116 research outputs found

    Practical recommendations to communicate with patients about health‐related conspiracy theories

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    Health-related conspiracy theories often advance the argument that information is being kept secret from the public by powerful individuals or groups within the government or health industry. They are widespread and are associated with important health attitudes, intentions, and behaviours. Recent research suggests that individuals are attracted to conspiracy theories to satisfy three important and fundamental psychological needs: epistemic, existential, and social needs. Understanding these underlying motivations associated with health-related conspiracy theories can help address patients’ beliefs. Debunking and inoculation are discussed as approaches that can be used to address patients’ belief in health-related conspiracy theories

    Tribocorrosion behavior of Ti–C–O–N nanostructured thin films (black) for decorative applications

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    In the past few years, tribocorrosion has become a focus of research because of its relevance in terms of the future in-service degradation mechanisms of materials. In the particular case of decorative coatings, tribocorrosion is certainly one of the most important issues, and sweat corrosion and human contact wear are two other factors that may act as material selection tools. Thus, the current study aimed to investigate the tribocorrosion behavior of a new class of thin films, the Ti–C–O–N system, which is being developed to be used as a surface decorative material due to its relatively dark appearance. The films were prepared by reactive magnetron sputtering. The influence of the structural features on the tribocorrosion behavior is discussed.This research is supported by FEDER funds through COMPETE-Programa Operacional Factores de Competitividade and by national funds through the Fundacao para a Ciencia e a Tecnologia, project PTDC/CTM/69362/2006 and contract SFRH/BD/27569/2006

    Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria

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    Acetate is a short-chain fatty acid secreted by Propionibacteria from the human intestine, known to induce mitochondrial apoptotic death in colorectal cancer (CRC) cells. We previously established that acetate also induces lysosome membrane permeabilization in CRC cells, associated with release of the lysosomal protease cathepsin D (CatD), which has a well-established role in the mitochondrial apoptotic cascade. Unexpectedly, we showed that CatD has an antiapoptotic role in this process, as pepstatin A (a CatD inhibitor) increased acetate-induced apoptosis. These results mimicked our previous data in the yeast system showing that acetic acid activates a mitochondria-dependent apoptosis process associated with vacuolar membrane permeabilization and release of the vacuolar protease Pep4p, ortholog of mammalian CatD. Indeed, this protease was required for cell survival in a manner dependent on its catalytic activity and for efficient mitochondrial degradation independently of autophagy. In this study, we therefore assessed the role of CatD in acetate-induced mitochondrial alterations. We found that, similar to acetic acid in yeast, acetate-induced apoptosis is not associated with autophagy induction in CRC cells. Moreover, inhibition of CatD with small interfering RNA or pepstatin A enhanced apoptosis associated with higher mitochondrial dysfunction and increased mitochondrial mass. This effect seems to be specific, as inhibition of CatB and CatL with E-64d had no effect, nor were these proteases significantly released to the cytosol during acetate-induced apoptosis. Using yeast cells, we further show that the role of Pep4p in mitochondrial degradation depends on its protease activity and is complemented by CatD, indicating that this mechanism is conserved. In summary, the clues provided by the yeast model unveiled a novel CatD function in the degradation of damaged mitochondria when autophagy is impaired, which protects CRC cells from acetate-induced apoptosis. CatD inhibitors could therefore enhance acetate-mediated cancer cell death, presenting a novel strategy for prevention or therapy of CRC.FEDER through POFC – COMPETE and by Fundação para a Ciência e Tecnologia through projects PEst-OE/BIA/UI4050/2014 and FCT ANR/BEX-BCM/0175/201

    The Atacama Cosmology Telescope: Cosmology from cross-correlations of unWISE galaxies and ACT DR6 CMB lensing

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    We present tomographic measurements of structure growth using cross-correlations of Atacama Cosmology Telescope (ACT) DR6 and Planck CMB lensing maps with the unWISE Blue and Green galaxy samples, which span the redshift ranges 0.2z1.10.2 \lesssim z \lesssim 1.1 and 0.3z1.80.3 \lesssim z \lesssim 1.8, respectively. We improve on prior unWISE cross-correlations not just by making use of the new, high-precision ACT DR6 lensing maps, but also by including additional spectroscopic data for redshift calibration and by analysing our measurements with a more flexible theoretical model. An extensive suite of systematic and null tests within a blind analysis framework ensures that our results are robust. We determine the amplitude of matter fluctuations at low redshifts (z0.21.6z\simeq 0.2-1.6), finding S8σ8(Ωm/0.3)0.5=0.813±0.021S_8 \equiv \sigma_8 (\Omega_m / 0.3)^{0.5} = 0.813 \pm 0.021 using the ACT cross-correlation alone and S8=0.810±0.015S_8 = 0.810 \pm 0.015 with a combination of Planck and ACT cross-correlations; these measurements are fully consistent with the predictions from primary CMB measurements assuming standard structure growth. The addition of Baryon Acoustic Oscillation data breaks the degeneracy between σ8\sigma_8 and Ωm\Omega_m, allowing us to measure σ8=0.813±0.020\sigma_8 = 0.813 \pm 0.020 from the cross-correlation of unWISE with ACT and σ8=0.813±0.015\sigma_8 = 0.813\pm 0.015 from the combination of cross-correlations with ACT and Planck. These results also agree with the expectations from primary CMB extrapolations in Λ\LambdaCDM cosmology; the consistency of σ8\sigma_8 derived from our two redshift samples at z0.6z \sim 0.6 and 1.11.1 provides a further check of our cosmological model. Our results suggest that structure formation on linear scales is well described by Λ\LambdaCDM even down to low redshifts z1z\lesssim 1.Comment: 73 pages (incl. 30 pages of appendices), 50 figures, 16 tables, to be submitted to ApJ. Watch G. S. Farren and A. Krolewski discuss the analysis and results under https://cosmologytalks.com/2023/09/11/act-unwis

