Emerging insights into atypical B cells in pediatric chronic infectious diseases and immune system disorders: T(o)-bet on control of B-cell immune activation

: repetitive or persistent cellular stimulation in vivo has been associated with the development of a heterogeneous B-cell population that exhibits a distinctive phenotype and, in addition to classical B-cell markers, often expresses the transcription factor T-bet and myeloid marker CD11c. research suggests that this atypical population consists of B cells with distinct B-cell receptor specificities capable of binding the antigens responsible for their development. the expansion of this population occurs in the presence of chronic inflammatory conditions and autoimmune diseases where different nomenclatures have been used to describe them. however, as a result of the diverse contexts in which they have been investigated, these cells have remained largely enigmatic, with much ambiguity remaining regarding their phenotype and function in humoral immune response as well as their role in autoimmunity. atypical B cells have garnered considerable interest because of their ability to produce specific antibodies and/or autoantibodies and because of their association with key disease manifestations. although they have been widely described in the context of adults, little information is present for children. Therefore, the aim of this narrative review is to describe the characteristics of this population, suggest their function in pediatric immune-related diseases and chronic infections, and explore their potential therapeutic avenues

Cybersecurity Impacts of the Covid-19 Pandemic in Italy

The Covid-19 pandemic has pushed companies to the extensive use of digital services, to implement home working and provide online services to people in lockdown. As a consequence, it is interesting to study how this has affected the number, kind and distribution of cybersecurity attacks. This paper gives an empirical evaluation of the cybersecurity attacks at the beginning of the Covid-19 pandemic in Italy, based on data collected from the questionnaires of the annual Digital Attacks Observatory. It shows that the overall number of attacks has not increased, but attacks have affected smaller companies than before. This can be explained with the fact that the Italian industrial scenario is mostly populated by small and medium enterprises, that have been obliged to a quick reconversion of their IT systems and typically lack the necessary cybersecurity culture

Rationalizing Sequence and Conformational Effects on the Guanine Oxidation in Different DNA Conformations

The effect of the environment on the guanine redox potential is studied by means of a theoretical-computational approach. Our data, in agreement with previous experimental findings, clearly show that the presence of consecutive guanine bases in both single-and double-stranded DNA oligomers lowers their reduction potential. Such an effect is even more marked when a G-rich quadruplex is considered, where the oxidized form of guanine is particularly stabilized. To the best of our knowledge, this is the first computational study reporting on a quantitative estimate of the dependence of the guanine redox potential on sequence and conformational effects in complex DNA molecules, ranging from single-stranded DNA to G-quadruplex

Modelling complex bimolecular reactions in a condensed phase: the case of phosphodiester hydrolysis

Background: the theoretical modelling of reactions occurring in liquid phase is a research line of primary importance both in theoretical-computational chemistry and in the context of organic and biological chemistry. Here we present the modelling of the kinetics of the hydroxide-promoted hydrolysis of phosphoric diesters. Method: the theoretical-computational procedure involves a hybrid quantum/classical approach based on the perturbed matrix method (PMM) in conjunction with molecular mechanics. Results: the presented study reproduces the experimental data both in the rate constants and in the mechanistic aspects (C-O bond vs. O-P bond reactivity). The study suggests that the basic hydrolysis of phosphodiesters occurs through a concerted ANDN mechanism, with no formation of penta-coordinated species as reaction intermediates. Conclusions: the presented approach, despite the approximations, is potentially applicable to a large number of bimolecular transformations in solution and therefore leads the way to a fast and general method to predict the rate constants and reactivities/selectivities in complex environments

Synthesis and anti-picornavirus activity of homo-isoflavonoids

Substituted homo-isoflavonoids were synthesized in order to study their in vitro anti-picornavirus activity. The maximum non-toxic concentration of the compounds for susceptible cells (HeLa) was determined, and the ability of non-cytotoxic concentrations to interfere with plaque formation by human rhinovirus (HRV) 1B and 14 and poliovirus (PV) 2 was examined. All the tested compounds were weakly effective against PV-2, while they exhibited a variable degree of activity against HRV-1B and -14 infection. Serotype 1B was much more sensitive than 14 to the action of the compounds, and the presence of one or more chlorine atoms increased the antiviral effect in all homo-isoflavonoids tested, confirming the positive influence of this substituent on activity

