thus overall mitochondrial energetic capacity

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

O-Glycosylation Regulates Ubiquitination and Degradation of the Anti-Inflammatory Protein A20 to Accelerate Atherosclerosis in Diabetic ApoE-Null Mice

Background: Accelerated atherosclerosis is the leading cause of morbidity and mortality in diabetic patients. Hyperglycemia is a recognized independent risk factor for heightened atherogenesis in diabetes mellitus (DM). However, our understanding of the mechanisms underlying glucose damage to the vasculature remains incomplete. Methodology/Principal Findings: High glucose and hyperglycemia reduced upregulation of the NF-κB inhibitory and atheroprotective protein A20 in human coronary endothelial (EC) and smooth muscle cell (SMC) cultures challenged with Tumor Necrosis Factor alpha (TNF), aortae of diabetic mice following Lipopolysaccharide (LPS) injection used as an inflammatory insult and in failed vein-grafts of diabetic patients. Decreased vascular expression of A20 did not relate to defective transcription, as A20 mRNA levels were similar or even higher in EC/SMC cultured in high glucose, in vessels of diabetic C57BL/6 and FBV/N mice, and in failed vein grafts of diabetic patients, when compared to controls. Rather, decreased A20 expression correlated with post-translational O-Glucosamine-N-Acetylation (O-GlcNAcylation) and ubiquitination of A20, targeting it for proteasomal degradation. Restoring A20 levels by inhibiting O-GlcNAcylation, blocking proteasome activity, or overexpressing A20, blocked upregulation of the receptor for advanced glycation end-products (RAGE) and phosphorylation of PKCβII, two prime atherogenic signals triggered by high glucose in EC/SMC. A20 gene transfer to the aortic arch of diabetic ApoE null mice that develop accelerated atherosclerosis, attenuated vascular expression of RAGE and phospho-PKCβII, significantly reducing atherosclerosis. Conclusions: High glucose/hyperglycemia regulate vascular A20 expression via O-GlcNAcylation-dependent ubiquitination and proteasomal degradation. This could be key to the pathogenesis of accelerated atherosclerosis in diabetes

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations