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A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.
The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using gamma-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant gamma-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section <sigma nu >. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach <sigma nu > values of 6 x 10(-26) cm(3) s(-1) in the W+W- channel for a DM particle mass of 1.5 TeV, and 2 x 10(-26) cm(3) s(-1) in the tau(+)tau(-) channel for a 1 TeV mass. For the first time, ground-based gamma-ray observations have reached sufficient sensitivity to probe <sigma nu > values expected from the thermal relic density for TeV DM particles.
The selaginella genome identifies genetic changes associated with the evolution of vascular plants
(2011)
Vascular plants appeared similar to 410 million years ago, then diverged into several lineages of which only two survive: the euphyllophytes (ferns and seed plants) and the lycophytes. We report here the genome sequence of the lycophyte Selaginella moellendorffii (Selaginella), the first nonseed vascular plant genome reported. By comparing gene content in evolutionarily diverse taxa, we found that the transition from a gametophyte- to a sporophyte-dominated life cycle required far fewer new genes than the transition from a nonseed vascular to a flowering plant, whereas secondary metabolic genes expanded extensively and in parallel in the lycophyte and angiosperm lineages. Selaginella differs in posttranscriptional gene regulation, including small RNA regulation of repetitive elements, an absence of the trans-acting small interfering RNA pathway, and extensive RNA editing of organellar genes.
Myriapods (e. g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.
The results of follow-up observations of the TeV gamma-ray source HESS J1640-465 from 2004 to 2011 with the High Energy Stereoscopic System (HESS) are reported in this work. The spectrum is well described by an exponential cut-off power law with photon index Gamma = 2.11 +/- 0.09(stat) +/- 0.10(sys), and a cut-off energy of E-2 = 6.0(-1.2)(+2.0) TeV. The TeV emission is significantly extended and overlaps with the northwestern part of the shell of the SNR G338.3-0.0. The new HESS results, a re-analysis of archival XMM-Newton data and multiwavelength observations suggest that a significant part of the gamma-ray emission from HESS J1640-465 originates in the supernova remnant shell. In a hadronic scenario, as suggested by the smooth connection of the GeV and TeV spectra, the product of total proton energy and mean target density could be as high as W(p)n(H) similar to 4 x 10(52)(d/10kpc)(2) erg cm(-3).
The 2010 very high energy gamma-ray flare and 10 years ofmulti-wavelength oservations of M 87
(2012)
The giant radio galaxy M 87 with its proximity (16 Mpc), famous jet, and very massive black hole ((3-6) x 10(9) M-circle dot) provides a unique opportunity to investigate the origin of very high energy (VHE; E > 100 GeV) gamma-ray emission generated in relativistic outflows and the surroundings of supermassive black holes. M 87 has been established as a VHE gamma-ray emitter since 2006. The VHE gamma-ray emission displays strong variability on timescales as short as a day. In this paper, results from a joint VHE monitoring campaign on M 87 by the MAGIC and VERITAS instruments in 2010 are reported. During the campaign, a flare at VHE was detected triggering further observations at VHE (H.E.S.S.), X-rays (Chandra), and radio (43 GHz Very Long Baseline Array, VLBA). The excellent sampling of the VHE gamma-ray light curve enables one to derive a precise temporal characterization of the flare: the single, isolated flare is well described by a two-sided exponential function with significantly different flux rise and decay times of tau(rise)(d) = (1.69 +/- 0.30) days and tau(decay)(d) = (0.611 +/- 0.080) days, respectively. While the overall variability pattern of the 2010 flare appears somewhat different from that of previous VHE flares in 2005 and 2008, they share very similar timescales (similar to day), peak fluxes (Phi(>0.35 TeV) similar or equal to (1-3) x 10(-11) photons cm(-2) s(-1)), and VHE spectra. VLBA radio observations of 43 GHz of the inner jet regions indicate no enhanced flux in 2010 in contrast to observations in 2008, where an increase of the radio flux of the innermost core regions coincided with a VHE flare. On the other hand, Chandra X-ray observations taken similar to 3 days after the peak of the VHE gamma-ray emission reveal an enhanced flux from the core (flux increased by factor similar to 2; variability timescale <2 days). The long-term (2001-2010) multi-wavelength (MWL) light curve of M 87, spanning from radio to VHE and including data from Hubble Space Telescope, Liverpool Telescope, Very Large Array, and European VLBI Network, is used to further investigate the origin of the VHE gamma-ray emission. No unique, common MWL signature of the three VHE flares has been identified. In the outer kiloparsec jet region, in particular in HST-1, no enhanced MWL activity was detected in 2008 and 2010, disfavoring it as the origin of the VHE flares during these years. Shortly after two of the three flares (2008 and 2010), the X-ray core was observed to be at a higher flux level than its characteristic range (determined from more than 60 monitoring observations: 2002-2009). In 2005, the strong flux dominance of HST-1 could have suppressed the detection of such a feature. Published models for VHE gamma-ray emission from M 87 are reviewed in the light of the new data.
