421 research outputs found

    Identification of a novel ubiquitin binding site of STAM1 VHS domain by NMR spectroscopy

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    AbstractInteraction between the signal-transducing adapter molecule 1 (STAM1) Vps27/Hrs/Stam (VHS) domain and ubiquitin was investigated by nuclear magnetic resonance (NMR) spectroscopy. NMR evidence showed that the structure of STAM1 VHS domain resembles that of other VHS domains, especially the homologous domain of STAM2. We found that the VHS domain binds to ubiquitin via its hydrophobic patch consisting of N-terminus of helix 2 and C-terminus of helix 4 in which Trp26 on helix 2 plays a pivotal role in the binding. The binding between VHS and ubiquitin seems to be very similar to that between ubiquitin associated domain (UBA) and ubiquitin, however, the direction of α-helices involved in the ubiquitin binding is opposite. Here, we propose a novel ubiquitin binding site and the manner of ubiquitin recognition of the STAM1 VHS domain.Structured summaryMINT-6804185:STAM1 (uniprotkb:Q92783) binds (MI:0407) to ubiquitin (uniprotkb:P62988) by nuclear magnetic resonance (MI:0077

    Selection of internal reference genes for SYBR green qRT-PCR studies of rhesus monkey (Macaca mulatta) tissues

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    <p>Abstract</p> <p>Background</p> <p>The rhesus monkey (<it>Macaca mulatta</it>) is a valuable and widely used model animal for biomedical research. However, quantitative analyses of rhesus gene expression profiles under diverse experimental conditions are limited by a shortage of suitable internal controls for the normalization of mRNA levels. In this study, we used a systematic approach for the selection of potential reference genes in the rhesus monkey and compared their suitability to that of the corresponding genes in humans.</p> <p>Results</p> <p>Eight housekeeping genes (HKGs) (<it>GAPDH, SDHA, ACTB, RPL13A, RPL32, UBA52, PGK1Y</it>, and <it>YWHAZ</it>) from rhesus monkeys and humans were selected to test for normalization of expression levels in six different tissue types (brain, colon, kidney, liver, lung, and stomach). Their stability and suitability as reference genes were validated by <it>geNorm</it>, <it>NormFinder </it>and <it>BestKeeper </it>programs. Intriguingly, <it>RPL13A </it>and <it>RPL32 </it>were selected as ideal reference genes only in rhesus monkeys.</p> <p>Conclusion</p> <p>The results clearly indicated the necessity of using different reference genes for normalization of expression levels between rhesus monkeys and humans in various tissues.</p

    Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society

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    There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody–drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer. Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan–Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups. HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49–0.93; P = 0.019). These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer

    A Survey of Korean Physicians’ Prescription Patterns for Allergic Rhinitis

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    Objectives The aim of this study was to compare the prescription patterns according to characteristics of physicians using a survey distributed amongst physicians in Korea. Methods We surveyed the prescription patterns for allergic rhinitis (AR) of the members of the Korean Academy of Asthma, Allergy and Clinical Immunology (KAAACI) and the Korean Association of Otorhinolaryngologists (KAO). Questionnaire contained 4 categories with 28 queries. 448 physicians including 98 internal medicine (IM), 113 pediatrics (PED), and 237 otorhinolaryngology (ENT) were responded. Results Although the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines are most frequently used in all specialties, seasonal or perennial AR is the most frequent classification system. For the definitive diagnosis of AR, ENT physicians reported using multiple allergen simultaneous test (MAST)/radio allergy sorbent test (RAST) more than others (IM, 10.9%; PED, 20.6%; ENT, 44.2%; P<0.001). In treatment, most physicians reported that antihistamine medication is the initial treatment for AR. PED physicians prescribed fewer intranasal steroid to combinations with an antihistamine than other specialists (IM, 65.3%; PED, 42.5%; ENT, 63.3%), but preferred leukotriene antagonists (IM, 4.1%; PED, 23.0%; ENT, 3.9%; P=0.041). Overall, 53% (235/448) of the physicians performed allergen immunotherapy (AIT), and IM administers the most AIT (IM, 71.6%; PED, 42.0%; ENT, 39.5%; P=0.019). Furthermore, university and general hospital physicians prescribed more AIT than doctors at other hospital types (university hospital, 76.4%; general hospital, 64.3%; local hospital, 21.4%; private clinic, 20.2%; P<0.001). Conclusion The prescription patterns for AR were different according to the physicians’ characteristics and general rate of prescribing AIT is just about 53% in Korea. Thus, the development of complementary Korean-specific guidelines is needed and proper clinical instruction of AIT would be necessary
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