The diffusion coefficient for PGK folding in eukaryotic cells.
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ABSTRACT:
SUBMITTER: Dhar A
PROVIDER: S-EPMC2965994 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Phosphatidylinositol 4,5-bisphosphate (PIP(2)) controls a surprisingly large number of processes in cells. Thus, many investigators have suggested that there might be different pools of PIP(2) on the inner leaflet of the plasma membrane. If a significant fraction of PIP(2) is bound electrostatically to unstructured clusters of basic residues on membrane proteins, the PIP(2) diffusion constant, D, should be reduced. We microinjected micelles of Bodipy TMR-PIP(2) into cells, and we measured D on the inner leaflet of fibroblasts and epithelial cells by using fluorescence correlation spectroscopy. The average +/- SD value from all cell types was D = 0.8 +/- 0.2 microm(2)/s (n = 218; 25 degrees C). This is threefold lower than the D in blebs formed on Rat1 cells, D = 2.5 +/- 0.8 microm(2)/s (n = 26). It is also significantly lower than the D in the outer leaflet or in giant unilamellar vesicles and the diffusion coefficient for other lipids on the inner leaflet of these cell membranes. The simplest interpretation is that approximately two thirds of the PIP(2) on inner leaflet of these plasma membranes is bound reversibly.
| S-EPMC2291420 | biostudies-literature
Project description:PurposeTo characterize the diffusion coefficient of human blood for accurate results in intravoxel incoherent motion imaging.MethodsDiffusion-weighted MRI of blood samples from 10 healthy volunteers was acquired with a single-shot echo-planar-imaging sequence at body temperature. Effects of gradient profile (monopolar or flow-compensated), diffusion time (40-100 ms), and echo time (60-200 ms) were investigated.ResultsAlthough measured apparent diffusion coefficients of blood were larger for flow-compensated than for monopolar gradients, no dependence of the apparent diffusion coefficient on the diffusion time was found. Large differences between individual samples were observed, with results ranging from 1.26 to 1.66 µm2 /ms for flow-compensated and 0.94 to 1.52 µm2 /ms for monopolar gradients. Statistical analysis indicates correlations of the flow-compensated apparent diffusion coefficient with hematocrit (P = 0.007) and hemoglobin (P = 0.017), but not with mean corpuscular volume (P = 0.64). Results of Monte-Carlo simulations support the experimental observations.ConclusionsMeasured blood apparent diffusion coefficient values depend on hematocrit/hemoglobin concentration and applied gradient profile due to non-Gaussian diffusion. Because in vivo measurement is delicate, an estimation based on blood count results could be an alternative. For intravoxel incoherent motion modeling, the use of a blood self-diffusion constant Db = 1.54 ± 0.12 µm2 /ms for flow-compensated and Db = 1.30 ± 0.18 µm2 /ms for monopolar encoding is suggested. Magn Reson Med 79:2752-2758, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
| S-EPMC5836916 | biostudies-literature
Project description:Single-particle tracking is increasingly used to extract quantitative parameters on single molecules and their environment, while advances in spatial and temporal resolution of tracking techniques inspire new questions and avenues of investigation. Correspondingly, sophisticated analytical methods are constantly developed to obtain more refined information from measured trajectories. Here we point out some fundamental limitations of these approaches due to the finite length of trajectories, the presence of localization error, and motion blur, focusing on the simplest motion regime of free diffusion in an isotropic medium (Brownian motion). We show that two recently proposed algorithms approach the theoretical limit of diffusion coefficient uncertainty. We discuss the practical performance of the algorithms as well as some important implications of these results for single-particle tracking.