This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.
Prospects for Cherenkov Telescope Array Observations of the Young Supernova Remnant RX J1713.7-3946
(2017)
We perform simulations for future Cherenkov Telescope Array (CTA) observations of RX J1713.7-3946, a young supernova remnant (SNR) and one of the brightest sources ever discovered in very high energy (VHE) gamma rays. Special attention is paid to exploring possible spatial (anti) correlations of gamma rays with emission at other wavelengths, in particular X-rays and CO/H I emission. We present a series of simulated images of RX J1713.7-3946 for CTA based on a set of observationally motivated models for the gamma-ray emission. In these models, VHE gamma rays produced by high-energy electrons are assumed to trace the nonthermal X-ray emission observed by XMM-Newton, whereas those originating from relativistic protons delineate the local gas distributions. The local atomic and molecular gas distributions are deduced by the NANTEN team from CO and H I observations. Our primary goal is to show how one can distinguish the emission mechanism(s) of the gamma rays (i.e., hadronic versus leptonic, or a mixture of the two) through information provided by their spatial distribution, spectra, and time variation. This work is the first attempt to quantitatively evaluate the capabilities of CTA to achieve various proposed scientific goals by observing this important cosmic particle accelerator.
Aims. Previous observations with the High Energy Stereoscopic System (H.E.S.S.) have revealed an extended very-high-energy (VHE; E > 100 GeV) gamma-ray source, HESS J1834-087, coincident with the supernova remnant (SNR) W41. The origin of the gamma-ray emission was investigated in more detail with the H.E.S.S. array and the Large Area Telescope (LAT) onboard the Fermi Gamma-ray Space Telescope.
Methods. The gamma-ray data provided by 61 h of observations with H.E.S.S., and four years with the Fermi LAT were analyzed, covering over five decades in energy from 1.8 GeV up to 30 TeV. The morphology and spectrum of the TeV and GeV sources were studied and multiwavelength data were used to investigate the origin of the gamma-ray emission toward W41.
Results. The TeV source can be modeled with a sum of two components: one point-like and one significantly extended (sigma(TeV) = 0.17 degrees +/- 0.01 degrees), both centered on SNR W41 and exhibiting spectra described by a power law with index Gamma(TeV) similar or equal to 2.6. The GeV source detected with Fermi LAT is extended (sigma(GeV) = 0.15 degrees +/- 0.03 degrees) and morphologically matches the VHE emission. Its spectrum can be described by a power-law model with an index Gamma(GeV) = 2.15 +/- 0.12 and smoothly joins the spectrum of the whole TeV source. A break appears in the gamma-ray spectra around 100 GeV. No pulsations were found in the GeV range.
Conclusions. Two main scenarios are proposed to explain the observed emission: a pulsar wind nebula (PWN) or the interaction of SNR W41 with an associated molecular cloud. X-ray observations suggest the presence of a point-like source (a pulsar candidate) near the center of the remnant and nonthermal X-ray diffuse emission that could arise from the possibly associated PWN. The PWN scenario is supported by the compatible positions of the TeV and GeV sources with the putative pulsar. However, the spectral energy distribution from radio to gamma-rays is reproduced by a one-zone leptonic model only if an excess of low-energy electrons is injected following a Maxwellian distribution by a pulsar with a high spin-down power (> 10(37) erg s(-1)). This additional low-energy component is not needed if we consider that the point-like TeV source is unrelated to the extended GeV and TeV sources. The interacting SNR scenario is supported by the spatial coincidence between the gamma-ray sources, the detection of OH (1720 MHz) maser lines, and the hadronic modeling.
