julilili42/papers huggingface dataset:
The relationship between microbial population size and disease in the Arabidopsis thaliana phyllosphere
2019-11-02

Abstract A central goal in microbiome research is to learn what distinguishes a healthy from a dysbiotic microbial community. Shifts in diversity and taxonomic composition are important indicators of dysbiosis, but a full understanding also requires knowledge of absolute microbial population sizes. In addition to the number of microbial cells, information on taxonomic composition can provide important insight into microbiome function and disease state. Here we use shotgun metagenomics to simultaneously assess microbiome composition and microbial load in the phyllosphere of wild populations of the plant Arabidopsis thalian a. We find that wild plants vary substantially in the load of colonizing microbes, and that high loads are typically associated with the proliferation of single taxa, with only a few putatively pathogenic taxa achieving high abundances in the field. Our results suggest (i) that the inside of a plant leaf is on average sparsely colonized with an estimated two bacterial genomes per plant genome and an order of magnitude fewer eukaryotic microbial genomes, and (ii) that higher levels of microbial cells often indicate successful colonization by pathogens. Lastly, our results show that load is a significant explanatory variable for loss of estimated Shannon diversity in phyllosphere microbiomes, implying that reduced diversity may be a significant predictor of microbial dysbiosis in a plant leaf.
The adolescent motor performance development of elite female soccer players: A study of prognostic relevance for future success in adulthood using multilevel modelling
2019-11-02

Considering the scarce empirical evidence regarding talent predictors in female youth soccer, the present study aimed to investigate the long-term prognostic validity of elite female soccer players' adolescent motor performance for future success in adulthood. Additionally, the three-year development of highly talented girls' motor performance and the predictive value of this motor development for reaching a professional adult performance level (APL) was analysed. Overall, <i>N</i> = 737 female players participated in nationwide motor diagnostics (sprinting, agility, dribbling, ball control, shooting) within the German Soccer Association's talent identification and development programme at least twice between the age groups Under-12 (U12) and U15. Based on their APL at least four years later, participants were assigned to a professional (first German division, 6.2%) or non-professional group (lower divisions, 93.8%). Multilevel regression analyses revealed a general prognostic relevance for the investigated parameters with respect to players' APL. In addition, there was a non-linear improvement in participants' motor performance across all variables from U12 to U15. However, non-significant interactions between APL and these improvements indicate motor performance development itself cannot adequately predict players' future success in adulthood. Findings provide insightful information that can help coaches foster optimal support for young female soccer players' development.
Faculty Opinions recommendation of Inducing and exploiting vulnerabilities for the treatment of liver cancer.
2019-11-03

Liver cancer remains difficult to treat, owing to a paucity of drugs that target critical dependencies1,2; broad-spectrum kinase inhibitors such as sorafenib provide only a modest benefit to patients with hepatocellular carcinoma3. The induction of senescence may represent a strategy for the treatment of cancer, especially when combined with a second drug that selectively eliminates senescent cancer cells (senolysis)4,5. Here, using a kinome-focused genetic screen, we show that pharmacological inhibition of the DNA-replication kinase CDC7 induces senescence selectively in liver cancer cells with mutations in TP53. A follow-up chemical screen identified the antidepressant sertraline as an agent that kills hepatocellular carcinoma cells that have been rendered senescent by inhibition of CDC7. Sertraline suppressed mTOR signalling, and selective drugs that target this pathway were highly effective in causing the apoptotic cell death of hepatocellular carcinoma cells treated with a CDC7 inhibitor. The feedback reactivation of mTOR signalling after its inhibition6 is blocked in cells that have been treated with a CDC7 inhibitor, which leads to the sustained inhibition of mTOR and cell death. Using multiple in vivo mouse models of liver cancer, we show that treatment with combined inhibition of of CDC7 and mTOR results in a marked reduction of tumour growth. Our data indicate that exploiting an induced vulnerability could be an effective treatment for liver cancer. PMID: 31578521 Funding information This work was supported by: European Research Council, International Grant ID: 787925
Inception loops discover what excites neurons most using deep predictive models
2019-11-04

