Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production

The ever-increasing incidence of antibiotic-resistant infections combined with a weak pipeline of new antibiotics has created a global public health crisis1. Accordingly, novel strategies for enhancing our antibiotic arsenal are needed. As antibiotics kill bacteria in part by inducing reactive oxygen species (ROS)2–4, we reasoned that targeting microbial ROS production might potentiate antibiotic activity. Here we show that ROS production can be predictably enhanced in Escherichia coli, increasing the bacteria’s susceptibility to oxidative attack. We developed an ensemble, genome-scale metabolic modeling approach capable of predicting ROS production in E. coli. The metabolic network was systematically perturbed and its flux distribution analyzed to identify targets predicted to increase ROS production. In silico–predicted targets were experimentally validated and shown to confer increased susceptibility to oxidants. Validated targets also increased susceptibility to killing by antibiotics. This work establishes a systems-based method to tune ROS production in bacteria and demonstrates that increased microbial ROS production can potentiate killing by oxidants and antibiotics

Phage typing or CRISPR typing for epidemiological surveillance of Salmonella Typhimurium?

Objective: Salmonella Typhimurium is the most dominant Salmonella serovar around the world. It is associated with foodborne gastroenteritis outbreaks but has recently been associated with invasive illness and deaths. Characterization of S. Typhimurium is therefore very crucial for epidemiological surveillance. Phage typing has been used for decades for subtyping of S. Typhimurium to determine the epidemiological relation among isolates. Recent studies however have suggested that high throughput clustered regular interspaced short palindromic repeats (CRISPR) typing has the potential to replace phage typing. This study aimed to determine the efficacy of highthroughput CRISPR typing over conventional phage typing in epidemiological surveillance and outbreak investigation of S. Typhimurium. Results: In silico analysis of whole genome sequences (WGS) of well-documented phage types of S. Typhimurium reveals the presence of different CRISPR type among strains belong to the same phage type. Furthermore, different phage types of S. Typhimurium share identical CRISPR type. Interestingly, identical spacers were detected among outbreak and non-outbreak associated DT8 strains of S. Typhimurium. Therefore, CRISPR typing is not useful for the epidemiological surveillance and outbreak investigation of S. Typhimurium and phage typing, until it is replaced by WGS, is still the gold standard method for epidemiological surveillance of S. Typhimurium

SPIRITS 16tn in NGC 3556: A Heavily Obscured and Low-luminosity Supernova at 8.8 Mpc

We present the discovery by the SPitzer InfraRed Intensive Transients Survey (SPIRITS) of a likely supernova (SN) in NGC 3556 (M108) at only 8.8 Mpc that was not detected by optical searches. A luminous infrared (IR) transient at M [4.5] = −16.7 mag (Vega), SPIRITS 16tn is coincident with a dust lane in the inclined, star-forming disk of the host. Using observations in the IR, optical, and radio, we attempt to determine the nature of this event. We estimate A V ≈ 8–9 mag of extinction, placing it among the three most highly obscured IR-discovered SNe. The [4.5] light curve declined at a rate of 0.013 mag day−1, and the [3.6]–[4.5] color increased from 0.7 to gsim1.0 mag by 184.7 days post discovery. Optical/IR spectroscopy shows a red continuum but no clearly discernible features, preventing a definitive spectroscopic classification. Radio observations constrain the radio luminosity of SPIRITS 16tn to L ν lesssim 1024 erg s−1 Hz−1 between 3 and 15 GHz, excluding many varieties of core-collapse SNe. An SN Ia is ruled out by the observed IR color and lack of spectroscopic features from Fe-peak elements. SPIRITS 16tn was fainter at [4.5] than typical stripped-envelope SNe by ≈1 mag. Comparison of the spectral energy distribution to SNe II suggests that SPIRITS 16tn was both highly obscured and intrinsically dim, possibly akin to the low-luminosity SN 2005cs. We infer the presence of an IR dust echo powered by an initial peak luminosity of the transient of 5 × 1040 erg s−1 lesssim L peak lesssim 4 × 1043 erg s−1, consistent with the observed range for SNe II. This discovery illustrates the power of IR surveys to overcome the compounding effects of visible extinction and optically subluminous events in completing the inventory of nearby SNe

