Kelleherguthrie1241

MicroRNAs and RNA-binding proteins (RBPs) primarily target the 3' UTR of mRNAs to control their translation and stability. However, their co-regulatory effects on specific mRNAs in physiology and disease are yet to be fully explored. CSDE1 is an RBP that promotes metastasis in melanoma and mechanisms underlying its oncogenic activities need to be completely defined. Here we report that CSDE1 interacts with specific miRNA-induced silencing complexes (miRISC) in melanoma. We find an association of CSDE1 with AGO2, the essential component of miRISC, which is facilitated by target mRNAs and depends on the first cold shock domain of CSDE1. Both CSDE1 and AGO2 bind to 3' UTR of PMEPA1. CSDE1 counters AGO2 binding, leading to an increase of PMEPA1 expression. We also identify a miRNA, miR-129-5p, that represses PMEPA1 expression in melanoma. Collectively, our results show that PMEPA1 promotes tumorigenic traits and that CSDE1 along with miR-129-5p/AGO2 miRISC act antagonistically to fine-tune PMEPA1 expression toward the progression of melanoma.Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a poor prognosis for which no effective therapeutic measures are currently available. The present study aimed to investigate whether interactions with endothelial colony-forming cells (ECFCs) promote aggressive progression of TNBC cells. Herein, using an indirect co-culture system, we showed that co-culture increased the invasive and migratory phenotypes of both MDA-MB-231 TNBC cells and ECFCs. Through a cytokine antibody array and RT-PCR analysis, we revealed that co-culture markedly induced secretion of the chemokine C-C motif ligand (CCL)8 from ECFCs and that of interleukin (IL)-8 from MDA-MB-231 cells. CCL8 was crucial for ECFC-induced IL-8 secretion and invasion of MDA-MB-231 cells as well as for MDA-MB-231-enhanced MMP-2 secretion and angiogenesis of ECFCs. We suggest c-Jun as a transcription factor for CCL8-induced IL-8 expression in MDA-MB-231 cells. IL-8 was important for co-culture-induced CCL8 and MMP-2 upregulation and invasion of ECFCs. Notably, our findings reveal a positive feedback loop between CCL8 and IL-8, which contributes to the aggressive phenotypes of both ECFC and TNBC cells. Using an MDA-MB-231 cell-based xenograft model, we show that tumor growth and metastasis are increased by co-injected ECFCs in vivo. Increased expression of IL-8 was observed in tissues with bone metastases in mice injected with conditioned media from co-cultured cells. High IL-8 levels are correlated with poor recurrence-free survival in TNBC patients. Together, these results suggest that CCL8 and IL-8 mediate the crosstalk between ECFCs and TNBC, leading to aggravation of tumorigenicity in TNBC.The electro-mechanical and electro-thermal properties of high-performance Restacked-Rod-Process (RRP) Nb3Sn wires are key factors in the realization of compact magnets above 15 T for the future particle physics experiments. Combining X-ray micro-tomography with unsupervised machine learning algorithm, we provide a new tool capable to study the internal features of RRP wires and unlock different approaches to enhance their performances. Such tool is ideal to characterize the distribution and morphology of the voids that are generated during the heat treatment necessary to form the Nb3Sn superconducting phase. Two different types of voids can be detected in this type of wires one inside the copper matrix and the other inside the Nb3Sn sub-elements. The former type can be related to Sn leaking from sub-elements to the copper matrix which leads to poor electro-thermal stability of the whole wire. The second type is detrimental for the electro-mechanical performance of the wires as superconducting wires experience large electromagnetic stresses in high field and high current conditions. We analyze these aspects thoroughly and discuss the potential of the X-ray tomography analysis tool to help modeling and predicting electro-mechanical and electro-thermal behavior of RRP wires and optimize their design.This work studies the evolution in time of several varieties of apples with application in quality storage maintenance. Two different methods were used to evaluate long-stored apples for better sorting and degradation assessment. The first method was laser photoacoustic spectroscopy for the detection of ethylene and ethanol compounds from the internal atmosphere of apples. The second method was multispectral imaging that measures the image and the spectrum combined and also can be used to address features such as ripening and external defects. The experiments showed that, the ethylene value decreases and the value of ethanol increases, which sometimes we may associate with a drift of the images toward darker tones, because the apple is slowly degrading. Non-invasive, real-time inspection can reveal when the degradation process begins, improving the capability of sorting, maintaining their quality and storability.An important role that the leading-edge cross-section shape plays in the wing flight performance is well known in aeronautics. However, little is known about the shape of the leading-edge cross section of an insect's wing and its contribution to remarkable qualities of insect flight. In this paper, we reveal, in the first time, the shape of the leading-edge cross section of a cicada's wing and analyze its variability along the wing. We also identify and quantify similarities in characteristic dimensions of this shape in the wings of three different cicada species.In the design of a microstrip power divider, there are some important factors, including harmonic suppression, insertion loss, and size reduction, which affect the quality of the final product. Thus improving each of these factors contributes to a more efficient design. In this respect, a hybrid technique to reduce the size and improve the performance of a Wilkinson power divider (WPD) is introduced in this paper. The proposed method includes a typical series LC circuit, a miniaturizing inductor, and two transmission lines, which make an LC branch. Accordingly, two quarter-wavelength branches of the conventional WPD are replaced by two proposed LC branches. Not only does this modification lead to a 100% size reduction, an infinite number of harmonics suppression, and high-frequency selectivity theoretically, but it also results in a noticeable performance improvement