Status of the Endangered Indian Knob Mountainbalm Eriodictyon altissimum (Namaceae) in Central Coastal California

Indian Knob Mountainbalm Eriodictyon altissimum (Namaceae) is a shrub endemic to western San Luis Obispo County in central coastal California, and little has been published regarding it. The species was listed as endangered under the California Endangered Species Act in 1979 and the U.S. Endangered Species Act in 1995. At Federal listing in 1995, Indian Knob mountainbalm was known from six occurrences, two of which were in protected areas, with a total population estimate of 2018, Indian Knob mountainbalm is known from seven occurrences, six of which are in protected areas and one (the largest) mostly in a protected area, with a total population count of 6,489+ individuals in 2016. Two occurrences are likely extirpated. Indian Knob mountainbalm is considered a fire-adapted chaparral plant. Reproduction is reported to be primarily vegetative by underground rhizomes, and it is specialized for substrates with physical disturbances, including: steep rocky slopes, cliff faces, fallen rock debris, sand dunes (shifting sand), roadsides, old graded substrates such as dirt/rock roads, the talus of graded substrates, and trails. We report the species grows up to 5.5 m tall and at 98 to 263 m elevation. In consideration of the life history traits used by Anacker et al. (2013) for rare plants in California, Indian Knob mountainbalm would be considered highly vulnerable to climate change. Using the international standards of IUCN, Indian Knob mountainbalm meets the criteria for classification as critically endangered including the following: geographic range, severely fragmented; extent of occurrence, 34 km2 (km2); area of occupancy, 2 (km2); and quality of habitat, continuing to decline (dense vegetation, lack of recent fire). Coordinated conservation and research are needed to further understand the species, and to restore and maintain the five extant occurrences

Aedes aegypti Saliva Alters Leukocyte Recruitment and Cytokine Signaling by Antigen-Presenting Cells during West Nile Virus Infection

West Nile virus (WNV) is transmitted during mosquito bloodfeeding. Consequently, the first vertebrate cells to contact WNV are cells in the skin, followed by those in the draining lymph node. Macrophages and dendritic cells are critical early responders in host defense against WNV infection, not just because of their role in orchestrating the immune response, but also because of their importance as sites of early peripheral viral replication. Antigen-presenting cell (APC) signals have a profound effect on host antiviral responses and disease severity. During transmission, WNV is intimately associated with mosquito saliva. Due to the ability of mosquito saliva to affect inflammation and immune responses, and the importance of understanding early events in WNV infection, we investigated whether mosquito saliva alters APC signaling during arbovirus infection, and if alterations in cell recruitment occur when WNV infection is initiated with mosquito saliva. Accordingly, experiments were performed with cultured dendritic cells and macrophages, flow cytometry was used to characterize infiltrating cell types in the skin and lymph nodes during early infection, and real-time RT-PCR was employed to evaluate virus and cytokine levels. Our in vitro results suggest that mosquito saliva significantly decreases the expression of interferon-β and inducible nitric oxide synthase in macrophages (by as much as 50 and 70%, respectively), whilst transiently enhancing interleukin-10 (IL-10) expression. In vivo results indicate that the predominate effect of mosquito feeding is to significantly reduce the recruitment of T cells, leading the inoculation site of mice exposed to WNV alone to have up to 2.8 fold more t cells as mice infected in the presence of mosquito saliva. These shifts in cell population are associated with significantly elevated IL-10 and WNV (up to 4.0 and 10 fold, respectively) in the skin and draining lymph nodes. These results suggest that mosquito saliva dysregulates APC antiviral signaling, and reveal a possible mechanism for the observed enhancement of WNV disease mediated by mosquito saliva via a reduction of T lymphocyte and antiviral activity at the inoculation site, an elevated abundance of susceptible cell types, and a concomitant increase in immunoregulatory activity of IL-10

Investigating the timecourse of accessing conversational implicatures during incremental sentence interpretation

Many contextual inferences in utterance interpretation are explained as following from the nature of conversation and the assumption that participants are rational. Recent psycholinguistic research has focussed on certain of these ‘Gricean’ inferences and have revealed that comprehenders can access them in online interpretation. However there have been mixed results as to the time-course of access. Some results show that Gricean inferences can be accessed very rapidly, as rapidly as any other contextually specified information (Sedivy, 2003; Grodner, Klein, Carbery, & Tanenhaus, 2010); while other studies looking at the same kind of inference suggest that access to Gricean inferences are delayed relative to other aspects of semantic interpretation (Huang & Snedeker, 2009; in press). While previous timecourse research has focussed on Gricean inferences that support the online assignment of reference to definite expressions, the study reported here examines the timecourse of access to scalar implicatures, which enrich the meaning of an utterance beyond the semantic interpretation. Even if access to Gricean inference in support of reference assignment may be rapid, it is still unknown whether genuinely enriching scalar implicatures are delayed. Our results indicate that scalar implicatures are accessed as rapidly as other contextual inferences. The implications of our results are discussed in reference to the architecture of language comprehension