Mediterranean-climate streams and rivers: geographically separated but ecologically comparable freshwater systems

Streams and rivers in mediterranean-climate regions (med-rivers in med-regions) are ecologically unique, with flow regimes reflecting precipitation patterns. Although timing of drying and flooding is predictable, seasonal and annual intensity of these events is not. Sequential flooding and drying, coupled with anthropogenic influences make these med-rivers among the most stressed riverine habitat worldwide. Med-rivers are hotspots for biodiversity in all med-regions. Species in med-rivers require different, often opposing adaptive mechanisms to survive drought and flood conditions or recover from them. Thus, metacommunities undergo seasonal differences, reflecting cycles of river fragmentation and connectivity, which also affect ecosystem functioning. River conservation and management is challenging, and trade-offs between environmental and human uses are complex, especially under future climate change scenarios. This overview of a Special Issue on med-rivers synthesizes information presented in 21 articles covering the five med-regions worldwide: Mediterranean Basin, coastal California, central Chile, Cape region of South Africa, and southwest and southern Australia. Research programs to increase basic knowledge in less-developed med-regions should be prioritized to achieve increased abilities to better manage med-rivers

Development of sentinel node localization and ROLL in breast cancer in Europe

The concept of a precise region in which to find the lymph nodes that drain the lymph directly from the primary tumor site can be traced back to a century ago to the observations of Jamieson and Dobson who described how cancer cells spread from cancer of the stomach in a single lymph node, which they called the â\u80\u9cprimary glandâ\u80\u9d. However, Cabanas was the first in 1977 to realize the importance of this concept in clinical studies following lymphography performed in patients with penile cancer. Thanks to Mortonâ\u80\u99s studies on melanoma in 1992, we began to understand the potential impact of the sentinel lymph node (SN) on the surgical treatment of this type of cancer. The use of a vital dye (blue dye) administered subdermally in the region surrounding the melanoma lesion led to the identification of the sentinel node, and the vital dye technique was subsequently applied to other types of solid tumors, e.g. breast, vulva. However, difficulties in using this technique in anatomical regions with deep lymphatic vessels, e.g. axilla, led to the development of lymphoscintigraphy, started by Alex and Krag in 1993 on melanoma and breast cancer and optimized by our group at European Institute of Oncology (IEO) in Milan in 1996. Today, lymphoscintigraphy is still considered as the most reliable method for the detection of the SN. In 1996, a new method for the localization of non-palpable breast lesion called radioguided occult lesion localization (ROLL) was also developed at IEO. Retrospective and prospective studies have since shown that the ROLL procedure permits the easy and accurate surgical removal of non-palpable breast lesions, overcoming the limitations of previous techniques such as the wire-guided localization. The purpose of this paper is to describe the evolution of SN biopsy and radioguided surgery in the management of breast cancer. We also include a review of the literature on the clinical scenarios in which SN biopsy in breast cancer is currently used, with particular reference to controversies and future prospects

The Gaia-ESO Survey: A lithium-rotation connection at 5 Myr?

