Structural and functional characterization of Nucleophosmin domain associated with Acute Myeoloid Leukemia

Nucleophosmin is a shuttleing protein mainly localizated in nucleolus. It is involved in many different cellular processes like ribogenesis, centrosome duplication, apoptotic response. In more then 35% of Acute Myeloyd Leukemic patient with Normal Kariotype, the Nucleophosmin gene is mutated, causing aberrant cytoplasmatic accumulation, imparing DNA binding activity. In this work we describe the structural and functional feuteres of Nucleophosmin DNA binding domain, to better understand its activy both in phisiological and pathologial conditions

Commissioning of the ATLAS Muon Trigger System with early data

An overview of the early results on commissioning and performance of the ATLAS Muon Trigger System is shown. The ATLAS Muon Trigger has been designed to cope with the high interaction rate expected at the LHC. The presented performance studies have been obtained using both cosmic-ray and 900GeV collision data

In vivo delivery of transcription factors with multifunctional oligonucleotides.

Therapeutics based on transcription factors have the potential to revolutionize medicine but have had limited clinical success as a consequence of delivery problems. The delivery of transcription factors is challenging because it requires the development of a delivery vehicle that can complex transcription factors, target cells and stimulate endosomal disruption, with minimal toxicity. Here, we present a multifunctional oligonucleotide, termed DARTs (DNA assembled recombinant transcription factors), which can deliver transcription factors with high efficiency in vivo. DARTs are composed of an oligonucleotide that contains a transcription-factor-binding sequence and hydrophobic membrane-disruptive chains that are masked by acid-cleavable galactose residues. DARTs have a unique molecular architecture, which allows them to bind transcription factors, trigger endocytosis in hepatocytes, and stimulate endosomal disruption. The DARTs have enhanced uptake in hepatocytes as a result of their galactose residues and can disrupt endosomes efficiently with minimal toxicity, because unmasking of their hydrophobic domains selectively occurs in the acidic environment of the endosome. We show that DARTs can deliver the transcription factor nuclear erythroid 2-related factor 2 (Nrf2) to the liver, catalyse the transcription of Nrf2 downstream genes, and rescue mice from acetaminophen-induced liver injury

Identification of Cannabis sativa L. (hemp) Retailers by Means of Multivariate Analysis of Cannabinoids

In this work, the concentration of nine cannabinoids, six neutral cannabinoids (THC, CBD, CBC, CBG, CBN and CBDV) and three acidic cannabinoids (THCA CBGA and CBDA), was used to identify the Italian retailers of Cannabis sativa L. (hemp), reinforcing the idea that the practice of categorizing hemp samples only using THC and CBD is inadequate. A high-performance liquid chromatography/high-resolution mass spectrometry (HPLC-MS/MS) method was developed for screening and simultaneously analyzing the nine cannabinoids in 161 hemp samples sold by four retailers located in different Italian cities. The hemp samples dataset was analyzed by univariate and multivariate analysis with the aim to identify the hemp retailers without any other information on the hemp samples like Cannabis strains, seeds, soil and cultivation characteristics, geographical origin, product storage, etc. The univariate analysis highlighted that the hemp samples could not be differentiated by using any of the nine cannabinoids analyzed. To evaluate the real efficiency of the discrimination among the four hemp retailers a partial least squares discriminant analysis (PLS-DA) was applied. The PLS-DA results showed a very good discrimination between the four hemp retailers with an explained variance of 100% and low classification errors in both calibration (5%) and cross validation (6%). A total of 92% of the hemp samples were correctly classified by the cannabinoid variables in both fitting and cross validation. This work contributed to show that an analytical method coupled with multivariate analysis can be used as a powerful tool for forensic purposes

Effect of the distillation time on the chemical composition, antioxidant potential and antimicrobial activity of essential oils from different cannabis sativa L. Cultivars

Within the unavoidable variability of various origins in the characteristics of essential oils, the aim of this study was to evaluate the effect of the distillation time on the chemical composition and biological activity of Cannabis sativa essential oils (EOs). The dry inflorescences came from Carmagnola, Kompolti, Futura 75, Gran Sasso Kush and Carmagnola Lemon varieties from Abruzzo region (Central Italy), the last two being new cultivar here described for the first time. EOs were collected at 2 h and 4 h of distillation; GC/MS technique was applied to characterize their volatile fraction. The EOs were evaluated for total polyphenol content (TPC), antioxidant capacity (AOC) and antimicrobial activity against food-borne pathogens and spoilage bacteria. The time of distillation particularly influenced EOs chemical composition, extracting more or less terpenic components, but generally enriching with minor sesquiterpenes and cannabidiol. A logical response in ratio of time was observed for antioxidant potential, being the essential oils at 4 h of distillation more active than those distilled for 2 h, and particularly Futura 75. Conversely, except for Futura 75, the effect of time on the antimicrobial activity was variable and requires further investigations; nevertheless, the inhibitory activity of all EOs against Pseudomonas fluorescens P34 was an interesting result