Copper and Zinc Metal–Organic Frameworks with Bipyrazole Linkers Display Strong Antibacterial Activity against Both Gram+ and Gram− Bacterial Strains

: Here, we report a new synthetic protocol based on microwave-assisted synthesis (MAS) for the preparation of higher yields of zinc and copper in MOFs based on different bis(pyrazolyl)-tagged ligands ([M(BPZ)]n where M = Zn(II), Cu(II), H2BPZ = 4,4'-bipyrazole, [M(BPZ-NH2)]n where M = Zn(II), Cu(II); H2BPZ-NH2 = 3-amino-4,4'-bipyrazole, and [Mx(Me4BPZPh)] where M = Zn(II), x = 1; Cu(II), x = 2; H2Me4BPZPh = bis-4'-(3',5'-dimethyl)-pyrazolylbenzene) and, for the first time, a detailed study of their antibacterial activity, tested against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, as representative agents of infections. The results show that all MOFs exert a broad-spectrum activity and strong efficiency in bacterial growth inhibition, with a mechanism of action based on the surface contact of MOF particles with bacterial cells through the so-called "chelation effect" and reactive oxygen species (ROS) generation, without a significant release of Zn(II) and Cu(II) ions. In addition, morphological changes were elucidated by using a scanning electron microscope (SEM) and bacterial cell damage was further confirmed by a confocal laser scanning microscopy (CLSM) test

Novel protein-truncating variant in the APOB gene may protect from coronary artery disease and adverse cardiovascular events

Background and aims: Genetic testing is still rarely used for the diagnosis of dyslipidemia, even though gene variants determining plasma lipids levels are not uncommon.Methods: Starting from a a pilot-analysis of targeted Next Generation Sequencing (NGS) of 5 genes related to familial hypercholesterolemia (LDLR, APOB, PCSK9, HMGCR, APOE) within a cardiovascular cohort in subjects with extreme plasma concentrations of low-density lipoprotein (LDL) cholesterol, we discovered and characterized a novel point mutation in the APOB gene, which was associated with very low levels of apolipoprotein B (ApoB) and LDL cholesterol.Results: APOB c.6943 G > T induces a premature stop codon at the level of exon 26 in the APOB gene and generates a protein which has the 51% of the mass of the wild type ApoB-10 0 (ApoB-51), with a trun-cation at the level of residue 2315. The premature stop codon occurs after the one needed for the synthesis of ApoB-4 8, allowing chylomicron production at intestinal level and thus avoiding potential nutritional impairments. The heterozygous carrier of APOB c.6943G > T, despite a very high-risk profile encompassing all the traditional risk factors except for dyslipidemia, had normal coronary arteries by angiography and did not report any major adverse cardiovascular event during a 20-years follow-up, thereby obtaining advantage from the gene variant as regards protection against atherosclerosis, apparently without any metabolic retaliation.Conclusions: Our data support the use of targeted NGS in well-characterized clinical settings, as well as they indicate that.a partial block of ApoB production may be well tolerated and improve cardiovascular outcomes. (C) 2022 The Authors. Published by Elsevier B.V

Confronto fra sistemi foraggero-zootecnici per ovini da latte in ambiente asciutto: nota II: risultati zootecnici del triennio 1990-93

Three 5 ha dairy sheep systems with different input levels were compared during three years. The percentage oftotal system area conventionally cultivated each year was equal to 80%, 20% and 30% in systems C, EPM and EPMP respectively. Each system was rotationally grazed by 30 dairy ewes. Milk yield was significantly higher in EPM group, the total annual yield for each system being equal to 1.10 (C), 1.33 (EPM) and 1.17 (EPMP) t ha-1 of milk. Hay consumption tended to be lower in the system EPM in comparison with system C and EPMP averaging to 0.30 (EPM), 0.34 (C) and 0.36 t ha-1 of DM (EPMP). On the basis of overall results, the EPM system showed the best performances. Nel triennio 1990-93 sono stati confrontati tre sistemi foraggero zootecnici C (Cereali), EPM (Erbaio Pascolo Migliorato) e EPMP (Erbaio Pascolo Migliorato Prati), caratterizzati da una percentuale di SAU coltivata rispettivamente pari all'80, 20 e 30%. Ciascun sistema è stato pascolato da 30 pecore da latte di razza Sarda. La produzione di latte è stata significativamente più elevata nel sistema EPM e la produzione totale media annua è stata di 1,10 (C), 1,33 (EPM) e 1,17 (EPMP) t ha-1. Il consumo di fieno è stato in media 0,30 (EPM), 0,34 (C) e 0,36 (EPMP) t ha-1 di sostanza secca. In conclusione il sistema EPM, fra quelli a confronto, ha mostrato i migliori risultati sia in termini di produzione di latte e di carne e nel contempo di un minore consumo di supplementi

