Short-term household income mobility before and after the Great Recession: A four-country study

This paper analyses short-term intra-generational income mobility in France, Italy, Spain and the UK by exploiting the longitudinal component of EU-SILC for the periods 2005-2008 and 2012-2015. We investigate whether and to what extent the ability of households to move along the income distribution changed after the 2008 crisis and whether heterogeneities among countries exist. For this purpose, we employ mobility indexes and transition matrices as well as estimation of a 2SLS regression and of a dynamic ordered probit with random effects. Overall, indexes and transition matrices point to a decrease of mobility in the aftermath of the crisis. The econometric analyses suggest both the existence of a convergence process of incomes and state dependence of current and lagged income in both periods. We also observe sluggish income convergence and lower upward mobility in the second period. Among the microeconomic drivers, education and employment status are positive determinants of mobility. Finally, our results confirm crosscountry heterogeneity

Mucuna pruriens (Velvet bean) Rescues Motor, Olfactory, Mitochondrial and Synaptic Impairment in PINK1(B9) Drosophila melanogaster Genetic Model of Parkinson's Disease

The fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD). Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe), a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3–6 (I), 10–15 (II) and 20–25 (III) days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1%) ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT) levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment

The Effect of Trust on Gaze-Mediated Attentional Orienting

© Copyright © 2020 Barbato, Almulla and Marotta. The last two decades have witnessed growing interest in the study of social cognition and its multiple facets, including trust. Interpersonal trust is generally understood as the belief that others are not likely to harm you. When meeting strangers, judgments of trustworthiness are mostly based on fast evaluation of facial appearance, unless information about past behavior is available. In the past decade, studies have tried to understand the complex relationship between trust and gaze-cueing of attention (GCA) (i.e., attentional orienting following another person’s gaze). This review will focus on the studies that used a gaze-cueing paradigm to explore this relationship. While the predictivity of the gaze-cue seems to consistently influence trustworthiness judgments, the impact of trust on gaze-cueing is less clear. Four studies found enhanced gaze-cueing effects with trustworthy faces; one found stronger effects of gaze-cueing with faces associated with undesirable behavior, but only when the observer’s personal evaluations were taken into account. Four studies did not observe an effect of trust on gaze-cueing. Overall, studies have highlighted the complexity of this relationship, suggesting that multiple factors (including age, gender, the characteristics of the observer, and whether or not a threat is perceived) are likely to intervene in the interplay between trust and gaze-triggered attentional orienting. After discussing results in the context of existing theories of gaze-cueing and trust, we conclude that further investigation is needed to better understand this relationship and the contribution of social factors to attentional shifts guided by gaze

The Effect of Trust on Gaze-Mediated Attentional Orienting

The last two decades have witnessed growing interest in the study of social cognition and its multiple facets, including trust. Interpersonal trust is generally understood as the belief that others are not likely to harm you. When meeting strangers, judgments of trustworthiness are mostly based on fast evaluation of facial appearance, unless information about past behavior is available. In the past decade, studies have tried to understand the complex relationship between trust and gaze-cueing of attention (GCA) (i.e., attentional orienting following another person’s gaze). This review will focus on the studies that used a gaze-cueing paradigm to explore this relationship. While the predictivity of the gaze-cue seems to consistently influence trustworthiness judgments, the impact of trust on gaze-cueing is less clear. Four studies found enhanced gazecueing effects with trustworthy faces; one found stronger effects of gaze-cueing with faces associated with undesirable behavior, but only when the observer’s personal evaluations were taken into account. Four studies did not observe an effect of trust on gaze-cueing. Overall, studies have highlighted the complexity of this relationship, suggesting that multiple factors (including age, gender, the characteristics of the observer, and whether or not a threat is perceived) are likely to intervene in the interplay between trust and gaze-triggered attentional orienting. After discussing results in the context of existing theories of gaze-cueing and trust, we conclude that further investigation is needed to better understand this relationship and the contribution of social factors to attentional shifts guided by gaze.Zayed University R1905