The gamma-ray spectrum of the low-frequency-peaked BL Lac (LBL) object AP Librae is studied, following the discovery of very-high-energy (VHE; E > 100 GeV) gamma-ray emission up to the TeV range by the H.E.S.S. experiment. Thismakes AP Librae one of the few VHE emitters of the LBL type. The measured spectrum yields a flux of (8.8 +/- 1.5(stat) +/- 1.8(sys)) x 10(-12) cm(-2) s(-1) above 130 GeV and a spectral index of Gamma = 2.65 +/- 0.19(stat) +/- 0.20(sys). This study also makes use of Fermi-LAT observations in the high energy (HE, E > 100 MeV) range, providing the longest continuous light curve (5 years) ever published on this source. The source underwent a flaring event between MJD 56 306-56 376 in the HE range, with a flux increase of a factor of 3.5 in the 14 day bin light curve and no significant variation in spectral shape with respect to the low-flux state. While the H.E.S.S. and (low state) Fermi-LAT fluxes are in good agreement where they overlap, a spectral curvature between the steep VHE spectrum and the Fermi-LAT spectrum is observed. The maximum of the gamma-ray emission in the spectral energy distribution is located below the GeV energy range.
HESS J1640-465 - an exceptionally luminous TeV gamma-ray supernova remnant (vol 439, pg 2828, 2014)
(2014)
Geomagnetic indices are convenient quantities that distill the complicated physics of some region or aspect of near-Earth space into a single parameter. Most of the best-known indices are calculated from ground-based magnetometer data sets, such as Dst, SYM-H, Kp, AE, AL, and PC. Many models have been created that predict the values of these indices, often using solar wind measurements upstream from Earth as the input variables to the calculation. This document reviews the current state of models that predict geomagnetic indices and the methods used to assess their ability to reproduce the target index time series. These existing methods are synthesized into a baseline collection of metrics for benchmarking a new or updated geomagnetic index prediction model. These methods fall into two categories: (1) fit performance metrics such as root-mean-square error and mean absolute error that are applied to a time series comparison of model output and observations and (2) event detection performance metrics such as Heidke Skill Score and probability of detection that are derived from a contingency table that compares model and observation values exceeding (or not) a threshold value. A few examples of codes being used with this set of metrics are presented, and other aspects of metrics assessment best practices, limitations, and uncertainties are discussed, including several caveats to consider when using geomagnetic indices. Plain Language Summary One aspect of space weather is a magnetic signature across the surface of the Earth. The creation of this signal involves nonlinear interactions of electromagnetic forces on charged particles and can therefore be difficult to predict. The perturbations that space storms and other activity causes in some observation sets, however, are fairly regular in their pattern. Some of these measurements have been compiled together into a single value, a geomagnetic index. Several such indices exist, providing a global estimate of the activity in different parts of geospace. Models have been developed to predict the time series of these indices, and various statistical methods are used to assess their performance at reproducing the original index. Existing studies of geomagnetic indices, however, use different approaches to quantify the performance of the model. This document defines a standardized set of statistical analyses as a baseline set of comparison tools that are recommended to assess geomagnetic index prediction models. It also discusses best practices, limitations, uncertainties, and caveats to consider when conducting a model assessment.