| S-EPMC4917385 | biostudies-literature
Project description:Background and Purpose- In this era of endovascular therapy (EVT) with early, complete recanalization and reperfusion, we have observed an even more rapid apparent diffusion coefficient (ADC) normalization within the acute ischemic lesion compared with the natural history or IV-tPA-treated patient. In this study, we aimed to evaluate the effect of revascularization on ADC evolution within the core lesion in the first 24 hours in acute ischemic stroke patients. Methods- This retrospective study included anterior circulation acute ischemic stroke patients treated with EVT with or without intravenous tPA (IVT) from 2015 to 2017 compared with a consecutive cohort of IVT-only patients treated before 2015. Diffusion-weighted imaging and ADC maps were used to quantify baseline core lesions. Median ADC value change and core reversal were determined at 24 hours. Diffusion-weighted imaging lesion growth was measured at 24 hours and 5 days. Good clinical outcome was defined as modified Rankin Scale score of 0 to 2 at 90 days. Results- Twenty-five patients (50%) received IVT while the other 25 patients received EVT (50%) with or without IVT. Between these patient groups, there were no differences in age, sex, baseline National Institutes of Health Stroke Scale, interhospital transfer, or IVT rates. Thirty-two patients (64%) revascularized with 69% receiving EVT. There was a significant increase in median ADC value of the core lesion at 24 hours in patients who revascularized compared with further ADC reduction in nonrevascularization patients. Revascularization patients had a significantly higher rate of good clinical outcome at 90 days, 63% versus 9% (P=0.003). Core reversal at 24 hours was significantly higher in revascularization patients, 69% versus 22% (P=0.002). Conclusions- ADC evolution in acute ischemic stroke patients with early, complete revascularization, now more commonly seen with EVT, is strikingly different from our historical understanding. The early ADC normalization we have observed in this setting may include a component of secondary injury and serve as a potential imaging biomarker for the development of future adjunctive therapies. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00009243.
| S-EPMC6646065 | biostudies-literature
Project description:Background and purposeIntramedullary high signal intensity on T2-weighted imaging was frequently observed in patients with CSM, although this finding does not well correlate with severity or prognosis of CSM. Instead of this nonquantitative information, another measure for CSM is desired. The work was focused primarily on assessing the relationships between ADC values and clinical and radiologic severity for the diagnosis of CSM.Materials and methodsThe relationship between ADC values measured in the spinal cord at 322 intervertebral levels of 66 patients and clinical factors were analyzed.ResultsADC values in the spinal cord significantly increased with the degree of spinal cord compression and decreased with time after decompression surgery. Patients with higher ADC values had lower preoperative JOA scores and tended to show poorer clinical recovery.ConclusionsADC values appear to indicate the severity of spinal cord compression and clinical recovery after decompression surgery, so spondylotic myelopathy may partly be predicted preoperatively by using ADC values.
| S-EPMC7964806 | biostudies-literature
Project description:Monte Carlo simulations and integral equation techniques allow for the flexible and efficient computation of drag and diffusion coefficients for virus mimetic particles. We highlight a Monte Carlo method that is useful for computing the drag on biomimetic particles in the free-molecular regime and a numerical technique to solve a boundary integral equation (related to the Stokes equation) in the hydrodynamic limit. The free-molecular and the continuum results allow the construction of an approximation for the drag applicable over the full range of Knudsen numbers. Finally, we outline how this work will be useful in modeling viral transport in air and fluids and in viral morphology measurements and in viral separations via electrospray-differential mobility analyzers (ES-DMA).
| S-EPMC8103743 | biostudies-literature
Project description:Diffusion on a low-dimensional free-energy surface is a remarkably successful model for the folding dynamics of small single-domain proteins. Complicating the interpretation of both simulations and experiments is the expectation that the effective diffusion coefficient D will in general depend on the position along the folding coordinate, and this dependence may vary for different coordinates. Here we explore the position dependence of D, its connection to protein internal friction, and the consequences for the interpretation of single-molecule experiments. We find a large decrease in D from unfolded to folded, for reaction coordinates that directly measure fluctuations in Cartesian configuration space, including those probed in single-molecule experiments. In contrast, D is almost independent of Q, the fraction of native amino acid contacts: Near the folded state, small fluctuations in position cause large fluctuations in Q, and vice versa for the unfolded state. In general, position-dependent free energies and diffusion coefficients for any two good reaction coordinates that separate reactant, product, and transition states, are related by a simple transformation, as we demonstrate. With this transformation, we obtain reaction coordinates with position-invariant D. The corresponding free-energy surfaces allow us to justify the assumptions used in estimating the speed limit for protein folding from experimental measurements of the reconfiguration time in the unfolded state, and also reveal intermediates hidden in the original free-energy projection. Lastly, we comment on the design of future single-molecule experiments that probe the position dependence of D directly.
