bluuebunny/crossref_metadata_2025 huggingface dataset:
Assay of disaturated phosphatidylcholine in amniotic fluid as a test of fetal lung maturity: experience with 2000 analyses.
Authors: Tsai M Y , Shultz E K , Williams P P , Bendel R , Butler J , Farb H , Wager G , Knox E G , Julian T , Thompson T R
Published: February 2020

We determined concentrations of disaturated phosphatidylcholine (DSPC) in nearly 2000 amniotic fluid samples obtained either transabdominally or as vaginal pools. Here we report our comparison of these DSPC values with the lecithin/sphingomyelin (L/S) ratios for amniotic fluid samples obtained from diabetic and nondiabetic pregnancies and also between transabdominally or vaginally collected samples uncontaminated by blood or meconium. DSPC measurement is at least as good as the L/S ratio in predicting the absence of respiratory distress syndrome. DSPC concentrations were, however, lower in diabetic than in nondiabetic pregnancies, supporting the hypothesis that DSPC synthesis may be impaired in fetuses of diabetic mothers. Visually uncontaminated samples collected transabdominally or vaginally, when grouped according to length of gestation, have similar DSPC values but different L/S ratios. Thus, even in the absence of blood or meconium, DSPC may be a more useful test than the L/S ratio for vaginally pooled samples.
Comparison of long-term mortality between living alone patients vs. living together patients with acute coronary syndrome treated with percutaneous coronary intervention
Authors: Takeuchi Mitsuhiro , Ogita Manabu , Wada Hideki , Takahashi Daigo , Nozaki Yui , Nishio Ryota , Yasuda Kentaro , Takahashi Norihito , Sonoda Taketo , Yatsu Shoichiro , Shitara Jun , Tsuboi Shuta , Dohi Tomotaka , Suwa Satoru , Miyauchi Katsumi , Daida Hiroyuki
Published: February 2020

Aims

Living alone is reported as an independent risk factor for cardiovascular disease. However, little is known about the association between clinical outcomes and living alone in patients with acute coronary syndrome (ACS). The aim of this study was to determine whether living alone is an independent prognostic risk factor for long-term mortality stratified by age in patients with ACS who were treated with primary percutaneous coronary intervention (PCI).

Methods and results

We conducted an observational cohort study of ACS patients who underwent PCI between January 1999 and May 2015 at Juntendo University Shizuoka Hospital, Japan. The primary endpoint was all-cause death. Among 2547 ACS patients, 381 (15.0%) patients were living alone at the onset of ACS. The cumulative incidence of all-cause death was comparable between living alone and living together (34.8% vs. 34.4%, log-rank P = 0.63). However, among younger population (aged <65 years), the incidence of all-cause death was significantly higher in the living alone group (log-rank P = 0.01). Multivariate Cox hazard analysis revealed a significant association between living alone and all-cause death, even after adjusting for other risk factors (hazard ratio 2.30, 95% confidence interval 1.38–3.84, P = 0.001).

Conclusion

Although living alone was not significantly associated with long-term clinical outcomes in patients with ACS, it was a predictive risk factor among younger ACS patients. Careful attention should be paid to patients’ lifestyle, especially younger patients with ACS.
Electrical conductivity in the mantle transition zone beneath Eastern China derived from L1-Norm C-responses
Authors: Zhang Yanhui , Weng Aihua , Li Shiwen , Yang Yue , Tang Yu , Liu Yunhe
Published: February 2020

Constraining the distribution of water in different regions of the mantle remains one of the significant challenges to comprehend the global deep water cycle. Geomagnetic depth soundings can provide such constraint through the electrical conductivity structure. Hence, this study aims to propose a regularization technique that can estimate previously unavailable C-response. In the method, the objective function comprised an L1-norm measured data prediction error and a spectral smoothness constraint term. We used the data error of C-response to weight the predicted error. The L-BFGS method was introduced to determine the minimum point of the objective function, and the regularization parameter decreased adaptively during inversion. Thus, the geomagnetic data processed yielded high-quality C-responses in 31 stations in Eastern China. In addition, we obtained 1-D electrical conductivity profiles in the mantle transition zone (MTZ) beneath Eastern China from C-responses using the L-BFGS method. Compared with the global 1-D model, the conductivity–depth profiles revealed that the MTZ beneath Eastern China is more conductive in the east but more resistive in the west. The conversion of these conductivities to water content based on the mineral physics suggested that the MTZ beneath Eastern China is characterized by a high water concentration, approximately 0.2 and 1 wt per cent in the upper and lower MTZ, respectively. Owing to the inclusion of more stations, the water-rich region could be constrained roughly to the east of the North–South Gravity Lineament (NSGL). Further considering seismic images in the same area, this water content distribution pattern suggested that the front of the stagnant Pacific Plate in the lower MTZ might have reached the NSGL. However, the dehydration reactions in the stagnant slab were more active in the eastern part. Perhaps, some of these fluids migrated into the upper MTZ and could be the source of the trapped water found in the xenoliths from the deep upper mantle beneath Eastern China.
Flow plane orientation in the upper mantle under the Western/Central United States from SKS shear-wave splitting observations
Authors: Löberich Eric , Bokelmann Götz
Published: February 2020

