Subcellular localization of the five members of the human steroid 5α-reductase family

In humans the steroid 5a-reductase (SRD5A) family comprises five integral membrane enzymes that carry out reduction of a double bond in lipidic substrates: D4-3-keto steroids, polyprenol and trans-enoyl CoA. The best-characterized reaction is the conversion of testosterone into the more potent dihydrotestosterone carried out by SRD5A1-2. Some controversy exists on their possible nuclear or endoplasmic reticulum localization. We report the cloning and transient expression in HeLa cells of the five members of the human steroid 5a-reductase family as both N- and Cterminus green fluorescent protein tagged protein constructs. Following the intrinsic fluorescence of the tag, we have determined that the subcellular localization of these enzymes is in the endoplasmic reticulum, upon expression in HeLa cells. The presence of the tag at either end of the polypeptide chain can affect protein expression and, in the case of trans enoyl-CoA reductase, it induces the formation of protein aggregates

The time evolution of Md/M˙M_{\mathrm{d}}/\dot M in protoplanetary discs as a way to disentangle between viscosity and MHD winds

As the classic viscous paradigm for protoplanetary disk accretion is challenged by the observational evidence of low turbulence, the alternative scenario of MHD disk winds is being explored as potentially able to reproduce the same observed features traditionally explained with viscosity. Although the two models lead to different disk properties, none of them has been ruled out by observations - mainly due to instrumental limitations. In this work, we present a viable method to distinguish between the viscous and MHD framework based on the different evolution of the distribution in the disk mass ($M_{\mathrm{d}}$) - accretion rate ($\dot M$) plane of a disk population. With a synergy of analytical calculations and 1D numerical simulations, performed with the population synthesis code \texttt{Diskpop}, we find that both mechanisms predict the spread of the observed ratio $M_{\mathrm{d}}/\dot M$ in a disk population to decrease over time; however, this effect is much less pronounced in MHD-dominated populations as compared to purely viscous populations. Furthermore, we demonstrate that this difference is detectable with the current observational facilities: we show that convolving the intrinsic spread with the observational uncertainties does not affect our result, as the observed spread in the MHD case remains significantly larger than in the viscous scenario. While the most recent data available show a better agreement with the wind model, ongoing and future efforts to obtain direct gas mass measurements with ALMA and ngVLA will cause a reassessment of this comparison in the near future.Comment: 11 pages, 6 figures, 1 table. Published in ApJ

Engineered ferritin for lanthanide binding

Ferritin H-homopolymers have been extensively used as nanocarriers for diverse applications in the targeted delivery of drugs and imaging agents, due to their unique ability to bind the transferrin receptor (CD71), highly overexpressed in most tumor cells. In order to incorporate novel fluorescence imaging properties, we have fused a lanthanide binding tag (LBT) to the C-terminal end of mouse H-chain ferritin, HFt. The HFt-LBT possesses one high affinity Terbium binding site per each of the 24 subunits provided by six coordinating aminoacid side chains and a tryptophan residue in its close proximity and is thus endowed with strong FRET sensitization properties. Accordingly, the characteristic Terbium emission band at 544 nm for the HFt-LBT Tb(III) complex was detectable upon excitation of the tag enclosed at two order of magnitude higher intensity with respect to the wtHFt protein. X-ray data at 2.9 Å and cryo-EM at 7 Å resolution demonstrated that HFt-LBT is correctly assembled as a 24-mer both in crystal and in solution. On the basis of the intrinsic Tb(III) binding properties of the wt protein, 32 additional Tb(III) binding sites, located within the natural iron binding sites of the protein, were identified besides the 24 Tb(III) ions coordinated to the LBTs. HFt-LBT Tb(III) was demonstrated to be actively uptaken by selected tumor cell lines by confocal microscopy and FACS analysis of their FITC derivatives, although direct fluorescence from Terbium emission could not be singled out with conventional, 295–375 nm, fluorescence excitation

