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This study explored process synergies attainable by integrating a vacuum ultraviolet-based advanced oxidation process with biofiltration. A comparison using granular activated carbon or granular zeolite as filtration media were examined in context of advanced wastewater treatment for potable reuse. Six biofiltration columns, three with granular activated carbon and three with granular zeolite, were operated in parallel and batch-fed daily with nitrified secondary effluent. After achieving a pseudo-steady state through the filter columns, vacuum ultraviolet treatment was applied as pre-treatment or as post-treatment, at two different applied energies (i.e., VUV-E1=1 kWh/m3 and VUV-E10=10 kWh/m3). Once granular activated carbon had transitioned to biologically activated carbon, as determined based on soluble chemical oxygen demand removal, adsorption was still observed as the main mechanism for contaminants of emerging concern and nitrate removal. Vacuum ultraviolet pre-treatment markedly improved contaminants of emerging concern removal through the integrated system, achieving 40% at VUV-E1 and 90% at VUV-E10. When applied as post-treatment to zeolite column effluents, VUV-E1 and VUV-E10 further increased contaminants of emerging concern removal by 20% and 90%, respectively. In the zeolite system, vacuum ultraviolet pre-treatment also increased soluble chemical oxygen demand removal efficiency, indicating that higher energy vacuum ultraviolet increased biodegradability. Total prokaryotes were two-fold more abundant in biologically activated carbon than in zeolite, with vacuum ultraviolet pretreatment markedly affecting microbial diversity, both in terms of richness and composition. Media type only marginally affected microbial richness in the biofilters but showed a marked impact on structural composition. No clear relationship between compositional structure and depth was observed.

The Human Variome Project (HVP) is an international effort aiming systematically to collect and share information on all human genetic variants. It has been working for years in collaboration with local scientific societies by establishing systems to collect every genetic variant reported in a country and to store these variants within a database repository: LOVD (Argentinian chapter: ar.lovd.org). Formally established in 2017 in the Argentinian Node, up to June 2019 we collected more than 25,000 genetic variants deposited by 17 different laboratories. Nowadays the HVP country nodes represent more than 30 countries. In Latin America there are four country nodes: Argentina, Brazil, Mexico and Venezuela; the first two interacted recently launching the LatinGen database. In the present work we want to share our experience in applying the HVP project focusing on its organization, rules and nomenclature to reach the goal of sharing genetic variants and depositing them in the Leiden Open Variation Database. Contributing laboratories are seeking to share variant data to gain access all over the country. It is one of our goals to stimulate the highest quality by organizing courses, applying current nomenclature rules, sponsoring lectures in national congresses, distributing newsletter to serve the Argentinian genomics community and to stimulate the interaction among Latin America countries. El Proyecto Varioma Humano (HVP) es un esfuerzo internacional que tiene como objetivo recopilar y compartir sistemáticamente información sobre todas las variantes genéticas humanas. Hemos estado trabajando durante tres años en colaboración con sociedades científicas locales, mediante el establecimiento de sistemas para recolectar todas las variantes genéticas reportadas en el país y almacenarlas dentro de la base de datos LOVD (capítulo argentino: ar.lovd.org). En el año 2017 fue establecido formalmente el Nodo Argentino del HVP, habiéndose recolectado más de 25.000 variantes genéticas depositadas por 17 laboratorios diferentes hasta junio de 2019. Hoy en día existen al menos 30 nodos del HVP, correspondientes a diferentes países. En América Latina hay cuatro nodos: Argentina, Brasil, México y Venezuela; Los dos primeros interactuaron recientemente lanzando la base de datos LatinGen. En el presente trabajo queremos compartir nuestra experiencia en la aplicación del proyecto HVP centrándonos en su organización, reglas y nomenclatura para alcanzar el objetivo de compartir variantes genéticas y depositarlas en la base de datos de variaciones abiertas de Leiden (LOVD). Es uno de nuestros objetivos estimular la más alta calidad mediante la organización de cursos, aplicación de las reglas de nomenclatura actuales, patrocinio de conferencias en congresos nacionales, distribución de boletines informativos para la comunidad de genómica argentina, y estimulación de la interacción entre los países de América Latina.

