1,721,010 research outputs found
Synthesis of orthogonally protected labionin
No full textWe report the first synthesis of the complex amino acid labionin in a fully orthogonally protected and stereopure form. The structure-which incorporates five orthogonal protecting groups and three stereogenic centers-was assembled using two key synthetic steps: (1) a thia-Michael addition for installing the thioether bridge; (2) an electrophilic azidation for creating the central quaternary α-amino acid carbon in a stereochemically pure form. This work is expected to enable the solid phase synthesis of both natural and synthetic analogues labyrinthopeptins
Lymphopenia in covid-19: γδ t cells-based therapeutic opportunities
Full text linkSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection dysregulates the immune system by lymphopenia of B cells, monocytes, eosinophils, basophils, and cytotoxic cells such as CD8, γδ T cells, and natural killer (NK) cells. Despite many studies being conducted to better understand the effects of SARS-CoV-2 on the immune system, many mechanisms still remain unclear, hindering the development of novel therapeutic approaches and strategies to improve the host’s immune defense. This mini-review summarizes the findings on the role of γδ T cells in coronavirus disease 2019 (COVID-19), providing an overview of the excellent anti-viral therapeutic potential of γδ T cells, that had not yet been exploited in depth
γδ cell-based immunotherapy for cancer.
No full textIntroduction: Cancer immunotherapy relies on the development of an efficient and long-lasting anti-tumor response, generally mediated by cytotoxic T cells. gamma delta T cells possess distinctive features that justify their use in cancer immunotherapy. Areas covered: Here we will review our current knowledge on the functions of human gamma delta T cells that may be relevant in tumor immunity and the most recent advances in our understanding of how these functions are regulated in the tumor microenvironment. We will also discuss the major achievements and limitations of gamma delta T cell-based immunotherapy of cancer. Expert opinion: Several small-scale clinical trials have been conducted in cancer patients using either in vivo activation of gamma delta T cells or adoptive transfer of ex vivo-expanded gamma delta T cells. Both strategies are safe and give some clinical benefit to patients, thus providing a proof of principle for their utilization in addition to conventional therapies. However, low objective response rates have been obtained in both settings and therefore larger and well-controlled trials are needed. Discovering the factors which influence the success of gamma delta T cell-based immunotherapy will lead to a better understanding of their mechanism of action and to harness these cells for effective and durable anti-tumor responses
Deciphering human γδ T cell response in cancer: Lessons from tumor-infiltrating γδ T cells
No full textThe finding that γδ T cells are present among tumor-infiltrating lymphocytes in humans suggests they participate in tumor immune surveillance, but their relevance is unclear because the relative abundance of tumor-infiltrating γδ T cells correlates with positive or negative, or even do not correlate with prognosis. This likely depends on the fact that tumor-infiltrating γδ T cells may play substantially different effector or regulatory functions, and correlation with patient's prognosis relies on distinct γδ T cell subsets in the context of the tumor. There is interest to exploit γδ T cells in tumor immunotherapy, but to make this approach successful there is urgent need to fully understand the biological functions of γδ T cells and of how they can be manipulated in vivo and ex vivo to safely provide benefit to the host. This review focuses on our previous and ongoing studies of tumor-infiltrating γδ T lymphocytes in different types of human cancer. Moreover, we discuss the interaction of tumor-infiltrating γδ T cells with other cells and molecules present in the tumor microenvironment, and their clinical relevance on the ground, that deep knowledge in this field can be used further for better immunotherapeutic intervention in cancer
GORIZIA E I REATI DI CONFINE NEL COMPLESSO NOVECENTO
No full textIl presente studio si propone di analizzare l’interessante e
originale argomento dei reati legati alla presenza di un confine,
con particolare riferimento al reato di contrabbando. In relazione alle vicende della frontiera orientale italiana nel Novecento, l’Autore si propone di approfondire, non solo il contrasto sociale e culturale che favorisce la commissione di tale reato, ma anche le iniziative promosse dallo Stato italiano nel tentativo di arginare questo fenomeno delittuoso
I SUDDITI AUSTRIACI DI GORIZIA E L’ELETTORATO AMMINISTRATIVO NEL REGNO D’ITALIA: IL CASO DEI CONTI ATTIMIS (1887).
