Detecting significant features in modeling microRNA-target interactions

MicroRNAs (miRNAs) are small non-coding RNA molecules mediating the translational repression and degradation of target mRNAs in the cell. Mature miRNAs are used as a template by the RNA-induced silencing complex (RISC) to recognize the complementary mRNAs to be regulated. Up to 60% of human genes are putative targets of one or more miRNAs. Several prediction tools are available to suggest putative miRNA targets, however, only a small part of the interaction pairs has been validated by experimental approaches. The analysis of the expression profile of the RNA fraction immunoprecipitated (IP) with the RISC proteins is an established method to detect which genes are actually regulated by the RISC machinery. In fact, genes that result over-expressed in the IP sample with respect to the whole cell lysate RNA, are considered as involved in the RISC complex, then miRNA targets. Here, we aim to find the features useful to predict which genes are overexpressed in IP, i.e. miRNA targets, without actually performing the IP experiments. To this purpose, we compiled and analyzed a novel high throughput data set suitable to unravel the features involved in the miRNA regulatory activities. We analyzed IP samples obtained by the immunoprecipitation of two RISC proteins, AGO2 and GW182. The two proteins shows different behaviors, in terms of enriched genes and features characterizing the immunoprecipitated RNA fractio. Further analysis is needed to unravel the reason of such different behavior

Swab test in biological fluids as predictor of COVID-19 transmission risk during surgery: a prospective cross-sectional study from an Italian COVID center

Background The contamination of body fluids by Severe Acute Respiratory Syndrome Coronavirus 2 during surgery is current matter of debate in the scientific literature concerning CoronaVIrus Disease 2019. Surgical guidelines were published during the first wave of the COVID-19 pandemic and recommended to avoid laparoscopic surgery as much as possible, in fear that the chimney effect of high flow intraperitoneal gas escape during, and after, the procedure would increase the risk of viral transmission. Aim The aim of this study was to evaluate the possibility of SARS-CoV-2 transmission during surgery by searching for viral RNA in serial samplings of biological liquids. Methods This is a single center prospective cross-sectional study. We used a real-time reverse transcriptase (RT) polymerase chain reaction (PCR) test to perform swab tests for the qualitative detection of nucleic acid from SARS-CoV-2 in abdominal fluids, during emergency surgery and on the first post-operative day. In the case of thoracic surgery, we performed a swab test of pleural fluids during chest drainage placement as well as on the first post-operative day. Results A total of 20 samples were obtained: 5 from pleural fluids, 13 from peritoneal fluids and two from biliary fluid. All 20 swabs performed from biological fluids resulted negative for SARS-CoV-2 RNA detection. Conclusion To date, there is no scientific evidence of possible contagion by laparoscopic aerosolization of SARS-CoV-2, neither is certain whether the virus is effectively present in biological fluids

Pro-invasive stimuli and the interacting protein Hsp70 favour the route of alpha-enolase to the cell surface

Cell surface expression of alpha-enolase, a glycolytic enzyme displaying moonlighting activities, has been shown to contribute to the motility and invasiveness of cancer cells through the protein non-enzymatic function of binding plasminogen and enhancing plasmin formation. Although a few recent records indicate the involvement of protein partners in the localization of alpha-enolase to the plasma membrane, the cellular mechanisms underlying surface exposure remain largely elusive. Searching for novel interactors and signalling pathways, we used low-metastatic breast cancer cells, a doxorubicin-resistant counterpart and a non-tumourigenic mammary epithelial cell line. Here, we demonstrate by a combination of experimental approaches that epidermal growth factor (EGF) exposure, like lipopolysaccharide (LPS) exposure, promotes the surface expression of alpha-enolase. We also establish Heat shock protein 70 (Hsp70), a multifunctional chaperone distributed in intracellular, plasma membrane and extracellular compartments, as a novel alpha-enolase interactor and demonstrate a functional involvement of Hsp70 in the surface localization of alpha-enolase. Our results contribute to shedding light on the control of surface expression of alpha-enolase in non-tumourigenic and cancer cells and suggest novel targets to counteract the metastatic potential of tumours

An excess power statistic for detection of burst sources of gravitational radiation

We examine the properties of an excess power method to detect gravitational waves in interferometric detector data. This method is designed to detect short-duration (< 0.5 s) burst signals of unknown waveform, such as those from supernovae or black hole mergers. If only the bursts' duration and frequency band are known, the method is an optimal detection strategy in both Bayesian and frequentist senses. It consists of summing the data power over the known time interval and frequency band of the burst. If the detector noise is stationary and Gaussian, this sum is distributed as a chi-squared (non-central chi-squared) deviate in the absence (presence) of a signal. One can use these distributions to compute frequentist detection thresholds for the measured power. We derive the method from Bayesian analyses and show how to compute Bayesian thresholds. More generically, when only upper and/or lower bounds on the bursts duration and frequency band are known, one must search for excess power in all concordant durations and bands. Two search schemes are presented and their computational efficiencies are compared. We find that given reasonable constraints on the effective duration and bandwidth of signals, the excess power search can be performed on a single workstation. Furthermore, the method can be almost as efficient as matched filtering when a large template bank is required. Finally, we derive generalizations of the method to a network of several interferometers under the assumption of Gaussian noise.Comment: 22 pages, 6 figure

