Estimation of electron density in the nighttime ionosphere based on remote sensing of the 135.6 nm far ultraviolet emission

This thesis develops a method to accurately estimate the electron density altitude profiles of the nighttime ionosphere, as well as important parameters such as the peak height and density, using nighttime far ultraviolet (FUV) measurements of the 135.6 nm nighttime emissions. Specifically, we will describe a method to accurately obtain the electron density content of the ionosphere by using brightness measurements of the nighttime 135.6 nm emission. The method is applied and tested using simulated measurements to relate to those to be obtained by the limb-viewing FUV instrument on board the Ionospheric Connection Explorer (ICON) satellite scheduled to be launched in 2017. The OI 135.6 nm emission can be used as a proxy of the ionosphere's electron density and is related through an integral equation of the volume emission rate to the brightness measured by the FUV instrument. The instrument's observation geometry allows for the discretization of the problem, thus connecting the ionosphere's electron density with the measured brightness through a matrix equation. Regularization methods are used in order to enforce constraints of smoothness and continuity on the estimation of the volume emission rate, to compensate for the noise amplification in the inversion process. Tikhonov regularization, generalized cross-validation, total variation and Bayesian methods that assume prior knowledge of the ionosphere's electron density distribution are investigated. Comprehensive simulations are used to explore the different brightness intensities for all longitudes, and for latitudes from -40 to 40 degrees, in order to allow the characterization of the effect of different SNR values on the electron density reconstruction accuracy. FUV measurements are simulated using the International Reference Ionosphere (IRI) and Mass Spectrometer and Incoherent Radar (MSIS) models to create a forward model which can be inverted in order to validate the altitude profile reconstruction as well as the peak height and density accuracy. This allows us to investigate the expected performance of the FUV instrument

Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility

Copyright © 2020 The Authors.Meiotic reductional division depends on the synaptonemal complex (SC), a supramolecular protein assembly that mediates homologous chromosomes synapsis and promotes crossover formation. The mammalian SC has eight structural components, including SYCE1, the only central element protein with known causative mutations in human infertility. We combine mouse genetics, cellular, and biochemical studies to reveal that SYCE1 undergoes multivalent interactions with SC component SIX6OS1. The N terminus of SIX6OS1 binds and disrupts SYCE1’s core dimeric structure to form a 1:1 complex, while their downstream sequences provide a distinct second interface. These interfaces are separately disrupted by SYCE1 mutations associated with nonobstructive azoospermia and premature ovarian failure (POF), respectively. Mice harboring SYCE1’s POF mutation and a targeted deletion within SIX6OS1’s N terminus are infertile with failure of chromosome synapsis. We conclude that both SYCE1-SIX6OS1 binding interfaces are essential for SC assembly, thus explaining how SYCE1’s reported clinical mutations give rise to human infertility.O.R.D. is a Sir Henry Dale Fellow jointly funded by the Wellcome Trust and Royal Society (grant number 104158/Z/14/Z). This work was supported by MINECO (BFU2017-89408-R) and by Junta de Castilla y Leon (CSI239P18). F.S.-S., L.G.-H., and N.F.-M. are supported by European Social Fund/JCyLe grants (EDU/556/2019, EDU/1083/2013, and EDU/310/2015). CIC-IBMCC is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia cofunded by the Castilla–León autonomous government and the European Regional Development Fund (CLC–2017–01)

Identification of Interleukin-27 (IL-27)/IL-27 Receptor Subunit Alpha as a Critical Immune Axis for In Vivo HIV Control

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (>50,000) or low (600 soluble proteins, our data highlight the importance of Th17 cells and Wnt/β-catenin signaling in HIV control and especially identify the IL-27/IL-27 receptor subunit alpha (IL-27RA) axis as a predictor of plasma viral load and proviral copy number in the peripheral blood. These data may provide important guidance to therapeutic approaches in the HIV cure agenda

Rapidly progressive Bronchiolitis Obliterans Organising Pneumonia presenting with pneumothorax, persistent air leak, acute respiratory distress syndrome and multi-organ dysfunction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Bronchiolitis Obliterans Organising Pneumonia (BOOP) may often present initially as a recurrent spontaneous pneumothorax and then develop multi-system complications.</p> <p>Case presentation</p> <p>A 17-year-old boy presented with a pneumothorax, which developed into rapidly progressive Bronchiolitis Obliterans Organising Pneumonia (BOOP). He developed multi-organ dysfunction (including adult respiratory distress syndrome, oliguric renal failure, acute coronary syndrome, cardiac failure and a right atrial thrombus) which necessitated prolonged intensive care. Diagnosis was confirmed on open lung biopsy and he responded well to treatment with corticosteroids.</p> <p>Conclusion</p> <p>BOOP is exquisitely sensitive to oral corticosteroids but if the diagnosis is not considered in such patients and appropriate treatment instituted early, BOOP may often lead to prolonged hospital admission with considerable morbidity.</p