Finding sensory stimuli that drive neurons optimally is central to understanding information processing in the brain. However, optimizing sensory input is difficult due to the predominantly nonlinear nature of sensory processing and high dimensionality of the input. We developed 'inception loops', a closed-loop experimental paradigm combining in vivo recordings from thousands of neurons with in silico nonlinear response modeling. Our end-to-end trained, deep-learning-based model predicted thousands of neuronal responses to arbitrary, new natural input with high accuracy and was used to synthesize optimal stimuli-most exciting inputs (MEIs). For mouse primary visual cortex (V1), MEIs exhibited complex spatial features that occurred frequently in natural scenes but deviated strikingly from the common notion that Gabor-like stimuli are optimal for V1. When presented back to the same neurons in vivo, MEIs drove responses significantly better than control stimuli. Inception loops represent a widely applicable technique for dissecting the neural mechanisms of sensation.
Glucose and insulin levels are associated with arterial stiffness and concentric remodeling of the heart
2019-11-04

Abstract Background Mortality attributable to heart failure remains high. The prevalence of heart failure in patients with diabetes mellitus ranges from 19 to 26%. It is estimated that up to 21.1 million adults in the United States have diagnosed diabetes mellitus and around 80.8 million have impaired fasting glucose. We investigated the associations of fasting glucose (FG) and fasting insulin (FI), the homeostasis model assessment-insulin resistance index (HOMA-IR) and 2-h postload glucose (2HG) and insulin (2HI) with parameters of left ventricular geometry and function and arterial stiffness determined by magnetic resonance imaging in individuals without diagnosed type 2 diabetes. Methods Cross-sectional analyses of 1001 individuals (453 women, 45.3%), aged 21 to 80 years, from two independent population-based studies, the Study of Health in Pomerania (SHIP-TREND-0) and KORA FF4 Study. FG, FI, HOMA-IR, 2HG and 2HI, as well as glucose tolerance categories, were analyzed for associations with heart and arterial parameters using multivariable-adjusted linear regression models. Results In total, 390 individuals (39%) had prediabetes (isolated impaired fasting glucose, isolated glucose tolerance or both), and 49 (4.9%) were found to have unknown type 2 diabetes. In the multivariable-adjusted analysis, positive linear associations of FG, FI, HOMA-IR, 2HG and 2HI with arterial stiffness index and left ventricular wall-thickness and concentricity and inverse linear associations with left ventricular end-diastolic volume were observed. A 1 mmol/l higher FG was associated with a 1.18 ml/m 2.7 (1.80 to 0.57; p &lt; 0.001) lower left ventricular end-diastolic volume index, a 0.042 mm/m 2.7 (0.014 to 0.070) higher left ventricular wall-thickness index, a 0.12 mmHg m 2.7 /ml (0.06 to 0.17; p &lt; 0.001) greater arterial stiffness index and a 0.037 g/ml (0.018 to 0.056; p &lt; 0.001) higher left ventricular concentricity. Conclusions Our findings suggest that higher glucose levels in the prediabetic range and insulin resistance might lead to higher arterial stiffness and concentric remodeling of the heart.
Pulsed Facilitation of Corticospinal Excitability by the Sensorimotor μ-Alpha Rhythm
2019-11-04

