bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of polygenic risk scores and other molecular markers to enhance cardiovascular risk prediction: prospective cohort study and modelling analysis
Authors: Sun Luanluan , Pennells Lisa , Kaptoge Stephen , Nelson Christopher P , Abraham Gad , Arnold Matthew , Bell Steven , Bolton Thomas , Burgess Stephen , Dudbridge Frank , Guo Qi , Ritchie Scott C , Sofianopoulou Eleni , Stevens David , Thompson John R , Butterworth Adam S , Wood Angela , Danesh John , Samani Nilesh J , Inouye Michael , Angelantonio Emanuele Di 
Published: August 2019

AbstractBackgroundThere is debate about the value of adding information on genetic and other molecular markers to conventional cardiovascular disease (CVD) risk predictors.MethodsUsing data on 306,654 individuals without a history of CVD from UK Biobank, we calculated measures of risk-discrimination and reclassification upon addition of polygenic risk scores (PRS) and a panel of 27 clinical biochemistry markers to a conventional risk prediction model (i.e., including age, sex, systolic blood pressure, smoking status, history of diabetes, total cholesterol and HDL cholesterol). We then modelled implications of initiating guideline-recommended statin therapy after the assessment of molecular markers for a UK primary-care setting.FindingsThe C-index was 0.710 (95% CI, 0.703-0.717) for a CVD prediction model containing conventional risk predictors alone. The C-index increased by similar amounts when adding information on PRS or biochemistry markers (0.011 and 0.014, respectively; P<0.001), and it increased still further (0.022; P<0.001) when information on both was combined. Among cases and controls, continuous net reclassification improvements were about 12% and 19%, respectively, when both PRS and biochemistry markers were added. If PRS and biochemistry markers were to be assessed in the entire primary care population aged 40-75, then it could help prevent one additional CVD event for every 893 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5-10%) 10-year CVD risk could help prevent one additional CVD event for every 233 individuals screened. This targeted strategy could help reclassify 16% of the intermediate-risk group to the high-risk (i.e., ≥10%) category, preventing 11% more CVD events than conventional risk prediction.InterpretationAdding information on both PRS and selected biochemistry markers moderately enhanced CVD predictive accuracy and could improve primary prevention of CVD. However, our modelling suggested that targeted assessment of molecular markers among individuals at intermediate-risk would be more efficient than blanket approaches.
Energy flux controls tetraether lipid cyclization in Sulfolobus acidocaldarius
Authors: Zhou Alice , Chiu Beverly K. , Weber Yuki , Elling Felix J. , Cobban Alec B. , Pearson Ann , Leavitt William D. 
Published: August 2019

SummaryMicroorganisms regulate the composition of their membranes in response to environmental cues. Many archaea maintain the fluidity and permeability of their membranes by adjusting the number of cyclic moieties within the cores of their glycerol dibiphytanyl glycerol tetraether (GDGT) lipids. Cyclized GDGTs increase membrane packing and stability, which has been shown to help cells survive shifts in temperature and pH. However, the extent of this cyclization also varies with growth phase and electron acceptor or donor limitation. These observations indicate a relationship between energy metabolism and membrane composition. Here we show that the average degree of GDGT cyclization increases with doubling time in continuous cultures of the thermoacidophile Sulfolobus acidocaldarius (DSM 639). This is consistent with the behavior of a mesoneutrophile, Nitrosopumilus maritimus SCM1. Together, these results demonstrate that archaeal GDGT distributions can shift in response to electron donor flux and energy availability, independent of pH or temperature. Paleoenvironmental reconstructions based on GDGTs thus capture the energy available to microbes, which encompasses fluctuations in temperature and pH, as well as electron donor and acceptor availability. The ability of Archaea to adjust membrane composition and packing may be an important strategy that enables survival during episodes of energy stress.Significance StatementMicrobial lipid membranes protect and isolate a cell from its environment while regulating the flow of energy and nutrients to metabolic reaction centers within. We demonstrate that membrane lipids change as a function of energy flux using a well-studied archaeon that thrives in acidic hot springs and observe an increase in membrane packing as energy becomes more limited. These observations are consistent with chemostat experiments utilizing a low temperature, neutral pH, marine archaeon. This strategy appears to regulate membrane homeostasis is common across GDGT-producing lineages, demonstrating that diverse taxa adjust membrane composition in response to chronic energy stress.
Complex+: Aided Decision-Making for the Study of Protein Complexes
Authors: Oghbaie Mehrnoosh , Šulc Petr , Fenyö David , Pennock Michael , LaCava John 
Published: August 2019