Context. The evolution of lithium abundance in cool dwarfs provides a unique probe of non-standard processes in stellar evolution. Aims. We investigate here the lithium content of young low-mass stars in the 5 Myr-old star forming region NGC 2264 and its relationship with rotation. Methods. We combine lithium equivalent width measurements (EW(Li)) from the Gaia-ESO Survey with the determination of rotational periods from the CSI 2264 survey.We consider only bona fide non accreting cluster members in order to minimize uncertainties on EW(Li). Results. We report the existence of a relationship between lithium content and rotation in NGC 2264 at an age of 5 Myr. The Lirotation connection is seen over a restricted temperature range (Te_=3800–4400 K) where fast rotators are Li-rich compared to slow ones. This correlation is similar to, albeit of lower amplitude than, the Li-rotation connection previously reported for K dwarfs in the 125 Myr-old Pleiades cluster. We investigate whether the non-standard pre-main sequence models developed so far to explain the Pleiades results, which are based on episodic accretion, pre-main sequence core-envelope decoupling, and/or radius inflation due to enhanced magnetic activity, can account for an early development of the Li-rotation connection. While radius inflation appears to be the most promising possibility, each of these models has issues. We therefore also discuss external causes that might operate during the first few Myr of pre-main sequence evolution, such as planet engulfment and/or steady disk accretion, as possible candidates for the common origin for Li-excess and fast rotation in young low-mass pre-main sequence stars. Conclusions. The emergence of a connection between lithium content and rotation rate at such an early age as 5 Myr suggests a complex link between accretion processes, early angular momentum evolution, and possibly planet formation, which likely impactsearly stellar evolution and still is to be fully deciphered

New Pleiades Eclipsing Binaries and a Hyades Transiting System Identified by K2

We present the discovery in Kepler's K2 mission observations and our follow-up radial velocity (RV) observations from Keck/HIRES for four eclipsing binary (EB) star systems in the young benchmark Pleiades and Hyades clusters. Based on our modeling results, we announce two new low mass (${M}_{\mathrm{tot}}\lt 0.6$ ${M}_{\odot }$) EBs among Pleiades members (HCG 76 and MHO 9) and we report on two previously known Pleiades binaries that are also found to be EB systems (HII 2407 and HD 23642). We measured the masses of the binary HCG 76 to lesssim2.5% precision, and the radii to lesssim4.5% precision, which together with the precise effective temperatures yield an independent Pleiades distance of 132 ± 5 pc. We discuss another EB toward the Pleiades that is a possible but unlikely Pleiades cluster member (AK II 465). The two new confirmed Pleiades systems extend the mass range of Pleiades EB components to 0.2–2 ${M}_{\odot }$. Our initial measurements of the fundamental stellar parameters for the Pleiades EBs are discussed in the context of the current stellar models and the nominal cluster isochrone, finding good agreement with the stellar models of Baraffe et al. at the nominal Pleiades age of 120 Myr. Finally, in the Hyades, we report a new low mass eclipsing system (vA 50) that was concurrently discovered and studied by Mann et al. We confirm that the eclipse is likely caused by a Neptune-sized transiting planet, and with the additional RV constraints presented here we improve the constraint on the maximum mass of the planet to be lesssim1.2 MJup

Photo-reverberation mapping of a protoplanetary accretion disk around a T Tauri star

This is the final version. Available from the American Astronomical Society via the DOI in this recordTheoretical models and spectroscopic observations of newborn stars suggest that protoplantary disks have an inner "wall" at a distance set by the disk interaction with the star. Around T Tauri stars, the size of this disk hole is expected to be on a 0.1 au scale that is unresolved by current adaptive optics imaging, though some model-dependent constraints have been obtained by near-infrared interferometry. Here we report the first measurement of the inner disk wall around a solar-mass young stellar object, YLW 16B in the ρ Ophiuchi star-forming region, by detecting the light-travel time of the variable radiation from the stellar surface to the disk. Consistent time lags were detected on two nights, when the time series in H (1.6 μm) and K (2.2 μm) bands were synchronized while the 4.5 μm emission lagged by 74.5 ± 3.2 s. Considering the nearly edge-on geometry of the disk, the inner rim should be 0.084 au from the protostar on average, with an error of order 0.01 au. This size is likely larger than the range of magnetospheric truncations and consistent with an optically and geometrically thick disk front at the dust sublimation radius at ∼1500 K. The widths of the cross-correlation functions between the data in different wavebands place possible new constraints on the geometry of the disk.National Science Foundation (NSF

Binary systems and their nuclear explosions

Peer ReviewedPreprin