Nuclear Quasi-Elastic Electron Scattering Limits Nucleon Off-Mass Shell Properties

The use of quasi-elastic electron nucleus scattering is shown to provide significant constraints on models of the proton electromagnetic form factor of off-shell nucleons. Such models can be constructed to be consistent with constraints from current conservation and low-energy theorems, while also providing a contribution to the Lamb shift that might potentially resolve the proton radius puzzle in muonic hydrogen. However, observations of quasi-elastic scattering limit the overall strength of the off-shell form factors to values that correspond to small contributions to the Lamb shift.Comment: 11 pages, 2 figures. Resubmission to improve the clarity, and correct possible misconception

Activation of the Listeria monocytogenes Virulence Program by a Reducing Environment.

Upon entry into the host cell cytosol, the facultative intracellular pathogen Listeria monocytogenes coordinates the expression of numerous essential virulence factors by allosteric binding of glutathione (GSH) to the Crp-Fnr family transcriptional regulator PrfA. Here, we report that robust virulence gene expression can be recapitulated by growing bacteria in a synthetic medium containing GSH or other chemical reducing agents. Bacteria grown under these conditions were 45-fold more virulent in an acute murine infection model and conferred greater immunity to a subsequent lethal challenge than bacteria grown in conventional media. During cultivation in vitro, PrfA activation was completely dependent on the intracellular levels of GSH, as a glutathione synthase mutant (ΔgshF) was activated by exogenous GSH but not reducing agents. PrfA activation was repressed in a synthetic medium supplemented with oligopeptides, but the repression was relieved by stimulation of the stringent response. These data suggest that cytosolic L. monocytogenes interprets a combination of metabolic and redox cues as a signal to initiate robust virulence gene expression in vivoIMPORTANCE Intracellular pathogens are responsible for much of the worldwide morbidity and mortality from infectious diseases. These pathogens have evolved various strategies to proliferate within individual cells of the host and avoid the host immune response. Through cellular invasion or the use of specialized secretion machinery, all intracellular pathogens must access the host cell cytosol to establish their replicative niches. Determining how these pathogens sense and respond to the intracellular compartment to establish a successful infection is critical to our basic understanding of the pathogenesis of each organism and for the rational design of therapeutic interventions. Listeria monocytogenes is a model intracellular pathogen with robust in vitro and in vivo infection models. Studies of the host-sensing and downstream signaling mechanisms evolved by L. monocytogenes often describe themes of pathogenesis that are broadly applicable to less tractable pathogens. Here, we describe how bacteria use external redox states as a cue to activate virulence

Repeating Spatial Activations in Human Entorhinal Cortex

SummaryThe ability to remember and navigate spatial environments is critical for everyday life. A primary mechanism by which the brain represents space is through hippocampal place cells, which indicate when an animal is at a particular location [1]. An important issue is understanding how the hippocampal place-cell network represents specific properties of the environment, such as signifying that a particular position is near a doorway or that another position is near the end of a corridor. The entorhinal cortex (EC), as the main input to the hippocampus, may play a key role in coding these properties because it contains neurons that activate at multiple related positions per environment [2–6]. We examined the diversity of spatial coding across the human medial temporal lobe by recording neuronal activity during virtual navigation of an environment containing four similar paths. Neurosurgical patients performed this task as we recorded from implanted microelectrodes, allowing us to compare the human neuronal representation of space with that of animals. EC neurons activated in a repeating manner across the environment, with individual cells spiking at the same relative location across multiple paths. This finding indicates that EC cells represent non-specific information about location relative to an environment’s geometry, unlike hippocampal place cells, which activate at particular random locations. Given that spatial navigation is considered to be a model of how the brain supports non-spatial episodic memory [7–10], these findings suggest that EC neuronal activity is used by the hippocampus to represent the properties of different memory episodes [2, 11]

Lipid coated liquid crystal droplets for the on-chip detection of antimicrobial peptides

We describe a novel biosensor based on phospholipid-coated nematic liquid crystal (LC) droplets and demonstrate the detection of Smp43, a model antimicrobial peptide (AMP) from the venom of North African scorpion Scorpio maurus palmatus. Mono-disperse lipid-coated LC droplets of diameter 16.7 ± 0.2 μm were generated using PDMS microfluidic devices with a flow-focusing configuration and were the target for AMPs. The droplets were trapped in a bespoke microfluidic trap structure and were simultaneously treated with Smp43 at gradient concentrations in six different chambers. The disruption of the lipid monolayer by the Smp43 was detected (<6 μM) at concentrations well within its biologically active range, indicated by a dramatic change in the appearance of the droplets associated with the transition from a typical radial configuration to a bipolar configuration, which is readily observed by polarizing microscopy. This suggests the system has feasibility as a drug-discovery screening tool. Further, compared to previously reported LC droplet biosensors, this LC droplet biosensor with a lipid coating is more biologically relevant and its ease of use in detecting membrane-related biological processes and interactions has the potential for development as a reliable, low-cost and disposable point of care diagnostic tool

