86,517 research outputs found
Microtubule and microtubule associated protein anomalies in psychiatric disease
No full textAnomalies in neuronal cell architecture, in particular dendritic complexity and synaptic density changes, are widely observed in the brains of subjects with schizophrenia or mood disorders. The concept that a disturbed microtubule cytoskeleton underlies these abnormalities and disrupts synaptic connectivity is supported by evidence from clinical studies and animal models. Prominent changes in tubulin expression levels are commonly found in disease specific regions such as the hippocampus and prefrontal cortex of psychiatric patients. Genetic linkage studies associate tubulin-binding proteins such as the dihydropyrimidinase family with an increased risk to develop schizophrenia and bipolar disorder. For many years, altered immunoreactivity of microtubule associated protein-2 has been a hallmark found in the brains of individuals with schizophrenia. In this review, we present a growing body of evidence that connects a dysfunctional microtubule cytoskeleton with neuropsychiatric illnesses. Findings from animal models are discussed together with clinical data with a particular focus on tubulin post-translational modifications and on microtubule-binding proteins
JNK regulation of depression and anxiety
No full textDepression and anxiety are the most common mood disorders affecting 300 million sufferers worldwide. Maladaptive changes in the neuroendocrine stress response is cited as the most common underlying cause, though how the circuits underlying this response are controlled at the molecular level, remains largely unknown. Approximately 40% of patients do not respond to current treatments, indicating that untapped mechanisms exist. Here we review recent evidence implicating JNK in the control of anxiety and depressive-like behavior with a particular focus on its action in immature granule cells of the hippocampal neurogenic niche and the potential for therapeutic targeting for affective disorders
Author response
No full textRas-ERK signalling in the brain plays a central role in drug addiction. However, to date, no clinically relevant inhibitor of this cascade has been tested in experimental models of addiction, a necessary step toward clinical trials. We designed two new cell-penetrating peptides - RB1 and RB3 - that penetrate the brain and, in the micromolar range, inhibit phosphorylation of ERK, histone H3 and S6 ribosomal protein in striatal slices. Furthermore, a screening of small therapeutics currently in clinical trials for cancer therapy revealed PD325901 as a brain-penetrating drug that blocks ERK signalling in the nanomolar range. All three compounds have an inhibitory effect on cocaine-induced ERK activation and reward in mice. In particular, PD325901 persistently blocks cocaine-induced place preference and accelerates extinction following cocaine self- administration. Thus, clinically relevant, systemically administered drugs that attenuate Ras-ERK signalling in the brain may be valuable tools for the treatment of cocaine addiction
Detection of platelet-activating factor in gingival tissue surrounding failed dental implants
No full textVariations on the Author
No full text“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
[Newspaper Clipping: Author Claims Evidence of Second JFK Assassin #1]
No full textNewspaper article titled "Author Claims Evidence of Second JFK Assassin." The article states that author Richard J. Whalen concluded "that there is circumstantial evidence to support the theory of a second assassin in the shooting of President John F. Kennedy.
Also By The Same Author: AKTiveAuthor, a Citation Graph Approach to Name Disambiguation
No full textThe desire for definitive data and the semantic web drive for inference over heterogeneous data sources requires co-reference resolution to be performed on those data. In particular, name disambiguation is required to allow accurate publication lists, citation counts and impact measures to be determined. This paper describes a graph-based approach to author disambiguation on large-scale citation networks. Using self-citation, co-authorship and document source analyses, AKTiveAuthor clusters papers, achieving precision of 0.997 and recall of 0.818 over a test group of eight surname clusters
John F. Kennedy telegram to Roosevelt
No full textJersey Homesteads (later the Borough of Roosevelt) was established in the 1930s as an agro-industrial cooperative community. It was established specifically for urban Jewish garment workers, many of whom had emigrated from Europe. President John F. Kennedy sent a telegram to the citizens of Roosevelt, New Jersey, apologizing for not being able to attend the memorial dedication in honor of former President Franklin Delano Roosevelt. (Jersey Homesteads became Roosevelt in 1945 in honor of the president.) President Kennedy expressed his gratitude to the people of Roosevelt for constructing the memorial, and commented that it will serve as a constant reminder of Roosevelt's good works
Logarithmic variance profiles and the corresponding f-1 spectra of temperature fluctuations in turbulent Rayleigh-Bénard convection
No full textWe report experimental results for the temperature variance 2(z) and the corresponding frequency spectra P(f) in turbulent Rayleigh-Bénard convection (RBC) in a cylindrical sample of aspect ratioT= D/L = 1:00 (D = 1:12 m is the diameter and L = 1:12 m the height). The measurements were conducted in the Rayleigh-number range 1011 < Ra < 1:35 1014 and Pr ' 0:8. For Ra = 1:35x1014, 2(z) could be described well by a logarithmic dependence on the vertical position z in a range of z 1 < z < z 2 with z 1 ' 70 and z 2 = 0:1L. Here L=(2Nu) is the thickness of a thin thermal sublayer adjacent to the horizontal plate where the heat flux (denoted by the Nusselt number Nu) is carried mostly by thermal diffusion. In the log layer, we found that the temperature spectra had a significant frequency range over which P(f) f with close to 1. As Ra decreased, increased so that the log layer became thinner. At Ra = 2:05 1011, z 2 < z 1 and therefore there was no range for a log layer. Correspondingly, the temperature spectrum near the horizontal plate did not have the f1 scaling form either
Maine author Franklin F. Gould recalls his first glimpse of the outside world
No full textMaine author Franklin F. Gould recalls his first glimpse of the outside world as he relates how, as a young farm boy in the late 1800\u27s, he drove his father\u27s horses on an errand to an icebound river
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