Glioblastoma, which occurs in adults primarily between ages of 40 to 70 years and accounts for 15% of all brain tumors, is a devastating diagnosis with a median survival rate of less than a year. Invasiveness of glioblastoma cells significantly reduces the effectiveness of current treatments, highlighting the importance of...
Cell motility and invasion are important for development, immunity, wound healing, and tumor cell metastasis. Cells on two dimensional substrates migrate in three steps: protrusion of the front end, translocation of the cell body, and retraction of the rear end. For cells to migrate efficiently, these steps need to be...
Glioblastoma is the most malignant primary brain tumor with the average
patients surviving only one year after diagnosis, even with aggressive therapy. The
formation of numerous micro-tumors dispersed into the brain due to rapid invasion of
tumor cells, presents the primary challenge to the surgical removal of tumors and
limits...
Glioblastoma multiforme is a form of primary brain cancer in humans with a 5 year survival rate of less than 4%. Glioblastoma cells are characterized by their highly invasive nature linked to mutations in key signaling proteins such as PTEN, resulting in loss of expression of this lipid phosphatase. When...
The cysteine-rich protein (CRP) family is a subgroup of LIM domain proteins. CRP1, which cross-links actin filaments to make actin bundles, is the only CRP family member expressed in the CNS with little known about its function in nerve cells. Here, we report that CRP1 colocalizes with actin in the...
Hallmarks of aging include the accumulation of aberrant proteins and a lower resistance to stresses. Because the endoplasmic reticulum (ER) functions to fold proteins and possesses unique stress sensing pathways, the central hypothesis of this dissertation is that the ER is a target of cellular aging and significantly underlies these...
Glioblastoma Multiform
• Type of aggressive brain cancer
• Five year survival rate of 4.70%
• Not often detected until it’s in the later stages when
the symptoms appear
• Surgery is not an effective option due to invasion and
proliferation of glioblastoma cells outside of the tumor
mass before...
Natural products from both terrestrial and marine sources represent a significant source of novel drug leads, and have previously been developed into clinically-approved agents for the treatment of various human diseases. This work represents the biological characterization of the mechanistic basis for activity of several natural product structures in models...
Glioblastoma is a malignant brain tumor that has extremely poor prognoses with a 5 year survival rate of less than 5%. The low survival rates of glioblastoma patients is attributed to glioblastoma cells being extremely resistant to radiotherapy and chemotherapy as well as being very invasive. We previously identified calpain...
Fluorinated alkyl substances, which can be persistent, toxic, and
bioaccumulative, have been quantitated in many densely populated and
remote regions, including in air, surface waters, groundwater, and biota;
however, little is known about their transport or behavior in the environment.
Wastewater effluent is one of the principal routes for introducing...
The atmospheric transport and deposition of semi-volatile organic compounds (SOCs), including current and historic use pesticides, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), to mountain ecosystems may result in the exposure of tadpoles to these SOCs. This exposure has been implicated in amphibian population declines in California. Tadpoles encounter...
Chemicals must be bioavailable for there to be a potential for exposure and consequent risk to human or environmental health. Passive sampling devices (PSDs) are used to quantify the time-integrated concentration of bioavailable contaminants. We demonstrate that PSDs can be paired with the zebrafish developmental toxicity bioassay to produce site-specific,...
Glioblastoma multiforme is the most common primary brain tumor in adults ages 45-70, with over 12,120 new cases in the U.S. predicted for 2016 alone. Glioblastoma is also one of the most difficult cancers to treat because the tumor cells tend to invade into the surrounding healthy tissue, making it...
Glioblastoma multiforme is the most common primary brain tumor in adults ages 45-70, with over 12,120 new cases in the U.S. predicted for 2016 alone. Glioblastoma is also one of the most difficult cancers to treat because the tumor cells tend to invade into the surrounding healthy tissue, making it...
Glioblastoma multiforme is a devastating primary brain tumor with a median five year survival rate of less than 5%. It is a cancer that is resistant to current cancer treatments, such as surgery and chemotherapy, as well as one that is prone to recurrence after surgical removal. This highlights the...
Frequency distributions are calculated for the optical
decay of two atomic states which are coupled by a strong,
linear rf field. Both the rotating and the counter-rotating
components of the field are maintained throughout the
calculations. For strong fields many peaks are present in
the frequency spectrum and are explained...
A comparative investigation of the phenotypic properties of environmental and clinical strains of the lactose-positive human pathogen, Vibrio vulnificus, revealed that they are indistinguishable in traits commonly used for identification in clinical and public health laboratories. It has also been confirmed that there are other strains of undefined Vibrio spp.,...