The causes of seismic anisotropy are still under debate. In particular, it is important to understand the extent to which seismic anisotropy is due to more recent geodynamic activities in the asthenosphere, or to frozen-in deformation in the lithosphere. We show that these two endmember cases can in principle be distinguished using shear-wave splitting observations from SKS waves. This is illustrated by the simple example of pure olivine with horizontal a-axis, and differing orientations of the other two axes, namely, vertical b and vertical c. The azimuthal dependence of shear-wave splitting measurements is described by two parameters, which can provide additional information about subsurface deformation. In particular, the oscillation parameter d1 constrains the orientation of foliation. We demonstrate that shear-wave splitting in the Western and Central United States indeed shows the predicted azimuthal dependence, related to a mainly subhorizontally oriented flow plane of deformation in the upper mantle. This has important implications for asthenospheric flow.
The welfare and productivity of sows and piglets in group lactation from 7, 10, or 14 d postpartum
Authors: Verdon Megan , Morrison Rebecca S , Rault Jean-Loup
Published: February 2020

Transferring sows and their litters to group lactation (GL) after an initial period of farrowing crate (FC) housing could enhance the viability of GL for commercial production. Group lactation from 7 d postpartum would reduce the time sows spend in confinement, but the effects of early mixing on animal welfare and productivity require examination. Two experiments were conducted on sows and piglets kept in GL from 7, 10, or 14 d postpartum, compared with FC. Experiment 1 utilized 180 sows and 1,887 piglets over five time replicates (n = 60 sow and litter units per treatment) comparing GL from 7 or 14 d postpartum to FC. In experiment 2, 108 sows and 1,179 piglets were studied over three time replicates (n = 36 sow and litter units per treatment) comparing GL from 10 or 14 d postpartum to FC. All sows farrowed in FC. Group lactation sows were transferred to pens (one pen of five sows at 8.4 m2/sow and one pen of seven sows at 8.1 m2/sow, per GL treatment and replicate) with their litters at 7 (GL7), 10 (GL10), or 14 (GL14) d postpartum. Farrowing crate sows and their litters remained in their FC. Data were collected on sow feed intake and reproduction, piglet mortality (from day 6 postpartum), and sow and piglet weight changes, plasma cortisol concentrations, and injuries. Piglet mortality was greater in the GL7 (17 ± 1.8%) and GL10 treatments (12 ± 0.9%) compared with GL14 (8.3 ± 1.8% P ≤ 0.001 and 8.1 ± 0.9% P ≤ 0.001 in experiments 1 and 2), and greater in GL overall compared with FC (2.7 ± 1.5% and 1.8 ± 0.9% in FC in experiments 1 and 2; P ≤ 0.001). Piglets from GL7 were also lighter at weaning than GL14 piglets (P < 0.001), whereas GL10 and GL14 did not differ (P > 0.05). Overall, piglets in GL were lighter at weaning than piglets in FC (P ≤ 0.01). Sows from GL7 were heavier at weaning (P = 0.001), and GL10 sows tended to be heavier at weaning (P = 0.08), than GL14 and FC sows. Post-mixing, sow cortisol (P ≤ 0.01) and sow and piglet injuries (P ≤ 0.02) were greater in GL than FC. Treatment had no effect on sow feed intake or reproductive performance (P > 0.05). Under the conditions of this research, the known benefits of two-stage GL housing were achieved at a cost particularly to piglets in terms of increased piglet mortality and injuries after mixing, and reduced piglet growth. The risk of piglet mortality decreased with older age at mixing.
Fitting CAD data to scanned data with large deformation☆
Authors: Suzuki Shintaro , Ohtake Yutaka , Suzuki Hiromasa
Published: February 2020

Recently, largely deformed simulation models, such as car crash simulations, have been in high demand. To evaluate such models, it is necessary to use actual deformation results to compare and validate them. When measuring actual deformed objects, an X-ray CT is useful because it is non-destructive. However, matching undeformed CAD data and scanned deformation data is difficult. We propose a system for users to set control points or control lines on feature points and predict deformation using affine transformation with the moving least squares method. In the proposed method, undesirable distortions are reduced by evaluating scaling using singular value index and introducing offset control points. The deformed CAD data are obtained by matching predicted CAD data and a polygon mesh generated by deformed CT data. In addition, the surface elements of the generated deformed CAD data are evaluated for CAE.
Large-Scale Operational Pyriproxyfen Autodissemination Deployment to Suppress the Immature Asian Tiger Mosquito (Diptera: Culicidae) Populations
Authors: Unlu Isik , Rochlin Ilia , Suman Devi S , Wang Yi , Chandel Kshitij , Gaugler Randy
Published: February 2020

