681 research outputs found

    Can enlightenment be traced to specific neural correlates, cognition, or behavior? No, and (a qualified) Yes

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    The field of contemplative science is rapidly growing and integrating into the basic neurosciences, psychology, clinical sciences, and society-at-large. Yet the majority of current research in the contemplative sciences has been divorced from the soteriological context from which these meditative practices originate and has focused instead on clinical applications with goals of stress reduction and psychotherapeutic health. In the existing research on health outcomes of mindfulness-based clinical interventions, for example, there have been almost no attempts to scientifically investigate the goal of enlightenment. This is a serious oversight, given that such profound transformation across ethical, perceptual, emotional, and cognitive domains are taken to be the natural outcome and principle aim of mindfulness practice in the traditional Buddhist contexts from which these practices are derived. If short-term interventions as short as a few sessions are now beginning to produce neuroplastic changes, it may be that even in secular contexts, practitioners are already developing states and traits that are associated with progress toward enlightenment. In order to carefully assess the potential effects of meditative interventions it is of singular importance to ask whether enlightenment can be traced to specific neural correlates, cognition, or behavior

    Degradation of microbial fluorescence biosignatures by solar ultraviolet radiation on Mars

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    Recent and proposed robotic missions to Mars are equipped with implements to expose or excavate fresh material from beneath the immediate surface. Once brought into the open, any organic molecules or potential biosignatures of present or past life will be exposed to the unfiltered solar ultraviolet (UV) radiation and face photolytic degradation over short time courses. The key question, then, is what is the window of opportunity for detection of recently exposed samples during robotic operations? Detection of autofluorescence has been proposed as a simple method for surveying or triaging samples for organic molecules. Using a Mars simulation chamber we conduct UV exposures on thin frozen layers of two model microorganisms, the radiation-resistant polyextremophile Deinococcus radiodurans and the cyanobacterium Synechocystis sp. PCC 6803. Excitation–emission matrices (EEMs) are generated of the full fluorescence response to quantify the change in signal of different cellular fluorophores over Martian equivalent time. Fluorescence of Deinococcus cells, protected by a high concentration of carotenoid pigments, was found to be relatively stable over 32 h of Martian UV irradiation, with around 90% of the initial signal remaining. By comparison, fluorescence from protein-bound tryptophan in Synechocystis is much more sensitive to UV photodegradation, declining to 50% after 64 h exposure. The signal most readily degraded byUV irradiation is fluorescence of the photosynthetic pigments – diminished to only 35% after 64 h. This sensitivity may be expected as the biological function of chlorophyll and phycocyanin is to optimize the harvesting of light energy and so they are readily photobleached. A significant increase in a *450 nm emission feature is interpreted as accumulation of fluorescent cellular degradation products from photolysis. Accounting for diurnal variation in Martian sunlight, this study calculates that frozen cellular biosignatures would remain detectable by fluorescence for at least several sols; offering a sufficient window for robotic exploration operations

    Thiahelicene-grafted halloysite nanotubes: Characterization, biological studies and pH triggered release

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    A novel drug delivery nanosystem was here designed, linking thiahelicenes to halloysite nanotubes. Tetrathia[7]helicenes are very promising DNA intercalators, whose usage in biomedical field has been so far limited by their poor bioavailability. The study of appropriate drug delivery systems is needed to exploit helicenes as therapeutics. In this work, imine chemistry was adopted to covalently attach the bioactive compound and release it in acidic environments such as those surrounding tumour cells. To this aim, halloysite nanotubes were functionalized with (3-aminopropyl)triethoxysilane. The latter acted as linker providing NH2 groups to react with the formyl moiety of the thiahelicene derivative. The nanoconstruct preparation was studied in depth by surface-sensitive spectroscopies and angle-resolved X-ray absorption, to investigate the attachment mode, surface coverage and molecular orientation of the thiahelicene units. Release tests were carried out also in vitro on two tumour cell lines with different extracellular pH values. Mildly acidic pH conditions catalyzed the hydrolysis of the imine bond and promoted the cytotoxic compound release, which proved selective to slight pH differences, confirming the potential of this novel nanoconstruct

    Clinical application of tumour-in-normal contamination assessment from whole genome sequencing

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    The unexpected contamination of normal samples with tumour cells reduces variant detection sensitivity, compromising downstream analyses in canonical tumour-normal analyses. Leveraging whole-genome sequencing data available at Genomics England, we develop a tool for normal sample contamination assessment, which we validate in silico and against minimal residual disease testing. From a systematic review of 771 patients with haematological malignancies and sarcomas, we find contamination across a range of cancer clinical indications and DNA sources, with highest prevalence in saliva samples from acute myeloid leukaemia patients, and sorted CD3+ T-cells from myeloproliferative neoplasms. Further exploration reveals 108 hotspot mutations in genes associated with haematological cancers at risk of being subtracted by standard variant calling pipelines. Our work highlights the importance of contamination assessment for accurate somatic variants detection in research and clinical settings, especially with large-scale sequencing projects being utilised to deliver accurate data from which to make clinical decisions for patient care

