bluuebunny/crossref_metadata_2025_split huggingface dataset:
Action Control Deficits in Patients With Essential Tremor
Authors: Hughes Shelby , Claassen Daniel O. , van den Wildenberg Wery P.M. , Phibbs Fenna T. , Bradley Elise B. , Wylie Scott A. , van Wouwe Nelleke C. 
Published: December 2018

AbstractObjectives: Essential tremor (ET) is a movement disorder characterized by action tremor which impacts motor execution. Given the disrupted cerebellar-thalamo-cortical networks in ET, we hypothesized that ET could interfere with the control mechanisms involved in regulating motor performance. The ability to inhibit or stop actions is critical for navigating many daily life situations such as driving or social interactions. The current study investigated the speed of action initiation and two forms of action control, response stopping and proactive slowing in ET. Methods: Thirty-three ET patients and 25 healthy controls (HCs) completed a choice reaction task and a stop-signal task, and measures of going speed, proactive slowing and stop latencies were assessed. Results: Going speed was significantly slower in ET patients (649 ms) compared to HCs (526 ms; F(1,56) = 42.37; p <.001; η2 = .43), whereas proactive slowing did not differ between groups. ET patients exhibited slower stop signal reaction times (320 ms) compared to HCs (258 ms, F(1,56) = 15.3; p <.00; η2 = .22) and more severe motor symptoms of ET were associated with longer stopping latencies in a subset of patients (Spearman rho = .48; p <.05). Conclusions: In line with previous studies, ET patients showed slower action initiation. Additionally, inhibitory control was impaired whereas proactive slowing remained intact relative to HCs. More severe motor symptoms of ET were associated with slower stopping speed, and may reflect more progressive changes to the cerebellar-thalamo-cortical network. Future imaging studies should specify which structural and functional changes in ET can explain changes in inhibitory action control. (JINS, 2019, 25, 156–164)
Offspring from maternal nutrient restriction in mice show variations in adult glucose metabolism similar to human fetal growth restriction
Authors: Radford B. N. , Han V. K. M. 
Published: December 2018

AbstractFetal growth restriction (FGR) is a pregnancy condition in which fetal growth is suboptimal for gestation, and this population is at increased risk for type 2 diabetes as adults. In humans, maternal malnutrition and placental insufficiency are the most common causes of FGR, and both result in fetal undernutrition. We hypothesized that maternal nutrient restriction (MNR) in mice will cause FGR and alter glucose metabolism in adult offspring. Pregnant CD-1 mice were subjected to MNR (70% of average ad libitum) or control (ad libitum) from E6.5 to birth. Following birth, mice were fostered by mothers on ad libitum feeds. Weight, blood glucose, glucose tolerance and tissue-specific insulin sensitivity were assessed in male offspring. MNR resulted in reduced fetal sizes but caught up to controls by 3 days postnatal age. As adults, glucose intolerance was detected in 19% of male MNR offspring. At 6 months, liver size was reduced (P = 0.01), but pAkt-to-Akt ratios in response to insulin were increased 2.5-fold relative to controls (P = 0.004). These data suggest that MNR causes FGR and long-term glucose intolerance in a population of male offspring similar to human populations. This mouse model can be used to investigate the impacts of FGR on tissues of importance in glucose metabolism.
Ocean Circulation Causes Strong Variability in the Mid‐Atlantic Bight Nitrogen Budget
Authors: Friedrichs Marjorie A. M. , St‐Laurent Pierre , Xiao Yongjin , Hofmann Eileen , Hyde Kimberly , Mannino Antonio , Najjar Raymond G. , Narváez Diego A. , Signorini Sergio R. , Tian Hanqin , Wilkin John , Yao Yuanzhi , Xue Jianhong 
Published: December 2018

