Altered expression of cytokines in mice infected intranasally with two syncytial variants of Herpes simplex virus type 1

Immune evasion strategies are important for the onset and the maintenance of viral infections. Many viruses have evolved mechanisms to counteract or suppress the host immune response. We have previously characterized two syncytial (syn) variants of Herpes simplex 1 (HSV-1) strain F, syn14-1 and syn17-2, obtained by selective pressure with a natural carrageenan. These variants showed a differential pathology in vaginal and respiratory mucosa infection in comparison with parental strain. In this paper, we evaluated the modulation of immune response in respiratory mucosa by these HSV-1 variants. We observed altered levels of Tumor Necrosis Factor-α and Interleukin-6 in lungs of animals infected with the syn14-1 and syn17-2 variants compared with the parental strain. Also, we detected differences in the recruitment of immune cells to the lung in syn variants infected mice. Both variants exhibit one point mutation in the sequence of the gene of glycoprotein D detected in the ectodomain of syn14-1 and the cytoplasmic tail of syn17-2. Results obtained in the present study contribute to the characterization of HSV-1 syn variants and the participation of the cellular inflammatory response in viral pathogenesis.Fil: Artuso, María Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Linero, Florencia Natalia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gazzaniga, Silvina Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Scolaro, Luis Alberto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica. Laboratorio de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pujol, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Wainstok, Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Carlucci, Maria Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

Remote Glucose Monitoring Platform for Multiple Simultaneous Patients at Coronavirus Disease 2019 Intensive Care Units: Case Report including Adults and Children

This work focuses on remote glucose monitoring at COVID-19 Intensive Care Units (ICU)in Argentina. We report the first cases using a new emergency platform for multi-centermulti-patient on-line remote glucose monitoring, which is accessible for everyone ondemand and which allows the integration of different glucose sensors. Five critical patientshave been monitored, two children and three adults, together with an ambulatory patient totest the platform versatility. All ICU patients have recovered or have been metabolicallycontrolled by the date of the submission of this report. Relevant lessons have been learnedfor the glucose management of critical patients, resulting in a new protocol in one of theparticipant hospitals.Fil: Garelli, Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Rosales, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Fushimi, Emilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Arambarri, Delfina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Mendoza, Leandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: de Battista, Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Sanchez Peña, Ricardo Salvador. Instituto Tecnológico de Buenos Aires. Departamento de Matemática. Centro de Sistemas y Control; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García Arabehety, Julia. Hospital Italiano; ArgentinaFil: DIstefano, Sabrina. Hospital Italiano; ArgentinaFil: Barcala, Consuelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Giunta, Javier. Hospital Italiano; ArgentinaFil: Las Heras, Marcos. Hospital Italiano; ArgentinaFil: Martinez Mateu, Carolina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Prieto, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: San Román, Eduardo. Hospital Italiano; ArgentinaFil: Krochik, Andrea Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Grosembacher, Luis. Hospital Italiano; Argentin

Report of high insulin requirements in pediatric critically ill patients with COVID-19: Experience with continuous remote glucose monitoring