Acetylation Suppresses the Proapoptotic Activity of GD3 Ganglioside

GD3 synthase is rapidly activated in different cell types after specific apoptotic stimuli. De novo synthesized GD3 accumulates and contributes to the apoptotic program by relocating to mitochondrial membranes and inducing the release of apoptogenic factors. We found that sialic acid acetylation suppresses the proapoptotic activity of GD3. In fact, unlike GD3, 9-O-acetyl-GD3 is completely ineffective in inducing cytochrome c release and caspase-9 activation on isolated mitochondria and fails to induce the collapse of mitochondrial transmembrane potential and cellular apoptosis. Moreover, cells which are resistant to the overexpression of the GD3 synthase, actively convert de novo synthesized GD3 to 9-O-acetyl-GD3. The coexpression of GD3 synthase with a viral 9-O-acetyl esterase, which prevents 9-O-acetyl-GD3 accumulation, reconstitutes GD3 responsiveness and apoptosis. Finally, the expression of the 9-O-acetyl esterase is sufficient to induce apoptosis of glioblastomas which express high levels of 9-O-acetyl-GD3. Thus, sialic acid acetylation critically controls the proapoptotic activity of GD3

Radio multiwavelength analysis of the compact disk CX Tau: strong free-free variability or anomalous microwave emission?

Protoplanetary disks emit radiation across a broad range of wavelengths, requiring a multiwavelength approach to fully understand their physical mechanisms and how they form planets. Observations at sub-millimeter to centimeter wavelengths can provide insights into the thermal emission from dust, free-free emission from ionized gas, and possible gyro-synchrotron emission from the stellar magnetosphere. This Letter focuses on CX Tau, a ${\sim}0.4\,M_\odot$ star with an extended gas emission and a compact and apparently structureless dust disk, with an average millimeter flux when compared to Class II sources in Taurus. We present Karl G. Jansky Very Large Array (VLA) observations in 4 bands (between 9.0 mm and 6.0 cm) and combine them with archival data from the Atacama Large Millimeter/submillimeter Array (ALMA), the Submillimeter Array (SMA) and the Plateau de Bure Interferometer (PdBI). Such a multiwavelength approach allows to separate the dust continuum from other emissions. After isolating the dust thermal emission, we derived an upper limit of the dust disk extent at 1.3 cm which is consistent with theoretical predictions of a radial drift-dominated disk. Centimeter data show a peculiar behavior: deep observations at 6.0 cm did not detect the source, while at 1.3 cm the flux density is anomalously higher than adjacent bands. Intraband spectral indices suggest a dominant contribution from free-free emission, whereas gyro-synchrotron emission is excluded. To explain these observations, we propose strong variability of the free-free emission with timescales shorter than a month. Another possible interpretation is the presence of anomalous microwave emission from spinning dust grains.Comment: Accepted for publication in A&A Letters; 13 pages, 13 figures, 1 tabl

The Bolocam Galactic Plane Survey: Survey Description and Data Reduction

We present the Bolocam Galactic Plane Survey (BGPS), a 1.1 mm continuum survey at 33" effective resolution of 170 square degrees of the Galactic Plane visible from the northern hemisphere. The survey is contiguous over the range -10.5 < l < 90.5, |b| < 0.5 and encompasses 133 square degrees, including some extended regions |b| < 1.5. In addition to the contiguous region, four targeted regions in the outer Galaxy were observed: IC1396, a region towards the Perseus Arm, W3/4/5, and Gem OB1. The BGPS has detected approximately 8400 clumps over the entire area to a limiting non-uniform 1-sigma noise level in the range 11 to 53 mJy/beam in the inner Galaxy. The BGPS source catalog is presented in a companion paper (Rosolowsky et al. 2010). This paper details the survey observations and data reduction methods for the images. We discuss in detail the determination of astrometric and flux density calibration uncertainties and compare our results to the literature. Data processing algorithms that separate astronomical signals from time-variable atmospheric fluctuations in the data time-stream are presented. These algorithms reproduce the structure of the astronomical sky over a limited range of angular scales and produce artifacts in the vicinity of bright sources. Based on simulations, we find that extended emission on scales larger than about 5.9' is nearly completely attenuated (> 90%) and the linear scale at which the attenuation reaches 50% is 3.8'. Comparison with other millimeter-wave data sets implies a possible systematic offset in flux calibration, for which no cause has been discovered. This presentation serves as a companion and guide to the public data release through NASA's Infrared Processing and Analysis Center (IPAC) Infrared Science Archive (IRSA). New data releases will be provided through IPAC IRSA with any future improvements in the reduction.Comment: Accepted for publication in Astrophysical Journal Supplemen