AbstractUnderstanding of nitrogen cycling on continental shelves, a critical component of global nutrient cycling, is hampered by limited observations compared to the strong variability on a wide range of time and space scales. Numerical models have the potential to partially alleviate this issue by filling spatiotemporal data gaps and hence resolving annual area‐integrated nutrient fluxes. In this study, a three‐dimensional biogeochemical‐circulation model was implemented to simulate the Mid‐Atlantic Bight (MAB) nitrogen budget. Model results demonstrate that, on average, MAB net community production (NCP) was positive (+0.27 Tg N/year), indicating net autotrophy. Interannual variability in NCP was strong, with annual values ranging between 0.19 and 0.41 Tg N/year. Along‐shelf and across‐shelf horizontal transport fluxes were the other dominant terms in the nitrogen budget and were primarily responsible for this NCP variability. The along‐shelf current transported nitrogen from the north (0.65 Tg N/year) into the MAB, supplementing the nitrogen entering from terrestrial inputs (0.27 Tg N/year). However, NCP was highest in the year when total water volume transport and inorganic nitrogen input was strongest across the continental slope in the southern MAB, rather than when terrestrial inputs were greatest. Interannual variability of NCP appears to be linked to changes in the positions of the Gulf Stream and Slope Water Gyre. Overall, the strong spatiotemporal variability of the nitrogen fluxes highlights the importance of observations throughout all seasons and multiple years in order to accurately resolve the current status and future changes of the MAB nitrogen budget.
The Role of Reactive Iron in the Preservation of Terrestrial Organic Carbon in Estuarine Sediments
Authors: Zhao B. , Yao P. , Bianchi T. S. , Shields M. R. , Cui X. Q. , Zhang X. W. , Huang X. Y. , Schröder C. , Zhao J. , Yu Z. G. 
Published: December 2018

AbstractTo better understand the role of reactive Fe (FeR) in the preservation of sedimentary organic carbon (SOC) in estuarine sediments, we examined specific surface area, grain size composition, total OC (TOC), lignin phenols, FeR, FeR‐associated OC (Fe‐OC) and lignin phenols (Fe‐lignin), and δ13C of FeR‐associated OC (δ13CFe‐OC) in surface sediments of the Changjiang Estuary and adjacent shelf. An estimated 7.4 ± 3.5% of the OC was directly bound with FeR in the Changjiang Estuary and adjacent shelf. Unusually low TOC/specific surface area loadings and Fe‐OC/Fe ratios in mobile muds suggest that frequent physical reworking may reduce FeR binding with OC, with selective loss of marine OC. More depleted 13CFe‐OC relative to 13C of TOC (13Cbulk) in deltaic regions and mobile muds showed that FeR was largely associated with terrestrial OC, derived from extensive riverine OC and Fe inputs. A higher proportion of hematite in the mobile muds compared to the offshore samples indicated that Fe oxides are likely subjected to selective sorting and/or become mature during long‐term sediment transport. When considering the percentage of Fe‐OC to SOC and SOC burial rates in different marine environments (e.g., nondeltaic shelf, anoxic basins, slope, and deep sea), our findings suggest that about 15.6 ± 6.5% of SOC is directly bound to FeR on a global scale, which is lower than the previous estimation (~21.5%). This work further supports the notion of a Rusty Sink where, in this case, FeR plays an important role in the preservation and potential transport of terrestrial OC in the marine environment.
Childhood adversity and DNA methylation in two population-based cohorts
Authors: Houtepen L. C. , Hardy R. , Maddock J. , Kuh D. , Anderson E. L. , Relton C. L. , Suderman M. J. , Howe L. D. 
Published: December 2018

AbstractChildhood adversity affects later health, but the underlying molecular mechanisms are unclear. Although there is some evidence from animal models and case-control studies of a role for DNA methylation, evidence from human population-based studies is limited. In two cohorts (mothers from the Avon Longitudinal Study of Parents and Children, ALSPAC,n = 780 and women from the MRC National Survey of Health and Development, NSHD,n = 552), we assessed the association of seven adverse childhood experiences (ACEs: parental physical illness, parental mental illness, parental death, parental separation, suboptimal maternal bonding, childhood illness and child maltreatment) as well as their combination (ACE score) with genome-wide DNA methylation levels measured using the Illumina Infinium HumanMethylation450 BeadChip in peripheral blood at mean age 47 years (ALSPAC) and in buccal cells at age 53 years (NSHD). CpG sites with a genome-wide false discovery rate (FDR) below 0.05 and differentially methylated regions (DMRs) with one-step Šidák correctionp-values below 0.05 in each cohort were examined in the other cohort. No individual CpG sites replicated across cohorts. However, nine DMRs replicated across cohorts respectively associated with the ACE score (one region), parental mental illness (two regions), parental physical illness (three regions) and parental death (three regions). These observations indicate that some adverse childhood experiences, notably those related to parental health, may leave imprints on peripheral DNA methylation that persist to mid-life.
Neural network analysis of sleep stages enables efficient diagnosis of narcolepsy
Authors: Stephansen Jens B. , Olesen Alexander N. , Olsen Mads , Ambati Aditya , Leary Eileen B. , Moore Hyatt E. , Carrillo Oscar , Lin Ling , Han Fang , Yan Han , Sun Yun L. , Dauvilliers Yves , Scholz Sabine , Barateau Lucie , Hogl Birgit , Stefani Ambra , Hong Seung Chul , Kim Tae Won , Pizza Fabio , Plazzi Giuseppe , Vandi Stefano , Antelmi Elena , Perrin Dimitri , Kuna Samuel T. , Schweitzer Paula K. , Kushida Clete , Peppard Paul E. , Sorensen Helge B. D. , Jennum Poul , Mignot Emmanuel 
Published: December 2018