AbstractProteins are the chief effectors of cell biology and their functions are typically carried out in the context of multi-protein assemblies; large collections of such interacting protein assemblies are often referred to as interactomes. Knowing the constituents of protein complexes is therefore important for investigating their molecular biology. Many experimental methods are capable of producing data of use for detecting and inferring the existence of physiological protein complexes. Each method has associated pros and cons, affecting the potential quality and utility of the data. Numerous informatic resources exist for the curation, integration, retrieval, and processing of protein interactions data. While each resource may possess different merits, none are definitive and few are wieldy, potentially limiting their effective use by non-experts. In addition, contemporary analyses suggest that we may still be decades away from a comprehensive map of a human protein interactome. Taken together, we are currently unable to maximally impact and improve biomedicine from a protein interactome perspective – motivating the development of experimental and computational techniques that help investigators to address these limitations. Here, we present a resource intended to assist investigators in (i) navigating the cumulative knowledge concerning protein complexes and (ii) forming hypotheses concerning protein interactions that may yet lack conclusive evidence, thus (iii) directing future experiments to address knowledge gaps. To achieve this, we integrated multiple data-types/different properties of protein interactions from multiple sources and after applying various methods of regularization, compared the protein interaction networks computed to those available in the EMBL-EBI Complex Portal, a manually curated, gold-standard catalog of macromolecular complexes. As a result, our resource provides investigators with reliable curation of bona fide and candidate physical interactors of their protein or complex of interest, prompting due scrutiny and further validation when needed. We believe this information will empower a wider range of experimentalists to conduct focused protein interaction studies and to better select research strategies that explicitly target missing information.
Refinement and reactivation of a taste-responsive hippocampal network
Authors: Herzog Linnea E. , Katz Donald B. , Jadhav Shantanu P. 
Published: August 2019

SummaryAnimals need to remember the locations of nourishing and toxic food sources for survival, a fact that necessitates a mechanism for associating taste experiences with particular places. We have previously identified such responses within hippocampal place cells [1], the activity of which is thought to aid memory-guided behavior by forming a mental map of an animal’s environment that can be reshaped through experience [2–7]. It remains unknown, however, whether taste-responsiveness is intrinsic to a subset of place cells, or emerges as a result of experience that reorganizes spatial maps. Here, we recorded from neurons in the dorsal CA1 region of rats running for palatable tastes delivered via intra-oral cannulae at specific locations on a linear track. We identified a subset of taste-responsive cells that, even prior to taste exposure, had larger place fields than non-taste-responsive cells overlapping with stimulus delivery zones. Taste-responsive cells’ place fields then contracted, as a result of taste experience, leading to a stronger representation of stimulus delivery zones on the track. Taste-responsive units exhibited increased sharp-wave ripple co-activation during the taste delivery session and subsequent rest periods, which correlated with the degree of place field contraction. Our results reveal that novel taste experience evokes responses within a preconfigured network of taste-responsive hippocampal place cells with large fields, whose spatial representations are refined by sensory experience to signal areas of behavioral salience. This represents a possible mechanism by which animals identify and remember locations where ecologically relevant stimuli are found within their environment.
Machine learning based imputation techniques for estimating phylogenetic trees from incomplete distance matrices
Authors: Bhattacharjee Ananya , Bayzid Md. Shamsuzzoha 
Published: August 2019

AbstractBackgroundDue to the recent advances in sequencing technologies and species tree estimation methods capable of taking gene tree discordance into account, notable progress has been achieved in constructing large scale phylogenetic trees from genome wide data. However, substantial challenges remain in leveraging this huge amount of molecular data. One of the foremost among these challenges is the need for efficient tools that can handle missing data. Popular distance-based methods such as neighbor joining and UPGMA require that the input distance matrix does not contain any missing values.ResultsWe introduce two highly accurate machine learning based distance imputation techniques. One of our approaches is based on matrix factorization, and the other one is an autoencoder based deep learning technique. We evaluate these two techniques on a collection of simulated and biological datasets, and show that our techniques match or improve upon the best alternate techniques for distance imputation. Moreover, our proposed techniques can handle substantial amount of missing data, to the extent where the best alternate methods fail.ConclusionsThis study shows for the first time the power and feasibility of applying deep learning techniques for imputing distance matrices. The autoencoder based deep learning technique is highly accurate and scalable to large dataset. We have made these techniques freely available as a cross-platform software (available at https://github.com/Ananya-Bhattacharjee/ImputeDistances).
Intrinsically ball retrieving wolf puppies reveal standing ancestral variation for human-directed play behaviour
Authors: Wheat Christina Hansen , Temrin Hans 
Published: August 2019

