Human metapneumovirus: Mechanisms and molecular targets used by the virus to avoid the immune system

Indexación: Scopus.This work was supported by Comisión Nacional de Investigación Científica y Tecnolígica (CONICYT) N◦21151028 and FONDECYT (N◦1070352 and N◦1170964) and the Millennium Institute on Immunology and Immunotherapy (P09/016-F).Human metapneumovirus (hMPV) is a respiratory virus, first reported the year 2001. Since then, it has been described as one of the main etiological agents that causes acute lower respiratory tract infections (ALRTIs), which is characterized by symptoms such as bronchiolitis, wheezing and coughing. Susceptible population to hMPV-infection includes newborn, children, elderly and immunocompromised individuals. This viral agent is a negative-sense, single-stranded RNA enveloped virus, that belongs to the Pneumoviridae family and Metapneumovirus genus. Early reports-previous to 2001-state several cases of respiratory illness without clear identification of the responsible pathogen, which could be related to hMPV. Despite the similarities of hMPV with several other viruses, such as the human respiratory syncytial virus or influenza virus, mechanisms used by hMPV to avoid the host immune system are still unclear. In fact, evidence indicates that hMPV induces a poor innate immune response, thereby affecting the adaptive immunity. Among these mechanisms, is the promotion of an anergic state in T cells, instead of an effective polarization or activation, which could be induced by low levels of cytokine secretion. Further, the evidences support the notion that hMPV interferes with several pattern recognition receptors (PRRs) and cell signaling pathways triggered by interferon-associated genes. However, these mechanisms reported in hMPV are not like the ones reported for hRSV, as the latter has two non-structural proteins that are able to inhibit these pathways. Several reports suggest that viral glycoproteins, such as G and SH, could play immune-modulator roles during infection. In this work, we discuss the state of the art regarding the mechanisms that underlie the poor immunity elicited by hMPV. Importantly, these mechanisms will be compared with those elicited by other common respiratory viruses. © 2018 Frontiers Media S.A. All rights reserved.https://www.frontiersin.org/articles/10.3389/fimmu.2018.02466/ful

Interleukin-1 receptor antagonist mediates toll-like receptor 3-induced inhibition of trophoblast adhesion to endometrial cells in vitro

STUDY QUESTION Is interleukin-1 receptor antagonist (IL-1RA) involved in the toll-like receptor 3 (TLR 3)-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro? SUMMARY ANSWER IL-1RA mediates the TLR 3-induced inhibition of trophoblast cells' adhesion to endometrial cells in vitro. WHAT IS KNOWN ALREADY It is well documented that endometrial TLR 3 activation leads to impairment of trophoblast binding to endometrial cells in vitro. IL-1RA is known as an anti-implantation factor, as its injection significantly reduced implantation rates in mice by an effect on endometrial receptivity. STUDY DESIGN, SIZE, DURATION Poly I:C was used as a TLR3 specific ligand and endometrial cells were either treated or not with Poly I:C (treated versus control) in vitro. IL-1RA was applied to block IL-1 signal transduction. IL-1RA was knocked down by Accell Human IL1RN siRNA. Flagellin was used to stimulate TLR 5. SP600125 (JNK) was applied to inhibit the mitogen-activated protein kinases (MAPK) pathway. BAY11 -7082 was used to inhibit the nuclear factor-κB (NF-κB) pathway. The experiments were performed in three replicates on three separate days. PARTICIPANTS/MATERIALS, SETTING, METHODS An in vitro assay was developed using RL95-2 (an endometrial cell line) and JAr (a trophoblast cell line) cells. Initially, the production of IL-1RA in RL95-2 cells in response to TLR 3 activation was measured. To determine whether the TLR 3-induced inhibition of trophoblast binding was mediated through IL-1RA: (i) we evaluated the effect of IL-1RA on the attachment of trophoblast cells to endometrial cells; (ii) we knocked down TLR3-induced IL-1RA gene expression by IL-1RA Small interfering RNA (siRNA) and evaluated trophoblast attachment to endometrial cells. Finally, to clarify through which pathway TLR 3-induced inhibition of trophoblast binding occurs: (i) activation of NF-κB and MAPK was detected by transfecting the cells with secreted placental alkaline phosphatase reporter plasmids bearing promoter sequences for each transcription factor; (ii) the inhibitors for NF-κB and MAPK were used to block signaling; (iii) it was then investigated whether addition of these inhibitors could restore the TLR 3-induced impairment of trophoblast attachment to the endometrial cells. MAIN RESULTS AND THE ROLE OF CHANCE Our results showed that addition of polyinosinic:polycytidylic acid (Poly I:C) to RL95-2 cells significantly increased the production of IL-1RA (P < 0.05). Addition of human recombinant IL-1RA to RL95-2 cells remarkably decreased the adhesion rate of trophoblast cells to endometrial cells (P < 0.05). In addition, suppression of TLR3-induced IL-1RA gene expression in RL95-2 cells significantly restored trophoblast cells attachment to endometrial cells in the presence of Poly I:C (P < 0.05). Only TLR3 and not TLR5 induced MAPK activation (P < 0.05). TLR3 ligation did not affect NF-κB activation. Of NF-kB and MAPK inhibitors, only MAPK's inhibitor could achieve restoration of spheroid adhesion to endometrial cells (P < 0.05). LIMITATIONS, REASONS FOR CAUTION This study has been only done in vitro. Future in vivo studies will confirm our data. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study have a potential clinical application in introducing IL-1RA as one of the diagnostic infertility markers in the endometrium, which can affect the process of embryo adhesion at the time of implantation. Moreover, based on the novel data obtained in the current study, blocking and regulating the MAPK pathway by its inhibitors can be used as a new strategy to prevent and treat virus-induced infertility cases in ART techniques. STUDY FUNDING/COMPETING INTEREST This study was partially funded by a Marie Curie IIF-253948 grant to I.C. and was partially funded by the author's institutions. The authors have no conflict of interest to declare