Effective suppression of container-inhabiting Asian Tiger [Aedes albopictus (Skuse)] (Diptera: Culicidae) and yellow fever [Aedes aegypti (L.)] (Diptera: Culicidae) mosquitoes presents one of the most intractable problems for modern mosquito control. Traditional tools often fail to control populations of these mosquito species, and are prohibitively expensive or have negative environmental impacts. Novel approaches and tools are urgently needed for integrated container-inhabiting mosquito management programs. One of the most promising techniques is autodissemination. We present the results of a long-term large-scale study conducted in a temperate urbanized environment representing typical Ae. albopictus habitats. Three treatment sites with autodissemination stations and three nearby reference sites were monitored for eggs, immature, and adult mosquitoes over a period of 3 yr from 2014 to 2016. Elevated larval and pupal mortality of 12–19% on average was the most notable outcome in sentinel cups of the treatment sites. The number of eggs in the treatment sites was significantly reduced in 2014, but not in 2015 or 2016. Adult populations remained similar in treatment and reference sites throughout the study. The impact of autodissemination on mosquito populations was lower than reported by previous investigations. Technical and logistical problems associated with wider coverage and working in multiple urban neighborhoods contributed to reduced efficacy. Incorporating autodissemination with routine mosquito control operations and commercializing this methodology for general public use will require further research on combining this tool with other novel or conventional technologies.
Macrophyte Diversity and Complexity Reduce Larval Mosquito Abundance
Authors: Lumpkin Will P , Stirek Kincade R , Dyer Lee A
Published: February 2020

The role of aquatic arthropod diversity and community interactions of larval mosquitoes are important for understanding mosquito population dynamics. We tested the effects of aquatic macrophyte diversity and habitat structural complexity in shaping the predator and competitor invertebrate communities associated with mosquito larvae. Experimental mesocosms were planted with live aquatic macrophytes and allowed to be naturally colonized by local invertebrates. Results indicated a positive effect of macrophyte diversity on competitor diversity and a negative effect on predator diversity. In turn, predator diversity negatively impacted mosquito abundance through a direct effect, while competitor diversity showed an indirect negative effect on mosquito larval abundance through its positive effect on predator diversity. The enhancement of aquatic macrophyte diversity and structural complexity has practical applications for the reduction of mosquito populations in managed systems where complete source elimination is not possible.
Small-Molecule Inhibitors of Inward Rectifier Potassium (Kir) Channels Reduce Bloodmeal Feeding and Have Insecticidal Activity Against the Horn Fly (Diptera: Muscidae)
Authors: Li Zhilin , Guerrero Felix , Pérez de León Adalberto A , Foil Lane D , Swale Daniel R
Published: February 2020

Bloodmeal feeding by the horn fly, Haematobia irritans (L.), is associated with reduced milk production and blood loss that ultimately prevents weight gain of calves and yearlings. Thus, blood feeding by H. irritans causes significant economic losses in several continents. As with other arthropods, resistance to the majority of commercialized insecticides reduces the efficacy of current control programs. Thus, innovative technologies and novel biochemical targets for horn fly control are needed. Salivary gland and Malpighian tubule function are critical for H. irritans survivorship as they drive bloodmeal acquisition and maintain ion- and fluid homeostasis during bloodmeal processing, respectively. Experiments were conducted to test the hypothesis that pharmacological modulation of H. irritans inward rectifier potassium (Kir) channels would preclude blood feeding and induce mortality by reducing the secretory activity of the salivary gland while simultaneously inducing Malpighian tubule failure. Experimental results clearly indicate structurally diverse Kir channel modulators reduce the secretory activity of the salivary gland by up to fivefold when compared to control and the reduced saliva secretion was highly correlated to a reduction in bloodmeal acquisition in adult flies. Furthermore, adult feeding on blood treated with Kir channel modulators resulted in significant mortality. In addition to validating the Kir channels of H. irritans as putative insecticide targets, the knowledge gained from this study could be applied to develop novel therapeutic technologies targeting salivary gland or Malpighian tubule function to reduce the economic burden of horn fly ectoparasitism on cattle health and production.
Travellers give wings to novel coronavirus (2019-nCoV)
Authors: Wilson Mary E , Chen Lin H
Published: February 2020

A novel coronavirus, probably of bat origin, has caused an outbreak of severe respiratory infection in humans in Wuhan, China and has been dispersed globally by travelers. The WHO has declared the spread of the infection a Public Health Emergency of International Concern.
Definability in first-order theories of graph orderings ⋆
Authors: Ramanujam R , Thinniyam Ramanathan S
Published: February 2020

We study definability in the first-order theory of graph order: i.e. the set of all isomorphism types of simple finite graphs ordered by either the minor, subgraph or induced subgraph relation. Natural graph families like cycles and trees are definable in these orders, as also notions like connectivity, maximum degree, etc. This machinery allows us to show mutual interpretability with arithmetic for all orders. We discuss implications for formalizing statements of graph theory in such theories of order. 1
Signatures of the core-powered mass-loss mechanism in the exoplanet population: dependence on stellar properties and observational predictions
Authors: Gupta Akash , Schlichting Hilke E
Published: February 2020

