LncRNA LINC01857 drives pancreatic adenocarcinoma progression via modulating miR-19a-3p/SMOC2

Objectives: Emerging evidence has demonstrated that LINC01857 exerts a pivotal function in many cancers. However, its function in Pancreatic Ductal Adenocarcinoma (PDAC) still remains unclear. This study was designed to investigate the regulatory character of LINC01857 in PDAC. Methods: Bioinformatic tools and databases were used to seek potential miRNAs and mRNAs. Gene expression was evaluated by Reverse Transcription quantitative real-time Polymerase Chain Reaction (RT-qPCR), and western blot was used for protein level detection. A subcellular fraction assay was done to ascertain the location of LINC01857 in PANC-1 and BxPC-3 human pancreatic cancer cells. CCK-8, EdU, wound healing and Transwell assays were performed to inquire into the influence of LINC01857, and SPARC -related Modular Calcium-binding protein-2 (SMOC2) on cell viability, proliferation, migration, and invasion, respectively. The interaction between LINC01857 and its downstream genes was explored by RNA immunoprecipitation and luciferase reporter assays. Results: LINC01857 levels were significantly elevated in PDAC. Knockdown of LINC01857 significantly restrained the proliferation, migration, invasion, and Epithelial-Mesenchymal Transition (EMT) process of PDAC cells. MiR-19a-3p was a downstream target of LINC01857, and miR-19a-3p levels were significantly decreased in PDAC cells. In addition, SMOC2 expression had a negative correlation with that of miR-19a-3p, and SMOC2 was a downstream target of miR-19a-3p. Furthermore, SMOC2 upregulation partially abolished the inhibitive influence of LINC01857 downregulation on cell proliferation, migration, invasion, and the EMT process. Conclusion: LINC01857 promotes malignant phenotypes of PDAC cells via upregulation of SMOC2 by interacting with miR-19a-3p

Accuracies of field CO2–H2O data from open-path eddy-covariance flux systems: assessment based on atmospheric physics and biological environment

Ecosystem CO2–H2O data measured by infrared gas analyzers in open-path eddy-covariance (OPEC) systems have numerous applications, such as estimations of CO2 and H2O fluxes in the atmospheric boundary layer. To assess the applicability of the data for these estimations, data uncertainties from analyzer measurements are needed. The uncertainties are sourced from the analyzers in zero drift, gain drift, cross-sensitivity, and precision variability. These four uncertainty sources are individually specified for analyzer performance, but so far no methodology exists yet to combine these individual sources into a composite uncertainty for the specification of an overall accuracy, which is ultimately needed. Using the methodology for closed-path eddy-covariance systems, this overall accuracy for OPEC systems is determined from all individual uncertainties via an accuracy model and further formulated into CO2 and H2O accuracy equations. Based on atmospheric physics and the biological environment, for EC150 infrared CO2–H2O analyzers, these equations are used to evaluate CO2 accuracy (±1.22 mgCO2 m−3, relatively ±0.19 %) and H2O accuracy (±0.10 gH2O m−3, relatively ±0.18 % in saturated air at 35 ∘C and 101.325 kPa). Both accuracies are applied to conceptual models addressing their roles in uncertainty analyses for CO2 and H2O fluxes. For the high-frequency air temperature derived from H2O density along with sonic temperature and atmospheric pressure, the role of H2O accuracy in its uncertainty is similarly addressed. Among the four uncertainty sources, cross-sensitivity and precision variability are minor, although unavoidable, uncertainties, whereas zero drift and gain drift are major uncertainties but are minimizable via corresponding zero and span procedures during field maintenance. The accuracy equations provide rationales to assess and guide the procedures. For the atmospheric background CO2 concentration, CO2 zero and CO2 span procedures can narrow the CO2 accuracy range by 40 %, from ±1.22 to ±0.72 mgCO2 m−3. In hot and humid weather, H2O gain drift potentially adds more to the H2O measurement uncertainty, which requires more attention. If H2O zero and H2O span procedures can be performed practically from 5 to 35 ∘C, the H2O accuracy can be improved by at least 30 %: from ±0.10 to ±0.07 gH2O m−3. Under freezing conditions, the H2O span procedure is impractical but can be neglected because of its trivial contributions to the overall uncertainty. However, the zero procedure for H2O, along with CO2, is imperative as an operational and efficient option under these conditions to minimize H2O measurement uncertainty.</p

