In vivo studies of mitochondrial tRNA mutations in S. cerevisiae

Yeast mitochondria were taken as a versatile tool to investigate the pathogenecity and the mechanism of mitochondrial dysfunction due to point mutations in tRNA genes correlated in humans with neurodegenerative diseases. The biolistic mutants LysG38A, equivalent to the G8328A mutation correlated in humans with mitochondrial encephalomyopathy, and IleT33A, equivalent to the human position 4290 of tRNAIle, were constructed and characterized. The analysis of two other yeast mutants in the anticodon region revealed that mutations involving the same position even on different tRNA genes may cause similar defects. Moreover, the efficiency of the mt-tRNA-synthetases as well as the EF-Tu to suppress the defective phenotype was tested. Finally, the importance of the nuclear background in which the mitochondrial mutation is expressed was investigated by changing the nuclear context of each mutant and quantifying the expression level of the TUF1 gene in different wild-type and/or rho° strains. The results here described may allow the possibility to investigate the pathogenic potential of some tRNA human mutations and to search for nuclear genes that can either suppress or modify the defective phenotyp

List context manipulation reveals orthographic deficits in Italian readers with developmental dyslexia.

We tested the influence of list context on word frequency and length effects on the reading aloud of Italian developmental dyslexics and skilled peers. The stimuli were presented either in mixed blocks (alternating words and non-words) or in pure blocks. The analyses based on the rate-and-amount-model (Faust et al., 1999) indicated that group differences in reaction times between dyslexic and skilled readers: a) were well accounted for in terms of global components and b) were modulated by context in the case of words but not in the case of non-words. ANOVAs on z-transformed reaction time data further indicated the influence of stimulus length. Importantly, the frequency effect interacted with context: controls showed a list context effect for high and low frequency words, while dyslexics showed a list context effect only for high frequency words. The effect of length on reading times remained unaffected by context manipulation. It is proposed that this pattern of results may be accounted for by hypothesizing two separate deficits: An early graphemic impairment affecting performance independently of context and a later inefficiency in activating entries in the orthographic lexicon as a function of context demands

Morpheme-based reading aloud: Evidence from dyslexic and skilled Italian readers

The role of morphology in reading aloud was examined measuring naming latencies to pseudowords and words composed of morphemes (roots and derivational suffixes) and corresponding simple pseudowords and words. Three groups of Italian children of different ages and reading abilities, including dyslexic children, as well as one group of adult readers participated in the study. All four groups read faster and more accurately pseudowords composed of root and suffix than simple pseudowords (Experiment 1). Unlike skilled young and adult readers, both dyslexics and younger children benefited from morphological structure also in reading aloud words (Experiment 2). It is proposed that the morpheme is a unit of intermediate grain size that proves useful in processing all linguistic stimuli, including words, in individuals with limited reading ability (dyslexics and younger readers) who did not fully develop mastering of whole-word processing. For skilled readers, morphemic parsing is useful for reading those stimuli (i.e., pseudowords made up of morphemes), for which a whole-word lexical unit does not exist; where such whole-word lexical units do exist, skilled readers do not need to rely on morphological parsing because they can rely on a lexical (whole-word) reading unit that is larger than the morpheme. (C) 2008 Elsevier B.V. All rights reserved

Dimensional crossover and incipient quantum size effects in superconducting niobium nanofilms

Superconducting and normal state properties of sputtered Niobium nanofilms have been systematically investigated, as a function of film thickness in a d=9-90 nm range, on different substrates. The width of the superconducting-to-normal transition for all films remained in few tens of mK, thus remarkably narrow, confirming their high quality. We found that the superconducting critical current density exhibits a pronounced maximum, three times larger than its bulk value, for film thickness around 25 nm, marking the 3D-to-2D crossover. The extracted magnetic penetration depth shows a sizeable enhancement for the thinnest films, aside the usual demagnetization effects. Additional amplification effects of the superconducting properties have been obtained in the case of sapphire substrates or squeezing the lateral size of the nanofilms. For thickness close to 20 nm we also measured a doubled perpendicular critical magnetic field compared to its saturation value for d>33 nm, indicating shortening of the correlation length and the formation of small Cooper pairs in the condensate. Our data analysis evidences an exciting interplay between quantum-size and proximity effects together with strong-coupling effects and importance of disorder in the thinnest films, locating the ones with optimally enhanced critical properties close to the BCS-BEC crossover regime

