A5029741276- Lipid Membrane Structure and Behavior
- Viral Infections and Outbreaks Research
- Carcinogens and Genotoxicity Assessment
- Viral Infections and Vectors
- Cholinesterase and Neurodegenerative Diseases
- Pesticide Exposure and Toxicity
- Neuroscience and Neural Engineering
- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Photoreceptor and optogenetics research
- Blood properties and coagulation
- Toxic Organic Pollutants Impact
- Bacterial biofilms and quorum sensing
- Advanced biosensing and bioanalysis techniques
- Bacterial Identification and Susceptibility Testing
- Glycosylation and Glycoproteins Research
- Phytoplasmas and Hemiptera pathogens
- Liver Disease Diagnosis and Treatment
- Animal Disease Management and Epidemiology
- Graphene and Nanomaterials Applications
- 3D Printing in Biomedical Research
- Drug Solubulity and Delivery Systems
- Vector-Borne Animal Diseases
- Metalloenzymes and iron-sulfur proteins
- Legionella and Acanthamoeba research
Lawrence Livermore National Laboratory
2012-2024
University of Oxford
2017
University of Georgia
2009
Lawrence Livermore National Security
2009
Washington State University
2005-2006
Desert Research Institute
2000
University of Nevada, Reno
2000
Here we demonstrate rapid production of solubilized and functional membrane protein by simultaneous cell-free expression an apolipoprotein a in the presence lipids, leading to self-assembly protein-containing nanolipoprotein particles (NLPs). NLPs have shown great promise as biotechnology platform for solubilizing characterizing proteins. However, current approaches are limited because they require extensive efforts express, purify, solubilize prior insertion into NLPs. By simple addition...
Spontaneous interaction of purified apolipoproteins and phospholipids results in formation lipoprotein particles with nanometer-sized dimensions; we refer to these assemblies as nanolipoprotein or NLPs. These bilayer constructs can serve suitable mimetics biological membranes are fully soluble aqueous environments. We made NLPs from dimyristoylphospatidylcholine (DMPC) combination each four different apolipoproteins: apoA-I, Δ-apoA-I fragment, apoE4 apolipophorin III (apoLp-III) the silk...
Biodistribution is an important factor in better understanding silica dioxide nanoparticle (SiNP) safety. Currently, comprehensive studies on biodistribution are lacking, most likely due to the lack of suitable analytical methods. Accelerator mass spectrometry was used investigate relationship between administered dose, pharmacokinetics (PK), and long-term 14C-SiNPs vivo. PK analysis showed that SiNPs were rapidly cleared from central compartment, distributed tissues reticuloendothelial...
Quantitatively benchmarking similarities and differences between the in vivo central nervous system vitro neuronal cultures can qualify discrepancies functional responses establish utility of platforms. In this work, extracellular electrophysiology cortical neurons awake, freely-moving animals were compared to dissociated neurons. After exposure two well-characterized drugs, atropine ketamine, a number key points observed: (1) significant spontaneous firing activity for systems, (2) similar...
We tested environmental data from remote sensing and geographic information system maps as indicators of Sin Nombre virus (SNV) infections in deer mouse (Peromyscus maniculatus) populations the Walker River Basin, Nevada California. determined by serologic testing presence SNV mice 144 field sites. used systems to characterize vegetation type density, elevation, slope, hydrologic features each site. The retroactively predicted infection status with up 80% accuracy. If models temporal...
Self-assembly of purified apolipoproteins and phospholipids results in the formation nanometer-sized lipoprotein complexes, referred to as nanolipoprotein particles (NLPs). These bilayer constructs are fully soluble aqueous environments hold great promise a model system aid solubilizing membrane proteins. Size variability self-assembly process has been recognized for some time, yet limited studies have conducted examine this phenomenon. Understanding source heterogeneity may lead methods...
Nanolipoprotein particles (NLPs) are nanometer-sized, discoidal that self-assemble from purified apolipoprotein and phospholipid. Their size facile functionalization suggest potential application of NLPs as platforms for the presentation delivery recombinant proteins. To this end, we investigated incorporation nickel-chelating lipids into (NiNLPs) subsequent sequestration polyhistidine (His)-tagged From initial lipid screens NLP formation, two phospholipids DMPC DOPC were identified suitable...
Hydrogenases constitute a promising class of enzymes for ex vivo hydrogen production. Implementation such applications is currently hindered by oxygen sensitivity and, in the case membrane-bound hydrogenases (MBHs), poor water solubility. Nanolipoprotein particles (NLPs) formed from apolipoproteins and phospholipids offer novel means incorporating MBHs into well-defined water-soluble matrix that maintains enzymatic activity amenable to incorporation more complex architectures. We report...
Osteoarthritis (OA) is a painful and debilitating disease characterized by the chronic progressive degradation of articular cartilage. Post-traumatic OA (PTOA) secondary form that develops in ~50% cases severe injury. Inflammation re-occurring injury have been implicated as contributing to progression PTOA after initial However, there very little known about external factors prior could affect risk development. To examine how gut microbiome affects development we used antibiotic treatment...
