NMR interaction studies of Neu5Ac-α-(2,6)-Gal-β-(1-4)-GlcNAc with influenza-virus hemagglutinin expressed in transfected human cells

The emergence of escape-mutants of influenza hemagglutinin (HA) following vaccination compels the yearly re-formulation of flu vaccines. Since binding the sialic acid receptor remains in all cases essential for infection, small-molecule inhibitors of HA binding to sialic acid could be interesting therapeutic complements or alternatives to immuno-prophylaxis in the control of flu epidemics. In this work, we made use of NMR spectroscopy to study the interaction between a derivative of sialic acid (the Neu5Ac-\u3b1-(2,6)-Gal-\u3b2-(1-4)-GlcNAc trisaccharide) and HAs (H1 and H5) from human and avian strains of influenza virus, directly expressed on the surface of stable transfected 293 T human cells. The HAs were shown to retain their native trimeric conformation and binding properties. Exploiting the magnetization transfer between the proteins and the ligand, we obtained evidence of the binding event and mapped the (non-identical) sugar epitopes recognized by the two HA species. The rapid and reliable method for screening sialic acid-related HA ligands we have developed could yield useful information for an efficient drug design

Assessment of maize nitrogen uptake from PRISMA hyperspectral data through hybrid modelling

The spaceborne imaging spectroscopy mission PRecursore IperSpettrale della Missione Applicativa (PRISMA), launched on 22 March 2019 by the Italian Space Agency, opens new opportunities in many scientific domains, including precision farming and sustainable agriculture. This new Earth Observation (EO) data stream requires new-generation approaches for the estimation of important biophysical crop variables (BVs). In this framework, this study evaluated a hybrid approach, combining the radiative transfer model PROSAIL-PRO and several machine learning (ML) regression algorithms, for the retrieval of canopy chlorophyll content (CCC) and canopy nitrogen content (CNC) from synthetic PRISMA data. PRISMA-like data were simulated from two images acquired by the airborne sensor HyPlant, during a campaign performed in Grosseto (Italy) in 2018. CCC and CNC estimations, assessed from the best performing ML algorithms, were used to define two relations with plant nitrogen uptake (PNU). CNC proved to be slightly more correlated to PNU than CCC (R-2 = 0.82 and R-2 = 0.80, respectively). The CNC-PNU model was then applied to actual PRISMA images acquired in 2020. The results showed that the estimated PNU values are within the expected ranges, and the temporal trends are compatible with plant phenology stages

Haspin regulates Ras localization to promote Cdc24-driven mitotic depolarization

Cell polarization is of paramount importance for proliferation, differentiation, development, and it is altered during carcinogenesis. Polarization is a reversible process controlled by positive and negative feedback loops. How polarized factors are redistributed is not fully understood and is the focus of this work. In Saccharomyces cerevisiae, mutants defective in haspin kinase exhibit stably polarized landmarks and are sensitive to mitotic delays. Here, we report a new critical role for haspin in polarisome dispersion; failure to redistribute polarity factors, in turn, leads to nuclear segregation defects and cell lethality. We identified a mitotic role for GTP-Ras in regulating the local activation of the Cdc42 GTPase, resulting in its dispersal from the bud tip to a homogeneous distribution over the plasma membrane. GTP-Ras2 physically interacts with Cdc24 regulateing its mitotic distribution. Haspin is shown to promote a mitotic shift from a bud tip-favored to a homogenous PM fusion of Ras-containing vesicles. In absence of haspin, active Ras is not redistributed from the bud tip; Cdc24 remains hyperpolarized promoting the activity of Cdc42 at the bud tip, and the polarisome fails to disperse leading to erroneously positioned mitotic spindle, defective nuclear segregation, and cell death after mitotic delays. These findings describe new functions for key factors that modulate cell polarization and mitotic events, critical processes involved in development and tumorigenesis

Hypercoagulability of COVID-19 patients in Intensive Care Unit: A Report of Thromboelastography Findings and other Parameters of Hemostasis

BACKGROUND: The severe inflammatory state secondary to Covid-19 leads to a severe derangement of hemostasis that has been recently described as a state of disseminated intravascular coagulation (DIC) and consumption coagulopathy, defined as decreased platelet count, increased fibrin(ogen) degradation products such as D-dimer as well as low fibrinogen. AIMS: Whole blood from 24 patients admitted at the intensive care unit because of Covid-19 was collected and evaluated with thromboelastography by the TEG point-of-care device on a single occasion and six underwent repeated measurements on two consecutive days for a total of 30 observations. Plasma was evaluated for the other parameters of hemostasis. RESULTS: TEG parameters are consistent with a state of hypercoagulability as shown by decreased R and K values, and increased values of K angle and MA. Platelet count was normal or increased, prothrombin time and activated partial thromboplastin time were near(normal). Fibrinogen was increased and D-dimer was dramatically increased. C-reactive protein was increased. Factor VIII and von Willebrand factor (n=11) were increased. Antithrombin (n=11) was marginally decreased and protein C (n=11) was increased. CONCLUSION: The results of this cohort of patients with Covid-19 are not consistent with acute DIC, rather they support hypercoagulability together with a severe inflammatory state. These findings may explain the events of venous thromboembolism observed in some of these patients and support antithrombotic prophylaxis/treatment. Clinical trials are urgently needed to establish the type of drug, dosage and optimal duration of prophylaxis

Long-term clinical outcomes in critical limb ischemia--A retrospective study of 181 patients

Critical limb ischemia (CLI) is the most severe manifestation of the peripheral arterial disease. To date, several prognostic factors have been identified but the data of long-term follow-up in real life setting are scarce. The aim of our study is to describe a large group of CLI patients and identify possible prognostic factors, in a long-term follow-up

Long-term survival of patients with critical limb ischemia treated with iloprost: response rate and predictive criteria. A retrospective analysis of 102 patients

Critical limb ischemia (CLI) patients have poor long-term prognosis. We showed that iloprost improves outcomes (major amputation and survival) up a 5-year follow-up, but it is not known if in this length of time the survival curves, of clinical responders and non-responders, differ