AbstractDomestication dramatically alters phenotypes. Standing variation among ancestral populations often drives phenotypic change during domestication, but some changes are caused by novel mutations. Dogs (Canis familiaris) engage in interspecific play with humans and it has specifically been suggested that the ability to interpret social-communicative behaviour expressed by humans is a novel dog-specific skill. Thus, wolves (Canis lupus) are not expected to engage in interspecific play with a human based on social-communicative cues. Here we report the observation of three eight week-old wolf puppies spontaneously responding to social-communicative behaviours from a stranger by retrieving a ball. This unexpected and novel observation has significant implications for our understanding and expectations of the genetic foundations of dog behaviour. Importantly, our observations indicate that behavioural responses to human social-communicative cues are not unique to dogs. This suggests that, while probably rare, standing variation in the expression of human-directed behaviour in ancestral populations could have been an important target for early selective pressures exerted during dog domestication.
Trueness of digital intraoral impression in reproducing multiple implant position
Authors: Kim Ryan Jin-Young , Benic Goran I. , Park Ji-Man 
Published: August 2019

AbstractThe aim of this study was to evaluate the trueness of 5 intraoral scanners (IOSs) for digital impression of simulated implant scan bodies in a complete-arch model. A 3D printed full-arch mandible model made of Co-Cr with a total of 6 bilaterally positioned cylinders in the canine, second premolar, and second molar area served as the study model. Digital scans of the model were made with a reference scanner (steroSCAN neo) and 5 IOSs (CEREC Omnicam, CS3600, i500, iTero Element, and TRIOS 3) (n=10). For each IOS’s dataset, the XYZ coordinates of the cylinders were obtained from the reference point and the deviations from the reference scanner were calculated using a 3D reverse engineering program (Rapidform). The trueness values were analyzed by Kruskal-Wallis test and Mann-Whitney post hoc test. Direction and amount of deviation differed among cylinder position and among IOSs. Regardless of the IOS type, the cylinders positioned on the left second molar, nearest to the scanning start point, showed the smallest deviation. The deviation generally increased further away from scanning start point towards the right second molar. TRIOS 3 and i500 outperformed the other IOSs for complete-arch digital impression. The accuracy of the CEREC Omnicam, CS3600, and iTero Element were similar on the left side, but they showed more deviations on the right side of the arch when compared to the other IOSs. The accuracy of IOS is still an area that needs to be improved.
The nuclear receptor NR4A1 is regulated by SUMO modification to induce autophagic cell death
Authors: Zárraga-Granados Gabriela , Muciño-Hernández Gabriel , Sánchez-Carbente María R. , Villamizar-Gálvez Wendy , Peñas-Rincón Ana , Arredondo Cristian , Andrés María E. , Wood Christopher , Covarrubias Luis , Castro-Obregón Susana 
Published: August 2019

AbstractNR4A is a nuclear receptor protein family whose members act as sensors of cellular environment and regulate multiple processes such as metabolism, proliferation, migration, apoptosis, and autophagy. Since the ligand binding domains of these receptors have no cavity for ligand interaction, their function is most likely regulated by protein abundance and post-translational modifications. In particular, NR4A1 is regulated by protein abundance, phosphorylation, and subcellular distribution (nuclear-cytoplasmic translocation), and acts both as a transcription factor and as a regulator of other interacting proteins. SUMOylation is a post-translational modification that can affect protein stability, transcriptional activity, alter protein-protein interactions and modify intracellular localization of target proteins. In the present study we evaluated the role of SUMOylation as a posttranslational modification that can regulate the activity of NR4A1 to induce autophagy-dependent cell death. We focused on a model potentially relevant for neuronal cell death and demonstrated that NR4A1 needs to be SUMOylated to induce autophagic cell death. We observed that a triple mutant in SUMOylation sites has reduced SUMOylation, increased transcriptional activity, altered intracellular distribution, and more importantly, its ability to induce autophagic cell death is impaired.Summary StatementThe modification of the nuclear receptor NR4A1 by SUMO regulates its transcriptional activity, intracellular localization and is required to induce autophagic cell death.
Spatial and temporal partitioning and tree preference in California woodland ants
Authors: MacArthur-Waltz Dylan , Nelson Rebecca , Lee Gail , Gordon Deborah M. 
Published: August 2019

