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61.
Vernalization is the process by which sensing a prolonged exposure to winter cold leads to competence to flower in the spring. In winter annual Arabidopsis thaliana accessions, flowering is suppressed in the fall by expression of the potent floral repressor FLOWERING LOCUS C (FLC). Vernalization promotes flowering via epigenetic repression of FLC. Repression is accompanied by a series of histone modifications of FLC chromatin that include dimethylation of histone H3 at Lys9 (H3K9) and Lys27 (H3K27). Here, we report that A. thaliana LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) is necessary to maintain the epigenetically repressed state of FLC upon return to warm conditions typical of spring. LHP1 is enriched at FLC chromatin after prolonged exposure to cold, and LHP1 activity is needed to maintain the increased levels of H3K9 dimethylation at FLC chromatin that are characteristic of the vernalized state.  相似文献   
62.
Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of neuronal death in PD is largely unknown, but several genetic loci, including PTEN-induced putative kinase 1 (PINK1), have been linked to early onset autosomal recessive forms of familial PD. PINK1 encodes a serine/threonine kinase, which phosphorylates several substrates and consequently leads to cell protection against apoptosis induced by various stresses. In addition, research has shown that inflammation largely contributes to the pathogenesis of PD, but the functional link between PINK1 and PD-linked neuroinflammation remains poorly understood. Therefore, in the present study, we investigated the functional role of PINK1 in interleukin (IL)-1β-mediated inflammatory signaling. We show that PINK1 specifically binds to TRAF6 and TAK1, and facilitates the autodimerization and autoubiquitination of TRAF6. PINK1 also enhances the association between TRAF6 and TAK1, phosphorylates TAK1, and stimulates polyubiquitination of TAK1. Furthermore, PINK1 leads to the potentiation of IL-1β-mediated NF-κB activity and cytokine production. These findings suggest that PINK1 positively regulates two key molecules, TRAF6 and TAK1, in the IL-1β-mediated signaling pathway, consequently up-regulating their downstream inflammatory events.  相似文献   
63.
Chen Q  Bae SC  Granick S 《Nature》2011,469(7330):381-384
A challenging goal in materials chemistry and physics is spontaneously to form intended superstructures from designed building blocks. In fields such as crystal engineering and the design of porous materials, this typically involves building blocks of organic molecules, sometimes operating together with metallic ions or clusters. The translation of such ideas to nanoparticles and colloidal-sized building blocks would potentially open doors to new materials and new properties, but the pathways to achieve this goal are still undetermined. Here we show how colloidal spheres can be induced to self-assemble into a complex predetermined colloidal crystal-in this case a colloidal kagome lattice-through decoration of their surfaces with a simple pattern of hydrophobic domains. The building blocks are simple micrometre-sized spheres with interactions (electrostatic repulsion in the middle, hydrophobic attraction at the poles, which we call 'triblock Janus') that are also simple, but the self-assembly of the spheres into an open kagome structure contrasts with previously known close-packed periodic arrangements of spheres. This open network is of interest for several theoretical reasons. With a view to possible enhanced functionality, the resulting lattice structure possesses two families of pores, one that is hydrophobic on the rims of the pores and another that is hydrophilic. This strategy of 'convergent' self-assembly from easily fabricated colloidal building blocks encodes the target supracolloidal architecture, not in localized attractive spots but instead in large redundantly attractive regions, and can be extended to form other supracolloidal networks.  相似文献   
64.
Protein toxicity can be defined as all the pathological changes that ensue from accumulation, mis-localization, and/or multimerization of disease-specific proteins. Most neurodegenerative diseases manifest protein toxicity as one of their key pathogenic mechanisms, the details of which remain unclear. By systematically deconstructing the nature of toxic proteins, we aim to elucidate and illuminate some of the key mechanisms of protein toxicity from which therapeutic insights may be drawn. In this review, we focus specifically on protein toxicity from the point of view of various cellular compartments such as the nucleus and the mitochondria. We also discuss the cell-to-cell propagation of toxic disease proteins that complicates the mechanistic understanding of the disease progression as well as the spatiotemporal point at which to therapeutically intervene. Finally, we discuss selective neuronal vulnerability, which still remains largely enigmatic.  相似文献   
65.
66.
Potent inhibitors of human peptide deformylase (HsPDF) were screened using known PMT analog inhibi- tors of bacterial peptide deformylase. Forty-three species of PMT analogs that are non-peptidyl bacterial PDF inhibitors like actinonin were selected using virtual screening GOLD. Ten species out of 43 that could bind to HsPDF were selected and their antitumor activities were tested. Among them, four species (PMT-172, PMT-173, PMT-199, and PMT-201) showed excellent growth inhibition of cancer cell in the MTT assay. HsPDF-PMT binding was confirmed through a 1H-CPMG-T2 filter NMR experiment leading to a significant change in peak intensity for PMT-172 and PMT-199. These results suggest that PMT analogs could possibly interact with HsPDF and be a novel anticancer drug candidate.  相似文献   
67.
Ti_(45)Cu_(40)Ni_7Zr_5Sn_(2.5)Si_(0.5) alloys were prepared under various cooling rate conditions during solidification.The alloys exhibited different volume fractions of B2 particles with 0~40 vol%in an amorphous matrix.Monolithic bulk metallic glass of 1 mm diameter showed no macroscopic plasticity and exhibited the typical vein patterns in a maximum shear stress plane on the fracture surface.However,a bulk metallic glass composite containing the B2 particles revealed obvious plasticity(~5.6%)with a remarkable work-hardening behavior that resulted from a stress-induced martensitic transformation of the B2 particles.Moreover,the composite displayed the complicated fracture morphologies containing of three types of fracture features.Through detailed investigations on the microstructural evolution,mechanical,deformation and fracture characteristics,the influence of B2 particle on overall behavior of the TiCu-based bulk metallic glass composites was elucidated.  相似文献   
68.
The oxidation behavior of three high-strength FeCrAl alloys was investigated in supercritical carbon dioxide environment at 650 ℃. After exposure for 500 h, the weight gains of the FeCrAl alloys gradually decreased with increasing Al content. The oxide scales are primarily composed of α-Al_2O_3 and spinel oxides. With increasing Al content, the amount of α-Al_2O_3 increases and the C content decreased in the oxide scale and sub-scale matrix.Moreover, larger(Nb,Mo)C carbides formed in the sub-scale matrix and their number decreased with the increase of Al content.  相似文献   
69.
本文给出了多元Pade′逼近的三项恒等式以及基于这些恒等式的一个递推算法。  相似文献   
70.
We developed a hybrid scaffold and a bioreactor for cartilage regeneration. The hybrid scaffold was developed as combination of two components: a biodegradable framework and hydrogel-containing chondrocytes. We performed the MTT cell proliferation assay to compare the proliferation and viability of chondrocytes on three types of scaffolds: an aiginate gel, the hybrid scaffold, and an alginate sponge. Cells were encapsulated in 2% agarose gel. The bioreactor consisted of a circulation system and a compression system. We performed dynamic cell culture on these agarose gels in the bioreactor for 3 days.  相似文献   
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