Перспективи використання тонкодисперсних вуглецевих матеріалів

У останні десятиліття особливу увагу вчених привертає дослідження різних алотропних видозмін вуглецю, зокрема природних: алмазу, графіту, лонсдейліту, фулерену, вуглецевих нанотрубок (у тому числі шунгіту – природного нанотехн-логічного матеріалу) і штучних: карбіну, графену, аморфного вуглецю (кокс, вугілля, технічний вуглець, сажа, активоване вугілля). Водночас у техніці все більше розповсюдження отримують тонкодисперсні вуглецеві матеріали, зокрема тонкодисперсне вугілля та технічний вуглець, тонкоподрібнений аморфний вуглець, активоване вугілля, дослідженню яких присвячено ряд окремих досліджень, у т.ч. і авторів статті

Prognostic biomarkers in primary progressive multiple sclerosis: validating and scrutinizing multimodal evoked potentials

OBJECTIVE: To validate the prognostic value of multimodal evoked potentials (mmEP) in primary progressive multiple sclerosis (PPMS) and to determine the most predictive EP-modalities. METHODS: Thirty-nine patients with PPMS (expanded disability status scale (EDSS): 2.0-6.5; mean clinical follow-up: 2.8 years) had visual (VEP), upper and lower limb somatosensory (SEP) and motor EP (MEP) at baseline. Quantitative EP-scores for single (qVEP, qSEP, qMEP) and combined modalities were correlated to EDSS and compared to previously published data of 21 PPMS patients. Predictors of EDSS-change were analyzed in pooled data by linear regression. RESULTS: Samples were comparable. Except qVEP, all EP-scores were correlated to EDSS at baseline (Rho: 0.45-0.69; p < 0.01) and follow-up (Rho: 0.59-0.80; p < 0.001). Combined EP-modalities significantly predicted EDSS-change (R(2)adj: 0.24), while EDSS and age did not. Tibial qSEP (R(2)adj: 0.22) and qMEP (R(2)adj: 0.26) were the best single modality predictors, outperformed by their combination (R(2)adj: 0.32). CONCLUSIONS: Quantitative EP-scores predict up to 32% of EDSS-change over three years. Modalities representing motor and long tract function carry the main prognostic information. SIGNIFICANCE: Replication of previous results corroborates the use of mmEP as a prognostic biomarker candidate in PPMS

Texture Features of Proton Density Fat Fraction Maps from Chemical Shift Encoding-Based MRI Predict Paraspinal Muscle Strength

Texture analysis (TA) has shown promise as a surrogate marker for tissue structure, based on conventional and quantitative MRI sequences. Chemical-shift-encoding-based MRI (CSE-MRI)-derived proton density fat fraction (PDFF) of paraspinal muscles has been associated with various medical conditions including lumbar back pain (LBP) and neuromuscular diseases (NMD). Its application has been shown to improve the prediction of paraspinal muscle strength beyond muscle volume. Since mean PDFF values do not fully reflect muscle tissue structure, the purpose of our study was to investigate PDFF-based TA of paraspinal muscles as a predictor of muscle strength, as compared to mean PDFF. We performed 3T-MRI of the lumbar spine in 26 healthy subjects (age = 30 ± 6 years; 15 females) using a six-echo 3D spoiled gradient echo sequence for chemical-shift-encoding-based water–fat separation. Erector spinae (ES) and psoas (PS) muscles were segmented bilaterally from level L2–L5 to extract mean PDFF and texture features. Muscle flexion and extension strength was measured with an isokinetic dynamometer. Out of the eleven texture features extracted for each muscle, Kurtosis(global) of ES showed the highest significant correlation (r = 0.59, p = 0.001) with extension strength and Variance(global) of PS showed the highest significant correlation (r = 0.63, p = 0.001) with flexion strength. Using multivariate linear regression models, Kurtosis(global) of ES and BMI were identified as significant predictors of extension strength (R2adj = 0.42; p &lt; 0.001), and Variance(global) and Skewness(global) of PS were identified as significant predictors of flexion strength (R2adj = 0.59; p = 0.001), while mean PDFF was not identified as a significant predictor. TA of CSE-MRI-based PDFF maps improves the prediction of paraspinal muscle strength beyond mean PDFF, potentially reflecting the ability to quantify the pattern of muscular fat infiltration. In the future, this may help to improve the pathophysiological understanding, diagnosis, monitoring and treatment evaluation of diseases with paraspinal muscle involvement, e.g., NMD and LBP

T2-Weighted Dixon Turbo Spin Echo for Accelerated Simultaneous Grading of Whole-Body Skeletal Muscle Fat Infiltration and Edema in Patients With Neuromuscular Diseases

