Coriander (Coriandrum sativum L.) in Combination with Organic Amendments and Arbuscular Mycorrhizal Inoculation: An Efficient Option for the Phytomanagement of Trace Elements-Polluted Soils

The cultivation of coriander (Coriandrum sativum L.) destined for essential oils production was recently presented as an innovative and economically viable alternative for the phytomanagement of trace elements (TE)-polluted soils. However, Cd accumulation in shoots has proven to be an obstacle in the valorization of the distillation residues and the development of these phytotechnologies. The present study aimed to evaluate the effect of arbuscular mycorrhizal fungus (Funneliformis mosseae) inoculation and organic amendment application on the soil TE bioavailability and plant uptake, as well as on the soil quality and health improvement. The application of compost and sewage sludge improved the growth of coriander and Cd and Zn immobilization in soil, resulting in reduced Cd plant uptake. A synergistic effect of arbuscular mycorrhizal fungi (AMF) inoculation and organic amendments was observed in the decrease in the extractable soil Cd and Zn concentrations, but not in the Cd plant uptake. Despite a significant decrease in Cd accumulation in shoots, coriander retained its accumulative phenotype, with a metal bioconcentration factor close to 1. Furthermore, both the vegetation and the organic amendments improved the soil quality and health by increasing its microbial biomass, as estimated by phospholipid fatty acids, soil enzyme activities (dehydrogenase, phosphatase, β-glucosidase, and cellubiosidase), and the bacterial metabolic function and diversity. The findings demonstrate the potential of C. sativum, particularly in combination with organic amendments and AMF inoculation, for the phytomanagement of TE-polluted soils and soil quality and health improvement

Prospective Evaluation of First-Line Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation: A Multicenter Academic Phase II Study in Caucasian Patients (FIELT)

Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibition is the preferred first-line treatment of advanced adenocarcinoma of the lung that harbors EGFR activating tyrosine kinase domain mutations. Most data available pertain to Asian populations in which such mutations are more prevalent. We report on the long-term results of first-line treatment with erlotinib in Caucasian patients with advanced adenocarcinoma of the lung that have a somatic EGFR mutation in their tumor.status: publishe

Codon-specific translation reprogramming promotes resistance to targeted therapy

Reprogramming of mRNA translation has a key role in cancer development and drug resistance(1). However, the molecular mechanisms that are involved in this process remain poorly understood. Wobble tRNA modifications are required for specific codon decoding during translation(2,3). Here we show, in humans, that the enzymes that catalyse modifications of wobble uridine 34 (U-34) tRNA (U-34 enzymes) are key players of the protein synthesis rewiring that is induced by the transformation driven by the BRAF(V600E) oncogene and by resistance to targeted therapy in melanoma. We show that BRAF(V600E)-expressing melanoma cells are dependent on U34 enzymes for survival, and that concurrent inhibition of MAPK signalling and ELP3 or CTU1 and/or CTU2 synergizes to kill melanoma cells. Activation of the PI3K signalling pathway, one of the most common mechanisms of acquired resistance to MAPK therapeutic agents, markedly increases the expression of U-34 enzymes. Mechanistically, U-34 enzymes promote glycolysis in melanoma cells through the direct, codon-dependent, regulation of the translation of HIF1A mRNA and the maintenance of high levels of HIF1 alpha protein. Therefore, the acquired resistance to anti-BRAF therapy is associated with high levels of U-34 enzymes and HIF1 alpha. Together, these results demonstrate that U-34 enzymes promote the survival and resistance to therapy of melanoma cells by regulating specific mRNA translation

Proviral role of human respiratory epithelial cell‐derived small extracellular vesicles in SARS‐CoV‐2 infection

Abstract Small Extracellular Vesicles (sEVs) are 50–200 nm in diameter vesicles delimited by a lipid bilayer, formed within the endosomal network or derived from the plasma membrane. They are secreted in various biological fluids, including airway nasal mucus. The goal of this work was to understand the role of sEVs present in the mucus (mu‐sEVs) produced by human nasal epithelial cells (HNECs) in SARS‐CoV‐2 infection. We show that uninfected HNECs produce mu‐sEVs containing SARS‐CoV‐2 receptor ACE2 and activated protease TMPRSS2. mu‐sEVs cleave prefusion viral Spike proteins at the S1/S2 boundary, resulting in higher proportions of prefusion S proteins exposing their receptor binding domain in an ‘open’ conformation, thereby facilitating receptor binding at the cell surface. We show that the role of nasal mu‐sEVs is to complete prefusion Spike priming performed by intracellular furin during viral egress from infected cells. This effect is mediated by vesicular TMPRSS2 activity, rendering SARS‐CoV‐2 virions prone to entry into target cells using the ‘early’, TMPRSS2‐dependent pathway instead of the ‘late’, cathepsin‐dependent route. These results indicate that prefusion Spike priming by mu‐sEVs in the nasal cavity plays a role in viral tropism. They also show that nasal mucus does not protect from SARS‐CoV‐2 infection, but instead facilitates it

Common toxicities.

<p>Common toxicities.</p

Mutations found.

<p>Mutations found.</p

Characteristics of patients that failed early on erlotinib.

<p>Characteristics of patients that failed early on erlotinib.</p

Survival outcome.

<p>Kaplan-Meier curves for overall and progression free survival of the FIELT cohort.</p