95 research outputs found
Gene silencing by siRNA nanoparticles synthesized via sonochemical method
The knowledge that small RNAs can affect gene expression has had a tremendous impact on basic and applied research, and gene silencing is currently one of the most promising new approaches for disease therapy. However, RNAs cannot easily penetrate cell membranes, therefore RNA delivery become one of the major challenges for gene silencing technology. In the current paper we discuss a general approach for converting siRNA molecules into a dense siRNA nanoparticles using environmentally friendly sonochemical method. The RNA nanoparticulation enhance its gene-silencing activity in vascular bovine endothelial as well as in cancer 293T/GFP-Puro cell lines without causing any toxic effect. We show that ultrasonic waves do not lead to RNA degradation or any changes in its chemical structure. Moreover, sonochemically produced siRNA nanoparticles have been shown to be resistant to a variety of environmental stresses including pH levels, enzymes and temperatures, hence solving problem of the short half-life of the RNA molecules. As the siRNA nanoparticles are biocompatibile and biodegradabile, and their RNA release properties may be controlled within limits, sonochemical formation of siRNA nanoparticles represent a new promising approach for generation of functional bionano materials.(undefined
O corpo humano e o discurso expositivo em museus universitários de ciências
Os atuais desafios colocados aos museus e centros de ciências visam aproximar a produção do conhecimento científico e a população. Neste contexto, a concepção e o desenvolvimento das exposições científicas e, mais especificamente, os processos de transformação do conhecimento científico para fins educacionais e de divulgação científica necessitam de debate. Este trabalho tem como foco o estudo das exposições de longa duração de três museus universitários brasileiros que abordam o corpo humano. A perspectiva adotada articula os conceitos de transposição didática e museográfica a fim de empreender a análise dos objetos e textos identificados. A partir dos dados obtidos buscou-se compreender os conceitos abordados, as estratégias museográficas assumidas, a relação entre textos e objetos e a possibilidade de interação público-objeto
MOLDING SAND PREPARATION METHOD
FIELD: foundry.SUBSTANCE: method comprises steps of charging granular filler into mixer; at first charging one doze of filler and mixing it with binder till uniform distribution of binder on surface of grains of filler; adding second doze of filler and mixing it till uniform distribution of filler in the whole mass of molding sand. Invention provides shortened time period of distributing binder on surface of filler grains.EFFECT: enhanced strength of molding sand without increased consumption of binder.1 ex.Изобретение относится к литейному производству. Зернистый наполнитель загружают в смеситель по частям. Первую часть смешивают со связующим до равномерного распределения его по поверхности зерен наполнителя. Добавляют вторую часть наполнителя и перемешивают до равномерного распределения наполнителя в общей массе смеси. Снижается время распределения связующего по поверхности зерен наполнителя. Обеспечивается повышение прочности смеси без увеличения расхода связующего
Latent cluster analysis of ALS phenotypes identifies prognostically differing groups
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes.
METHODS
Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method.
RESULTS
The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001).
CONCLUSION
The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research
Wild-type and mutant SOD1 share an aberrant conformation and a common pathogenic pathway in ALS.
Many mutations confer one or more toxic function(s) on copper/zinc superoxide dismutase 1 (SOD1) that impair motor neuron viability and cause familial amyotrophic lateral sclerosis (FALS). Using a conformation-specific antibody that detects misfolded SOD1 (C4F6), we found that oxidized wild-type SOD1 and mutant SOD1 share a conformational epitope that is not present in normal wild-type SOD1. In a subset of human sporadic ALS (SALS) cases, motor neurons in the lumbosacral spinal cord were markedly C4F6 immunoreactive, indicating that an aberrant wild-type SOD1 species was present. Recombinant, oxidized wild-type SOD1 and wild-type SOD1 immunopurified from SALS tissues inhibited kinesin-based fast axonal transport in a manner similar to that of FALS-linked mutant SOD1. Our findings suggest that wild-type SOD1 can be pathogenic in SALS and identify an SOD1-dependent pathogenic mechanism common to FALS and SALS
Benchmark thermochemistry of the C_nH_{2n+2} alkane isomers (n=2--8) and performance of DFT and composite ab initio methods for dispersion-driven isomeric equilibria
The thermochemistry of linear and branched alkanes with up to eight carbons
has been reexamined by means of W4, W3.2lite and W1h theories. `Quasi-W4'
atomization energies have been obtained via isodesmic and hypohomodesmotic
reactions. Our best atomization energies at 0 K (in kcal/mol) are: 1220.04
n-butane, 1497.01 n-pentane, 1774.15 n-hexane, 2051.17 n-heptane, 2328.30
n-octane, 1221.73 isobutane, 1498.27 isopentane, 1501.01 neopentane, 1775.22
isohexane, 1774.61 3-methylpentane, 1775.67 diisopropyl, 1777.27 neohexane,
2052.43 isoheptane, 2054.41 neoheptane, 2330.67 isooctane, and 2330.81
hexamethylethane. Our best estimates for are: -30.00
n-butane, -34.84 n-pentane, -39.84 n-hexane, -44.74 n-heptane, -49.71 n-octane,
-32.01 isobutane, -36.49 isopentane, -39.69 neopentane, -41.42 isohexane,
-40.72 3-methylpentane, -42.08 diisopropyl, -43.77 neohexane, -46.43
isoheptane, -48.84 neoheptane, -53.29 isooctane, and -53.68 hexamethylethane.