Recent studies have shown that atmospheric mass-loss powered by the cooling luminosity of a planet’s core can explain the observed radius valley separating super-Earths and sub-Neptunes, even without photoevaporation. In this work, we investigate the dependence of this core-powered mass-loss mechanism on stellar mass (M*), metallicity (Z*), and age (τ*). Without making any changes to the underlying planet population, we find that the core-powered mass-loss model yields a shift in the radius valley to larger planet sizes around more massive stars with a slope given by dlog Rp/dlog M* ≃ 0.35, in agreement with observations. To first order, this slope is driven by the dependence of core-powered mass-loss on the bolometric luminosity of the host star and is given by dlog Rp/dlog M* ≃ (3α − 2)/36 ≃ 0.33, where (L*/L⊙) = (M*/M⊙)α is the stellar mass–luminosity relation and α ≃ 4.6 for the CKS data set. We therefore find, in contrast to photoevaporation models, no evidence for a linear correlation between planet and stellar mass, but cannot rule it out either. In addition, we show that the location of the radius valley is, to first order, independent of stellar age and metallicity. Since core-powered mass-loss proceeds over Gyr time-scales, the abundance of super-Earths relative to sub-Neptunes increases with age but decreases with stellar metallicity. Finally, due to the dependence of the envelope’s cooling time-scale on metallicity, we find that the radii of sub-Neptunes increase with metallicity and decrease with age with slopes given by dlog Rp/dlog Z* ≃ 0.1 and dlog Rp/dlog τ* ≃ −0.1, respectively. We conclude with a series of observational tests that can differentiate between core-powered mass-loss and photoevaporation models.
On the comparison of AGN with GRMHD simulations: I. Sgr A*
Authors: Anantua Richard , Ressler Sean , Quataert Eliot
Published: February 2020

We present models of Galactic Centre emission in the vicinity of Sagittarius A* that use parametrizations of the electron temperature or energy density. These models include those inspired by two-temperature general relativistic magnetohydrodynamic (GRMHD) simulations as well as jet-motivated prescriptions generalizing equipartition of particle and magnetic energies. From these models, we calculate spectra and images and classify them according to their distinct observational features. Some models produce morphological and spectral features, e.g. image sizes, the sub-mm bump, and low-frequency spectral slope compatible with observations. Models with spectra consistent with observations produce the most compact images, with the most prominent, asymmetric photon rings. Limb-brightened outflows are also visible in many models. Of all the models we consider, that which represents the current data the best is one in which electrons are relativistically hot when magnetic pressure is larger than the thermal pressure, but cold (i.e. negligibly contributing to the emission) otherwise. This work is part of a series also applying the ‘observing’ simulations methodology to near-horizon regions of supermassive black holes in M87 and 3C 279.
Point spread function modelling for wide-field small-aperture telescopes with a denoising autoencoder
Authors: Jia Peng , Li Xiyu , Li Zhengyang , Wang Weinan , Cai Dongmei
Published: February 2020

The point spread function reflects the state of an optical telescope and it is important for the design of data post-processing methods. For wide-field small-aperture telescopes, the point spread function is hard to model because it is affected by many different effects and has strong temporal and spatial variations. In this paper, we propose the use of a denoising autoencoder, a type of deep neural network, to model the point spread function of wide-field small-aperture telescopes. The denoising autoencoder is a point spread function modelling method, based on pure data, which uses calibration data from real observations or numerical simulated results as point spread function templates. According to real observation conditions, different levels of random noise or aberrations are added to point spread function templates, making them realizations of the point spread function (i.e. simulated star images). Then we train the denoising autoencoder with realizations and templates of the point spread function. After training, the denoising autoencoder learns the manifold space of the point spread function and it can map any star images obtained by wide-field small-aperture telescopes directly to its point spread function. This could be used to design data post-processing or optical system alignment methods.
Ages and kinematics of chemically selected, accreted Milky Way halo stars
Authors: Das Payel , Hawkins Keith , Jofré Paula
Published: February 2020

We exploit the [Mg/Mn]-[Al/Fe] chemical abundance plane to help identify nearby halo stars in the 14th data release from the APOGEE survey that have been accreted on to the Milky Way. Applying a Gaussian Mixture Model, we find a ‘blob’ of 856 likely accreted stars, with a low disc contamination rate of ∼7 per cent. Cross-matching the sample with the second data release from Gaia gives us access to parallaxes and apparent magnitudes, which place constraints on distances and intrinsic luminosities. Using a Bayesian isochrone pipeline, this enables us to estimate new ages for the accreted stars, with typical uncertainties of ∼20 per cent. This does not account for systematic uncertainties. Our new catalogue is further supplemented with estimates of orbital parameters. The blob stars span [Fe/H] between −2.5 to −0.5, and [Mg/Fe] between −0.1 to 0.5. They constitute ∼30 per cent of the metal-poor ([Fe/H] < −0.8) halo at [Fe/H] ∼ −1.4. Our new ages mainly range between 8 to 13 Gyr, with the oldest stars the metal-poorest, and with the highest [Mg/Fe] abundance. If the blob stars are assumed to belong to a single progenitor, the ages imply that star formation lasted 5 Gyr after which the system merged with our Milky Way around 8 Gyr ago. Dynamical arguments suggest that such a single progenitor would have had a total mass of $\sim 10^{11}\, \mathrm{M}_{\odot }$, similar to that found by other authors using chemical evolution models and simulations.
Land–atmosphere–ocean coupling associated with the Tibetan Plateau and its climate impacts
Authors: Liu Yimin , Lu Mengmeng , Yang Haijun , Duan Anmin , He Bian , Yang Song , Wu Guoxiong
Published: February 2020