Lesiones destructivas de la línea media: diagnóstico diferencial con Vasculitis Asociada a ANCA

Presentamos los casos clínicos de tres pacientes adultos jóvenes de origen boliviano, que fueron hospitalizados en salas de clínica médica de un hospital de tercer nivel por manifestaciones de la vía aérea superior y lesiones de las estructuras de la línea media. Reumatología evaluó la posibilidad del diagnóstico de Vasculitis asociada a ANCA, la cual es un diagnóstico diferencial de la entidad conocida como “lesión destructiva de la línea media”. En todos los casos se arribó al diagnóstico definitivo de Linfoma T luego de un exhaustivo estudio histopatológico

Vasculitis cutáneas: etiología y características clínicas en pacientes adultos en un centro de tercer nivel

Introducción: diversas entidades clínicas, como enfermedades autoinmunes, infecciones, neoplasias y fármacos pueden manifestarse con lesiones vasculíticas en la piel. Debido a la heterogeneidad de las causas, suelen representar un desafío diagnóstico. El objetivo de este estudio es describir la etiología de las vasculitis cutáneas (VC) y evaluar las características clínicas, histológicas y de laboratorio halladas en estos pacientes. Material y métodos: se realizó un estudio retrospectivo con revisión de historias clínicas de pacientes mayores de 16 años con VC por diagnóstico clínico y/o histológico evaluados en el período 2010-2018. Resultados: se incluyeron 74 pacientes. El 69% son mujeres con una edad media al diagnóstico de 41 años (DE 16.5, rango 16 -75). Las causas más frecuentes asociadas a las VC fueron las enfermedades autoinmunes (EAI) en un 50% de los pacientes evaluados. En el 29.7% de los casos no pudo identificarse una causa subyacente. En el 2.7% de los casos se asoció a neoplasias, otro 2.7% a fármacos y un 12% a otras etiologías. El 76% de los pacientes presentaron formas clínicas no severas, predominando la púrpura palpable en el 65% de los casos. Entre los pacientes biopsiados, el 76% fueron vasculitis leucocitoclásticas (VLC). Como manifestaciones extracutáneas asociadas, predominó el compromiso articular (43,2%). En las vasculitis asociadas a EAI, el 33 % presentó compromiso renal, en tanto que éste no se observó en ninguno de los pacientes con vasculitis idiopáticas. El 78% de los pacientes recibieron glucocorticoides sistémicos. Conclusión: en nuestro centro, la etiología más común de VC fue la asociada a EAI. La mayoría de los pacientes eran mujeres. Clínicamente predominaron las manifestaciones cutáneas no severas y la VLC fue el hallazgo más frecuente en las biopsias

Un modello predittivo dell’intensità assistenziale delle cure domiciliari. Analisi di un caso

Il lavoro si propone di individuare predittori della complessità e intensità delle cure domiciliari per anziani fragili, al fine di identificare profili omogenei di assorbimento di risorse. Il campione è costituito da 200 anziani non autosufficienti arruolati nell’ambito di un progetto finanziato dalMinistero della Salute ex art. 12 in diversi bacini di utenza nella città di Genova. Attraverso l’utilizzo di alberi decisionali si esplorano le interazioni tra condizioni clinico-funzionali dei pazienti, variabili demografiche e socioeconomiche e l’assorbimento di risorse. I risultati evidenziano quali predittori del costo medio mensile e delle sue componenti (intensità e complessità) non soltanto variabili cliniche, ma anche socioeconomiche