Magnetoresistance and electronic structure of asymmetric GaAs/AlGaAs double quantum wells in the in-plane/tilted magnetic field

Bilayer two-dimensional electron systems formed by a thin barrier in the GaAs buffer of a standard heterostructure were investigated by magnetotransport measurements. In magnetic fields oriented parallel to the electron layers, the magnetoresistance exhibits an oscillation associated with the depopulation of the higher occupied subband and the field-induced transition into a decoupled bilayer. Shubnikov-de Haas oscillations in slightly tilted magnetic fields allow to reconstruct the evolution of the electron concentration in the individual subbands as a function of the in-plane magnetic field. The characteristics of the system derived experimentally are in quantitative agreement with numerical self-consistent-field calculations of the electronic structure.Comment: 6 pages, 5 figure

Correlations, compressibility, and capacitance in double-quantum-well systems in the quantum Hall regime

In the quantum Hall regime, electronic correlations in double-layer two-dimensional electron systems are strong because the kinetic energy is quenched by Landau quantization. In this article we point out that these correlations are reflected in the way the partitioning of charge between the two-layers responds to a bias potential. We report on illustrative calculations based on an unrestricted Hartree-Fock approximation which allows for spontaneous inter-layer phase coherence. The possibility of studying inter-layer correlations by capacitive coupling to separately contacted two-dimensional layers is discussed in detail.Comment: RevTex style, 21 pages, 6 postscript figures in a separate file; Phys. Rev. B (in press

Water waves generated by a moving bottom

Tsunamis are often generated by a moving sea bottom. This paper deals with the case where the tsunami source is an earthquake. The linearized water-wave equations are solved analytically for various sea bottom motions. Numerical results based on the analytical solutions are shown for the free-surface profiles, the horizontal and vertical velocities as well as the bottom pressure.Comment: 41 pages, 13 figures. Accepted for publication in a book: "Tsunami and Nonlinear Waves", Kundu, Anjan (Editor), Springer 2007, Approx. 325 p., 170 illus., Hardcover, ISBN: 978-3-540-71255-8, available: May 200

The Influence of an Adsorbate Layer on Adatom Diffusion and Island Nucleation: Fe on Si(111)-√3 x √3-Au

Using scanning tunneling microscopy, the influence of a thin Au layer on the diffusion of Fe adatoms and the subsequent island nucleation on a Si(111) surface is investigated. The adsorbate induces thestructure that increases the surface mobility of subsequently deposited Fe atoms, resulting in the formation well-defined nanoclusters. Surprisingly, the domain walls—inherent to the reconstruction—do not influence the surface diffusion, which demonstrates that the passivation is of much more importance for the self-assembly than the surface corrugation. Using the decoupling of the diffusion and nucleationonthe surface and the reactionwiththe surface and conventional nucleation theory, the activation energy for surface diffusionEd = 0.61 eV and the critical cluster sizei = 3 are determined, which reveal the microscopic details of the diffusion and nucleation processes

Expanding indication of padeliporfin (WST11) vascular-targeted photodynamic therapy: results of prostate cancer Latin-American multicenter study

OBJECTIVES: To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). METHODS: Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. RESULTS: In the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%,83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%,88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. CONCLUSIONS: Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa

Use of the osmotic membrane bioreactor for the management of tannery wastewater using absorption liquid waste as draw solution

[EN] The performance of an osmotic membrane bioreactor (OMBR) for treating tannery wastewater at laboratory scale has been evaluated in this study. The forward osmosis (FO) membrane tested was CTA-NW from HTI. As draw solution, actual waste water from an absorption column for ammonia separation, which consists mainly of ammonium sulphate was used. The study was focused on the salt reverse flux during the OMBR operation, membrane water flux, biomass characteristics and membrane fouling. Regarding membrane water flux change with the time, the measured values diminished from 3.44 to 0.72 LMH due to the membrane fouling and the salt accumulation in the biological reactor. The stable mixed liquor conductivity value at the end of the experiment was 29.8 mS·cm¿1. The chemical oxygen demand (COD) removal efficiencies were maintained near 80% until the first 50 days of operation, considering the soluble COD in the reactor instead of the COD in the membrane permeate for the performance calculation. Thence, COD removal efficiencies decreased progressively due to the accumulation of non degradable COD coming from the tannery wastewater. Concerning to the membrane fouling, FESEM/EDX analysis corroborated that organic fouling was predominant on the membrane active layer.This study was supported by the Spanish Ministry of Economy and Competitiveness through the project RTC-2015-3582-5-AR.Lujan Facundo, MJ.; Mendoza Roca, JA.; Soler Cabezas, JL.; Bes-Piá, M.; Vincent Vela, MC.; Pastor Alcañiz, L. (2019). Use of the osmotic membrane bioreactor for the management of tannery wastewater using absorption liquid waste as draw solution. Process Safety and Environmental Protection. 131:292-299. https://doi.org/10.1016/j.psep.2019.09.024S29229913

The differential diagnosis of chronic daily headaches: an algorithm-based approach

Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for “red flags” that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is ≥4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review