| S-EPMC2824289 | biostudies-literature
Project description:Purpose To assess the repeatability of apparent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic resonance imaging across a wide range of imaging protocols and patient populations. Materials and Methods Nine prospective patient studies and one prospective volunteer study, performed between 2006 and 2016 with research ethics committee approval and written informed consent from each subject, were included in this single-institution study. A total of 141 tumors and healthy organs were imaged twice (interval between repeated examinations, 45 minutes to 10 days, depending the on study) to assess the repeatability of median and mean ADC estimates. The Levene test was used to determine whether ADC repeatability differed between studies. The Pearson linear correlation coefficient was used to assess correlation between coefficient of variation (CoV) and the year the study started, study size, and volumes of tumors and healthy organs. The repeatability of ADC estimates from small, medium, and large tumors and healthy organs was assessed irrespective of study, and the Levene test was used to determine whether ADC repeatability differed between these groups. Results CoV aggregated across all studies was 4.1% (range for each study, 1.7%-6.5%). No correlation was observed between CoV and the year the study started or study size. CoV was weakly correlated with volume (r = -0.5, P = .1). Repeatability was significantly different between small, medium, and large tumors (P < .05), with the lowest CoV (2.6%) for large tumors. There was a significant difference in repeatability between studies-a difference that did not persist after the study with the largest tumors was excluded. Conclusion ADC is a robust imaging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor sites, sizes, patient populations, and imaging protocol variations. Online supplemental material is available for this article.
| S-EPMC6063352 | biostudies-literature
Project description:ObjectiveThe apparent diffusion coefficient (ADC) is increasingly used as a quantitative biomarker in oncological imaging. ADC calculation is based on raw diffusion-weighted imaging (DWI) data, and multiple post-processing methods (PPMs) have been proposed for this purpose. We investigated whether PPM has an impact on final ADC values.MethodsSixty-five lesions scanned with a standardized whole-body DWI-protocol at 3 T served as input data (EPI-DWI, b-values: 50, 400 and 800 s/mm2). Using exactly the same ROI coordinates, four different PPM (ADC_1-ADC_4) were executed to calculate corresponding ADC values, given as [10-3 mm2/s] of each lesion. Statistical analysis was performed to intra-individually compare ADC values stratified by PPM (Wilcoxon signed-rank tests: ??=?1 %; descriptive statistics; relative difference/?; coefficient of variation/CV).ResultsStratified by PPM, mean ADCs ranged from 1.136-1.206 *10-3 mm2/s (??=?7.0 %). Variances between PPM were pronounced in the upper range of ADC values (maximum: 2.540-2.763 10-3 mm2/s, ??=?8 %). Pairwise comparisons identified significant differences between all PPM (P???0.003; mean CV?=?7.2 %) and reached 0.137 *10-3 mm2/s within the 25th-75th percentile.ConclusionAltering the PPM had a significant impact on the ADC value. This should be considered if ADC values from different post-processing methods are compared in patient studies.Key points• Post-processing methods significantly influenced ADC values. • The mean coefficient of ADC variation due to PPM was 7.2 %. • To achieve reproducible ADC values, standardization of post-processing is recommended.
| S-EPMC5591618 | biostudies-literature
Project description:Background and purposeApparent diffusion coefficient (ADC) reflects micro-enviromental changes and therefore might be useful in predicting recurrence prior to brachytherapy. The purpose of this study is to evaluate change in ADC of the primary tumour and pathologic lymph nodes during treatment and to correlate this with clinical outcome.Material and methodsTwenty patients were included who received chemoradiation for locally advanced cervical cancer between July 2016 and November 2017. All patients underwent magnetic resonance imaging (MRI) prior to treatment, and three MRIs in weeks 1/2, 3 and 4 of treatment, including T2 and diffusion weighted imaging (b-values 0, 200, 800 s/mm2) for determining an ADC-map. Primary tumour was delineated on T2 and ADC-map and pathologic lymph nodes were delineated only on ADC-map.ResultsAt time of analysis median follow-up was 15 (range 7-22) months. From MRI one to four, primary tumour on ADC-map showed a significant signal increase of 0.94 (range 0.74-1.46) × 10-3 mm2/s to 1.13 (0.98-1.49) × 10-3 mm2/s (p < 0.001). When tumour was delineated on T2, ADC-value signal increase (in tumour according to T2) was similar. All 46 delineated pathologic lymph nodes showed an ADC-value increase on average from 0.79 (range 0.33-1.12) × 10-3 mm2/s to 1.14 (0.59-1.75) × 10-3 mm2/s (p < 0.001). The mean tumour/suspected lymph node volumes decreased respectively 51/40%. Four patients developed relapse (one local and three nodal), without clear relation with ΔADC. However, the median volume decrease of the primary tumour was substantially lower in the failing patients compared to the group without relapse (19 vs. 57%).ConclusionsADC values can be acquired using T2-based tumour delineations unless there are substantial shifts between ADC-mapping and T2 acquisition. It remains plausible that ΔADC is a predictor for response to EBRT. However, the correlation in this study was not statistically significant.
| S-EPMC7807732 | biostudies-literature