This paper reviews recent advances regarding land–atmosphere–ocean coupling associated with the Tibetan Plateau (TP) and its climatic impacts. Thermal forcing over the TP interacts strongly with that over the Iranian Plateau, forming a coupled heating system that elevates the tropopause, generates a monsoonal meridional circulation over South Asia and creates conditions of large-scale ascent favorable for Asian summer monsoon development. TP heating leads to intensification and westward extension (northward movement) of the South Asian High (Atlantic Intertropical Convergence Zone), and exerts strong impacts on upstream climate variations from North Atlantic to West Asia. It also affects oceanic circulation and buoyancy fields via atmospheric stationary wave trains and air–sea interaction processes, contributing to formation of the Atlantic Meridional Overturning Circulation. The TP thermal state and atmospheric–oceanic conditions are highly interactive and Asian summer monsoon variability is controlled synergistically by internal TP variability and external forcing factors.
Factor Xa Inhibition Reduces Coagulation Activity but Not Inflammation Among People With HIV: A Randomized Clinical Trial
Authors: Baker Jason V , Wolfson Julian , Peterson Tess , Mooberry Micah , Gissel Matthew , Mystakelis Harry , Henderson Michael W , Garcia-Myers Kelly , Rhame Frank S , Schacker Timothy W , Brummel-Ziedins Kathleen E , Sereti Irini , Key Nigel S , Tracy Russell P
Published: February 2020

Background

Coagulation activity among persons with HIV is associated with end-organ disease risk, but the pathogenesis is not well characterized. We tested a hypothesis that hypercoagulation contributes to disease risk, in part, via upregulation of inflammation.

Methods

Treatment effects of edoxaban (30 mg), a direct factor Xa inhibitor, vs placebo were investigated in a randomized, double-blind crossover trial among participants with HIV and viral suppression and D-dimer levels ≥100 ng/mL. During each 4-month crossover period, blood measures of coagulation, inflammation, and immune activation were assessed. Analyses of change on edoxaban vs change on placebo used linear mixed models.

Results

Forty-four participants were randomized, and 40 completed at least 1 visit during each study period. The mean age was 49 years, and the CD4+ count was 739 cells/mm3. Edoxaban treatment led to declines in D-dimer (44%) and thrombin-antithrombin complex (26%) but did not lower inflammatory or immune activation measures. More bruising or bleeding events occurred during edoxaban (n = 28) than during placebo or no drug periods (n = 15).

Conclusions

The direct factor Xa inhibitor edoxaban led to a substantial reduction in coagulation but no effect on inflammation or immune activation. These results do not support that hypercoagulation contributes to ongoing inflammation during chronic antiretroviral therapy–treated HIV disease.
Independent Validation in a Large Privately Insured Population of the Risk Index for Serious Prescription Opioid–Induced Respiratory Depression or Overdose
Authors: Metcalfe Leanne , Murrelle E Lenn , Vu Lan , Joyce Andrew R , Averhart Preston Veronica , Maryon Thomas , McDanald Conway , Yoo Phillip
Published: February 2020

Objective

To assess the generalizability of the overdose or serious opioid-induced respiratory depression risk index (VHA-RIOSORD), created by Zedler et al., using claims data from a large private insurer.

Design

A retrospective nested case–control analysis of health care claims data.

Subjects

Commercially insured individuals with a claim for an opioid prescription between October 1, 2014, and September 30, 2016 (N = 1,431,737).

Methods

An overdose or serious opioid–induced respiratory depression (OSORD) occurred in 1,097 patients. Ten controls were selected per case (N = 10,970). Items and the assignment of point values to predictors were consistent with those determined by Zedler et al. Modeling of risk index scores produced predicted probabilities of OSORD; risk classes were defined by the predicted probability distribution.

Results

All 15 items of the VHA-RIOSORD were used to determine a member’s risk of OSORD. The average predicted probability of experiencing OSORD ranged from 3% in the lowest risk decile to 90% in the highest, with excellent agreement between predicted and observed incidence across risk classes. The model’s C-statistic was 0.88.

Conclusions

Consistent with the findings of its developers, the VHA-RIOSORD performed well in identifying members of a large private insurance company who were medical users of prescription opioids at elevated risk of overdose or life-threatening respiratory depression, those most likely to benefit from preventive interventions.
Modelling the epidemic trend of the 2019-nCOV outbreak in Hubei Province, China
Authors: Ai Lizhe
Published: February 2020

As of 8am 30th January (Beijing Time) 2020, Approximate 8000 cases across the world have been confirmed. It’s necessary to simulate epidemic trend of the 2019-nCOV outbreak in Hubei Province, the hardest-hit area. By SEIR simulation, the predicted epidemic peak in Hubei will be within 28th January 2020 to 7th February 2020, up to 7000-9000 infectious cases in total. The estimate above was based on some assumptions and limitations exited.
Skill-specific changes in cortical preparatory activity during motor learning
Authors: Sun Xulu , O’Shea Daniel J. , Golub Matthew D. , Trautmann Eric M. , Vyas Saurabh , Ryu Stephen I. , Shenoy Krishna V.
Published: February 2020

