ABCC6 is a basolateral plasma membrane protein

RATIONALE:: ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein. OBJECTIVE:: In a recent article in Circulation Research, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment. METHODS AND RESULTS:: We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum. CONCLUSIONS:: Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation. © 2013 American Heart Association, Inc

The BarYon CYCLE Project (ByCycle): Identifying and Localizing MgII Metal Absorbers with Machine Learning

The upcoming ByCycle project on the VISTA/4MOST multi-object spectrograph will offer new prospects of using a massive sample of $\sim 1$ million high spectral resolution ($R$ = 20,000) background quasars to map the circumgalactic metal content of foreground galaxies (observed at $R$ = 4000 - 7000), as traced by metal absorption. Such large surveys require specialized analysis methodologies. In the absence of early data, we instead produce synthetic 4MOST high-resolution fibre quasar spectra. To do so, we use the TNG50 cosmological magnetohydrodynamical simulation, combining photo-ionization post-processing and ray tracing, to capture MgII ($\lambda2796$, $\lambda2803$) absorbers. We then use this sample to train a Convolutional Neural Network (CNN) which searches for, and estimates the redshift of, MgII absorbers within these spectra. For a test sample of quasar spectra with uniformly distributed properties ($\lambda_{\rm{MgII,2796}}$, $\rm{EW}_{\rm{MgII,2796}}^{\rm{rest}} = 0.05 - 5.15$ \AA, $\rm{SNR} = 3 - 50$), the algorithm has a robust classification accuracy of 98.6 per cent and a mean wavelength accuracy of 6.9 \AA. For high signal-to-noise spectra ($\rm{SNR > 20}$), the algorithm robustly detects and localizes MgII absorbers down to equivalent widths of $\rm{EW}_{\rm{MgII,2796}}^{\rm{rest}} = 0.05$ \AA. For the lowest SNR spectra ($\rm{SNR=3}$), the CNN reliably recovers and localizes EW$_{\rm{MgII,2796}}^{\rm{rest}}$ $\geq$ 0.75 \AA\, absorbers. This is more than sufficient for subsequent Voigt profile fitting to characterize the detected MgII absorbers. We make the code publicly available through GitHub. Our work provides a proof-of-concept for future analyses of quasar spectra datasets numbering in the millions, soon to be delivered by the next generation of surveys.Comment: 13 pages, 9 figures, 1 table. Accepted for publication in MNRA

ALMACAL IX: Multiband ALMA survey for dusty star-forming galaxies and the resolved fractions of the cosmic infrared background

Wide, deep, blind continuum surveys at submillimetre/millimetre (submm/mm) wavelengths are required to provide a full inventory of the dusty, distant Universe. However, conducting such surveys to the necessary depth, with sub-arcsec angular resolution, is prohibitively time-consuming, even for the most advanced submm/mm telescopes. Here, we report the most recent results from the ALMACAL project, which exploits the ‘free’ calibration data from the Atacama Large Millimetre/submillimetre Array (ALMA) to map the lines of sight towards and beyond the ALMA calibrators. ALMACAL has now covered 1001 calibrators, with a total sky coverage around 0.3 deg2, distributed across the sky accessible from the Atacama desert, and has accumulated more than 1000 h of integration. The depth reached by combining multiple visits to each field makes ALMACAL capable of searching for faint, dusty, star-forming galaxies (DSFGs), with detections at multiple frequencies to constrain the emission mechanism. Based on the most up-to-date ALMACAL data base, we report the detection of 186 DSFGs with flux densities down to S870 µm ∼ 0.2 mJy, comparable with existing ALMA large surveys but less susceptible to cosmic variance. We report the number counts at five wavelengths between 870 μm and 3 mm, in ALMA bands 3, 4, 5, 6, and 7, providing a benchmark for models of galaxy formation and evolution. By integrating the observed number counts and the best-fitting functions, we also present the resolved fraction of the cosmic infrared background (CIB) and the CIB spectral shape. Combining existing surveys, ALMA has currently resolved about half of the CIB in the submm/mm regime

Global sexual fertility in the opportunistic pathogen aspergillus fumigatus and identification of new supermater strains

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. A sexual cycle in Aspergillus fumigatus was first described in 2009 with isolates from Dublin, Ireland. However, the extent to which worldwide isolates can undergo sexual reproduction has remained unclear. In this study a global collection of 131 isolates was established with a near 1:1 ratio of mating types. All isolates were crossed to MAT1-1 or MAT1-2 Irish strains, and a subset of isolates from different continents were crossed together. Ninety seven percent of isolates were found to produce cleistothecia with at least one mating partner, showing that sexual fertility is not limited to the Irish population but is a characteristic of global A. fumigatus. However, large variation was seen in numbers of cleistothecia produced per cross, suggesting differences in the possibility for genetic exchange between strains in nature. The majority of crosses produced ascospores with >50% germination rates, but with wide variation evident. A high temperature heat shock was required to induce ascospore germination. Finally, a new set of highly fertile MAT1-1 and MAT1-2 supermater strains were identified and pyrimidine auxotrophs generated for community use. Results provide insights into the potential for the A. fumigatus sexual cycle to generate genetic variation and allow gene flow of medically important traits