Bufo houstonensis

Number of Pages: 2Integrative BiologyGeological Science

Rana blairi

Number of Pages: 6Integrative BiologyGeological Science

Similarities in Evasive Behavior of Wolf Spiders (Araneae: Lycosidae), American Toads (Anura: Bufonidae) and Ground Beetles (Coleopterea: Carabidae)

(excerpt) While collecting newly metalnorphosed American toads, Bufo anlericanus Holbrook, we have observed that they exhibited evasive behavior similar to that of adults of the wolf spiders, Pardosa saxatilis (Hentz), Pirata insularis Emerton, Pirata arerzicola Emerton, Pirata piratica (Oliver), and adults of the ground beetle, Elaplrrus ruscarius Say. When pursued or disturbed, the spiders, beetles and toads ran across the pound rapidly for short distances (ca. 1-50 cm). They then stopped abruptly and remained motionless. If they were further pursued, this escape sequence was repeated in the same or another direction. Toads and spiders occasionally moved to shallow water to avoid capture. Spiders ran across the water surface whereas the toads swam partially submerged. N\u27e observed this resemblance in evasive behavior on numerous occasions at ponds on the south edge of Carbondale, Illinois (spiders and toads), 1 krn west of Grinnell, Iowa (spiders and toads), and 1.5 km west of Bloomington, Illinois (spiders, toads and beetles). (Specimens were collected for identification from the latter site.

BARRIERS TO CHANGE FOR AUGMENTATIVE AND ALTERNATIVE COMMUNICATION USE

Title: BARRIERS TO CHANGE FOR AUGMENTATIVE AND ALTERNATIVE COMMUNICATION USE Keywords: speech language pathology, augmentative and alternative communication, counseling, readiness to change, self-efficacy In recent literature, there has been a marked increase in importance placed upon understanding what factors both positively and negatively impact the progress made by a client and that client’s family in response to speech and language therapy. Today, clinicians prioritize evidence based practice (EBP) when making clinical decisions, focusing on not only clinical expertise and best evidence, but also client and caregiver perspectives, or preferences (ASHA, 2018). In consideration of EBP for augmentative and alternative communication (AAC), Beukelman and Mirenda (2005) in their book Augmentative and Alternative Communication, note several Barriers to Participation which hinder a client or client’s family from adequately accepting the use of an AAC device. These barriers could be overcome faster and more efficiently through the use of counseling tools and counseling techniques. Specifically, training to determine current levels of self-efficacy will be the used for both the training and application for speech pathologists in the West Kentucky Special Education Cooperative. The study addressed three questions, the identification of participant’s competency in addressing negative attitudes toward AAC, competency in applying Readiness to Change techniques in treatment with clients who use AAC devices and how SLPs typically counsel stakeholders in the use of AAC. Upon initial review of the data analysis, there was a significant change in training participant’s perceived competency regarding their ability to use counseling tools for AAC clients

BARRIERS TO CHANGE FOR AUGMENTATIVE AND ALTERNATIVE COMMUNICATION

The purpose of this study was to identify the effects of counseling training on speech language pathologists’ (SLPs) perceived competency to address Attitude Barriers within the augmentative and alternative communication (AAC) assessment process as presented by Beukelman and Mirenda (2005). Counseling techniques, such as the use of the Readiness to Change© tool, are within the scope of practice for SLPs. Unfortunately, there is a lack of research on how to apply these tools and techniques with individuals who use AAC . A training seminar was conducted to educate participants in the use of the Readiness to Change© tool. Data was collected using a mixed-methods pre-and post-test survey. The quantitative results indicated a statistically significant change in participants’ perceived competency to use the counseling tools. The qualitative results identified several interesting themes within SLPs responses. Continuation of this research topic is recommended based on the both the outcomes of the data as well as the need for further knowledge on the subject

Development of fungal-selective resorcylate aminopyrazole Hsp90 inhibitors

Session: “Infectious Disease Drug Discovery in New England”514815 Subgrant 1 - Governing Council of the University of TorontoOthe

Diastereodivergent synthesis of chiral tetrahydropyrrolodiazepinediones via a one-pot intramolecular aza-Michael/lactamization sequence

A modular and diastereodivergent synthesis of tetrahydro-1H-pyrrolo[1,2d]diazepine-(2,5)-diones is presented. The tetrahydropyrrolodiazepinedione scaffold is obtained via a base-mediated three-step isomerization/tandem cyclization of amino acid-coupled homoallylic amino esters. Diastereoselectivity of the process is mediated by the interplay of a kinetic cyclization event and a propensity for thermodynamic epimerization at two labile chiral centers, giving rise to two distinct major diastereomers dependent on starting material stereochemistry and reaction conditions selected. Herein, we present a synthetic and computational study for this tandem process on a variety of amino ester substrates.Work at the BU-CMD is supported by R24GM111625. The authors wish to thank Dr. Jeffrey Bacon for assistance with Xray crystallographic analysis, Dr. Norman Lee for assistance with high-resolution mass spectrometry analysis, and Dr. Paul Ralifo for assistance with NMR analysis. NMR (CHE-0619339) and MS (CHE-0443618) facilities at Boston University are supported by the NSF. (CHE-0619339 - NSF; CHE-0443618 - NSF; R24GM111625)Published versionSupporting documentationAccepted manuscrip

Translation inhibition by rocaglates activates a species-specific cell death program in the emerging fungal pathogen Candida auris

