- EGF Receptor Stalls upon Activation as Evidenced by Complementary Fluorescence Correlation Spectroscopy and Fluorescence Recovery after Photobleaching Measurements. [Journal Article]
- IJInt J Mol Sci 2019 Jul 09; 20(13)
- To elucidate the molecular details of the activation-associated clustering of epidermal growth factor receptors (EGFRs), the time course of the mobility and aggregation states of eGFP tagged EGFR in …
To elucidate the molecular details of the activation-associated clustering of epidermal growth factor receptors (EGFRs), the time course of the mobility and aggregation states of eGFP tagged EGFR in the membranes of Chinese hamster ovary (CHO) cells was assessed by in situ mobility assays. Fluorescence correlation spectroscopy (FCS) was used to probe molecular movements of small ensembles of molecules over short distances and time scales, and to report on the state of aggregation. The diffusion of larger ensembles of molecules over longer distances (and time scales) was investigated by fluorescence recovery after photobleaching (FRAP). Autocorrelation functions could be best fitted by a two-component diffusion model corrected for triplet formation and blinking. The slow, 100-1000 ms component was attributed to membrane localized receptors moving with free Brownian diffusion, whereas the fast, ms component was assigned to cytosolic receptors or their fragments. Upon stimulation with 50 nM EGF, a significant decrease from 0.11 to 0.07 μm2/s in the diffusion coefficient of membrane-localized receptors was observed, followed by recovery to the original value in ~20 min. In contrast, the apparent brightness of diffusing species remained the same. Stripe FRAP experiments yielded a decrease in long-range molecular mobility directly after stimulation, evidenced by an increase in the recovery time of the slow component from 13 to 21.9 s. Our observations are best explained by the transient attachment of ligand-bound EGFRs to immobile or slowly moving structures such as the cytoskeleton or large, previously photobleached receptor aggregates.
- Eigenvector Centrality Dynamics From Resting-State fMRI: Gender and Age Differences in Healthy Subjects. [Journal Article]
- FNFront Neurosci 2019; 13:648
- With the increasing use of functional brain network properties as markers of brain disorders, efficient visualization and evaluation methods have become essential. Eigenvector centrality mapping (ECM…
With the increasing use of functional brain network properties as markers of brain disorders, efficient visualization and evaluation methods have become essential. Eigenvector centrality mapping (ECM) of functional MRI (fMRI) data enables the representation of per-node graph theoretical measures as brain maps. This paper studies the use of centrality dynamics for measuring group differences in imaging studies. Imaging data were used from a publicly available imaging study, which included resting fMRI data. After warping the images to a standard space and masking cortical regions, ECM were computed in a sliding window. The dual regression method was used to identify dynamic centrality differences inside well-known resting-state networks between gender and age groups. Gender-related differences were found in the medial and lateral visual, motor, default mode, and executive control RSN, where male subjects had more consistent centrality variations within the network. Age-related differences between the youngest and oldest subjects, based on a median split, were found in the medial visual, executive control and left frontoparietal networks, where younger subjects had more consistent centrality variations within the network. Our findings show that centrality dynamics can be used to identify between-group functional brain network centrality differences, and that age and gender distributions studies need to be taken into account in functional imaging studies.
- Acquired epileptiform opercular syndrome evaluated with real-time transcranial Doppler ultrasound-video-electroencephalogram before and after treatment: a case report. [Journal Article]
- BNBMC Neurol 2019 Jul 17; 19(1):166
- CONCLUSIONS: The real-time TCD-SDvEEG was highly sensitive in detecting therapeutic changes. The findings might facilitate the understanding of the mechanisms underlying neurovascular coupling in patients with AEOS accompanied by ESES.
- Nudge nudge, wink wink. [Editorial]
- CMClin Med (Lond) 2019; 19(4):265
- Jatrorrhizine inhibits mammary carcinoma cells by targeting TNIK mediated Wnt/β-catenin signalling and epithelial-mesenchymal transition (EMT). [Journal Article]
- PPhytomedicine 2019 Jul 03; 63:153015
- CONCLUSIONS: These findings provide an overall perspective that jatrorrhizine potentially restrains TNIK regulating Wnt/β-catenin signalling and EMT expression for mammary cancer targeted therapy.
- Topical sustained drug delivery to the retina with a drug-eluting contact lens. [Journal Article]
- BBiomaterials 2019; 217:119285
- Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to…
Intravitreal injections and implants are used to deliver drugs to the retina because therapeutic levels of these medications cannot be provided by topical administration (i.e. eye drops). In order to reach the retina, a topically applied drug encounters tear dilution, reflex blinking, and rapid fluid drainage that collectively reduce the drug's residence time on the ocular surface. Residing under the tears, the cornea is the primary gateway into the eye for many topical ophthalmic drugs. We hypothesized that a drug-eluting contact lens that rests on the cornea would therefore be well-suited for delivering drugs to the eye including the retina. We developed a contact lens based dexamethasone delivery system (Dex-DS) that achieved sustained drug delivery to the retina at therapeutic levels. Dex-DS consists of a dexamethasone-polymer film encapsulated inside a contact lens. Rabbits wearing Dex-DS achieved retinal drug concentrations that were 200 times greater than those from intensive (hourly) dexamethasone drops. Conversely, Dex-DS demonstrated lower systemic (blood serum) dexamethasone concentrations. In an efficacy study in rabbits, Dex-DS successfully inhibited retinal vascular leakage induced by intravitreal injection of vascular endothelial growth factor (VEGF). Dex-DS was found to be safe in a four-week repeated dose biocompatibility study in healthy rabbits.