Versatile stereoselective oxidative alkoxycarbonylation of styrenes at room-temperature

Carbonylation reactions carried out at room temperature and at atmospheric pressure of carbon monoxide are highly attractive and extremely rare at the same time. Here, the oxidative alkoxycarbonylation of styrenes to industrially relevant cinnamates has been developed under such a mild conditions (rt, 1 atm of CO) in the presence of a palladium(II) complex bearing a bis(aryl)acenaphthenequinonediimine ligand, benzoquinone and p-toluenesulfonic acid. Remarkably, variously substituted styrene derivatives have been efficiently carbonylated using a nearly stoichiometric amount of alcohols, with a dramatic reduction of waste. Even reluctant internal alkenes have shown to be compatible under these carbonylative conditions. In consideration of experimental results and DFT calculations a mechanistic rationale has been proposed. Based on this study, the benzoquinone has been found to promote the final palladium reoxidation, and to boost the reaction under such unprecedent mild conditions. The present methodology has been successfully exploited for the synthesis of high value-added cinnamoyl glycerols and cinnamic acid sugar esters, including the 6-O-p-coumaroyl-D-glucose natural product

Not Just Arterial Damage: Increased Incidence of Venous Thromboembolic Events in Cardiovascular Patients With Elevated Plasma Levels of Apolipoprotein CIII

Background Apolipoprotein CIII (apo CIII ) is a crucial player in triglyceride-rich lipoprotein metabolism, but may also act pleiotropically, provoking inflammatory responses and stimulating coagulation. Elevated apo CIII plasma levels have been associated with increased activity of coagulation factors. Since these features of prothrombotic diathesis are linked with venous thromboembolism ( VTE ), we hypothesized that apo CIII plays a role in VTE . Methods and Results We recorded nonfatal VTE events in 1020 patients (age 63.3\ub111.4 years; 29.1% women) with or without coronary artery disease (79.1% with coronary artery disease and 20.9% without coronary artery disease) during a long follow-up. Complete plasma lipid and apolipoproteins were available for all patients. Forty-five patients (4.4%) experienced nonfatal VTE events during a median follow-up period of 144 months. Apo CIII plasma concentration at enrollment was higher in patients with VTE compared with patients without VTE (12.2 [95% CI, 11.10-13.5] mg/dL vs 10.6 [95% CI, 10.4-10.9] mg/dL, respectively; P=0.011). Patients with apo CIII levels above the median value (10.6 mg/dL) exhibited an increased risk of VTE (incidence rate, 6.0 [95% CI , 4.0-8.0] vs 1.8 [95% CI, 0.7-2.9] VTE events/1000 person-years; unadjusted hazard ratio [ HR ], 3.42 [95% CI , 1.73-6.75]; P<0.001). This association was confirmed after adjustment for sex, age, coronary artery disease diagnosis, body mass index, hypertension, and anticoagulant treatment at enrollment ( HR , 2.66; 95% CI , 1.31-5.37 [ P=0.007]), with inclusion of lipid parameters in the Cox model (HR, 3.74; 95% CI , 1.24-11.33 [ P=0.019]), and even with exclusion of patients who died at follow-up ( HR, 3.92; 95% CI , 1.68-9.14 [ P=0.002]) or patients taking anticoagulants ( HR , 3.39; 95% CI , 1.72-6.69 [ P<0.001]). Conclusions Our results suggest that high plasma apo CIII concentrations may predict an increased risk of VTE in patients with cardiovascular disease