| 1. |
- Kelly, Kristen L., et al.
(författare)
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Conformational Ensembles of Calmodulin Revealed by Nonperturbing Site-Specific Vibrational Probe Groups
- 2018
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Ingår i: Journal of Physical Chemistry A. - : American Chemical Society (ACS). - 1089-5639 .- 1520-5215. ; 122:11, s. 2947-2955
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Tidskriftsartikel (refereegranskat)abstract
- Seven native residues on the regulatory protein calmodulin, including three key methionine residues, were replaced (one by one) by the vibrational probe amino acid cyanylated cysteine, which has a unique CN stretching vibration that reports on its local environment. Almost no perturbation was caused by this probe at any of the seven sites, as reported by CD spectra of calcium-bound and apo calmodulin and binding thermodynamics for the formation of a complex between calmodulin and a canonical target peptide from skeletal muscle myosin light chain kinase measured by isothermal titration. The surprising lack of perturbation suggests that this probe group could be applied directly in many protein-protein binding interfaces. The infrared absorption bands for the probe groups reported many dramatic changes in the probes' local environments as CaM went from apo- to calcium-saturated to target peptide-bound conditions, including large frequency shifts and a variety of line shapes from narrow (interpreted as a rigid and invariant local environment) to symmetric to broad and asymmetric (likely from multiple coexisting and dynamically exchanging structures). The fast intrinsic time scale of infrared spectroscopy means that the line shapes report directly on site-specific details of calmodulin's variable structural distribution. Though quantitative interpretation of the probe line shapes depends on a direct connection between simulated ensembles and experimental data that does not yet exist, formation of such a connection to data such as that reported here would provide a new way to evaluate conformational ensembles from data that directly contains the structural distribution. The calmodulin probe sites developed here will also be useful in evaluating the binding mode of calmodulin with many uncharacterized regulatory targets.
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| 2. |
- Saager, Rolf B., 1974-, et al.
(författare)
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Method using in vivo quantitative spectroscopy to guide design and optimization of low-cost, compact clinical imaging devices : emulation and evaluation of multispectral imaging systems
- 2018
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Ingår i: Journal of Biomedical Optics. - : SPIE - International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 23:4
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Tidskriftsartikel (refereegranskat)abstract
- With recent proliferation in compact and/or low-cost clinical multispectral imaging approaches and commercially available components, questions remain whether they adequately capture the requisite spectral content of their applications. We present a method to emulate the spectral range and resolution of a variety of multispectral imagers, based on in-vivo data acquired from spatial frequency domain spectroscopy (SFDS). This approach simulates spectral responses over 400 to 1100 nm. Comparing emulated data with full SFDS spectra of in-vivo tissue affords the opportunity to evaluate whether the sparse spectral content of these imagers can (1) account for all sources of optical contrast present (completeness) and (2) robustly separate and quantify sources of optical contrast (crosstalk). We validate the approach over a range of tissue-simulating phantoms, comparing the SFDS-based emulated spectra against measurements from an independently characterized multispectral imager. Emulated results match the imager across all phantoms (<3 % absorption, <1 % reduced scattering). In-vivo test cases (burn wounds and photoaging) illustrate how SFDS can be used to evaluate different multispectral imagers. This approach provides an in-vivo measurement method to evaluate the performance of multispectral imagers specific to their targeted clinical applications and can assist in the design and optimization of new spectral imaging devices.
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| 3. |
- Smith, William J., et al.
(författare)
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Limited domestic introgression in a final refuge of the wild pigeon
- 2022
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Ingår i: iScience. - : Cell Press. - 2589-0042. ; 25:7
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Tidskriftsartikel (refereegranskat)abstract
- Domesticated animals have been culturally and economically important throughout history. Many of their ancestral lineages are extinct or genetically endangered following hybridization with domesticated relatives. Consequently, they have been understudied compared to the ancestral lineages of domestic plants. The domestic pigeon Columba livia, which was pivotal in Darwin's studies, has maintained outsized cultural significance. Its role as a model organism spans the fields of behavior, genetics, and evolution. Domestic pigeons have hybridized with their progenitor, the Rock Dove, rendering the latter of dubious genetic status. Here, we use genomic and morphological data from the putative Rock Doves of the British Isles to identify relictual undomesticated populations. We reveal that Outer Hebridean Rock Doves have experienced minimal levels of introgression. Our results outline the contemporary status of these wild pigeons, high-lighting the role of hybridization in the homogenization of genetic lineages.