These are in excellent agreement (typically better than 1 kJ/mol) with the
experimental heats of formation at 298 K obtained from the CCCBDB and/or NIST
Chemistry WebBook databases. However, at 0 K a large discrepancy between theory
and experiment (1.1 kcal/mol) is observed for only neopentane. This deviation
is mainly due to the erroneous heat content function for neopentane used in
calculating the 0 K CCCBDB value. The thermochemistry of these systems,
especially of the larger alkanes, is an extremely difficult test for density
functional methods. A posteriori corrections for dispersion are essential.
Particularly for the atomization energies, the B2GP-PLYP and B2K-PLYP
double-hybrids, and the PW6B95 hybrid-meta GGA clearly outperform other DFT
functionals.Comment: (J. Phys. Chem. A, in press
In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS
Mutations in the enzyme superoxide dismutase-1 (SOD1) cause hereditary variants
of the fatal motor neuronal disease Amyotrophic lateral sclerosis (ALS).
Pathophysiology of the disease is non-cell-autonomous: neurotoxicity is derived
not only from mutant motor neurons but also from mutant neighbouring
non-neuronal cells. In vivo imaging by two-photon
laser-scanning microscopy was used to compare the role of
microglia/macrophage-related neuroinflammation in the CNS and PNS using
ALS-linked transgenic SOD1G93A mice. These mice contained labeled
projection neurons and labeled microglia/macrophages. In the affected lateral
spinal cord (in contrast to non-affected dorsal columns), different phases of
microglia-mediated inflammation were observed: highly reactive microglial cells
in preclinical stages (in 60-day-old mice the reaction to axonal transection was
∼180% of control) and morphologically transformed microglia that have
lost their function of tissue surveillance and injury-directed response in
clinical stages (reaction to axonal transection was lower than 50% of
control). Furthermore, unlike CNS microglia, macrophages of the PNS lack any
substantial morphological reaction while preclinical degeneration of peripheral
motor axons and neuromuscular junctions was observed. We present in
vivo evidence for a different inflammatory activity of microglia
and macrophages: an aberrant neuroinflammatory response of microglia in the CNS
and an apparently mainly neurodegenerative process in the PNS
Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis
Astrocytes isolated from individuals with amyotrophic lateral sclerosis (ALS) are toxic to motor neurons (MNs) and play a non–cell autonomous role in disease pathogenesis. The mechanisms underlying the susceptibility of MNs to cell death remain unclear. Here we report that astrocytes derived from either mice bearing mutations in genes associated with ALS or human subjects with ALS reduce the expression of major histocompatibility complex class I (MHCI) molecules on MNs; reduced MHCI expression makes these MNs susceptible to astrocyte-induced cell death. Increasing MHCI expression on MNs increases survival and motor performance in a mouse model of ALS and protects MNs against astrocyte toxicity. Overexpression of a single MHCI molecule, HLA-F, protects human MNs from ALS astrocyte–mediated toxicity, whereas knockdown of its receptor, the killer cell immunoglobulin-like receptor KIR3DL2, on human astrocytes results in enhanced MN death. Thus, our data indicate that, in ALS, loss of MHCI expression on MNs renders them more vulnerable to astrocyte-mediated toxicity
Expressão gênica induzida por estresses abióticos em nódulos de feijão-caupi
O objetivo deste trabalho foi avaliar o efeito isolado ou simultâneo dos estresses hídrico e térmico na expressão gênica em nódulos de feijão-caupi. A bactéria Bradyrhizobium japonicum (estirpe BR 3267) foi inoculada em sementes de feijão-caupi da cultivar IPA 206 e, 35 dias após a germinação, as plantas foram submetidas a diferentes regimes de disponibilidade hídrica e a estresse térmico, em casa de vegetação. Para a identificação dos genes diferencialmente expressos, foi utilizada a técnica de cDNA-AFLP, tendo-se isolado 67 fragmentos derivados de transcritos (FDTs) diferencialmente expressos. Após o sequenciamento dos FDTs e das análises de similaridade, com uso do programa Blastx, foram identificados 14 genes diferencialmente expressos envolvidos em diferentes processos metabólicos. O padrão de expressão de seis genes sob estresse abiótico foi confirmado por RT-qPCR, e observou-se indução de genes pertencentes a diferentes categorias funcionais, como biossíntese de ácido abscísico, sinalização celular, transportador de prolina e biossíntese de lipídeos de membranas. A expressão desses genes indica sua participação em processos relacionados à proteção dos nódulos ao estresse abiótico
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