Triclocarban (TCC) is among the top 10 most commonly detected wastewater contaminants in both concentration and frequency. Its presence water, as well its propensity to bioaccumulate, has raised numerous questions about potential endocrine developmental effects. Here, we investigated whether exposure an environmentally relevant of TCC could result transfer from mother offspring CD-1 mice during gestation lactation using accelerator mass spectrometry (AMS). 14C-TCC (100 nM) was administered...
Abstract The gut microbiota is a vast and diverse microbial community that has co-evolved with its host to perform variety of essential functions involved in the utilization nutrients processing xenobiotics. Shifts composition can disturb balance organisms which influence biodisposition orally administered drugs. To determine how changes microbiome alter drug disposition, pharmacokinetics (PK), biodistribution acetaminophen were assessed C57Bl/6 mice after treatment antibiotics...
ABSTRACT Data from naturally infected deer mice ( Peromyscus maniculatus ) were used to investigate vertical transmission of Sin Nombre virus (SNV) and SNV-specific antibody. The antibody prevalence in juvenile (14 g or less) was inversely proportional the mass animal, with weighing less than 11 most likely be positive (26.9%) between 13 14 least (12.9%). Although a significant sex bias seropositivity detected adult mice, no animals. Ten identified that had initially tested for...
ABSTRACT Bacterial source tracking is used to apportion fecal pollution among putative sources. Within this context, library-independent markers are genetic or phenotypic traits that can be identify the host origin without a need for library-dependent classification functions. The objective of project was use mixed-genome Enterococcus microarrays markers. Separate shotgun libraries were prepared five groups (cow, dog, elk/deer, human, and waterfowl), using genomic DNAs (gDNAs) from ca. 50...
Nanolipoprotein particles (NLPs) are nanometer-scale discoidal that feature a phospholipid bilayer confined within an apolipoprotein "scaffold," which useful for solubilizing hydrophobic molecules such as drugs and membrane proteins. NLPs synthesized either by mixing the purified with phospholipids other cofactors or cell-free protein synthesis followed self-assembly of nanoparticles in reaction mixture. Either method can be problematic regarding production homogeneous monodispersed...
Background Nanolipoprotein particles (NLPs) are discoidal, nanometer-sized comprised of self-assembled phospholipid membranes and apolipoproteins. NLPs assembled with human apolipoproteins have been used for myriad biotechnology applications, including membrane protein solubilization, drug delivery, diagnostic imaging. To expand the repertoire lipoproteins these insect apolipophorin-III (apoLp-III) was evaluated ability to form discretely-sized, homogeneous, stable NLPs. Methodology Four NLP...
Heterogeneity is a fact that plagues the characterization and application of many self-assembled biological constructs. The importance obtaining particle homogeneity in assemblies critical goal, as bulk analysis tools often require identical species for reliable interpretation results—indeed, important such x-ray diffraction typically over 90% purity effectiveness. This issue bears particular case lipoproteins. Lipid-binding proteins known apolipoproteins can self assemble with liposomes to...
Nerve agents have experienced a resurgence in recent times with their use against civilian targets during the attacks Syria (2012), poisoning of Sergei and Yulia Skripal United Kingdom (2018) Alexei Navalny Russia (2020), strongly renewing importance antidote development these lethal substances. The current standard treatment effects relies on small molecule-based oximes that can efficiently restore acetylcholinesterase (AChE) activity. Despite efficacy reactivating AChE, action drugs like...
Subetadex-α-methyl (SBX-Me), a modified, polyanionic cyclodextrin scaffold, has been evaluated for its utilization as medical countermeasure (MCM) to neutralize the effects of fentanyl and related opioids. Initial in vitro toxicity assays demonstrate that SBX-Me nontoxic profile, comparable FDA-approved cyclodextrin-based drug Sugammadex. Pharmacokinetic analysis showed rapid clearance with an elimination half-life ∼7.4 h little accumulation major organs. was also ability counteract...
Pancreatic cancer is the fourth leading cause of death in U.S. Once diagnosed, prognosis poor with a 5-year survival rate less than 5%. Exposure to carcinogenic heterocyclic amines (HCAs) derived from cooked meat has been shown be positively associated pancreatic risk. To evaluate processes that determine potential HCAs for human pancreas, 14-carbon labeled 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), putative HCA found well-done meat, was administered at dietary relevant dose...
Bangladesh has made significant progress towards elimination of visceral leishmaniasis, and is on track to achieve its target less than one case per 10,000 inhabitants in each subdistrict 2017. As the incidence disease falls, it likely that political capital financial resources dedicated leishmaniasis may decrease, raising prospect resurgence. Policy memos play a crucial role during transition plan from 'attack' 'consolidation' 'maintenance' phases, highlighting key stakeholders areas where...
Many researchers have speculated that infection dynamics of Sin Nombre virus are driven by density patterns its major host, Peromyscus maniculatus. Few, if any, studies examined this question systematically at a realistically large spatial scale, however. We collected data from 159 independent field sites within 1 million-hectare study area in Nevada and California, 1995-1998. In 1997, there was widespread substantial reduction host density. This did not reduce seroprevalence antibody to...