Supersymmetry breaking in two dimensions: the lattice N=1 Wess-Zumino model

We study dynamical supersymmetry breaking by non perturbative lattice techniques in a class of two-dimensional N=1 Wess-Zumino models. We work in the Hamiltonian formalism and analyze the phase diagram by analytical strong-coupling expansions and explicit numerical simulations with Green Function Monte Carlo methods.Comment: 53 pages, 17 figures, revtex

Apparent Diffusion Coefficient Assessment of Brain Development in Normal Fetuses and Ventriculomegaly

Diffusion neuro-MRI has benefited significantly from sophisticated pre-processing procedures aimed at improving image quality and diagnostic. In this work, diffusion-weighted imaging (DWI) was used with artifact correction and the apparent diffusion coefficient (ADC) was quantified to investigate fetal brain development. The DWI protocol was designed in order to limit the acquisition time and to estimate ADC without perfusion bias. The ADC in normal fetal brains was compared to cases with isolated ventriculomegaly (VM), a common fetal disease whose DWI studies are still scarce. DWI was performed in 58 singleton fetuses (Gestational age (GA) range: 19–38w) at 1.5T. In 31 cases, VM was diagnosed on ultrasound. DW-Spin Echo EPI with b-values = 50, 200, 700 s/mm2 along three orthogonal axes was used. All images were corrected for noise, Gibbs-ringing, and motion artifacts. The signal-to-noise ratio (SNR) was calculated and the ADC was measured with a linear least-squared algorithm. A multi-way ANOVA was used to evaluate differences in ADC between normal and VM cases and between second and third trimester in different brain regions. Correlation between ADC and GA was assessed with linear and quadratic regression analysis. Noise and artifact correction considerably increased SNR and the goodness-of-fit. ADC measurements were significantly different between second and third trimester in centrum semiovale, frontal white matter, thalamus, cerebellum and pons of both normal and VM brains (p ≤ 0.03). ADC values were significantly different between normal and VM in centrum semiovale and frontal white matter (p ≤ 0.02). ADC values in centrum semiovale, thalamus, cerebellum and pons linearly decreased with GA both in normal and VM brains, while a quadratic relation with GA was found in basal ganglia and occipital white matter of normal brains and in frontal white matter of VM (p ≤ 0.02). ADC values in all fetal brain regions were lower than those reported in literature where DWI with b = 0 was performed. Conversely, they were in agreement with the results of other authors who measured perfusion and diffusion contributions separately. By optimizing our DWI protocol we achieved an unbiased quantification of brain ADC in reasonable scan time. Our findings suggested that ADC can be a useful biomarker of brain abnormalities associated with VM

Apparent diffusion coefficient assessment of brain development in normal fetuses and ventriculomegaly

Diffusion neuro-MRI has benefited significantly from sophisticated pre-processing procedures aimed at improving image quality and diagnostic. In this work, diffusion-weighted imaging (DWI) was used with artifact correction and the apparent diffusion coefficient (ADC) was quantified to investigate fetal brain development. The DWI protocol was designed in order to limit the acquisition time and to estimate ADC without perfusion bias. The ADC in normal fetal brains was compared to cases with isolated ventriculomegaly (VM), a common fetal disease whose DWI studies are still scarce. DWI was performed in 58 singleton fetuses (Gestational age (GA) range: 19–38w) at 1.5T. In 31 cases, VM was diagnosed on ultrasound. DW-Spin Echo EPI with b-values = 50, 200, 700 s/mm2 along three orthogonal axes was used. All images were corrected for noise, Gibbs-ringing, and motion artifacts. The signal-to-noise ratio (SNR) was calculated and the ADC was measured with a linear least-squared algorithm. A multi-way ANOVA was used to evaluate differences in ADC between normal and VM cases and between second and third trimester in different brain regions. Correlation between ADC and GA was assessed with linear and quadratic regression analysis. Noise and artifact correction considerably increased SNR and the goodness-of-fit. ADC measurements were significantly different between second and third trimester in centrum semiovale, frontal white matter, thalamus, cerebellum and pons of both normal and VM brains (p ≤ 0.03). ADC values were significantly different between normal and VM in centrum semiovale and frontal white matter (p ≤ 0.02). ADC values in centrum semiovale, thalamus, cerebellum and pons linearly decreased with GA both in normal and VM brains, while a quadratic relation with GA was found in basal ganglia and occipital white matter of normal brains and in frontal white matter of VM (p ≤ 0.02). ADC values in all fetal brain regions were lower than those reported in literature where DWI with b = 0 was performed. Conversely, they were in agreement with the results of other authors who measured perfusion and diffusion contributions separately. By optimizing our DWI protocol we achieved an unbiased quantification of brain ADC in reasonable scan time. Our findings suggested that ADC can be a useful biomarker of brain abnormalities associated with VM