Context. Solar wind electrons play an important role in the energy balance of the solar wind acceleration by carrying energy into interplanetary space in the form of electron heat flux. The heat flux is stored in the complex electron velocity distribution functions (VDFs) shaped by expansion, Coulomb collisions, and field-particle interactions. Aims. We investigate how the suprathermal electron deficit in the anti-strahl direction, which was recently discovered in the near-Sun solar wind, drives a kinetic instability and creates whistler waves with wave vectors that are quasi-parallel to the direction of the background magnetic field. Methods. We combined high-cadence measurements of electron pitch-angle distribution functions and electromagnetic waves provided by Solar Orbiter during its first orbit. Our case study is based on a burst-mode data interval from the Electrostatic Analyser System (SWA-EAS) at a distance of 112 RS (0.52 au) from the Sun, during which several whistler wave packets were detected by Solar Orbiter’s Radio and Plasma Waves (RPW) instrument. Results. The sunward deficit creates kinetic conditions under which the quasi-parallel whistler wave becomes unstable. We directly test our predictions for the existence of these waves through solar wind observations. We find whistler waves that are quasi-parallel and almost circularly polarised, propagating away from the Sun, coinciding with a pronounced sunward deficit in the electron VDF. The cyclotron-resonance condition is fulfilled for electrons moving in the direction opposite to the direction of wave propagation, with energies corresponding to those associated with the sunward deficit. Conclusions. We conclude that the sunward deficit acts as a source of quasi-parallel whistler waves in the solar wind. The quasilinear diffusion of the resonant electrons tends to fill the deficit, leading to a reduction in the total electron heat flux.

Copper corrosion in acidic cleaning solutions is a major worry for heat exchangers. Corrosion inhibitors derived from natural sources might be a viable option. The isolation of Oleuropein compound from olive leaf and investigation of its anticorrosion potential for copper in 1.0 M H

Context. We demonstrate the calculation of solar wind electron bulk parameters based on recent observations by Solar Wind Analyser – Electron Analyser System on board Solar Orbiter. We use our methods to derive the electron bulk parameters in a time interval spanning several hours. We attempt a preliminary examination of the polytropic behavior of the electrons by analyzing the derived electron density and temperature. Moreover, we discuss the challenges in analyzing the observations due to the spacecraft charging and photo-electron contamination in the energy range below 10 eV. Aims. We derived bulk parameters for thermal solar wind electrons by analyzing Solar Orbiter observations and we investigated whether there is any typical polytropic model that is applicable to the electron density and temperature fluctuations. Methods. We used the appropriate transformations to convert the observations to velocity distribution functions in the instrument frame. We then derived the electron bulk parameters by: (a) calculating the statistical moments of the constructed velocity distribution functions and (b) fitting the constructed distributions with analytical expressions. We first tested our methods by applying them to an artificial data set, which we produced by using the forward modeling technique. Results. The forward model validates the analysis techniques we use to derive the electron bulk parameters. The calculation of the statistical moments and the fitting method determines bulk parameters that are identical (within the uncertainty limits) to the input parameters that we use to simulate the plasma electrons in the first place. An application of our analysis technique to the data reveals a nearly isothermal electron “core”. The results are affected by the spacecraft potential and the photo-electron contamination, which should be characterized in detail as part of future analyses.

Context.The Alfvénic slow solar wind is of particular interest, as it is often characterized by intense magnetic turbulence, complex proton 3D velocity distribution functions (VDF), and an ensuing richness of kinetic and dynamic processes.Aims.We take advantage of the fast time cadence of measurements taken by the Proton-Alpha Sensor (PAS) on board Solar Orbiter to analyze the kinetic properties of the proton population, the variability of their VDFs, and the possible link with propagating magnetic structures. We also study the magnetic (B) and velocity (V) correlation that characterizes this type of wind down to the ion gyroperiod.Methods.We analyzed the VDFs measured by PAS, a novelty that take advantages of the capability of 3D measurements at a 4 Hz cadence. In addition, we considered MAG observations.Results.We first show that there is a remarkable correlation between theBandVcomponents observed down to timescales approaching the ion gyrofrequency. This concerns a wide variety of fluctuations, such as waves, isolated peaks, and discontinuities. The great variability of the proton VDFs is also documented. The juxtaposition of a core and a field-aligned beam is the norm but the relative density of the beam, drift speed, and temperatures can considerably change on scales as short as as a few seconds. The characteristics of the core are comparatively more stable. These variations in the beam characteristics mostly explain the variations in the total parallel temperature and, therefore, in the total anisotropy of the proton VDFs. Two magnetic structures that are associated with significant changes in the shape of VDFs, one corresponding to relaxation of total anisotropy and the other to its strong increase, are analyzed here. Our statistical analysis shows a clear link between total anisotropy (and, thus, beam characteristics) and the direction ofBwith respect to the Parker spiral. In the present case, flux tubes aligned with Parker spiral contain an average proton VDF with a much more developed beam (thus, with larger total anisotropy) than those that are inclined, perpendicular, or even reverse with regard to the outward direction.Conclusions.These observations document the variability of the proton VDF shape in relation to the propagation of magnetic structures. This is a key area of interest for understanding of the effect of turbulence on solar wind dynamics.