Glutathione (GSH) is the predominant low molecular weight thiol antioxidant
in liver tissue. GSH plays an important role in maintaining the intracellular thiol redox
ratio as well as detoxification of electrophiles and xenobiotics. Aging leads to a significant decline (35%; P ≤ 0.05) in hepatocellular GSH levels. Using young (2-4...
Phospholipase C-β (PLC-β) isozymes are key effectors in G protein-coupled
signaling pathways. Prior research suggested that some isoforms of PLC-β may exist
and function as dimers, but little is known about dimerization of PLC-β. Data from coimmunoprecipitation
assays of differentially-tagged PLC-β constructs and sizeexclusion
chromatography of native PLC-β support homodimerization...
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. Defining toxicity mechanisms for this large family of multi-ring structures and substituted derivatives is a substantial challenge. Several PAHs, such as benzo(a)pyrene (BaP), are mutagenic, toxic to wildlife, and classified as probable...
Prior to cell cleavage, cytokinetic proteins are recruited into the nascent actomyosin contractile ring. Interactions between spindle microtubules and the cell cortex play a critical role in this recruitment. However, direct evidence for physical interaction between microtubules and the cortex has been lacking. Here we reveal the physical connection between...
Studies using the pluripotent embryonic carcinoma cell line, P19, as a retinoic acid (RA)-responsive model system have been instrumental towards our understanding of the RA-dependent signaling pathways in development and homeostasis. Grp1-associated scaffold protein (GRASP; also known as Tamalin) was first identified by our group, as a gene robustly induced...
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Mark Leid
Studies using the pluripotent embryonic carcinoma cell line, P19, as a
Coibamide A is a methyl-stabilized cyclic depsipeptide with a lariat side chain that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups program based in Panama. Previous testing of this potent and selective growth-inhibitory agent in the National Cancer Institute (NCI) in vitro 60 human...
Passive sampling is a popular technology for environmental monitoring, and silicone is an ideal choice for a variety of passive sampling applications. The silicone work described here encompasses laboratory and field studies that demonstrate the use of this polymer in novel environments, for new applications, and for emerging compounds. Unique...
Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by the progressive degeneration of motor neurons. Dominantly-inherited mutations to the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) cause 3-6% of all ALS cases. The complete mechanism behind the toxicity of mutant SOD1 remains unclear, although significant evidence points to aberrant or...
Mutations to superoxide dismutase were the first proven cause of Lou
Gehrig’s disease (amyotrophic lateral sclerosis; ALS) implicating superoxide in
the selective death of motor neurons that characterizes ALS. Nitric oxide
competes effectively with superoxide dismutase for superoxide to form the
powerful oxidant peroxynitrite. Endogenous formation of peroxynitrite can kill...
Coibamide A is an N-methyl-stabilized depsipeptide that was isolated from a marine cyanobacterium as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. Previous testing of coibamide A in the NCI in vitro 60 cancer cell line panel revealed a potent anti-proliferative response and "COMPARE-negative" profile indicative...
The goal of this dissertation was to improve our abilities in acquiring critical in vivo data by establishing embryo-larva zebrafish as an exemplary model to quantitatively evaluate cancer progression. The living environment that encompasses a tumor has a significant effect on how cancer develops, grows and metastasizes. In order to...
The numerous different types of nanomaterials and paucity of reliable in vivo information on toxicity has resulted in enduring uncertainties associated with health and safety risks, thereby slowing progress in nanotherapeutic assessment and development. This dissertation explores how the embryonic zebrafish model can be applied to prioritize commonly used nanomaterial...
Pacific Northwest and California freshwater resources are key elements in the life history and ecology of Pacific salmon and steelhead listed as threatened or endangered under the Endangered Species Act. Risk to listed Pacific salmonid species can be assessed by evaluating the spatial and temporal co-occurrence of salmonid species at...
The tadpoles of several anuran species with groupforming
larvae are relatively unpalatable to many of
their potential predators. To more fully understand the
role of palatability and its relationship to group
formation as an antipredator defense in anuran amphibian
larvae, I investigated the palatabilities of the larvae
of three species...
Despite the belief that fuels management, a form of prescribed fire that reduces accumulated fuels in commercially thinned forests, is necessary to restore forest 'health' in the Pacific Northwest, its effects on wildlife has received little attention in the scientific literature. Because fuels management is supported, funded, and implemented nationwide...
Positively-charged gold nanoparticles (0.8-nm core diameter) reduced yeast
survival, but not growth, at a concentration of 10 to 100 μg/ml. Among 17 resistant
deletion mutants isolated in a genome-wide screen, highly significant enrichment
was observed for respiration-deficient mutants lacking genes encoding proteins
associated with the mitochondrion.
