A5091768520- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Supramolecular Self-Assembly in Materials
- Mechanisms of cancer metastasis
- Protein Structure and Dynamics
- Advanced NMR Techniques and Applications
- Tracheal and airway disorders
- Alzheimer's disease research and treatments
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Chemical Synthesis and Analysis
- Asthma and respiratory diseases
- Lipid Membrane Structure and Behavior
- Advanced biosensing and bioanalysis techniques
- Inhalation and Respiratory Drug Delivery
- NMR spectroscopy and applications
- Ion channel regulation and function
- Solid-state spectroscopy and crystallography
- Ion Transport and Channel Regulation
- Cancer Mechanisms and Therapy
- MXene and MAX Phase Materials
- RNA and protein synthesis mechanisms
- Prion Diseases and Protein Misfolding
- Polydiacetylene-based materials and applications
- Electron Spin Resonance Studies
University of California, San Francisco
2025
Emory University
2013-2024
Western University of Health Sciences
2024
University of Rajasthan
2013-2023
Banasthali University
2023
University of Jammu
2023
Ninewells Hospital
2010-2020
University of Dundee
2010-2020
Resonance Research (United States)
2020
University of Florida
2019-2020
Amyloids are self-assembled protein architectures implicated in dozens of misfolding diseases. These assemblies appear to emerge through a "selection" specific conformational "strains" which nucleate and propagate within cells cause disease. The short Abeta(16-22) peptide, includes the central core Alzheimer's disease Abeta generates an amyloid fiber is morphologically indistinguishable from full-length peptide fiber, but it can also form other morphologies under distinct conditions. Here we...
Restoration of BECN1/Beclin 1-dependent autophagy and depletion SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models human cystic fibrosis (CF). These measures rescue the functional expression most frequent pathogenic CFTR mutant, F508del, at respiratory epithelial surface reduce lung inflammation in Cftr(F508del) homozygous mice. Cysteamine, reduced form is an FDA-approved drug. Here, we report that...
Design of a structurally defined helical assembly is described that involves recoding the amino acid sequence peptide GCN4-pAA. In solution and crystalline state, GCN4-pAA adopts 7-helix bundle structure resembles supramolecular lock washer. Structurally informed mutagenesis afforded 7HSAP1, which undergoes self-association into nanotube via noncovalent interactions between complementary interfaces coiled-coil lock-washer structures. Biophysical measurements conducted in solid state over...
We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for CFTR Phe508del mutation. Here we provide proof-of-concept this treatment restored function reduced lung inflammation (P<0.001) Phe508del/Phe508del or Phe508del/null-Cftr (but not Cftr-null mice), provided such mice were...
Previously, we showed that serum and monocytes from patients with CF exhibit an enhanced NLRP3-inflammasome signature increased IL-18, IL-1β, caspase-1 activity ASC speck release (Scambler et al. eLife 2019). Here show CFTR modulators down regulate this exaggerated proinflammatory response following LPS/ATP stimulation. In vitro application of ivacaftor/lumacaftor or ivacaftor/tezacaftor to a significant reduction in whereas IL-1β was only reduced ivacaftor/tezacaftor. Thirteen adults...
Abstract In neurodegenerative diseases, polymorphism and supramolecular assembly of β-sheet amyloids are implicated in many different etiologies may adopt either a left- or right-handed chirality. Yet, the underlying principles how sequence regulates chirality remains unknown. Here, we characterize specificity central core amyloid-β 42 design derivatives which enable inversion at biologically relevant temperatures. We further find that C-terminal modifications can tune energy barrier...
Protein and peptide assembly into amyloid has been implicated in functions that range from beneficial epigenetic controls to pathological etiologies. However, the exact structures of assemblies regulate biological activity remain poorly defined. We have previously used Zn(2+) modulate kinetics morphology congeners beta (Abeta) associated with Alzheimer's disease. now reveal a correlation among Abeta-Cu(2+) coordination, self-assembly, neuronal viability. By using central segment Abeta,...
Newborn screening for cystic fibrosis remains controversial because improved pulmonary function has not been established. Studies to date have accounted differences in treatments delivered clinically diagnosed children and newborn-screened controls. Here, we compare outcomes treatment of patients within the newborn-screening reporting window (early-clinically diagnosed), those presenting after this period (late-clinically by newborn screening.In a cross-sectional analysis cohorts...
Abstract The strain energy release rate ( G ) converges rapidly in finite element approximations which the mesh is fixed and order of polynomial displacement interpolations p increased. Numerical experiments indicate that error very closely estimated, even for small coarse meshes, by an expression form k (NDF) ‐1 a dependent constant NDF number degrees‐of‐freedom. method provides efficient accurate computation without use special techniques.
In contrast to an expected Ostwald-like ripening of amyloid assemblies, the nucleating core Dutch mutant Aβ peptide Alzheimer’s disease assembles through a series conformational transitions. Structural characterization intermediate assemblies by isotope-edited IR and solid-state NMR reveals unexpected strand orientation intermediates suggests new nucleation mechanisms in progressive assembly pathway.
Energetic insights emerging from the structural characterization of peptide cross-β assemblies have enabled design and construction robust asymmetric bilayer membranes. Two peptides differing only in their N-terminal residue, phosphotyrosine vs lysine, coassemble as stacks antiparallel β-sheets with precisely patterned charged lattices stabilizing leaflet interface. Either homogeneous or mixed composition is possible, both create nanotubes dense negative external positive internal solvent...
Disease registries have the invaluable potential to provide an insight into natural history of disease under investigation, useful information (e.g. through health indicators) for planning care services and identify suitable groups patients clinical trials enrolment. However, establishment maintenance is a burdensome initiative from economical organisational points view experience sharing on management important avoid waste resources. The aim this paper discuss problems embedded in...
A polyoxometalate-based polymer with multifunctional capabilities including rapid gelation and catalytic decontamination of toxic or odorous compounds is realized.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP and protein kinase A (PKA)-regulated Cl(-) channel in the apical membrane of epithelial cells. metabolically regulated adenosine monophosphate-stimulated (AMPK) colocalized with CFTR attenuates its function. However, sites for phosphorylation precise mechanism inhibition by AMPK remain obscure. We demonstrate that normally remains closed at baseline, but nevertheless, opens after AMPK. phosphorylates vitro two essential...
Amyloid fibers, independent of primary amino acid sequence, share a common cross-β structure and bind the histochemical dye Congo Red (CR). Despite extensive use CR in amyloid diagnostics, remarkably little is known about specific characteristic binding interactions. Fibril insolubility, morphological inhomogeneity, multiple possible ligand sites all conspire to limit characterization. Here, we have exploited nanotubes, which number potential sites, directly interrogate laminate grooves....
A buried polar bilayer interface composed of interdigitated peptide ends and a high density CF3COO− counterions passifying lysine amines are identified in nanotubes obtained by self-assembly short peptides. The structure reveals distinct characteristics that differentiate bilayers lipid can now be exploited for the construction lipid-like nanomaterials with protein functionality.