Design and synthesis of Nrf2-derived hydrocarbon stapled peptides for the disruption of protein-DNA-interactions.

Misregulation and mutations of the transcription factor Nrf2 are involved in the development of a variety of human diseases. In this study, we employed the technology of stapled peptides to address a protein-DNA-complex and designed a set of Nrf2-based derivatives. Varying the length and position of the hydrocarbon staple, we chose the best peptide for further evaluation in both fixed and living cells.

Synthesis and Characterization of Cationic Hydrogels from Thiolated Copolymers for Independent Manipulation of Mechanical and Chemical Properties of Cell Substrates.

Cells sense both mechanical and chemical properties in their environment and respond to these inputs with altered phenotypes. Precise and selective experimental manipulations of these environmental cues require biocompatible synthetic materials, for which multiple properties can be fine-tuned independently from each other. For example, cells typically show critical thresholds for cell adhesion as a function of substrate parameters such as stiffness and the degree of functionalization.

Monitoring the Response of Multiple Signal Network Components to Acute Chemo-Optogenetic Perturbations in Living Cells.

Cells process information via signal networks that typically involve multiple components which are interconnected by feedback loops. The combination of acute optogenetic perturbations and microscopy-based fluorescent response readouts enables the direct investigation of causal links in such networks. However, due to overlaps in spectra of photosensitive and fluorescent proteins, current approaches that combine these methods are limited.

Optogenetic Tuning Reveals Rho Amplification-Dependent Dynamics of a Cell Contraction Signal Network.

Local cell contraction pulses play important roles in tissue and cell morphogenesis. Here, we improve a chemo-optogenetic approach and apply it to investigate the signal network that generates these pulses. We use these measurements to derive and parameterize a system of ordinary differential equations describing temporal signal network dynamics.

CLASS-WIDE FUNCTION-RELATED INTERVENTION TEAMS (CW-FIT): Student and Teacher Outcomes from a Multisite Randomized Replication Trial.

The purpose of the study was to conduct a randomized controlled trial (RCT) to demonstrate efficacy of the Classwide Function-Related Intervention Teams (CW-FIT) program. The study was designed to replicate an initial RCT conducted by the CW-FIT developers in 1 site, with 2 additional research groups not involved in its development. The study was conducted across 3 states, in 21 culturally diverse schools, and with 83 teachers (classrooms) assigned to CW-FIT and 74 teachers (classrooms) assigned to the comparison group.

An excitable Rho GTPase signaling network generates dynamic subcellular contraction patterns.

Rho GTPase-based signaling networks control cellular dynamics by coordinating protrusions and retractions in space and time. Here, we reveal a signaling network that generates pulses and propagating waves of cell contractions. These dynamic patterns emerge via self-organization from an activator-inhibitor network, in which the small GTPase Rho amplifies its activity by recruiting its activator, the guanine nucleotide exchange factor GEF-H1.

Deblurring Signal Network Dynamics.

To orchestrate the function and development of multicellular organisms, cells integrate intra- and extracellular information. This information is processed via signal networks in space and time, steering dynamic changes in cellular structure and function. Defects in those signal networks can lead to developmental disorders or cancer.

"Molecular Activity Painting": Switch-like, Light-Controlled Perturbations inside Living Cells.

Acute subcellular protein targeting is a powerful tool to study biological networks. However, signaling at the plasma membrane is highly dynamic, making it difficult to study in space and time. In particular, sustained local control of molecular function is challenging owing to the lateral diffusion of plasma membrane targeted molecules.

Impact of a Teacher-as-Coach Model: Improving Paraprofessionals Fidelity of Implementation of Discrete Trial Training for Students with Moderate-to-Severe Developmental Disabilities.

Ensuring educational progress for students with moderate-to-severe developmental disabilities requires exposure to well executed evidence-based practices. This necessitates that the special education workforce, including paraprofessionals, be well-trained. Yet evidence regarding effective training mechanisms for paraprofessionals is limited.

A Group Contingency Plus Self-Management Intervention Targeting At-Risk Secondary Students' Class-Work and Active Engagement.

The purpose of the present study is to show that an independent group contingency (GC) combined with self-management strategies and randomized-reinforcer components can increase the amount of written work and active classroom responding in high school students. Three remedial reading classes and a total of 15 students participated in this study. Students used self-management strategies during independent reading time to increase the amount of writing in their reading logs.

Social Communication Effects of Peer-Mediated Recess Intervention for Children with Autism.

Children with ASD face enormous challenges in the area of social functioning. Research has shown that impairments in social functioning distinguish this population from both typically developing children and children with disabilities. This study incorporated several evidence-based social skills-teaching procedures (i.

Class-Wide Function-Related Intervention Teams "CW-FIT" Efficacy Trial Outcomes.

