16S rRNA deep sequencing identifies Actinotignum schaalii as the major component of a polymicrobial intra-abdominal infection and implicates a urinary source

Introduction. It can be difficult to catalogue the individual organisms comprising polymicrobial patient infections, both because conventional clinical microbiological culture does not facilitate the isolation and enumeration of all members of a complex microbial community, and because fastidious organisms may be mixed with organisms that grow rapidly in vitro. Empiric antimicrobial treatment is frequently employed based on the anatomical site and the suspected source of the infection, especially when an appropriately collected surgical specimen is not obtained., Case presentation. We present a case of an intra-abdominal infection in a patient with complex anatomy and recurrent urinary tract infections. Imaging did not reveal a clear source of infection, no growth was obtained from urine cultures and initial abdominal fluid cultures were also negative. In contrast, 16S rRNA deep sequencing of abdominal fluid samples revealed mixed bacterial populations with abundant anaerobes, including Actinotignum schaalii (Actinobaculum schaalii). Ultimately, only Enterobacter cloacae complex and meticillin-resistant Staphylococcus aureus, both of which were identified by sequencing, were recovered by culture., Conclusion. The clinical application of 16S rRNA deep sequencing can more comprehensively and accurately define the organisms present in an individual patient's polymicrobial infection than conventional microbiological culture, detecting species that are not recovered under standard culture conditions or that are otherwise unexpected. These results can facilitate effective antimicrobial stewardship and help elucidate the possible origins of infections

Simultaneous quantitation of five triazole anti-fungal agents by paper spray-mass spectrometry

Introduction: Invasive fungal disease is a life-threatening condition that can be challenging to treat due to pathogen resistance, drug toxicity, and therapeutic failure secondary to suboptimal drug concentrations. Frequent therapeutic drug monitoring (TDM) is required for some anti-fungal agents to overcome these issues. Unfortunately, TDM at the institutional level is difficult, and samples are often sent to a commercial reference laboratory for analysis. To address this gap, the first paper spray-mass spectrometry assay for the simultaneous quantitation of five triazoles was developed. Methods: Calibration curves for fluconazole, posaconazole, itraconazole, hydroxyitraconazole, and voriconazole were created utilizing plasma-based calibrants and four stable isotopic internal standards. No sample preparation was needed. Plasma samples were spotted on a paper substrate in pre-manufactured plastic cartridges, and the dried plasma spots were analyzed directly utilizing paper spray-mass spectrometry (paper spray MS/MS). All experiments were performed on a Thermo Scientific TSQ Vantage triple quadrupole mass spectrometer. Results: The calibration curves for the five anti-fungal agents showed good linearity (R2 = 0.98 – 1.00). The measured assay ranges (LLOQ – ULOQ) for fluconazole, posaconazole, itraconazole, hydroxyitraconazole, and voriconazole were 0.5 – 50 μg/mL, 0.1 – 10 μg/mL, 0.1 – 10 μg/mL, 0.1 – 10 μg/mL, and 0.1 – 10 μg/mL, respectively. The inter- and intra-day accuracy and precision were less than 25% over the respective ranges. Conclusion: We developed the first rapid paper spray MS/MS assay for simultaneous quantitation of five triazole anti-fungal agents in plasma. The method may be a powerful tool for near point-of-care TDM aimed at improving patient care by reducing turnaround time and for use in clinical research

Science Impacts of the SPHEREx All-Sky Optical to Near-Infrared Spectral Survey: Report of a Community Workshop Examining Extragalactic, Galactic, Stellar and Planetary Science