Context. Rapid polarity reversals of the radial heliospheric magnetic field were discovered by Ulysses and they are now frequently observed as a common near-Sun phenomenon by NASA’s Parker Solar Probe (PSP). Other solar wind missions, including ESA-NASA Solar Orbiter (SolO), also observe similar phenomena. The nature of these fluctuations is unclear, and the relation between the “switchbacks” observed near the Sun and similar events observed at 1 AU is unknown. Aims. We make a detailed case study of the SolO plasma and magnetic field data obtained in a region that is magnetically connected to a coronal hole. We aim to check whether such fluctuations might have the same origin as the “switchbacks” observed by PSP. Methods. We used PSP magnetic field and plasma data to support our analysis of SolO data. We used the magnetic field data, electron pitch angle distributions, proton velocity distribution functions, and α-particle parameters measured by SolO to perform a detailed analysis of the observed solar wind perturbations. Results. On 27 September 2020, PSP and SolO were located around the same Carrington longitude and their latitudinal separation was very small. Solar wind plasma and magnetic field data during this time interval confirms that (at least at certain times) the solar wind observed by both spacecraft does originate from the same coronal hole region and that during these time intervals, SolO experiences several short variations similar to the “switchbacks” regularly observed by PSP. Conclusions. The suprathermal electron pitch angle distributions and α-particle speed variations indicate that the magnetic field line was bent by 180° by solar wind velocity shear. Variations in electron and proton velocity distribution functions suggest that bent field lines reconnect with each other, producing flux ropes. The observed flux ropes might be the surviving and modified remains of the switchbacks created near Sun and observed by PSP.

Small-scale kinetic processes associated with turbulence, plasma instabilities, magnetic reconnection, etc., play a major role in dissipating energy and governing the large-scale evolution of the solar wind. However, a general impediment to improving the understanding of the kinetic physics of the solar wind is in the limitations on measurement cadences of particle instruments, which are usually several orders of magnitude below the equivalent cadences of field instruments. Nevertheless, knowledge of the details of the particle velocity distribution functions (VDFs) at sub-second cadence is required to make progress in this area. This is particularly true for the electron VDFs, which play a significant role in the overall energetics of the solar wind through their transmission of heat flux from the Sun. In this paper, we detail and illustrate a novel measurement scheme deployed on Solar Orbiter’s Solar Wind Analyser Electron Analyser System (SWA-EAS), which allows for 2D pitch angle distributions (PAD) to be returned over short periods (5–10 min) at a cadence of 0.125 s. This is achieved through the use of a B-field vector shared by the magnetometer (MAG) instrument to steer the SWA-EAS system to record only that part of the full SWA-EAS field-of-view needed to construct the PAD. We provide an example of early observations using this scheme to illustrate that it is working well. Given that the electrons are usually gyrotropic, these measurements provide a new tool with which to derive details of the electron VDFs at high cadence for the study of the solar wind’s kinetic processes.

