The VLTI/MIDI survey of massive young stellar objects - Sounding the inner regions around intermediate- and high-mass young stars using mid-infrared interferometry

We aim to characterize the distribution and composition of circumstellar material around young massive stars, and to investigate exactly which physical structures in these objects are probed by long-baseline mid-infrared interferometric observations. We used the two-telescope interferometric instrument MIDI of the Very Large Telescope Interferometer of the European Southern Observatory to observe a sample of 24 intermediate- and high-mass young stellar objects in the N band (8-13 micron). We had successful fringe detections for 20 objects, and present spectrally-resolved correlated fluxes and visibility levels for projected baselines of up to 128 m. We fit the visibilities with geometric models to derive the sizes of the emitting regions, as well as the orientation and elongation of the circumstellar material. Fourteen objects in the sample show the 10 micron silicate feature in absorption in the total and correlated flux spectra. For 13 of these objects, we were able to fit the correlated flux spectra with a simple absorption model, allowing us to constrain the composition and absorptive properties of the circumstellar material. Nearly all of the massive young stellar objects observed show significant deviations from spherical symmetry at mid-infrared wavelengths. In general, the mid-infrared emission can trace both disks and outflows, and in many cases it may be difficult to disentangle these components on the basis of interferometric data alone, because of the sparse spatial frequency coverage normally provided by current long-baseline interferometers. For the majority of the objects in this sample, the absorption occurs on spatial scales larger than those probed by MIDI. Finally, the physical extent of the mid-infrared emission around these sources is correlated with the total luminosity, albeit with significant scatter.Comment: 36 pages, 22 figures. Accepted to Astronomy and Astrophysic

From high-mass starless cores to high-mass protostellar objects

Aims: Our aim is to understand the evolutionary sequence of high-mass star formation from the earliest evolutionary stage of high-mass starless cores, via high-mass cores with embedded low- to intermediate-mass objects, to finally high-mass protostellar objects. Methods: Herschel far-infrared PACS and SPIRE observations are combined with existing data at longer and shorter wavelengths to characterize the spectral and physical evolution of massive star-forming regions. Results: The new Herschel images spectacularly show the evolution of the youngest and cold high-mass star-forming regions from mid-infrared shadows on the Wien-side of the spectral energy distribution (SED), via structures almost lost in the background emission around 100mum, to strong emission sources at the Rayleigh-Jeans tail. Fits of the SEDs for four exemplary regions covering evolutionary stages from high-mass starless cores to high-mass protostellar objects reveal that the youngest regions can be fitted by single-component black-bodies with temperatures on the order of 17K. More evolved regions show mid-infrared excess emission from an additional warmer component, which however barely contributes to the total luminosities for the youngest regions. Exceptionally low values of the ratio between bolometric and submm luminosity additionally support the youth of the infrared-dark sources. Conclusions: The Herschel observations reveal the spectral and physical properties of young high-mass star-forming regions in detail. The data clearly outline the evolutionary sequence in the images and SEDs. Future work on larger samples as well as incorporating full radiative transfer calculations will characterize the physical nature at the onset of massive star formation in even more depth.Comment: 4 pages, A&A Herschel special issu

Reactivated endogenous retroviruses promote protein aggregate spreading

Endogenous retroviruses, or genomic relics of ancient viral infection, have been associated with certain neurodegenerative diseases. Here, Liu et al. report a pathway by which reactivated viral gene products contribute to intercellular protein aggregate spreading. Prion-like spreading of protein misfolding is a characteristic of neurodegenerative diseases, but the exact mechanisms of intercellular protein aggregate dissemination remain unresolved. Evidence accumulates that endogenous retroviruses, remnants of viral germline infections that are normally epigenetically silenced, become upregulated in neurodegenerative diseases such as amyotrophic lateral sclerosis and tauopathies. Here we uncover that activation of endogenous retroviruses affects prion-like spreading of proteopathic seeds. We show that upregulation of endogenous retroviruses drastically increases the dissemination of protein aggregates between cells in culture, a process that can be inhibited by targeting the viral envelope protein or viral protein processing. Human endogenous retrovirus envelopes of four different clades also elevate intercellular spreading of proteopathic seeds, including pathological Tau. Our data support a role of endogenous retroviruses in protein misfolding diseases and suggest that antiviral drugs could represent promising candidates for inhibiting protein aggregate spreading