No full textPričujoča študija želi bralcu odkriti pomemben trenutek prehoda v zgodovini mesta Gorica, ki sega od leta 1848 (obdobje,
ko se je Gorica še lahko ponašala z vzdevkom »vec mest v
enem«) do leta 1887 (leto v katerem je bila razglašena zgodovinska sodba prizivnega sodišca v Benetkah v zadevi Martinuzzi
proti Attimis). Sodba, ki z odlocitvijo o upravicenosti uvrstitve
grofov Attimis na volilne sezname obcine Attimis, zaznamuje
prehod iz obcutka velike kulturne odprtosti k izrazitejšemu nacionalisticnemu obcutku.Il presente studio vuole fare scoprire al lettore un importante momento di transizione nella storia della città di Gorizia va dal 1848 (periodo nel quale Gorizia poteva ancora vantare
l’appellativo di «più città in una») al 1887 (anno in cui venne
pronunciata la storica sentenza della Corte di Appello di Venezia
sul caso “Martinuzzi contro Attimis”). Un provvedimento questo che, decidendo sulla legittimità dell’iscrizione dei Conti Attimis nelle liste elettorali del Comune di Attimis, segna il passaggio da un sentimento di grande apertura culturale ad un sentimento più spiccatamente nazionalistic
3-Acetyl-5-acylpyridin-2(1H)-ones and 3-acetyl-7,8-dihydro-2,5(1H,6H)-quinolinediones: synthesis, cardiotonic activity and computational studies
No full textA series of milrinone analogues, namely 6-substituted 3-acetyl-5-acylpyridin-2(1H)-ones 4a-c, e, f and 7-substituted or unsubstituted 3-acetyl-7,8-dihydro-2,5(1H,6H)-quinolinediones 4g-j, in which the cyano group was replaced by the acetyl function, was prepared. In a preliminary pharmacological investigation on spontaneously beating atria from reserpine-treated guinea-pigs, all new compounds did not induce any inotropic effect equivalent or higher than that of the milrinone chosen as the reference compound. In order to rationalise how the structure modifications influence the activity and the selectivity of the title compounds, a computational study has been performed. The important role of the substituents in positions-3 and -6 on the pyridone nucleus has been highlighted
Early Effects of No-Till Use on Durum Wheat (Triticum durum Desf.): Productivity and Soil Functioning Vary between Two Contrasting Mediterranean Soils
Full text linkThe diffusion of no-tillage (NT) is to be encouraged because of the benefits it can provide in terms of improving soil fertility and counteracting global warming and climate change as part of climate-smart agriculture practices. However, the introduction of this management can be difficult, especially in the first years of application, and can lead to unpredictable yield results depending on the soil type. Therefore, the aim of this experiment was to evaluate the early effect of NT use, compared to the conventional mouldboard ploughing (CT), on two different soils, a clay-loam (GAL) and a sandy-clay-loam soil (SMA), by monitoring a set of 43 different soil and plant variables that were expected to vary with tillage and/or soil type. At both experimental sites, NT showed lower wheat total biomass (−29%) and grain yields (−17%) than CT with a more pronounced decrease in GAL than in SMA. Yield differences were accompanied by modifications in nutrient, microbial community and soil enzyme activity dynamics which highlighted higher stress in GAL, than in SMA soil, attributable to lower crop residues decomposition and substrate availability. Therefore, our findings suggest that the negative consequences due to the transition to NT depend on specific soil characteristics, like texture and organic matter concentration, with different repercussions on soil quality as well as on wheat growth and productivity
An efficient synthesis of functionalized 2-pyridones by direct route or via amide/enolate ammonium salt intermediates
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