The purpose of the study was to determine the efficacy of the Class-wide Function-related Intervention Teams (CW-FIT) program for improving students' on-task behavior, and increasing teacher recognition of appropriate behavior. The intervention is a group contingency classroom management program consisting of teaching and reinforcing appropriate behaviors (i.e.

A comprehensive peer network intervention to improve social communication of children with autism spectrum disorders: a randomized trial in kindergarten and first grade.

The purpose of this randomized control group study was to examine the effects of a peer network intervention that included peer mediation and direct instruction for Kindergarten and First-grade children with autism spectrum disorders. Trained school staff members provided direct instruction for 56 children in the intervention group, and 39 children participated in a comparison group. Results showed children in the intervention group displayed significantly more initiations to peers than did the comparison group during non-treatment social probes and generalization probes.

Peer Mediation to Increase Communication and Interaction at Recess for Students with Autism Spectrum Disorders.

Recess plays an integral role in the social and emotional development of children given the time provided to engage in interactions with others and practice important social skills. Students with ASD, however, typically fail to achieve even minimal benefit from recess due to social and communication impairments as well as a tendency to withdraw. Implementation of evidence-based interventions such as peer-mediated social skills groups, are necessary to ensure recess is an advantageous learning environment for students with ASD.

Effects of small-group reading instruction and curriculum differences for students most at risk in kindergartenL: two-year results for secondary- and tertiary-level interventions.

This article describes the implementation of small-group reading instruction as secondary- and tertiary-level components of a three-tier model of prevention and intervention. The study consisted of 83 students who were targeted in the winter of kindergarten as being at high risk for reading failure. Intervention consisted of evidence-based curriculum delivered in groups of one to six students during 30- to 40-min sessions a minimum of three times per week over a 2-year period.

The effects of a group contingency intervention on academic engagement and problem behavior of at-risk students.

A successful learning environment can be characterized by actively engaged students displaying appropriate student behavior. We implemented a group contingency intervention as a novel component to a school-wide behavior management system to decrease the frequency of inappropriate behaviors and, conversely, increase the academic engagement of students in four elementary school classrooms. Twelve students with behavioral risks served as target students to monitor effects.

Formulating secondary-level reading interventions.

Recent advances concerning emerging/beginning reading skills, positive behavioral support (PBS), and three-tiered schoolwide prevention models combined with federal mandates (i.e., IDEA and No Child Left Behind) have stimulated interest in providing early and intensive instructional intervention services to children at risk for reading and behavior problems.

Brief report: increasing communication skills for an elementary-aged student with autism using the Picture Exchange Communication System.

The purpose of this study was to examine the effects of the Picture Exchange Communication System (PECS) on the spontaneous communication skills of a 6-year-old girl with autism across her home and school environments. The effects of the PECS were also examined for social interaction. Results indicated increases in spontaneous language (i.

Brief report: reduction of inappropriate vocalizations for a child with autism using a self-management treatment program.

Self-management procedures that incorporate elements of self-assessment, self-recording, and self-reinforcement have reduced stereotypic (i.e., repetitive) behaviors in children with autism in clinical settings.

Effects of cooperative learning groups during social studies for students with autism and fourth-grade peers.

We investigated the use of cooperative learning groups as an instructional strategy for integrating 2 students with autism into a fourth-grade social studies class. Baseline consisted of 40 min of teacher-led sessions including lecture, questions and discussion with students, and the use of maps. The intervention condition consisted of 10 min of teacher introduction of new material, followed by cooperative learning groups that included tutoring on key words and facts, a team activity, and a whole class wrap-up and review.

Enhanced small group instruction using choral responding and student interaction for children with autism and developmental disabilities.

The use of effective instructional strategies in small groups was investigated to determine learning effects for 24 elementary age students with autism and developmental disabilities. Effective strategies included (a) the use of choral responding; (b) the use of student-to-student responding; (c) the rotation of materials every 5 minutes during the 30-minute group while teaching 2 to 3 concepts; and (d) the use of random, unpredictable trials for student responding. Thirty-minute language groups were targeted to teach receptive and expressive skills using pictures and common objects across five categories (e.

Classwide peer tutoring: an integration strategy to improve reading skills and promote peer interactions among students with autism and general education peers.

A multiple baseline design across subjects with a reversal was used to examine the effects of classwide peer tutoring relative to traditional reading instruction on reading skills and social interaction time for 3 high-functioning students with autism and their typical peers in integrated, general education classrooms. Traditional reading instruction consisted largely of teacher-led instruction with individual student participation and seat work. Classwide peer tutoring consisted of 25 to 30 min of well-specified instruction in which tutor-learner pairs worked together on a classwide basis on reading fluency and comprehension skills.