Bundles over Nearly-Kahler Homogeneous Spaces in Heterotic String Theory

We construct heterotic vacua based on six-dimensional nearly-Kahler homogeneous manifolds and non-trivial vector bundles thereon. Our examples are based on three specific group coset spaces. It is shown how to construct line bundles over these spaces, compute their properties and build up vector bundles consistent with supersymmetry and anomaly cancelation. It turns out that the most interesting coset is $SU(3)/U(1)^2$. This space supports a large number of vector bundles which lead to consistent heterotic vacua, some of them with three chiral families.Comment: 32 pages, reference adde

Interferometric multi-wavelength (sub)millimeter continuum study of the young high-mass protocluster IRAS05358+3543

The young massive star-forming region IRAS05358+3543 was observed at high-spatial resolution in the continuum emission at 3.1 and 1.2mm with the Plateau de Bure Interferometer, and at 875 and 438mum with the Submillimeter Array. We resolve at least four continuum sub-sources that are likely of protostellar nature. Two of them are potentially part of a proto-binary system with a projected separation of 1700AU. Additional (sub)mm continuum peaks are not necessarily harboring protostars but maybe caused by the multiple molecular outflows. The spectral energy distributions (SEDs) of the sub-sources show several features. The main power house mm1, which is associated with CH3OH maser emission, a hypercompact HII region and a mid-infrared source, exhibits a typical SED with a free-free emission component at cm and long mm wavelengths and a cold dust component in the (sub)mm part of the spectrum (spectral index between 1.2mm and 438mum alpha~3.6). The free-free emission corresponds to a Lyman continuum flux of an embedded 13Msun B1 star. The coldest source of the region, mm3, has alpha~3.7 between 1.2mm and 875mum, but has lower than expected fluxes in the shorter wavelength 438mum band. This turnover of the Planck-function sets an upper limit on the dust temperature of mm3 of approximately 20K. The uv-data analysis of the density structure of individual sub-cores reveals distributions with power-law indices between 1.5 and 2. This resembles the density distributions of the larger-scale cluster-forming clump as well as those from typical low-mass cores.Comment: 13 pages, 7 figures, accepted for Astronomy and Astrophysics, a high-resolution version of the paper is also available at http://www.mpia.de/homes/beuther/papers.htm

Monoculture of Leafcutter Ant Gardens

Background -- Leafcutter ants depend on the cultivation of symbiotic Attamyces fungi for food, which are thought to be grown by the ants in single-strain, clonal monoculture throughout the hundreds to thousands of gardens within a leafcutter nest. Monoculture eliminates cultivar-cultivar competition that would select for competitive fungal traits that are detrimental to the ants, whereas polyculture of several fungi could increase nutritional diversity and disease resistance of genetically variable gardens. Methodology/Principal Findings -- Using three experimental approaches, we assessed cultivar diversity within nests of Atta leafcutter ants, which are most likely among all fungus-growing ants to cultivate distinct cultivar genotypes per nest because of the nests' enormous sizes (up to 5000 gardens) and extended lifespans (10–20 years). In Atta texana and in A. cephalotes, we resampled nests over a 5-year period to test for persistence of resident cultivar genotypes within each nest, and we tested for genetic differences between fungi from different nest sectors accessed through excavation. In A. texana, we also determined the number of Attamyces cells carried as a starter inoculum by a dispersing queens (minimally several thousand Attamyces cells), and we tested for genetic differences between Attamyces carried by sister queens dispersing from the same nest. Except for mutational variation arising during clonal Attamyces propagation, DNA fingerprinting revealed no evidence for fungal polyculture and no genotype turnover during the 5-year surveys. Conclusions/Significance -- Atta leafcutter ants can achieve stable, fungal monoculture over many years. Mutational variation emerging within an Attamyces monoculture could provide genetic diversity for symbiont choice (gardening biases of the ants favoring specific mutational variants), an analog of artificial selection.The research was supported by National Science Foundation awards DEB-0920138, DEB-0639879, and DEB-0110073 to UGM; DEB-0949689 to T.R. Schultz, N. Mehdiabadi, and UGM; and a Fellowship (02/05) from the Conselho Nacional de Desenvolvimento Científico e Tecnológico to AR. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o

