Search

Los carragenanos (CGNs), galactanos sulfatados aislados de algas rojas, han sidoidentificados como potentes inhibidores del virus Herpes simplex tipo 1 y 2 (HSV-1 y HSV-2) afectando principalmente la adsorción de HSV a la célula, etapa inicial del cicloviral. Dado que presentan una similitud estructural con el heparan sulfato (HS), receptorcelular que media la adsorción de HSV a la célula, actúan bloqueando la interacciónvirus-HS, en la que participan glicoproteínas de la envoltura viral. En estudios previosse seleccionaron y caracterizaron variantes virales sinciciales (syn) de HSV-1 (F) porpasajes sucesivos del virus en células Vero en presencia de un CGN natural 1C3 (deestructura relacionada con CGNs Iota (ι) y Kappa (κ)) con el fin de evaluar la capacidadde los CGNs de generar variantes virales resistentes durante el proceso de selección. Enel presente trabajo se profundizó el estudio de la caracterización citopática y patogénicade las variantes 1C314-1 y 1C317-2. Las variantes mostraron un bajo nivel deresistencia a 1C3, heparina, aciclovir (ACV) y foscarnet (PFA). Las mismas resultaronavirulentas en ratones BALB/c infectados por vía intravaginal respecto de la cepa patrónque mostró alta mortalidad. La atenuación se correlacionó con bajos niveles de04:00 p.m. 22/12/2014citoquinas pro-inflamatorias (TNF-α, IL-6) en lavados vaginales, aunque el título viralfue similar al obtenido con la cepa patrón. Por vía intranasal las variantes mostraron unamarcada virulencia en ratones BALB/c, conduciendo a una generalizada diseminaciónviral. En ratones C57BL/6 resultaron avirulentas empleando las mismas vías deinfección. Para evaluar la capacidad de generar variantes atenuadas con otro serotipo de HSV empleando la misma estrategia usada con HSV-1, se realizaron pasajes seriados de HSV-2 cepa MS en células Vero en presencia de concentraciones crecientes de CGNs ιy κ. Se seleccionaron 4 clones, ι22-9, ι22-12, κ22-12 y κ22-13, los cuales mostrarontener fenotipo syn, leve resistencia a los CGNs y a la heparina, pero variablesusceptibilidad al ACV y al PFA. Todos los clones fueron menos virulentos que la cepapatrón (100% mortalidad) particularmente para ratones C57BL/6 por inoculaciónintravaginal e intranasal. La atenuación de las variantes de HSV-2 se correlacionó conaltos niveles de TNF-α e IL-6 en lavados vaginales, y la infectividad cuantificada en losmismos fue similar a la obtenida con la cepa parental. Las variantes mostraron unareplicación similar a la cepa parental en células Vero. Sin embargo, en cultivosprimarios de astrocitos murinos mostraron un menor rendimiento viral. Los estudios invitro realizados, mostraron que los CGNs ι y κ estimulan la proliferación celular y laliberación de citoquinas en macrófagos murinos (RAW264.7). Sin embargo, inoculadosen ratones BALB/c por vía intravenosa no lograron elevar los niveles de citoquinasséricas. El conjunto de estos resultados indica que el sistema inmune innato,especialmente en la regulación de los niveles de TNF-α e IL-6, juega un rol deimportancia en la patología del virus herpes simplex y apunta a considerar la posibilidadque este tipo de variantes virales tanto de HSV-1 como de HSV-2 emerjan durante lasterapias antivirales basadas en CGNs. Natural carrageenans (CGNs), extracted from red seaweeds, are well known as potentand selective inhibitors of Herpes Simplex virus type 1 and 2 (HSV-1 and HSV-2). They have a chemical structure similar to heparan sulfate (HS) that serves as a primaryreceptor for adsorption. Their mode of antiviral action is by interference with HSVattachment to cells, blocking the interaction virus-HS, involving viral glycoprotein‟s. Ina previous work, viral variants of HSV-1 were obtained by successive passages on Verocells under selective pressure with the CGN 1C3, (partially cyclized μ/v-carrageenan,related to ι and κ CGNs) in order to test the ability of the carrageenan to generateresistant variants during the selection process. In the present work, a more detailedstudy of the cytopathic and pathogenic behavior of HSV-1 syncytial (syn) variants 1C314-1 and 1C317-2 was carried out. The variants showed low levels of resistance to 1C3, heparin, Aciclovir (ACV), and Foscarnet (PFA). They also showed to be avirulentfor BALB/c mice infected by intravaginal route, although the parental strain F washighly lethal. The attenuation of the variants was correlated with lower levels of proinflammatorycytokines (IL-6 and TNF-α) in vaginal lavages with respect to theparental strain, despite that viral titers were similar between the viral variants and the Fstrain. Nevertheless, the variants were highly lethal for BALB/c mice inoculated by theintranasal route, with a generalized organ spreading. To evaluate the capacity togenerate attenuated variants using another HSV serotype employing the same strategyused before, 22 passages of HSV-2 (MS) were made on Vero cells with increasingamounts of κ or ι carrageenan. As a result of this, four clones were selected and named,ι22-9, ι22-12, κ22-12 and κ22-13. The clones showed a 100% syn phenotype, a mildresistance to CGNs and heparin and a variable susceptibility to ACV and PFA. All theclones were less virulent for mice intravaginal and intranasal inoculated, particularly for C57BL/6 strain, whereas MS strain produced 100% of mortality. In contrast to HSV-1variants, the attenuation was correlated with high levels of pro-inflammatory cytokines (TNF-α y IL-6), on vaginal lavages. The variants of HSV-2 showed that although all ofthem grew equally on Vero cells, a partially restricted phenotype was observed when aprimary culture of mouse astrocytes was employed. Finally, the CGNs were able tostimulate the proliferation of several cells lines and cytokines secretion in vitro but theydid not showed this behavior on BALB/c mice inoculated by intravenous route. Taking all these results together, we can conclude that the innate immune system,specially TNF-α and IL-6 expression, plays an important role in the pathology of herpessimplex virus, and the possibility that this kind of HSV-1 and HSV-2 variants couldemerge during an antiviral therapy for humans based on CGNs, must be considered. Fil: Mateu, Cecilia Gabriela. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.

