Determining the effects of cattle grazing treatments on Yosemite toads (Anaxyrus [=Bufo] canorus) in montane meadows.

Amphibians are experiencing a precipitous global decline, and population stability on public lands with multiple uses is a key concern for managers. In the Sierra Nevada Mountains (California, USA), managers have specifically identified livestock grazing as an activity that may negatively affect Yosemite toads due to the potential overlap of grazing with toad habitat. Grazing exclusion from Yosemite toad breeding and rearing areas and/or entire meadows have been proposed as possible management actions to alleviate the possible impact of cattle on this species. The primary objective of this study was to determine if different fencing treatments affect Yosemite toad populations. We specifically examined the effect of three fencing treatments on Yosemite toad breeding pool occupancy, tadpoles, and young of the year (YOY). Our hypothesis was that over the course of treatment implementation (2006 through 2010), Yosemite toad breeding pool occupancy and early life stage densities would increase within two fencing treatments relative to actively grazed meadows due to beneficial changes to habitat quality in the absence of grazing. Our results did not support our hypothesis, and showed no benefit to Yosemite toad presence or early life stages in fenced or partially fenced meadows compared to standard USDA Forest Service grazing levels. We found substantial Yosemite toad variation by both meadow and year. This variation was influenced by meadow wetness, with water table depth significant in both the tadpole and YOY models

Mutation of a nicotinic acetylcholine receptor β subunit is associated with resistance to neonicotinoid insecticides in the aphid Myzus persicae

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly citedBackground: Myzus persicae is a globally important aphid pest with a history of developing resistance to insecticides. Unusually, neonicotinoids have remained highly effective as control agents despite nearly two decades of steadily increasing use. In this study, a clone of M. persicae collected from southern France was found, for the first time, to exhibit sufficiently strong resistance to result in loss of the field effectiveness of neonicotinoids. Results: Bioassays, metabolism and gene expression studies implied the presence of two resistance mechanisms in the resistant clone, one based on enhanced detoxification by cytochrome P450 monooxygenases, and another unaffected by a synergist that inhibits detoxifying enzymes. Binding of radiolabeled imidacloprid (a neonicotinoid) to whole body membrane preparations showed that the high affinity [3H]-imidacloprid binding site present in susceptible M. persicae is lost in the resistant clone and the remaining lower affinity site is altered compared to susceptible clones. This confers a significant overall reduction in binding affinity to the neonicotinoid target: the nicotinic acetylcholine receptor (nAChR). Comparison of the nucleotide sequence of six nAChR subunit (Mp alpha 1-5 and Mp beta 1) genes from resistant and susceptible aphid clones revealed a single point mutation in the loop D region of the nAChR beta 1 subunit of the resistant clone, causing an arginine to threonine substitution (R81T). Conclusion: Previous studies have shown that the amino acid at this position within loop D is a key determinant of neonicotinoid binding to nAChRs and this amino acid change confers a vertebrate-like character to the insect nAChR receptor and results in reduced sensitivity to neonicotinoids. The discovery of the mutation at this position and its association with the reduced affinity of the nAChR for imidacloprid is the first example of field-evolved target-site resistance to neonicotinoid insecticides and also provides further validation of exisiting models of neonicotinoid binding and selectivity for insect nAChRs.Peer reviewedFinal Published versio

The care of older cancer patients in the United Kingdom

The ageing population poses new challenges globally. Cancer care for older patients is one of these challenges, and it has a significant impact on societies. In the United Kingdom (UK), as the number of older cancer patients increases, the management of this group has become part of daily practice for most oncology teams in every geographical area. Older cancer patients are at a higher risk of both under- and over-treatment. Therefore, the assessment of a patient’s biological age and effective organ functional reserve becomes paramount. This may then guide treatment decisions by better estimating a prognosis and the risk-to-benefit ratio of a given therapy to anticipate and mitigate against potential toxicities/difficulties. Moreover, older cancer patients are often affected by geriatric syndromes and other issues that impact their overall health, function and quality of life. Comprehensive geriatric assessments offer an opportunity to identify and address health problems which may then optimise one’s fitness and well-being. Whilst it is widely accepted that older cancer patients may benefit from such an approach, resources are often scarce, and access to dedicated services and research remains limited to specific centres across the UK. The aim of this project is to map the current services and projects in the UK to learn from each other and shape the future direction of care of older patients with cancer

Label-free chemically specific imaging in planta with stimulated Raman scattering microscopy.