Golgi-localized STELLO proteins regulate the assembly and trafficking of cellulose synthase complexes in Arabidopsis

As the most abundant biopolymer on Earth, cellulose is a key structural component of the plant cell wall. Cellulose is produced at the plasma membrane by cellulose synthase (CesA) complexes (CSCs), which are assembled in the endomembrane system and trafficked to the plasma membrane. While several proteins that affect CesA activity have been identified, components that regulate CSC assembly and trafficking remain unknown. Here we show that STELLO1 and 2 are Golgi-localized proteins that can interact with CesAs and control cellulose quantity. In the absence of STELLO function, the spatial distribution within the Golgi, secretion and activity of the CSCs are impaired indicating a central role of the STELLO proteins in CSC assembly. Point mutations in the predicted catalytic domains of the STELLO proteins indicate that they are glycosyltransferases facing the Golgi lumen. Hence, we have uncovered proteins that regulate CSC assembly in the plant Golgi apparatus

SDSS Standard Star Catalog for Stripe 82: the Dawn of Industrial 1% Optical Photometry

We describe a standard star catalog constructed using multiple SDSS photometric observations (at least four per band, with a median of ten) in the $ugriz$ system. The catalog includes 1.01 million non-variable unresolved objects from the equatorial stripe 82 ($|\delta_{J2000}|<$ 1.266$^\circ$) in the RA range 20h 34m to 4h 00m, and with the corresponding $r$ band (approximately Johnson V band) magnitudes in the range 14--22. The distributions of measurements for individual sources demonstrate that the photometric pipeline correctly estimates random photometric errors, which are below 0.01 mag for stars brighter than (19.5, 20.5, 20.5, 20, 18.5) in $ugriz$, respectively (about twice as good as for individual SDSS runs). Several independent tests of the internal consistency suggest that the spatial variation of photometric zeropoints is not larger than $\sim$0.01 mag (rms). In addition to being the largest available dataset with optical photometry internally consistent at the $\sim$1% level, this catalog provides practical definition of the SDSS photometric system. Using this catalog, we show that photometric zeropoints for SDSS observing runs can be calibrated within nominal uncertainty of 2% even for data obtained through 1 mag thick clouds, and demonstrate the existence of He and H white dwarf sequences using photometric data alone. Based on the properties of this catalog, we conclude that upcoming large-scale optical surveys such as the Large Synoptic Survey Telescope will be capable of delivering robust 1% photometry for billions of sources.Comment: 63 pages, 24 figures, submitted to AJ, version with correct figures and catalog available from http://www.astro.washington.edu/ivezic/sdss/catalogs/stripe82.htm

Results from the Supernova Photometric Classification Challenge

We report results from the Supernova Photometric Classification Challenge (SNPCC), a publicly released mix of simulated supernovae (SNe), with types (Ia, Ibc, and II) selected in proportion to their expected rate. The simulation was realized in the griz filters of the Dark Energy Survey (DES) with realistic observing conditions (sky noise, point-spread function and atmospheric transparency) based on years of recorded conditions at the DES site. Simulations of non-Ia type SNe are based on spectroscopically confirmed light curves that include unpublished non-Ia samples donated from the Carnegie Supernova Project (CSP), the Supernova Legacy Survey (SNLS), and the Sloan Digital Sky Survey-II (SDSS-II). A spectroscopically confirmed subset was provided for training. We challenged scientists to run their classification algorithms and report a type and photo-z for each SN. Participants from 10 groups contributed 13 entries for the sample that included a host-galaxy photo-z for each SN, and 9 entries for the sample that had no redshift information. Several different classification strategies resulted in similar performance, and for all entries the performance was significantly better for the training subset than for the unconfirmed sample. For the spectroscopically unconfirmed subset, the entry with the highest average figure of merit for classifying SNe~Ia has an efficiency of 0.96 and an SN~Ia purity of 0.79. As a public resource for the future development of photometric SN classification and photo-z estimators, we have released updated simulations with improvements based on our experience from the SNPCC, added samples corresponding to the Large Synoptic Survey Telescope (LSST) and the SDSS, and provided the answer keys so that developers can evaluate their own analysis.Comment: accepted by PAS

Golgi-localized STELLO proteins regulate the assembly and trafficking of cellulose synthase complexes in Arabidopsis.

