Real Ways of Talking and School Talking: One Appalachian Student\u27s Perception of Teacher Discourse During Writing Conferences

A barrier to school literacy is created when teachers fail to build upon the familiar language of students. These research findings indicate that when students perceive that nonstandard ways of talking are not as highly valued by the school as Standard English is valued, they deliberately fail to produce written products that match their teacher\u27s expectations

Investigating Connections Between Teacher Beliefs and Instructional Practices with Struggling Readers

This study examines and describes the changes in four teachers\u27 beliefs and practices in literacy and literacy assessment over the course of a yearlong graduate level clinical experience. Four teachers who worked in the university literacy clinic as part of their graduate course work participated in this study. Two of the four teachers teach elementary aged pupils in a public school, another serves as a reading resource educator at a public elementary school, and the fourth teaches high school-aged students at an alternative school associated with a public school. Findings indicate that teacher beliefs and their classroom instruction are often inconsistent due to a variety of variables such as the pressure to conform to a particular school philosophy and/or government mandates. In spite of these pressures the findings confirm that these teachers serve as the key evaluator of their students\u27 literacy development

Genetic Analysis of Central Carbon Metabolism Unveils an Amino Acid Substitution That Alters Maize NAD-Dependent Isocitrate Dehydrogenase Activity

Background: Central carbon metabolism (CCM) is a fundamental component of life. The participating genes and enzymes are thought to be structurally and functionally conserved across and within species. Association mapping utilizes a rich history of mutation and recombination to achieve high resolution mapping. Therefore, applying association mapping in maize (Zea mays ssp. mays), the most diverse model crop species, to study the genetics of CCM is a particularly attractive system. Methodology/Principal Findings: We used a maize diversity panel to test the CCM functional conservation. We found heritable variation in enzyme activity for every enzyme tested. One of these enzymes was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41), in which we identified a novel amino-acid substitution in a phylogenetically conserved site. Using candidate gene association mapping, we identified that this non-synonymous polymorphism was associated with IDH activity variation. The proposed mechanism for the IDH activity variation includes additional components regulating protein level. With the comparison of sequences from maize and teosinte (Zea mays ssp. Parviglumis), the maize wild ancestor, we found that some CCM genes had also been targeted for selection during maize domestication. Conclusions/Significance: Our results demonstrate the efficacy of association mapping for dissecting natural variation in primary metabolic pathways. The considerable genetic diversity observed in maize CCM genes underlies heritable phenotypic variation in enzyme activities and can be useful to identify putative functional sites

Elevated protein concentrations in newborn blood and the risks of autism spectrum disorder, and of social impairment, at age 10 years among infants born before the 28th week of gestation

Among the 1 of 10 children who are born preterm annually in the United States, 6% are born before the third trimester. Among children who survive birth before the 28th week of gestation, the risks of autism spectrum disorder (ASD) and non-autistic social impairment are severalfold higher than in the general population. We examined the relationship between top quartile inflammation-related protein concentrations among children born extremely preterm and ASD or, separately, a high score on the Social Responsiveness Scale (SRS total score ≥65) among those who did not meet ASD criteria, using information only from the subset of children whose DAS-II verbal or non-verbal IQ was ≥70, who were assessed for ASD, and who had proteins measured in blood collected on ≥2 days (N = 763). ASD (N = 36) assessed at age 10 years is associated with recurrent top quartile concentrations of inflammation-related proteins during the first post-natal month (e.g., SAA odds ratio (OR); 95% confidence interval (CI): 2.5; 1.2–5.3) and IL-6 (OR; 95% CI: 2.6; 1.03–6.4)). Top quartile concentrations of neurotrophic proteins appear to moderate the increased risk of ASD associated with repeated top quartile concentrations of inflammation-related proteins. High (top quartile) concentrations of SAA are associated with elevated risk of ASD (2.8; 1.2–6.7) when Ang-1 concentrations are below the top quartile, but not when Ang-1 concentrations are high (1.3; 0.3–5.8). Similarly, high concentrations of TNF-α are associated with heightened risk of SRS-defined social impairment (N = 130) (2.0; 1.1–3.8) when ANG-1 concentrations are not high, but not when ANG-1 concentrations are elevated (0.5; 0.1–4.2)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Role of the 2 subunit of voltage-dependent calcium channels in the retinal outer plexiform layer

