The draft genome of the pear (Pyrus bretschneideri) using a combination of BAC-by-BAC and next-generation sequencing is reported. A 512.0-Mb sequence corresponding to 97.1% of the estimated genome size of this highly heterozygous species is assembled with 1943 coverage. High-density genetic maps comprising 2005 SNP markers anchored 75.5% of the sequence to all 17 chromosomes. The pear genome encodes 42,812 protein-coding genes, and of these,~28.5% encode multiple isoforms. Repetitive sequences of 271.9 Mb in length, accounting for 53.1% of the pear genome, are identified. Simulation of eudicots to the ancestor of Rosaceae has reconstructed nine ancestral chromosomes. Pear and apple diverged from each other~5.4-21.5 million years ago, and a recent whole-genome duplication (WGD) event must have occurred 30-45 MYA prior to their divergence, but following divergence from strawberry. When compared with the apple genome sequence, size differences between the apple and pear genomes are confirmed mainly due to the presence of repetitive sequences predominantly contributed by transposable elements (TEs), while genic regions are similar in both species. Genes critical for self-incompatibility, lignified stone cells (a unique feature of pear fruit), sorbitol metabolism, and volatile compounds of fruit have also been identified. Multiple candidate SFB genes appear as tandem repeats in the S-locus region of pear; while lignin synthesis-related gene family expansion and highly expressed gene families of HCT, C39H, and CCOMT contribute to high accumulation of both G-lignin and S-lignin. Moreover, alpha-linolenic acid metabolism is a key pathway for aroma in pear fruit.

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Several populations of memory T cells have been described that differ in their migration and function. Here, we have identified a unique subset of memory T cells, which we have named recirculating memory T cells (TRCM). By exposing Kaede transgenic mouse skin to violet light, we tracked the fate of cutaneous T cells. One population of memory CD4+ T cells remained in the skiñA second population migrated from the skin into draining lymph nodes (LNs) in a CCR7-dependent manner. These migrating CD4+ T cells expressed a novel cell surface phenotype (CCR7int/+ CD62Lint CD69− CD103+/− E-selectin ligands+), distinct from memory T cell subsets described to date. Unlike memory T cell subsets that remain resident within tissues long-term, or that migrate either exclusively between lymphoid tissues or into peripheral nonlymphoid sites, CD4+ TRCM migrate from the skin into draining LNs. From the draining LN, they reenter into the circulation, distal LNs and sites of non-specific cutaneous inflammation. Additionally, CD4+ TRCM up-regulated CD40L and secreted IL-2 following polyclonal stimulation. Together, our results identify a novel subset of recirculating memory CD4+ T cells equipped to deliver help to both distal lymphoid and cutaneous tissues.

[tBu 4 PcIn] 2 O are almost identical despite the difference in their saturation energy densities.In summary, spectroscopic data and excited relaxation data of the In-and Ga-Pcs employed in the present study do not show aggregation phenomena to reduce the effective nonlinear absorption. [8,13] The optical limiting in these compounds is very effective compared to other phthalocyanines [18] exhibiting a range of saturation densities and absorption cross-section ratios. Axial substitution of the p-TMP functional group at the central gallium and indium in 1 and 3 results in a reduction of the saturation energy density by a factor in excess of 3. This method of tailoring the saturation of the optical limiters will prove to be very useful in the construction of passive organic optical limiters where multiple layers of effective absorbers with decreasing saturation may be desirable. ExperimentalThe synthesis and structural characterization of compounds 1±5 have been previously reported [9,11,12]. All solvents used were purified, dried and distilled under dry nitrogen. UV-vis spectra were recorded in Shimadzu UV-365. Fluorescence spectra and lifetimes were measured by a single-photon counting method using an argon ion laser, a pumped Ti:sapphire laser (Spectra-Physics, Tsunami 3960, FWHM 150 fs) with a pulse selector (Spectra-Physics, 3980), a second harmonic generator (Spectra-Physics, GWU-23PS), and a streakscope (Hamamatsu Photonics, C4334-01). Each sample was excited in toluene with 410 nm laser light.The open aperture of a Z-scan experiment [16] was used to measure the optical limiting response in the samples. All experiments described in this study were performed using 6 ns 532 nm laser light pulses from a Q switched frequency doubled Nd:YAG laser with a pulse repetition rate of 10 Hz. The beam was spatially filtered to remove the higher order modes and tightly focused using a 9 cm focal length lens. All samples were measured in quartz cells with a 1 mm optical path length, and at concentrations of 0.5 g L ±1 (~10 ±4 M) in toluene. There is growing interest in attempts to combine biomaterials and inorganic nanoparticles and investigating their properties. One of the research motivations for this combination is to take advantage of the well-defined structures and special properties of biomolecules and their supermolecular structures to organize the nanoparticles into predefined, topologically intricate nanostructures or to synthesize miscellaneous materials for potential applications in electronic, optical, and chemical devices.[1] Several kinds of biomaterials have been

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic technique that can induce the regression of targeted lesions via generating excess cytotoxic reactive oxygen species. However, due to the limited penetration depth of visible excitation light and the intrinsic hypoxia microenvironment of solid tumors, the efficacy of PDT in the treatment of cancer, especially deep-seated or large tumors, is unsatisfactory. Herein, we developed an efficient in vivo PDT system based on a nanomaterial, dihydrolipoic acid coated gold nanocluster (AuNC@DHLA), that combined the advantages of large penetration depth in tissue, extremely high two-photon (TP) absorption cross section (σ 2 ∼ 10 6 GM), efficient ROS generation, a type I photochemical mechanism, and negligible in vivo toxicity. With AuNC@DHLA as the photosensitizer, highly efficient in vivo TP-PDT has been achieved.

No abstract

A major hallmark of prion diseases is the cerebral amyloid accumulation of the pathogenic PrP(Sc), an abnormally misfolded, protease-resistant, and beta-sheet rich protein. PrP106-126 is the key domain responsible for the conformational conversion and aggregation of PrP. It shares important physicochemical characteristics with PrP(Sc) and presents similar neurotoxicity as PrP(Sc). By combination of fluorescence polarization, dye release assay and in situ time-lapse atomic force microscopy (AFM), we investigated the PrP106-126 amide interacting with the large unilamellar vesicles (LUVs) and the supported lipid bilayers (SLBs). The results suggest that the interactions involve a poration-mediated process: firstly, the peptide binding results in the formation of pores in the membranes, which penetrate only half of the membranes; subsequently, PrP106-126 amide undergoes the poration-mediated diffusion in the SLBs, represented by the formation and expansion of the flat high-rise domains (FHDs). The possible mechanisms of the interactions between PrP106-126 amide and lipid membranes are proposed based on our observations.

SUMMARY MDM2 and XIAP are mutually regulated: Binding of MDM2 RING protein to the IRES region on XIAP mRNA results in MDM2 protein stabilization and enhanced XIAP translation. In this study, we developed a protein-RNA fluorescence polarization (FP) assay for high-throughput screening (HTS) of chemical libraries. Our FP-HTS identified eight inhibitors that blocked the MDM2 protein-XIAP RNA interaction, leading to MDM2 degradation. The compound-induced MDM2 downregulation resulted not only in inhibition of XIAP expression, but also in activation of p53, which contributed to cancer cell apoptosis in vitro and inhibition of cancer cell proliferation in vivo. Importantly, one of the MDM2/XIAP inhibitors, MX69, showed minimal inhibitory effect on normal human hematopoiesis in vitro and was very well tolerated in animal models.