Identification of interleukin-27 (IL-27)/IL-27 receptor subunit alpha as a critical immune axis for in vivo hiv control

Intact and broad immune cell effector functions and specific individual cytokines have been linked to HIV disease outcome, but their relative contribution to HIV control remains unclear. We asked whether the proteome of secreted cytokines and signaling factors in peripheral blood can be used to discover specific pathways critical for host viral control. A custom glass-based microarray, able to measure >600 plasma proteins involved in cell-to-cell communication, was used to measure plasma protein profiles in 96 HIV-infected, treatment-naive individuals with high (> 50,000) or low (<10,000 HIV RNA copies/ml) viral loads. Univariate and regression model analysis demonstrate that plasma levels of soluble interleukin-27 (IL-27) are significantly elevated in individuals with high plasma viremia (P < 0.0001) and are positively correlated with proviral HIV-DNA copy numbers in peripheral blood mononuclear cells (PBMC) (Rho = 0.4011; P = 0.0027). Moreover, soluble IL-27 plasma levels are negatively associated with the breadth and magnitude of the total virus-specific T-cell responses and directly with plasma levels of molecules involved in Wnt/beta-catenin signaling. In addition to IL-27, gene expression levels of the specific IL-27 receptor (IL27RA) in PBMC correlated directly with both plasma viral load (Rho = 0.3531; P = 0.0218) and the proviral copy number in the peripheral blood as an indirect measure of partial viral reservoir (Rho = 0.4580; P = 0.0030). These results were validated in unrelated cohorts of early infected subjects as well as subjects before and after initiation of antiretroviral treatment, and they identify IL-27 and its specific receptor as a critical immune axis for the antiviral immune response and as robust correlates of viral load and proviral reservoir size in PBMC. IMPORTANCE The detailed knowledge of immune mechanisms that contribute to HIV control is a prerequisite for the design of effective treatment strategies to achieve HIV cure. Cells communicate with each other by secreting signaling proteins, and the blood is a key conduit for transporting such factors. Investigating the communication factors promoting effective immune responses and having potentially antiviral functions against HIV using a novel focused omics approach (Peer ReviewedPostprint (published version

Real-life outcomes in biotypes of psychotic disorders based on neurocognitive performance

Producción CientíficaAiming at discerning potential biotypes within the psychotic syndrome, we have recently reported the possible existence of two clusters or biotypes across schizophrenia and bipolar disorder characterized by their cognitive performance using the Brief Assessment of Cognition in Schizophrenia (BACS) instrument and validated with independent biological and clinical indexes (Fernández-Linsenbarth et al. in Schizophr Res 229:102–111, 2021). In this previous work, the group with larger cognitive deficits (N = 93, including 69 chronic schizophrenia, 17 first episodes (FE) of schizophrenia and 7 bipolar disorder patients) showed smaller thalamus and hippocampus volume and hyper-synchronic electroencephalogram than the group with milder deficits (N = 105, including 58 chronic schizophrenia, 25 FE and 22 bipolar disorder patients). We predicted that if these biotypes indeed corresponded to different cognitive and biological substrates, their adaptation to real life would be different. To this end, in the present work we have followed up the patients’ population included in that work at 1st and 3rd years after the date of inclusion in the 2021 study and we report on the statistical comparisons of each clinical and real-life outcomes between them. The first cluster, with larger cognitive deficits and more severe biological alterations, showed during that period a decreased capacity for job tenure (1st and 3rd years), more admissions to a psychiatric ward (1st year) and a higher likelihood for quitting psychiatric follow-up (3rd year). Patients in the second cluster, with moderate cognitive deficits, were less compliant with prescribed treatment at the 3rd year. The differences in real-life outcomes may give additional external validity to that yielded by biological measurements to the described biotypes based on neurocognition.Instituto de Salud Carlos III (grant ID PI18/00178)Dirección Regional de Salud de Castilla y León (grant ID GRS 2121/A/2020)Junta de Castilla y León - predoctoral grants from the Consejería de Educación and the European Social Fund (grant IDs VA-183-18 to IFL and VA- 223-19 to RMBRS)Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Mediciones de gases en la pluma cratérica y en fumarolas hidrotermales del Complejo Copahue - Caviahue