Objective The assessment of fatty infiltration and edema in the musculature of patients with neuromuscular diseases (NMDs) typically requires the separate performance of T-1-weighted and fat-suppressed T-2-weighted sequences. T-2-weighted Dixon turbo spin echo (TSE) enables the generation of T-2-weighted fat- and water-separated images, which can be used to assess both pathologies simultaneously. The present study examines the diagnostic performance of T-2-weighted Dixon TSE compared with the standard sequences in 10 patients with NMDs and 10 healthy subjects. Methods Whole-body magnetic resonance imaging was performed including T-1-weighted Dixon fast field echo, T-2-weighted short-tau inversion recovery, and T-2-weighted Dixon TSE. Fatty infiltration and intramuscular edema were rated by 2 radiologists using visual semiquantitative rating scales. To assess intermethod and interrater agreement, weighted Cohen's coefficients were calculated. Results The ratings of fatty infiltration showed high intermethod and high interrater agreement (T-1-weighted Dixon fast field echo vs T-2-weighted Dixon TSE fat image). The evaluation of edematous changes showed high intermethod and good interrater agreement (T-2-weighted short-tau inversion recovery vs T-2-weighted Dixon TSE water image). Conclusions T-2-weighted Dixon TSE imaging is an alternative for accelerated simultaneous grading of whole-body skeletal muscle fat infiltration and edema in patients with NMDs

Ebola virus VP35 induces high-level production of recombinant TPL-2–ABIN-2–NF-κB1 p105 complex in co-transfected HEK-293 cells

Activation of PKR (double-stranded-RNA-dependent protein kinase) by DNA plasmids decreases translation, and limits the amount of recombinant protein produced by transiently transfected HEK (human embryonic kidney)-293 cells. Co-expression with Ebola virus VP35 (virus protein 35), which blocked plasmid activation of PKR, substantially increased production of recombinant TPL-2 (tumour progression locus 2)–ABIN-2 [A20-binding inhibitor of NF-κB (nuclear factor κB) 2]–NF-κB1 p105 complex. VP35 also increased expression of other co-transfected proteins, suggesting that VP35 could be employed generally to boost recombinant protein production by HEK-293 cells

H3K9 Methyltransferases and Demethylases Control Lung Tumor-Propagating Cells and Lung Cancer Progression

Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition impairs lung adenocarcinoma progression in vivo. Therefore, inhibition of G9a is dangerous in certain cancer contexts, and targeting the histone demethylases is a more suitable approach for lung cancer treatment. Understanding cellular context and specific tumor populations is critical when targeting epigenetic regulators in cancer for future therapeutic development

Associations Between Lumbar Vertebral Bone Marrow and Paraspinal Muscle Fat Compositions—An Investigation by Chemical Shift Encoding-Based Water-Fat MRI

Purpose: Advanced magnetic resonance imaging (MRI) methods enable non-invasive quantification of body fat situated in different compartments. At the level of the lumbar spine, the paraspinal musculature is the compartment spatially and functionally closely related to the vertebral column, and both vertebral bone marrow fat (BMF) and paraspinal musculature fat contents have independently shown to be altered in various metabolic and degenerative diseases. However, despite their close relationships, potential correlations between fat compositions of these compartments remain largely unclear.Materials and Methods: Thirty-nine female subjects (38.5% premenopausal women, 29.9 ± 7.1 years; 61.5% postmenopausal women, 63.2 ± 6.3 years) underwent MRI at 3T of the lumbar spine using axially- and sagittally-prescribed gradient echo sequences for chemical shift encoding-based water-fat separation. The erector spinae muscles and vertebral bodies of L1–L5 were segmented to determine the proton density fat fraction (PDFF) of the paraspinal and vertebral bone marrow compartments. Correlations were calculated between the PDFF of the paraspinal muscle and bone marrow compartments.Results: The average PDFF of the paraspinal muscle and bone marrow compartments were significantly lower in premenopausal women when compared to postmenopausal women (11.6 ± 2.9% vs. 24.6 ± 7.1% &amp; 28.8 ± 8.3% vs. 47.2 ± 8.5%; p &lt; 0.001 for both comparisons). In premenopausal women, no significant correlation was found between the PDFF of the erector spinae muscles and the PDFF of the bone marrow of lumbar vertebral bodies (p = 0.907). In contrast, a significant correlation was shown in postmenopausal women (r = 0.457, p = 0.025). Significance was preserved after inclusion of age and body mass index (BMI) as control variables (r = 0.472, p = 0.027).Conclusion: This study revealed significant correlations between the PDFF of paraspinal and vertebral bone marrow compartments in postmenopausal women. The PDFF of the paraspinal and vertebral bone marrow compartments and their correlations might potentially serve as biomarkers; however, future studies including more subjects are required to evaluate distinct clinical value and reliability. Future studies should also follow up our findings in patients suffering from metabolic and degenerative diseases to clarify how these correlations change in the course of such diseases

Spinal cord grey matter segmentation challenge

An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication

Folic Acid Exposure Rescues Spina Bifida Aperta Phenotypes in Human Induced Pluripotent Stem Cell Model

Neural tube defects (NTDs) are severe congenital abnormalities, caused by failed closure of neural tube during early embryonic development. Periconceptional folic acid (FA) supplementation greatly reduces the risk of NTDs. However, the molecular mechanisms behind NTDs and the preventive role of FA remain unclear. Here, we use human induced pluripotent stem cells (iPSCs) derived from fetuses with spina bifida aperta (SBA) to study the pathophysiology of NTDs and explore the effects of FA exposure. We report that FA exposure in SBA model is necessary for the proper formation and maturation of neural tube structures and robust differentiation of mesodermal derivatives. Additionally, we show that the folate antagonist methotrexate dramatically affects the formation of neural tube structures and FA partially reverts this aberrant phenotype. In conclusion, we present a novel model for human NTDs and provide evidence that it is a powerful tool to investigate the molecular mechanisms underlying NTDs, test drugs for therapeutic approaches