The crystal structure of the transcription factor IIB (TFIIB)/TATA box-binding protein (TBP)/TATA-element ternary complex is described at 2.7 A resolution. Core TFIIB resembles cyclin A, and recognizes the preformed TBP-DNA complex through protein-protein and protein-DNA interactions. The amino-terminal domain of core TFIIB forms the downstream surface of the ternary complex, where it could fix the transcription start site. The remaining surfaces of TBP and the TFIIB can interact with TBP-associated factors, other class II initiation factors, and transcriptional activators and coactivators.
ultivated peanut or groundnut (A. hypogaea L.) is among the most important oil and food legumes, grown on 25 million ha between latitudes 40° N and 40° S with annual production of ~46 million tons (http://www.fao.org/faostat/en/#home). It presumably was domesticated in South America ~6,000 years ago and then was widely distributed in post-Columbian times 1. Combining richness in seed oil (~46-58%) and protein (~22-32%), peanut is important in fighting malnutrition and ensuring food security.
Altered estrogen signaling may play a role in induction of HCC by arsenic exposure in utero. Specifically, overexpression of ER-alpha, potentially through promoter region hypomethylation, in livers of such mice may be linked to the hepatocarcinogenicity of arsenic.
BackgroundTemporal lobe epilepsy (TLE) is often characterized pathologically by severe neuronal loss in the hippocampus. Understanding the mechanisms of neuron death is key to preventing the neurodegeneration associated with TLE. However, the involvement of neuronal loss to the epileptogenic process has yet to be fully determined. Recent studies have shown that the activation of NLRP1 can generate a functional caspase-1-containing inflammasome in vivo to drive the proinflammatory programmed cell death termed ‘pyroptosis’, which has a key role in the pathogenesis of neurological disorders. To the best of our knowledge, there are no reported studies that performed detailed identification and validation of NLRP1 inflammasome during the epileptogenic process.MethodsWe first compared expression of NLRP1 and caspase-1 in resected hippocampus from patients with intractable mesial temporal lobe epilepsy (mTLE) with that of matched control samples. To further examine whether the activation of NLRP1 inflammasome contributes to neuronal pyroptosis, we employed a nonviral strategy to knock down the expression of NLRP1 and caspase-1 in the amygdala kindling-induced rat model. Proinflammatory cytokines levels and hippocampal neuronal loss were evaluated after 6 weeks of treatment in these NLRP1 or caspase-1 deficiency TLE rats.ResultsWestern blotting detected upregulated NLRP1 levels and active caspase-1 in mTLE patients in comparison to those levels seen in the controls, suggesting a role for this inflammasome in mTLE. Moreover, we employed direct in vivo infusion of nonviral small interfering RNA to knockdown NLRP1 or caspase-1 in the amygdala kindling-induced rat model, and discovered that these NLRP1 or caspase-1 silencing rats resulted in significantly reduced neuronal pyroptosis.ConclusionsOur data suggest that NLRP1/caspase-1 signaling participates in the seizure-induced degenerative process in humans and in the animal model of TLE and points to the silencing of NLRP1 inflammasome as a promising strategy for TLE therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0233-0) contains supplementary material, which is available to authorized users.
The dielectric, ferroelectric, and electric field-induced strain response of (1-x)(Na 0.5 Bi 0.5 )TiO 3 -xBaTiO 3 (NBT-BT) (0.04 e x e 0.10) ceramics has been systematically investigated as a function of temperature. It is found that ferroelectric and antiferroelectric (AFE)-like behavior can coexist at temperatures significantly lower than the depolarization temperature T d (even down to as low as ambient temperature). Electron microscopy suggests that such behavior results from the electric field-dependence of fine scale octahedral tilt twinning disorder and the associated disorder in the local (ferroic) off-center displacements of the Na/Bi/Ba and Ti ions. The existence of the AFE-like behavior significantly enhances the electric field-induced strain. High bipolar strain of 0.40% and unipolar strain of 0.27% has thereby been achieved at ambient temperature in an NBT-BT, x = 0.07, ceramic. The bipolar and unipolar strains reach almost identical maximum values when the temperature is close to T d . Giant unipolar strains of 0.42%, 0.41%, and 0.29% were observed in NBT-BT ceramics with x = 0.06, 0.07, and 0.08 at temperatures close to their T d 's of 100°C, 50°C, and 87°C, respectively. This work thus provides new insight into ways to further optimize lead-free NBT-BT piezoelectric ceramics for practical use in different temperature ranges.
Nearly one-third of elderly nursing home residents with dementia received antipsychotic medications, mainly atypical agents. Predisposing, enabling and need factors influenced the use of atypical agents in dementia patients. These findings suggest a need to optimize use of atypical antipsychotics in elderly dementia patients in nursing homes in the light of recent efficacy and safety data.
A surrogate end point is often used to evaluate the effects of treatments or exposures on the true end point in medical researches. Various criteria for the statistical surrogate, principal surrogate and strong surrogate have been proposed. We first illustrate that, with a surrogate end point that is defined by these criteria, it is possible that a treatment has a positive effect on the surrogate, which in turn has a positive effect on the true end point, but the treatment has a negative effect on the true end point. We define such a phenomenon as a surrogate paradox. The surrogate paradox also means that the sign of the treatment effect on the true end point is unpredictable by the effect signs of both the treatment on the surrogate and the surrogate on the true end point. Then we propose two notions for a consistent surrogate and a strictly consistent surrogate to avoid the surrogate paradox. With the causal network that was presented by Lauritzen, we discuss the conditions for a strong surrogate to be a consistent surrogate and a strictly consistent surrogate. Copyright 2007 Royal Statistical Society.
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