AbstractAnalysis of sleep for the diagnosis of sleep disorders such as Type-1 Narcolepsy (T1N) currently requires visual inspection of polysomnography records by trained scoring technicians. Here, we used neural networks in approximately 3,000 normal and abnormal sleep recordings to automate sleep stage scoring, producing a hypnodensity graph—a probability distribution conveying more information than classical hypnograms. Accuracy of sleep stage scoring was validated in 70 subjects assessed by six scorers. The best model performed better than any individual scorer (87% versus consensus). It also reliably scores sleep down to 5 s instead of 30 s scoring epochs. A T1N marker based on unusual sleep stage overlaps achieved a specificity of 96% and a sensitivity of 91%, validated in independent datasets. Addition of HLA-DQB1*06:02 typing increased specificity to 99%. Our method can reduce time spent in sleep clinics and automates T1N diagnosis. It also opens the possibility of diagnosing T1N using home sleep studies.
Machine learning applied to enzyme turnover numbers reveals protein structural correlates and improves metabolic models
Authors: Heckmann David , Lloyd Colton J. , Mih Nathan , Ha Yuanchi , Zielinski Daniel C. , Haiman Zachary B. , Desouki Abdelmoneim Amer , Lercher Martin J. , Palsson Bernhard O. 
Published: December 2018

AbstractKnowing the catalytic turnover numbers of enzymes is essential for understanding the growth rate, proteome composition, and physiology of organisms, but experimental data on enzyme turnover numbers is sparse and noisy. Here, we demonstrate that machine learning can successfully predict catalytic turnover numbers in Escherichia coli based on integrated data on enzyme biochemistry, protein structure, and network context. We identify a diverse set of features that are consistently predictive for both in vivo and in vitro enzyme turnover rates, revealing novel protein structural correlates of catalytic turnover. We use our predictions to parameterize two mechanistic genome-scale modelling frameworks for proteome-limited metabolism, leading to significantly higher accuracy in the prediction of quantitative proteome data than previous approaches. The presented machine learning models thus provide a valuable tool for understanding metabolism and the proteome at the genome scale, and elucidate structural, biochemical, and network properties that underlie enzyme kinetics.
Binding of HMGN proteins to cell specific enhancers stabilizes cell identity
Authors: He Bing , Deng Tao , Zhu Iris , Furusawa Takashi , Zhang Shaofei , Tang Wei , Postnikov Yuri , Ambs Stefan , Li Caiyi Cherry , Livak Ferenc , Landsman David , Bustin Michael 
Published: December 2018

AbstractThe dynamic nature of the chromatin epigenetic landscape plays a key role in the establishment and maintenance of cell identity, yet the factors that affect the dynamics of the epigenome are not fully known. Here we find that the ubiquitous nucleosome binding proteins HMGN1 and HMGN2 preferentially colocalize with epigenetic marks of active chromatin, and with cell-type specific enhancers. Loss of HMGNs enhances the rate of OSKM induced reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs), and the ASCL1 induced conversion of fibroblast into neurons. During transcription factor induced reprogramming to pluripotency, loss of HMGNs accelerates the erasure of the MEF-specific epigenetic landscape and the establishment of an iPSCs-specific chromatin landscape, without affecting the pluripotency potential and the differentiation potential of the reprogrammed cells. Thus, HMGN proteins modulate the plasticity of the chromatin epigenetic landscape thereby stabilizing, rather than determining cell identity.
Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis
Authors: Campa Carlo C. , Silva Rangel L. , Margaria Jean P. , Pirali Tracey , Mattos Matheus S. , Kraemer Lucas R. , Reis Diego C. , Grosa Giorgio , Copperi Francesca , Dalmarco Eduardo M. , Lima-Júnior Roberto C. P. , Aprile Silvio , Sala Valentina , Dal Bello Federica , Prado Douglas Silva , Alves-Filho Jose Carlos , Medana Claudio , Cassali Geovanni D. , Tron Gian Cesare , Teixeira Mauro M. , Ciraolo Elisa , Russo Remo C. , Hirsch Emilio 
Published: December 2018

