Increased Autotaxin Levels in Severe COVID-19, Correlating with IL-6 Levels,Endothelial Dysfunction Biomarkers,and Impaired Functions of Dendritic Cells

Autotaxin (ATX; ENPP2) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling phospholipid. Genetic and pharmacologic studies have previously established a pathologic role for ATX and LPA signaling in pulmonary injury, inflammation, and fibrosis. Here, increased ENPP2 mRNA levels were detected in immune cells from nasopharyngeal swab samples of COVID-19 patients, and increased ATX serum levels were found in severe COVID-19 patients. ATX serum levels correlated with the corresponding increased serum levels of IL-6 and endothelial damage biomarkers, suggesting an interplay of the ATX/LPA axis with hyperinflammation and the associated vascular dysfunction in COVID-19. Accordingly, dexamethasone (Dex) treatment of mechanically ventilated patients reduced ATX levels, as shown in two independent cohorts, indicating that the therapeutic benefits of Dex include the suppression of ATX. Moreover, large scale analysis of multiple single cell RNA sequencing datasets revealed the expression landscape of ENPP2 in COVID-19 and further suggested a role for ATX in the homeostasis of dendritic cells, which exhibit both numerical and functional deficits in COVID-19. Therefore, ATX has likely a multifunctional role in COVID-19 pathogenesis, suggesting that its pharmacological targeting might represent an additional therapeutic option, both during and after hospitalization.     

Synthesis and biological evaluation of novel EG5 inhibitors

Human Eg5 is a mitotic kinesin that is essential for bipolar spindle formation and maintenance during mitosis. Recently, the discovery of compounds that inhibit Eg5 and cause mitotic arrest has attracted great interest, due to their potential use as the next generation of antimitotics. Here, we present the synthesis and biological investigation of 3,4-dihydrophenylquinazoline-2(1H)-thiones as selective and potent Eg5 inhibitors.     

Long chain phenols—part 30: A rate study of the mannich reaction of phenols (with particular reference to 3-pentadecylphenol)

The rate of the Mannich reaction between 3-pentadecylphenol, di-n-propylamine and 40% aqueous formaldehyde in aqueous ethanol under basic conditions has been studied by an HPLC analytical technique following preliminary experiments with dimethylamine, diethylamine and morpholine. The effect of excess amine and excess formaldehyde, different temperatures and the influence of pH were investigated. Kinetic expressions involving the concentrations of the phenol, amine and formaldehyde have been obtained on the assumption of the participation of either (a) the aminal (methylene-bis-amine) or (b) the aminol (methylolamine) for five cases covering the various molar proportions of reactant used experimentally. Initially, to test the equations for reactions effected at constant water concentration, theoretical values of t (time) were obtained as the initial concentration (a) of the phenol was varied by increments by a/20 using trial values for the composite rate constant. In this manner the best visual fit between the experimental points and the theoretical curves was obtained. The rate constant corresponding to such a curve was subsequently refined using a least squares procedure to yield the value which minimised the sum of the residuals between the experimental and theoretical values. In all cases the sum of the residuals was smaller when the kinetic expression derived assuming participation of the aminal was employed. The latter assumption also led to a smaller dispersion in the values obtained for the composite reaction constant from the different experiments.     

Application of statistical physics methods and conceptsto the study of science & technology systems

We apply methods and concepts of statistical physics to the study of science & technology(S&T) systems. Specifically, our research is motivated by two concepts of fundamentalimportance in modern statistical physics: scaling and universality. We try to identify robust,universal, characteristics of the evolution of S&T systems that can provide guidance to forecastingthe impact of changes in funding. We quantify the production of research in a novel fashioninspired by our previous study of the growth dynamics of business firms. We study the productionof research from the point of view both of inputs (R&D funding) and of outputs (publications andpatents) and find the existence of scaling laws describing the growth of these quantities.We also analyze R&D systems of different countries to test the "universality" of our results.We hypothesize that the proposed methods may be particularly useful for fields of S&T (or forlevels of aggregation) for which either not enough information is available, or for which evolutionis so fast that there is not enough time to collect enough data to make an informed decision.     

Compression of gellan gels. Part II: Effect of sugars

The effect of sucrose, glucose, fructose and their mixtures on the gelation of 0.5 wt% low acyl gellan in the presence of potassium chloride (100 mM) was investigated by large deformation compression experiments. The sugar concentration varied from 0 to 15 wt% whereas all their combinations at a final concentration of 15 wt% were also studied. Stress at failure and strain at failure along with Young's modulus were calculated from each compression curve. Samples prior to compression were refrigerated at 5 °C for 1, 2 and 24 h. Glucose showed no contribution to the gellan network strength but decreased the firmness of the gels. On the other hand, fructose and sucrose enhanced the strength of the network, with sucrose being slightly more effective, but had no effect on firmness. This behaviour depended solely on the presence of each sugar and not in their concentration. The elasticity of the gels was not significantly altered by the addition of sugars or their mixtures. Strength and firmness shared similar profiles when mixtures of sugars were used to promote gelation. Sugars, when in mixtures, showed no synergistic interactions whereas their type seems to affect the properties of the resulting gels.     