El Complejo Copahue - Caviahue (provincia de Neuquén) aloja un sistema hidrotermal con un interesante potencial geotérmico y, además, a uno de los volcanes más activos de Argentina: el volcán Copahue. Tanto este volcán como las áreas termales periféricas presentan emisiones gaseosas, las cuales permanentemente aportan información acerca de la actividad del volcán y de las condiciones de los fluidos en el acuífero geotermal. Por este motivo, llevar a cabo un seguimiento de las manifestaciones gaseosas consiste en una actividad relevante y con diversas aplicaciones.En febrero del 2020 se llevó a cabo una campaña de medición de gases en el complejo mencionado. El instrumental utilizado consistió en un equipo Multigas desarrollado por el ICES ? CNEA, capaz de tomar mediciones en tiempo real de concentraciones de CO2, SO2 y H2S, así como de condiciones atmosféricas tales como la presión y la temperatura. Este instrumento fue utilizado para tomar mediciones de la composición de: (i) la pluma cratérica del volcán Copahue y (ii) de las fumarolas en dos sitios termales (Villa de Copahue y Las Maquinitas), emitidas desde el acuífero geotermal periférico. Además, en el sitio Villa de Copahue se realizaron mediciones de flujo de CO2 emitido a través del suelo, con un flujómetro comercial West Systems.Las mediciones en la pluma cratérica del volcán Copahue permitieron obtener relaciones CO2/SO2. Esta valiosa relación constituye una señal geoquímica precursora de erupciones volcánicas. Por otro lado, en las dos áreas termales periféricas se obtuvieron relaciones CO2/H2S. Por último, en la Villa de Copahue se realizó un mapa de flujo del CO2 del suelo, se cuantificó la cantidad de este gas liberado a la atmósfera y, utilizando la relación CO2/H2S, se obtuvo una estimación de la cantidad de H2S emitido.Fil: Lamberti, María Clara Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Geológicas. Grupo de Estudio y Seguimiento de Volcanes Activos; ArgentinaFil: Núñez, N.. Comisión Nacional de Energía Atómica; ArgentinaFil: Sánchez, H.. Comisión Nacional de Energía Atómica; ArgentinaFil: Llano, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Geológicas. Grupo de Estudio y Seguimiento de Volcanes Activos; ArgentinaFil: Carbajal, F.. Secretaría de Industria y Minería. Servicio Geológico Minero Argentino; ArgentinaFil: Vesga Ramires, A.. Comisión Nacional de Energía Atómica; ArgentinaFil: Forte, Pablo Brian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Geológicas. Grupo de Estudio y Seguimiento de Volcanes Activos; ArgentinaFil: Massenzio, Antonella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Geológicas. Grupo de Estudio y Seguimiento de Volcanes Activos; ArgentinaFil: García, S.. Secretaría de Industria y Minería. Servicio Geológico Minero Argentino; ArgentinaFil: Agusto, Mariano Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ciencias Geológicas. Grupo de Estudio y Seguimiento de Volcanes Activos; ArgentinaFil: Gómez, M.. Comisión Nacional de Energía Atómica; Argentina15° Encuentro del Centro Internacional de Ciencias de la TierraMendozaArgentinaUniversidad Nacional de CuyoComisión Nacional de Energía Atómic

HIVconsv Vaccines and Romidepsin in Early-Treated HIV-1-Infected Individuals: Safety, Immunogenicity and Effect on the Viral Reservoir (Study BCN02)

Kick&kill strategies combining drugs aiming to reactivate the viral reservoir with therapeutic vaccines to induce effective cytotoxic immune responses hold potential to achieve a functional cure for HIV-1 infection. Here, we report on an open-label, single-arm, phase I clinical trial, enrolling 15 early-treated HIV-1-infected individuals, testing the combination of the histone deacetylase inhibitor romidepsin as a latency-reversing agent and the MVA.HIVconsv vaccine. Romidepsin treatment resulted in increased histone acetylation, cell-associated HIV-1 RNA, and T-cell activation, which were associated with a marginally significant reduction of the viral reservoir. Vaccinations boosted robust and broad HIVconsv-specific T cells, which were strongly refocused toward conserved regions of the HIV-1 proteome. During a monitored ART interruption phase using plasma viral load over 2,000 copies/ml as a criterium for ART resumption, 23% of individuals showed sustained suppression of viremia up to 32 weeks without evidence for reseeding the viral reservoir. Results from this pilot study show that the combined kick&kill intervention was safe and suggest a role for this strategy in achieving an immune-driven durable viremic control

Definition of the viral targets of protective HIV-1-specific T cell responses

<p>Abstract</p> <p>Background</p> <p>The efficacy of the CTL component of a future HIV-1 vaccine will depend on the induction of responses with the most potent antiviral activity and broad HLA class I restriction. However, current HIV vaccine designs are largely based on viral sequence alignments only, not incorporating experimental data on T cell function and specificity.</p> <p>Methods</p> <p>Here, 950 untreated HIV-1 clade B or -C infected individuals were tested for responses to sets of 410 overlapping peptides (OLP) spanning the entire HIV-1 proteome. For each OLP, a "protective ratio" (PR) was calculated as the ratio of median viral loads (VL) between OLP non-responders and responders.</p> <p>Results</p> <p>For both clades, there was a negative relationship between the PR and the entropy of the OLP sequence. There was also a significant additive effect of multiple responses to beneficial OLP. Responses to beneficial OLP were of significantly higher functional avidity than responses to non-beneficial OLP. They also had superior in-vitro antiviral activities and, importantly, were at least as predictive of individuals' viral loads than their HLA class I genotypes.</p> <p>Conclusions</p> <p>The data thus identify immunogen sequence candidates for HIV and provide an approach for T cell immunogen design applicable to other viral infections.</p