AbstractPI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis.
Discovering de novo peptide substrates for enzymes using machine learning
Authors: Tallorin Lorillee , Wang JiaLei , Kim Woojoo E. , Sahu Swagat , Kosa Nicolas M. , Yang Pu , Thompson Matthew , Gilson Michael K. , Frazier Peter I. , Burkart Michael D. , Gianneschi Nathan C. 
Published: December 2018

AbstractThe discovery of peptide substrates for enzymes with exclusive, selective activities is a central goal in chemical biology. In this paper, we develop a hybrid computational and biochemical method to rapidly optimize peptides for specific, orthogonal biochemical functions. The method is an iterative machine learning process by which experimental data is deposited into a mathematical algorithm that selects potential peptide substrates to be tested experimentally. Once tested, the algorithm uses the experimental data to refine future selections. This process is repeated until a suitable set of de novo peptide substrates are discovered. We employed this technology to discover orthogonal peptide substrates for 4’-phosphopantetheinyl transferase, an enzyme class that covalently modifies proteins. In this manner, we have demonstrated that machine learning can be leveraged to guide peptide optimization for specific biochemical functions not immediately accessible by biological screening techniques, such as phage display and random mutagenesis.
Magnetic excitations in non-collinear antiferromagnetic Weyl semimetal Mn3Sn
Authors: Park Pyeongjae , Oh Joosung , Uhlířová Klára , Jackson Jerome , Deák András , Szunyogh László , Lee Ki Hoon , Cho Hwanbeom , Kim Ha-Leem , Walker Helen C. , Adroja Devashibhai , Sechovský Vladimír , Park Je-Geun 
Published: December 2018

AbstractMn3Sn has recently attracted considerable attention as a magnetic Weyl semimetal exhibiting concomitant transport anomalies at room temperature. The topology of the electronic bands, their relation to the magnetic ground state and their nonzero Berry curvature lie at the heart of the problem. The examination of the full magnetic Hamiltonian reveals otherwise hidden aspects of these unusual physical properties. Here, we report the full spin wave spectra of Mn3Sn measured over a wide momentum—energy range by the inelastic neutron scattering technique. Using a linear spin wave theory, we determine a suitable magnetic Hamiltonian which not only explains the experimental results but also stabilizes the low-temperature helical phase, consistent with our DFT calculations. The effect of this helical ordering on topological band structures is further examined using a tight binding method, which confirms the elimination of Weyl points in the helical phase. Our work provides a rare example of the intimate coupling between the electronic and spin degrees of freedom for a magnetic Weyl semimetal system.
The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group
Authors: Leung Nelson , Bridoux Frank , Batuman Vecihi , Chaidos Aristeidis , Cockwell Paul , D’Agati Vivette D. , Dispenzieri Angela , Fervenza Fernando C. , Fermand Jean-Paul , Gibbs Simon , Gillmore Julian D. , Herrera Guillermo A. , Jaccard Arnaud , Jevremovic Dragan , Kastritis Efstathios , Kukreti Vishal , Kyle Robert A. , Lachmann Helen J. , Larsen Christopher P. , Ludwig Heinz , Markowitz Glen S. , Merlini Giampaolo , Mollee Peter , Picken Maria M. , Rajkumar Vincent S. , Royal Virginie , Sanders Paul W. , Sethi Sanjeev , Venner Christopher P. , Voorhees Peter M. , Wechalekar Ashutosh D. , Weiss Brendan M. , Nasr Samih H. 
Published: December 2018

