A5039649492- Lipid Membrane Structure and Behavior
- Neuroscience and Neuropharmacology Research
- Fluid Dynamics and Thin Films
- Receptor Mechanisms and Signaling
- Nanomaterials and Printing Technologies
- High-pressure geophysics and materials
- Semiconductor Quantum Structures and Devices
- Ion channel regulation and function
- Surface Modification and Superhydrophobicity
- Photoreceptor and optogenetics research
- Surfactants and Colloidal Systems
- nanoparticles nucleation surface interactions
- Geological and Geochemical Analysis
- Cell death mechanisms and regulation
- Erythrocyte Function and Pathophysiology
- Fluid Dynamics and Turbulent Flows
- Force Microscopy Techniques and Applications
- RNA Interference and Gene Delivery
- Nerve injury and regeneration
- Spectroscopy and Quantum Chemical Studies
- Advanced Fluorescence Microscopy Techniques
- Neurobiology and Insect Physiology Research
- Neurogenesis and neuroplasticity mechanisms
- Adhesion, Friction, and Surface Interactions
- Thin-Film Transistor Technologies
University of California, Berkeley
2007-2024
New South Wales Department of Primary Industries
2023
University of Oxford
2023
National Park Service
2017-2022
University of California, Los Angeles
2020
St Thomas' Hospital
2016
BioPhage Pharma (Canada)
2014
Aegera Therapeutics (Canada)
2002-2010
Google (United States)
2010
Northwestern University
2009
We examined the biosynthesis and post-translational processing of brain-derived neurotrophic factor precursor (pro-BDNF) in cells infected with a pro-BDNF-encoding vaccinia virus. Metabolic labeling, immunoprecipitation, SDS-polyacrylamide gel electrophoresis reveal that pro-BDNF is generated as 32-kDa N-glycosylated glycosulfated on site, within pro-domain. Some released extracellularly biologically active demonstrated by its ability to mediate TrkB phosphorylation. The undergoes N-terminal...
Amplification of the CCNE1 locus on chromosome 19q12 is prevalent in multiple tumour types, particularly high-grade serous ovarian cancer, uterine tumours and gastro-oesophageal cancers, where high cyclin E levels are associated with genome instability, whole-genome doubling resistance to cytotoxic targeted therapies
Nerve growth factor (NGF) is released through the constitutive secretory pathway from cells in peripheral tissues and nerves where it can act as a target-derived survival factor. In contrast, brain-derived neurotrophic (BDNF) appears to be processed regulated of brain neurons secreted an activity-dependent manner play role synaptic plasticity. To determine whether sorting differences are intrinsic neurotrophins or reflect between cell types, we compared NGF BDNF processing cultured...
Foam in porous media exhibits an unusually high apparent viscosity, making it useful many industrial processes. The rheology of foam, however, is complex and not well understood. Previous pore-level models foam are based primarily on studies bubble flow circular capillaries. A capillary, lacks the corners that characterize geometry pores. We study pressure–velocity relation polygonal long a capillary acts as leaky piston. ‘piston’ reluctant to move because large drag exerted by sidewalls....
This work determines the pressure–velocity relation of bubble flow in polygonal capillaries. The liquid pressure drop needed to drive a long at given velocity U is solved by an integral method. In this method, shown balance drag bubble, which determined films two ends bubble. Using liquid-film results Part 1 (Wong, Radke & Morris 1995), we find that scales as Ca 2/3 limit → 0 ( μ /σ, where viscosity and σ surface tension). Thus, also . proportionality constant for six different...
In an attempt to understand the temperature distribution in earth, experimental constraints on geotherm crust and mantle are considered. The basic form of is interpreted basis two dominant mechanisms by which heat transported earth: (1) conduction through rock, (2) advection thermal flow. Data reveal that: distributions continental lithosphere oceanic more than 60 million years old practically indistinguishable, crustal uplift instrumental modifying geotherms, (3) average Archean was similar...
We have monitored kinetics of fusion between cell pairs consisting a single influenza hemaglutinin (HA)-expressing and erythrocyte (RBC) that had been labeled with both fluorescent lipid (Dil) in the membrane solute (calcein) aqueous space. Initial pore opening RBC HA-expressing produced change potential (delta psi) was by decrease Dil fluorescence. This event followed two distinct stages dilation: flux (phi L) large dye s). analyzed events occur as result transitions (FP) permissive (FPs)....