Sage Grouse Groceries: Forb Response to Piñon-Juniper Treatments

AbstractJuniper and piñon coniferous woodlands have increased 2- to 10-fold in nine ecoregions spanning the Intermountain Region of the western United States. Control of piñon-juniper woodlands by mechanical treatments and prescribed fire are commonly applied to recover sagebrush steppe rangelands. Recently, the Sage Grouse Initiative has made conifer removal a major part of its program to reestablish sagebrush habitat for sage grouse (Centrocercus urophasianus) and other species. We analyzed data sets from previous and ongoing studies across the Great Basin characterizing cover response of perennial and annual forbs that are consumed by sage grouse to mechanical, prescribed fire, and low-disturbance fuel reduction treatments. There were 11 sites in western juniper (Juniperus occidentalis Hook.) woodlands, 3 sites in singleleaf piñon (Pinus monophylla Torr. & Frém.) and Utah juniper (Juniperus osteosperma [Torr.] Little), 2 sites in Utah juniper, and 2 sites in Utah juniper and Colorado piñon (Pinus edulis Engelm). Western juniper sites were located in mountain big sagebrush (A. tridentata ssp. vaseyana) steppe associations, and the other woodlands were located in Wyoming big sagebrush (A. tridentata ssp. wyomingensis) associations. Site potential appears to be a major determinant for increasing perennial forbs consumed by sage grouse following conifer control. The cover response of perennial forbs, whether increasing (1.5- to 6-fold) or exhibiting no change, was similar regardless of conifer treatment. Annual forbs favored by sage grouse benefitted most from prescribed fire treatments with smaller increases following mechanical and fuel reduction treatments. Though forb abundance may not consistently be enhanced, mechanical and fuel reduction conifer treatments remain good preventative measures, especially in phase 1 and 2 woodlands, which, at minimum, maintain forbs on the landscape. In addition, these two conifer control measures, in the short term, are superior to prescribed fire for maintaining the essential habitat characteristics of sagebrush steppe for sage grouse

Western Juniper Field Guide: Asking the Right Questions to Select Appropriate Management Actions

Strong evidence indicates that western juniper has significantly expanded its range since the late 1800s by encroaching into landscapes once dominated by shrubs and herbaceous vegetation (fig. 1). Woodland expansion affects soil resources, plant community structure and composition, water, nutrient and fire cycles, forage production, wildlife habitat, and biodiversity. Goals of juniper management include an attempt to restore ecosystem function and a more balanced plant community that includes shrubs, grasses, and forbs, and to increase ecosystem resilience to disturbances. Developing a management strategy can be a difficult task due to uncertainty about how vegetation, soils, hydrologic function, and wildlife will respond to treatments. When developing a management strategy, the first and possibly most important step towards success is asking the right questions. Identifying the attributes of the area to be treated and selecting the right treatments to be applied are of utmost importance. One must ask questions addressing the kind of site (that is, potential natural vegetation, soils, etc.), the current state of the site (that is, successional, hydrologic, etc.), what components need to be restored, how the management unit fits in with the overall landscape mosaic, and the long-term goals and objectives for the area or region. Keep in mind sagebrush-steppe vegetation is dynamic and management strategies must take into account multi-decade time frames. This guide provides a set of tools that will help field biologists, land managers, and private landowners conduct rapid qualitative field assessments that address the kind of site and its current state. These tools include a list of questions to be addressed and a series of photographs, keys, tables, and figures to help evaluate a site. Conducting this assessment will help prioritize sites to be treated, select the best treatment, and predict outcomes. Success of a juniper management program may be greatly enhanced if an interdisciplinary team of local managers and resource specialists, who are experienced with vegetation, fuels, soils, hydrology, wildlife, and economic and sociological aspects of the local resource, use this guide to aid their decision-making

Structurally diverse hamigerans from the New Zealand marine sponge Hamigera tarangaensis: NMR-directed isolation, structure elucidation and antifungal activity

The NMR-directed investigation of the New Zealand marine sponge Hamigera tarangaensis has afforded ten new compounds of the hamigeran family, and a new 13-epi-verrucosane congener. Notably, hamigeran F (6) possesses an unusual carbon–carbon bond between C-12 and C-13, creating an unprecedented skeleton within this class. In particular, the structural features of 6, hamigeran H (10) and hamigeran J (12) imply a diterpenoid origin, which has allowed the putative biogenesis of three hamigeran carbon skeletons to be proposed based on geranyl geranyl pyrophosphate. All new hamigerans exhibited micromolar activity towards the HL-60 promyelocytic leukaemic cell line, and hamigeran G also selectively displayed antifungal activity in the budding yeast Saccharomyces cerevisiae. Homozygous deletion profiling (HOP) analysis suggests Golgi apparatus function as a potential target of this unusual class of sponge-derived terpenoids