Alpha oscillations (8–14 Hz) are assumed to gate information flow in the brain by means of pulsed inhibition; that is, the phasic suppression of cortical excitability and information processing once per alpha cycle, resulting in stronger net suppression for larger alpha amplitudes due to the assumed amplitude asymmetry of the oscillation. While there is evidence for this hypothesis regarding occipital alpha oscillations, it is less clear for the central sensorimotor μ-alpha rhythm. Probing corticospinal excitability via transcranial magnetic stimulation (TMS) of the primary motor cortex and the measurement of motor evoked potentials (MEPs), we have previously demonstrated that corticospinal excitability is modulated by both amplitude and phase of the sensorimotor μ-alpha rhythm. However, the direction of this modulation, its proposed asymmetry, and its underlying mechanisms remained unclear. We therefore used real-time EEG-triggered single- and paired-pulse TMS in healthy humans of both sexes to assess corticospinal excitability and GABA-A-receptor mediated short-latency intracortical inhibition (SICI) at rest during spontaneous high amplitude μ-alpha waves at different phase angles (peaks, troughs, rising and falling flanks) and compared them to periods of low amplitude (desynchronized) μ-alpha. MEP amplitude was facilitated during troughs and rising flanks, but no phasic suppression was observed at any time, nor any modulation of SICI. These results are best compatible with sensorimotor μ-alpha reflecting asymmetric pulsed facilitation but not pulsed inhibition of motor cortical excitability. The asymmetric excitability with respect to rising and falling flanks of the μ-alpha cycle further reveals that voltage differences alone cannot explain the impact of phase. SIGNIFICANCE STATEMENT The pulsed inhibition hypothesis, which assumes that alpha oscillations actively inhibit neuronal processing in a phasic manner, is highly influential and has substantially shaped our understanding of these oscillations. However, some of its basic assumptions, in particular its asymmetry and inhibitory nature, have rarely been tested directly. Here, we explicitly investigated the asymmetry of modulation and its direction for the human sensorimotor μ-alpha rhythm. We found clear evidence of pulsed facilitation, but not inhibition, in the human motor cortex, challenging the generalizability of the pulsed inhibition hypothesis and advising caution when interpreting sensorimotor μ-alpha changes in the sensorimotor system. This study also demonstrates how specific assumptions about the neurophysiological underpinnings of cortical oscillations can be experimentally tested noninvasively in humans.
Ketamine-induced changes in plasma brain-derived neurotrophic factor (BDNF) levels are associated with the resting-state functional connectivity of the prefrontal cortex
2019-11-04

Our findings indicate BDNF level dynamics following ketamine are related to acute and 24 h RSFC changes. Particularly when BDNF increases are observed after ketamine infusion, a disconnection from dmPFC after 24 h is seen and may reflect synaptic plasticity effects.
Microphase separation in a two-dimensional colloidal system with competing attractive critical Casimir and repulsive magnetic dipole interactions
2019-11-04

We propose and study theoretically a colloidal system in two dimensions with attractive critical Casimir and repulsive magnetic dipole forces, wherein the strength of attraction and repulsion can be easily and independently tuned by adjusting the temperature and an external magnetic field, respectively. We expect this setup to be experimentally accessible and are confident that it can serve to deepen our understanding of the mechanisms behind microphase separation due to competing interactions. We develop a density functional theory for our model and present first results of our calculations in the form of a phase diagram for fixed temperature, but varying magnetic fields and bulk densities. For certain values of these parameters, we are able to confirm the existence of thermodynamically stable inhomogeneous density profiles in the bulk, such as parallel lamellar stripes, as well as clusters and voids on a hexagonal lattice.
Microglia in neuropathology caused by protozoan parasites
2019-11-04

ABSTRACT Involvement of the central nervous system (CNS) is the most severe consequence of some parasitic infections. Protozoal infections comprise a group of diseases that together affect billions of people worldwide and, according to the World Health Organization, are responsible for more than 500000 deaths annually. They include African and American trypanosomiasis, leishmaniasis, malaria, toxoplasmosis, and amoebiasis. Mechanisms underlying invasion of the brain parenchyma by protozoa are not well understood and may depend on parasite nature: a vascular invasion route is most common. Immunosuppression favors parasite invasion into the CNS and therefore the host immune response plays a pivotal role in the development of a neuropathology in these infectious diseases. In the brain, microglia are the resident immune cells active in defense against pathogens that target the CNS. Beside their direct role in innate immunity, they also play a principal role in coordinating the trafficking and recruitment of other immune cells from the periphery to the CNS. Despite their evident involvement in the neuropathology of protozoan infections, little attention has given to microglia–parasite interactions. This review describes the most prominent features of microglial cells and protozoan parasites and summarizes the most recent information regarding the reaction of microglial cells to parasitic infections. We highlight the involvement of the periphery–brain axis and emphasize possible scenarios for microglia–parasite interactions.
Sediment history mirrors Pleistocene aridification in the Gobi Desert (Ejina Basin, NW China)
2019-11-04