Utility of ultra-sensitive qPCR to detect Plasmodium falciparum and Plasmodium vivax infections under different transmission intensities

Background: The use of molecular diagnostics has revealed an unexpectedly large number of asymptomatic low-density malaria infections in many malaria endemic areas. This study compared the gains in parasite prevalence obtained by the use of ultra-sensitive (us)-qPCR as compared to standard qPCR in cross-sectional surveys conducted in Thailand, Brazil and Papua New Guinea (PNG). The compared assays differed in the copy number of qPCR targets in the parasite genome. Methods: Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) parasites were quantified by qPCR amplifying the low-copy Pf_ and Pv_18S rRNA genes or the multi-copy targets Pf_varATS and Pv_mtCOX1. Cross-sectional surveys at the three study sites included 2252 participants of all ages and represented different transmission intensities. Results: In the two low-transmission areas, P. falciparum positivity was 1.3% (10/773) (Thailand) and 0.8% (5/651) (Bra- zil) using standard Pf_18S rRNA qPCR. In these two countries, P. falciparum positivity by Pf_varATS us-qPCR increased to 1.9% (15/773) and 1.7% (11/651). In PNG, an area with moderate transmission intensity, P. falciparum positivity significantly increased from 8.6% (71/828) by standard qPCR to 12.2% (101/828) by us-qPCR. The proportions of P. falciparum infections not detected by standard qPCR were 33%, 55% and 30% in Thailand, Brazil and PNG. Plasmodium vivax was the predominating species in Thailand and Brazil, with 3.9% (30/773) and 4.9% (32/651) positivity by Pv_18S rRNA qPCR. In PNG, P. vivax positivity was similar to P. falciparum, at 8.0% (66/828). Use of Pv_mtCOX1 us-qPCR led to a significant increase in positivity to 5.1% (39/773), 6.4% (42/651) and 11.5% (95/828) in Thailand, Brazil, and PNG. The proportions of P. vivax infections missed by standard qPCR were similar at all three sites, with 23%, 24% and 31% in Thailand, Brazil and PNG. Conclusion: The proportional gains in the detection of P. falciparum and P. vivax infections by ultra-sensitive diag- nostic assays were substantial at all three study sites. Thus, us-qPCR yields more precise prevalence estimates for both P. falciparum and P. vivax at all studied levels of endemicity and represents a significant diagnostic improvement

Massively distributed authorship of academic papers

Wiki-like or crowdsourcing models of collaboration can provide a number of benefits to academic work. These techniques may engage expertise from different disciplines, and potentially increase productivity. This paper presents a model of massively distributed collaborative authorship of academic papers. This model, developed by a collective of thirty authors, identifies key tools and techniques that would be necessary or useful to the writing process. The process of collaboratively writing this paper was used to discover, negotiate, and document issues in massively authored scholarship. Our work provides the first extensive discussion of the experiential aspects of large-scale collaborative researc

Physical structure of the envelopes of intermediate-mass protostars

Context: Intermediate mass protostars provide a bridge between low- and high-mass protostars. Furthermore, they are an important component of the UV interstellar radiation field. Despite their relevance, little is known about their formation process. Aims: We present a systematic study of the physical structure of five intermediate mass, candidate Class 0 protostars. Our two goals are to shed light on the first phase of intermediate mass star formation and to compare these protostars with low- and high-mass sources. Methods: We derived the dust and gas temperature and density profiles of the sample. We analysed all existing continuum data on each source and modelled the resulting SED with the 1D radiative transfer code DUSTY. The gas temperature was then predicted by means of a modified version of the code CHT96. Results: We found that the density profiles of five out of six studied intermediate mass envelopes are consistent with the predictions of the "inside-out" collapse theory.We compared several physical parameters, like the power law index of the density profile, the size, the mass, the average density, the density at 1000 AU and the density at 10 K of the envelopes of low-, intermediate, and high-mass protostars. When considering these various physical parameters, the transition between the three groups appears smooth, suggesting that the formation processes and triggers do not substantially differ

