Elevated alpha-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patient-derived induced pluripotent stem cells

We have assessed the impact of α-synuclein overexpression on the differentiation potential and phenotypic signatures of two neural-committed induced pluripotent stem cell lines derived from a Parkinson´s disease patient with a triplication of the human SNCA genomic locus. In parallel, comparative studies were performed on two control lines derived from healthy individuals and lines generated from the patient iPS-derived neuroprogenitor lines infected with a lentivirus incorporating a small hairpin RNA to knock down the SNCA mRNA. The SNCA triplication lines exhibited a reduced capacity to differentiate into dopaminergic or GABAergic neurons and decreased neurite outgrowth and lower neuronal activity compared with control cultures. This delayed maturation phenotype was confirmed by gene expression profiling, which revealed a significant reduction in mRNA for genes implicated in neuronal differentiation such as delta-like homolog 1 (DLK1), gamma-aminobutyric acid type B receptor subunit 2 (GABABR2), nuclear receptor related 1 protein (NURR1), G-protein-regulated inward-rectifier potassium channel 2 (GIRK-2) and tyrosine hydroxylase (TH). The differentiated patient cells also demonstrated increased autophagic flux when stressed with chloroquine. We conclude that a two-fold overexpression of α-synuclein caused by a triplication of the SNCA gene is sufficient to impair the differentiation of neuronal progenitor cells, a finding with implications for adult neurogenesis and Parkinson´s disease progression, particularly in the context of bioenergetic dysfunction.Fil: Oliveira, L. M. A.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Falomir Lockhart, Lisandro Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Botelho, M. G.. Max-Planck-Institut für biophysikalische Chemie; Alemania. Universidade Federal do Rio de Janeiro; BrasilFil: Lin, K. H.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Wales, P.. Universität Göttingen; AlemaniaFil: Koch, J. C.. Universität Göttingen; AlemaniaFil: Gerhardt, Elizabeth. Universität Göttingen; AlemaniaFil: Taschenberger, H.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Outeiro, T. F.. Universität Göttingen; AlemaniaFil: Lingor, P.. Universität Göttingen; AlemaniaFil: Schüele, B.. The Parkinson’s Institute; Estados UnidosFil: Arndt Jovin, D. J.. Max-Planck-Institut für biophysikalische Chemie; AlemaniaFil: Jovin, T. M.. Max-Planck-Institut für biophysikalische Chemie; Alemani

A neutrosophic enhanced best–worst method for considering decision-makers’ confidence in the best and worst criteria

The best–worst method (BWM) is a multiple criteria decision-making (MCDM) method for evaluating ≤a set of alternatives based on a set of decision criteria where two vectors of pairwise comparisons are used to calculate the importance weight of decision criteria. The BWM is an efficient and mathematically sound method used to solve a wide range of MCDM problems by reducing the number of pairwise comparisons and identifying the inconsistencies derived from the comparison process. In spite of its simplicity and efficiency, the BWM does not consider the decision-makers’ (DMs’) confidence in their pairwise comparisons. We propose a neutrosophic enhancement to the original BWM by introducing two new parameters as the DMs’ confidence in the best-to-others preferences and the DMs’ confidence in the others-to-worst preferences. We present two real-world cases to illustrate the applicability of the proposed neutrosophic enhanced BWM (NE-BWM) by considering confidence rating levels of the DMs

Uso do clorofilômetro como indicador da necessidade de adubação nitrogenada em cobertura em arroz irrigado.

O objetivo desse estudo foi determinar a resposta do arroz irrigado a doses de N e avaliar a influência do manejo desse nutriente baseado no uso do clorofilômetro no desempenho da cultivar BRS Tropical

Radiação solar no sub-bosque de sistema agrossilvipastoril com eucalipto em diferentes arranjos estruturais.

A radiação solar no sub-bosque de povoamentos de eucalipto torna-se decisiva para implantação de culturas intercalares e consórcio com pastagens em sistemas agrossilvipastoris. Objetivou-se determinar a incidência e distribuição da densidade de fluxo de fótons, radiação solar global e iluminância no sub-bosque de diferentes arranjos estruturais de sistema agrossilvipatoril com eucalipto. O experimento foi implantado em dezembro de 1999, em área de cerrado. Realizou-se o plantio de mudas clonais de um híbrido natural de Eucalyptus camaldulensis Dehnh com Eucalyptus urophylla S.T. Blake, em consórcio com arroz no primeiro ano, soja no segundo e pastagem de Brachiaria brizantha (Hochst. ex A. Rich.) Stapf cv. Marandu nos anos consecutivos. O delineamento utilizado foi blocos casualizados em esquema de parcelas subdivididas, com cinco repetições. Nas parcelas, estudou-se o efeito dos arranjos 3,33 x 2 m, 3,33 x 3 m, 5 x 2 m, 10 x 2 m, 10 x 3 m, 10 x 4 m, (3 x 4)+7 m, (3 x 3)+10 m, (3 x 4)+10 m e (3 x 3)+15 m. As subparcelas corresponderam às avaliações na linha e entrelinha de plantio, realizadas aos 27, 38 e 54 meses. A radiação solar no subbosque varia em função dos arranjos. Nos 3,33 x 2 m e 3,33 x 3 m, o fechamento do dossel promove sombreamento geral do sub-bosque aos dois anos. Nos arranjos mais amplos, a distribuição espacial da radiação solar e o sombreamento variam com a época do ano

Desempenho do arroz irrigado afetado pelo manejo de nitrogênio monitorado com o uso do clorofilômetro e fungicidas.