Microlensing is the only known direct method to measure the masses of stars that lack visible companions. In terms of microlensing observables, the mass is given by M (c(2)/4G)(r) over tilde (E)theta(E) and so requires the measurement of both the angular Einstein radius theta(E) and the projected Einstein radius (r) over tilde (E). Simultaneous measurement of these two parameters is extremely rare. Here we analyze OGLE-2003-BLG-238, a spectacularly bright (I-min 10.3), high-magnification (A(max) 170) microlensing event. Pronounced finite-source effects permit a measurement of theta(E) = 650 muas. Although the timescale of the event is only t(E) 38 days, one can still obtain weak constraints on the microlens parallax: 4.4 AU < <(r)over tilde>(E) < 18 AU at the 1 σ level. Together these two parameter measurements yield a range for the lens mass of 0.36 M-&ODOT; < M < 1.48 M-&ODOT;. As was the case for MACHO- LMC-5, the only other single star (apart from the Sun) whose mass has been determined from its gravitational effects, this estimate is rather crude. It does, however, demonstrate the viability of the technique. We also discuss future prospects for single-lens mass measurements
We analyze the photometric data obtained by PLANET and OGLE on the caustic-crossing binary-lens microlensing event OGLE-2002-BLG-069. Thanks to the excellent photometric and spectroscopic coverage of the event, we are able to constrain the lens model up to the known ambiguity between close and wide binary lenses. The detection of annual parallax in combination with measurements of extended-source effects allows us to determine the mass, distance and velocity of the lens components for the competing models. While the model involving a close binary lens leads to a Bulge- Disc lens scenario with a lens mass of M = (0.51 ± 0.15) M-&ODOT; and distance of D-L = (2.9 ± 0.4) kpc, the wide binary lens solution requires a rather implausible binary black-hole lens ( M &GSIM; 126 M-&ODOT;). Furthermore we compare current state-of-the-art numerical and empirical models for the surface brightness profile of the source, a G5III Bulge giant. We find that a linear limb-darkening model for the atmosphere of the source star is consistent with the data whereas a PHOENIX atmosphere model assuming LTE and with no free parameter does not match our observations
We discuss high-resolution, time-resolved spectra of the caustic exit of the binary microlensing event OGLE 2002-BLG-069 obtained with UVES on the VLT. The source star is a G5III giant in the Galactic Bulge. During such events, the source star is highly magnified, and a strong differential magnification around the caustic resolves its surface. Using an appropriate model stellar atmosphere generated by the PHOENIX v2.6 code we obtain a model light curve for the caustic exit and compare it with a dense set of photometric observations obtained by the PLANET microlensing follow up network. We further compare predicted variations in the Halpha equivalent width with those measured from our spectra. While the model and observations agree in the gross features, there are discrepancies suggesting shortcomings in the model, particularly for the Halpha line core, where we have detected amplified emission from the stellar chromosphere after the source star's trailing limb exited the caustic. This achievement became possible by the provision of the very efficient OGLE-III Early Warning System, a network of small telescopes capable of nearly-continuous round-the-clock photometric monitoring, on-line data reduction, daily near-real-time modelling in order to predict caustic crossing parameters, and a fast and efficient response of a 8 m class telescope to a "Target-of-Opportunity" observation request
Due to their extremely small luminosity compared to the stars they orbit, planets outside our own Solar System are extraordinarily difficult to detect directly in optical light. Careful photometric monitoring of distant stars, however, can reveal the presence of exoplanets via the microlensing or eclipsing effects they induce. The international PLANET collaboration is performing such monitoring using a cadre of semi-dedicated telescopes around the world. Their results constrain the number of gas giants orbiting 1-7 AU from the most typical stars in the Galaxy. Upgrades in the program are opening regions of ''exoplanet discovery space'' - toward smaller masses and larger orbital radii - that are inaccessible to the Doppler velocity technique.
Intensive land use is a major cause of biodiversity loss, but most studies comparing the response of multiple taxa rely on simple diversity measures while analyses of other community attributes are only recently gaining attention. Species-abundance distributions (SADs) are a community attribute that can be used to study changes in the overall abundance structure of species groups, and whether these changes are driven by abundant or rare species. We evaluated the effect of grassland management intensity for three land-use modes (fertilization, mowing, grazing) and their combination on species richness and SADs for three belowground (arbuscular mycorrhizal fungi, prokaryotes and insect larvae) and seven aboveground groups (vascular plants, bryophytes and lichens; arthropod herbivores; arthropod pollinators; bats and birds). Three descriptors of SADs were evaluated: general shape (abundance decay rate), proportion of rare species (rarity) and proportional abundance of the commonest species (dominance). Across groups, taxonomic richness was largely unaffected by land-use intensity and only decreased with increasing mowing intensity. Of the three SAD descriptors, abundance decay rate became steeper with increasing combined land-use intensity across groups. This reflected a decrease in rarity among plants, herbivores and vertebrates. Effects of fertilization on the three descriptors were similar to the combined land-use intensity effects. Mowing intensity only affected the SAD descriptors of insect larvae and vertebrates, while grazing intensity produced a range of effects on different descriptors in distinct groups. Overall, belowground groups had more even abundance distribtitions than aboveground groups. Strong differences among aboveground groups and between above- and belowground groups indicate that no single taxonomic group can serve as an indicator for effects in other groups. In the past, the use of SADs has been hampered by concerns over theoretical models underlying specific forms of SADs. Our study shows that SAD descriptors that are not connected to a particular model are suitable to assess the effect of land use on community structure.