Positively-charged gold nanoparticles (0.8-nm core diameter) reduced yeast
survival, but not growth, at a concentration of 10 to 100 μg/ml. Among 17 resistant
deletion mutants isolated in a genome-wide screen, highly significant enrichment
was observed for respiration-deficient mutants lacking genes encoding proteins
associated with the mitochondrion.
Full Text:
. Boenzli,a Vihangi Hindagolla,a Jun Ding,a,b John M. Miller,c,d James E. Hutchison,c,d
JeffreyA
Positively-charged gold nanoparticles (0.8-nm core diameter) reduced yeast
survival, but not growth, at a concentration of 10 to 100 μg/ml. Among 17 resistant
deletion mutants isolated in a genome-wide screen, highly significant enrichment
was observed for respiration-deficient mutants lacking genes encoding proteins
associated with the mitochondrion.
Full Text:
, John M. Miller3,4, 4
James E. Hutchison3,4, JeffreyA. Greenwood2, Hagai Abeliovich5, Alan T
Positively-charged gold nanoparticles (0.8-nm core diameter) reduced yeast
survival, but not growth, at a concentration of 10 to 100 μg/ml. Among 17 resistant
deletion mutants isolated in a genome-wide screen, highly significant enrichment
was observed for respiration-deficient mutants lacking genes encoding proteins
associated with the mitochondrion.
Full Text:
cells of DAPI-stained AuTMAT-resistant mutants 1
exhibiting mitochondrial DNA-negative (type A) and
Positively-charged gold nanoparticles (0.8-nm core diameter) reduced yeast
survival, but not growth, at a concentration of 10 to 100 μg/ml. Among 17 resistant
deletion mutants isolated in a genome-wide screen, highly significant enrichment
was observed for respiration-deficient mutants lacking genes encoding proteins
associated with the mitochondrion.
Full Text:
.
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The effect of changes in employment hours on changes in household task hours
was studied. Data were used from the National Survey of Families and Households
(NSFH) waves one and two. Wave one was a probability sample of 13,017 age 19 and
older in the United States who were interviewed...
A mechanistic based critical heat flux (CHF) correlation has been developed derived from a mass, momentum, and energy balance at a nucleation site for water. The trigger mechanism for the CHF condition is postulated to be related to the maximum boiling frequency on a heated surface. It is observed that...
In order to better predict the aggregation state of nanomaterials, the factors that influence aggregation must be understood. The combined effects of natural and engineered coatings have been shown to factor into nanoparticle aggregation behavior in preliminary research. In this study, aggregation behaviors of gold nanoparticles with two different engineered...
Soft magnetic composites, consisting of fine metallic particles in a non-magnetic, insulating matrix, have great potential for integrated inductor and antenna applications. The dielectric and magnetic properties of soft magnetic composites can be tailored by the choice of matrix as well as particle composition, size, and concentration for reduction in...
Fungi are the primary biological agents of wood deterioration and cause major economic losses of wood products globally. Wood in outdoor applications tends to remain wet for extended time periods, making it susceptible to fungal attack. Understanding the factors involved in fungal colonization of wood is important for developing improved...
Due to its frequent use in agriculture and its frequent detection in surface water,
atrazine was chosen as a model compound to study the treatment capability of a surface flow wetland used to remediate irrigation runoff at a container nursery near Portland, Oregon. Further evaluation of treatment of atrazine was...
The dominant controls on flow generation in steep, forested hillslopes are poorly understood. This dissertation examined the dominant flow processes operating at the hillslope scale, using a combined macroscale measurement and model development and analysis framework. Irrigation experiments at two steep forested hillslopes were conducted to isolate individual hillslope flow...
Throughout a large portion of our planet, malaria has been nearly eradicated or reduced to levels that are highly manageable, and many countries possess the means to effectively treat the disease. However, many areas of the world, such as Sub-Saharan Africa and Southeast Asia, are still heavily burdened by malaria....
Untreated wood is inherently hygroscopic and moisture content variations can have substantial effects on dimensional stability leading to the development of deep surface checks that further enhance moisture uptake and ultimately encourage deterioration. The horizontal exposure of wood crossties makes water repellency and dimensional stability particularly important in railroad applications....
The purpose of this study was to examine the evidence of construct validity for self-report with assistance from a secondary source as a measure of physical activity (PA) in adults with intellectual disabilities (ID) in free-living environments. Thirty-seven participants (21 females, 16 males) with mild to moderate ID aged 19-74...