    Oxidation of benzoin catalyzed by oxovanadium (IV) schiff base complexes

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    BACKGROUND: The oxidative transformation of benzoin to benzil has been accomplished by the use of a wide variety of reagents or catalysts and different reaction procedures. The conventional oxidizing agents yielded mainly benzaldehyde or/and benzoic acid and only a trace amount of benzil. The limits of practical utilization of these reagents involves the use of stoichiometric amounts of corrosive acids or toxic metallic reagents, which in turn produce undesirable waste materials and required high reaction temperatures. In recent years, vanadium complexes have attracted much attention for their potential utility as catalysts for various types of reactions. RESULTS: Active and selective catalytic systems of new unsymmetrical oxovanadium(IV) Schiff base complexes for the oxidation of benzoin is reported. The Schiff base ligands are derived between 2-aminoethanol and 2-hydroxy-1- naphthaldehyde (H2L1) or 3-ethoxy salicylaldehyde (H2L3); and 2-aminophenol and 3-ethoxysalicylaldehyde (H2L2) or 2-hydroxy-1-naphthaldehyde (H2L4). The unsymmetrical Schiff bases behave as tridentate dibasic ONO donor ligands. Reaction of these Schiff base ligands with oxovanadyl sulphate afforded the mononuclear oxovanadium(IV) complexes (VIVOLx.H2O), which are characterized by various physico-chemical techniques. The catalytic oxidation activities of these complexes for benzoin were evaluated using H2O2 as an oxidant. The best reaction conditions are obtained by considering the effect of solvent, reaction time and temperature. Under the optimized reaction conditions, VOL4 catalyst showed high conversion (>99%) with excellent selectivity to benzil (~100%) in a shorter reaction time compared to the other catalysts considered. CONCLUSION: Four tridentate ONO type Schiff base ligands were synthesized. Complexation of these ligands with vanadyl(IV) sulphate leads to the formation of new oxovanadium(IV) complexes of type VIVOL.H2O. Elemental analyses and spectral data of the free ligands and their oxovanadium(IV) complexes were found to be in good agreement with their structures, indicating high purity of all the compounds. Oxovanadium complexes were screened for the oxidation of benzoin to benzil using H2O2 as oxidant. The effect of time, solvent and temperature were optimized to obtain maximum yield. The catalytic activity results demonstrate that these catalytic systems are both highly active and selective for the oxidation of benzoin under mild reaction conditions.Web of Scienc

    Mechanisms of TSC-mediated Control of Synapse Assembly and Axon Guidance

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    Tuberous sclerosis complex is a dominant genetic disorder produced by mutations in either of two tumor suppressor genes, TSC1 and TSC2; it is characterized by hamartomatous tumors, and is associated with severe neurological and behavioral disturbances. Mutations in TSC1 or TSC2 deregulate a conserved growth control pathway that includes Ras homolog enriched in brain (Rheb) and Target of Rapamycin (TOR). To understand the function of this pathway in neural development, we have examined the contributions of multiple components of this pathway in both neuromuscular junction assembly and photoreceptor axon guidance in Drosophila. Expression of Rheb in the motoneuron, but not the muscle of the larval neuromuscular junction produced synaptic overgrowth and enhanced synaptic function, while reductions in Rheb function compromised synapse development. Synapse growth produced by Rheb is insensitive to rapamycin, an inhibitor of Tor complex 1, and requires wishful thinking, a bone morphogenetic protein receptor critical for functional synapse expansion. In the visual system, loss of Tsc1 in the developing retina disrupted axon guidance independently of cellular growth. Inhibiting Tor complex 1 with rapamycin or eliminating the Tor complex 1 effector, S6 kinase (S6k), did not rescue axon guidance abnormalities of Tsc1 mosaics, while reductions in Tor function suppressed those phenotypes. These findings show that Tsc-mediated control of axon guidance and synapse assembly occurs via growth-independent signaling mechanisms, and suggest that Tor complex 2, a regulator of actin organization, is critical in these aspects of neuronal development