Air temperature equation derived from sonic temperature and water vapor mixing ratio for air flow sampled through closed-path eddy-covariance flux systems

Air temperar (T) plays a fundamental role in many aspects of the flux exchanges between the atmosphere and ecosystems. Additionally, it is critical to know where (in relation to other essential measurements) and at what frequency T must be measured to accurately describe such exchanges. In closed-path eddy-covariance (CPEC) flux systems, T can be computed from the sonic temperature (Ts) and water vapor mixing ratio that are measured by the fast-response senosrs of three-dimensional sonic anemometer and infrared gas analyzer, respectively. T then is computed by use of either T = Ts( 1+0.51 q), where q is specific humidity, or T = Ts( 1 + 0.32e∕ P) − 1 , where e is water vapor pressure and P is atmospheric pressure. Converting q and e/P into the same water vapor mixing ratio analytically reveals the difference between these two equations. This difference in a CPEC system could reach ±0.18 K, bringing an uncertainty into the accuracy of T from both equations and raises the question of which equation is better. To clarify the uncertainty and to answer this question, the derivation of T equations in terms of Ts and H2O-related variables is thoroughly studied. The two equations above were developed with approximations. Therefore, neither of their accuracies were evaluated, nor was the question answered. Based on the first principles, this study derives the T equation in terms of Ts and water vapor molar mixing ratio (c H2O) without any assumption and approximation. Thus, this equation itself does not have any error and the accuracy in T from this equation (equation-computed T) depends solely on the measurement accuracies of Ts and c H2O . Based on current specifications for Ts and c H2O in the CPEC300 series and given their maximized measurement uncertainties, the accuracy in equation-computed T is specified within ±1.01 K. This accuracy uncertainty is propagated mainly (±1.00K) from the uncertainty in Ts measurements and little (±0.03K) from the uncertainty in c H2O measurements. Apparently, the improvement on measurement technologies particularly for Ts would be a key to narrow this accuracy range. Under normal sensor and weather conditions, the specified accuracy is overestimated and actual accuracy is better. Equation-computed T has frequency response equivalent to high-frequency Ts and is insensitive to solar contamination during measurements. As synchronized at a temporal scale of measurement frequency and matched at a spatial scale of measurement volume with all aerodynamic and thermodynamic variables, this T has its advanced merits in boundary-layer meteorology and applied meteorology

Based on Atmospheric Physics and Ecological Principle to Assess the Accuracies of Field CO2 /H2O Measurements From Infrared Gas Analyzers in Closed-Path Eddy-Covariance Systems

Field CO2 /H2O measurements from infrared gas analyzers in closed-path eddy-covariance systems have wide applications in earth sciences. Knowledge about exactness of these measurements is required to assess measurement applicability. Although the analyzers are specified with uncertainty components (zero drift, gain drift, cross-sensitivities, and precision), exactness for individual measurements is unavailable due to an absence of methodology to comprehend the components as an overall uncertainty. Adopting an advanced definition of accuracy as a range of all measurement uncertainty sources, the specified components are composited into a model formulated for studying analyzers’ CO2 /H2O accuracy equations. Based on atmospheric physics and environmental parameters, the analyzers are evaluated using the equations for CO2 accuracy (±0.78 µmolCO2 mol−1, relatively ±0.18%) and H2O accuracy (±0.15 mmolH2 O mol−1). Evaluation shows that precision and cross-sensitivity are minor uncertainties while zero and gain drifts are major uncertainties. Both drifts need adjusting through zero/span procedures during field maintenance. The equations provide rationales to guide and assess the procedures. H2O span needs more attentions under humid conditions. Under freezing conditions while H2O span is impractical, this span is fortunately unnecessary. Under the same conditions, H2O zero drift dominates H2O measurement uncertainty. Therefore, automatic zero becomes a more applicable and necessary tactic. In general cases of atmospheric CO2 background, automatic CO2 zero/ span procedures can narrow CO2 accuracy by 36% (±0.74 to ± 0.47 µmolCO2 mol−1). Automatic/manual H2 O zero/span procedures can narrow H2O accuracy by 27% (±0.15 to ±0.11 mmolH2O mol−1). While ensuring system specifications, the procedures guided by equations improve measurement accuracies

