Effects of a Developmental English Program Redesign on Underprepared Students’ Academic Success

The study explored first-year composition (FYC) success by students who were initially enrolled in developmental English at a public university in the western United States. The study site redesigned its developmental English program to increase time to completion and completion rates of FYC and minimize time to completion of that course by developmental students, yet no evaluation had been conducted to determine the effects of the redesigned program. The framework that supported this study was Adelman’s theory of academic momentum. Using a quantitative nonexperimental, causal-comparative design and census sample, the research question explored two dimensions of FYC completion, including (a) whether the curriculum redesign had decreased time to enrollment in FYC and (b) whether the redesign had decreased the time required to successfully complete FYC (N = 132). An independent samples t test revealed that on average, the post-redesign group (n = 92) enrolled in FYC .89 semesters faster than the pre-redesign group (n = 40), t(160) = 4.91, p \u3c 0.01. For those who completed the FYC, the post-redesign group (n = 92) averaged completing 1.05 semesters faster than the pre-redesign group (n = 38), t(128) = 5.0, p \u3c 0.01. A project position paper supporting the redesign is included with recommendations for continuation of the program, additional research, and other methods of delivering and evaluating developmental education. The study results in positive social change by confirming the efficacy of the redesigned developmental English program and by serving as a model for the evaluation of similar programs in other institutions of higher learning

GATA3 and MDM2 are synthetic lethal in estrogen receptor-positive breast cancers.

Synthetic lethal interactions, where the simultaneous but not individual inactivation of two genes is lethal to the cell, have been successfully exploited to treat cancer. GATA3 is frequently mutated in estrogen receptor (ER)-positive breast cancers and its deficiency defines a subset of patients with poor response to hormonal therapy and poor prognosis. However, GATA3 is not yet targetable. Here we show that GATA3 and MDM2 are synthetically lethal in ER-positive breast cancer. Depletion and pharmacological inhibition of MDM2 significantly impaired tumor growth in GATA3-deficient models in vitro, in vivo and in patient-derived organoids/xenograft (PDOs/PDX) harboring GATA3 somatic mutations. The synthetic lethality requires p53 and acts via the PI3K/Akt/mTOR pathway. Our results present MDM2 as a therapeutic target in the substantial cohort of ER-positive, GATA3-mutant breast cancer patients. With MDM2 inhibitors widely available, our findings can be rapidly translated into clinical trials to evaluate in-patient efficacy

Large-scale mapping of mutations affecting zebrafish development

BACKGROUND: Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. RESULTS: We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. CONCLUSION: By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations

The transcriptional landscape of hematopoietic stem cell ontogeny

Transcriptome analysis of adult hematopoietic stem cells (HSCs) and their progeny has revealed mechanisms of blood differentiation and leukemogenesis, but a similar analysis of HSC development is lacking. Here, we acquired the transcriptomes of developing HSCs purified from >2,500 murine embryos and adult mice. We found that embryonic hematopoietic elements clustered into three distinct transcriptional states characteristic of the definitive yolk sac, HSCs undergoing specification, and definitive HSCs. We applied a network-biology-based analysis to reconstruct the gene regulatory networks of sequential stages of HSC development and functionally validated candidate transcriptional regulators of HSC ontogeny by morpholino-mediated knockdown in zebrafish embryos. Moreover, we found that HSCs from in vitro differentiated embryonic stem cells closely resemble definitive HSCs, yet lack a Notch-signaling signature, likely accounting for their defective lymphopoiesis. Our analysis and web resource will enhance efforts to identify regulators of HSC ontogeny and facilitate the engineering of hematopoietic specification

Robotic injection of zebrafish embryos for high-throughput screening in disease models

The increasing use of zebrafish larvae for biomedical research applications is resulting in versatile models for a variety of human diseases. These models exploit the optical transparency of zebrafish larvae and the availability of a large genetic tool box. Here we present detailed protocols for the robotic injection of zebrafish embryos at very high accuracy with a speed of up to 2000 embryos per hour. These protocols are benchmarked for several applications: (1) the injection of DNA for obtaining transgenic animals, (2) the injection of antisense morpholinos that can be used for gene knock-down, (3) the injection of microbes for studying infectious disease, and (4) the injection of human cancer cells as a model for tumor progression. We show examples of how the injected embryos can be screened at high-throughput level using fluorescence analysis. Our methods open up new avenues for the use of zebrafish larvae for large compound screens in the search for new medicines

The Effects of Music on Memory for a Word List

Using 40 university students as participants, memory for a word list was tested using different conditions in which subjects had to listen to music or no music during study and test phases. Previous research has indicated that music can enhance mood and sports performance (Fassbender et al., 2012) and Mann (2008) found that sounds in an environment enhance learning. The context in which something is learned and encoded was found by Balch et al. (1992) to enhance memory if such conditions are repeated in the test phase. This led to the hypothesis that the condition in which no music was played during study or test would produce the best results. The results of the experiment did not reflect the hypothesis in that it only mattered if there was music playing during the study phase as it had a negative effect on encoding. Other reasons included small representation of the gross population and lack of control in the test environment as well as lack of reliability and validity