The challenge of detecting intracluster filaments with Faraday Rotation

The detection of filaments in the cosmic web will be crucial to distinguish between the possible magnetogenesis scenarios and future large polarization surveys will be able to shed light on their magnetization level. In this work, we use numerical simulations of galaxy clusters to investigate their possible detection. We compute the Faraday Rotation signal in intracluster filaments and compare it to its surrounding environment. We find that the expected big improvement in sensitivity with the SKA-MID will in principle allow the detection of a large fraction of filaments surrounding galaxy clusters. However, the contamination of the intrinsic Faraday Rotation of background polarized sources will represent a big limiter to the number of objects that can be significantly detected. We discuss possible strategies to minimize this effect and increase the chances of detection of the cosmic web with the large statistics expected from future surveys.Comment: 16 pages, accepted to Galaxie

Comparative analysis of a portable smartphone­based electrocardiograph (D­Heart®) versus standard 6­leads electrocardiograph in the canine patient.

D-Heart® is a portable, smartphone-based device, which streams tracing via Bluetooth, enabling multiple leads electrocardiograms (ECGs) acquisition, currently used in human cardiology (Maurizi et al. 2017).The aim was to determine the accuracy of D­Heart® compared with the gold standard non­portable 6­lead electrocardiograph in the evaluation of cardiac rhythm in dogs.Standard 6­lead and D­Heart® ECGs were acquired in conscious dogs. Concordance between methods was assessed by weighted k Cohen index, with its relative significance, taking as end point variable standard 6­lead ECG group. Bland ­ Altman method (95% confidence level) was applied for P, PR, QRS, T and QT. Since differences didn’t follow a normal distribution, a non­parametric approach was used to determine limits of agreement. P was significant when < 0.05 (Maurizi et al. 2017). Amplitude of waves was not considered because currently the software doesn’t allow voltage variation.115 dogs of different weights and breeds admitted to the Cardiology Service of DIMEVET were enrolled. Mean age was 7,5±4 years. Most were intact males (45%, n=51). The most represented breed was mongrel (27%, n=32).Weighted Cohen's kappa test demonstrated excellent concordance in the evaluation of the heart rhythm (0.989, p<0.001), for ST segment morphology (0.991, p<0,001) and for T wave morphology (0.838, p=0.040). There was a 100% concordance in P morphology determination. P, PR, QRS, T and QT intervals comparison with Bland­Altman showed an extremely good concordance for D­Heart® measurements (95% limit of agreement ±0.9 ms for P, ±10 ms for PR, ±35 ms for QRS, ±5 ms for T wave). Less concordance resulted for QT (±80 ms).In Conclusion, D­Heart® proved effective accurate recording of ECG comparable to standard 6­lead electrocardiographs, opening new perspectives to improve diagnostic tools in veterinary cardiology. Future perspective will be the development of a telecardiology network and to improve arrhythmia’s diagnosis in small animal practice (Bruining et al., 2014; Haberman et al., 2015).

Beyond Trial and Error: A Systematic Development of Liposomes Targeting Primary Macrophages

Monocytes/macrophages are phagocytic innate immune cells playing a pivotal role in tissue homeostasis, inflammation, and antitumor immunity in a microenvironment-dependent manner. By expressing pattern recognition and scavenger receptors on their surface, macrophages selectively take up pathogens, cellular debris, and often—undesirably—drug delivery systems. On the other hand, the propensity of phagocytic cells to internalize particulate drug carriers is used to load them with a cargo of choice, turning the monocytes/macrophages into a diagnostic or therapeutic Trojan horse. Identifying the ideal physicochemical properties of particulate carriers such as liposomes to achieve the most efficient macrophage-mediated drug delivery has been object of extensive research in the past, but the studies reported so far rely solely on trial-and-error approaches. Herein, a design of experiment (DoE) strategy to identify the optimal liposomal formulation is proposed, fully characterized in terms of size, surface charge, and membrane fluidity, to maximize macrophage targeting. The findings are validated using mouse bone marrow-derived macrophages, a primary preparation modeling in vivo monocyte-derived macrophages, thus confirming the robustness and versatility of the systematic and iterative approach and suggesting the promising potential of the DoE approach for the design of cell-targeting delivery systems

Antiviral and antioxidant activity of a hydroalcoholic extract from Humulus lupulus L.