Characterization of reward and effort mechanisms in apathy

AbstractApathy is a common but poorly understood condition with a wide societal impact observed in several brain disorders as well as, to some extent, in the normal population. Hence the need for better characterization of the underlying mechanisms. The processes by which individuals decide to attribute physical effort to obtain rewards might be particularly relevant to relate to apathy traits. Here, we designed two paradigms to assess individual differences in physical effort production and effort-based decision-making and their relation to apathy in healthy people. Apathy scores were measured using a modified version of the Lille Apathy Rating Scale, suitable for use in a non-clinical population.In the first study, apathy scores were correlated with the degree to which stake (reward on offer) and difficulty level impacts on physical effort production. Individuals with relatively high apathy traits showed an increased modulation of effort while more motivated individuals generally exerted greater force across different levels of stake. To clarify the underlying mechanisms for this behavior, we designed a second task that allows independent titration of stake and effort levels for which subjects are willing to engage in an effortful response to obtain a reward. Our results suggest that apathy traits in the normal population are related to the way reward subjectively affects the estimation of effort costs, and more particularly manifest as decreased willingness to exert effort when rewards are small, or below threshold. The tasks we introduce here may provide useful tools to further investigate apathy in clinical populations

Defensive responses to stressful life events associated with cancer diagnosis

Objectives: Stressful life events (SLEs) are common in patients who developed both physical and psychological syndromes. Research shown the role of psychological defense mechanisms in cancer progression and survival probability. The present study analyzed recent SLEs and defense mechanisms as characteristic of cancer patients and tested their role as potential predisposing factors to cancer development. Methods: This cross-sectional study enrolled 145 participants: 48 recently diagnosed cancer patients (CP), 43 recently diagnosed benignant tumor patients (BT), and 54 healthy subjects (HC). Non-blinded raters assessed participants’ defense mechanisms using the Defense Mechanisms Rating Scales Q-sort version (DMRS-Q). Groups were compared on the presence of SLEs and on the maturity of defensive functioning. Associations between SLE and defense mechanisms as statistically associated with cancer diagnosis was explored. Results: Higher overall defensive functioning was associated with good physical conditions. Recent SLEs, higher use of neurotic defenses and lower use of obsessional defenses characterized cancer patients. CP showed higher use of suppression, repression, dissociation, rationalization and passive aggression and lower use of affiliation, sublimation, undoing, and devaluation of self-image as compared to controls. Hierarchical regression analysis showed that recent SLEs and defense mechanisms of suppression, repression, dissociation, displacement and omnipotence were associated with cancer diagnosis. Discussion: Recent SLEs and repressive defensive functioning characterized the CP’s defensive response to stress. Despite the relevance of present findings, this study shows several limitations. Prospective and longitudinal studies are needed to confirm these results and to investigate the potential role played by SLEs and defense mechanisms in cancer development

Defensive responses to stressful life events associated with cancer diagnosis

Objectives: Stressful life events (SLEs) are common in patients who developed both physical and psychological syndromes. Research shown the role of psychological defense mechanisms in cancer progression and survival probability. The present study analyzed recent SLEs and defense mechanisms as characteristic of cancer patients and tested their role as potential predisposing factors to cancer development. Methods: This cross-sectional study enrolled 145 participants: 48 recently diagnosed cancer patients (CP), 43 recently diagnosed benign tumor patients (BT), and 54 healthy subjects (HC). Non-blinded raters assessed participants’ defense mechanisms using the Defense Mechanisms Rating Scales Q-sort version (DMRS-Q). Groups were compared on the presence of SLEs and on the maturity of defensive functioning. Significant associations between SLE and defense mechanisms as related to cancer diagnosis were explored. Results: Higher overall defensive functioning was associated with good physical conditions. Recent SLEs, higher use of neurotic defenses and lower use of obsessional defenses characterized cancer patients. CP showed higher use of suppression, repression, dissociation, rationalization and passive aggression and lower use of affiliation, sublimation, undoing, and devaluation of self-image as compared to controls. Hierarchical regression analysis showed that recent SLEs and defense mechanisms of suppression, repression, dissociation, displacement and omnipotence were associated with cancer diagnosis. Discussion: Recent SLEs and repressive defensive functioning characterized the CP’s defensive response to stress. Despite the relevance of present findings, this study shows several limitations. Prospective and longitudinal studies are needed to confirm these results and to investigate the potential role played by SLEs and defense mechanisms in cancer development

Salmonella enterica Control in Stick Carrots Through Incorporation of Coriander Seeds Essential Oil in Sustainable Washing Treatments

Chemical disinfectants represent one of the commonly used practice in minimally processed vegetables food-chain. However, the scarce safety and sustainability of these agents force food industry to move toward more sustainable “green washing solutions.” Among the latter, while the application of plant derivates for the control of several pathogens is already well-known, the potential anti-Salmonella activity of Coriandrum sativum seeds derivates is still unexplored and was therefore investigated in this study. In detail, Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) of different coriander seed derivates (i.e., essential oil, hydrosol, and ethanolic extract) were determined by broth dilution against six Salmonella enterica strains isolated from fresh and minimally processed fruits and vegetables. Only the essential oil (EO) was effective in vitro with strain-dependent results. In addition, when mixed in co-culture, the strains were more sensitive to the essential oil treatment. Chemical investigations allowed to define (s)-(+)-linalool as major compound in the essential oil, and to underline interesting phenolic content with correlated antioxidant capacity. A cocktail of three strains of different serovars was selected and employed for a preliminary in situ trial on stick carrots. The obtained results allowed to establish that the application of coriander seed EO at concentrations of 5 μL mL−1 was able to reduce and contain the growth of the Salmonella cocktail up to 24 h at 10°C. Good sensory evaluation results were obtained by applying this EO concentration as washing treatment, especially in terms of color parameter. Further studies should be undertaken to emphasize the upstream activity, improving the formulation or exploiting a combined effect with other sanitizers or treatments (e.g., physical treatments). The present study contributes to the knowledge on coriander derivates activity against Salmonella spp. and on the potential application as sustainable washing treatment in removing this pathogen from fresh cut carrots