WNT activates the AAK1 kinase to promote clathrin-mediated endocytosis of LRP6 and establish a negative feedback loop

beta-Catenin-dependent WNT signal transduction governs development, tissue homeostasis, and a vast array of human diseases. Signal propagation through a WNT-Frizzled/LRP receptor complex requires proteins necessary for clathrin-mediated endocytosis (CME). Paradoxically, CME also negatively regulates WNT signaling through internalization and degradation of the receptor complex. Here, using a gain-of-function screen of the human kinome, we report that the AP2 associated kinase 1 (AAK1), a known CME enhancer, inhibits WNT signaling. Reciprocally, AAK1 genetic silencing or its pharmacological inhibition using a potent and selective inhibitor activates WNT signaling. Mechanistically, we show that AAK1 promotes clearance of LRP6 from the plasma membrane to suppress the WNT pathway. Time-course experiments support a transcription-uncoupled, WNT-driven negative feedback loop; prolonged WNT treatment drives AAK1-dependent phosphorylation of AP2M1, clathrin-coated pit maturation, and endocytosis of LRP6. We propose that, following WNT receptor activation, increased AAK1 function and CME limits WNT signaling longevity2617993FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2013/50724-5; 2016/17469-0M.B.M. acknowledges support from the NIH (RO1-CA187799 and U24-DK116204-01). M.J.A. received financial support from NIH T32 Predoctoral Training Grants in Pharmacology (T32-GM007040-43 and T32-GM007040-42), an Initiative for Maximizing Student Diversity Grant (R25-GM055336-16), and the NIH National Cancer Institute (NCI) NRSA Predoctoral Fellowship to Promote Diversity in Health-Related Research (F31CA228289). M.P.W. received support from the Lymphoma Research Foundation (337444) and the NIH (T32-CA009156-35). Y.N. was supported by grants-in-aid from the Japan Society for the Promotion of Science (JSPS) (15KK0356 and 16K11493). T.T. was supported by the Howard Hughes Medical Institute Gilliam Fellowship for Advanced Study. M.V.G. was supported by Cancer Research UK (grants C7379/A15291 and C7379/A24639 to Mariann Bienz). The UNC Flow Cytometry Core Facility is supported in part by Cancer Center Core Support Grant P30 CA016086 to the UNC Lineberger Comprehensive Cancer Center, and research reported in this publication was supported by the Center for AIDS Research (award number 5P30AI050410), and the content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The Structural Genomics Consortium (SGC) is a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, the Canada Foundation for Innovation, the Eshelman Institute for Innovation, Genome Canada, the Innovative Medicines Initiative (European Union [EU]/European Federation of Pharmaceutical Industries and Associations [EFPIA]) (ULTRA-DD grant no. 115766), Janssen, Merck & Company, Merck KGaA, Novartis Pharma AG, the Ontario Ministry of Economic Development and Innovation, Pfizer, the São Paulo Research Foundation (FAPESP) (2013/50724-5), Takeda, and the Wellcome Trust (106169/ZZ14/Z). R.R.R. received financial support from FAPESP (2016/17469-0). We would also like to thank Claire Strain-Damerell and Pavel Savitsky for cloning various mutants of AAK1 and BMP2K proteins that were used in the crystallization trials. Additionally, we thank Dr. Sean Conner for providing the AAK1 plasmids, Dr. Stephane Angers for kindly providing the HEK293T DVL TKO cells, and Dr. Mariann Bienz for providing comments and feedback. We would like to thank members of the Major laboratory for their feedback and expertise regarding experimental design and project directio