The growing world population puts ever-increasing demands on the agricultural and agrochemical industries to increase agricultural yields. This can only be achieved by investing in fundamental plant and agrochemical research and in the development of improved analytical tools to support research in these areas. There is currently a lack of analytical tools that provide noninvasive structural and chemical analysis of plant tissues at the cellular scale. Imaging techniques such as coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) microscopy provide label-free chemically specific image contrast based on vibrational spectroscopy. Over the past decade, these techniques have been shown to offer clear advantages for a vast range of biomedical research applications. The intrinsic vibrational contrast provides label-free quantitative functional analysis, it does not suffer from photobleaching, and it allows near real-time imaging in 3D with submicrometer spatial resolution. However, due to the susceptibility of current detection schemes to optical absorption and fluorescence from pigments (such as chlorophyll), the plant science and agrochemical research communities have not been able to benefit from these techniques and their application in plant research has remained virtually unexplored. In this paper, we explore the effect of chlorophyll fluorescence and absorption in CARS and SRS microscopy. We show that with the latter it is possible to use phase-sensitive detection to separate the vibrational signal from the (electronic) absorption processes. Finally, we demonstrate the potential of SRS for a range of in planta applications by presenting in situ chemical analysis of plant cell wall components, epicuticular waxes, and the deposition of agrochemical formulations onto the leaf surface

The GALAH Survey: Chemical Clocks

Previous studies have found that the elemental abundances of a star correlate directly with its age and metallicity. Using this knowledge, we derive ages for a sample of 250,000 stars taken from GALAH DR3 using only their overall metallicity and chemical abundances. Stellar ages are estimated via the machine learning algorithm $XGBoost$, using main sequence turnoff stars with precise ages as our input training set. We find that the stellar ages for the bulk of the GALAH DR3 sample are accurate to 1-2 Gyr using this method. With these ages, we replicate many recent results on the age-kinematic trends of the nearby disk, including the age-velocity dispersion relationship of the solar neighborhood and the larger global velocity dispersion relations of the disk found using $Gaia$ and GALAH. The fact that chemical abundances alone can be used to determine a reliable age for a star have profound implications for the future study of the Galaxy as well as upcoming spectroscopic surveys. These results show that the chemical abundance variation at a given birth radius is quite small, and imply that strong chemical tagging of stars directly to birth clusters may prove difficult with our current elemental abundance precision. Our results highlight the need of spectroscopic surveys to deliver precision abundances for as many nucleosynthetic production sites as possible in order to estimate reliable ages for stars directly from their chemical abundances. Applying the methods outlined in this paper opens a new door into studies of the kinematic structure and evolution of the disk, as ages may potentially be estimated for a large fraction of stars in existing spectroscopic surveys. This would yield a sample of millions of stars with reliable age determinations, and allow precise constraints to be put on various kinematic processes in the disk, such as the efficiency and timescales of radial migration.Comment: 13 pages, 15 figures, submitted to MNRA

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality: An Individual-Level Pooled Analysis of 30 Cohort Studies

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance–weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88–0.99), 0.78 (0.70–0.85), and 0.88 (0.79–0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88–1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86–0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention

The GALAH survey: accurate radial velocities and library of observed stellar template spectra

GALAH is a large-scale magnitude-limited southern stellar spectroscopic survey. Its second data release (GALAH DR2) provides values of stellar parameters and abundances of 23 elements for 342 682 stars (Buder et al.). Here we add a description of the public release of radial velocities with a typical accuracy of 0.1 km s-1 for 336 215 of these stars, achievable due to the large wavelength coverage, high resolving power, and good signal-to-noise ratio of the observed spectra, but also because convective motions in stellar atmosphere and gravitational redshift from the star to the observer are taken into account. In the process we derive medians of observed spectra that are nearly noiseless, as they are obtained from between 100 and 1116 observed spectra belonging to the same bin with a width of 50 K in temperature, 0.2 dex in gravity, and 0.1 dex in metallicity. Publicly released 1181 median spectra have a resolving power of 28 000 and trace the well-populated stellar types with metallicities between -0.6 and +0.3. Note that radial velocities from GALAH are an excellent match to the accuracy of velocity components along the sky plane derived by Gaia for the same stars. The level of accuracy achieved here is adequate for studies of dynamics within stellar clusters, associations, and streams in the Galaxy. So it may be relevant for studies of the distribution of dark matter

The GALAH survey: chemical clocks

We present the first large-scale study that demonstrates how ages can be determined for large samples of stars through Galactic chemical evolution. Previous studies found that the elemental abundances of a star correlate directly with its age and metallicity. Using this knowledge, we derive ages for 214 577 stars in GALAH DR3 using only overall metallicities and chemical abundances. Stellar ages are estimated via the machine learning algorithm XGBoost for stars belonging to the Milky Way disc with metallicities in the range -1 < [Fe/H] < 0.5, using main-sequence turn-off stars as our training set. We find that stellar ages for the bulk of GALAH DR3 are precise to 1-2 Gyr using this method. With these ages, we replicate many recent results on the age-kinematic trends of the nearby disc, including the solar neighbourhood's age-velocity dispersion relationship and the larger global velocity dispersion relations of the disc found using Gaia and GALAH. These results show that chemical abundance variations at a given birth radius are small, and that strong chemical tagging of stars directly to birth clusters may prove difficult with our current elemental abundance precision. Our results highlight the need to measure abundances for as many nucleosynthetic production sites as possible in order to estimate reliable ages from chemistry. Our methods open a new door into studies of the kinematic structure and evolution of the disc, as ages may potentially be estimated to a precision of 1-2 Gyr for a large fraction of stars in existing spectroscopic surveys