ZrO2 Based materials as photocatalysts for 2-propanol oxidation by using UV and solar light irradiation and tests for CO2 reduction

Bare ZrO2, Ce doped ZrO2 and Er doped ZrO2 samples have been prepared by a hydrothermal process and have been used as photocatalysts for 2-propanol oxidation reaction in gas solid regime. Moreover, some preliminary tests have been carried out for CO2 reduction. The samples were physico-chemically characterized and both bare and doped ZrO2 based materials resulted active for oxidation and reduction reactions by using UV and solar irradiation. The reactivity results have been correlated with the compositional, structural and morphological features of the photocatalysts

Screening of olive germplasm for resistance to Xylella fastidiosa ST53: the state of the art

While different sources of natural resistance to X. fastidiosa have been described in grapevines and citrus, lack of solid information exists on possible sources of resistance/tolerance in the cultivars that characterize the wide olive germplasm. Preliminary field observations and laboratory analyses of a few cultivars, have shown that differential responses to X. fastidiosa infections exist. To confirm these preliminary findings, a large panel of olive cultivars is being specifically investigated. Currently, the screening procedure relies on field observations looking for symptomless subjects (trees of known cultivars/volunteer seedlings), mechanical inoculations, qualitative and quantitative diagnostic assays (ELISA & qPCR) and, in selected cases, comparative transcriptomic profiling. Field experiments include the planting of the target cultivars/selections in an infected area under high inoculum pressure. All the plots are located in the Apulia Region (Italy) in the demarcated infected area, surrounded by X. fastidiosa heavily affected olive groves. A first experimental plot was established in April 2015 with 10 different cultivars, which was extended in 2016 to 49 cultivars, and will be further enlarged in 2017 with the addition of 40 new accessions. Other plots, comprising newly planted or grafted cultivars (over 260 cvs) have been also established, bringing to over 300 the total number of accessions under evaluation. Cvs Leccino and FS-17®, both expressing interesting traits of resistance, have already been identified

MYC regulates metabolism through vesicular transfer of glycolytic kinases

Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.5713034.Copyright © 2021 The Authors. Amplification of the proto-oncogene MYCN is a key molecular aberration in high-risk neuroblastoma and predictive of poor outcome in this childhood malignancy. We investigated the role of MYCN in regulating the protein cargo of extracellular vesicles (EVs) secreted by tumour cells that can be internalized by recipient cells with functional consequences. Using a switchable MYCN system coupled to mass spectrometry analysis, we found that MYCN regulates distinct sets of proteins in the EVs secreted by neuroblastoma cells. EVs produced by MYCN-expressing cells or isolated from neuroblastoma patients induced the Warburg effect, proliferation and c-MYC expression in target cells. Mechanistically, we linked the cancer-promoting activity of EVs to the glycolytic kinase pyruvate kinase M2 (PKM2) that was enriched in EVs secreted by MYC-expressing neuroblastoma cells. Importantly, the glycolytic enzymes PKM2 and hexokinase II were detected in the EVs circulating in the bloodstream of neuroblastoma patients, but not in those of non-cancer children. We conclude that MYC-activated cancers might spread oncogenic signals to remote body locations through EVs.Neuroblastoma UK to AS and FAPESP SPRINT Award (50356-4); FAPESP (2014/06863-3, 2018/18257-1, 2018/15549-1, 16/50356-4); CNPq “bolsa de produtividade”; Ricerca Finalizzata GR11-172.https://doi.org/10.6084/m9.figshare.c.571303

Technical challenges of working with extracellular vesicles

Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review

In situ simultaneous photovoltaic and structural evolution of perovskite solar cells during film formation

Metal-halide perovskites show remarkably clean semiconductor behaviour, as evidenced by their excellent solar cell performance, in spite of the presence of many structural and chemical defects. Here, we show how this clean semiconductor performance sets in during the earliest phase of conversion from the metal salts and organic-based precursors and solvent, using simultaneous in situ synchrotron X-ray and in operando current–voltage measurements on films prepared on interdigitated back-contact substrates. These structures function as working solar cells as soon as sufficient semiconductor material is present across the electrodes. We find that at the first stages of conversion from the precursor phase, at the percolation threshold for bulk conductance, high photovoltages are observed, even though the bulk of the material is still present as precursors. This indicates that at the earliest stages of perovskite structure formation, the semiconductor gap is already well-defined and free of sub-gap trap states. The short circuit current, in contrast, continues to grow until the perovskite phase is fully formed, when there are bulk pathways for charge diffusion and collection. This work reveals important relationships between the precursors conversion and device performance and highlights the remarkable defect tolerance of perovskite materials