Study of Formulation and Stability of Co-surfactant Free Water-in-Olive Oil Nano- and Submicron Emulsions with Food Grade Non-ionic Surfactants

Nanoemulsions are of great interest in food industry finding various food applications. However, oil-in-water (o/w) nanoemulsions have been intensively investigated, but there are few studies on w/o nanoemulsions. In the present work the preparation of nanoemulsions with olive oil using non-ionic surfactants (Tween 20, 40, 60, 80, Span 20, 80) without the addition of a co-surfactant was studied and their emulsion properties and stability were examined. The stable nanoemulsions were presented in ternary phase diagrams (oil–water-surfactant) for each surfactant and the emulsifying ability of the efficient surfactants was determined. The nanoemulsions properties were evaluated in relationship to compositional components. From the results of this study it can be concluded that stable olive oil nanoemulsions without use of a co-surfactant were obtained and moreover the most efficient type of emulsifier and its ratio of addition in the system were determined.     

Combined effect of MAP and thyme essential oil on the microbiological,chemical and sensory attributes of organically aquacultured sea bass (Dicentrarchus labrax) fillets

The present study evaluated the combined effect of Modified Atmosphere Packaging (MAP) using two different gas mixtures (40% CO₂/50% N₂/10% O₂; treatment M1, 60% CO₂/30% N₂/10% O₂, treatment M2), and thyme oil (0.2% v/w, T) used as a natural preservative, on the quality and shelf life extension of fresh filleted sea bass, product of organic aquaculture, during refrigerated storage (4± 0.5 °C), for a period of 21 days. Aerobically packaged sea bass fillets (A) were used as control samples. The dominant bacteria in the microflora of sea bass fillets, irrespective of treatment, were the pseudomonads and the H₂S-producing bacteria while lactic acid bacteria were also part of the dominant microflora. Total viable counts for fresh sea bass fillets stored aerobically exceeded 7 log CFU/g after 7 days, while treatments A+T, M1, M2 and M2+T reached the same value on days 9, 10, 12 and 19, respectively. Among the chemical indices determined, TBA values were within the good quality limits (2–4 mg MDA/kg), during the sensory shelf lives of sea bass samples, irrespective of treatment. TVB-N proved to be a suitable index for the spoilage of sea bass fillets stored at 4 °C. Samples A and A+T, M1, M2, M2+T exceeded the proposed upper TVB-N acceptability limit (10 mg N/100 g) on days 6, 8, 9, 13 and 17 of storage respectively. TMA-N values of the samples A, A+T and M1, M2, M2+T exceeded the proposed limit (4 mg N/100 g) on days 6, 9, 9–10, 13 and 19 of storage, respectively, and correlated well with the microbiological data, indicating that along with TVB-N, TMA-N may serve as a useful index for sea bass fillets spoilage. As regards sensory evaluation, the presence of thyme oil proved to improve the sensory quality of sea bass fillets when used in combination with MAP2, providing a shelf life of 17 days as compared to 6 days of the control samples.     

Different Types of Chronic Inflammation Engender Distinctive Immunosenescent Profiles in Affected Patients

Immunosenescence encompasses a spectrum of lymphocyte phenotypic alterations. The aim of the study was to evaluate immunosenescent effect of two different forms of chronic inflammation, Systemic Lupus Erythematosous (SLE), a systemic autoimmune disease, and End-Stage Kidney Disease (ESKD), a chronic inflammatory disorder. Certain lymphocyte surface molecules, including CD31, CD45RA, CCR7, CD28, CD57, for T, and IgD, CD27 for B lymphocytes, were analyzed by flow cytometry in 30 SLE and 53 ESKD patients on hemodialysis (HD), and results were compared to 31 healthy controls (HC) of similar age, gender, and nationality. Significant Lymphopenia was evident in both SLE and ESKD-HD patients, compared to HC, affecting B cells 75.4 (14.4–520.8), 97 (32–341), and 214 (84–576) cells/μL, respectively, p < 0.0001, and CD4 cells 651.2 (71.1–1478.2), 713 (234–1509), and 986 (344–1591) cells/μL, respectively, p < 0.0001. The allocation of B cell subpopulations was remarkably different between SLE and ESKD-HD patients. SLE showed a clear shift to senescence (CD19IgD-CD27−) cells, compared to ESKD-HD and HC, 11.75 (10)% vs. 8 (6) vs. 8.1 (10), respectively. Regarding T lymphocytes, Central Memory CD8 cells predominated in both SLE and ESKD-HD patients compared to HC, 53 (50)%, 52 (63), and 24 (64)%, respectively, while ESKD-HD but not SLE patients also had increased expression of CD4CD28− and CD8CD28− cells. In conclusion, both diseases are followed by significant lymphopenia; however, the senescent phenomenon affects the B lymphocyte compartment in SLE patients and T lymphocytes in ESKD-HD patients.     

α-Helices in the Type III Secretion Effectors: A Prevalent Feature with Versatile Roles

Type III Secretion Systems (T3SSs) are multicomponent nanomachines located at the cell envelope of Gram-negative bacteria. Their main function is to transport bacterial proteins either extracellularly or directly into the eukaryotic host cell cytoplasm. Type III Secretion effectors (T3SEs), latest to be secreted T3S substrates, are destined to act at the eukaryotic host cell cytoplasm and occasionally at the nucleus, hijacking cellular processes through mimicking eukaryotic proteins. A broad range of functions is attributed to T3SEs, ranging from the manipulation of the host cell’s metabolism for the benefit of the bacterium to bypassing the host’s defense mechanisms. To perform this broad range of manipulations, T3SEs have evolved numerous novel folds that are compatible with some basic requirements: they should be able to easily unfold, pass through the narrow T3SS channel, and refold to an active form when on the other side. In this review, the various folds of T3SEs are presented with the emphasis placed on the functional and structural importance of α-helices and helical domains.