Fungal infections are a major contributor to infectious disease-related deaths worldwide. Recently, global emergence of the fungal pathogen Candida auris has caused considerable concern because most C. auris isolates are resistant to fluconazole, the most commonly administered antifungal, and some isolates are resistant to drugs from all three major antifungal classes. To identify novel agents with bioactivity against C. auris, we screened 2,454 compounds from a diversity-oriented synthesis collection. Of the five hits identified, most shared a common rocaglate core structure and displayed fungicidal activity against C. auris These rocaglate hits inhibited translation in C. auris but not in its pathogenic relative Candida albicans Species specificity was contingent on variation at a single amino acid residue in Tif1, a fungal member of the eukaryotic initiation factor 4A (eIF4A) family of translation initiation factors known to be targeted by rocaglates. Rocaglate-mediated inhibition of translation in C. auris activated a cell death program characterized by loss of mitochondrial membrane potential, increased caspase-like activity, and disrupted vacuolar homeostasis. In a rocaglate-sensitized C. albicans mutant engineered to express translation initiation factor 1 (Tif1) with the variant amino acid that we had identified in C. auris, translation was inhibited but no programmed cell death phenotypes were observed. This surprising finding suggests divergence between these related fungal pathogens in their pathways of cellular responses to translation inhibition. From a therapeutic perspective, the chemical biology that we have uncovered reveals species-specific vulnerability in C. auris and identifies a promising target for development of new, mechanistically distinct antifungals in the battle against this emerging pathogen. IMPORTANCE Emergence of the fungal pathogen Candida auris has ignited intrigue and alarm within the medical community and the public at large. This pathogen is unusually resistant to antifungals, threatening to overwhelm current management options. By screening a library of structurally diverse molecules, we found that C. auris is surprisingly sensitive to translation inhibition by a class of compounds known as rocaglates (also known as flavaglines). Despite the high level of conservation across fungi in their protein synthesis machinery, these compounds inhibited translation initiation and activated a cell death program in C. auris but not in its relative Candida albicans Our findings highlight a surprising divergence across the cell death programs operating in Candida species and underscore the need to understand the specific biology of a pathogen in attempting to develop more-effective treatments against it.Published versio

Sensitization of renal carcinoma cells to TRAIL-induced apoptosis by rocaglamide and analogs

Rocaglamide has been reported to sensitize several cell types to TRAIL-induced apoptosis. In recent years, advances in synthetic techniques have led to generation of novel rocaglamide analogs. However, these have not been extensively analyzed as TRAIL sensitizers, particularly in TRAIL-resistant renal cell carcinoma cells. Evaluation of rocaglamide and analogs identified 29 compounds that are able to sensitize TRAIL-resistant ACHN cells to TRAIL-induced, caspase-dependent apoptosis with sub-µM potency which correlated with their potency as protein synthesis inhibitors and with loss of cFLIP protein in the same cells. Rocaglamide alone induced cell cycle arrest, but not apoptosis. Rocaglates averaged 4–5-fold higher potency as TRAIL sensitizers than as protein synthesis inhibitors suggesting a potential window for maximizing TRAIL sensitization while minimizing effects of general protein synthesis inhibition. A wide range of other rocaglate effects (e.g. on JNK or RAF-MEK-ERK signaling, death receptor levels, ROS, ER stress, eIF4E phosphorylation) were assessed, but did not contribute to TRAIL sensitization. Other than a rapid loss of MCL-1, rocaglates had minimal effects on mitochondrial apoptotic pathway proteins. The identification of structurally diverse/mechanistically similar TRAIL sensitizing rocaglates provides insights into both rocaglate structure and function and potential further development for use in RCC-directed combination therapy.This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of NIH, Frederick. National Lab, Center for Cancer Research. Research performed at Boston University was supported in part by NIH R35 GM118173. Work at the BU-CMD is supported by R24 GM111625. (HHSN261200800001E - National Cancer Institute, National Institutes of Health; Intramural Research Program of NIH, Frederick. National Lab, Center for Cancer Research; R35 GM118173 - NIH; R24 GM111625)Published versio

Fabrication of extracellular matrix-derived foams and microcarriers as tissue-specific cell culture and delivery platforms

© 2017 Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Cell function is mediated by interactions with the extracellular matrix (ECM), which has complex tissue-specific composition and architecture. The focus of this article is on the methods for fabricating ECM-derived porous foams and microcarriers for use as biologically-relevant substrates in advanced 3D in vitro cell culture models or as pro-regenerative scaffolds and cell delivery systems for tissue engineering and regenerative medicine. Using decellularized tissues or purified insoluble collagen as a starting material, the techniques can be applied to synthesize a broad array of tissue-specific bioscaffolds with customizable geometries. The approach involves mechanical processing and mild enzymatic digestion to yield an ECM suspension that is used to fabricate the three-dimensional foams or microcarriers through controlled freezing and lyophilization procedures. These pure ECM-derived scaffolds are highly porous, yet stable without the need for chemical crosslinking agents or other additives that may negatively impact cell function. The scaffold properties can be tuned to some extent by varying factors such as the ECM suspension concentration, mechanical processing methods, or synthesis conditions. In general, the scaffolds are robust and easy to handle, and can be processed as tissues for most standard biological assays, providing a versatile and user-friendly 3D cell culture platform that mimics the native ECM composition. Overall, these straightforward methods for fabricating customized ECM-derived foams and microcarriers may be of interest to both biologists and biomedical engineers as tissue-specific cell-instructive platforms for in vitro and in vivo applications