Activity

The functional characterization and regulation of this second pyruvate uptake system provides valuable information for understanding the complexity of pyruvate sensing and uptake in E. coli.The present overview describes the evolution of new microdosimeters developed in the National Microelectronics Center in Spain (IMB-CNM, CSIC), ranging from the first ultra-thin 3D diodes (U3DTHINs) to the advanced 3D cylindrical microdetectors, which have been developed over the last 10 years. In this work, we summarize the design, main manufacture processes, and electrical characterization of these devices. These sensors were specifically customized for use in particle therapy and overcame some of the technological challenges in this domain, namely the low noise capability, well-defined sensitive volume, high spatial resolution, and pile-up robustness. Likewise, both architectures reduce the loss of charge carriers due to trapping effects, the charge collection time, and the voltage required for full depletion compared to planar silicon detectors. In particular, a 3D‒cylindrical architecture with electrodes inserted into the silicon bulk and with a very well‒delimited sensitive volume (SV) mimicked a cell aand steeper dopant profiles. We also summarize the successive microdosimetric characterizations performed with both devices in proton and carbon beamlines.Previous studies have clarified that many patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) have burdensome symptom profiles and accordingly impaired functioning and quality of life (QoL). In Denmark, all MPN patients are affiliated with public hospitals and because of a healthcare system financed by taxpayers these patients do not have any financial costs related to the hematological disease. Diagnoses are recorded for all patients in hospitals, and diagnosis codes are communicated to the National Patient Register (NPR). Owing to this, it was possible to contribute to the elucidation of Philadelphia-negative MPN patients’ health-related quality of life (HRQoL), by conducting a nationwide, population-based, cross-sectional HRQoL survey of these patients with cost-free access to the best available, suitable medical treatment. The survey contained validated questionnaires covering functioning, symptom burden, symptom profile, QoL, and additional questions on lifestyle. Information on comorbid diagnoses was obtained from the NPR. The participants’ HRQoL was compared to the general population. Moreover, differences in HRQoL across essential thrombocythemia, polycythemia vera, myelofibrosis, and unclassifiable MPN participants were investigated, adjusted for age, sex, comorbidity, and lifestyle. To the best of our knowledge this is the first survey of HRQoL in patients with unclassifiable MPN. A total of 2228 Philadelphia-negative MPN patients participated. The participants reported their HRQoL to be inferior to the general population, but the difference was minor. The differences in HRQoL across groups of participants with different MPN subtypes were subtle. Fatigue and sexual problems were prevalent and burdensome. Overall, participants reported a slightly healthier lifestyle compared to the general population.Hepatocellular carcinoma (HCC) is one of the common malignancies leading to death. Although radiotherapy and chemotherapy have certain effects, their side effects limit their therapeutic effect. Phytochemicals have recently been given more attention as promising resources for cancer chemoprevention or chemotherapy due to their safety. In this study, the effects of grape seed proanthocyanidins (GSPs) on the apoptosis, cell cycle, and mitogen-activated protein kinase (MAPK) pathway-related proteins and non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) expression of HepG2 cells were investigated. The results showed that GSPs inhibited the viability of HepG2 cells in a time- and dose-dependent manner, induced apoptosis and G2/M phase cell cycle arrest, and regulated cell cycle-related proteins, cyclin B1, cyclin-dependent kinase 1, and p21. GSPs also increased reactive oxygen species production and caspase-3 activity. In addition, GSPs also increased the expression of p-ERK, p-JNK, p-p38 MAPK and NAG-1, and GSPs-induced NAG-1 expression was related to the MAPK pathway-related proteins. These data suggest that GSPs may be promising phytochemicals for HCC chemoprevention or chemotherapy.Subcutaneous masses smaller than 5 cm can be malignant, in contrast with the international guidelines. Ultrasound (US) and magnetic resonance imaging (MRI) are useful to distinguish a potentially malignant mass from the numerous benign soft tissue (ST) lesions. Contrast-enhanced ultrasound (CEUS) was applied in ST tumors, without distinguishing the subcutaneous from the deep lesions. We evaluated CEUS and MRI accuracy in comparison to histology in differentiating malignant from nonmalignant superficial ST masses, 50% smaller than 5 cm. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) with their 95% confidence intervals (CI) were calculated. selleck products Of malignant cases, 44.4% measured ≤5 cm. At univariate analysis, no statistically significant differences emerged between benign and malignant tumors in relation with clinical characteristics, except for relationship with the deep fascia (p = 0.048). MRI accuracy sensitivity 52.8% (CI 37.0, 68.0), specificity 74.1% (CI 55.3, 86.8), PPV 73.1% (CI 53.9, 86.3), and NPV 54.1% (CI 38.4, 69.0). CEUS accuracy sensitivity 75% (CI 58.9, 86.3), specificity 37% (CI 21.5, 55.8), PPV 61.4% (CI 46.6, 74.3), and NPV 52.6% (CI 31.7, 72.7). CEUS showed a sensitivity higher than MRI, whereas PPV and NPV were comparable. Also, masses measuring less than 5 cm can be malignant and referral criteria for centralization could be revised.B-cell precursor acute lymphoblastic leukaemia (B-ALL) is a malignancy of lymphoid progenitor cells with altered genes including the Janus kinase (JAK) gene family. Among them, tyrosine kinase 2 (TYK2) is involved in signal transduction of cytokines such as interferon (IFN) α/β through IFN-α/β receptor alpha chain (IFNAR1). To search for disease-associated TYK2 variants, bone marrow samples from 62 B-ALL patients at diagnosis were analysed by next-generation sequencing. TYK2 variants were found in 16 patients (25.8%) one patient had a novel mutation at the four-point-one, ezrin, radixin, moesin (FERM) domain (S431G) and two patients had the rare variants rs150601734 or rs55882956 (R425H or R832W). To functionally characterise them, they were generated by direct mutagenesis, cloned in expression vectors, and transfected in TYK2-deficient cells. Under high-IFNα doses, the three variants were competent to phosphorylate STAT1/2. While R425H and R832W induced STAT1/2-target genes measured by qPCR, S431G behaved as the kinase-dead form of the protein.