Host genetic and environmental factors shape the human gut resistome

BACKGROUND: Understanding and controlling the spread of antimicrobial resistance is one of the greatest challenges of modern medicine. To this end many efforts focus on characterising the human resistome or the set of antibiotic resistance determinants within the microbiome of an individual. Aside from antibiotic use, other host environmental and genetic factors that may shape the resistome remain relatively underexplored. METHODS: Using gut metagenome data from 250 TwinsUK female twins, we quantified known antibiotic resistance genes to estimate gut microbiome antibiotic resistance potential for 41 types of antibiotics and resistance mechanisms. Using heritability modelling, we assessed the influence of host genetic and environmental factors on the gut resistome. We then explored links between gut resistome, host health and specific environmental exposures using linear mixed effect models adjusted for age, BMI, alpha diversity and family structure. RESULTS: We considered gut microbiome antibiotic resistance to 21 classes of antibiotics, for which resistance genes were detected in over 90% of our population sample. Using twin modelling, we estimated that on average about 25% of resistome variability could be attributed to host genetic influences. Greatest heritability estimates were observed for resistance potential to acriflavine (70%), dalfopristin (51%), clindamycin (48%), aminocoumarin (48%) and the total score summing across all antibiotic resistance genes (38%). As expected, the majority of resistome variability was attributed to host environmental factors specific to an individual. We compared antibiotic resistance profiles to multiple environmental exposures, lifestyle and health factors. The strongest associations were observed with alcohol and vegetable consumption, followed by high cholesterol medication and antibiotic usage. Overall, inter-individual variation in host environment showed modest associations with antibiotic resistance profiles, and host health status had relatively minor signals. CONCLUSION: Our results identify host genetic and environmental influences on the human gut resistome. The findings improve our knowledge of human factors that influence the spread of antibiotic resistance genes and may contribute towards helping to attenuate it

ISML: an interface specification meta-language

In this paper we present an abstract metaphor model situated within a model-based user interface framework. The inclusion of metaphors in graphical user interfaces is a well established, but mostly craft-based strategy to design. A substantial body of notations and tools can be found within the model-based user interface design literature, however an explicit treatment of metaphor and its mappings to other design views has yet to be addressed. We introduce the Interface Specification Meta-Language (ISML) framework and demonstrate its use in comparing the semantic and syntactic features of an interactive system. Challenges facing this research are outlined and further work proposed

Non linear excess conductivity of Bi2_2Sr2_2Can−1_{n-1}Cun_nO2n+4+x_{2n+4+x} (n = 1,2), thin films

The suppression of excess conductivity with electric field is studied for Bi$_2$Sr$_2$Ca$_{n-1}$Cu$_n$O$_{2n+4+x}$ ($n$ = 1, 2) thin films. A pulse-probe technique is used, which allows for an estimate of the sample temperature. The characteristic electric field for fluctuations suppression is found well below the expected value for all samples. For the $n=1$ material, a scaling of the excess conductivity with electric field and temperature is obtained, similar to the scaling under strong magnetic field

Observational diagnostics of gas in protoplanetary disks

Protoplanetary disks are composed primarily of gas (99% of the mass). Nevertheless, relatively few observational constraints exist for the gas in disks. In this review, I discuss several observational diagnostics in the UV, optical, near-IR, mid-IR, and (sub)-mm wavelengths that have been employed to study the gas in the disks of young stellar objects. I concentrate in diagnostics that probe the inner 20 AU of the disk, the region where planets are expected to form. I discuss the potential and limitations of each gas tracer and present prospects for future research.Comment: Review written for the proceedings of the conference "Origin and Evolution of Planets 2008", Ascona, Switzerland, June 29 - July 4, 2008. Date manuscript: October 2008. 17 Pages, 6 graphics, 134 reference

Sub-terahertz, microwaves and high energy emissions during the December 6, 2006 flare, at 18:40 UT

The presence of a solar burst spectral component with flux density increasing with frequency in the sub-terahertz range, spectrally separated from the well-known microwave spectral component, bring new possibilities to explore the flaring physical processes, both observational and theoretical. The solar event of 6 December 2006, starting at about 18:30 UT, exhibited a particularly well-defined double spectral structure, with the sub-THz spectral component detected at 212 and 405 GHz by SST and microwaves (1-18 GHz) observed by the Owens Valley Solar Array (OVSA). Emissions obtained by instruments in satellites are discussed with emphasis to ultra-violet (UV) obtained by the Transition Region And Coronal Explorer (TRACE), soft X-rays from the Geostationary Operational Environmental Satellites (GOES) and X- and gamma-rays from the Ramaty High Energy Solar Spectroscopic Imager (RHESSI). The sub-THz impulsive component had its closer temporal counterpart only in the higher energy X- and gamma-rays ranges. The spatial positions of the centers of emission at 212 GHz for the first flux enhancement were clearly displaced by more than one arc-minute from positions at the following phases. The observed sub-THz fluxes and burst source plasma parameters were found difficult to be reconciled to a purely thermal emission component. We discuss possible mechanisms to explain the double spectral components at microwaves and in the THz ranges.Comment: Accepted version for publication in Solar Physic

