504 research outputs found
Stepwise synthesis via mechanochemical reaction for multistate redox-active 2D Zinc(ii) coordination network
No full textA multistate redox-active coordination network was prepared by stepwise synthesis via mechanochemical reaction to overcome the low solubility of ligands. Solid-state grinding between sparingly soluble ligands and metal ions lead to the formation of a soluble intermediate. A two-dimensional (2D) coordination network possessing open channels and iodinated pores was prepared by using the intermediate. The redox activity of the network, which was derived from ligands, was confirmed by electron spin resonance (ESR) spectroscopy and solid-state cyclic voltammetry. © 2018 The Chemical Society of Japa
A Sporadic Case of Mal de Meleda Caused by Gene Mutation in SLURP-1 in Korea
No full textMal de Meleda (MDM), also known as keratoderma palmoplantaris transgrediens, is a rare inherited form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles, extending to the dorsal aspects of the hands and feet. A 15-year-old Korean female presented with sharply demarcated hyperkeratotic plaques on the palms and soles, which extended to the dorsal surfaces of the hands and feet, in a "glove-and-socks" distribution. The histopathologic study showed marked hyperkeratosis, acanthosis, and normogranulosis, without epidermolysis. Her genetic study detected compound heterozygous mutation in exon 3 of the ARS gene encoding SLURP-1. Family history did not reveal any other affected members and no consanguineous relationship was found. In view of these findings, we diagnosed this case as the first reported sporadic case of MDM in Korea, the farthest location from the endemic island of Meleda. (Ann Dermatol 23(3) 396 similar to 399, 2011
Successful Treatment of Cutaneous Lesions of Dermatomyositis with Topical Pimecrolimus
No full textDermatomyositis (DM) is an idiopathic inflammatory process characterized by proximal muscle weakness and cutaneous lesions, such as the Gottron's sign, heliotrope rash, and erythematous photosensitive. rash. Administration of systemic agents for the treatment of underlying systemic diseases leads to remission of the cutaneous lesions in many cases. However, cutaneous lesions may remain refractory to treatment. Pimecrolimus is a calcineurin inhibitor with combined anti-inflammatory and immunomodulatory activity. It has high affinity to the skin and low permeation potential, even in patients with acute skin inflammation and in those undergoing post-topical corticosteroid therapy. We herein report two DM patients whose cutaneous lesions were refractory to conventional treatment but showed dramatic response to topical pimecrolimus. The clinical outcomes suggest that topical pimecrolimus may be a good therapeutic alternative for the management of the cutaneous lesions of DM. (Ann Dermatol 23(3) 348 similar to 351, 2011
A Case of Hereditary Hemorrhagic Telangiectasia
No full textHereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu disease, is an autosomal dominant disorder of the fibrovascular tissue. It is characterized by the classic triad of mucocutaneous telangiectasias, recurrent hemorrhages, and familial occurrence. The cutaneous manifestation appear clinically as punctuate, linear, or splinter-like telangiectasias of the upper body, oral, and nasal mucous membranes, and nail beds. A 73-year-old woman presented with purpuric, punctuate, and tiny macules on the finger tips of both hands and the tongue. The skin lesions were discovered about 50 years previously. She had a family history of cutaneous telangiectasia. Also, she had episodes of recurrent epistaxis, gastrointestinal bleeding, and anemia. The gastroendoscopy revealed gastric angiodysplasia of the fundus and body of the stomach. The histopathologic study showed dilated capillaries lined by flat endothelial cells in the papillary dermis. From these findings, we diagnosed this case as hereditary hemorrhagic telangiectasia, which has rarely been reported in the dermatologic literature. (Ann Dermatol 21(2) 206 similar to 208, 2009
Single-cell analysis of early antiviral gene expression reveals a determinant of stochastic IFNB1 expression
No full textRIG-I-like receptors (RLRs) are cytoplasmic sensors of viral RNA that trigger the signaling cascade that leads to type I interferon (IFN) production. Transcriptional induction of RLRs by IFN is believed to play the role of positive feedback to further amplify viral sensing. We found that RLRs and several other IFN-stimulated genes (ISGs) are induced early in viral infection independent of IFN. Expression of these early ISGs requires IRF3/IRF7 and is highly correlated amongst them. Simultaneous detection of mRNA of IFNB1, viral replicase, and ISGs revealed distinct populations of IFNB1 expressing and non-expressing cells which are highly correlated with the levels of early ISGs but are uncorrelated with IFN-dependent ISGs and viral gene expression. Individual expression of RLRs made IFNB1 expression more robust and earlier, suggesting a causal relation between levels of RLR and induction of IFN.112Ysciescopu
Computation-aided design of oxygen-ligand-steered single-atom catalysts: Sewing unzipped carbon nanotubes
No full textSingle-atom catalysts (SACs), among which nitrogen-doped graphene-supported SACs are successful models, have been extensively investigated for electrocatalysts. Although oxygen is a common impurity in graphene, metal-oxygen-based SACs are unutilized. Here, we devise a new type of oxygen-coordinated SAC (M-O-C) with a computation-aided approach. Theoretical modeling predicts that the metal atoms are strongly immobilized by carbonyl ligands in unzipped carbon nanotubes, and then the Ni-O-C SAC is synthesized for the oxygen evolution reaction (OER). It shows excellent OER activity with a low overpotential (228/325 mV at 10/100 mA cm−2), small Tafel slope (36 mV per decade), and long-term durability over 150 h. We find that the highly electronegative oxygen ligand deviates from the conventional linear scaling relationship by shifting toward a more reactive region, so the inductive effect of the oxygen ligand leads to superior OER activity. This “theory first followed by experiment” strategy would help in the design of various SACs.