    Identification of Conserved and HLA Promiscuous DENV3 T-Cell Epitopes

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    Anti-dengue T-cell responses have been implicated in both protection and immunopathology. However, most of the T-cell studies for dengue include few epitopes, with limited knowledge of their inter-serotype variation and the breadth of their human leukocyte antigen (HLA) affinity. In order to expand our knowledge of HLA-restricted dengue epitopes, we screened T-cell responses against 477 overlapping peptides derived from structural and non-structural proteins of the dengue virus serotype 3 (DENV3) by use of HLA class I and II transgenic mice (TgM): A2, A24, B7, DR2, DR3 and DR4. TgM were inoculated with peptides pools and the T-cell immunogenic peptides were identified by ELISPOT. Nine HLA class I and 97 HLA class II novel DENV3 epitopes were identified based on immunogenicity in TgM and their HLA affinity was further confirmed by binding assays analysis. A subset of these epitopes activated memory T-cells from DENV3 immune volunteers and was also capable of priming naïve T-cells, ex vivo, from dengue IgG negative individuals. Analysis of inter- and intra-serotype variation of such an epitope (A02-restricted) allowed us to identify altered peptide ligands not only in DENV3 but also in other DENV serotypes. These studies also characterized the HLA promiscuity of 23 HLA class II epitopes bearing highly conserved sequences, six of which could bind to more than 10 different HLA molecules representing a large percentage of the global population. These epitope data are invaluable to investigate the role of T-cells in dengue immunity/pathogenesis and vaccine design. © 2013 Nascimento et al

    Mutations in Wnt2 Alter Presynaptic Motor Neuron Morphology and Presynaptic Protein Localization at the Drosophila Neuromuscular Junction

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    Wnt proteins are secreted proteins involved in a number of developmental processes including neural development and synaptogenesis. We sought to determine the role of the Drosophila Wnt7b ortholog, Wnt2, using the neuromuscular junction (NMJ). Mutations in wnt2 produce an increase in the number of presynaptic branches and a reduction in immunolabeling of the active zone proteins, Bruchpilot and synaptobrevin, at the NMJ. There was no change, however, in immunolabeling for the presynaptic proteins cysteine-string protein (CSP) and synaptotagmin, nor the postsynaptic proteins GluRIIA and DLG at the NMJ. Consistent with the presynaptic defects, wnt2 mutants exhibit approximately a 50% reduction in evoked excitatory junctional currents. Rescue, RNAi, and tissue-specific qRT-PCR experiments indicate that Wnt2 is expressed by the postsynaptic cell where it may serve as a retrograde signal that regulates presynaptic morphology and the localization of presynaptic proteins

    The Atacama Cosmology Telescope: A Measurement of the DR6 CMB Lensing Power Spectrum and its Implications for Structure Growth

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    We present new measurements of cosmic microwave background (CMB) lensing over 94009400 sq. deg. of the sky. These lensing measurements are derived from the Atacama Cosmology Telescope (ACT) Data Release 6 (DR6) CMB dataset, which consists of five seasons of ACT CMB temperature and polarization observations. We determine the amplitude of the CMB lensing power spectrum at 2.3%2.3\% precision (43σ43\sigma significance) using a novel pipeline that minimizes sensitivity to foregrounds and to noise properties. To ensure our results are robust, we analyze an extensive set of null tests, consistency tests, and systematic error estimates and employ a blinded analysis framework. The baseline spectrum is well fit by a lensing amplitude of Alens=1.013±0.023A_{\mathrm{lens}}=1.013\pm0.023 relative to the Planck 2018 CMB power spectra best-fit Λ\LambdaCDM model and Alens=1.005±0.023A_{\mathrm{lens}}=1.005\pm0.023 relative to the ACT DR4+WMAP\text{ACT DR4} + \text{WMAP} best-fit model. From our lensing power spectrum measurement, we derive constraints on the parameter combination S8CMBLσ8(Ωm/0.3)0.25S^{\mathrm{CMBL}}_8 \equiv \sigma_8 \left({\Omega_m}/{0.3}\right)^{0.25} of S8CMBL=0.818±0.022S^{\mathrm{CMBL}}_8= 0.818\pm0.022 from ACT DR6 CMB lensing alone and S8CMBL=0.813±0.018S^{\mathrm{CMBL}}_8= 0.813\pm0.018 when combining ACT DR6 and Planck NPIPE CMB lensing power spectra. These results are in excellent agreement with Λ\LambdaCDM model constraints from Planck or ACT DR4+WMAP\text{ACT DR4} + \text{WMAP} CMB power spectrum measurements. Our lensing measurements from redshifts z0.5z\sim0.5--55 are thus fully consistent with Λ\LambdaCDM structure growth predictions based on CMB anisotropies probing primarily z1100z\sim1100. We find no evidence for a suppression of the amplitude of cosmic structure at low redshiftsComment: 45+21 pages, 50 figures. Prepared for submission to ApJ. Also see companion papers Madhavacheril et al and MacCrann et a
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