Temozolomide 3 weeks on and 1 week off as first-line therapy for recurrent glioblastoma: phase II study from gruppo italiano cooperativo di neuro-oncologia (GICNO)

The efficacy of temozolomide strongly depends on O6-alkylguanine DNA-alkyl transferase (AGAT), which repairs DNA damage caused by the drug itself. Low-dose protracted temozolomide administration can decrease AGAT activity. The main end point of the present study was therefore to test progression-free survival at 6 months (PFS-6) in glioblastoma patients following a prolonged temozolomide schedule. Chemonaïve glioblastoma patients with disease recurrence or progression after surgery and standard radiotherapy were considered eligible. Chemotherapy cycles consisted of temozolomide 75 mg/m2/daily for 21 days every 28 days until disease progression. O6-methyl-guanine-DNA-methyl-tranferase (MGMT) was determined in 22 patients (66.7%). A total of 33 patients (median age 57 years, range 31–71) with a median KPS of 90 (range 60–100) were accrued. The overall response rate was 9%, and PFS-6 30.3% (95% CI:18–51%). No correlation was found between the MGMT promoter methylation status of the tumours and the overall response rate, time to progression and survival. In 153 treatment cycles delivered, the most common grade 3/4 event was lymphopoenia. The prolonged temozolomide schedule considered in the present study is followed by a high PFS-6 rate; toxicity is acceptable. Further randomised trials should therefore be conducted to confirm the efficacy of this regimen

Analysis of congenital disorder of glycosylation-Id in a yeast model system shows diverse site-specific under-glycosylation of glycoproteins

Asparagine-linked glycosylation is a common post translational modification of proteins in eukaryotes. Mutations in the human ALG3 gene cause changed levels and altered glycan structures on mature glycoproteins and are the cause of a severe congenital disorder of glycosylation (CDG-Id). Diverse glycoproteins are also under-glycosylated in Saccharomyces cerevisae alg3 mutants. Here we analyzed site-specific glycosylation occupancy in this yeast model system using peptide-N-glycosidase F to label glycosylation sites with an asparagine-aspartate conversion that creates a new endoproteinase AspN cleavage site, followed by proteolytic digestion, and detection of peptides and glycopeptides by LC-ESI-MS/MS. We used this analytical method to identify and measure site specific glycosylation occupancy in alg3 mutant and wild type yeast strains. We found decreased site specific N-glycosylation occupancy in the alg3 knockout strain preferentially at Asn-Xaa-Ser sequences located in secondary structural elements, features previously associated with poor glycosylation efficiency. Furthermore, we identified 26 previously experimentally unverified glycosylation sites. Our results provide insights into the underlying mechanisms of disease in CDG-Id, and our methodology will be useful in site specific glycosylation analysis in many model systems and clinical applications

Unraveling incompatibility between wheat and the fungal pathogen Zymoseptoria tritici through apoplastic proteomics

Background: Hemibiotrophic fungal pathogen Zymoseptoria tritici causes severe foliar disease in wheat. However, current knowledge of molecular mechanisms involved in plant resistance to Z. tritici and Z. tritici virulence factors is far from being complete. The present work investigated the proteome of leaf apoplastic fluid with emphasis on both host wheat and Z. tritici during the compatible and incompatible interactions. Results: The proteomics analysis revealed rapid host responses to the biotrophic growth, including enhanced carbohydrate metabolism, apoplastic defenses and stress, and cell wall reinforcement, might contribute to resistance. Compatibility between the host and the pathogen was associated with inactivated plant apoplastic responses as well as fungal defenses to oxidative stress and perturbation of plant cell wall during the initial biotrophic stage, followed by the strong induction of plant defenses during the necrotrophic stage. To study the role of anti-oxidative stress in Z. tritici pathogenicity in depth, a YAP1 transcription factor regulating antioxidant expression was deleted and showed the contribution to anti-oxidative stress in Z. tritici ,but was not required for pathogenicity. This result suggests the functional redundancy of antioxidants in the fungus. Conclusions: The data demonstrate that incompatibility is probably resulted from the proteome-level activation of host apoplastic defenses as well as fungal incapability to adapt to stress and interfere with host cell at the biotrophic stage of the interaction

A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

<p>Abstract</p> <p>Background</p> <p>HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.</p> <p>Methods</p> <p>We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90^thday after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.</p> <p>Results</p> <p>The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.</p> <p>Conclusions</p> <p>GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.</p