Genome response to tissue plasminogen activator in experimental ischemic stroke

Background: Tissue plasminogen activator (tPA) is known to have functions beyond fibrinolysis in acute ischemic stroke, such as blood brain barrier disruption. To further delineate tPA functions in the blood, we examined the gene expression profiles induced by tPA in a rat model of ischemic stroke. Results: tPA differentially expressed 929 genes in the blood of rats (p ≤ 0.05, fold change ≥ |1.2|). Genes identified had functions related to modulation of immune cells. tPA gene expression was found to be dependent on the reperfusion status of cerebral vasculature. The majority of genes regulated by tPA were different from genes regulated by ischemic stroke. Conclusions: tPA modulates gene expression in the blood of rats involving immune cells in a manner that is dependent on the status of vascular reperfusion. These non-fibrinolytic activities of tPA in the blood serve to better understand tPA-related complications.Glen C Jickling, Xinhua Zhan, Bradley P Ander, Renee J Turner, Boryana Stamova, Huichun Xu, Yingfang Tian, Dazhi Liu, Ryan R Davis, Paul A Lapchak and Frank R Shar

Molecular markers and mechanisms of stroke: RNA studies of blood in animals and humans

Whole genome expression microarrays can be used to study gene expression in blood, which comes in part from leukocytes, immature platelets, and red blood cells. Since these cells are important in the pathogenesis of stroke, RNA provides an index of these cellular responses to stroke. Our studies in rats have shown specific gene expression changes 24 hours after ischemic stroke, hemorrhage, status epilepticus, hypoxia, hypoglycemia, global ischemia, and following brief focal ischemia that simulated transient ischemic attacks in humans. Human studies show gene expression changes following ischemic stroke. These gene profiles predict a second cohort with >90% sensitivity and specificity. Gene profiles for ischemic stroke caused by large-vessel atherosclerosis and cardioembolism have been described that predict a second cohort with >85% sensitivity and specificity. Atherosclerotic genes were associated with clotting, platelets, and monocytes, and cardioembolic genes were associated with inflammation, infection, and neutrophils. These gene profiles predicted the cause of stroke in 58% of cryptogenic patients. These studies will provide diagnostic, prognostic, and therapeutic markers, and will advance our understanding of stroke in humans. New techniques to measure all coding and noncoding RNAs along with alternatively spliced transcripts will markedly advance molecular studies of human stroke

Incorporating MicroRNA into molecular phenotypes of circulating tumor cells enhances the prognostic accuracy for patients with metastatic breast cancer

Background. The molecular phenotype of circulating tumor cells (CTCs) was associated with clinical outcome of patients with breast cancer. CTCs isolated from patients with metastatic breast cancer (MBC) display a unique microRNA (miRNA) expression profile. The aim of this study was to enhance the prognostic accuracy of the CTC phenotype in patients with MBC, by incorporating miRNA into a combined prediction model. Subjects, Materials, and Methods. CTCs were detected by CellSearch and enriched by magnetic cell sorting. miRNA deep sequencing and quantitative polymerase chain reaction were used to screen and verify potentially CTC‐specific miRNA candidates. Patients with MBC were enrolled from two independent cohorts, and overall survival (OS) and chemotherapy response were analyzed. Results. We screened and identified that miR‐106b was an upregulated molecule in patients with MBC with CTC ≥5/7.5 mL (n = 16) compared with patients with CTC = 0/7.5 mL (n = 16) and healthy donors (n = 8). The expression of CTC‐specific miR‐106b correlated with vimentin and E‐cadherin in CTC and acted as an independent factor for predicting OS (hazard ratio 2.157, 95% confidence interval [CI] 1.098–4.239, p = .026). Although CTC‐specific miR‐106b, E‐cadherin, and vimentin showed a prognostic potential independently, the prognostic performance for OS based on the combination of three markers was significantly enhanced in Cohort 1 (area under the curve [AUC] 0.752, 95% CI 0.658–0.847, n = 128) and further validated in Cohort 2 (AUC 0.726, 95% CI 0.595–0.856, n = 91). Besides, a combined model incorporating miR‐106b was associated with therapy response. Conclusion. The phenotypic assemblies of CTC incorporating miR‐106b show enhanced prognostic accuracy of overall survival in patients with MBC