Visual Impairment and Its Affects on Gross Motor Development: A Literature Review and Implications for Physical Therapy

Visual impairment, or blindness, in the pediatric population has been shown to affect several key areas of gross motor development. Many of these areas can be positively influenced by physical therapy techniques. However, some physical therapy curriculums do not teach this topic of study because the prevalence of blindness is low. The purpose of this study is to develop a teaching manual that will provide the physical therapist with specific exercises, activities, and helpful hints that will facilitate the treatment of a patient with blindness in a pediatric setting. The manual includes information regarding common mannerisms of the blind population and physical deficits that occur with blindness such as body spatial awareness deficits, weakness of certain muscle groups, abnormal gait patterns, and postural abnormalities. The procedure used to perform this study was a literature review that includes a thorough explanation of the developmental problems associated with visual impairment Information regarding the utilization of residual vision and treatment implications related to physical therapy is presented. Pictures of treatment techniques with a pre-school aged are shown for clearer representation of technique. This manual is designed to provide physical therapists with information to facilitate assessment and treatment of pediatric patients with visual impairments

Are Increasing Test Scores in Texas Really a Myth?

Pass rates by Texas tenth-graders on the high school exit exam improved from 52 percent in 1994 to 72 percent in 1998. In his article "The Myth of the Texas Miracle in Education" (EPAA, August 2000) Professor Walt Haney argued that some part of this increased pass rate was, as he put it, an illusion. Haney contended that the combined effects of students dropping out of school prior to taking the 10th grade TAAS and special education exemptions accounted for much of the increase in TAAS pass rates. Relying on the same methodology and data that Haney used, we demonstrate that his conclusion is incorrect. None of the 20 percent improvement in the TAAS exit test pass rate between 1994 and 1998 is explained by combined increases in dropout rates or special education exemptions

Characterization of the Effects of Exogenous Camp Combined on C. Albicans Morphogenesis in Strains Lacking NRG1P, RFG1P, or TUP1P (Poster)

The opportunistic human pathogen Candida albicans causes both superficial and lifethreatening systemic infections and is a leading cause of fungal disease in immunocompromised individuals.  C. albicans can grow in different cell shapes, or morphologies, including yeast-like cells and a variety of filamentous forms, such as true hyphae and pseudohyphae. Yeast, hyphae and pseudohyphae have been observed at the sites of Candida infection and there is strong evidence that morphogenesis, the transition between yeast and filamentous growth forms, is essential for virulence. Many studies have implicated cAMP in the regulation of morphogenesis. cAMP acts to activate filamentation. Our lab and others have previously characterized the impact of the negative regulators, Nrg1, Rfg1, and Tup1 on the expression of HWP1, a hyphal specific gene.  The goal of this project is to characterize whether the addition of exogenous cAMP will increase the expression oHWP1 in the absence of each of the negative regulators. This will help us better understand the signal transduction cascade that controls morphogenesis in C. albicans

Analysis of BH31-1 Derivative's Effect on Candida Species

Candida species are the most common and arguably the most important causative agents of human fungal infections. Oropharyngeal, esophageal, vulvovaginal, and cutaneous candidiasis leads to significant morbidity while systemic infections in immunocompromised patients (patients with AIDS, tissue transplants, central venous catheters, or those undergoing chemotherapy) has a 35% mortality rate. During infection, it is essential that the dimorphic Candida species switch between different morphological states including transitions between budded or yeast-like cells and hyphal forms. The small molecule BH3I-1 has shown promising results at inhibiting hyphal formation in several Candida species. The goal of this study is to find a BH3I-1 derivative that inhibits hyphal formation in several Candida species at a lower minimum inhibitory concentration (MIC) than BH3I-1. A derivative with a low MIC that affects several Candida species may have a potential to be a broad-spectrum antifungal drug. The Candida species being tested against the BH3I-1 derivatives are: C. albicans, C. glabrata, C. rugosa, C. krusei, C. tropicalis, C. lusitaniae, C. dubliniesis, and C. parapsilosis. Currently, 36 BH3I-1 derivatives have been tested. Molecule 25 has an MIC about 4 times lower than BH3I-1 in Candida albicans and has also been shown to work in other Candida species at inhibiting hyphal formation. Other derivatives such as molecule #10 did not inhibit many of the tested Candida species, but showed a much lower MIC than molecule #25 in C. rugosa. Out of the 36 tested derivatives, molecule #25 has shown the promise for a broad-ranged antifungal drug

Characteristics of the Effect of Exogenous Camp on C. Albicans Morphogenesis in Strains Lacking NRG1P, RFG1P, or TUP1P

The opportunistic human pathogen Candida albicans causes both superficial and life threatening systemic infections and is a leading cause of fungal disease in immunocompromised individuals such as those with AIDS. C. albicans can grow in different cell shapes, also known as morphologies, including yeast-like cells and a variety of filamentous forms, such as true hyphae and pseudohyphae. Yeast, hyphae and pseudohyphae, have been observed at the sites of Candida infection and there is strong evidence that morphogenesis, the transition between yeast and filamentous growth forms, is essential for its virulence. Many studies have implicated the second messenger molecule cAMP in the regulation of morphogenesis due to its role in activating filamentation. Our lab and others have previously characterized the impact of the negative regulators, Nrg1, Rfg1, and Tup1 on the expression of HWP1, a hyphal specific gene. The goal of this project is to characterize whether the addition of exogenous cAMP will increase the expression of HWP1 in the absence of each of the negative regulators as well as test a small molecule derivative of BH3I’s effects in conjunction with the exogenous cAMP. This will help us better understand the signal transduction cascade that controls morphogenesis in C. albicans