We use photometry from the DECam Legacy Survey to detect candidate tidal tails extending ~5 deg on either side of the Palomar 13 globular cluster. The tails are aligned with the proper motion of Palomar 13 and are consistent with its old, metal-poor stellar population. We identify three RR Lyrae stars that are plausibly associated with the tails, in addition to four previously known in the cluster. From these RR Lyrae stars, we find that the mean distance to the cluster and tails is $23.6 \pm 0.2$ kpc and estimate the total (initial) luminosity of the cluster to be $L_V=5.1^{+9.7}_{-3.4}\times 10^3 L_\odot$, consistent with previous claims that its initial luminosity was higher than its current luminosity. Combined with previously-determined proper motion and radial velocity measurements of the cluster, we find that Palomar 13 is on a highly eccentric orbit ($e\sim 0.8$) with a pericenter of ~9 kpc and an apocenter of ~69 kpc, and a recent pericentric passage of the cluster ~75 Myr ago. We note a prominent linear structure in the interstellar dust map that runs parallel to the candidate tidal features, but conclude that reddening due to dust is unlikely to account for the structure that we observe. If confirmed, the Palomar 13 stellar stream would be one of very few streams with a known progenitor system, making it uniquely powerful for studying the disruption of globular clusters, the formation of the stellar halo, and the distribution of matter within our Galaxy., 8 pages, 4 figures, 1 table. Submitted to AAS journals

RR Lyrae stars are an important and widely used tracer of the most ancient populations of our Galaxy, mainly due to their standard candle nature. The availability of large scale surveys of variable stars is allowing us to trace the structure of our entire Galaxy, even in previously inaccessible areas like the Galactic disc. In this work we aim to provide an empirical assessment of the completeness of the three largest RR Lyrae catalogues available: Gaia DR2, PanSTARRS-1 and ASAS-SN-II. Using a joint probabilistic analysis of the three surveys we compute 2D and 3D completeness maps in each survey's full magnitude range. At the bright end (G20deg); ASAS-SN-II has the best completeness at low latitude for RRab and at all latitudes for RRc. At the faint end (G>13), Gaia DR2 is the most complete catalogue for both RR Lyrae types, at any latitude, with median completeness rates of 95% (RRab) and >85% (RRc) outside the ecliptic plane (|��|>25deg). We confirm a high and uniform completeness of PanSTARRS-1 RR Lyrae at 91% (RRab) and 82% (RRc) down to G~18, and provide the first estimate of its completeness at low galactic latitude (|b, 15 pages, 14 figures, 4+10 tables. Accepted for publication at MNRAS. Completeness maps and Python utils to plot and/or recompute them, available at https://github.com/cmateu/rrl_completeness

The astrometric sample of Gaia allows us to study the outermost Galactic disc, the halo and their interface. It is precisely at the very edge of the disc where the effects of external perturbations are expected to be the most noticeable. Our goal is to detect the kinematic substructure present in the halo and at the edge of the Milky Way (MW) disc, and provide observational constraints on their phase-space distribution. We download, one HEALpix at a time, the proper motion histogram of distant stars, to which we apply a Wavelet Transformation to reveal the significant overdensities. We then analyse the large coherent structures that appear in the sky. We reveal a sharp yet complex anticentre dominated by Monoceros (MNC) and the Anticentre Stream (ACS) in the north, which we find with an intensity comparable to the Magellanic clouds and the Sagittarius stream, and by MNC south and TriAnd at negative latitudes. Our method allows us to perform a morphological analysis of MNC and ACS, both spanning more than 100$^\circ$ in longitude, and to provide a high purity sample of giants with which we track MNC down to latitudes as low as $\sim$5$^\circ$. Their colour-magnitude diagram is consistent with extended structures at a distance of $\sim$10-11 kpc originated in the disc, with a very low ratio of RR Lyrae over M giants, and kinematics compatible with the rotation curve at those distances or only slightly slower. We present a precise characterisation of MNC and ACS, two previously known structures that our method reveals naturally, allowing us to detect them without limiting ourselves to a particular stellar type and, for the first time, using only kinematics. Our results allow future studies to model their chemo-dynamics and evolution, thus constraining some of the most influential processes that shaped the MW., Submitted to Astronomy and Astrophysics. Online material available upon acceptance