Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) promotes glioma cell invasion through induction of NF-κB-inducing kinase (NIK) and noncanonical NF-κB signaling

BACKGROUND: High-grade gliomas are one of the most invasive and therapy-resistant cancers. We have recently shown that noncanonical NF-κB/RelB signaling is a potent driver of tumorigenesis and invasion in the aggressive, mesenchymal subtype of glioma. However, the relevant signals that induce activation of noncanonical NF-κB signaling in glioma and its function relative to the canonical NF-κB pathway remain elusive. METHODS: The ability of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) to regulate NF-κB signaling and promote tumor progression was investigated in both established and primary high-grade glioma tumor lines using a three-dimensional (3-D) collagen invasion assay. The roles of specific NF-κB proteins in regulating glioma cell invasion and expression of Matrix Metalloproteinase 9 (MMP9) in response to TWEAK were evaluated using shRNA-mediated loss-of-function studies. The ability of NF-κB-inducing kinase (NIK) to promote glioma growth in vivo was investigated using an orthotopic xenograft mouse model. RESULTS: In glioma cells that display elevated noncanonical NF-κB signaling, loss of RelB attenuates invasion without affecting RelA expression or phosphorylation and RelB is sufficient to promote invasion in the absence of RelA. The cytokine TWEAK preferentially activates the noncanonical NF-κB pathway through induction of p100 processing to p52 and nuclear accumulation of both RelB and p52 without activating the canonical NF-κB pathway. Moreover, TWEAK, but not TNFα, significantly increases NIK mRNA levels. TWEAK also promotes noncanonical NFκB-dependent MMP9 expression and glioma cell invasion. Finally, expression of NIK is sufficient to increase gliomagenesis in vivo. CONCLUSIONS: Our data establish a key role for NIK and noncanonical NF-κB in mediating TWEAK-induced, MMP-dependent glioma cell invasion. The findings also demonstrate that TWEAK induces noncanonical NF-κB signaling and signal-specific regulation of NIK mRNA expression. Together, these studies reveal the important role of noncanonical NF-κB signaling in regulating glioma invasiveness and highlight the therapeutic potential of targeting activation of NIK in this deadly disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-014-0273-1) contains supplementary material, which is available to authorized users

Outbreaks of mumps: an observational study over two decades in a single hospital in Korea

PurposeThe introduction of the mumps vaccine has dramatically reduced the number of mumps cases, but outbreaks have recently occurred among highly vaccinated populations in developed countries. Epidemiological and clinical characteristics of patients with mumps admitted between 1989 and 2012 in a single hospital in Korea are described in the present study.MethodsWe retrospectively evaluated inpatients with mumps between 1989 and 2012 and outpatients and inpatients with mumps in 2011-2012.ResultsA total of 152 patients with mumps were admitted between 1989 and 2012, and 163 patients were recorded in 2011-2012. The highest number of admitted cases occurred in 1998 and 2012 (35 and 34 cases, respectively). Among the patients admitted in 2011-2012, the highest frequency was observed among people aged 15-19 years, and low frequency was observed in those aged 20 years, compatible to the city data and national data. In patients admitted to our department in 1998 (35 cases) and in 2010-2012 (27 cases), there were significant differences in the mean age and the rate of secondary measles-mumps-rubella (MMR) vaccination, but had similar clinical features, including complications, except aseptic meningitis. Antimumps immunoglobulin (Ig) G was positive in 83% and 100%, and IgM was positive in 67% and 41%, respectively, in the two periods.ConclusionIn Korea, recent mumps outbreaks have occurred mainly among secondary school students who received two doses of the MMR vaccine. The vaccinees might have a modified immune reaction to viral insults, manifesting modified epidemiological and clinical features

Smart sensor systems for wearable electronic devices

Wearable human interaction devices are technologies with various applications for improving human comfort, convenience and security and for monitoring health conditions. Healthcare monitoring includes caring for the welfare of every person, which includes early diagnosis of diseases, real-time monitoring of the effects of treatment, therapy, and the general monitoring of the conditions of people's health. As a result, wearable electronic devices are receiving greater attention because of their facile interaction with the human body, such as monitoring heart rate, wrist pulse, motion, blood pressure, intraocular pressure, and other health-related conditions. In this paper, various smart sensors and wireless systems are reviewed, the current state of research related to such systems is reported, and their detection mechanisms are compared. Our focus was limited to wearable and attachable sensors. Section 1 presents the various smart sensors. In Section 2, we describe multiplexed sensors that can monitor several physiological signals simultaneously. Section 3 provides a discussion about short-range wireless systems including bluetooth, near field communication (NFC), and resonance antenna systems for wearable electronic devices

GWAS analysis reveals the genetic basis of blast resistance associated with heading date in rice

Rice blast is a destructive fungal disease affecting rice plants at various growth stages, significantly threatening global yield stability. Development of resistant rice cultivars stands as a practical means of disease control. Generally, association mapping with a diversity panel powerfully identifies new alleles controlling trait of interest. On the other hand, utilization of a breeding panel has its advantage that can be directly applied in a breeding program. In this study, we conducted a genome-wide association study (GWAS) for blast resistance using 296 commercial rice cultivars with low population structure but large phenotypic diversity. We attempt to answer the genetic basis behind rice blast resistance among early maturing cultivars by subdividing the population based on its Heading date 1 (Hd1) functionality. Subpopulation-specific GWAS using the mixed linear model (MLM) based on blast nursery screening conducted in three years revealed a total of 26 significant signals, including three nucleotide-binding site leucine-rich repeat (NBS-LRR) genes (Os06g0286500, Os06g0286700, and Os06g0287500) located at Piz locus on chromosome 6, and one at the Pi-ta locus (Os12g0281300) on chromosome 12. Haplotype analysis revealed blast resistance associated with Piz locus was exclusively specific to Type 14 hd1 among japonica rice. Our findings provide valuable insights for breeding blast resistant rice and highlight the applicability of our elite cultivar panel to detect superior alleles associated with important agronomic traits