Cannabis; epidemiological, neurobiological and psychopathological issues: an update

This document is the Accepted Manuscript version of the following article: Maria Antonietta De Luca, Gaetano Di Chiara, Cristina Cadoni, Daniele Lecca, Laura Orsolini, Duccio Papanti, John Corkery, Fabrizio Schifano, 'Cannabis; Epidemiological, Neurobiological and Psychopathological Issues: An Update', CNS & Neurological Disorders - Drug Targets, Vol. 16, 2017. The published manuscript is available at EurekaSelect via https://doi.org/10.2174/1871527316666170413113246. Published by Bentham Science.Cannabis is the illicit drug with both the largest current levels of consumption and the highest reported lifetime prevalence levels in the world. Across different countries, the prevalence of cannabis use varies according to the individual income, with the highest use being reported in North America, Australia and Europe. Despite its ‘soft drug’ reputation, cannabis misuse may be associated with several acute and chronic adverse effects. The present article aims at reviewing several papers on epidemiological, neurobiological and psychopathological aspects of the use of cannabis. The PubMed database was here examined in order to collect and discuss a range of identified papers. Cannabis intake usually starts during late adolescence/early adulthood (15-24 years) and drastically decreases in adulthood with the acquisition of working, familiar and social responsibilities. Clinical evidence supports the current socio-epidemiological alarm concerning the increased consumption among youngsters and the risks related to the onset of psychotic disorders. The mechanism of action of cannabis presents some analogies with other abused drugs, e.g. opiates. Furthermore, it has been well demonstrated that cannabis intake in adolescence may facilitate the transition to the use and/or abuse of other psychotropic drugs, hence properly being considered a ‘gateway drug’. Some considerations on synthetic cannabimimetics are provided here as well. In conclusion, the highest prevalence of cannabis use and the social perception of a relatively low associated risk are in contrast with current knowledge based on biological and clinical evidence. Indeed, there are concerns relating to cannabis intake association with detrimental effects on both cognitive impairment and mental health.Peer reviewe

Effect of Nitrogen-fixing Microorganisms and Amino Acid-based Biostimulants on Perennial Ryegrass

[EN] Due to restrictions on pesticide and nitrogen use in high-input European agricultural systems, many of the biostimulants used in horticulture are being incorporated into turfgrass management programs-although often with little understanding. A set of experiments was carried out on perennial ryegrass (Lolium perenne) cultivated in pots in a greenhouse in 2013 and 2014 to test the effect of three biostimulants: two composed of nitrifying bacteria (B1 and B2), and the other a mixture of amino acids, polysaccharides, nitrogen, and micronutrients (B3). Apart from the biostimulant treatment, nutritional stress was incorporated into the study to demonstrate if biostimulants could temporarily replace the fertilization role and so lessen the environmental impact. Turfgrass treated with B1 resulted in an increase in quality compared with untreated turf, and the positive effect lasted 2 and 3 months in 2013 and 2014, respectively. Additionally, an extended benefit was observed when the B1 interval application was longer, even temporarily replacing fertilization when applied on stressed turfgrass. The B2 produced similar results to B1, the effect was longer, and the turf exhibited a darker color-although it caused phytotoxicity at the tip of the leaves. The B3 led to a beneficial effect on turfgrass, especially under nutritional stress; it showed a better quality, darker green color, and more growth and yield than untreated turf (despite adding less nitrogen than during either mineral fertilizer treatment). Overall results show that the tested biostimulants increase turfgrass quality even when inducing a nutritional stress.De Luca, V.; Gómez De Barreda, D.; Lidón, A.; Lull Noguera, C. (2020). Effect of Nitrogen-fixing Microorganisms and Amino Acid-based Biostimulants on Perennial Ryegrass. HortTechnology. 30(2):280-291. https://doi.org/10.21273/HORTTECH04236-19S28029130

Core–Shell Pluronic-Organosilica Nanoparticles with Controlled Polarity and Oxygen Permeability