- Phytochemical profiling and seasonal variation of essential oils of three Callistemon species cultivated in Egypt. [Journal Article]
- PlosPLoS One 2019; 14(7):e0219571
- The genus Callistemon comprises evergreen shrubs or small trees, widely cultivated as ornamentals and for essential oil production. Callistemon is well-recognized in folk medicine for its anti-cough,…
The genus Callistemon comprises evergreen shrubs or small trees, widely cultivated as ornamentals and for essential oil production. Callistemon is well-recognized in folk medicine for its anti-cough, anti-bronchitis, and insecticidal activities. In the current study, we profiled the essential oil composition of the leaves of C. citrinus, C. rigidus and C. viminalis (Myrtaceae) collected during different seasons by GLC-MS coupled to multivariate data analysis. Antioxidant, anti-inflammatory and anti-proliferative activities of Callistemon essential oils were evaluated. A total of 29 compounds were tentatively identified. Oxygenated monoterpenes dominated in essential oils, where eucalyptol represented the major constituent in the three Callistemon species in all seasons. Multivariate data analysis including Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) were applied to discriminate between different Callistemon species in each season and to investigate any correlation between the metabolic profile of each species within different seasons. As expected, PCA plot could discriminate the three Callistemon species in the four seasons. The dendrogram from HCA confirmed the results of PCA as it showed the same segregation pattern regarding the discrimination of different Callistemon species. C. viminalis showed more pronounced antioxidant activity than C. citrinus, exhibiting IC50 values of 1.40 mg/mL and 1.77 mg/mL, respectively. Meanwhile, C. rigidus showed very weak antioxidant activity. All oils showed membrane stabilization activity in hypotonic solution induced haemolysis assay, where C. viminalis showed potent membrane stabilizing activity exhibiting IC50 value of 25.6 μg/mL comparable to that of the standard drug, indomethacin (17.02 μg/mL). Nevertheless, Callistemon essential oils were not cytotoxic in HCT-116 and Hela human cancer cell lines.
- Suppressed Blinking Under Normal Air Atmosphere in Toxic Metal Free, Small Sized, InP Based Core/Alloy-Shell/Shell Quantum Dot. [Journal Article]
- JPJ Phys Chem Lett 2019 Jul 11
- Suppressed blinking has been reported in large sized (diameter ~14.1 nm) core/shell InP QDs, under reduced air environment. We report here suppressed blinking with ~four times smaller (diameter ~3.6 …
Suppressed blinking has been reported in large sized (diameter ~14.1 nm) core/shell InP QDs, under reduced air environment. We report here suppressed blinking with ~four times smaller (diameter ~3.6 nm) core/alloy-shell/shell InP QD under ambient air atmosphere. <ON fraction> has been obtained to be 0.65. About 26 % of the single QDs exhibit ON fraction >80%. Smaller ON exponent (1.19) magnitude in comparison to OFF exponent (1.45) signifies longer ON events are interrupted by smaller OFF events. ON event truncation time is ~ 1.5 times that of OFF event, signifying detrapping rate is much higher than the trapping rate. Interestingly detrapping rate/trapping rate (single particle level property), could be directly correlated to the PLQY (ensemble level property). An additional exponential term required to fit probability density distribution of ON event duration could be correlated with hole trapping, leading to extended ON times (> 60s).
- Leaf extract of Caesalpinia mimosoides enhances oxidative stress resistance and prolongs lifespan in Caenorhabditis elegans. [Journal Article]
- BCBMC Complement Altern Med 2019 Jul 08; 19(1):164
- CONCLUSIONS: The results of this study establish the antioxidant activity of C. mimosoides extract in vivo and suggest its potential as a dietary supplement and alternative medicine to defend against oxidative stress and aging, which should be investigated in intervention studies.
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- Mechanistic investigation of mEos4b reveals a strategy to reduce track interruptions in sptPALM. [Journal Article]
- NMNat Methods 2019 Jul 08
- Green-to-red photoconvertible fluorescent proteins repeatedly enter dark states, causing interrupted tracks in single-particle-tracking localization microscopy (sptPALM). We identified a long-lived d…
Green-to-red photoconvertible fluorescent proteins repeatedly enter dark states, causing interrupted tracks in single-particle-tracking localization microscopy (sptPALM). We identified a long-lived dark state in photoconverted mEos4b that results from isomerization of the chromophore and efficiently absorbs cyan light. Addition of weak 488-nm light swiftly reverts this dark state to the fluorescent state. This strategy largely eliminates slow blinking and enables the recording of longer tracks in sptPALM with minimum effort.