practically compared to using quarter-wavelength branches in the conventional microstrip power dividers. The main important contributions of this technique are extreme size reduction and harmonic suppression for the implementation of a filtering power divider (FPD). Furthermore, by tuning the LC circuit, the arbitrary numbers of unwanted harmonics are blocked while the operating frequency, the stopband bandwidth, and the operating bandwidth are chosen optionally. The experimental result verifies the theoretical and simulated results of the proposed technique and demonstrates its potential for improving the performance and reducing the size of other similar microstrip components.The aim of this study was to compare secondary loss of reduction outcomes in dual plating fixation and dual plating combined with compression bolt fixation for bicondylar tibial plateau fractures (TPFs). We performed a retrospective study from January 2015 to April 2019. A consecutive series of 72 bicondylar TPFs underwent surgical treatment and was divided into two groups group 1 (dual plating, n = 46) and group 2 (dual plating combined with compression bolts, n = 26). The outcomes collected included demographic characteristics, imaging characteristics, intraoperative indicators, clinical outcomes and reduction quality after surgery. Functional outcome was rated according to the Hospital for Special Surgery (HSS) score and Lysholm score. The secondary loss of reduction rate in group 2 was reduced compared with that in group 1 (P = 0.025), and the mean HSS score of group 2 was higher than that of group 1 (P = 0.013). The rate of complications was 30.4% (14/46) in group 1 and 30.8% (8/26) in group 2 (P = 0.976). Compared with single dual plating fixation, dual plating combined with compressing bolt fixation reduced the secondary loss of reduction rate for patients with bicondylar TPFs and showed better functional outcomes.Molecular methods detect genetic mutations associated with drug resistance. This study detected resistance-conferring mutations in gyrA/gyrB for fluoroquinolones and rrs/eis genes for second-line injectable drugs (SLIDs) among multidrug-resistant Mycobacterium tuberculosis (MDR-TB) isolates in Kuwait. Fifty pansusceptible M. tuberculosis and 102 MDR-TB strains were tested. Phenotypic susceptibility testing was performed by MGIT 960 system using SIRE drug kit. GenoType MTBDRsl version 1 (gMTBDRslv1) and GenoType MTBDRsl version 2 (gMTBDRslv2) tests were used for mutation detection. Results were validated by PCR-sequencing of respective genes. Fingerprinting was performed by spoligotyping. No mutations were detected in pansusceptible isolates. gMTBDRslv1 detected gyrA mutations in 12 and rrs mutations in 8 MDR-TB isolates. gMTBDRsl2 additionally detected gyrB mutations in 2 and eis mutation in 1 isolate. Mutations in both gyrA/gyrB and rrs/eis were not detected. gMTBDRslv1 also detected ethambutol resistance-conferring embB mutations in 59 isolates. Although XDR-TB was not detected, frequency of resistance-conferring mutations for fluoroquinolones or SLIDs was significantly higher among isolates collected during 2013-2019 versus 2006-2012. https://www.selleckchem.com/products/relacorilant.html Application of both tests is warranted for proper management of MDR-TB patients in Kuwait as gMTBDRslv2 detected resistance to fluoroquinolones and/or SLIDs in 3 additional isolates while gMTBDRslv1 additionally detected resistance to ethambutol in 58% of MDR-TB isolates.Helicobacter pylori causes a wide range of human diseases including cancer. Carcinogenic foodborne trematodes Opisthorchis viverrini, Clonorchis sinensis, and O. felineus might promote transmission and spread of H. pylori infection in the definitive mammalian host, which in turn might contribute to the liver fluke-associated malignancy. Our objectives were to find out whether liver flukes O. felineus, O. viverrini, and C. sinensis are carriers of Helicobacter pylori and to determine whether H. pylori is present in feces, bile, and stomach samples from the experimentally infected hamsters. We found that liver flukes are not reservoirs of H. pylori. Nevertheless, the prevalence of H. pylori and the H. pylori ureA gene copy number were significantly elevated after the infection. Overall, although the liver flukes O. felineus, C. sinensis, and O. viverrini are not reservoirs of H. pylori, the infection with the liver flukes significantly modifies the biliary and gut microbiota by increasing H. pylori abundance. This may be a feature of any liver fluke pathogenesis that have not previously been taken into account. Our findings appear to be novel in terms of comparative assessment of the host microbiota and Helicobacter abundance during epidemiologically important liver fluke infections.Recent studies have reported numerous predictors for adverse outcomes in COVID-19 disease. However, there have been few simple clinical risk scores available for prompt risk stratification. The objective is to develop a simple risk score for predicting severe COVID-19 disease using territory-wide data based on simple clinical and laboratory variables. Consecutive patients admitted to Hong Kong's public hospitals between 1 January and 22 August 2020 and diagnosed with COVID-19, as confirmed by RT-PCR, were included. The primary outcome was composite intensive care unit admission, need for intubation or death with follow-up until 8 September 2020. An external independent cohort from Wuhan was used for model validation. COVID-19 testing was performed in 237,493 patients and 4442 patients (median age 44.8 years old, 95% confidence interval (CI) [28.9, 60.8]); 50% males) were tested positive. Of these, 209 patients (4.8%) met the primary outcome. A risk score including the following components was derived from Cox regression gender, age, diabetes mellitus, hypertension, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, stroke, dementia, liver diseases, gastrointestinal bleeding, cancer, increases in neutrophil count, potassium, urea, creatinine, aspartate transaminase, alanine transaminase, bilirubin, D-dimer, high sensitive troponin-I, lactate dehydrogenase, activated partial thromboplastin time, prothrombin time, and C-reactive protein, as well as decreases in lymphocyte count, platelet, hematocrit, albumin, sodium, low-density lipoprotein, high-density lipoprotein, cholesterol, glucose, and base excess.