The Number Of Titrated Microrna Species Dictates Cerna Regulation

microRNAs (miRNAs) play key roles in cancer, but their propensity to couple their targets as competing endogenous RNAs (ceRNAs) has only recently emerged. Multiple models have studied ceRNA regulation, but these models did not account for the effects of co-regulation by miRNAs with many targets. We modeled ceRNA and simulated its effects using established parameters for miRNA/mRNA interaction kinetics while accounting for co-regulation by multiple miRNAs with many targets. Our simulations suggested that co-regulation by many miRNA species is more likely to produce physiologically relevant context-independent couplings. To test this, we studied the overlap of inferred ceRNA networks from four tumor contexts-our proposed pan-cancer ceRNA interactome (PCI). PCI was composed of interactions between genes that were coregulated by nearly three-times as many miRNAs as other inferred ceRNA interactions. Evidence from expression-profiling datasets suggested that PCI interactions are predictive of gene expression in 12 independent tumor-and non-tumor contexts. Biochemical assays confirmed ceRNA couplings for two PCI subnetworks, including oncogenes CCND1, HIF1A and HMGA2, and tumor suppressors PTEN, RB1 and TP53. Our results suggest that PCI is enriched for context-independent interactions that are coupled by many miRNA species and are more likely to be context independent

Evaluation of Fetuses in the Preventive IVIG Therapy for Congenital Heart Block (PITCH) study

The recurrence rate of anti-SSA/Ro associated congenital heart block (CHB) is 17%. Reversal of 3rd degree block has never been achieved. Based on potential reduction of maternal autoantibody titers as well as fetal inflammatory responses, IVIG was evaluated as a preventative therapy for CHB

Relationship of body mass index and abdominal obesity in rural population of Krasnodarsky kray taken

The aim was to study the relationship of body mass index (BMI) and abdominal obesity with the frequency of comorbid pathology in rural population of Krasnodarsky kray.Materials and methods. The study included 700 rural workers (18 years of age and older) who underwent a preventive medical examination (57,2% of women and 42,8% of men, mean age 49,11±16,57 years).Results. In rural population of Krasnodarsky kray the proportion of the individuals with BMI 25.0–29.9 kg/m2 was 34.7% (statistically more significant in men than in women, р<0.0001), the proportion of the individuals with BMI ≥ 30.0 kg/m2 was 39.7% (statistically more significant in women than in men, р<0.0001). Abdominal obesity was found in 70.1% of individuals (77.3% of women and 60.5% of men, p=0.0001). In the group of patients with increased BMI, abdominal obesity was more common in women than in men (p=0.0001). In the group of patients with BMI ≥ 30.0 kg/m2 abdominal obesity was revealed in 100% of cases. Risk factors for chronic non-infectious diseases such as hypercholesterolemia (26.7%), hyperglycemia (16.4%), and arterial hypertension (26.1%) were statistically more frequent in the individuals with BMI ≥ 30.0 kg/m2 than in those with normal and increased BMI. The diseases that can be enhanced by the presence of abdominal obesity were registered more often in patients with BMI ≥ 30.0 kg/m2 (97.8%) in comparison with patients with elevated BMI (23.5%; р<0,0001) and with normal BMI (4%; р<0,0001).Conclusions. Elevated BMI, abdominal obesity and high frequency of comorbid pathology is prevalent in Krasnodarsky kray

Analysis of a fast-acting waveguide ferrite phase shifter with longitudinal magnetization phasing structure

The electrodynamic analysis and calculation of the phasing structure of a waveguide ferrite Faraday phase shifter with longitudinal magnetization of a ferrite rod with a square cross-section are performed. In the strict electrodynamic formulation, the Galerkin method solves the key problem for the design of the phase shifter: the problem of eigenwaves finding with a second-order differential magnetic operator in the projection procedure for a rectangular waveguide with a transversely inhomogeneous ferrite-dielectric filling under longitudinal magnetization. The problem is reduced to solving the complete eigenvalue problem of a complex matrix. The computational algorithm, implemented as a computer program in DELPHI, gives in one procedure the numerical values of the coefficients of the decomposition of fields in the form of eigenvectors of the matrix, and the coefficients of wave propagation in the form of its eigenvalues. The results of calculations of the phasing structure activity for two particular cases of its implementation are presented: on the basis of a ferrite rod both with a conductive coating and without a coating, it is shown that in the second case the activity of the phase shifter is 1.5 times higher. For the real parameters of the ferrite medium, the length of the phasing structure is calculated depending on the transverse dimensions of the ferrite rod and the square waveguide, which ensures the creation of a 360° controlled phase shift

Design of integrated Ka-band reflective phased array antenna element

The results of a constructively simple high-tech small-sized integrated element of the Ka-band electric beam scanning reflective phased array antenna (PAA) development are shown. Beam scanning sector of the phased array antenna is up to 60 by both coordinates. The PAA element is based on the Faraday type waveguide ferrite phase shifter, which works on the circular polarized electromagnetic waves. More than 30000 PAA elements has been produced, 100% control and statistical data processing of their main characteristics has been carried out. Graph for initial phases and steepness of linearized phase characteristics, medium and maximum losses of PAA elements are performed. Average value of the average deviation for parameters which is important for PAA and the beam control system design have been determined. The developed element can be used in PAA which have different sizes, forms and sectors of electrical beam scanning. Small deviations in the characteristics of PAA elements from the linearized characteristics indicate the high quality of the production and their identity, which makes it possible to create PAA without taking into account the real individual parameters of mass-produced PAA elements