Abstract. Central Asia is a large-scale source of dust transport, but also holds a prominent changing hydrological system during the Quaternary. A 223-m-long sediment core (GN200) was recovered from the Ejina Basin (synonymously Gaxun Nur Basin) in NW China to reconstructing the main transitional modes of water availability in the area during the Quaternary. The core has been drilled from the Heihe alluvial fan, one of the world's largest continental alluvial fan, which covers a part of the Gobi Desert. Grain-size distributions supported by endmember modelling analyses, geochemical-mineralogical compositions (based on XRF and XRD measurements), and bioindicator data (ostracods, gastropods, n-alkanes with leaf-wax δD) are used to infer the main transport processes and related environmental changes during the Pleistocene. Magnetostratigraphy supported by radionuclide dating provides the age model. Grain-size endmembers indicate that lake, playa (sheetflood), fluvial, and aeolian dynamics are the major factors influencing sedimentation in the Ejina Basin. Core GN200 reached the Pre-Quaternary quartz- and plagioclase-rich Red Clay Formation and reworked material derived from it in the core bottom. This part is overlain by silt-dominated sediments between 217 and 110 m core depth, which represent a period of lacustrine and playa-lacustrine sedimentation that presumably formed within an endorheic basin. The upper core half between 110 and 0 m is composed of mainly silty to sandy sediments derived from the Heihe River that have accumulated in a giant sediment fan until modern time. Apart from the transition from a siltier to a sandier environment with frequent switches between sediment types upcore, the clay mineral fraction is indicative for different environments. Mixed layer clay minerals (chlorite/smectite) are increased in the basal Red Clay Formation and reworked sediments, smectite is indicative for lacustrine-playa deposits, and an increased chlorite content is characteristic of the Heihe river deposits. The sediment succession in core GN200 based on the detrital proxy interpretation demonstrates that lake-playa sedimentation in the Ejina Basin has been disrupted likely due to tectonic events in the southern part of the catchment around 1 Ma BP. At this time Heihe river broke through from the Hexi Corridor through the Heli Shan ridge into the northern Ejina Basin. This initiated the alluvial fan progradation into the Ejina Basin. Presently the sediment bulge repels the diminishing lacustrine environment further north. In this sense, the uplift of the hinterland served as a tipping element that triggered landscape transformation in the Northern Tibetan foreland (i.e., the Hexi Corridor) and further on in the adjacent northern intracontinental Ejina Basin. The onset of alluvial fan formation coincides with increased sedimentation rates on the Chinese loess plateau, suggesting that the Heihe fluvial/alluvial fan may have served as a prominent upwind sediment source for it.
Effect of wind-driven accretion on planetary migration
2019-11-05

Context. Planetary migration is a key link between planet formation models and observed exoplanet statistics. So far, the theory of planetary migration has focused on the interaction of one or more planets with an inviscid or viscously evolving gaseous disk. Turbulent viscosity is thought to be the main driver of the secular evolution of the disk, and it is known to affect the migration process for intermediate- to high-mass planets. Recently, however, the topic of wind-driven accretion has experienced a renaissance because evidence is mounting that protoplanetary disks may be less turbulent than previously thought, and 3D non-ideal magnetohydrodynamic modeling of the wind-launching process is maturing. Aims. We investigate how wind-driven accretion may affect planetary migration. We aim for a qualitative exploration of the main effects and not for a quantitative prediction. Methods. We performed 2D hydrodynamic planet-disk interaction simulations with the FARGO3D code in the ( r , φ ) plane. The vertical coordinate in the disk and the launching of the wind are not treated explicitly. Instead, the torque caused by the wind onto the disk is treated using a simple two-parameter formula. The parameters are the wind mass-loss rate and the lever arm. Results. We find that the wind-driven accretion process replenishes the co-orbital region in a different way than the viscous accretion process. The former always injects mass from the outer edge of the co-orbital region, and always removes mass from the inner edge, while the latter injects or removes mass from the co-orbital region depending on the radial density gradients in the disk. As a consequence, the migration behavior can differ strongly, and can under certain conditions drive rapid type-III-like outward migration. We derive an analytic expression for the parameters under which this outward migration occurs. Conclusions. If wind-driven accretion plays a role in the secular evolution of protoplanetary disks, planetary migration studies have to include this process as well because it can strongly affect the resulting migration rate and migration direction.
A new alligatoroid from the Eocene of Vietnam highlights an extinct Asian clade independent from extantAlligator sinensis
2019-11-05