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| 4. |
- Sundqvist, Martina, et al.
(författare)
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Anti-neutrophil cytoplasmic antibodies (ANCA): Antigen interactions and downstream effects.
- 2020
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Ingår i: Journal of leukocyte biology. - 1938-3673. ; 108:2, s. 617-626
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Forskningsöversikt (refereegranskat)abstract
- Neutrophils are the most abundant leukocytes in circulation and are key "first responders" in the immune response to infectious and non-infectious stimuli. Unlike other immune cells, neutrophils can mount a robust response (including a change in surface markers and the production of extracellular traps and reactive oxygen species) just minutes after sensing a disturbance. It has been speculated that, in some individuals, the activation of neutrophils inadvertently leads to the generation of anti-neutrophil cytoplasmic autoantibodies (ANCA) against particular neutrophil proteins (antigens) such as myeloperoxidase (MPO) and proteinase 3 (PR3). In these individuals, continuous ANCA-antigen interactions are thought to drive persistent activation of neutrophils, chronic immune activation, and disease, most notably, small vessel vasculitis. There are significant gaps however in our understanding of the underlying mechanisms and even the pathogenicity of ANCA given that vasculitis can develop in the absence of ANCA, and that ANCA have been found in circulation in other conditions with no apparent contribution to disease. These gaps are particularly evident in the context of human studies. Herein, we review knowledge on neutrophil-derived ANCA antigens PR3 and MPO, ANCA generation, and ANCA-antigen interaction(s) that may promote immune activation and disease.
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| 5. |
- Vasefi, Fartash, et al.
(författare)
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Multimode optical dermoscopy (SkinSpect) analysis for skin with melanocytic nevus
- 2016
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Ingår i: Proceedings Volume 9711, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX; 971110 (2016). - : SPIE - International Society for Optical Engineering.
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Konferensbidrag (refereegranskat)abstract
- We have developed a multimode dermoscope (SkinSpect™) capable of illuminating human skin samples in-vivo with spectrally-programmable linearly-polarized light at 33 wavelengths between 468nm and 857 nm. Diffusely reflected photons are separated into collinear and cross-polarized image paths and images captured for each illumination wavelength. In vivo human skin nevi (N = 20) were evaluated with the multimode dermoscope and melanin and hemoglobin concentrations were compared with Spatially Modulated Quantitative Spectroscopy (SMoQS) measurements. Both systems show low correlation between their melanin and hemoglobin concentrations, demonstrating the ability of the SkinSpect™ to separate these molecular signatures and thus act as a biologically plausible device capable of early onset melanoma detection.
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| 6. |
- Vasefi, Fartash, et al.
(författare)
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Separating melanin from hemodynamics in nevi using multimode hyperspectral dermoscopy and spatial frequency domain spectroscopy
- 2016
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Ingår i: Journal of Biomedical Optics. - : SPIE - International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 21:11
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the pattern and distribution of both melanocytes (pigment producing) and vasculature (hemoglobin containing) are important in distinguishing melanocytic proliferations. The ability to accurately measure melanin distribution at different depths and to distinguish it from hemoglobin is clearly important when assessing pigmented lesions (benign versus malignant). We have developed a multimode hyperspectral dermoscope (SkinSpect™) able to more accurately image both melanin and hemoglobin distribution in skin. SkinSpect uses both hyperspectral and polarization-sensitive measurements. SkinSpect’s higher accuracy has been obtained by correcting for the effect of melanin absorption on hemoglobin absorption in measurements of melanocytic nevi. In vivo human skin pigmented nevi (N=20) were evaluated with the SkinSpect, and measured melanin and hemoglobin concentrations were compared with spatial frequency domain spectroscopy (SFDS) measurements. We confirm that both systems show low correlation of hemoglobin concentrations with regions containing different melanin concentrations (R=0.13 for SFDS, R=0.07 for SkinSpect).
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