Simple Summary Gene/s sequencing in hereditary breast/ovary cancer (HBOC) in routine diagnosis is challenged by the analysis of panels. The aim of this report is to describe a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in patients with breast/ovary cancer (BOC), including triple-negative breast cancer (TNBC). TNBC is associated to BRCA1/2 at a higher rate than the rest of the breast cancer types. The more prevalent pathogenic variants (PVs) in BRCA1/2 genes do not rule out the importance to panels of genes, although they are certainly far from shedding light on the gap of the 85% predicted linkage association of BOC with BRCA1/2 and are still not elucidated. This data is also of value in health programming for alerting risks in breast screening and knowledge of the regional spectrum of genetic variants. Abstract Gene/s sequencing in hereditary breast/ovary cancer (HBOC) in routine diagnosis is challenged by the analysis of panels. We aim to report a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in patients with breast/ovary cancer (BOC), including triple-negative breast cancer (TNBC), in our population. In total 2155 BOC patients (1900 analyzed in BRCA1/2 and 255 by multigenic panels) gave 372 (17.2.6%) and 107 (24.1%) likely pathogenic/pathogenic variants (LPVs/PVs), including BRCA and non-BRCA genes, for the total and TNBC patients, respectively. When BOC was present in the same proband, a 51.3% rate was found for LPVs/PVs in BRCA1/2. Most of the LPVs/PVs in the panels were in BRCA1/2; non-BRCA gene LPVs/PVs were in CDH1, CHEK2, CDKN2A, MUTYH, NBN, RAD51D, and TP53. TNBC is associated with BRCA1/2 at a higher rate than the rest of the breast cancer types. The more prevalent PVs in BRCA1/2 genes (mostly in BRCA1) do not rule out the importance to panels of genes, although they are certainly far from shedding light on the gap of the 85% predicted linkage association of BOC with BRCA1/2 and are still not elucidated.

Gene/s sequencing in hereditary breast/ovary cancer (HBOC) in routine diagnosis is challenged by the analysis of panels. We aim to report a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in patients with breast/ovary cancer (BOC), including triple-negative breast cancer (TNBC), in our population. In total 2155 BOC patients (1900 analyzed in BRCA1/2 and 255 by multigenic panels) gave 372 (17.2.6%) and 107 (24.1%) likely pathogenic/pathogenic variants (LPVs/PVs), including BRCA and non-BRCA genes, for the total and TNBC patients, respectively. When BOC was present in the same proband, a 51.3% rate was found for LPVs/PVs in BRCA1/2. Most of the LPVs/PVs in the panels were in BRCA1/2, non-BRCA gene LPVs/PVs were in CDH1, CHEK2, CDKN2A, MUTYH, NBN, RAD51D, and TP53. TNBC is associated with BRCA1/2 at a higher rate than the rest of the breast cancer types. The more prevalent PVs in BRCA1/2 genes (mostly in BRCA1) do not rule out the importance to panels of genes, although they are certainly far from shedding light on the gap of the 85% predicted linkage association of BOC with BRCA1/2 and are still not elucidated.

The Solar Orbiter mission seeks to make connections between the physical processes occurring at the Sun or in the solar corona and the nature of the solar wind created by those processes which is subsequently observed at the spacecraft. The mission also targets physical processes occurring in the solar wind itself during its journey from its source to the spacecraft. To meet the specific mission science goals, Solar Orbiter will be equipped with both remote-sensing and in-situ instruments which will make unprecedented measurements of the solar atmosphere and the inner heliosphere. A crucial set of measurements will be provided by the Solar Wind Analyser (SWA) suite of instruments. This suite consists of an Electron Analyser System (SWA-EAS), a Proton and Alpha particle Sensor (SWA-PAS), and a Heavy Ion Sensor (SWA-HIS) which are jointly served by a central control and data processing unit (SWA-DPU). Together these sensors will measure and categorise the vast majority of thermal and suprathermal ions and electrons in the solar wind and determine the abundances and charge states of the heavy ion populations. The three sensors in the SWA suite are each based on the top hat electrostatic analyser concept, which has been deployed on numerous space plasma missions. The SWA-EAS uses two such heads, each of which have 360° azimuth acceptance angles and ±45° aperture deflection plates. Together these two sensors, which are mounted on the end of the boom, will cover a full sky field-of-view (FoV) (except for blockages by the spacecraft and its appendages) and measure the full 3D velocity distribution function (VDF) of solar wind electrons in the energy range of a few eV to ∼5 keV. The SWA-PAS instrument also uses an electrostatic analyser with a more confined FoV (−24° to +42° × ±22.5° around the expected solar wind arrival direction), which nevertheless is capable of measuring the full 3D VDF of the protons and alpha particles arriving at the instrument in the energy range from 200 eV/q to 20 keV/e. Finally, SWA-HIS measures the composition and 3D VDFs of heavy ions in the bulk solar wind as well as those of the major constituents in the suprathermal energy range and those of pick-up ions. The sensor resolves the full 3D VDFs of the prominent heavy ions at a resolution of 5 min in normal mode and 30 s in burst mode. Additionally, SWA-HIS measures 3D VDFs of alpha particles at a 4 s resolution in burst mode. Measurements are over a FoV of −33° to +66° × ±20° around the expected solar wind arrival direction and at energies up to 80 keV/e. The mass resolution (m/Δm) is > 5. This paper describes how the three SWA scientific sensors, as delivered to the spacecraft, meet or exceed the performance requirements originally set out to achieve the mission’s science goals. We describe the motivation and specific requirements for each of the three sensors within the SWA suite, their expected science results, their main characteristics, and their operation through the central SWA-DPU. We describe the combined data products that we expect to return from the suite and provide to the Solar Orbiter Archive for use in scientific analyses by members of the wider solar and heliospheric communities. These unique data products will help reveal the nature of the solar wind as a function of both heliocentric distance and solar latitude. Indeed, SWA-HIS measurements of solar wind composition will be the first such measurements made in the inner heliosphere. The SWA data are crucial to efforts to link the in situ measurements of the solar wind made at the spacecraft with remote observations of candidate source regions. This is a novel aspect of the mission which will lead to significant advances in our understanding of the mechanisms accelerating and heating the solar wind, driving eruptions and other transient phenomena on the Sun, and controlling the injection, acceleration, and transport of the energetic particles in the heliosphere.