GrassPlot is a collaborative vegetation-plot database organised by the Eurasian Dry Grassland Group (EDGG) and listed in the Global Index of Vegetation-Plot Databases (GIVD ID EU-00-003). GrassPlot collects plot records (releves) from grasslands and other open habitats of the Palaearctic biogeographic realm. It focuses on precisely delimited plots of eight standard grain sizes (0.0001; 0.001;... 1,000 m(2)) and on nested-plot series with at least four different grain sizes. The usage of GrassPlot is regulated through Bylaws that intend to balance the interests of data contributors and data users. The current version (v. 1.00) contains data for approximately 170,000 plots of different sizes and 2,800 nested-plot series. The key components are richness data and metadata. However, most included datasets also encompass compositional data. About 14,000 plots have near-complete records of terricolous bryophytes and lichens in addition to vascular plants. At present, GrassPlot contains data from 36 countries throughout the Palaearctic, spread across elevational gradients and major grassland types. GrassPlot with its multi-scale and multi-taxon focus complements the larger international vegetationplot databases, such as the European Vegetation Archive (EVA) and the global database " sPlot". Its main aim is to facilitate studies on the scale-and taxon-dependency of biodiversity patterns and drivers along macroecological gradients. GrassPlot is a dynamic database and will expand through new data collection coordinated by the elected Governing Board. We invite researchers with suitable data to join GrassPlot. Researchers with project ideas addressable with GrassPlot data are welcome to submit proposals to the Governing Board.
On 2019 April 25.346 and 26.640 UT the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo gravitational-wave (GW) observatory announced the detection of the first candidate events in Observing Run 3 that contained at least one neutron star (NS). S190425z is a likely binary neutron star (BNS) merger at d(L) = 156 +/- 41 Mpc, while S190426c is possibly the first NS-black hole (BH) merger ever detected, at d(L) = 377 +/- 100 Mpc, although with marginal statistical significance. Here we report our optical follow-up observations for both events using the MMT 6.5 m telescope, as well as our spectroscopic follow-up of candidate counterparts (which turned out to be unrelated) with the 4.1 m SOAR telescope. We compare to publicly reported searches, explore the overall areal coverage and depth, and evaluate those in relation to the optical/near-infrared (NIR) kilonova emission from the BNS merger GW170817, to theoretical kilonova models, and to short gamma-ray burst (SGRB) afterglows. We find that for a GW170817-like kilonova, the partial volume covered spans up to about 40% for S190425z and 60% for S190426c. For an on-axis jet typical of SGRBs, the search effective volume is larger, but such a configuration is expected in at most a few percent of mergers. We further find that wide-field gamma-ray and X-ray limits rule out luminous on-axis SGRBs, for a large fraction of the localization regions, although these searches are not sufficiently deep in the context of the gamma-ray emission from GW170817 or off-axis SGRB afterglows. The results indicate that some optical follow-up searches are sufficiently deep for counterpart identification to about 300 Mpc, but that localizations better than 1000 deg(2) are likely essential.
Food system innovations will be instrumental to achieving multiple Sustainable Development Goals (SDGs). However, major innovation breakthroughs can trigger profound and disruptive changes, leading to simultaneous and interlinked reconfigurations of multiple parts of the global food system. The emergence of new technologies or social solutions, therefore, have very different impact profiles, with favourable consequences for some SDGs and unintended adverse side-effects for others. Stand-alone innovations seldom achieve positive outcomes over multiple sustainability dimensions. Instead, they should be embedded as part of systemic changes that facilitate the implementation of the SDGs. Emerging trade-offs need to be intentionally addressed to achieve true sustainability, particularly those involving social aspects like inequality in its many forms, social justice, and strong institutions, which remain challenging. Trade-offs with undesirable consequences are manageable through the development of well planned transition pathways, careful monitoring of key indicators, and through the implementation of transparent science targets at the local level.
