Voltammetric sensing of tryptophan in dark chocolate bars,skimmed milk and urine samples in the presence of dopamine and caffeine

Journal of Applied Electrochemistry - The present work reports the development of screen-printed electrode (SPE) using flexible polyester sheets modified with nanodiamond (ND), Au nanoparticles...     

SEC23B Loss-of-Function Suppresses Hepcidin Expression by Impairing Glycosylation Pathway in Human Hepatic Cells

Biallelic pathogenic variants in the SEC23B gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in SEC23B, which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload. Within our case series (28 CDA II patients), approximately 36% of them exhibit severe iron overload despite mild degree of anemia and slightly increased levels of ERFE (the only erythroid regulator of hepcidin suppression). Thus, we hypothesized a direct role of SEC23B loss-of-function in the pathomechanism of hepatic iron overload. We established a hepatic cell line, HuH7, stably silenced for SEC23B. In silenced cells, we observed significant alterations of the iron status, due to both the alteration in BMP/SMADs pathway effectors and a reduced capability to sense BMP6 stimulus. We demonstrated that the loss-of-function of SEC23B is responsible of the impairment in glycosylation of the membrane proteins involved in the activation of the BMP/SMADs pathway with subsequent hepcidin suppression. Most of these data were confirmed in another hepatic cell line, HepG2, stably silenced for SEC23B. Our findings suggested that the pathogenic mechanism of iron overload in CDA II is associated to both ineffective erythropoiesis and to a specific involvement of SEC23B pathogenic variants at hepatic level. Finally, we demonstrated the ability of SEC23B paralog, i.e., SEC23A, to rescue the hepcidin suppression, highlighting the functional overlap between the two SEC23 paralogs in human hepatic cells.     

Cytokines from Bench to Bedside: A Retrospective Study Identifies a Definite Panel of Biomarkers to Early Assess the Risk of Negative Outcome in COVID-19 Patients

The main aim of this study was to identify the most relevant cytokines which, when assessed in the earliest stages from hospital admission, may help to select COVID-19 patients with worse prognosis. A retrospective observational study was conducted in 415 COVID-19 patients (272 males; mean age 68 ± 14 years) hospitalized between May 2020 and March 2021. Within the first 72 h from hospital admission, patients were tested for a large panel of biomarkers, including C-reactive protein (CRP), Mid-regional proadrenomedullin (MR-proADM), Interferon-γ, interleukin 6 (IL-6), IL-1β, IL-8, IL-10, soluble IL2-receptor-α (sIL2Rα), IP10 and TNFα. Extensive statistical analyses were performed (correlations, t-tests, ranking tests and tree modeling). The mortality rate was 65/415 (15.7%) and a negative outcome (death and/or orotracheal intubation) affected 98/415 (23.6%) of cases. Univariate tests showed the majority of biomarkers increased in severe patients, but ranking tests helped to select the best variables to put on decisional tree modeling which identified IL-6 as the first dichotomic marker with a cut-off of 114 pg/mL. Then, a good synergy was found between IL-10, MR-proADM, sIL2Rα, IP10 and CRP in increasing the predictive value in classifying patients at risk or not for a negative outcome. In conclusion, beside IL-6, a panel of other cytokines representing the degree of immunoparalysis and the anti-inflammatory response (IP10, sIL2Rα and IL-10) showed synergic role when combined to biomarkers of systemic inflammation and endothelial dysfunction (CRP, MR-proADM) and may also better explain disease pathogenesis and suggests targeted intervention.     

ON THE RETRIEVAL OF URBAN AEROSOL MASS CONCENTRATION BY A 532 AND 1064 nm LIDAR

Based on the hypothesis of a monomodal, lognormal size distribution, the uncertainty affecting the humid-mass retrieval from LIDAR data was estimated by considering our ignorance of the distribution width to be a source of error. The mass to backscatter ratio and its uncertainty were computed for six accumulation-mode aerosol models as a function of the backscatter angstrom coefficient (α) and of the relative humidity (RH). A mass to backscatter uncertainty of less than ±30% was obtained for all six models. We computed the mass and simulated the expected LIDAR backscatter at 532 and 1064 nm for a test data set of 14 “real-world” multimodal size distributions obtained from the literature. The possible presence of 0–20%–50% water-insoluble compounds in each aerosol mode was assumed. An urban-type accumulation mode and 10 different coarse mode compositions were considered, including dust-like aerosols. The aerosol mass concentration was derived by fitting the simulated LIDAR data at 532 and 1064 nm with a monomodal distribution of urban aerosols of “unknown” width. The relative over- or underestimation of the mass with respect to the real aerosol mass was expressed in terms of α and RH for the 10 coarse aerosol types. The LIDAR-derived mass turned out to be underestimated by 0 – 15% in the case of (NH₄)₂SO₄, NaCl, maritime, and H₂SO₄ coarse aerosols. In the case coarse dust aerosols, the range of underestimation was wider (0–30%). Absorbing aerosols showed a maximum underestimation of 40–50%.     

Hydrotreating data interpretation by chemometrics

Hydrotreating in the presence of dispersed catalysts has been considered a promising route to obtain valuable fuels from heavy hydrocarbon cuts. A laboratory-scale study on the effect of operating conditions on heavy feedstock hydrotreating performances is reported. In order to maximise the effectiveness of the research activity, chemometrics was exploited both for experimental design and data interpretation.     

The influence of oxygen and carbon-content on aging of Ti-15-3

Optical microscopy, analytical transmission microscopy and scanning electron microscopy, and hardness tests have been carried out on quenched samples of Ti-15wt.%V-3wt.%Cr-3wt.%Al-3wt.%Sn containing different levels of oxygen and carbon that were aged at temperatures between 400 and 600 °C. The increase of oxygen content and the addition of carbon (C) increase the kinetics and the magnitude of age hardening. The addition of C greatly reduces the coarse grain boundary precipitation of α. Room temperature deformation has been shown to override compositional differences, and all deformed alloys age harden similarly. The role of oxygen and carbon additions and deformation on aging kinetics are discussed in terms of the factors, such as ω, dislocations, and grain boundary oxygen content that influence α precipitation. This paper was presented at the Beta Titanium Alloys of the 00’s Symposium sponsored by the Titanium Committee of TMS, held during the 2005 TMS Annual Meeting & Exhibition, February 13–16, 2005 in San Francisco, CA.     

Discovery of an Allosteric Ligand Binding Site in SMYD3 Lysine Methyltransferase

SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (K_D=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (K_D=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action.