Notes

Specific Issue involving International Diary associated with Molecular Sciences "Opioid Receptors and Endorphinergic Programs Two.0".
The stratum corneum (SC) acts as the main barrier of the skin against exogenous substances (e.g. air pollutants) and against the loss of endogenous substances such as water. The SC consists of keratin-rich dead cells surrounded by crystalline lamellar lipid regions. The main lipid classes are ceramides (CERs), free fatty acids (FFAs), and cholesterol (CHOL). Tropospheric ozone (O3) is a potent oxidant compound that reacts instantly with biological molecules such as lipids and proteins. Although it has been reported that O3 induces biological responses at the cellular level, to the best of our knowledge, there is no information related to the damages O3 can cause at the level of the SC extracellular lipid matrix. The aim of our work was to investigate which SC lipid subclasses are prone to oxidation when exposed to O3 and how the changes in chemical structures affect the lipid organization in a stratum corneum substitute (SCS) membrane. Ultimately, the barrier properties of the SCS were examined. Our studies revealed that O3 induces chemical modifications of the unsaturated bonds in CERs and CHOL. The appearance of carbonyl groups at the headgroup level and the removal of the linoleate moiety of omega‑O‑acylceramides (CER EOS) impact the lamellar organization of the lipid assembly and to a lesser extent the lateral packing of the lipids. Unexpectedly, these changes improved the barrier function of the SCS.Invasive as well as non-invasive conventional techniques for the detection of Helicobacter pylori (H. Harmine cost pylori) have several limitations that are being overcome by the development of novel, rapid and reliable biosensors. Herein, we describe several biosensors fabricated for the detection of H. pylori. This review aims to provide the principles of biosensors and their components including in the context to H. pylori detection. The major biorecognition elements in H. pylori detection include antigen/antibodies, oligonucleotides and enzymes. Furthermore, the review describes the transducers, such as electrochemical, optical and piezoelectric, also including microfluidics approaches. An overview of the biomarkers associated with H. pylori pathogenesis is also discussed. Finally, the prospects of advancement and commercialization of point-of-care tools are summarized.Spectrin tetramers of the membranes of enucleated mammalian erythrocytes play a critical role in red blood cell survival in circulation. One of the spectrins, αI, emerged in mammals with enucleated red cells after duplication of the ancestral α-spectrin gene common to all animals. The neofunctionalized αI-spectrin has moderate affinity for βI-spectrin, whereas αII-spectrin, expressed in nonerythroid cells, retains ancestral characteristics and has a 10-fold higher affinity for βI-spectrin. It has been hypothesized that this adaptation allows for rapid make and break of tetramers to accommodate membrane deformation. We have tested this hypothesis by generating mice with high-affinity spectrin tetramers formed by exchanging the site of tetramer formation in αI-spectrin (segments R0 and R1) for that of αII-spectrin. Erythrocytes with αIIβI presented normal hematologic parameters yet showed increased thermostability, and their membranes were significantly less deformable; under low shear forces, they displayed tumbling behavior rather than tank treading. The membrane skeleton is more stable with αIIβI and shows significantly less remodeling under deformation than red cell membranes of wild-type mice. These data demonstrate that spectrin tetramers undergo remodeling in intact erythrocytes and that this is required for the normal deformability of the erythrocyte membrane. We conclude that αI-spectrin represents evolutionary optimization of tetramer formation neither higher-affinity tetramers (as shown here) nor lower affinity (as seen in hemolytic disease) can support the membrane properties required for effective tissue oxygenation in circulation.
To elucidate morphological determinants of rod-and cone-dysfunction in Sorsby Fundus Dystrophy (SFD) and systematically compare visual function tests for interventional trials.

Prospective cross-sectional study METHODS Patients with SFD(n=16) and controls(n=20) underwent visual function testing (best-corrected and low-luminance visual acuity [BVCA, LLVA], contrast sensitivity, mesopic and dark-adapted fundus-controlled perimetry [FCP], rod-mediated dark adaptation [RMDA]), and multimodal imaging. Vision-related-quality-of-life (VRQoL) was evaluated. FCP and RMDA thresholds were analyzed using mixed-models and structure-function correlation using machine learning (ML). Longitudinal data of one patient with high-dose vitamin A supplementation were available.

