RSS 1.0Faculty, Student Works School of Medicine
Browse by
Recent Submissions
-
The nephrocyte actin and tubulin cytoskeleton networks model slit diaphragm structural defects pertaining to podocyte pathogenesis (b)The nephrocyte is the structural and functional equivalent of a human podocyte in Drosophila melanogaster, particularly the slit diaphragm. The nephrocyte was used to determine the relationship between nephrotic function, the actin and tubulin cytoskeletons, and their shared binding proteins. Of 18 shared binding proteins between the actin and tubulin cytoskeletons, the knockdown of Pigs results in the most dramatic phenotype. Immunofluorescent staining was used to see morphological differences in actin, tubulin, dual actin and tubulin binding protein, and insulin signaling genes. This information can be used to aid further research into causes and solutions to renal diseases such as Nephrotic Syndrome and Diabetic Nephropathy
-
The nephrocyte actin and tubulin cytoskeleton networks model slit diaphragm structural defects pertaining to podocyte pathogenesis (a)The nephrocyte is the Drosophila melanogaster equivalent of a human podocyte. Use the nephrocyte to determine the relationship between nephrotic function, the actin and tubulin cytoskeletons, and their shared binding proteins. RNA-seq, functional readouts, and immunofluorescent stains were conducted to understand the roles of each gene. 14 shared binding proteins between the actin and tubulin cytoskeletons, with Pigs causing the most dramatic phenotype. This information can be used to aid further research into causes and solutions to renal diseases such as Nephrotic Syndrome.
-
Using the Photo-crosslinkable non-canonical amino acid BZF to capture U.V.-driven, state-dependent disruption of kinetics and voltage dependence of activation in hERG potassium channelsHuman ether-á-go-go related gene (hERG) voltage-activated potassium channels are critical for cardiac excitability. Characteristic slow closing (deactivation) in hERG is regulated by direct interaction between the Nterminal Per-Arnt-Sim (PAS) domain and the C-terminal cyclic nucleotide binding homology domain (CNBHD). Now, we aim to understand the how the conformational dynamics and accessible landscape of the hERG PAS domain contributes to channel kinetics and voltage dependence. To achieve this, we utilized the non-canonical amino acid 4-Benzoyl-L-phenylalanine (BZF) which is a photo-activatable cross-linkable probe, that when irradiated with ultraviolet (U.V.) light forms a covalent cross-link with C-H bond-containing groups, enabling selective and potent U.V.-driven state-dependent photoinactivation modification of ion channel dynamics. This is because BZF can form bonds to nearby atoms via cross-linkable reactivity reducing degrees of freedom within a domain of the channel. Here we incorporate BZF directly into the hERG potassium channel using TAG codon suppression that, upon U.V exposure, shows a large change in the biophysical properties of the channel when irradiated at -100mV when the channels are closed. When compared to wild-type hERG1a, hERG1a-E50BZF shows a U.V. dose-dependent change (speeding up) of channel deactivation. Additionally, hERG1a-E50BZF exhibits a marked change (right-shift) in the voltage-dependence of activation when irradiated at -100 mV when the channels are closed. These effects are not observed when the hERG1a-BZF channel is irradiated in at 0mV when the channels are open. This approach demonstrates that direct photo-crosslinking of hERG channels causes a measurable change in biophysical parameters and this effect is state-dependent (occurring here in the closed state but not the open state). We propose that altered channel gating is as a direct result of reduced dynamic motions in the hERG channel due to photo-chemical crosslinking.
-
Designing and Implementing an Orthopedic Residency Program with a 4-month Inpatient Rotation: Benefits and ChallengesABPTRFE accreditation standards for orthopedic physical therapy residencies and the current ABPTRFE Description of Residency Practice for Orthopaedics [Jun 2017] are written with an exclusive focus on the outpatient setting. Physical therapists in the outpatient setting often care for postsurgical patients who have recently spent time in the inpatient setting. Significant exposure to the inpatient setting may be useful to support outpatient physical therapist practice. There are few orthopedic PT residency programs that include a full-time inpatient rotation, but none contains an inpatient rotation of this length. The University of Maryland is a graduate healthcare university that offers the possibility of many partnerships.