No association of goal-directed and habitual control with alcohol consumption in young adults
(2017)
Alcohol dependence is a mental disorder that has been associated with an imbalance in behavioral control favoring model-free habitual over model-based goal-directed strategies. It is as yet unknown, however, whether such an imbalance reflects a predisposing vulnerability or results as a consequence of repeated and/or excessive alcohol exposure. We, therefore, examined the association of alcohol consumption with model-based goal-directed and model-free habitual control in 188 18-year-old social drinkers in a two-step sequential decision-making task while undergoing functional magnetic resonance imaging before prolonged alcohol misuse could have led to severe neurobiological adaptations. Behaviorally, participants showed a mixture of model-free and model-based decision-making as observed previously. Measures of impulsivity were positively related to alcohol consumption. In contrast, neither model-free nor model-based decision weights nor the trade-off between them were associated with alcohol consumption. There were also no significant associations between alcohol consumption and neural correlates of model-free or model-based decision quantities in either ventral striatum or ventromedial prefrontal cortex. Exploratory whole-brain functional magnetic resonance imaging analyses with a lenient threshold revealed early onset of drinking to be associated with an enhanced representation of model-free reward prediction errors in the posterior putamen. These results suggest that an imbalance between model-based goal-directed and model-free habitual control might rather not be a trait marker of alcohol intake per se.
In detoxified alcohol-dependent patients, alcohol-related stimuli can promote relapse. However, to date, the mechanisms by which contextual stimuli promote relapse have not been elucidated in detail. One hypothesis is that such contextual stimuli directly stimulate the motivation to drink via associated brain regions like the ventral striatum and thus promote alcohol seeking, intake and relapse. Pavlovian-to-Instrumental-Transfer (PIT) may be one of those behavioral phenomena contributing to relapse, capturing how Pavlovian conditioned (contextual) cues determine instrumental behavior (e.g. alcohol seeking and intake). We used a PIT paradigm during functional magnetic resonance imaging to examine the effects of classically conditioned Pavlovian stimuli on instrumental choices in n=31 detoxified patients diagnosed with alcohol dependence and n=24 healthy controls matched for age and gender. Patients were followed up over a period of 3 months. We observed that (1) there was a significant behavioral PIT effect for all participants, which was significantly more pronounced in alcohol-dependent patients; (2) PIT was significantly associated with blood oxygen level-dependent (BOLD) signals in the nucleus accumbens (NAcc) in subsequent relapsers only; and (3) PIT-related NAcc activation was associated with, and predictive of, critical outcomes (amount of alcohol intake and relapse during a 3 months follow-up period) in alcohol-dependent patients. These observations show for the first time that PIT-related BOLD signals, as a measure of the influence of Pavlovian cues on instrumental behavior, predict alcohol intake and relapse in alcohol dependence.
Anomalous diffusion or, more generally, anomalous transport, with nonlinear dependence of the mean-squared displacement on the measurement time, is ubiquitous in nature. It has been observed in processes ranging from microscopic movement of molecules to macroscopic, large-scale paths of migrating birds. Using data from multiple empirical systems, spanning 12 orders of magnitude in length and 8 orders of magnitude in time, we employ a method to detect the individual underlying origins of anomalous diffusion and transport in the data. This method decomposes anomalous transport into three primary effects: long-range correlations (“Joseph effect”), fat-tailed probability density of increments (“Noah effect”), and nonstationarity (“Moses effect”). We show that such a decomposition of real-life data allows us to infer nontrivial behavioral predictions and to resolve open questions in the fields of single-particle tracking in living cells and movement ecology.