Animals have a remarkable capacity to learn new motor skills, but it remains an open question as to how learning changes neural population dynamics underlying movement1. Specifically, we asked whether changes in neural population dynamics relate purely to newly learned movements or if additional patterns are generated that facilitate learning without matching motor output. We trained rhesus monkeys to learn a curl force field2task that elicited new arm-movement kinetics for some but not all reach directions3,4. We found that along certain neural dimensions, preparatory activity in motor cortex reassociated existing activity patterns with new movements. These systematic changes were observed only for learning-altered reaches. Surprisingly, we also found prominent shifts of preparatory activity along a nearly orthogonal neural dimension. These changes in preparatory activity were observed uniformly for all reaches including those unaltered by learning. This uniform shift during learning implies formation of new neural activity patterns, which was not observed in other short-term learning contexts5–8. During a washout period when the curl field was removed, movement kinetics gradually reverted, but the learning-induced uniform shift of preparatory activity persisted and a second, orthogonal uniform shift occurred. This persistent shift may retain a motor memory of the learned field9–11, consistent with faster relearning of the same curl field observed behaviorally and neurally. When multiple different curl fields were learned sequentially, we found distinct uniform shifts, each reflecting the identity of the field applied and potentially separating the associated motor memories12,13. The neural geometry of these shifts in preparatory activity could serve to organize skill-specific changes in movement production, facilitating the acquisition and retention of a broad motor repertoire.
HIV-1 Viremia Not Suppressible By Antiretroviral Therapy Can Originate from Large T-Cell Clones Producing Infectious Virus
Authors: Halvas Elias K. , Joseph Kevin W. , Brandt Leah D. , Guo Shuang , Sobolewski Michele D. , Jacobs Jana L. , Tumiotto Camille , Bui John K. , Cyktor Joshua C. , Keele Brandon F. , Morse Gene D. , Bale Michael J. , Kearney Mary F. , Coffin John M. , Rausch Jason W. , Wu Xiaolin , Hughes Stephen H. , Mellors John W.
Published: February 2020

BACKGROUND

HIV-1 viremia that is not suppressed by combination antiretroviral therapy (ART) is generally attributed to incomplete medication adherence and/or drug resistance. We evaluated individuals referred for non-suppressible viremia (plasma HIV-1 RNA above 40 copies/ml) who reported adherence to ART and did not show drug resistance to their current regimen.

METHODS

Samples were collected from at least two time points from eight donors who had non-suppressible viremia for more than six months on ART. Single templates of HIV-1 RNA obtained from plasma and viral outgrowth of cultured cells and from proviral DNA were PCR-amplified and sequenced for evidence of clones of cells that produced infectious viruses. Clones were identified by host-proviral integration site analysis.

RESULTS

HIV-1 genomic RNAs with identical sequences were identified in plasma samples from all eight donors. The identical viral RNA sequences did not change over time and lacked resistance to the ART regimen. In four of the donors, viral RNA sequences obtained from plasma matched those sequences from viral outgrowth cultures, indicating that the viruses were replication-competent. Integration sites for infectious proviruses from those four donors were mapped to introns of theMATR3,ZNF268,ZNF721/ABCA11P, andABCA11Pgenes. The sizes of the clones were from 50 million to 350 million cells.

CONCLUSION

Clones of HIV-1-infected cells producing virus can cause failure of ART to suppress viremia despite medication adherence and absence of drug resistance. The mechanisms involved in clonal expansion and persistence need to be defined to eliminate viremia and the HIV-1 reservoir.
The immune response and microbiota profiles during co-infection withP. vivaxand soil-transmitted helminths
Authors: Easton Alice V. , Raciny-Aleman Mayra , Liu Victor , Ruan Erica , Yasnot Maria Fernanda , Rodriguez Ana , Loke P’ng
Published: February 2020

Co-infection with soil-transmitted helminths (STH) andPlasmodiumspp. parasites is a common occurrence in tropical low-income countries, but the consequences of this interaction remain poorly understood. Here, we performed a multi-omic analysis on peripheral blood and fecal samples from 130 individuals in Tierralta, Córdoba, Colombia who were infected withP. vivaxalone (n = 33), co-infected withP. vivaxand STH (n = 27), infected with STH alone (n = 39) or were infected with neitherP. vivaxnor STH (n = 31). In addition to Complete Blood Count (CBC) with differential, transcriptional profiling of peripheral blood samples was performed by RNA-Seq, fecal microbial communities were determined by 16S ribosomal RNA gene sequencing and circulating cytokine levels were measured by bead-based immunoassays. Differences in blood cell counts were driven primarily byP. vivaxinfection, including an increased percentage of neutrophils that was associated with a transcriptional signature of neutrophil activation in the blood.P. vivaxinfection was also associated with increased levels of IL-6, IL-8 and IL-10, and these cytokine levels were not affected by STH co-infection. Surprisingly,P. vivaxinfection was more strongly associated with changes in the microbiome than STH infection. Children infected withP. vivaxexhibited elevatedBacteroidesand reducedPrevotellaandClostridiaceae, but these differences were not observed in individuals co-infected with STH. We also observed thatP. vivaxparasitemia was higher in the STH-infected population. When we used machine learning to identify the most important predictors ofP. vivaxparasite burden from all measured variables, bacterial taxa were the strongest predictors of parasitemia levels. In contrast, circulating TGF-β was the strongest predictor ofT. trichiuraegg burden. This study provides unexpected evidence that the gut microbiota may have a stronger link withP. vivaxthan with STH infection.
aiMeRA: A generic modular response analysis R package and its application to estrogen and retinoic acid receptors crosstalk
Authors: Jimenez-Dominguez Gabriel , Ravel Patrice , Jalaguier Stéphan , Cavaillès Vincent , Colinge Jacques
Published: February 2020

Modular response analysis (MRA) is a widely used modeling technique to uncover coupling strengths in molecular networks under a steady-state condition by means of perturbation experiments. We propose an extension of this methodology to search genomic data for new associations with a network modeled by MRA and to improve the predictive accuracy of MRA models. These extensions are illustrated by exploring the cross talk between estrogen and retinoic acid receptors, two nuclear receptors implicated in several hormone-driven cancers such as breast. We also present a novel, rigorous and elegant mathematical derivation of MRA equations, which is the foundation of this work and of an R package that is freely available athttps://github.com/bioinfo-ircm/aiMeRA/. This mathematical analysis should facilitate MRA understanding by newcomers.