SPHEREx is a proposed SMEX mission selected for Phase A. SPHEREx will carry out the first all-sky spectral survey and provide for every 6.2" pixel a spectra between 0.75 and 4.18 $\mu$m [with R$\sim$41.4] and 4.18 and 5.00 $\mu$m [with R$\sim$135]. The SPHEREx team has proposed three specific science investigations to be carried out with this unique data set: cosmic inflation, interstellar and circumstellar ices, and the extra-galactic background light. It is readily apparent, however, that many other questions in astrophysics and planetary sciences could be addressed with the SPHEREx data. The SPHEREx team convened a community workshop in February 2016, with the intent of enlisting the aid of a larger group of scientists in defining these questions. This paper summarizes the rich and varied menu of investigations that was laid out. It includes studies of the composition of main belt and Trojan/Greek asteroids; mapping the zodiacal light with unprecedented spatial and spectral resolution; identifying and studying very low-metallicity stars; improving stellar parameters in order to better characterize transiting exoplanets; studying aliphatic and aromatic carbon-bearing molecules in the interstellar medium; mapping star formation rates in nearby galaxies; determining the redshift of clusters of galaxies; identifying high redshift quasars over the full sky; and providing a NIR spectrum for most eROSITA X-ray sources. All of these investigations, and others not listed here, can be carried out with the nominal all-sky spectra to be produced by SPHEREx. In addition, the workshop defined enhanced data products and user tools which would facilitate some of these scientific studies. Finally, the workshop noted the high degrees of synergy between SPHEREx and a number of other current or forthcoming programs, including JWST, WFIRST, Euclid, GAIA, K2/Kepler, TESS, eROSITA and LSST.Comment: Report of the First SPHEREx Community Workshop, http://spherex.caltech.edu/Workshop.html , 84 pages, 28 figure

SPHEREx: NASA's near-infrared spectrophotometric all-sky survey

SPHEREx, the Spectro-Photometer for the History of the Universe, Epoch of Reionization, and ices Explorer, is a NASA MIDEX mission planned for launch in 2024. SPHEREx will carry out the first all-sky spectral survey at wavelengths between 0.75µm and 5µm with spectral resolving power ~40 between 0.75 and 3.8µm and ~120 between 3.8 and 5µm At the end of its two-year mission, SPHEREx will provide 0.75-to-5µm spectra of each 6.”2 x 6.”2 pixel on the sky - 14 billion spectra in all. This paper updates an earlier description of SPHEREx presenting changes made during the mission's Preliminary Design Phase, including a discussion of instrument integration and test ow and a summary of the data processing, analysis, and distribution plans

Millisecond-Timescale Local Network Coding in the Rat Primary Somatosensory Cortex

Correlation among neocortical neurons is thought to play an indispensable role in mediating sensory processing of external stimuli. The role of temporal precision in this correlation has been hypothesized to enhance information flow along sensory pathways. Its role in mediating the integration of information at the output of these pathways, however, remains poorly understood. Here, we examined spike timing correlation between simultaneously recorded layer V neurons within and across columns of the primary somatosensory cortex of anesthetized rats during unilateral whisker stimulation. We used Bayesian statistics and information theory to quantify the causal influence between the recorded cells with millisecond precision. For each stimulated whisker, we inferred stable, whisker-specific, dynamic Bayesian networks over many repeated trials, with network similarity of 83.3±6% within whisker, compared to only 50.3±18% across whiskers. These networks further provided information about whisker identity that was approximately 6 times higher than what was provided by the latency to first spike and 13 times higher than what was provided by the spike count of individual neurons examined separately. Furthermore, prediction of individual neurons' precise firing conditioned on knowledge of putative pre-synaptic cell firing was 3 times higher than predictions conditioned on stimulus onset alone. Taken together, these results suggest the presence of a temporally precise network coding mechanism that integrates information across neighboring columns within layer V about vibrissa position and whisking kinetics to mediate whisker movement by motor areas innervated by layer V

Gas-Phase studies on the reactivity and formation of para-benzynes and carbon-nitrogen (CN) ortho-benzynes in a fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer

For over a century, the benzynes have been the focus of numerous theoretical and experimental studies. ortho-Benzynes, the most studied benzynes, were identified long ago as the key reaction intermediates of several organic reactions, including nucleophilic aromatic substitution and 1,3-cycloaddition. More recently, substituted para-benzynes have been suggested to act as the biologically-active intermediates of the enediyne antitumor antibiotics. This finding has led to an increased interest in the properties of benzynes. However, their intrinsic chemical properties are still largely unknown. Utilizing the distonic ion approach, the reactivities of para-benzynes and carbon-nitrogen (CN) ortho-benzynes were examined in a dual-cell Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR) in order to gain further insight on the chemical properties that control them

The “PepSAVI-MS” Pipeline for Natural Product Bioactive Peptide Discovery

The recent increase in extensively drug-resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs mass spectrometry and statistics to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. odorata cyclotides, including antibacterial activity of cycloviolacin O2 against A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast, and prostate cancer cell lines