Los pacientes en estado crítico con COVID-19 sufren hiperglucemias sostenidas de difícil manejo. A esto se suma el desafío de minimizar la exposición al contagio. En el presente artículo analizamos la evolución metabólica de dos pacientes pediátricos con COVID-19 admitidos en unidad de cuidados intensivos (UCI) para pacientes COVID-19 del Hospital “Prof. Dr. Juan P. Garrahan” de la Ciudad Autónoma de Buenos Aires, Argentina, que requirieron tratamiento con insulina endovenosa y cuya glucemia fue monitoreada de manera remota con la plataforma InsuMate® desarrollada en la Universidad Nacional de La Plata. Los pacientes requirieron tasas de infusión de insulina en dosis marcadamente mayores que las de otros pacientes críticos que impresionaron relacionadas con los valores de marcadores de inflamación. La infusión pudo ajustarse con cuatro monitoreos diarios de glucosa y las métricas obtenidas con el monitor de glucosa. El uso del sistema de monitoreo remoto continuo de glucosa permitió disminuir la frecuencia de monitoreo glucémico durante el tratamiento.Critically ill patients with COVID-19 suffer from sustained hyperglycemia that is difficult to manage. Added to this is the challenge of minimizing exposure to contagion. In this article we analyze the metabolic evolution of two pediatric patients with COVID-19 admitted to the intensive care unit (ICU) for COVID-19 patients at the Hospital “Prof. Dr. Juan P. Garrahan ”from the Autonomous City of Buenos Aires, Argentina, who required treatment with intravenous insulin and whose blood glucose was remotely monitored with the InsuMate® platform developed at the National University of La Plata. The patients required insulin infusion rates in doses markedly higher than those of other critically ill patients, who were impressively related to the values of inflammation markers. The infusion could be adjusted with four daily glucose monitors and the metrics obtained with the glucose monitor. The use of the continuous remote glucose monitoring system made it possible to decrease the frequency of glycemic monitoring during treatment.Fil: Krochik, Andrea Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Prieto, Mariana. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Martinez Mateu, Carolina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Barcala, Consuelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Gallagher, Rosario. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Filippini, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Arambarri, Delfina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Mendoza, Leandro Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Rosales, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: de Battista, Hernán. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; ArgentinaFil: Sanchez Peña, Ricardo Salvador. Instituto Tecnológico de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Garelli, Fabricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales. Universidad Nacional de La Plata. Instituto de Investigaciones en Electrónica, Control y Procesamiento de Señales; Argentin

Cancer immunotherapy in special challenging populations: recommendations of the Advisory Committee of Spanish Melanoma Group (GEM)

Cancer immunotherapy based on the use of antibodies targeting the so-called checkpoint inhibitors, such as programmed cell death-1 receptor, its ligand, or CTLA-4, has shown durable clinical benefit and survival improvement in melanoma and other tumors. However, there are some special situations that could be a challenge for clinical management. Persons with chronic infections, such as HIV-1 or viral hepatitis, latent tuberculosis, or a history of solid organ transplantation, could be candidates for cancer immunotherapy, but their management requires a multidisciplinary approach. The Spanish Melanoma Group (GEM) panel in collaboration with experts in virology and immunology from different centers in Spain reviewed the literature and developed evidence-based guidelines for cancer immunotherapy management in patients with chronic infections and immunosuppression. These are the first clinical guidelines for cancer immunotherapy treatment in special challenging populations. Cancer immunotherapy in chronically infected or immunosuppressed patients is feasible but needs a multidisciplinary approach in order to decrease the risk of complications related to the coexistent comorbidities

Resolving Structure and Mechanical Properties at the Nanoscale of Viruses with Frequency Modulation Atomic Force Microscopy

Structural Biology (SB) techniques are particularly successful in solving virus structures. Taking advantage of the symmetries, a heavy averaging on the data of a large number of specimens, results in an accurate determination of the structure of the sample. However, these techniques do not provide true single molecule information of viruses in physiological conditions. To answer many fundamental questions about the quickly expanding physical virology it is important to develop techniques with the capability to reach nanometer scale resolution on both structure and physical properties of individual molecules in physiological conditions. Atomic force microscopy (AFM) fulfills these requirements providing images of individual virus particles under physiological conditions, along with the characterization of a variety of properties including local adhesion and elasticity. Using conventional AFM modes is easy to obtain molecular resolved images on flat samples, such as the purple membrane, or large viruses as the Giant Mimivirus. On the contrary, small virus particles (25–50 nm) cannot be easily imaged. In this work we present Frequency Modulation atomic force microscopy (FM-AFM) working in physiological conditions as an accurate and powerful technique to study virus particles. Our interpretation of the so called “dissipation channel” in terms of mechanical properties allows us to provide maps where the local stiffness of the virus particles are resolved with nanometer resolution. FM-AFM can be considered as a non invasive technique since, as we demonstrate in our experiments, we are able to sense forces down to 20 pN. The methodology reported here is of general interest since it can be applied to a large number of biological samples. In particular, the importance of mechanical interactions is a hot topic in different aspects of biotechnology ranging from protein folding to stem cells differentiation where conventional AFM modes are already being used

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Stiffness as a source for dissipation.