AbstractSpatial and temporal partitioning of habitat may facilitate diversity and have important impacts on ant communities. To investigate niche overlap in an ant community in a northern California oak woodland, we observed ant foraging on trees in 4 seasonal surveys, each lasting 2 weeks, in a 9.5-hectare plot over the course of a year. Foraging activity in all 5 observed ant species differed by season, time of day, and/or the genera of trees used. Of the 3 ant species most frequently observed,Camponotus semitestaceuswas most active during spring and summer nights,Formica mokiwas most active during spring and summer days, andPrenolepis impariswas most active during both day and night of fall and winter. All ant species preferred native trees to exotic trees and preferred evergreen trees to deciduous trees. Our results suggest that native evergreen oaks such asQuercus agrifolia, currently threatened by sudden oak death (Phytophthora ramorum), may be important for supporting ant biodiversity.
A single cell transcriptome atlas of the developing zebrafish hindbrain
Authors: Tambalo Monica , Mitter Richard , Wilkinson David G. 
Published: August 2019

AbstractSegmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at bounderies and segment centres, in part mediated by Fgf20 signaling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.
High-pressure nuclear inelastic scattering with backscattering monochromatization
Authors: Sergueev Ilya , Glazyrin Konstantin , Herrmann Markus G. , Alexeev Pavel , Wille Hans-Christian , Leupold Olaf , May Andrew F. , Pandey Tribhuwan , Lindsay Lucas R. , Friese Karen , Hermann Raphael P. 
Published: August 2019

The capability to perform high-pressure low-temperature nuclear inelastic scattering on 125Te and 121Sb with a sapphire backscattering monochromator is presented. This technique was applied to measure nuclear inelastic scattering in TeO2 at pressures up to 10 GPa and temperatures down to 25 K. The evaluated partial Te densities of phonon states were compared with theoretical calculations and with Raman scattering measured under the same conditions. The high-pressure cell developed in this work can also be used for other techniques at pressures up to at least 100 GPa.
ASPW-DRL: assembly sequence planning for workpieces via a deep reinforcement learning approach
Authors: Zhao Minghui , Guo Xian , Zhang Xuebo , Fang Yongchun , Ou Yongsheng 
Published: August 2019

Purpose
This paper aims to automatically plan sequence for complex assembly products and improve assembly efficiency.

Design/methodology/approach
An assembly sequence planning system for workpieces (ASPW) based on deep reinforcement learning is proposed in this paper. However, there exist enormous challenges for using DRL to this problem due to the sparse reward and the lack of training environment. In this paper, a novel ASPW-DQN algorithm is proposed and a training platform is built to overcome these challenges.

Findings
The system can get a good decision-making result and a generalized model suitable for other assembly problems. The experiments conducted in Gazebo show good results and great potential of this approach.

Originality/value
The proposed ASPW-DQN unites the curriculum learning and parameter transfer, which can avoid the explosive growth of assembly relations and improve system efficiency. It is combined with realistic physics simulation engine Gazebo to provide required training environment. Additionally with the effect of deep neural networks, the result can be easily applied to other similar tasks.
Academics’ experience of copyright
Authors: Chauhan Vikee , Willett Peter 
Published: August 2019

PurposeThe purpose of this paper is to obtain a snapshot of attitudes and comprehension of the University of Greenwich (UoG) academics towards copyright and the impact of same on their teaching, complementing this with a survey of the experience of academic librarians (ALs) throughout the UK when dealing with faculty and copyright.Design/methodology/approachTwo questionnaires were created and circulated to capture information from two sampled groups: the UoG academic staff and UK-wide ALs. A total of 55 responses were received to the questionnaire distributed to the former, and 83 responses were received to the questionnaire distributed to the latter.FindingsThe majority of the UoG academics believed they possessed a fair, or better than fair, understanding of copyright, with numerous respondents self-taught on the subject. Nevertheless, a significant number thought they might have broken copyright when teaching, while also revealing the belief that copyright was a limitation on their teaching. The AL survey suggested an average comprehension of copyright among academics, while noting that some of the latter felt a degree of antipathy towards copyright.Originality/valueAlthough focused on a single institution, this study implies that copyright instruction for academic staff needs to be substantially improved, and it suggests the need for greater visibility of training programmes.