The Genetic Basis of Natural Variation in Drosophila melanogaster Immune Defense against Enterococcus faecalis

This work is licensed under a Creative Commons Attribution 4.0 International License.Dissecting the genetic basis of natural variation in disease response in hosts provides insights into the coevolutionary dynamics of host-pathogen interactions. Here, a genome-wide association study of Drosophila melanogaster survival after infection with the Gram-positive entomopathogenic bacterium Enterococcus faecalis is reported. There was considerable variation in defense against E. faecalis infection among inbred lines of the Drosophila Genetics Reference Panel. We identified single nucleotide polymorphisms associated with six genes with a significant (p < 10−08, corresponding to a false discovery rate of 2.4%) association with survival, none of which were canonical immune genes. To validate the role of these genes in immune defense, their expression was knocked-down using RNAi and survival of infected hosts was followed, which confirmed a role for the genes krishah and S6k in immune defense. We further identified a putative role for the Bomanin gene BomBc1 (also known as IM23), in E. faecalis infection response. This study adds to the growing set of association studies for infection in Drosophila melanogaster and suggests that the genetic causes of variation in immune defense differ for different pathogens

Capabilities, Performance, and Status of the SOFIA Science Instrument Suite

The Stratospheric Observatory for Infrared Astronomy (SOFIA) is an airborne observatory, carrying a 2.5 m telescope onboard a heavily modified Boeing 747SP aircraft. SOFIA is optimized for operation at infrared wavelengths, much of which is obscured for ground-based observatories by atmospheric water vapor. The SOFIA science instrument complement consists of seven instruments: FORCAST (Faint Object InfraRed CAmera for the SOFIA Telescope), GREAT (German Receiver for Astronomy at Terahertz Frequencies), HIPO (High-speed Imaging Photometer for Occultations), FLITECAM (First Light Infrared Test Experiment CAMera), FIFI-LS (Far-Infrared Field-Imaging Line Spectrometer), EXES (Echelon-Cross-Echelle Spectrograph), and HAWC (High-resolution Airborne Wideband Camera). FORCAST is a 540 m imager with grism spectroscopy, developed at Cornell University. GREAT is a heterodyne spectrometer providing high-resolution spectroscopy in several bands from 60240 m, developed at the Max Planck Institute for Radio Astronomy. HIPO is a 0.31.1 m imager, developed at Lowell Observatory. FLITECAM is a 15 m wide-field imager with grism spectroscopy, developed at UCLA. FIFI-LS is a 42210 m integral field imaging grating spectrometer, developed at the University of Stuttgart. EXES is a 528 m high-resolution spectrograph, developed at UC Davis and NASA ARC. HAWC is a 50240 m imager, developed at the University of Chicago, and undergoing an upgrade at JPL to add polarimetry capability and substantially larger GSFC detectors. We describe the capabilities, performance, and status of each instrument, highlighting science results obtained using FORCAST, GREAT, and HIPO during SOFIA Early Science observations conducted in 2011

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Safety and Pharmacokinetics of Intravenous Anidulafungin in Children with Neutropenia at High Risk for Invasive Fungal Infections

Anidulafungin is an echinocandin with activity against Candida species and Aspergillus species. Adult dosages under study are 50 mg/day for esophageal candidiasis and 100 mg/day for invasive candidiasis and aspergillosis. Little is known, however, about the safety and pharmacokinetics of anidulafungin in children. A multicenter, ascending-dosage study of neutropenic pediatric patients was therefore conducted. Patients were divided into two age cohorts (2 to 11 years and 12 to 17 years) and were enrolled into sequential groups to receive 0.75 or 1.5 mg/kg of body weight/day. Blood samples were obtained following the first and fifth doses. Anidulafungin was assayed in plasma, and pharmacokinetic parameters were determined. Safety was assessed using National Cancer Institute (NCI) common toxicity criteria. Pharmacokinetic parameters were determined for 12 patients at each dosage (0.75 mg/kg/day or 1.5 mg/kg/day). Concentrations and drug exposures were similar for patients between age cohorts, and weight-adjusted clearance was consistent across age. No drug-related serious adverse events were observed. One patient had fever (NCI toxicity grade of 3), and one patient had facial erythema, which resolved with slowing the infusion rate. Anidulafungin in pediatric patients was well tolerated and can be dosed based on body weight. Pediatric patients receiving 0.75 mg/kg/day or 1.5 mg/kg/day have anidulafungin concentration profiles similar to those of adult patients receiving 50 or 100 mg/day, respectively

Epigenetic cell fate in Candida albicans is controlled by transcription factor condensates acting at super-enhancer-like elements.

Cell identity in eukaryotes is controlled by transcriptional regulatory networks that define cell-type-specific gene expression. In the opportunistic fungal pathogen Candida albicans, transcriptional regulatory networks regulate epigenetic switching between two alternative cell states, 'white' and 'opaque', that exhibit distinct host interactions. In the present study, we reveal that the transcription factors (TFs) regulating cell identity contain prion-like domains (PrLDs) that enable liquid-liquid demixing and the formation of phase-separated condensates. Multiple white-opaque TFs can co-assemble into complex condensates as observed on single DNA molecules. Moreover, heterotypic interactions between PrLDs support the assembly of multifactorial condensates at a synthetic locus within live eukaryotic cells. Mutation of the Wor1 TF revealed that substitution of acidic residues in the PrLD blocked its ability to phase separate and co-recruit other TFs in live cells, as well as its function in C. albicans cell fate determination. Together, these studies reveal that PrLDs support the assembly of TF complexes that control fungal cell identity and highlight parallels with the 'super-enhancers' that regulate mammalian cell fate

Capabilities, performance, and status of the SOFIA science instrument suite

The Stratospheric Observatory for Infrared Astronomy (SOFIA) is an airborne observatory, carrying a 2.5 m telescope onboard a heavily modified Boeing 747SP aircraft. SOFIA is optimized for operation at infrared wavelengths, much of which is obscured for ground-based observatories by atmospheric water vapor. The SOFIA science instrument complement consists of seven instruments: FORCAST (Faint Object InfraRed CAmera for the SOFIA Telescope), GREAT (German Receiver for Astronomy at Terahertz Frequencies), HIPO (High-speed Imaging Photometer for Occultations), FLITECAM (First Light Infrared Test Experiment CAMera), FIFI-LS (Far-Infrared Field-Imaging Line Spectrometer), EXES (Echelon-Cross-Echelle Spectrograph), and HAWC (High-resolution Airborne Wideband Camera). FORCAST is a 5-40 μm imager with grism spectroscopy, developed at Cornell University. GREAT is a heterodyne spectrometer providing high-resolution spectroscopy in several bands from 60-240 μm, developed at the Max Planck Institute for Radio Astronomy. HIPO is a 0.3-1.1 μm imager, developed at Lowell Observatory. FLITECAM is a 1-5 μm wide-field imager with grism spectroscopy, developed at UCLA. FIFI-LS is a 42-210 μm integral field imaging grating spectrometer, developed at the University of Stuttgart. EXES is a 5-28 μm high-resolution spectrograph, developed at UC Davis and NASA ARC. HAWC is a 50-240 μm imager, developed at the University of Chicago, and undergoing an upgrade at JPL to add polarimetry capability and substantially larger GSFC detectors. We describe the capabilities, performance, and status of each instrument, highlighting science results obtained using FORCAST, GREAT, and HIPO during SOFIA Early Science observations conducted in 2011. © 2013 Copyright SPIE