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
Ancient mitochondrial DNA and the genetic history of Eurasian beaver (Castor fiber) in Europe
(2014)
After centuries of human hunting, the Eurasian beaver Castor fiber had disappeared from most of its original range by the end of the 19th century. The surviving relict populations are characterized by both low genetic diversity and strong phylogeographical structure. However, it remains unclear whether these attributes are the result of a human-induced, late Holocene bottleneck or already existed prior to this reduction in range. To investigate genetic diversity in Eurasian beaver populations during the Holocene, we obtained mitochondrial control region DNA sequences from 48 ancient beaver samples and added 152 modern sequences from GenBank. Phylogeographical analyses of the data indicate a differentiation of European beaver populations into three mitochondrial clades. The two main clades occur in western and eastern Europe, respectively, with an early Holocene contact zone in eastern Europe near a present-day contact zone. A divergent and previously unknown clade of beavers from the Danube Basin survived until at least 6000years ago, but went extinct during the transition to modern times. Finally, we identify a recent decline in effective population size of Eurasian beavers, with a stronger bottleneck signal in the western than in the eastern clade. Our results suggest that the low genetic diversity and the strong phylogeographical structure in recent beavers are artefacts of human hunting-associated population reductions. While beaver populations have been growing rapidly since the late 19th century, genetic diversity within modern beaver populations remains considerably reduced compared to what was present prior to the period of human hunting and habitat reduction.
Targeted capture coupled with high-throughput sequencing can be used to gain information about nuclear sequence variation at hundreds to thousands of loci. Divergent reference capture makes use of molecular data of one species to enrich target loci in other (related) species. This is particularly valuable for nonmodel organisms, for which often no a priori knowledge exists regarding these loci. Here, we have used targeted capture to obtain data for 809 nuclear coding DNA sequences (CDS) in a nonmodel organism, the Eurasian lynx Lynx lynx, using baits designed with the help of the published genome of a related model organism (the domestic cat Felis catus). Using this approach, we were able to survey intraspecific variation at hundreds of nuclear loci in L. lynx across the species’ European range. A large set of biallelic candidate SNPs was then evaluated using a high-throughput SNP genotyping platform (Fluidigm), which we then reduced to a final 96 SNP-panel based on assay performance and reliability; validation was carried out with 100 additional Eurasian lynx samples not included in the SNP discovery phase. The 96 SNP-panel developed from CDS performed very successfully in the identification of individuals and in population genetic structure inference (including the assignment of individuals to their source population). In keeping with recent studies, our results show that genic SNPs can be valuable for genetic monitoring of wildlife species.
Land-use intensification is a key driver of biodiversity change. However, little is known about how it alters relationships between the diversities of different taxonomic groups, which are often correlated due to shared environmental drivers and trophic interactions. Using data from 150 grassland sites, we examined how land-use intensification (increased fertilization, higher livestock densities, and increased mowing frequency) altered correlations between the species richness of 15 plant, invertebrate, and vertebrate taxa. We found that 54% of pairwise correlations between taxonomic groups were significant and positive among all grasslands, while only one was negative. Higher land-use intensity substantially weakened these correlations(35% decrease in rand 43% fewer significant pairwise correlations at high intensity), a pattern which may emerge as a result of biodiversity declines and the breakdown of specialized relationships in these conditions. Nevertheless, some groups (Coleoptera, Heteroptera, Hymenoptera and Orthoptera) were consistently correlated with multidiversity, an aggregate measure of total biodiversity comprised of the standardized diversities of multiple taxa, at both high and lowland-use intensity. The form of intensification was also important; increased fertilization and mowing frequency typically weakened plant-plant and plant-primary consumer correlations, whereas grazing intensification did not. This may reflect decreased habitat heterogeneity under mowing and fertilization and increased habitat heterogeneity under grazing. While these results urge caution in using certain taxonomic groups to monitor impacts of agricultural management on biodiversity, they also suggest that the diversities of some groups are reasonably robust indicators of total biodiversity across a range of conditions.
Anomalous diffusion or, more generally, anomalous transport, with nonlinear dependence of the mean-squared displacement on the measurement time, is ubiquitous in nature. It has been observed in processes ranging from microscopic movement of molecules to macroscopic, large-scale paths of migrating birds. Using data from multiple empirical systems, spanning 12 orders of magnitude in length and 8 orders of magnitude in time, we employ a method to detect the individual underlying origins of anomalous diffusion and transport in the data. This method decomposes anomalous transport into three primary effects: long-range correlations (“Joseph effect”), fat-tailed probability density of increments (“Noah effect”), and nonstationarity (“Moses effect”). We show that such a decomposition of real-life data allows us to infer nontrivial behavioral predictions and to resolve open questions in the fields of single-particle tracking in living cells and movement ecology.