Extracellular cues direct axon extension by regulating growth cone morphology. The netrin-1 receptor deleted in colorectal cancer (DCC) is required for commissural to the floor plate embryonic spinal cord. Here we demonstrate that challenging rat neurons with netrin-1, either solution or as a substrate, causes DCC-dependent increases surface area and filopodia number, which term expansion. We provide evidence DCC influences morphology at least two mechanisms. First, mediates an adhesive...
DNA polymerase theta (Polθ) is an attractive synthetic lethal target for drug discovery, predicted to be efficacious against breast and ovarian cancers harboring BRCA-mutant alleles. Here, we describe our hit-to-lead efforts in search of a selective inhibitor human Polθ (encoded by POLQ). A high-throughput screening campaign 350,000 compounds identified 11 micromolar hit, giving rise the N2-substituted fused pyrazolo series, which was validated biophysical methods. Structure-based design...
The fusion of cells by influenza hemagglutinin (HA) is the best characterized example protein-mediated membrane fusion. In simultaneous measurements pairs assays for fusion, we determined order detectable events during Fusion pore formation in HA-triggered cell-cell was first detected changes cell capacitance, next a flux fluorescent lipid, and finally aqueous dye. conductance increased small steps. A retardation lipid dyes occurred fluctuations. dye depended on size molecule. lack movement...
Fusion between membranes of 3T3 fibroblasts expressing hemagglutinin (HA) from the Japan strain influenza virus and human red blood cells (RBC) was measured using an assay for lipid mixing based on relief self-quenching (dequenching) fluorescence probe octadecylrhodamine (R18). The incorporated into membrane intact RBC at concentrations, RBCs were bound to cells. Fusion, which allowed movement R18 cell membranes, monitored by spectrofluorometry as increase in fluorescence. Upon lowering pH...
Abstract Purpose: Cancer cells can use X-linked inhibitor of apoptosis (XIAP) to evade apoptotic cues, including chemotherapy. The antitumor potential AEG35156, a novel second-generation antisense oligonucleotide directed toward XIAP, was assessed in human cancer models when given as single agent and combination with clinically relevant chemotherapeutics. Experimental Design: AEG35156 characterized for its ability cause dose-dependent reductions XIAP mRNA protein vitro vivo, sensitize cell...
X-linked inhibitor of apoptosis protein (XIAP) is an caspases 3 and 9 which are overexpressed in acute myeloid leukemia (AML) may contribute to chemoresistance. We report on a phase I/II trial the XIAP antisense oligonucleotide AEG35156 combination with reinduction chemotherapy.Twenty-four patients rapidly relapsed or refractory AML were treated escalating doses (12 250 mg/m(2)) as intravenous solution over 2 hours 32 highest planned dose 350 mg/m(2) idarubicin high-dose cytarabine...
We have monitored the mixing of both aqueous intracellular and membrane-bound fluorescent dyes during fusion human red blood cells to influenza hemagglutinin-expressing fibroblasts using fluorescence spectroscopy low light, image-enhanced video microscopy. The water-soluble dye, N-(7-nitrobenzofurazan-4-yl)taurine, was incorporated into intact cells. dye in cell partially quenched by hemoglobin. lipid fluorophore, octadecylrhodamine, membrane same at self-quenching concentrations (Morris, S....
A rapid method for purifying Torpedo electric organ vesicles is described, which employs an isoosmotic continuous sucrose-glycine gradient followed by chromagography on CPG-10-3000 porous glass beads. The synaptic have a buoyant density of 1.057 g/ml. purified are free cholinesterase, lactate dehydrogenase and Na+, K+-stimulated ATPase activity. They contain ouabaininsensitive, K+-inhibited, Mg2+, Ca2+-stimulated This further stimulated acetylcholine but not choline.
Pattern printing techniques have advanced rapidly in the past decade, driven by their potential applications printed electronics. Several realized features of 10 μm or smaller, but unfortunately, they suffer from disadvantages that prevent deployment real applications; particular, process throughput is a significant concern. Direct gravure promising this regard. Gravure delivers high and has proven history being manufacturing worthy. Unfortunately, it suffers scalability challenges because...
Hippocampal neurons release nerve growth factor (NGF) through the constitutive secretory pathway, thus allowing protein to be continuously available for promoting cell survival. In contrast, hippocampal use regulated pathway process brain-derived neurotrophic (BDNF), which alters synaptic activity when released acutely from dense-core vesicles. Thus, understanding how sort and deliver neurotrophins may provide clues their functions in brain. this study, we monitored processing delivery of...