PURPOSE. Mutations in the ␣ 1F subunit of voltage-dependent calcium channels (VDCCs) have been shown to cause incomplete congenital stationary night blindness (CSNB2). The purpose of this study was to identify which of the four ␤ subunits of VDCCs participates in the formation of this channel at the photoreceptor synapse and to determine how its absence affects visual processing. METHODS. Mice without each of the four known ␤ subunits of VDCCs were generated by gene targeting and transgenic rescue (CNS-␤ 1 , -␤ 2 ) or by gene targeting alone (␤ 3 ) or were obtained from a commercial provider (␤ 4 ). Retinal function and visual sensitivity were examined by electroretinography and an active avoidance behavioral test, respectively. The structure of the retina and expression of the ␣ 1F subunit were examined at the light microscopic level and by immunohistochemistry. RESULTS. Under dark-adapted conditions, CNS-␤ 2 -null mice had a normal ERG a-wave, but did not have a normal b-wave. In addition, these mice showed decreased sensitivity to light. Both the a-and b-waves appear normal in the CNS-␤ 1 -, ␤ 3 -, and ␤ 4 -null mice. Histologic analyses of all four mouse lines indicated that only the CNS-␤ 2 -null mice had altered retinal morphology. Eyes of these mice had a thinner outer plexiform layer (OPL) than eyes of control animals. In addition, the labeling pattern of the ␣ 1F subunit in the OPL was altered in CNS-␤ 2 -null mice. CONCLUSIONS. The normal distribution of the ␣ 1F subunit of the VDCCs in the OPL is dependent on the expression of the ␤ 2 subunit. The expression of both of these subunits is required for normal maintenance and/or formation of the OPL and synaptic transmission. (Invest Ophthalmol Vis Sci. 2002;43: 1595-1603 T he visual signal generated in the rod photoreceptors is transmitted to second-order neurons through ribbon synapses in the outer plexiform layer (OPL) of the retina. 1,2 These synapses are specialized structures in which glutamate release is mediated by calcium entry through slowly inactivating L-type voltage-dependent calcium channels (VDCCs). 3-8 The importance of these channels in visual function was recently highlighted by the discovery that mutations in the ␣ 1F subunit of VDCCs are responsible for an X-linked disorder, incomplete congenital stationary night blindness (CSNB2) in humans. 9,10 More recently, Morgans and colleagues Neuronal VDCCs are heteromultimers, composed of ␣ 1 , ␣ 2 /␦, and ␤-subunits and possibly a neuronal homologue of the skeletal ␥ subunit. 14 To date, 10 ␣ 1 -, 4 ␤-, 3 ␣ 2 /␦-, and 8 ␥-subunit 15 genes have been identified (for review see Ref. 16). In all VDCCs the ␣ 1 subunit forms the channel pore, which contains the voltage sensor and the drug-binding site used to define the channel type. The ␣ 2 /␦ and ␤ subunits are important in determining channel kinetics, and the ␤ subunits are necessary for expression of the channel. 23 To begin to identify the structural makeup of VDCCs at the photoreceptor ribbon synapse, we examined the role of the ␤ subunits in mouse visual function. We describe electrophysiological, anatomic, and behavioral studies in mice with no expression of the ␤ 2 subunit in the CNS. We show that the absence of the ␤ 2 subunit in the retina results in an abnormal distribution of the ␣ 1F subunit in the retina, which has profound effects on visual function and the ERG that are not seen in mice without the other ␤ subunits. These results indicate that normal function of the retinal VDCCs at the photoreceptor-to-bipolar cell synapse is highly dependent on the presence of the ␤ 2 subunit and that mice without this subunit provide an animal model for CSNB2. From th