The impact of the new ESTRO-ACROP target volume delineation guidelines for postmastectomy radiotherapy after implant-based breast reconstruction on breast complications

The European Society for Radiotherapy and Oncology–Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) updated a new target volume delineation guideline for postmastectomy radiotherapy (PMRT) after implant-based reconstruction. This study aimed to evaluate the impact on breast complications with the new guideline compared to the conventional guidelines. In total, 308 patients who underwent PMRT after tissue expander or permanent implant insertion from 2016 to 2021 were included; 184 received PMRT by the new ESTRO-ACROP target delineation (ESTRO-T), and 124 by conventional target delineation (CONV-T). The endpoints were major breast complications (infection, necrosis, dehiscence, capsular contracture, animation deformity, and rupture) requiring re-operation or re-hospitalization and any grade ≥2 breast complications. With a median follow-up of 36.4 months, the cumulative incidence rates of major breast complications at 1, 2, and 3 years were 6.6%, 10.3%, and 12.6% in the ESTRO-T group, and 9.7%, 15.4%, and 16.3% in the CONV-T group; it did not show a significant difference between the groups (p = 0.56). In multivariable analyses, target delineation is not associated with the major complications (sHR = 0.87; p = 0.77). There was no significant difference in any breast complications (3-year incidence, 18.9% vs. 23.3%, respectively; p = 0.56). Symptomatic RT-induced pneumonitis was developed in six (3.2%) and three (2.4%) patients, respectively. One local recurrence occurred in the ESTRO-T group, which was within the ESTRO-target volume. The new ESTRO-ACROP target volume guideline did not demonstrate significant differences in major or any breast complications, although it showed a tendency of reduced complication risks. As the dosimetric benefits of normal organs and comparable oncologic outcomes have been reported, further analyses with long-term follow-up are necessary to evaluate whether it could be connected to better clinical outcomes

VPS35 haploinsufficiency increases Alzheimer’s disease neuropathology

The retromer complex component VPS35 prevents activation of the BACE1 and Aβ production and thus plays an essential role in limiting Alzheimer’s disease neuropathology

Laser ablation MC-ICPMS U-Th and U-Th-Pb dating of Quaternary zircons from Jeju Island, Korea

Abstract Background Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) emerged in the mid-1980s and rapidly became a crucial dating tool. The advent of femtosecond LA systems has substantially reduced volatility-dependent mass fractionation. This study showcases U-Th and U-Th-Pb dating results of Quaternary zircons collected from Jeju Island, Korea, utilizing an advanced femtosecond laser-connected multi-collector (MC)-ICPMS. Findings Zircon grains from trachyte samples near the Baeknokdam lake (JJ616-1), Yeongsil (JJ08-1), Chunwangsa (JJ09-1), and Oraidong (JJ09-3) provided weighted mean 238U-230Th ages of 28.7 ± 1.6 ka (n = 56/64, MSWD = 3.8), 81.8 ± 10.9 ka (n = 11/12, MSWD = 1.6), 92.6 ± 4.6 ka (n = 49/51, MSWD = 2.2), and 117.6 ± 8.2 ka (n = 48/50, MSWD = 3.2), respectively. The age determination for JJ08-1 zircon aligned well with the recommended value (82 ± 6 ka). Zircons from Sanbangsan (JJ615-1) and Wonmansa (JJ08-2) trachytes yielded common Pb and radioactive disequilibrium-corrected weighted mean 238U-206Pb ages of 785 ± 5 ka (n = 27/28, MSWD = 0.90) and 743 ± 8 ka (n = 28/30, MSWD = 0.79), respectively. The weighted mean 238U-206Pb ages of Penglai and 61.308 reference zircons were determined to be 4226 ± 21 ka (n = 22/25, MSWD = 3.8) and 2488 ± 20 ka (n = 19/20, MSWD = 1.8), respectively. These ages are concordant with the recommended values. Conclusions Our data provides additional evidence of trachyte magmatism occurring in Jeju Island during the transitional period between the Early and Middle Pleistocene and the Late Pleistocene. The zircon samples analyzed in this study could serve as reference age data for Quaternary geochronology research

The Role of Periostin in Capsule Formation on Silicone Implants

Although silicone implants are widely used in breast and other reconstructive surgeries, the limited biocompatibility of these materials leads to severe complications, including capsular contracture. Here, we aimed to clarify the relationship between periostin and the process of capsule formation after in vivo implantation. Seven-week-old wild-type (WT) C57BL/6 mice and periostin-deficient mice were used. Round silicone implants were inserted into a subcutaneous pocket on the dorsum of the mice. After 8 weeks, the fibrous capsule around the implant was harvested and histologically examined to estimate capsular thickness and the number of inflammatory cells. Additionally, immunohistochemical analysis (periostin, α-SMA, and collagen type I) and western blotting (CTGF, TGF-β, VEGF, and MPO) were performed for a more detailed analysis of capsule formation. The capsules in periostin-knockout mice (PN-KO) were significantly thinner than those in WT mice. PN-KO mice showed significantly lower numbers of inflammatory cells than WT mice. Fibrous tissue formation markers (α-SMA, periostin, collagen type I, and CTGF) were significantly reduced in PN-KO mice. We also confirmed that inflammatory reaction and angiogenesis indicators (TGF-β, MPO, and VEGF) had lower expression in PN-KO mice. Inhibition of periostin could be important for suppressing capsule formation on silicone implants after in vivo implantation