A5081301991- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Protein Structure and Dynamics
- Lipid Membrane Structure and Behavior
- Lysosomal Storage Disorders Research
- melanin and skin pigmentation
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Neurological disorders and treatments
- Spectroscopy Techniques in Biomedical and Chemical Research
- Hemoglobin structure and function
- RNA regulation and disease
- Migration, Ethnicity, and Economy
- Prion Diseases and Protein Misfolding
- Nerve Injury and Rehabilitation
- Conducting polymers and applications
- School Choice and Performance
- Photosynthetic Processes and Mechanisms
- Mitochondrial Function and Pathology
- RNA Research and Splicing
- Neurological diseases and metabolism
- Nerve injury and regeneration
- Urban, Neighborhood, and Segregation Studies
- Racial and Ethnic Identity Research
- Cholinesterase and Neurodegenerative Diseases
National Institutes of Health
2016-2025
National Heart Lung and Blood Institute
2016-2025
Michigan Medicine
2022-2025
University of Michigan
2017-2023
Creative Commons
2023
Indiana University Bloomington
2007-2022
Indiana University
2007-2022
Temple University
2022
National Heart Institute
2018
Lung Institute
2018
The identification and assessment of myocardial infarction (MI) are important for therapeutic prognostic purposes, yet current recommended diagnostic strategies have significant limitations. We prospectively tested the performance delayed-enhancement magnetic resonance imaging (MRI) with gadolinium-based contrast detection MI in an international, multicenter trial.Patients their first were enrolled acute (< or = 16 days after MI; n=282) chronic (17 to 6 months; n=284) arm then randomized 1 4...
Significance Identifying factors that regulate the degradation of α-synuclein, protein at center Parkinson’s disease etiology, is vital in designing therapeutic strategies. This study provides new mechanistic insights into α-synuclein clearance lysosome, a cellular site for proteolysis by using purified mouse lysosomes and lysosomal proteases. Cathepsins B L are identified to be through peptide mapping mass spectrometry. Importantly, cathepsin degrades amyloid fibrils, materials associated...
Background. Work limitation rates are crucial indicators of the health status working people. If related to work productivity, may also supply important information about economic burden illness. Objective. Our objective was assess productivity impact on-the-job limitations due employees' physical or mental problems. Research Design. Subjects were asked complete a self-administered survey on job during 3 consecutive months. Using robust regression analysis, we tested relationship...
Variations in tryptophan fluorescence intensities confirm that copper(II) interacts with α-synuclein, a protein implicated Parkinson's disease. Trp4 decay kinetics measured for the F4W show Cu(II) binds tightly (Kd ∼ 100 nM) near N-terminus at pH 7. Work on F4W/H50S mutant indicates histidine imidazole is not ligand this high-affinity site.
Because of the generally high socioeconomic attainments and intermarriage rates Asian Americans, it has been suggested that Americans are reaching parity with whites assimilating to mainstream American society. However, other research shows continued significance race for regardless their status levels acculturation. This article provides a review recent on attainment among as well an overview less studied but increasingly important indicators: residential outcomes, political participation,...
An increasing number of human diseases has been shown to be linked aggregation and amyloid formation by intrinsically disordered proteins (IDPs). Amylin, amyloid-β, α-synuclein are, indeed, involved in type-II diabetes, Alzheimer's, Parkinson's, respectively. Despite the correlation toxicity these at early stages with membrane damage, molecular events underlying process is quite complex understand. In this study, we demonstrate crucial role free lipids lipid–protein complex, which enables an...
Prototypes are essential tools in product design processes, but often underutilized by novice designers. To help designers use prototypes more effectively, we must first determine how they currently prototypes. In this paper, describe conceptualized and reported using them throughout a project, compare prototyping to best practices. We found that some of the practices designers, such as inexpensive early define user requirements, occurred infrequently lacked intentionality. Participants'...
α-Synuclein (α-Syn), an intrinsically disordered protein, is associated with Parkinson's disease. Though molecular pathogenic mechanisms are ill-defined, mounting evidence connects its amyloid forming and membrane binding propensities to disease etiology. Contrary recent data suggesting that remodeling by α-syn involves anionic phospholipids helical structure, we discovered the protein deforms vesicles no net surface charge (phosphatidylcholine, PC) into tubules (average diameter ∼20 nm). No...
The generation of α-synuclein (α-syn) truncations from incomplete proteolysis plays a significant role in the pathogenesis Parkinson's disease. It is well established that C-terminal exhibit accelerated aggregation and serve as potent seeds fibril propagation. In contrast, mechanistic understanding N-terminal remains ill defined. Previously, we found disease-related resulted increased fibrillar twist, accompanied by modest conformational changes more compact core, suggesting region could be...
Human interleukin-8 receptors A (IL-8RA) and B (IL-8RB) are seven-transmembrane domain (TMD) neutrophil chemokine with similar sequences (77% amino acid identity) G protein selectivity, but markedly different selectivity for CXC chemokines. IL-8RB is selective IL-8, growth-related oncogene α (GROα) neutrophil-activating peptide-2 (NAP-2), whereas IL-8RA only IL-8. To identify determinants, we made eight chimeric exchanging: 1) the three main regions of sequence divergence between (the...
Parkinson's disease is associated with the deposition and accumulation of alpha-synuclein fibrils in brain. A30P A53T mutations have been linked to early-onset familial state. Time-resolved tryptophan fluorescence energy-transfer measurements used probe structures pseudo-wild-type mutant (A30P) alpha-synucleins at physiological pH (7.4), acidic (4.4) solutions, presence SDS micelles, a membrane mimic. Fluorescent donor-energy acceptor (DA) distance distributions for six different...
The protein alpha-synuclein, implicated in Parkinson's disease, was studied by combining nano-electrospray ionization (N-ESI) mass spectrometry and ion mobility. It found that both the charge-state distribution spectra average shape deduced from mobility data, depend on pH of spray solution. Negative-ion N-ESI 7 solutions yielded a broad -6 to -16, centered at -11, data consistent with extended structures. Data obtained for 2.5 solutions, other hand, showed narrow -8, mobilities agreement...
The attainment of financial independence is a key marker the contemporary transition to adulthood. In this study we ask, how do young adults gain capacity support themselves? We contend that communication about work in family during adolescence an important precursor economic self-efficacy adolescence, which positively associated with early Drawing upon rich longitudinal data span and adulthood, first ask whether socialization practices surrounding finances influence development ways...
Pmel17 is a functional amyloidogenic protein whose fibrils act as scaffolds for pigment deposition in human skin and eyes. We have used the repeat domain (RPT, residues 315-444), an essential luminal polypeptide region of Pmel17, model system to study conformational changes from soluble unstructured monomers β-sheet-containing fibrils. Specifically, we report on effects solution pH (4 → 7) mimicking conditions melanosomes, acidic organelles where are formed. Local, secondary, fibril...
While the association between teenagers' work and academic performance continues to be debated in studies of adolescent employment, many researchers have found that “intensive” involvement paid increases risk high school dropout. It is still unclear, however, whether this relationship spurious owing preexisting differences socioeconomic background, performance, aspirations, orientations toward school. Using propensity- score matching techniques, authors address issue assess variation effects...
The objective of this study was to assess the risk suicide attempts and suicides after initiation antidepressant medication use by children adolescents, for individual agents.We conducted a 9-year cohort using population-wide data from British Columbia. We identified new users antidepressants who were 10 18 years age with recorded diagnosis depression. Study outcomes hospitalization attributable intentional self-harm death.Of 20,906 initiated therapy, 16,774 (80%) had no previous use. During...