A comprehensive pilot study was carried out to experimentally assess the potential of newly developed treatment trains integrating two-stage AOPs and biofiltration to reach potable reuse water quality standards from municipal wastewater. The processes consisted of a two-stage AOPs with (carbon or limestone) biofiltration, the first AOP (O

Cytokinins (CK) are key hormones that control plant growth, leaf development, morphogenesis and senescence, nutrient allocation and stress responses, all crucial traits for crop productivity. We reconstructed the genetic pathway of cytokinins in the leafy crop Cichorium endivia and in the reference species for Asteraceae Lactuca sativa. Genes involved in cytokinin metabolism, perception and signaling, and candidates to nucleotide-nucleoside interconversion and transport were identified, classified and manually annotated. RNAseq expression profiles of edible leaves of four C. endivia commercial cultivars pointed to genes involved in cytokinin activation, O-glycosilation and response as the major source of variability among cultivars. Cytokinin metabolites analysis indicated cis-zeatin (cZ) derivatives as the most abundant forms of cytokinins in C. endivia leaves. Metabolite-transcript correlation identified candidate genes for cis- and trans-zeatin reversible O-glycosylation. Candidate genes involved in the two-step interconversion of cytokinin bases, nucleosides and nucleotides, which have remained elusive for a long time, were also found. Robust gene co-expression networks from RNAseq profiles of two production years validated our cytokinin pathway and revealed the intrinsic intra-modular structure of the CK pathway in leaves. Members of the TALE superclass of homeobox transcription factors were also identified as regulatory hubs that antagonize the AHK4/CRE1-driven CK co-expression network in C. endivia leaves.

Bulimia nervosa (BN) and binge eating disorder (BED) are psychiatric conditions marked by emotional disorders managed through the ingestion of great amount of food, with consequent vomiting for avoiding weight gain. Such behavioral habits are dysfunctional and severely impact both psychological and physical health, also compromising neurobiological processes. In the present review, we focus on recent neuroimaging findings (2010–2019) that provide insight into the neural bases of BN and BED. We describe the role of different neuroimaging techniques (magnetic resonance imaging, both structural and functional, positron emission tomography, single-photon emission computerized tomography, electroencephalography and magnetoencephalography) in the delineation of pathophysiological aspects of BN and BED. Results highlight the main involvement of the frontal system and its relationships with temporal areas for reward and self-regulatory processes modulation. The network that regulates food-stimuli control seems to be widespread across the brain, catching the insula, precentral gyrus, frontal cortex and extending until the visual cortex for processing of body image. These results demonstrate diffuse brain vulnerability associated with BN and BED and can confirm that symptomatology maintenance results from several neurostructural and neurofunctional alterations.