Crystal structure of bet3 reveals a novel mechanism for Golgi localization of tethering factor TRAPP
No full textNRC publication: Ye
Abstract 3606: RBP2 promotes tamoxifen resistance by altering ER function and activating IGF1R and EGFR/HER2 signaling in histone methylation-dependent and -independent manners in breast cancer
No full textAbstract
Retinoblastoma binding protein 2 (RBP2, also known as JARID1A), a member of the JARID1 family of histone H3 lysine K4 demethylases, has been considered to have an oncogenic potential in several types of human cancers including breast cancer. Although physical interaction between RBP2 and estrogen receptor (ER), a crucial factor for hormone-dependent breast cancer, has been implied, the role of RBP2 in ER-positive (ER+) breast cancer remains largely unknown. Here, we demonstrate that RBP2 is a novel therapeutic target for tamoxifen resistance in ER+ breast cancer as an ER co-regulator and an activator of receptor tyrosine kinase (RTK) signaling. In large cohorts of breast cancer patients including METABRIC, high expression of RBP2 was associated with poor response to tamoxifen therapy in ER+ breast cancer. Consistently, RBP2 induced tamoxifen resistance in ER+ breast cancer both in vitro and in vivo. Using RNA-sequencing analysis, we identified that many RBP2 target genes are overlapped with ER-dependent- and tamoxifen resistance-associated genes. Mechanistically, RBP2 induced not only hyperactivation of ER-dependent transcription but also estrogen agonist activity of tamoxifen-bound ER via the interaction with ER, thus increasing the expression of NRIP1, a co-repressor of ER. RBP2 also formed a transcriptional repressive complex with ER, NRIP1, and HDAC1 to induce H3K4 demethylation-mediated epigenetic gene silencing of IGFBP4 and IGFBP5, leading to the activation of IGF1R and its downstream, PI3K/AKT pathway. Furthermore, enhanced AKT phosphorylation by RBP2 was mediated by not only IGF1R but also EGFR/HER2 signaling via increasing the stability of EGFR and HER2 proteins in a demethylase activity-independent manner. We further confirmed that combinational treatment with tamoxifen and PI3K inhibitor BKM120 restored tamoxifen sensitivity in RBP2-overexpressing breast cancer. Taken together, these findings suggest that RBP2 mediates tamoxifen resistance in ER+ breast cancer by altering ER activity and activating IGF1R and EGFR/HER2 signal pathways in both a histone methylation-dependent and -independent manner. Therefore, RBP2 may be a promising prognostic marker and therapeutic target for endocrine therapy-resistant breast cancer.
Citation Format: Hee-Joo Choi, Taekwon Son, Hyung-Yong Kim, Kyueng-Whan Min, Young-Ha Oh, Jeong-Yeon Lee, Gu Kong. RBP2 promotes tamoxifen resistance by altering ER function and activating IGF1R and EGFR/HER2 signaling in histone methylation-dependent and -independent manners in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3606. doi:10.1158/1538-7445.AM2017-3606</jats:p
Analysis of Hover/Hovering Turn of a Complete Helicopter Configuration Using a Coupled Aerodynamics-Flight Dynamics Solver
No full textTrend, not severity, of acute kidney injury affects graft outcome in deceased donor kidney transplantation
No full textDeceased donor kidneys (DDKs) with acute kidney injury (AKI) are difficult to allocate for fear of the expected graft outcome. We aimed to evaluate the impact of donors' AKI severity and trend on graft outcomes in DDK transplantation. This was a retrospective study of DDK transplantation performed from 2005 to 2014. Based on maximum and terminal serum creatinine values before transplantation, the AKI trends were categorized as improving or worsening. Of 413 DDKs, 275 developed AKI: 177 stage 1, 52 stage 2, and 46 stage 3. DDKs with AKI had 212 improving AKI and 63 worsening AKI. Graft outcomes were similar based on AKI stage. Worsening AKI did not affect delayed graft function development; however, it significantly elevated graft failure risk even after adjusting for AKI stage and Kidney Donor Risk Index. Graft survival of the improving group was similar to DDKs with no AKI. This study showed that AKI severity of DDKs did not affect overall graft outcomes. Notably, DDKs with improving AKI showed a similar graft survival rate to DDKs without AKI, although worsening AKI had a worse prognosis. Consideration of the AKI trend, rather than its severity, is needed when DDKs with AKI are allocated.N
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