IDENTIFICATION OF POTENTIAL TARGETS OF THE GRR1P SCF UBIQUITIN LIGASE IN FUNGI

The opportunistic human pathogen Candida albicans causes both superficial and life-threatening systemic infections and is a leading cause of fungal disease in immunocompromised individuals.  C. albicans can grow in different cell shapes, or morphologies, including yeast-like cells and a variety of filamentous forms, such as true hyphae and pseudohyphae.   Yeast, hyphae and pseudohyphae have been observed at the sites of Candida infection and there is strong evidence that morphogenesis, the transition between yeast and filamentous growth forms, is essential for virulence. Several studies have implicated ubiquitin-dependent proteolysis in the regulation of morphogenesis, yet the mechanism by which this pathway does so is largely unknown.  Previously, we have shown that deletion of the GRR1 gene results in the constitutive formation of filamentous growth forms.  The Grr1 protein is a component of an SCF ubiquitin ligase system that selectively targets proteins for degradation.  Thus, the loss of Grr1-mediated proteolysis presumably leads to the aberrant accumulation, and inappropriate activity, of a protein or proteins that induce filamentous growth.  The spectrum of proteins targeted for degradation by Grr1 is not known.  The goal of this project is to identify Grr1 targets in Saccharomyces cerevisiae, an experimentally tractable model system for pathogenic fungi.  We are using a novel proteomics-based approach to isolate and characterize proteins that are ubiquitinated in a Grr1-dependent fashion. The successful identification of Grr1p targets will be important for developing a working model of the pathways involved in the yeast to filamentous growth transition in pathogenic fungi

BH3I-1 DERIVATIVES INHIBIT THE FILAMENTOUS GROWTH OF THE CEA10 STRAIN OF ASPERGILLUS FUMIGATUS

Recent and exciting advances in medical therapies for cancer and organ failures have greatly extended the life span of afflicted patients. However, these therapies often place the patient at risk for potentially lethal fungal infections. As the number of immunocompromised patients continues to rise, there has been an increase in associated opportunistic fungal infections. Treatment options for invasive mycoses caused by Candida albicans and Aspergillus fumigatus are surprisingly limited. A. fumigatus is the most common Aspergillus species associated with invasive pulmonary aspergillosis, accounting for over 60% of cases. Aspergillus grows as a filamentous mold with true hyphae originating from the germination of asexual conidia.  A. fumigatus is not a dimorphic fungi as is the case with C. albicans, however, as both grow in hyphal form it seems possible that small molecules that inhibit the transition of C. albicans budded cells to hyphal growth (often referred to as the germination of blastoconidia) may also inhibit the germination of Aspergillus conidia. We tested BH3I-1 and derivatives against A. fumigatus strain CEA10 in YPD media. BH3I-1 and five of the derivatives inhibited at a 200?M concentration based on general observation via microscopy as well as eleven showing promising inhibition at possible different concentrations. Out of these inhibiting molecules, seven also shown inhibition within the prior C. albicans assay. We are currently employing a micro-plate reader to obtain quantitative levels of inhibition with increasing concentrations of molecule. Molecule 54 at the 300?M concentration showed similar inhibition to that of BH3I-1 at the same concentration

Multisite Phosphorylation of the Guanine Nucleotide Exchange Factor Cdc24 during Yeast Cell Polarization

BACKGROUND:Cell polarization is essential for processes such as cell migration and asymmetric cell division. A common regulator of cell polarization in most eukaryotic cells is the conserved Rho GTPase, Cdc42. In budding yeast, Cdc42 is activated by a single guanine nucleotide exchange factor, Cdc24. The mechanistic details of Cdc24 activation at the onset of yeast cell polarization are unclear. Previous studies have suggested an important role for phosphorylation of Cdc24, which may regulate activity or function of the protein, representing a key step in the symmetry breaking process. METHODOLOGY/PRINCIPAL FINDINGS:Here, we directly ask whether multisite phosphorylation of Cdc24 plays a role in its regulation. We identify through mass spectrometry analysis over thirty putative in vivo phosphorylation sites. We first focus on sites matching consensus sequences for cyclin-dependent and p21-activated kinases, two kinase families that have been previously shown to phosphorylate Cdc24. Through site-directed mutagenesis, yeast genetics, and light and fluorescence microscopy, we show that nonphosphorylatable mutations of these consensus sites do not lead to any detectable consequences on growth rate, morphology, kinetics of polarization, or localization of the mutant protein. We do, however, observe a change in the mobility shift of mutant Cdc24 proteins on SDS-PAGE, suggesting that we have indeed perturbed its phosphorylation. Finally, we show that mutation of all identified phosphorylation sites does not cause observable defects in growth rate or morphology. CONCLUSIONS/SIGNIFICANCE:We conclude that lack of phosphorylation on Cdc24 has no overt functional consequences in budding yeast. Yeast cell polarization may be more tightly regulated by inactivation of Cdc42 by GTPase activating proteins or by alternative methods of Cdc24 regulation, such as conformational changes or oligomerization