While photopic BCVA was normative in SFD, LLVA was impaired (0.30 LogMAR [0.20;0.45] vs. 0.20 LogMAR [0.03;0.28],P<0.05), and scotopic visual function with a delayed rod-intercept-time (21 min [12.15;21] vs. 4.05 min [3.22;5.36],P<0.001), and materations on multimodal imaging. In contrast to BCVA, scotopic visual function tests are suitable to quantify dysfunction in early stages. Improvement of scotopic dysfunction after (off-label) high-dose vitamin A intake as observed in one patient in our study is compatible with the hypothesized local deficiency of vitamin A secondary to Bruch's membrane alterations.The enzyme cGAS functions as a sensor that recognizes the cytosolic DNA from foreign pathogen. The activation of the protein triggers the transcription of inflammatory genes, leading into the establishment of an antipathogen state. An interesting new discovery is that the detection of DNA by cGAS induced the formation of liquid-like droplets. However how cells regulate the formation of these droplets is still not fully understood. In order to unravel the molecular mechanism beneath the DNA-mediated phase separation of cGAS, we developed a polymer-based coarse-grained model which takes into accounts the basic structural organization in DNA and cGAS, as well as the binding properties between these biomolecules. This model was further integrated into a hybrid simulation algorithm. With this computational method, a multi-step kinetic process of aggregation between cGAS and DNA was observed. Moreover, we systematically tested the model under different concentrations and binding parameters. Our simulation results sical systems.Osteoarthritis (OA) is the most common painful disease with chronic articular cartilage degeneration. The pathological process of OA is complex and characterized by the imbalance between the synthesis and catabolism of chondrocytes and extracellular matrix, leading to the progressive destruction of articular cartilage damage. Because of the self-renewal and differentiation of mesenchymal stem cells (MSCs), various exogenous MSC-based cell therapies have been developed to treat OA. Moreover, the efficacy of MSC- based therapy is mainly attributed to the paracrine of cytokines, growth factors, and exosomes. Exosomes derived from MSCs can deliver various DNAs, RNAs, proteins and lipids, thus promoting MSCs migration and cartilage repair. Therefore, MSC-derived exosomes are considered as a promising alternative therapy for OA. In this review, we summarized properties of MSC-derived exosomes and the new role of MSC-derived exosomes in the treatment of OA. We also proposed possible perspectives of MSC-derived exosomes as cell-free regenerative reagents in the treatment of OA.HIV-1 entry into cells requires coordinated changes of the conformation and dynamics of both the fusion protein, gp41, and the lipids in the cell membrane and virus envelope. Commonly proposed features of membrane deformation during fusion include high membrane curvature, lipid disorder, and membrane surface dehydration. The virus envelope and target cell membrane contain a diverse set of phospholipids and cholesterol. To dissect how different lipids interact with gp41 to contribute to membrane fusion, here we use 31P solid-state NMR spectroscopy to investigate the curvature, dynamics, and hydration of POPE, POPC and POPS membranes, with and without cholesterol, in the presence of a peptide comprising the membrane proximal external region (MPER) and transmembrane domain (TMD) of gp41. Static 31P NMR spectra indicate that the MPER-TMD induces strong negative Gaussian curvature (NGC) to the POPE membrane but little curvature to POPC and POPCPOPS membranes. The NGC manifests as an isotropic peak in the static NMR spectra, whose intensity increases with the peptide concentration. Cholesterol inhibits the NGC formation and stabilizes the lamellar phase. Relative intensities of magic-angle spinning 31P cross-polarization and direct-polarization spectra indicate that all three phospholipids become more mobile upon peptide binding. Finally, 2D 1H-31P correlation spectra show that the MPER-TMD enhances water 1H polarization transfer to the lipids, indicating that the membrane surfaces become more hydrated. These results suggest that POPE is an essential component of the high-curvature fusion site, and lipid dynamic disorder is a general feature of membrane restructuring during fusion.The movement of individual molecules inside living cells has recently been resolved by single particles tracking (SPT) method which is a powerful tool for probing the organization and dynamics of the plasma membrane constituents. Effective treatment of metastatic cancers requires the toxic chemotherapy, however this therapy leads to the multidrug resistance phenomenon of the cancer cells, in which the cancer cells resist simultaneously to different drugs with different targets and chemical structures. P-glycoprotein molecules which are responsible for multidrug resistance of many cancer cells have been studied by cancer biologists during past haft of century. Recently, advances in laser and detector technologies have enabled single fluorophores to be visualized in aqueous solution. The development of the total internal reflection fluorescent microscope (TIRFM) provided means to monitor dynamic molecular localization in living cells. In this paper, P-glycoproteins (PGP) were labeled with green fluorescent protein (GFP) in living cell membrane of Madin-Darby canine kidney (MDCK) and the TIRFM method was used to characterize the dynamics of individual protein molecules on the surface of living cells. An evanescent field was produced by a totally internally reflected and a laser beam was illuminated the glass-water interface. GFP-PGP proteins that entered the evanescent field appeared as individual spots of light which were slighter than background fluorescence. We obtained high-resolution images and diffusion maps of membrane proteins on cell surface and showed the local diffusion properties of specific proteins on single cells. We also determined the diffusion coefficient, the mean square displacement and the average velocity of the tracked particles, as well as the heterogeneity of the cell environment. This study enabled us to understand single-molecule features in living cell and measure the diffusion kinetics of membrane-bound molecules.
To develop an algorithm for objective evaluation of distraction of surgeons during robot-assisted surgery (RAS).

Electroencephalogram (EEG) of 22 medical students was recorded while performing five key tasks on the robotic surgical simulator Instrument Control, Ball Placement, Spatial Control II, Fourth Arm Tissue Retraction, and Hands-on Surgical Training Tasks. All students completed the Surgery Task Load Index (SURG-TLX), which includes one domain for subjective assessment of distraction (scale 1-20). Scores were divided into low (score 1-6, subjective label 1), intermediate (score 7-12, subjective label 2), and high distraction (score 13-20, subjective label 3). These cut-off values were arbitrarily considered based on a verbal assessment of participants and experienced surgeons. A Deep Convolutional Neural Network (CNN) algorithm was trained utilizing EEG recordings from the medical students and used to classify their distraction levels. The accuracy of our method was determined by comparing the subjective distraction scores on SURG-TLX and the results from the proposed classification algorithm.
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