MAPK phosphatases (MKP) downregulate the activity of mitogen-activated protein kinases (MAPK), such as ERK1/2, and modulate the processes regulated by these kinases. ERK1/2 participate in a wide range of processes including tissue-specific hormone-stimulated steroidogenesis. H295R cells are a suitable model for the study of human adrenal cortex functions, particularly steroid synthesis, and respond to angiotensin II (Ang II) triggering ERK1/2 phosphorylation in a transient fashion. MKP-3 dephosphorylates ERK1/2 and, as recently reported, forkhead box protein 1 (FOXO1). Here, we analyzed MKP-3 expression in H295R cells and its putative regulation by Ang II. Results showed the expression of MKP-3 full length (L) and a short splice variant (S), and the upregulation of both isoforms by Ang II. L and S messenger and protein levels increased 30 min after Ang II stimulation and declined over the next 3 h, a temporal frame compatible with ERK1/2 dephosphorylation. In addition, FOXO1 activation is known to include its dephosphorylation and nuclear translocation. Therefore, we analyzed the effect of Ang II on FOXO1 modulation. Ang II induced FOXO1 transient phosphorylation and translocation and also the induction of p21, a FOXO1-dependent gene, whereas MKP-3 knock-down reduced both FOXO1 translocation and p21 induction. These data suggest that, through MKP-3, Ang II counteracts its own effects on ERK1/2 activity and also triggers the activation of FOXO-1 and the induction of cell cycle inhibitor p21. Taken together, the current findings reveal the participation of MKP-3 not only in turn–off but also in turn-on signals which control important cellular processes., Cell biology; Proteins; Biochemistry; Molecular biology; Biomolecules; MKP-3, DUSP6, FOXO1, p21, H295R, ERK1/2

Background: Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients. The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population. Results: A total of 96 patients carried a pathogenic germline mutation, accounting for an overall 24.1% mutation incidence. Among mutation carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient exhibited a mutation in both genes. Three pathogenic mutations were recurrent mutations detected five, three, and four times and represented 12.5% of the mutated samples. Worth highlighting, a 50% mutation incidence was detected when breast and ovarian cancer coexisted in the same patient. Novel mutations amounted to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational spectrum compared to our previously published data on breast cancer patients. Conclusions: In sum, our study provides novel data on ovarian BRCA1/2 mutation prevalence worldwide, enhances adequate patient selection for family counseling and prevention, and sheds light on the benefits of iPARP treatment. Fil: Cardozo, Florencia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Goncalves, Susana. AstraZeneca Argentina MC; Argentina Fil: Mele, Pablo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Liria, Natalia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Sganga, Leonardo. AstraZeneca Argentina MC; Argentina Fil: Diaz Perez, Ignacio. AstraZeneca Argentina MC; Argentina Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina

In Ashkenazi Jewish (AJ) high risk families 3 mutations [2 in BRCA1 (c. 68_69del and c.5266dup) and 1 in BRCA2 (c.5946del)] account for the majority of high risk breast and ovarian cancer cases in that ethnic group. Few studies with limited number of genotyped individuals have expanded the spectrum of mutations in both BRCA genes beyond the 3 mutation panel. In this study, 279 high risk individual AJ were counseled at CEMIC (Centro de Educación Médica e Investigaciones Clínicas), and were genotyped first for the 3 recurrent mutation panel followed by Next Generation Sequencing (NGS) of BRCA1 BRCA2 in 76 individuals who tested negative for the first genotyping step. Of 279 probands (259 women), 55 (50 women) harbored one of the 3 mutations (19.7%); Of 76 fully sequenced cases (73 women), 6 (5 women) (7.9%) carried a pathogenic mutation: in BRCA1, c.2728C > T - p.(Gln910*); c.5407-?_(*1_?)del and c.5445G > A - p.(Trp1815*); in BRCA2, c.5351dup - p.(Asn1784Lysfs*3); c.7308del - p.(Asn2436Lysfs*33) and c.9026_9030del - p.(Tyr3009Serfs*7). Of 61 mutation carriers the distribution was as follows: 11 cancer free at the time of genotyping, 34 female breast cancer cases with age range 28-72 years (41.6 ± 9.3), 3 male breast cancer cases with age range 59-75 years (65 ± 7.3), 6 breast and ovarian cancer cases with age range 35-60 years (breast 40.4 ± 5.2; ovary 47.8 ± 7.2) and 7 ovarian cancer cases with age range 41-77 years (60.6 ± 13.3). This information proved highly useful for counseling, treatment, and prevention for the patient and the family. In conclusion comprehensive BRCA1/2 testing in AJ high risk breast ovarian cancer cases adds valuable clinically relevant information in a subset of cases estimated up to 7% and is therefore recommended. Fil: Solano, Angela Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Liria, Natalia C.. Centro de Educación Medica E Invest.clinicas; Argentina Fil: Jalil, Fernanda. Centro de Educación Medica E Invest.clinicas; Argentina Fil: Faggionato, Daniela. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Mele, Pablo G.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Mampel, Alejandra. Universidad Nacional de Cuyo; Argentina Fil: Cardoso, Florencia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina Fil: Podesta, Ernesto J.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina

In steroid-producing cells, cholesterol transport from the outer to the inner mitochondrial membrane is the first and rate-limiting step for the synthesis of all steroid hormones. Cholesterol can be transported into mitochondria by specific mitochondrial protein carriers like the steroidogenic acute regulatory protein (StAR). StAR is phosphorylated by mitochondrial ERK in a cAMP-dependent transduction pathway to achieve maximal steroid production. Mitochondria are highly dynamic organelles that undergo replication, mitophagy and morphology changes, all processes allowed by mitochondrial fusion and fission, known as mitochondrial dynamics. Mitofusin (Mfn) 1 and 2 are GTPases involved in the regulation of fusion, while dynamin-related protein 1 (Drp1) is the major regulator of mitochondrial fission. Despite the role of mitochondrial dynamics in neurological and endocrine disorders, little is known about fusion/fission in steroidogenic tissues. In this context, the present work aimed to study the role of angiotensin II (Ang II) in protein subcellular compartmentalization, mitochondrial dynamics and the involvement of this process in the regulation of aldosterone synthesis. We demonstrate here that Ang II stimulation promoted the recruitment and activation of PKCε, ERK and its upstream kinase MEK to the mitochondria, all of them essential for steroid synthesis. Moreover, Ang II prompted a shift from punctate to tubular/elongated (fusion) mitochondrial shape, in line with the observation of hormone-dependent upregulation of Mfn2 levels. Concomitantly, mitochondrial Drp1 was diminished, driving mitochondria toward fusion. Moreover, Mfn2 expression is required for StAR, ERK and MEK mitochondrial localization and ultimately for aldosterone synthesis. Collectively, this study provides fresh insights into the importance of hormonal regulation in mitochondrial dynamics as a novel mechanism involved in aldosterone production. Fil: Helfenberger, Katia Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Castillo, Ana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Mele, Pablo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Fiore, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Herrera, Lucía Manuela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Finocchietto, Paola Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Poderoso, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina

Although the role of arachidonic acid (AA) in angiotensin II (ANG II)- and potassium-stimulated steroid production in zona glomerulosa cells is well documented, the mechanism responsible for AA release is not fully described. In this study we evaluated the mechanism involved in the release of intramitochondrial AA and its role in the regulation of aldosterone synthesis by ANG II in glomerulosa cells. We show that ANG II and potassium induce the expression of acyl-coenzyme A (CoA) thioesterase 2 and acyl-CoA synthetase 4, two enzymes involved in intramitochondrial AA generation/export system well characterized in other steroidogenic systems. We demonstrate that mitochondrial ATP is required for AA generation/export system, steroid production, and steroidogenic acute regulatory protein induction. We also demonstrate the role of protein tyrosine phosphatases regulating acyl-CoA synthetase 4 and steroidogenic acute regulatory protein induction, and hence ANG II-stimulated aldosterone synthesis. Copyright © 2012 by The Endocrine Society. Fil: Mele, Pablo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina Fil: Duarte, Alejandra Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina Fil: Paz, Cristina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina Fil: Capponi, Alessandro. University Hospital; Suiza Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica; Argentina

Background: A perceived risk of time-limited emergency department (ED) assessment of patients is inadequate workup leading to inappropriate disposition. The aim of this study was to examine the association of time to disposition plan (TDP) on ED length of stay (LOS) and correlate this to mortality. Methods: A retrospective review of data collected from ED information systems at three hospitals was conducted between June 2008 and October 2009. Included patients were admitted to a general medical unit. Patients were excluded if admitted to intensive care, coronary care, a cardiac monitored bed or required surgery in first 24 h or had an expected LOS of