Deceleration and trapping of heavy diatomic molecules using a ring-decelerator

We present an analysis of the deceleration and trapping of heavy diatomic molecules in low-field seeking states by a moving electric potential. This moving potential is created by a 'ring-decelerator', which consists of a series of ring-shaped electrodes to which oscillating high voltages are applied. Particle trajectory simulations have been used to analyze the deceleration and trapping efficiency for a group of molecules that is of special interest for precision measurements of fundamental discrete symmetries. For the typical case of the SrF molecule in the (N,M) = (2, 0) state, the ring-decelerator is shown to outperform traditional and alternate-gradient Stark decelerators by at least an order of magnitude. If further cooled by a stage of laser cooling, the decelerated molecules allow for a sensitivity gain in a parity violation measurement, compared to a cryogenic molecular beam experiment, of almost two orders of magnitude

Oxidative stress and life histories: unresolved issues and current needs

Life-history theory concerns the trade-offs that mold the patterns of investment by animals between reproduction, growth, and survival. It is widely recognized that physiology plays a role in the mediation of life-history trade-offs, but the details remain obscure. As life-history theory concerns aspects of investment in the soma that influence survival, understanding the physiological basis of life histories is related, but not identical, to understanding the process of aging. One idea from the field of aging that has gained considerable traction in the area of life histories is that life-history trade-offs may be mediated by free radical production and oxidative stress. We outline here developments in this field and summarize a number of important unresolved issues that may guide future research efforts. The issues are as follows. First, different tissues and macromolecular targets of oxidative stress respond differently during reproduction. The functional significance of these changes, however, remains uncertain. Consequently there is a need for studies that link oxidative stress measurements to functional outcomes, such as survival. Second, measurements of oxidative stress are often highly invasive or terminal. Terminal studies of oxidative stress in wild animals, where detailed life-history information is available, cannot generally be performed without compromising the aims of the studies that generated the life-history data. There is a need therefore for novel non-invasive measurements of multi-tissue oxidative stress. Third, laboratory studies provide unrivaled opportunities for experimental manipulation but may fail to expose the physiology underpinning life-history effects, because of the benign laboratory environment. Fourth, the idea that oxidative stress might underlie life-history trade-offs does not make specific enough predictions that are amenable to testing. Moreover, there is a paucity of good alternative theoretical models on which contrasting predictions might be based. Fifth, there is an enormous diversity of life-history variation to test the idea that oxidative stress may be a key mediator. So far we have only scratched the surface. Broadening the scope may reveal new strategies linked to the processes of oxidative damage and repair. Finally, understanding the trade-offs in life histories and understanding the process of aging are related but not identical questions. Scientists inhabiting these two spheres of activity seldom collide, yet they have much to learn from each other

Transverse Beam Spin Asymmetries in Forward-Angle Elastic Electron-Proton Scattering

We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely-polarized 3 GeV electrons from unpolarized protons at Q^2 = 0.15, 0.25 (GeV/c)^2. The results are inconsistent with calculations solely using the elastic nucleon intermediate state, and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A_n provides a direct probe of the imaginary component of the 2-gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.Comment: 5 pages, 3 figures, submitted to Physical Review Letters; shortened to meet PRL length limit, clarified some text after referee's comment

Strange Quark Contributions to Parity-Violating Asymmetries in the Forward G0 Electron-Proton Scattering Experiment

We have measured parity-violating asymmetries in elastic electron-proton scattering over the range of momentum transfers 0.12 < Q^2 < 1.0 GeV^2. These asymmetries, arising from interference of the electromagnetic and neutral weak interactions, are sensitive to strange quark contributions to the currents of the proton. The measurements were made at JLab using a toroidal spectrometer to detect the recoiling protons from a liquid hydrogen target. The results indicate non-zero, Q^2 dependent, strange quark contributions and provide new information beyond that obtained in previous experiments.Comment: 5 pages, 2 figure