AbstractThe term monoclonal gammopathy of renal significance (MGRS) was introduced by the International Kidney and Monoclonal Gammopathy Research Group (IKMG) in 2012. The IKMG met in April 2017 to refine the definition of MGRS and to update the diagnostic criteria for MGRS-related diseases. Accordingly, in this Expert Consensus Document, the IKMG redefines MGRS as a clonal proliferative disorder that produces a nephrotoxic monoclonal immunoglobulin and does not meet previously defined haematological criteria for treatment of a specific malignancy. The diagnosis of MGRS-related disease is established by kidney biopsy and immunofluorescence studies to identify the monotypic immunoglobulin deposits (although these deposits are minimal in patients with either C3 glomerulopathy or thrombotic microangiopathy). Accordingly, the IKMG recommends a kidney biopsy in patients suspected of having MGRS to maximize the chance of correct diagnosis. Serum and urine protein electrophoresis and immunofixation, as well as analyses of serum free light chains, should also be performed to identify the monoclonal immunoglobulin, which helps to establish the diagnosis of MGRS and might also be useful for assessing responses to treatment. Finally, bone marrow aspiration and biopsy should be conducted to identify the lymphoproliferative clone. Flow cytometry can be helpful in identifying small clones. Additional genetic tests and fluorescent in situ hybridization studies are helpful for clonal identification and for generating treatment recommendations. Treatment of MGRS was not addressed at the 2017 IKMG meeting; consequently, this Expert Consensus Document does not include any recommendations for the treatment of patients with MGRS.
Parent-embryo acoustic communication: a specialised heat vocalisation allowing embryonic eavesdropping
Authors: Mariette Mylene M. , Pessato Anaïs , Buttemer William A. , McKechnie Andrew E. , Udino Eve , Collins Rodney N. , Meillère Alizée , Bennett Andrew T. D. , Buchanan Katherine L. 
Published: December 2018

AbstractSound is arguably the external cue most accessible to embryos of many species, and as such may constitute an unrivalled source of early information. Recent evidence shows that prenatal sounds, similarly to maternal effects, may shape developmental trajectories. Establishing whether parental vocalisations are signals directed at embryos, or parental cues on which embryos eavesdrop, can elucidate whether parents or embryos control developmental outcomes. Prenatal exposure to a characteristic heat-related parental call was recently shown to alter zebra finch growth and fitness. Here, we test the ecological context of this behaviour in the wild, and assess the information value and specificity of this vocalisation for an embryonic audience. We show that wild zebra finches also produce this characteristic call, only at high temperatures. In addition, in the lab, we demonstrate experimentally that calling is specifically triggered by high air temperatures, can occur without an embryonic audience, and importantly, is predicted by individuals’ body mass. Overall, our findings reveal a specialised heat vocalisation that enables embryonic eavesdropping, by indicating high ambient temperatures, and parents’ capacity to cope with such conditions. This challenges the traditional view of embryos as passive agents of their development, and opens exciting research avenues on avian adaptation to extreme heat.
Effects of horizontal distance and limb crossing on perceived hand spacing and ownership: Differential sensory processing across hand configurations
Authors: Qureshi Hassan G. , Butler Annie A. , Kerr Graham K. , Gandevia Simon C. , Héroux Martin E. 
Published: December 2018

AbstractWe have previously shown that, with the hands apart vertically, passively grasping an artificial finger induces a sense of ownership over the artificial finger and coming-together of the hands. The present study investigated this grasp illusion in the horizontal plane. Thirty healthy participants were tested in two conditions (grasp and no grasp) with their hands at different distances apart, either crossed or uncrossed. After 3 min, participants reported perceived spacing between index fingers, perceived index finger location, and, for the grasp condition, perceived ownership over the artificial finger. On average, there was no ownership at any of the hand configurations. With the hands uncrossed 7.5, 15 or 24 cm apart, there was no difference in perceived spacing between the grasp and no grasp conditions. With the hands crossed and 15 cm apart, perceived spacing between index fingers was 3.2 cm [0.7 to 5.7] (mean [95% CI]) smaller during the grasp condition compared to no grasp. Therefore, compared to when the hands are vertically separated, there is an almost complete lack of a grasp illusion in the horizontal plane which indicates the brain may process sensory inputs from the hands differently based on whether the hands are horizontally or vertically apart.