A Neutralizing RNA Aptamer against EGFR Causes Selective Apoptotic Cell Death

Nucleic acid aptamers have been developed as high-affinity ligands that may act as antagonists of disease-associated proteins. Aptamers are non immunogenic and characterised by high specificity and low toxicity thus representing a valid alternative to antibodies or soluble ligand receptor traps/decoys to target specific cancer cell surface proteins in clinical diagnosis and therapy. The epidermal growth factor receptor (EGFR) has been implicated in the development of a wide range of human cancers including breast, glioma and lung. The observation that its inhibition can interfere with the growth of such tumors has led to the design of new drugs including monoclonal antibodies and tyrosine kinase inhibitors currently used in clinic. However, some of these molecules can result in toxicity and acquired resistance, hence the need to develop novel kinds of EGFR-targeting drugs with high specificity and low toxicity. Here we generated, by a cell-Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach, a nuclease resistant RNA-aptamer that specifically binds to EGFR with a binding constant of 10 nM. When applied to EGFR-expressing cancer cells the aptamer inhibits EGFR-mediated signal pathways causing selective cell death. Furthermore, at low doses it induces apoptosis even of cells that are resistant to the most frequently used EGFR-inhibitors, such as gefitinib and cetuximab, and inhibits tumor growth in a mouse xenograft model of human non-small-cell lung cancer (NSCLC). Interestingly, combined treatment with cetuximab and the aptamer shows clear synergy in inducing apoptosis in vitro and in vivo. In conclusion, we demonstrate that this neutralizing RNA-aptamer is a promising bio-molecule that can be developed as a more effective alternative to the repertoire of already existing EGFR-inhibitors

Fuel consumption and exhaust emissions of diesel vehicles in worldwide harmonized light vehicles test cycles and their sensitivities to eco-driving factors

Large amounts of fossil fuels are 14 consumed by motor vehicles annually, and hazardous exhaust emissions from the motor vehicles have caused serious problems to environment and human health. Eco-driving can effectively improve the fuel economy and decrease the exhaust emissions, which makes it vital to analyze the fuel consumption and exhaust emissions at given driving cycle, and investigate their sensitivities to eco-driving factors. In this paper, the fuel consumption and exhaust emissions of a Euro-6 compliant light-duty diesel vehicle were tested in Worldwide Harmonized Light Vehicles Test Cycles on a chassis dynamometer; further, the sensitivities of the eco-driving factors that influence the fuel economy and exhaust emissions were analyzed using validated vehicle model. For the vehicle model simulation, the effect of the coolant temperature on fuel consumption and exhaust emission only considered its effect on lubricating oil viscosity. The results showed that vehicle acceleration and velocity dominates the fuel consumption rates in Worldwide Harmonized Light Vehicles Test Cycles, where more than 50% of the exhaust emissions was emitted in the first 300 seconds; also, fuel economy and exhaust emission factors showed a significant dependency on the road grade, coolant temperature, vehicle velocity and mass. For the driver-controllable factors, high vehicle velocity and low road grade (via route-choice) were recommended to achieve low fuel consumption and exhaust emissions

Engineered Breast Cancer Cell Spheroids Reproduce Biologic Properties of Solid Tumors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135116/1/adhm201600644-sup-0001-S1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135116/2/adhm201600644.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135116/3/adhm201600644_am.pd

Enhanced catecholamine transporter binding in the locus coeruleus of patients with early Parkinson disease

<p>Abstract</p> <p>Background</p> <p>Studies in animals suggest that the noradrenergic system arising from the locus coeruleus (LC) and dopaminergic pathways mutually influence each other. Little is known however, about the functional state of the LC in patients with Parkinson disease (PD).</p> <p>Methods</p> <p>We retrospectively reviewed clinical and imaging data of 94 subjects with PD at an early clinical stage (Hoehn and Yahr stage 1-2) who underwent single photon computed tomography imaging with FP-CIT ([¹²³I] N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) tropane). FP-CIT binding values from the patients were compared with 15 healthy subjects: using both a voxel-based whole brain analysis and a volume of interest analysis of <it>a priori </it>defined brain regions.</p> <p>Results</p> <p>Average FP-CIT binding in the putamen and caudate nucleus was significantly reduced in PD subjects (43% and 57% on average, respectively; p < 0.001). In contrast, subjects with PD showed an increased binding in the LC (166% on average; p < 0.001) in both analyses. LC-binding correlated negatively with striatal FP-CIT binding values (caudate: contralateral, ρ = -0.28, p < 0.01 and ipsilateral ρ = -0.26, p < 0.01; putamen: contralateral, ρ = -0.29, p < 0.01 and ipsilateral ρ = -0.29, p < 0.01).</p> <p>Conclusions</p> <p>These findings are consistent with an up-regulation of noradrenaline reuptake in the LC area of patients with early stage PD, compatible with enhanced noradrenaline release, and a compensating activity for degeneration of dopaminergic nigrostriatal projections.</p