Analytical Solution for the Deformation of a Cylinder under Tidal Gravitational Forces

Quite a few future high precision space missions for testing Special and General Relativity will use optical resonators which are used for laser frequency stabilization. These devices are used for carrying out tests of the isotropy of light (Michelson-Morley experiment) and of the universality of the gravitational redshift. As the resonator frequency not only depends on the speed of light but also on the resonator length, the quality of these measurements is very sensitive to elastic deformations of the optical resonator itself. As a consequence, a detailed knowledge about the deformations of the cavity is necessary. Therefore in this article we investigate the modeling of optical resonators in a space environment. Usually for simulation issues the Finite Element Method (FEM) is applied in order to investigate the influence of disturbances on the resonator measurements. However, for a careful control of the numerical quality of FEM simulations a comparison with an analytical solution of a simplified resonator model is beneficial. In this article we present an analytical solution for the problem of an elastic, isotropic, homogeneous free-flying cylinder in space under the influence of a tidal gravitational force. The solution is gained by solving the linear equations of elasticity for special boundary conditions. The applicability of using FEM codes for these simulations shall be verified through the comparison of the analytical solution with the results gained within the FEM code.Comment: 23 pages, 3 figure

Nonredundant role of CCRL2 in lung dendritic cell trafficking.

Chemokine CC motif receptor-like 2 (CCRL2) is a heptahelic transmembrane receptor that shows the highest degree of homology with CCR1, an inflammatory chemokine receptor. CCRL2 mRNA was rapidly (30 minutes) and transiently (2-4 hours) regulated during dendritic cell (DC) maturation. Protein expression paralleled RNA regulation. In vivo, CCRL2 was expressed by activated DC and macrophages, but not by eosinophils and T cells. CCRL2(-/-) mice showed normal recruitment of circulating DC into the lung, but a defective trafficking of antigen-loaded lung DC to mediastinal lymph nodes. This defect was associated to a reduction in lymph node cellularity and reduced priming of T helper cell 2 response. CCRL2(-/-) mice were protected in a model of ovalbumin-induced airway inflammation, with reduced leukocyte recruitment in the BAL (eosinophils and mononuclear cells) and reduced production of the T helper cell 2 cytokines, interleukin-4 and -5, and chemokines CCL11 and CCL17. The central role of CCRL2 deficiency in DC was supported by the fact that adoptive transfer of CCRL2(-/-) antigen-loaded DC in wild-type animals recapitulated the phenotype observed in knockout mice. These data show a nonredundant role of CCRL2 in lung DC trafficking and propose a role for this receptor in the control of excessive airway inflammatory responses. (Blood. 2010;116(16):2942-2949

Sodium/glucose cotransporter 2 (SGLT2) inhibitors improve cardiac function by reducing JunD expression in human diabetic hearts

Background: The pathogenesis of experimental diabetic cardiomyopathy may involve the activator protein 1 (AP-1) member, JunD. Using non-diabetic heart transplant (HTX) in recipients with diabetes, we examined the effects of the diabetic milieu (hyperglycemia and insulin resistance) on cardiac JunD expression over 12 months. Because sodium/glucose cotransporter-2 inhibitors (SGLT2i) significantly reverse high glucose-induced AP-1 binding in the proximal tubular cell, we investigated JunD expression in a subgroup of type 2 diabetic recipients receiving SGLT2i treatment. Methods: We evaluated 77 first HTX recipients (40 and 37 patients with and without diabetes, respectively). Among the recipients with diabetes, 17 (45.9%) were receiving SGLT2i treatment. HTX recipients underwent standard clinical evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsy). In the biopsy samples, we evaluated JunD, insulin receptor substrates 1 and 2 (IRS1 and IRS2), peroxisome proliferator-activated receptor-γ (PPAR-γ), and ceramide levels using real-time polymerase chain reaction and immunofluorescence. The biopsy evaluations in this study were performed at 1–4 weeks (basal), 5–12 weeks (intermediate), and up to 48 weeks (final, end of 12-month follow-up) after HTX. Results: There was a significant early and progressive increase in the cardiac expression of JunD/PPAR-γ and ceramide levels, along with a significant decrease in IRS1 and IRS2 in recipients with diabetes but not in those without diabetes. These molecular changes were blunted in patients with diabetes receiving SGLT2i treatment. Conclusion: Early pathogenesis in human diabetic cardiomyopathy is associated with JunD/PPAR-γ overexpression and lipid accumulation following HTX in recipients with diabetes. Remarkably, this phenomenon was reduced by concomitant therapy with SGLT2i, which acted directly on diabetic hearts