Objetivou-se com este estudo determinar o desempenho do arroz irrigado influenciado pelo manejo de N baseado no uso do clorofilômetro e aplicação de fungicidas em várzea tropical

Oxidative Stress, DNA, Cell Cycle/Cell Cycle Associated Proteins and Multidrug Resistance Proteins: Targets of Human Amniotic Membrane in Hepatocellular Carcinoma

The anticancer effects of human amniotic membrane (hAM) have been studied over the last decade. However, the action mechanisms responsible for these effects are not fully understood until now. Previously results reported by our team proved that hAM is able to induce cytotoxicity and cell death in hepatocellular carcinoma (HCC), a worldwide high incident and mortal cancer. Therefore, this experimental study aimed to investigate the cellular targets of hAM protein extracts (hAMPE) in HCC through in vitro studies. Our results showed that hAMPE is able to modify oxidative stress environment in all HCC cell lines, as well as its cell cycle. hAMPE differently targets deoxyribonucleic acid (DNA), P21, P53, β-catenin and multidrug resistance (MDR) proteins in HCC cell lines. In conclusion, hAMPE has several targets in HCC, being clear that the success of this treatment depends of a personalized therapy based on the biological and genetic characteristics of the tumor

Observation of a pairing pseudogap in a two-dimensional Fermi gas

Pairing of fermions is ubiquitous in nature and it is responsible for a large variety of fascinating phenomena like superconductivity, superfluidity of $^3$He, the anomalous rotation of neutron stars, and the BEC-BCS crossover in strongly interacting Fermi gases. When confined to two dimensions, interacting many-body systems bear even more subtle effects, many of which lack understanding at a fundamental level. Most striking is the, yet unexplained, effect of high-temperature superconductivity in cuprates, which is intimately related to the two-dimensional geometry of the crystal structure. In particular, the questions how many-body pairing is established at high temperature and whether it precedes superconductivity are crucial to be answered. Here, we report on the observation of pairing in a harmonically trapped two-dimensional atomic Fermi gas in the regime of strong coupling. We perform momentum-resolved photoemission spectroscopy, analogous to ARPES in the solid state, to measure the spectral function of the gas and we detect a many-body pairing gap above the superfluid transition temperature. Our observations mark a significant step in the emulation of layered two-dimensional strongly correlated superconductors using ultracold atomic gases

Measurement of the mid-rapidity transverse energy distribution from sNN=130\sqrt{s_{NN}}=130 GeV Au+Au collisions at RHIC

The first measurement of energy produced transverse to the beam direction at RHIC is presented. The mid-rapidity transverse energy density per participating nucleon rises steadily with the number of participants, closely paralleling the rise in charged-particle density, such that E_T / N_ch remains relatively constant as a function of centrality. The energy density calculated via Bjorken's prescription for the 2% most central Au+Au collisions at sqrt(s_NN)=130 GeV is at least epsilon_Bj = 4.6 GeV/fm^3 which is a factor of 1.6 larger than found at sqrt(s_NN)=17.2 GeV (Pb+Pb at CERN).Comment: 307 authors, 6 pages, 4 figures, 1 table, submitted to PRL 4/18/2001; revised version submitted to PRL 5/24/200

Net Charge Fluctuations in Au + Au Interactions at sqrt(s_NN) = 130 GeV

Data from Au + Au interactions at sqrt(s_NN) = 130 GeV, obtained with the PHENIX detector at RHIC, are used to investigate local net charge fluctuations among particles produced near mid-rapidity. According to recent suggestions, such fluctuations may carry information from the Quark Gluon Plasma. This analysis shows that the fluctuations are dominated by a stochastic distribution of particles, but are also sensitive to other effects, like global charge conservation and resonance decays.Comment: 6 pages, RevTeX 3, 3 figures, 307 authors, submitted to Phys. Rev. Lett. on 21 March, 2002. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (will be made) publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm

Event-by-event fluctuations in Mean pTp_T and Mean eTe_T in sqrt(s_NN) = 130 GeV Au+Au Collisions

Distributions of event-by-event fluctuations of the mean transverse momentum and mean transverse energy near mid-rapidity have been measured in Au+Au collisions at sqrt(s_NN) = 130 GeV at RHIC. By comparing the distributions to what is expected for statistically independent particle emission, the magnitude of non-statistical fluctuations in mean transverse momentum is determined to be consistent with zero. Also, no significant non-random fluctuations in mean transverse energy are observed. By constructing a fluctuation model with two event classes that preserve the mean and variance of the semi-inclusive p_T or e_T spectra, we exclude a region of fluctuations in sqrt(s_NN) = 130 GeV Au+Au collisions.Comment: 10 pages, RevTeX 3, 7 figures, 4 tables, 307 authors, submitted to Phys. Rev. C on 22 March 2002. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (will be made) publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm