bluuebunny/crossref_metadata_2025_split huggingface dataset:
How a mouse licks a spout: Cortex-dependent corrections as the tongue reaches for, and misses, targets
Authors: Bollu Tejapratap , Ito Brendan , Whitehead Sam C. , Kardon Brian , Redd James , Liu Mei Hong , Goldberg Jesse H. 
Published: June 2019

Abstract:Precise tongue control is necessary for drinking, eating, and vocalizing1, 2. Yet because tongue movements are fast and difficult to resolve, neural control of lingual kinematics remains poorly understood. Here we combine kilohertz frame-rate imaging and a deep learning based neural network to resolve 3D tongue kinematics in mice drinking from a water spout. Successful licks required previously unobserved corrective submovements (CSMs) which, like online corrections during primate reaches3–10, occurred after the tongue missed unseen, distant, or displaced targets. Photoinhibition of anterolateral motor cortex (ALM) impaired online corrections, resulting in hypometric licks that missed the spout. ALM neural activity reflected upcoming, ongoing, and past CSMs, as well as errors in predicted spout contact. Though less than a tenth of a second in duration, a single mouse lick exhibits hallmarks of online motor control associated with a primate reach, including cortex-dependent corrections after misses.
Structuring the unstructured: estimating species-specific absence from multi-species presence data to inform pseudo-absence selection in species distribution models
Authors: Croft Simon , Smith Graham C. 
Published: June 2019

AbstractSpecies distribution models (SDMs) are an increasingly popular tool in ecology which, together with a vast wealth of data from citizen science projects, have the potential to dramatically improve our understanding of species behaviour for applications such as conservation and wildlife management. However, many of the best performing models require information regarding survey effort, specifically absence, which is typically lacking in opportunistic datasets. To facilitate the use of such models, pseudo-absences from locations without recorded presence must be assumed. Several studies have suggested that survey effort, and hence likely absence, could be estimated from presence-only data by considering records across “target groups” of species defined according to taxonomy.We performed a probabilistic analysis, computing the conditional probability of recording a species given a particular set of species are also recorded, to test the validity of defining target groups by taxonomic order and to explore other potential groupings. Based on this quantification of recording associations we outline a new method to inform pseudo-absence selection comparing predictive performance, measured the area under curve (AUC) statistic, against the standard method of selection across a series of SDMs.Our findings show some support for target grouping classification based on taxonomy but indicate that an alternative classification using survey method may be more appropriate for informing effort and consequently absence. Across 49 terrestrial mammal species, pseudo-absence selection using our proposed method outperformed that of the standard method showing an improvement in the predictive performance of presence-absence models for 17 out of 22 with sufficient data to elicit a significant difference. Based on our method we also observed a substantial improvement in the performance of presence-absence models compared to that of presence-only models (MaxEnt) with a higher AUC for all 22 species showing a significant difference between approaches.We conclude that our method produces sensible robust pseudo-absences which either compliment patterns in known presences or, where conflicts occur, are explainable in terms of ecological variables potentially improving our understanding of species behaviour. Furthermore, we suggest that presence-absence models using these pseudo-absences provide a viable alternative to MaxEnt when modelling using presence-only data.
A powerful and flexible tool for rapid and accurate differential expression and alternative splicing analysis of RNA-seq data for biologists
Authors: Guo Wenbin , Tzioutziou Nikoleta , Stephen Gordon , Milne Iain , Calixto Cristiane , Waugh Robbie , Brown John W. S. , Zhang Runxuan 
Published: June 2019

AbstractRNA-seq analysis of gene expression and alternative splicing should be routine and robust but is often a bottleneck for biologists because of reliance on specialized bioinformatics skills. Thus, we have developed “3D RNA-seq”, an R shiny App and web based service which provides an easy-to-use, flexible and powerful tool for three-component analysis of RNA-seq data: Differential Expression, Differential Alternative Splicing and Differential Transcript Usage. 3D RNA-seq integrates state-of-the-art, highly rated differential expression analysis tools and adopts best practice for RNA-seq analysis. It operates through a user-friendly graphical interface, can handle complex experimental designs, allows setting of statistical parameters, tracks results through graphics and tables, and generates figures and a comprehensive report that will guarantee reproducibility. 3D RNA-seq can be applied to any species and is designed to be run by biologists with no programming skills (or by bioinformaticians) allowing lab scientists to perform rapid and accurate analysis of RNA-seq data.
Inhibition stabilization is a widespread property of cortical networks
Authors: Sanzeni A. , Akitake B. , Goldbach H. C. , Leedy C. E. , Brunel N. , Histed M. H. 
Published: June 2019

AbstractMany cortical network models use recurrent coupling strong enough to require inhibition for stabilization. Yet it has been experimentally unclear whether inhibition-stabilized network (ISN) models describe cortical function well across areas and states. Here we test several ISN predictions, including the counterintuitive (paradoxical) suppression of inhibitory firing in response to optogenetic inhibitory stimulation. We find clear evidence for ISN operation in mouse visual, somatosensory, and motor cortex. Simple two-population ISN models describe the data well and let us quantify coupling strength. Though some models predict a non-ISN to ISN transition with increasingly strong sensory stimuli, we find ISN effects without sensory stimulation and even during light anesthesia. Additionally, average paradoxical effects result only with transgenic, not viral, opsin expression in parvalbumin (PV)-positive neurons; theory and expression data show this is consistent with ISN operation. Taken together, these results show strong coupling and inhibition stabilization are common features of cortex.
Defense hormones modulate root microbiome diversity and composition in tomato
Authors: French Elizabeth , Ghaste Manoj , Widhalm Joshua R. , Iyer-Pascuzzi Anjali S. 
Published: June 2019

ABSTRACTPlant roots live closely associated with soil microbes. Understanding how roots defend against pathogenic microbes while associating with non-pathogenic microbes is critical to using root microbiomes for successful outcomes. The aim of this study was to determine the contribution of the plant defense hormones ethylene (ET), jasmonic acid (JA), and salicylic acid (SA) to the tomato root microbiome. We used 16S rRNA amplicon sequencing to examine the root microbiome of four tomato genotypes defective in three hormone pathways. We found that ET and SA pathways, but not JA, were critical for root endosphere microbial alpha (α)-diversity. Root endosphere communities of ACD, deficient in a precursor of ET, and the SA-deficient NahG transgenic, had significantly less α-diversity than wild-type tomatoes. NahG and ACD root endosphere enrichment profiles were similar and driven by two taxa. In NahG, ACD, and in a panel of 24 wild-type tomatoes, the abundance of these two taxa was correlated with lower root endosphere α-diversity. The abundance of these taxa was also moderately negatively correlated with the level of SA in roots. Our results suggest that SA and ET pathways contribute to tomato root endosphere diversity by modulating the abundance of specific bacterial taxa.
Perceived Barriers in Accessing Sexual and Reproductive Health Services for Youth in Lao People’s Democratic Republic
Authors: Thongmixay Souksamone , Essink Dirk Rombout , de Greeuw Tim , Vongxay Viengnakhone , Sychareun Vanphanom , Broerse Jacqueline E.W. 
Published: June 2019

AbstractBackgroundSexual activity during youth is common in Lao PDR. However, young people seldom utilize sexual and reproductive health services and subsequently suffer from poor sexual and reproductive health. The aim of this qualitative study was to explore the barriers perceived by youth that prevent their access to sexual and reproductive health services.MethodsTwenty-nine semi-structured interviews were conducted with 22 participants aged 15-25 years, from urban and rural areas. A vignette was used during interviews with those who had no experience with sexual and reproductive health services. Additionally, seven semi-structured interviews were conducted with health providers from youth-friendly health clinics and from public sexual and reproductive health services. Data were analyzed using a thematic approach.ResultsThe main barriers preventing young people from accessing sexual and reproductive health services were related tocognitive accessibilityandpsychosocial accessibility. Thecognitive accessibilitybarriers were a lack of sexual knowledge and a lack of awareness of services. Perceived barriers inpsychosocial accessibilitywere the feelings of shyness and shame caused by negative cultural attitudes to premarital sex, and the fear of parents finding out about visits to public sexual and reproductive health services, due to lack of confidentiality in the services and among health providers. In addition, the barriers ofgeographical accessibility, mainly insufficient availability of youth-friendly health clinics.ConclusionTo improve access to services, a multi-component strategy is needed: promotion of youth-friendly health clinics; sexual education in schools; a formal referral system between schools and youth-friendly health clinics; and community support interventions. Prior to implementation, more research should be done on the applicability of these methods in the Laos context. Future research should try to determine the cost-effectiveness of youth-friendly health clinics integrated in a district hospital and stand-alone clinics, to provide insight into which form should be further developed.
A delay in sampling information from temporally autocorrelated visual stimuli
Authors: Callahan-Flintoft Chloe , Holcombe Alex O. , Wyble Brad 
Published: June 2019

AbstractMuch of our world changes smoothly in time, yet the allocation of attention is typically studied with sudden changes – transients. When stimuli change gradually there is a sizeable lag between when a cue is presented and when an object is sampled (Carlson, Hogendoorn, & Verstraten, 2006; Sheth, Nijhawan & Shimojo, 2000). Yet this lag is not seen with rapid serial visual presentation (RSVP) stimuli where temporally uncorrelated stimuli are presented (Vul, Kanwisher & Nieuwenstein 2008; Goodbourn & Holcombe, 2015). These findings collectively suggest that temporal autocorrelation of a feature paradoxically increases the latency at which information is sampled. This hypothesis was tested by comparing stimuli changing smoothly in time (autocorrelated) to stimuli that change randomly. Participants attempted to report the color coincident with a visual cue. The result was a smaller selection lag for the randomly varying condition relative to the condition with a smooth color trajectory. Our third experiment finds that the increase in selection latency is due to the smoothness of the color change after the cue rather than extrapolated predictions based on the color changes presented before the cue. Together, these results support a theory of attentional drag, whereby attention remains engaged at a location longer when features are changing smoothly. A computational model provides insights into neural mechanisms that might underlie the effect.
Extracellular matrix micropatterning technology for whole cell cryogenic electron microscopy studies
Authors: Engel Leeya , Gaietta Guido , Dow Liam P. , Swift Mark F. , Pardon Gaspard , Volkmann Niels , Weis William I. , Hanein Dorit , Pruitt Beth L. 
Published: June 2019

ABSTRACTCryogenic electron tomography is the highest resolution tool available for structural analysis of macromolecular organization inside cells. Micropatterning of extracellular matrix (ECM) proteins is an established in vitro cell culture technique used to control cell shape. Recent traction force microscopy studies have shown correlation between cell morphology and the regulation of force transmission. However, it remains unknown how cells sustain increased strain energy states and localized stresses at the supramolecular level. Here, we report a technology to enable direct observation of mesoscale organization in epithelial cells under morphological modulation, using a maskless protein photopatterning method to confine cells to ECM micropatterns on electron microscopy substrates. These micropatterned cell culture substrates can be used in mechanobiology research to correlate changes in nanometer-scale organization at cell-cell and cell-ECM contacts to strain energy states and traction stress distribution in the cell.
Occupancy distributions of membrane proteins in heterogeneous liposome populations
Authors: Cliff Lucy , Chadda Rahul , Robertson Janice L. 
Published: June 2019

AbstractMeasurements of membrane protein structure and function often rely on reconstituting the protein into lipid bilayers through the formation of liposomes. Many measurements conducted in proteoliposomes, e.g. transport rates, single-molecule dynamics, monomer-oligomer equilibrium, require some understanding of the occupancy statistics of the liposome population for correct interpretation of the results. In homogenous liposomes, this is easy to calculate as the act of protein incorporation can be described by the Poisson distribution. However, in reality, liposomes are heterogeneous, which alters the statistics of occupancy in several ways. Here, we determine the liposome occupancy distribution for membrane protein reconstitution while taking into account liposome size heterogeneity. We calculate the protein occupancy for a homogenous population of liposomes with radiusr= 200 nm, representing an idealization of vesicles extruded through 400 nm pores and compare it to the right-skewed distribution of 400 nm 2:1 POPE:POPG vesicles. As is the case forE. colipolar lipids, this synthetic composition yields a sub-population of small liposomes, ∼25 nm in radius with a long tail of larger vesicles. Previously published microscopy data of the co-localization of the CLC-ec1 Cl-/H+transporter with liposomes, and vesicle occupancy measurements using functional transport assays, shows agreement with the heterogeneous 2:1 POPE:POPG population. Next, distributions of 100 nm and 30 nm extruded 2:1 POPE:POPG liposomes are measured by cryo-electron microscopy, demonstrating that extrusion through smaller pores does not shift the peak, but reduces polydispersity arising from large liposomes. Single-molecule photobleaching analysis of CLC-ec1-Cy5 shows the 30 nm extruded population increases the ‘Poisson-dilution’ range, reducing the probability of vesicles with more than one protein at higher protein/lipid densities. These results demonstrate that the occupancy distributions of membrane proteins into vesicles can be accurately predicted in heterogeneous populations with experimental knowledge of the liposome size distribution.
Neanderthal-Denisovan ancestors interbred with a distantly-related hominin
Authors: Rogers Alan R. , Harris Nathan S. , Achenbach Alan A. 
Published: June 2019

Previous research has shown that modern Eurasians interbred with their Neanderthal and Denisovan predecessors. We show here that hundreds of thousands of years earlier, the ancestors of Neanderthals and Denisovans interbred with their own Eurasian predecessors—members of a “superarchaic” population that separated from other humans about 2 mya. The superarchaic population was large, with an effective size between 20 and 50 thousand individuals. We confirm previous findings that: (1) Denisovans also interbred with superarchaics, (2) Neanderthals and Denisovans separated early in the middle Pleistocene, (3) their ancestors endured a bottleneck of population size, and (4) the Neanderthal population was large at first but then declined in size. We provide qualified support for the view that (5) Neanderthals interbred with the ancestors of modern humans.One-sentence summaryWe document the earliest known interbreeding between ancient human populations and an expansion out of Africa early in the middle Pleistocene.
Glycogen metabolism jump-starts photosynthesis through the oxidative pentose phosphate pathway (OPPP) in cyanobacteria
Authors: Shinde Shrameeta , Singapuri Sonali P. , Zhang Xiaohui , Kalra Isha , Liu Xianhua , Morgan-Kiss Rachael M. , Wang Xin 
Published: June 2019

AbstractCyanobacteria experience drastic changes in their carbon metabolism under daily light-dark cycles. In the light, the Calvin-Benson cycle fixes CO2and divert excess carbon into glycogen storage. At night, glycogen is degraded to support cellular respiration. Dark-light transition represents a universal environmental stress for cyanobacteria and other photosynthetic lifeforms. Recent studies in the field revealed the essential genetic background necessary for the fitness of cyanobacteria during diurnal growth. However, the metabolic engagement behind the dark-light transition is not well understood. In this study, we discovered that glycogen metabolism can jump-start photosynthesis in the cyanobacteriumSynechococcus elongatusPCC 7942 when photosynthesis reactions start upon light. Compared to the wild type, the glycogen mutant (ΔglgC) showed much lower photosystem II efficiency and slower photosystem I-mediated cyclic electron flow rate when photosynthesis starts. Proteomics analyses indicated that glycogen is degraded through the oxidative pentose phosphate pathway (OPPP) during dark-light transition. We confirmed that the OPPP is essential for the initiation of photosynthesis, and further showed that glycogen degradation through the OPPP is likely to contribute to the activation of key Calvin-Benson cycle enzymes by modulating NADPH levels during the transition period. This ingenious strategy helps jump-start photosynthesis in cyanobacteria following dark respiration, and stabilize the Calvin-Benson cycle under fluctuating environmental conditions. It has evolutionary advantages for the survival of photosynthetic organisms using the Calvin-Benson cycle for carbon fixation.
High-throughput transmission electron microscopy with automated serial sectioning
Authors: Graham Brett J. , Hildebrand David Grant Colburn , Kuan Aaron T. , Maniates-Selvin Jasper T. , Thomas Logan A. , Shanny Brendan L. , Lee Wei-Chung Allen 
Published: June 2019

AbstractTransmission electron microscopy (TEM) is an essential tool for studying cells and molecules. We present a tape-based, reel-to-reel pipeline that combines automated serial sectioning with automated high-throughput TEM imaging. This acquisition platform provides nanometer-resolution imaging at fast rates for a fraction of the cost of alternative approaches. We demonstrate the utility of this imaging platform for generating datasets of biological tissues with a focus on examining brain circuits.
General and robust covalently linked graphene oxide affinity grids for high-resolution cryo-EM
Authors: Wang Feng , Liu Yanxin , Yu Zanlin , Li Sam , Cheng Yifan , Agard David A. 
Published: June 2019

AbstractDespite their great potential to facilitate rapid preparation of quite impure samples, affinity grids have not yet been widely employed in single particle cryo-EM. Here, we chemically functionalize graphene oxide coated grids and use a highly specific covalent affinity tag system. Importantly, our polyethylene glycol spacer keeps particles away from the air-water interface and graphene oxide surface, protecting them from denaturation or aggregation and permits high-resolution reconstructions of small particles.
PI3K/AKT inhibition in tumor propagating cells of DLBCL reverses R-CHOP resistance by destabilizing SOX2
Authors: Chen Jianfeng , Ge Xiaowen , Zhang Wei , Ding Peipei , Du Yiqun , Wang Qi , Li Ling , Fang Lan , Sun Yujing , Zhang Pingzhao , Zhou Yuzhen , Zhang Long , Lv Xinyue , Li Luying , Zhang Xin , Zhang Qunling , Xue Kai , Gu Hongyu , Lei Qunying , Wong Jiemin , Hu Weiguo 
Published: June 2019

AbstractDrug resistance is a major obstacle for the success of conventional anticancer therapy, and the development of drug resistance is at least partly attributed to tumor propagating cells (TPCs). Up to one-third of diffuse large B cell lymphoma (DLBCL) patients eventually develop resistance to R-CHOP regimen. We found that the TPC proportion was remarkably increased in resistant germinal center B cell-like (GCB) and activated B cell-like (ABC) DLBCL subtypes. Elevated SOX2 was the determinant for resistance development, and SOX2 was phosphorylated by activated PI3K/AKT1 signaling, thus preventing ubiquitin-mediated SOX2 degradation. Furthermore, multiple factors, including BCR, integrins, chemokines and FGFR1/2 signaling, regulated PI3K/AKT1 activation. CDK6 in the GCB subtype and FGFR1/2 in the ABC subtype were SOX2 targets in the PI3K/AKT1 pathway. Chemical inhibition of PI3K/AKT1 in both subtypes, CDK6 in the GCB subtype, and FGFR1/2 in the ABC subtype significantly enhanced the susceptibility of resistant cells to CHO treatment. More importantly, PI3K and FGFR1/2 inhibitors but not a CDK6 inhibitor effectively suppressed the tumor growth of R-CHO-resistant DLBCL cells, most likely by converting TPCs to chemo-sensitive differentiated cells. Therefore, this pro-differentiation therapy against TPCs warrants further study in clinical trials for the treatment of resistant DLBCL.
High Spatial Resolution Ambient Ionization Mass Spectrometry Imaging Using Microscopy Image Fusion Determines Tumor Margins
Authors: Lin Li-En , Chen Chih-Lin , Huang Ying-Chen , Chung Hsin-Hsiang , Lin Chiao-Wei , Chen Ko-Chien , Peng Yu-Ju , Ding Shih-Torng , Wang Ming-Yang , Shen Tang-Long , Hsu Cheng-Chih 
Published: June 2019

AbstractMass spectrometry imaging (MSI) using ambient ionization technique enables a direct chemical investigation of biological samples with minimal sample pretreatment. However, detailed morphological information of the sample is often lost due to its limited spatial resolution. In this study, predictive high-resolution molecular imaging was produced by the fusion of ambient ionization MSI with optical microscopy of routine hematoxylin and eosin (H&E) staining produces. Specifically, desorption electrospray ionization (DESI) and nanospray desorption electrospray ionization (nanoDESI) mass spectrometry are employed to visualize lipid and protein species on mice tissue sections. The resulting molecular distributions obtained by ambient ionization MSI-microscopy fusion are verified with matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) MSI and immunohistochemistry (IHC) staining. Label-free molecular imaging with 5-μm spatial resolution can be acquired using DESI and nanoDESI, whereas the typical spatial resolution of ambient ionization MSI is ~100 μm. In this regard, sharpened molecular histology of tissue sections is achieved, providing complementary references to the pathology. Such a multimodality integration enables the discovery of potential tumor biomarkers. After image fusion, more than a dozen of potential biomarkers that could be used to determine the tumor margins on a metastatic mouse lung tissue section and Luminal B breast tumor tissue section are identified.