During systematic paleontological surveys in the Na Duong Basin in North Vietnam between 2009 and 2012, well-preserved fossilized cranial and postcranial remains belonging to at least 29 individuals of a middle to late Eocene (late Bartonian to Priabonian age (39–35 Ma)) alligatoroid were collected. Comparative anatomical study of the material warrants the diagnosis of a new taxon, Orientalosuchus naduongensis gen. et sp. nov. The combined presence of an enlarged fifth maxillary tooth, prominent preorbital ridges, a large supraoccipital exposure on the skull table, a palatine-pterygoid suture anterior to the posterior end of the suborbital fenestra, and a pterygoid forming a neck surrounding the choana is unique to this species. Unlike previous phylogenies, our parsimony analysis recovers a monophyletic Late Cretaceous to Paleogene East to Southeastern Asian alligatoroid group, here named Orientalosuchina. The group includes Orientalosuchus naduongensis , Krabisuchus siamogallicus , Eoalligator chunyii , Jiangxisuchus nankangensis and Protoalligator huiningensis , all of them sharing a medial shifted quadrate foramen aerum. The recognition of this clade indicates at least two separate dispersal events from North America to Asia: one during the Late Cretaceous by Orientalosuchina and one by the ancestor of Alligator sinensis during the Paleogene or Neogene, the timing of which is poorly constrained.
Insulin Action in the Hypothalamus Increases Second-Phase Insulin Secretion in Humans
2019-11-05

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Animal studies and initial correlative data in humans indicate that insulin action in the brain may affect pancreatic insulin secretion. An important brain region for this process is the hypothalamus, an area that can develop insulin resistance. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Fifteen young, healthy men (27 ± 3 years) with a wide BMI spectrum (20–30 kg/m&lt;sup&gt;2&lt;/sup&gt;) underwent 2 hyperglycemic clamps (target blood glucose: 10 mmol/L). In this double-blind study, subjects received 160 U of insulin or placebo as a nasal spray on 2 days in randomized order. On another day, insulin sensitivity of the hypothalamus was determined by functional magnetic resonance imaging. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Glucose levels were comparable on both study days. In the whole group, C-peptide levels were not significantly different between conditions. Though, there was a significant interaction between insulin sensitivity of the hypothalamus × nasal spray × time on C-peptide levels (&lt;i&gt;p&lt;/i&gt; = 10&lt;sup&gt;–6&lt;/sup&gt;). The group was therefore divided according to median hypothalamic insulin sensitivity. C-peptide concentrations were higher after intranasal insulin compared to placebo spray in the group with a strong hypothalamic insulin response (&lt;i&gt;p&lt;/i&gt; &amp;#x3c; 0.0001, β = 6.00 ± 1.24) and lower in the brain insulin-resistant group (&lt;i&gt;p&lt;/i&gt; = 0.005, β = –2.68 ± 0.95). Neither somatostatin nor glucagon kinetics was altered by the nasal spray. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; In participants with high hypothalamic insulin sensitivity, insulin action in the brain enhanced second-phase insulin secretion from pancreatic beta cells. This reaction could, for example, contribute to late postprandial glucose regulation by suppressing hepatic glucose production by portal venous insulin.
Team Sports Off the Field: Competing Excludes Cooperating for Individual but Not for Team Athletes
2019-11-05

Both team and individual sports require competition, whereas cooperation is more prevalent in team than in individual sports. In particular, team athletes have to compete (for starting roles) while cooperating (for team success) with the same teammates. For team athletes, competition and cooperative behavior, two mutually exclusive constructs according to earlier psychological research, might therefore be less incompatible than for individual athletes. In Study 1, team athletes attributed a higher demand to compete and cooperate with the same teammates or training partners to their sport than individual athletes to their sport. Study 2 showed that experiencing competition (vs. control) undermines information sharing less for team than for individual athletes. In addition, Study 2 demonstrated that priming competition undermines the accessibility of cooperative thoughts less for team than for individual athletes. Therefore, team athletes might be better at competing without ceasing to cooperate. Implications for collaboration in groups are discussed.