The Small Molecule Inhibitor QLT0267 Radiosensitizes Squamous Cell Carcinoma Cells of the Head and Neck

BACKGROUND: The constant increase of cancer cell resistance to radio- and chemotherapy hampers improvement of patient survival and requires novel targeting approaches. Integrin-Linked Kinase (ILK) has been postulated as potent druggable cancer target. On the basis of our previous findings clearly showing that ILK transduces antisurvival signals in cells exposed to ionizing radiation, this study evaluated the impact of the small molecule inhibitor QLT0267, reported as putative ILK inhibitor, on the cellular radiation survival response of human head and neck squamous cell carcinoma cells (hHNSCC). METHODOLOGY/PRINCIPAL FINDINGS: Parental FaDu cells and FaDu cells stably transfected with a constitutively active ILK mutant (FaDu-IH) or empty vectors, UTSCC45 cells, ILK(floxed/floxed(fl/fl)) and ILK(-/-) mouse fibroblasts were used. Cells grew either two-dimensionally (2D) on or three-dimensionally (3D) in laminin-rich extracellular matrix. Cells were treated with QLT0267 alone or in combination with irradiation (X-rays, 0-6 Gy single dose). ILK knockdown was achieved by small interfering RNA transfection. ILK kinase activity, clonogenic survival, number of residual DNA double strand breaks (rDSB; gammaH2AX/53BP1 foci assay), cell cycle distribution, protein expression and phosphorylation (e.g. Akt, p44/42 mitogen-activated protein kinase (MAPK)) were measured. Data on ILK kinase activity and phosphorylation of Akt and p44/42 MAPK revealed a broad inhibitory spectrum of QLT0267 without specificity for ILK. QLT0267 significantly reduced basal cell survival and enhanced the radiosensitivity of FaDu and UTSCC45 cells in a time- and concentration-dependent manner. QLT0267 exerted differential, cell culture model-dependent effects with regard to radiogenic rDSB and accumulation of cells in the G2 cell cycle phase. Relative to corresponding controls, FaDu-IH and ILK(fl/fl) fibroblasts showed enhanced radiosensitivity, which failed to be antagonized by QLT0267. A knockdown of ILK revealed no change in clonogenic survival of the tested cell lines as compared to controls. CONCLUSIONS/SIGNIFICANCE: Our data clearly show that the small molecule inhibitor QLT0267 has potent cytotoxic and radiosensitizing capability in hHNSCC cells. However, QLT0267 is not specific for ILK. Further in vitro and in vivo studies are necessary to clarify the potential of QLT0267 as a targeted therapeutic in the clinic

Functional Characterization of MODY2 Mutations Highlights the Importance of the Fine-Tuning of Glucokinase and Its Role in Glucose Sensing

Glucokinase (GK) acts as a glucose sensor in the pancreatic beta-cell and regulates insulin secretion. Heterozygous mutations in the human GK-encoding GCK gene that reduce the activity index increase the glucose-stimulated insulin secretion threshold and cause familial, mild fasting hyperglycaemia, also known as Maturity Onset Diabetes of the Young type 2 (MODY2). Here we describe the biochemical characterization of five missense GK mutations: p.Ile130Thr, p.Asp205His, p.Gly223Ser, p.His416Arg and p.Ala449Thr. The enzymatic analysis of the corresponding bacterially expressed GST-GK mutant proteins show that all of them impair the kinetic characteristics of the enzyme. In keeping with their position within the protein, mutations p.Ile130Thr, p.Asp205His, p.Gly223Ser, and p.His416Arg strongly decrease the activity index of GK, affecting to one or more kinetic parameters. In contrast, the p.Ala449Thr mutation, which is located in the allosteric activator site, does not affect significantly the activity index of GK, but dramatically modifies the main kinetic parameters responsible for the function of this enzyme as a glucose sensor. The reduced Kcat of the mutant (3.21±0.28 s−1 vs 47.86±2.78 s−1) is balanced by an increased glucose affinity (S0.5 = 1.33±0.08 mM vs 7.86±0.09 mM) and loss of cooperativity for this substrate. We further studied the mechanism by which this mutation impaired GK kinetics by measuring the differential effects of several competitive inhibitors and one allosteric activator on the mutant protein. Our results suggest that this mutation alters the equilibrium between the conformational states of glucokinase and highlights the importance of the fine-tuning of GK and its role in glucose sensing