As the most abundant biopolymer on Earth, cellulose is a key structural component of the plant cell wall. Cellulose is produced at the plasma membrane by cellulose synthase (CesA) complexes (CSCs), which are assembled in the endomembrane system and trafficked to the plasma membrane. While several proteins that affect CesA activity have been identified, components that regulate CSC assembly and trafficking remain unknown. Here we show that STELLO1 and 2 are Golgi-localized proteins that can interact with CesAs and control cellulose quantity. In the absence of STELLO function, the spatial distribution within the Golgi, secretion and activity of the CSCs are impaired indicating a central role of the STELLO proteins in CSC assembly. Point mutations in the predicted catalytic domains of the STELLO proteins indicate that they are glycosyltransferases facing the Golgi lumen. Hence, we have uncovered proteins that regulate CSC assembly in the plant Golgi apparatus.The work presented in this paper was supported by grants from the BBSRC: BB/G016240/1 BBSRC Sustainable Energy Centre Cell Wall Sugars Programme (BSBEC) and the European Community’s Seventh Framework Programme SUNLIBB (FP7/2007-2013) under the grant agreement n° 251132 to PD. The UK 850 MHz solid-state NMR Facility was funded by EPSRC and BBSRC, as well as the University of Warwick including via part funding through Birmingham Science City Advanced Materials Projects 1 and 2 supported by Advantage West Midlands (AWM) and the European Regional Development Fund (ERDF); we thank Dinu Iuga for experimental assistance, and Chris Somerville for helpful discussions and suggesting the name STELLO. The authors acknowledge LNBio and LNLS for providing X-ray beam time (proposal GAR 15208), and the Sainsbury Laboratory Cambridge University for imaging facilities. TV was supported by an EMBO long-term fellowship (ALTF 711-2012) and by postdoctoral funding from the Philomathia Foundation. HEM was supported by an EMBO Long Term Fellowship (ALTF-1246-2013) and an NSERC Postdoctoral Fellowship (PDF-454454-2014). SP and YZ were supported by the Max-Planck Gesellschaft, and SP was also supported by a R@MAP Professor position at UoM. We thank the Biological Optical Microscopy Platform (BOMP) at University of Melbourne, and Tom Simmons and Rita Marques for assistance on sugar analyses.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms11656

Characterizing the heterogeneity of triple-negative breast cancers using microdissected normal ductal epithelium and RNA-sequencing

Triple-negative breast cancers (TNBCs) are a heterogeneous set of tumors defined by an absence of actionable therapeutic targets (ER, PR, and HER-2). Microdissected normal ductal epithelium from healthy volunteers represents a novel comparator to reveal insights into TNBC heterogeneity and to inform drug development. Using RNA-sequencing data from our institution and The Cancer Genome Atlas (TCGA) we compared the transcriptomes of 94 TNBCs, 20 microdissected normal breast tissues from healthy volunteers from the Susan G. Komen for the Cure Tissue Bank, and 10 histologically normal tissues adjacent to tumor. Pathway analysis comparing TNBCs to optimized normal controls of microdissected normal epithelium versus classic controls composed of adjacent normal tissue revealed distinct molecular signatures. Differential gene expression of TNBC compared with normal comparators demonstrated important findings for TNBC-specific clinical trials testing targeted agents; lack of over-expression for negative studies and over-expression in studies with drug activity. Next, by comparing each individual TNBC to the set of microdissected normals, we demonstrate that TNBC heterogeneity is attributable to transcriptional chaos, is associated with non-silent DNA mutational load, and explains transcriptional heterogeneity in addition to known molecular subtypes. Finally, chaos analysis identified 146 core genes dysregulated in >90 % of TNBCs revealing an over-expressed central network. In conclusion, use of microdissected normal ductal epithelium from healthy volunteers enables an optimized approach for studying TNBC and uncovers biological heterogeneity mediated by transcriptional chaos

Multi-Institutional FASTQ File Exchange as a Means of Proficiency Testing for Next-Generation Sequencing Bioinformatics and Variant Interpretation

Next-generation sequencing is becoming increasingly common in clinical laboratories worldwide and is revolutionizing clinical molecular testing. However, the large amounts of raw data produced by next-generation sequencing assays and the need for complex bioinformatics analyses present unique challenges. Proficiency testing in clinical laboratories has traditionally been designed to evaluate assays in their entirety; however, it can be alternatively applied to separate assay components. We developed and implemented a multi-institutional proficiency testing approach to directly assess custom bioinformatics and variant interpretation processes. Six clinical laboratories, all of which use the same commercial library preparation kit for next-generation sequencing analysis of tumor specimens, each submitted raw data (FASTQ files) from four samples. These 24 file sets were then deidentified and redistributed to five of the institutions for analysis and interpretation according to their clinically validated approach. Among the laboratories, there was a high rate of concordance in the calling of single-nucleotide variants, in particular those we considered clinically significant (100% concordance). However, there was significant discordance in the calling of clinically significant insertions/deletions, with only two of seven being called by all participating laboratories. Missed calls were addressed by each laboratory to improve their bioinformatics processes. Thus, through our alternative proficiency testing approach, we identified the bioinformatic detection of insertions/deletions as an area of particular concern for clinical laboratories performing next-generation sequencing testing