The C2 Domain and Altered ATP-Binding Loop Phosphorylation at Ser359 Mediate the Redox-Dependent Increase in Protein Kinase C-δ Activity

The diverse roles of protein kinase C-δ (PKCδ) in cellular growth, survival, and injury have been attributed to stimulus-specific differences in PKCδ signaling responses. PKCδ exerts membrane-delimited actions in cells activated by agonists that stimulate phosphoinositide hydrolysis. PKCδ is released from membranes as a Tyr(313)-phosphorylated enzyme that displays a high level of lipid-independent activity and altered substrate specificity during oxidative stress. This study identifies an interaction between PKCδ's Tyr(313)-phosphorylated hinge region and its phosphotyrosine-binding C2 domain that controls PKCδ's enzymology indirectly by decreasing phosphorylation in the kinase domain ATP-positioning loop at Ser(359). We show that wild-type (WT) PKCδ displays a strong preference for substrates with serine as the phosphoacceptor residue at the active site when it harbors phosphomimetic or bulky substitutions at Ser(359.) In contrast, PKCδ-S359A displays lipid-independent activity toward substrates with either a serine or threonine as the phosphoacceptor residue. Additional studies in cardiomyocytes show that oxidative stress decreases Ser(359) phosphorylation on native PKCδ and that PKCδ-S359A overexpression increases basal levels of phosphorylation on substrates with both phosphoacceptor site serine and threonine residues. Collectively, these studies identify a C2 domain-pTyr(313) docking interaction that controls ATP-positioning loop phosphorylation as a novel, dynamically regulated, and physiologically relevant structural determinant of PKCδ catalytic activity

Downregulation of Friend Leukemia Integration 1 (FLI1) follows the stepwise progression to gastric adenocarcinoma

© 2020 Ivyspring International Publisher. All rights reserved. Gastric adenocarcinoma (GC) is a leading cause of cancer-related deaths worldwide. The transcription factor gene Friend Leukemia Integration 1 (FLI1) is methylated and downregulated in human GC tissues. Using human GC samples, we determined which cells downregulate FLI1, when FLI1 downregulation occurs, if FLI1 downregulation correlates with clinical-pathologic characteristics, and whether FLI1 plays a role in invasion and/or proliferation of cultured cells. We analyzed stomach tissues from 98 patients [8 normal mucosa, 8 intestinal metaplasia (IM), 7 dysplasia, 91 GC] by immunohistochemistry for FLI1. Epithelial cells from normal, IM, and low-grade dysplasia (LGD) showed strong nuclear FLI1 staining. GC epithelial cells showed significantly less nuclear FLI1 staining as compared to normal epithelium, IM and LGD (P=1.2×10-5, P=1.4×10-6 and P=0.006, respectively). FLI1 expression did not correlate with tumor stage or differentiation, but was associated with patient survival, depending on tumor differentiation. We tested the functional role of FLI1 by assaying proliferation and invasion in cultured GC cells. Lentiviral-transduced FLI1 overexpression in GC AGS cells inhibited invasion by 73.5% (P = 0.001) and proliferation by 31.5% (P = 0.002), as compared to controls. Our results support a combined role for FLI1 as a suppressor of invasiveness and proliferation in gastric adenocarcinoma, specifically in the transition from pre-cancer lesions and dysplasia to invasive adenocarcinoma, and suggest that FLI1 may be a prognostic biomarker of survival in gastric cancers

The Number Of Titrated Microrna Species Dictates Cerna Regulation

microRNAs (miRNAs) play key roles in cancer, but their propensity to couple their targets as competing endogenous RNAs (ceRNAs) has only recently emerged. Multiple models have studied ceRNA regulation, but these models did not account for the effects of co-regulation by miRNAs with many targets. We modeled ceRNA and simulated its effects using established parameters for miRNA/mRNA interaction kinetics while accounting for co-regulation by multiple miRNAs with many targets. Our simulations suggested that co-regulation by many miRNA species is more likely to produce physiologically relevant context-independent couplings. To test this, we studied the overlap of inferred ceRNA networks from four tumor contexts-our proposed pan-cancer ceRNA interactome (PCI). PCI was composed of interactions between genes that were coregulated by nearly three-times as many miRNAs as other inferred ceRNA interactions. Evidence from expression-profiling datasets suggested that PCI interactions are predictive of gene expression in 12 independent tumor-and non-tumor contexts. Biochemical assays confirmed ceRNA couplings for two PCI subnetworks, including oncogenes CCND1, HIF1A and HMGA2, and tumor suppressors PTEN, RB1 and TP53. Our results suggest that PCI is enriched for context-independent interactions that are coupled by many miRNA species and are more likely to be context independent