Author summary

Estrogen and retinoic acid receptors play an important role in several hormone-driven cancers and share co-regulators and co-repressors that modulate their transcription factor activity. The literature shows evidence for crosstalk between these two receptors and suggests that spatial competition on the promoters could be a mechanism. We used MRA to explore the possibility that key co-repressors, i.e., NRIP1 (RIP140) and LCoR could also mediate crosstalk by exploiting new quantitative (qPCR) and RNA sequencing data. The transcription factor role of the receptors and the availability of genome-wide data enabled us to explore extensions of the MRA methodology to explore genome-wide data setsa posteriori, searching for genes associated with a molecular network that was sampled by perturbation experiments. Despite nearly two decades of use, we felt that MRA lacked a systematic mathematical derivation. We present here an elegant and rather simple analysis that should greatly facilitate newcomers’ understanding of MRA details. Moreover, an easy-to-use R package is released that should make MRA accessible to biology labs without mathematical expertise. Quantitative data are embedded in the R package and RNA sequencing data are available from GEO.
Impacts of predator-mediated interactions along a climatic gradient on the population dynamics of an alpine bird
Authors: Bowler Diana E. , Kvasnes Mikkel A. J. , Pedersen Hans C. , Sandercock Brett K. , Nilsen Erlend B.
Published: February 2020

According to classic theory, species’ population dynamics and distributions are less influenced by species interactions under harsh climatic conditions compared to under more benign climatic conditions. In alpine and boreal ecosystems in Fennoscandia, the cyclic dynamics of rodents strongly affect many other species, including ground-nesting birds such as ptarmigan. According to the ‘alternative prey hypothesis’ (APH), the densities of ground-nesting birds and rodents are positively associated due to predator-prey dynamics and prey-switching. However, it remains unclear how the strength of these predator-mediated interactions change along a climatic harshness gradient in comparison with the effects of climatic variation. We built a hierarchical Bayesian model to estimate the sensitivity of ptarmigan populations to interannual variation in climate and rodent occurrence across Norway during 2007–2017. Ptarmigan abundance was positively linked with rodent occurrence, consistent with the APH. Moreover, we found that rodent dynamics had stronger effects on ptarmigan in colder regions. Our study highlights how species interactions play an important role for the population dynamics of species at higher latitudes and suggests that they can become even more important in the most climatically harsh regions.
Rapid evolution of coordinated and collective movement in response to artificial selection
Authors: Kotrschal Alexander , Szorkovszky Alexander , Herbert-Read James , Bloch Natasha I. , Romenskyy Maksym , Buechel Séverine Denise , Eslava Ada Fontrodona , Sánchez Alòs Laura , Zeng Hongli , Le Foll Audrey , Braux Ganaël , Pelckmans Kristiaan , Mank Judith E. , Sumpter David , Kolm Niclas
Published: February 2020

Collective motion occurs when individuals use social interaction rules to respond to the movements and positions of their neighbors. How readily these social decisions are shaped by selection remains unknown. Through artificial selection on fish (guppies,Poecilia reticulata) for increased social coordination (group polarization), we demonstrate that social interaction rules can evolve remarkably fast. Within just three generations, groups of polarization selected females showed a 15% increase in polarization, coupled with increased cohesiveness, compared to fish from control lines. They did not differ in physical swimming ability or exploratory behavior. However, polarization selected fish adopted faster speeds, particularly in social contexts, and showed stronger alignment and attraction responses to multiple neighbors. Our results demonstrate that animals’ social interactions can rapidly evolve under strong selection, and reveal which social interaction rules change when collective behavior evolves.
Single-cell transcriptome analyses recapitulate the cellular and developmental responses to abiotic stresses in rice
Authors: Wang Yu , Huan Qing , Chu Xiao , Li Ke , Qian Wenfeng
Published: February 2020

The metabolism and reproduction of plants depend on the division of labors among cells. However, cells with various functions are often studied as a bulk where their specificities were diluted. Here, we apply single-cell RNA sequencing to the aerial part of rice seedlings growing in various environments. We capture the transcriptomes of thousands of cells, identify all major cell types, and reconstruct their developmental trajectories. We find that abiotic stresses not only affect gene expression in a cell-type-specific manner but also have impacts on the physical size of cells and the composition of cell populations. We validate some of these conclusions with microscopy and provide developmental mechanisms with computational analyses. Collectively, our study represents a benchmark-setting data resource of single-cell transcriptome atlas in rice and an illustration of exploiting such resource to drive discoveries in plant biology.
The functional foundations of episodic memory remain stable throughout the lifespan
Authors: Vidal-Piñeiro D. , Sneve MH. , Amlien IK. , Grydeland H. , Mowinckel AM. , Roe J.M. , Sørensen Ø. , Nyberg LH. , Walhovd KB. , Fjell AM.
Published: February 2020