A hydroalcoholic extract from female inflorescences of Humulus lupulus L. (HOP extract) was evaluated for its anti-influenza activity. The ability of the extract to interfere with different phases of viral replication was assessed, as well as its effect on the intracellular redox state, being unbalanced versus the oxidative state in infected cells. The radical scavenging power, inhibition of lipoperoxidation, and ferric reducing activity were assayed as antioxidant mechanisms. A phytochemical characterization of the extract was also performed. We found that HOP extract significantly inhibited replication of various viral strains, at different time from infection. Viral replication was partly inhibited when virus was incubated with extract before infection, suggesting a direct effect on the virions. Since HOP extract was able to restore the reducing conditions of infected cells, by increasing glutathione content, its antiviral activity might be also due to an interference with redox-sensitive pathways required for viral replication. Accordingly, the extract exerted radical scavenging and reducing effects and inhibited lipoperoxidation and the tBOOH-induced cytotoxicity. At phytochemical analysis, different phenolics were identified, which altogether might contribute to HOP antiviral effect. In conclusion, our results highlighted anti-influenza and antioxidant properties of HOP extract, which encourage further in vivo studies to evaluate its possible application

Preliminary evaluation of an ELISA kit for the detection of Aldosterone concentration in dog’s urine

Aldosterone is a corticosteroid hormone that plays a pivotal role in homeostatic regulation of water and salt reabsorption, blood volume and pressure. Aldosterone levels tent to rise in humans in hypertension, chronic and acute congestive heart failure (CHF); detrimental effects are opposed by drugs like ACE inhibitors and anti-mineralocorticoid. Aldosterone has a pulsatile secretion, so measurement in serum is less indicative than in urine, where concentration can be indexed to creatinine ratio for estimation of the 24-h aldosterone excretion.Few studies have evaluated aldosterone in canine urine patients, and none by ELISA. Aim of the study was to evaluate a commercial ELISA kit for measuring aldosterone in dog’s urine.Urine was collectedby free catchfrom four dogs. Two were healthy, one was affected by CHF and prescribed anti-mineralocorticoiddaily, one was affected by chronic kidney disease (CKD). Urine was centrifuged (1250g/5 min) and supernatant frozen (-20°C). Aldosterone was measured by a competitive ELISA previously validated for dogs. Twenty-four hours acid hydrolysis was performed on urinary samples before assay.The ELISA standard curve in a semi-log plot was linear between 2.5 and 3.9 ng/mL. Spike-and-recovery, linearity-of-dilution and parallelism experiments showed accuracy inmeasuring aldosterone in dog urine samples. The intra-assay coefficient of variation showed good reproducibility of the assay.Urinary samples are easy to collect, and the ELISA used in this preliminary study seems promising in determining aldosterone in dog urine. Its levels can be of great diagnostic and prognostic value for dogs affected by acute and chronic CHF, in order to assess the best therapeutic strategy. This preliminary analysis will be followed by further studies in patients affected by acute and chronic CHF

Allogeneic mesenchymal stromal cells overexpressing mutant human Hypoxia-inducible factor 1-α (HIF1-α) in an ovine model of acute myocardial infarction

Background-Bone marrow mesenchymal stromal cells (BMMSCs) are cardioprotective in acute myocardial infarction (AMI) because of release of paracrine angiogenic and prosurvival factors. Hypoxia-inducible factor 1-α (HIF1-α), rapidly degraded during normoxia, is stabilized during ischemia and upregulates various cardioprotective genes. We hypothesized that BMMSCs engineered to overexpress mutant, oxygen-resistant HIF1-α would confer greater cardioprotection than nontransfected BMMSCs in sheep with AMI. Methods and Results-Allogeneic BMMSCs transfected with a minicircle vector encoding mutant HIF1-α (BMMSC-HIF) were injected in the peri-infarct of sheep (n=6) undergoing coronary occlusion. Over 2 months, infarct volume measured by cardiac magnetic resonance (CMR) imaging decreased by 71.7±1.3% (P < 0.001), and left ventricular (LV) percent ejection fraction (%EF) increased near 2-fold (P < 0.001) in the presence of markedly decreased end-systolic volume. Sheep receiving nontransfected BMMSCs (BMMSC; n=6) displayed less infarct size limitation and percent LVEF improvement, whereas in placebo-treated animals (n=6), neither parameters changed over time. HIF1-α-transfected BMMSCs (BMMSC-HIF) induced angio-/arteriogenesis and decreased apoptosis by HIF1-mediated overexpression of erythropoietin, inducible nitrous oxide synthase, vascular endothelial growth factor, and angiopoietin-1. Cell tracking using paramagnetic iron nanoparticles in 12 additional sheep revealed enhanced long-term retention of BMMSC-HIF. Conclusions-Intramyocardial delivery of BMMSC-HIF reduced infarct size and improved LV systolic performance compared to BMMSC, attributed to increased neovascularization and cardioprotective effects induced by HIF1-mediated overexpression of paracrine factors and enhanced retention of injected cells. Given the safety of the minicircle vector and the feasibility of BMMSCs for allogeneic application, this treatment may be potentially useful in the clinic.Fil: Hnatiuk, Anna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Ong, Sang-Ging. Stanford University School of Medicine; Estados UnidosFil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Riegler, Johannes. Stanford University School of Medicine; Estados UnidosFil: Lee, Won Hee. Stanford University School of Medicine; Estados UnidosFil: Jen, Cheng Hao. University of London; Reino UnidoFil: De Lorenzi, Andrea. Fundación Favaloro; ArgentinaFil: Giménez, Carlos Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Laguens, Rubén. Universidad Favaloro; ArgentinaFil: Wu, Joseph C.. Stanford University School of Medicine; Estados UnidosFil: Crottogini, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

