LncRNA LINC00662 Exerts a good Oncogenic Relation to Osteosarcoma through the miR165pITPR1 Axis

BACKGROUND Despite well-described sex differences in asthma incidence, there remains uncertainty about the role of female sex hormones in the development of asthma. OBJECTIVE We sought to investigate whether hormonal contraceptive use, its subtypes, and duration of use were associated with new-onset asthma in reproductive-age women. METHODS Using the Optimum Patient Care Research Database, a UK national primary care database, we constructed an open cohort of 16- to 45-year-old women (N = 564,896) followed for up to 17 years (ie, January 1, 2000, to December 31, 2016). We fitted multilevel Cox regression models to analyze the data. RESULTS At baseline, 26% of women were using any hormonal contraceptives. During follow-up (3,597,146 person-years), 25,288 women developed asthma, an incidence rate of 7.0 (95% CI, 6.9-7.1) per 1000 person-years. Compared with nonuse, previous use of any hormonal contraceptives (hazard ratio [HR], 0.70; 95% CI, 0.68-0.72), combined (HR, 0.70; 95% CI, 0.68-0.72), and progestogen-only therapy (HR, 0.70; 95% CI, 0.67-0.74) was associated with reduced risk of new-onset asthma. For current use, the estimates were as follows any (HR, 0.63; 95% CI, 0.61-0.65), combined (HR, 0.65; 95% CI, 0.62-0.67), and progestogen-only therapy (HR, 0.59; 95% CI, 0.56-0.62). Longer duration of use (1-2 years HR, 0.83; 95% CI, 0.81-0.86; 3-4 years HR, 0.64; 95% CI, 0.61-0.67; 5+ years HR, 0.46; 95% CI, 0.44-0.49) was associated with a lower risk of asthma onset than nonuse. CONCLUSIONS Hormonal contraceptive use was associated with reduced risk of new-onset asthma in women of reproductive age. Mechanistic investigations to uncover the biological processes for these observations are required. Clinical trials investigating the safety and effectiveness of hormonal contraceptives for primary prevention of asthma will be helpful to confirm these results. Stress is a commonly reported precipitant of overeating. Understanding the relationship between stress and food intake is important, particularly in view of the increasing prevalence of obesity. The purpose of this review is to examine how stress-related eating has been defined and measured in the literature to date. There are no established diagnostic criteria or gold standards for quantification of stress-related eating. Questionnaires relying on the accuracy of self-report are the mainstay of identifying people who tend to eat in response to stress and emotions. There is a paucity of clinical research linking objective measurements of stress and appetite with self-reported eating behaviour. Limitations of the methodological approaches used and the heterogeneity between studies leave significant knowledge gaps in our understanding of the mechanism of stress related eating, and how best to identify it. These issues are discussed, and areas for further research are explored. The traditional focus of physiological and functional genomic research is on molecular processes that play out within a single multicellular organism. In the colonial (eusocial) insects such as ants, bees, and termites, molecular and behavioral responses of interacting nestmates are tightly linked, and key physiological processes are regulated at the scale of the colony. Such colony-level physiological processes regulate nestmate physiology in a distributed fashion, through various social communication mechanisms. As a result of physiological decentralization over evolutionary time, organismal mechanisms, for example related to pheromone detection, hormone signaling, and neural signaling pathways, are deployed in novel contexts to influence nestmate and colony traits. Here we explore how functional genomic, physiological, and behavioral studies can benefit from considering the traits of eusocial insects in this light. We highlight functional genomic work exploring how nestmate-level and colony-level traits arise and are influenced by interactions among physiologically-specialized nestmates of various developmental stages. We also consider similarities and differences between nestmate-level (organismal) and colony-level (superorganismal) physiological processes, and make specific hypotheses regarding the physiology of eusocial taxa. Integrating theoretical models of distributed systems with empirical functional genomics approaches will be useful in addressing fundamental questions related to the evolution of eusociality and collective behavior in natural systems. Etomoxir CPT inhibitor Recent insights have implicated mesothelial-to-mesenchymal transition (MMT) as a mechanism by which mesothelial cells can transdifferentiate into cancer-associated fibroblasts (CAFs) in several cancers metastasizing to the peritoneum. However, this was not evaluated extensively in colorectal cancer. We examined the presumed mesothelial origin of CAFs in three types of colorectal carcinoma conventional type adenocarcinoma, mucinous carcinoma and signet ring cell carcinoma. We evaluated the expression of mesothelial, mesenchymal, angiogenesis and colorectal cancer-related markers in peritoneal samples of twelve colorectal cancer patients with peritoneal carcinomatosis and four control patients by immunohistochemistry. We observed morphological and immunohistochemical changes in the vicinity of tumor implants in all studied colorectal cancer types. Mesothelial cells acquired a spindle-shaped myofibroblast-like morphology, lost expression of mesothelial markers, and gained expression of mesenchymal markers. Analysis of consecutive tissue sections and double staining for mesothelial and mesenchymal markers revealed overlap in expression of mesothelial and CAF markers. These findings are highly suggestive of a mesothelial origin of CAFs in peritoneal carcinomatosis in colorectal cancer. Interfering with the process of MMT might be a valuable approach in treating and preventing peritoneal carcinomatosis. Differences observed between colorectal cancer types suggest that one single strategy might not be