<p>(a) and (d) FM-AFM topographies showing, each of them, two virus MVM particles containing genetic material. In both images the particles have different spring constant since they are sitting on different fold-symmetries <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030204#pone.0030204-Carrasco2" target="_blank">[10]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030204#pone.0030204-Carrasco3" target="_blank">[11]</a>. (b) and (e) Drive amplitude maps taken simultaneously with a and d. Since the adhesion is negligible, the compositional map is only plotting the elastic modulus. As expected for the different fold-symmetries, the virus showing the 5 fold-symmetry has lower stiffness than the other one which is showing the 3 fold-symmetry. Furthermore the viruses are softer than the substrate. (c) Simulation of the drive signal versus elastic modulus and viscosity. If the adhesion is close to zero, the drive signal is basically the elastic modulus of the sample, with the exception of samples that could have an extremely high viscosity orders of magnitude higher that the expected for virus particles. Fig c despites the corresponding profiles across the two virus particles observed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030204#pone-0030204-g006" target="_blank">fig. 6a</a>. Cantilever oscillation amplitude 1.0 nm and frequency shift 32 Hz, scan speed 350 nm/s, Resonance frequency 21 KHz, calibrated spring constant of 0.6 N/m.</p

High resolution FM-AFM. Seeing individual features.

<p>(a) Image of a muscovite mica surface (001) showing true atomic resolution. The mica was immersed into a physiological buffer to ensure that under these conditions we are able to obtain true atomically resolved images. Parameters of the image: cantilever oscillation amplitude 0.5 nm and frequency shift 36 Hz, scan speed 800 nm/s, Resonance frequency 130 KHz, nominal spring constant 40 N/m. (b) View of a MVM particle oriented with a 5-fold symmetry axis on top as obtained from a molecular surface model derived from crystallographic data <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030204#pone.0030204-AgbandjeMcKenna1" target="_blank">[36]</a> as rendered in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030204#pone.0030204-Carrasco3" target="_blank">[11]</a>. The capsid diameter is 25 nm. (c) FM-AFM topographic image of an individual MVM particle in the same orientation shown in (b).Virus particles were adsorbed on a glass surface immersed into a physiological buffer (PBS, 137 mM NaCl, 2.7 mM KCl, 1.5 mM NaH₂PO₄, 8.1 mM KH2PO₄). Parameters of the image: cantilever oscillation amplitude 0.9 nm and frequency shift 30 Hz, speed 350 nm/s, Resonance frequency 19 KHz. Calibrated spring constant of 0.6 N/m. (d) Cryo-EM model of the φ29 bacteriophage <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030204#pone.0030204-Tang1" target="_blank">[24]</a> (equatorial diameter ∼45 nm) after a <i>dilation</i> process using a size tip of 0.2 nm. Reconstruction techniques are extremely precise but require the merging and averaging of a large set of images of individual viruses and, consequently, they tend to neglect individual particle features. (e) FM-AFM topographic image of an individual φ29 particle in TMS buffer (50 mM Tris pH7.8, 10 mM Mg Cl₂, 100 mM Na Cl). This virus presents a damaged tail (see white arrow). Parameters of the image: cantilever oscillation amplitude 1.0 nm and frequency shift 31 Hz, scan speed 350 nm/s, Resonance frequency 35 KHz, calibrated spring constant of 1.8 N/m. (f) Another φ29 virus particle with a clear and well resolved tail but with some material bound to its head, forming extra protrusions. Parameters of the image: cantilever oscillation amplitude 1.0 nm and frequency shift 25 Hz, scan speed 350 nm/s, Resonance frequency 19 KHz calibrated spring constant of 0.6 N/m.</p