It is suggested that the functional mechanisms behind specific forms of cognition, particularly episodic memory, may be dynamic over the lifespan and that cognitive preservation or decay in older age thus relies on age-specific mechanisms such as compensatory processes. Here instead, we tested whether the functional foundations of successful episodic memory encoding adhere to a principle of lifespan continuity, shaped by developmental, structural and evolutionary influences. We identified the generic lifespan patterns of memory encoding function across the brain (n = 540; age range = 6 – 82 years). The lifespan trajectories of brain activity were organized in a topologically meaningful manner and aligned to fundamental aspects of brain organization, such as large-scale connectivity hierarchies and evolutionary cortical expansion gradients. None of the normative trajectories of encoding function was solely determined by late-life patterns of activity, but rather showed continuities across development and adulthood. Inter-individual differences in activity in age-sensitive regions were predicted by general cognitive abilities and variation in grey matter structure, which are core variables of cognitive and structural change throughout the lifespan. Altogether, the results provide evidence for the lifelong continuity of the functional foundations of episodic memory which are bounded by both brain architecture and core mechanisms of cognitive and structural change over life. We provide novel support for a perspective on memory aging in which maintenance and decay of episodic memory in older age needs to be understood from a comprehensive life-long perspective rather than as a late-life phenomenon only.

Significance statement

It is suggested that cognitive function in older age largely relies on late-life specific mechanisms such as compensatory processes. In contrast, here we tested whether and to what degree brain activity during episodic memory encoding adheres to fundamental principles of life-long brain organization and continuity. The results revealed that generic lifespan trajectories of memory encoding function were not specific to late-life. Instead, the age-trajectories showed a continuity through life, were related to fundamental features of brain structure and cognition and to functional and evolutionary hierarchies. We argue that rather than focusing on older-age specific mechanisms, a framework that takes lifespan mechanisms of cognition and brain anatomy into account is necessary to understand episodic memory vulnerability in older age.
In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia
Authors: Farrell Jordan S. , Colangeli Roberto , Dudok Barna , Wolff Marshal D. , Nguyen Sarah L. , Jackson Jesse , Dickson Clayton T. , Soltesz Ivan , Teskey G. Campbell
Published: February 2020

Long-lasting confusion and memory difficulties during the postictal state remain a major unmet problem in epilepsy that lacks pathophysiological explanation and treatment. We previously identified that long-lasting periods of severe postictal hypoperfusion/hypoxia, not seizuresper se, are associated with memory impairment after temporal lobe seizures. While this observation suggests a key pathophysiological role for insufficient energy delivery, it is unclear how the networks that underlie episodic memory respond to vascular constraints that ultimately give rise to amnesia. Here, we focused on cellular/network level analyses in the CA1 of hippocampusin vivoto determine if neural activity, network oscillations, synaptic transmission, and/or synaptic plasticity are impaired following kindled seizures. Importantly, the induction of severe postictal hypoperfusion/hypoxia was prevented in animals treated by a COX-2 inhibitor, which experimentally separated seizures from their vascular consequences. We observed complete activation of CA1 pyramidal neurons during brief seizures, followed by a short period of reduced activity and flattening of the local field potential that resolved within minutes. During the postictal state, constituting tens of minutes to hours, we observed no changes in neural activity, network oscillations, and synaptic transmission. However, long-term potentiation of the temporoammonic pathway to CA1 was impaired in the postictal period, but only when severe local hypoxia occurred. Lastly, we tested the ability of rats to perform object-context discrimination, which has been proposed to require temporoammonic input to differentiate between sensory experience and the stored representation of the expected object-context pairing. Deficits in this task following seizures were reversed by COX-2 inhibition, which prevented severe postictal hypoxia. These results support a key role for hypoperfusion/hypoxia in postictal memory impairments and identify that many aspects of hippocampal network function are resilient during severe hypoxia except for long-term synaptic plasticity.
Gold-standard diagnostics are tarnished by lytic bacteriophage
Authors: Nelson E.J. , Grembi J.A. , Chao D.L. , Andrews J.R. , Alexandrova L. , Rodriguez P. H. , Ramachandran V.V. , Sayeed Md.A. , Wamala W. J. , Debes A.K. , Sack D.A. , Hryckowian A. J. , Haque F. , Khatun S. , Rahman M. , Chien A. , Spormann A.M. , Schoolnik G.K.
Published: February 2020

Background

A fundamental clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity.

Methods

Cholera was chosen as a model disease to investigate this important question. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection, as well as exposure to the first-line antibiotic azithromycin detected by mass spectrometry.

Results

Among diarrheal samples positive by nanoliter quantitative PCR forVibrio cholerae(n=78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (OR 0.108; 95%CI 0.002-0.872) and 87% (OR 0.130; 95%CI 0.022-0.649) when lytic bacteriophage were detected, respectively. The odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by more than 99% (OR 0.00; 95% CI: 0.00-0.28) and 89% (OR 0.11; 95% CI: 0.03-0.44) when azithromycin was detected, respectively.

Conclusions

Estimations of cholera burden may improve by accommodating for the negative effect of antimicrobial exposure on diagnostic positivity. Furthermore, the findings herein challenge our current approach to interpreting and developing bacterial diagnostics given variable rates of lytic bacteriophage and antibiotic exposure.