An ovine model of postinfarction dilated cardiomyopathy in animals with highly variable coronary anatomy

Studies on cardiac regeneration require large mammalian models of dilated cardiomyopathy (DCM) after acute myocardial infarction (AMI), and pig and sheep models are increasingly used in this field of preclinical research. Given the large interindividual variability in ovine left anterior descending artery (LAD) anatomy, protocols based on the coronary arteries to be ligated often lead to significant variation in infarct sizes and hence to heterogeneous results, ranging from no ventricular remodeling to acute, lethal left ventricular (LV) failure. We designed an ovine model of postinfarction DCM based on estimated infarct size rather than on a predetermined menu of coronary artery ligatures. In seven adult sheep we induced an anterolateral AMI of approximately 25% of the LV mass by ligating the branches of the LAD that, by visual inspection, would lead to such an infarct size. In 10 to 12 weeks, LV end-diastolic volume more than doubled and LV end-systolic volume almost tripled. LV ejection fraction decreased dramatically, as did LV percent fractional shortening and LV percent wall thickening. Infarct size (planimetry) was approximately 25% of the LV endocardial surface. We conclude that in sheep, an anterolateral AMI of approximately 25% of the LV mass--regardless of the coronary branches ligated to attain that infarct size--results in a model of postinfarction DCM that may prove useful in preclinical research on myocardial regeneration.Fil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; ArgentinaFil: Mendiz, Oscar. Fundación Favaloro; ArgentinaFil: Salmo, Fabián. Fundación Favaloro; ArgentinaFil: Fazzi, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación Favaloro; ArgentinaFil: Hnatiuk, Anna. Universidad Favaloro; ArgentinaFil: Laguens, Rubén. Fundación Favaloro; ArgentinaFil: Crottogini, Alberto Jose. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro; Argentin

β-arrestin1-mediated acetylation of Gli1 regulates Hedgehog/Gli signaling and modulates self-renewal of SHH medulloblastoma cancer stem cells

Background Aberrant Sonic Hedgehog/Gli (Hh/Gli) signaling pathway is a critical regulator of Sonic hedgehog medulloblastoma (SHH-MB). Cancer stem cells (CSCs), thought to be largely responsible for tumor initiation, maintenance, dissemination and relapse, have been identified in SHH-MB. Since we previously demonstrated that Hh/Gli signaling controls CSCs features in SHH-MB and that in these tumors miR-326 is down regulated, here we investigated whether there is a functional link between Hh/Gli signaling and miR-326. Methods We evaluated β-arrestin1 (Arrb1) and its intragenic miR-326 levels in CSCs derived from SHH-MB. Subsequently, we modulated the expression of Arrb1 and miR-326 in CSCs in order to gain insight into their biological role. We also analyzed the mechanism by which Arrb1 and miR-326 control Hh/Gli signaling and self-renewal, using luciferase and protein immunoprecipitation assays. Results Low levels of Arrb1 and miR-326 represent a feature of CSCs derived from SHH-MB. We observed that re-expression of Arrb1 and miR-326 inhibits Hh/Gli signaling pathway at multiple levels, which cause impaired proliferation and self-renewal, accompanied by down regulation of Nanog levels. In detail, miR-326 negatively regulates two components of the Hh/Gli pathway the receptor Smoothened (Smo) and the transcription factor Gli2, whereas Arrb1 suppresses the transcriptional activity of Gli1, by potentiating its p300-mediated acetylation. Conclusions Our results identify a new molecular mechanism involving miR-326 and Arrb1 as regulators of SHH-MB CSCs. Specifically, low levels of Arrb1 and miR-326 trigger and maintain Hh/Gli signaling and self-renewal