4 research outputs found
Structural characterization of a novel Ca<SUP>2+</SUP>-binding protein from Entamoeba histolytica: structural basis for the observed functional differences with its isoform
A novel Ca2+-binding protein (EhCaBP2) was identified from the protozoan parasite Entamoeba histolytica. EhCaBP2 has 79% sequence identity with calcium-binding protein EhCaBP1. The 3D structure of EhCaBP2 was determined using multidimensional nuclear magnetic resonance spectroscopic techniques. The study reveals that the protein consists of two globular domains connected by a short flexible linker region of four residues. On comparison of the 3D structure and dynamics of EhCaBP2 with those of EhCaBP1, it is found that they vary significantly in their N-terminal domains and interdomain linker. Immunofluorescence localization experiments revealed that EhCaBP1 and EhCaBP2 may not carry out similar functions, as their cellular distribution patterns are not the same. The functional differences between the two isoforms are explained on the basis of results obtained from the structural studies. The structural variation in the interdomain linker region and the formation of functionally important hydrophobic clefts in different regions of EhCaBP1 and EhCaBP2 provide interesting insights into the differences in the functionality of these two isoforms
White matter alterations in early-stage Alzheimer's disease: A tract-specific study
Introduction Diffusion magnetic resonance imaging may allow for microscopic characterization of white matter degeneration in early stages of Alzheimer's disease. Methods Multishell Diffusion magnetic resonance imaging data were acquired from 100 participants (40 cognitively normal, 38 with subjective cognitive decline, and 22 with mild cognitive impairment [MCI]). White matter microscopic degeneration in 27 major tracts of interest was assessed using diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging, and q‐space imaging. Results Lower DTI fractional anisotropy and higher radial diffusivity were observed in the cingulum, thalamic radiation, and forceps major of participants with MCI. These tracts of interest also had the highest predictive power to discriminate groups. Diffusion metrics were associated with cognitive performance, particularly Rey Auditory Verbal Learning Test immediate recall, with the highest association observed in participants with MCI. Discussion While DTI was the most sensitive, neurite orientation dispersion and density imaging and q‐space imaging complementarily characterized reduced axonal density accompanied with dispersed and less restricted white matter microstructures
The Impact of Edema and Fiber Crossing on Diffusion MRI Metrics: DBSI vs. Diffusion ODF
Purpose
Diffusion tensor imaging (DTI) has been employed for over two decades to noninvasively quantify
central nervous system (CNS) diseases/injuries. However, DTI is an inadequate simplification
of diffusion modeling in the presence of co-existing inflammation, edema, and crossing nerve fibers.
Methods
We employed a tissue phantom using fixed mouse trigeminal nerves coated with various amounts
of agarose gel to mimic crossing fibers in the presence of vasogenic edema. Diffusivity measures
derived by DTI and diffusion basis spectrum imaging (DBSI) were compared at increasing levels
of simulated edema and degrees of fiber crossing. Further, we assessed the ability of DBSI, diffusion
kurtosis imaging (DKI), generalized q-sampling imaging (GQI), q-ball imaging (QBI), and
neurite orientation dispersion and density imaging (NODDI) to resolve fiber crossing, in reference
to the gold standard angles measured from structural images.
Results
DTI-computed diffusivities and fractional anisotropy (FA) were significantly confounded by gelmimicked
edema and crossing fibers. Conversely, DBSI calculated accurate diffusivities of individual
fibers regardless of the extent of simulated edema and degrees of fiber crossing angles.
Additionaly, DBSI accurately and consistently estimated crossing angles in various conditions of
gel-mimicked edema when comparing with gold standard (r2=0.92, p=1.9×10-9, bias=3.9°). Small
crossing angles and edema sinficantly impact dODF, making DKI, GQI and QBI less accurate in
detecting and estimating fibers corrsing angles. Lastly, we demonstrate DBSI’s superiority over
DTI for recovering and delineating white matter tracts in peritumoral edema for preoperative planning
of surgical resection.
Conclusions
DBSI is able to separate two crossing fibers and accurately recover their diffusivities in a complex
environment characterized by increasing crossing angles and amounts of gel-mimicked edema.
DBSI also indicated better angular resolution capability compared with DKI, QBI and GQI
Acute White-Matter Abnormalities in Sports-Related Concussion: A Diffusion Tensor Imaging Study from the NCAA-DoD CARE Consortium
Sports-related concussion (SRC) is an important public health issue. Although standardized assessment tools are useful in the clinical management of acute concussion, the underlying pathophysiology of SRC and the time course of physiological recovery after injury remain unclear. In this study, we used diffusion tensor imaging (DTI) to detect white matter alterations in football players within 48 h after SRC. As part of the NCAA-DoD CARE Consortium study of SRC, 30 American football players diagnosed with acute concussion and 28 matched controls received clinical assessments and underwent advanced magnetic resonance imaging scans. To avoid selection bias and partial volume effects, whole-brain skeletonized white matter was examined by tract-based spatial statistics to investigate between-group differences in DTI metrics and their associations with clinical outcome measures. Mean diffusivity was significantly higher in brain white matter of concussed athletes, particularly in frontal and subfrontal long white matter tracts. In the concussed group, axial diffusivity was significantly correlated with the Brief Symptom Inventory and there was a similar trend with the symptom severity score of the Sport Concussion Assessment Tool. In addition, concussed athletes with higher fractional anisotropy performed better on the cognitive component of the Standardized Assessment of Concussion. Overall, the results of this study are consistent with the hypothesis that SRC is associated with changes in white matter tracts shortly after injury, and these differences are correlated clinically with acute symptoms and functional impairments