    Direct comparison of B-Type Natriuretic Peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val-HeFT) data

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    Background: The B-type or brain natriuretic peptides (BNP) and the amino-terminal probrain natriuretic peptide (NT-proBNP) are good markers of prognosis and diagnosis in chronic heart failure (HF). It is unclear, however, whether differences in their biological characteristics modify their clinical correlates and prognostic performance in HF. This work aimed to provide a direct comparison of the prognostic value of BNP and NTproBNP in patients with chronic and stable HF. Methods: We measured BNP and NT-proBNP at baseline in 3916 patients enrolled in the Valsartan Heart Failure Trial. To identify the variables associated with both peptides, we conducted simple and multivariable linear regression analyses. We used Cox multivariable regression models to evaluate the independent prognostic value for all-cause mortality, mortality and morbidity, and hospitalization for HF. Prognostic performance was assessed by pairwise comparisons of the area under the curve of receiver-operator characteristic curves. Results: NT-proBNP and BNP had similar relationships with age, left ventrical ejection fraction, and internal diameter and creatinine clearance. Either peptide ranked as the first independent predictor of outcome after adjustment for major confounding clinical characteristics. ROC curves were almost superimposable for all-cause mortality (area under the curve (SE): BNP 0.665 (0.011) vs NT-proBNP 0.679 (0.011); P 0.0734), but NT-proBNP was superior to BNP for predicting mortality and morbidity (P 0.032) or hospitalization for HF (P 0.0143). Overall sensitivity and specificity ranged from 0.590 to 0.696. Conclusions: The natriuretic peptides BNP and NTproBNP showed subtle differences in their relation to clinical characteristics and prognostic performance in a large population of patients with chronic and stable HF. They were the most powerful independent markers of outcome in HF

    Membrane-binding peptides for extracellular vesicles on-chip analysis

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    Small extracellular vesicles (sEVs) present fairly distinctive lipid membrane features in the extracellular environment. These include high curvature, lipid-packing defects and a relative abundance in lipids such as phosphatidylserine and ceramide. sEV membrane could be then considered as a "universal" marker, alternative or complementary to traditional, characteristic, surface-associated proteins. Here, we introduce the use of membrane-sensing peptides as new, highly efficient ligands to directly integrate sEV capturing and analysis on a microarray platform. Samples were analysed by label-free, single-particle counting and sizing, and by fluorescence co-localisation immune staining with fluorescent anti-CD9/anti-CD63/anti-CD81 antibodies. Peptides performed as selective yet general sEV baits and showed a binding capacity higher than anti-tetraspanins antibodies. Insights into surface chemistry for optimal peptide performances are also discussed, as capturing efficiency is strictly bound to probes surface orientation effects. We anticipate that this new class of ligands, also due to the versatility and limited costs of synthetic peptides, may greatly enrich the molecular toolbox for EV analysis

    First Record of Fusarium verticillioides as an Entomopathogenic Fungus of Grasshoppers

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    Fusarium verticillioides (Saccardo) Nirenberg (Ascomycota: Hypocreales) is the most common fungus reported on infected corn kernels and vegetative tissues, but has not yet been documented as being entomopathogenic for grasshoppers. Grasshoppers and locusts represent a large group of insects that cause economic damage to forage and crops. Tropidacris collaris (Stoll) (Orthoptera: Acridoidea: Romaleidae) is a large and voracious grasshopper that in recent years has become an increasingly recurrent and widespread pest in progressively more greatly extended areas of some of in Argentina's northern provinces, with chemical insecticides being currently the only means of control. During February and March of 2008–09, nymphs and adults of T. collaris were collected with sweep nets in dense woodland vegetation at a site near Tres Estacas in western Chaco Province, Argentina, and kept in screened cages. F. verticillioides was isolated from insects that died within 10 days and was cultured in PGA medium. Pathogenicity tests were conducted and positive results recorded. Using traditional and molecular-biological methods, an isolate of F. verticillioides was obtained from T. collaris, and its pathogenecity in the laboratory was shown against another harmful grasshopper, Ronderosia bergi (Stål) (Acridoidea: Acrididae: Melanoplinae). The mortality caused by F. verticillioides on R. bergi reached 58 ± 6.53% by 10 days after inoculation. This is the first record of natural infection caused by F. verticillioides in grasshoppers
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