Nanostructured systems constitute versatile carriers with multiple functions engineered in a nanometric space. Yet, such multimodality often requires adapting the chemistry of the nanostructure to the properties of the hosted functional molecules. Here, we show the preparation of core-shell Pluronic-organosilica "PluOS" nanoparticles with the use of a library of organosilane precursors. The precursors are obtained via a fast and quantitative click reaction, starting from cost-effective reagents such as diamines and an isocyanate silane derivative, and they condensate in building blocks characterized by a balance between hydrophobic and H-bond-rich domains. As nanoscopic probes for local polarity, oxygen permeability, and solvating properties, we use, respectively, solvatochromic, phosphorescent, and excimer-forming dyes covalently linked to the organosilica matrix during synthesis. The results obtained here clearly show that the use of these organosilane precursors allows for finely tuning polarity, oxygen permeability, and solvating properties of the resulting organosilica core, expanding the toolbox for precise engineering of the particle properties

Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma

BACKGROUND: Growing evidence is showing that metastatic cell populations are able to transfer their characteristics to less malignant cells. Exosomes (EXOs) are membrane vesicles of endocytic origin able to convey their cargo of mRNAs, microRNAs (miRs), proteins and lipids from donors to proximal as well as distant acceptor cells. Our previous results indicated that miR-221&222 are key factors for melanoma development and dissemination. The aim of this study was to verify whether the tumorigenic properties associated with miR-222 overexpression can be also propagated by miR-222-containing EXOs. METHODS: EXOs were isolated by UltraCentrifugation or Exoquick-TC(®) methods. Preparations of melanoma-derived vesicles were characterized by using the Nanosight™ technology and the expression of exosome markers analyzed by western blot. The expression levels of endogenous and exosomal miRNAs were examined by real time PCR. Confocal microscopy was used to evaluate transfer and uptake of microvesicles from donor to recipient cells. The functional significance of exosomal miR-222 was estimated by analyzing the vessel-like process formation, as well as cell cycle rates, invasive and chemotactic capabilities. RESULTS: Besides microvesicle marker characterization, we evidenced that miR-222 exosomal expression mostly reflected its abundance in the cells of origin, correctly paralleled by repression of its target genes, such as p27Kip1, and induction of the PI3K/AKT pathway, thus confirming its functional implication in cancer. The possible differential significance of PI3K/AKT blockade was assessed by using the BKM120 inhibitor in miR-222-transduced cell lines. In addition, in vitro cultures showed that vesicles released by miR-222-overexpressing cells were able to transfer miR-222-dependent malignancy when taken-up by recipient primary melanomas. Results were confirmed by antagomiR-221&222 treatments and by functional observations after internalization of EXOs devoid of these miRs

Aortic stenting in the growing sheep causes aortic endothelial dysfunction but not hypertension: Clinical implications for coarctation repair

Stent implantation is the treatment of choice for adolescents and adults with aortic coarctation (CoAo). Despite excellent short-term results, 20%-40% of the patients develop arterial hypertension later in life, which was attributed to inappropriate response of the aortic baroreceptors to increased stiffness of the ascending aorta (ASAO), either congenital or induced by CoAo repair. In particular, it has been hypothesized that stent itself may cause or sustain hypertension. Therefore, we aimed to study the hemodynamic and structural impact following stent implantation in the normal aorta of a growing animal

Relationship between prolactin plasma levels and white matter volume in women with multiple sclerosis

BACKGROUND: The role of prolactin (PRL) on tissue injury and repair mechanisms in multiple sclerosis (MS) remains unclear. The aim of this work was to investigate the relationship between PRL plasma levels and brain damage as measured by magnetic resonance imaging (MRI). METHODS: We employed a chemiluminescence immunoassay for measuring plasma levels of PRL. We used a 1.5 T scanner to acquire images and Jim 4.0 and SIENAX software to analyse them. RESULTS: We included 106 women with relapsing remitting (RR) MS and stable disease in the last two months. There was no difference in PRL plasma levels between patients with and without gadolinium enhancement on MRI. PRL plasma levels correlated with white matter volume (WMV) (rho = 0.284, p = 0.014) but not with grey matter volume (GMV). Moreover, PRL levels predicted changes in WMV (Beta: 984, p = 0.034). CONCLUSIONS: Our data of a positive association between PRL serum levels and WMV support the role of PRL in promoting myelin repair as documented in animal models of demyelination. The lack of an increase of PRL in the presence of gadolinium enhancement, contrasts with the view considering this hormone as an immune-stimulating and detrimental factor in the inflammatory process associated with MS