applicable. A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of Muscovy duck reovirus (MDRV) RNA in clinical samples is described. The assay is based on TaqMan-MGB technology, consisting of two primers and one probe labeled with the reporter dye 6-carboxyfluorescein that binds selectively to the sigma B-protein gene of MDRV. This technique also includes an Internal Positive Control (IPC). The real-time RT-PCR assay was able to detect MDRVs, whereas other common waterfowl-origin viral pathogens were not recognised by the established oligonucleotide set, thus showing that the test was specific for MDRV. The sensitivity of the assay was 2.83 × 101 copies/μL and was 100 times higher than that of the conventional RT-PCR. The variation coefficients of intra-assay and inter-assay were less than 1.5% which verified sufficient repeatability of this assay. The use of β-actin mRNA as an IPC in order not to reduce the efficiency of the assay was adopted. The detection for 100 clinical samples showed that the positive rate of the established TaqMan-MGB real-time RT-PCR method was 87% (87/100), while the positive rate of the conventional RT-PCR was 83% (83/100), with the coincidence rate was 97.14%. Sensitivity and positive rate for clinical samples of TaqMan fluorescent quantitative RT-PCR were higher than conventional RT-PCR. The high specificity, sensitivity, and rapidity TaqMan-MGB real-time RT-PCR assay with the use of IPC to monitor for false negative results can make this method suitable for the pathogenic surveillance and epidemiological investigation of MDRV infection. BACKGROUND Determination of proton uptake pathways in Cytochrome c Oxidase is difficult due to the complexity of the system. The transition networks approach allows sampling of proton transfer pathways without predefined reaction coordinate. METHODS Computation of the proton transfer pathways in a model of the D-channel of cytochrome c oxidase has been performed by a transition network approach that combines discrete, optimisation based and molecular dynamics based sampling. RESULTS The optimal pathway involves an opening of the so-called asparagine gate, hydration of the asparagine region, the formation of a hydrogen-bonded chain, and finally concerted proton hole transport along this chain. The optimal pathway finds the protonation of residue H26 close to the channel entrance favourable for lowering the transition energies of subsequent steps, in particular, opening of the Asn gate and formation of a hydrogen-bonded chain. Residue Y33 plays an important role in shuttling the transferred proton hole. CONCLUSIONS The optimal pathway found by the transition network approach shows the same important characteristics as pathways determined earlier by other methods. The computed barrier and reaction energies are also in good agreement with previous studies. The transition network approach provides an alternative to explore pathways in complex systems. GENERAL SIGNIFICANCE The correct function of the enzyme as oxidase and proton pump depends on the interplay of several redox and proton transport steps. Understanding the proton transport mechanism is therefore key to understanding the protein's function. The complex nature of long- distances proton transfer through a protein requires a non-trivial simulation strategy. BACKGROUND Sorcin is a calcium sensor that exerts many calcium-related functions in the cells, e.g. it regulates calcium concentration in the cytoplasm, endoplasmic reticulum (ER) and mitochondria, by interacting with calcium pumps, exchangers and channels. Albeit Sorcin is an interesting potential cancer target, little is known about its interactors upon calcium-mediated activation. Our previous study suggested that Sorcin may recognize short linear binding motifs as the crystal structure revealed a self-interaction with a GYYPGG stretch in its N-terminus, and combinatorial peptide-phage display provided support for peptide-mediated interactions. METHODS In this study we screened for motif-based interactions between Sorcin and intrinsically disordered regions of the human proteome using proteomic peptide phage display (ProP-PD). We identified a peptide belonging to protein phosphatase 1 regulatory subunit 3G (PPP1R3G) as a potential novel interactor and confirm the interaction through biophysical and cell-based approaches, and provide structural information through molecular dynamics simulations. RESULTS Altogether, we identify a preferred motif in the enriched pool of binders and a peptide belonging to protein phosphatase 1 regulatory subunit 3G (PPP1R3G) as a preferred ligand. CONCLUSION Through this study we gain information on a new Sorcin binding partner and profile Sorcin's motif-based interaction. GENERAL SIGNIFICANCE The interaction between Sorcin and PPP1R3G may suggest a close dependence between glucose homeostasis and calcium concentration in the different cell compartments, opening a completely new and interesting scenery yet to be fully disclosed. V.OBJECTIVE Personal statements are a requirement of general surgery residency applications. Yet, their role in an applicant's final rank within a program remains unclear. This study explores the language used in personal statements to differentiate applicants in the general surgery residency ranking process. DESIGN A textual analysis of general surgery residency applicant personal statements was performed. Using inductive coding and grounded theory, 3 main themes from personal statements were identified my story, my future, my goals. These themes were utilized to build a dictionary consisting of over 400 descriptive terms in multiple categories. Data was extracted using the Linguistics Inquiry and Word Count program, which can linguistically determine basic characteristics from text. The data was stratified according to final rank and gender for analysis, using correlation and descriptive statistics. SETTING Large, urban, academic general surgery residency program. PARTICIPANTS One hundred nineteen personal statements during the 2018 to 2019 application cycle were analyzed.