bluuebunny/crossref_metadata_2025 huggingface dataset:
The failure of stellar feedback, magnetic fields, conduction, and morphological quenching in maintaining red galaxies
Authors: Su Kung-Yi , Hopkins Philip F , Hayward Christopher C , Ma Xiangcheng , Faucher-Giguère Claude-André , Kereš Dušan , Orr Matthew E , Chan T K , Robles Victor H
Published: June 2019

The quenching ‘maintenance’ and related ‘cooling flow’ problems are important in galaxies from Milky Way mass through clusters. We investigate this in haloes with masses ∼$10^{12}\!-\!10^{14}\, {\rm M}_{\odot }$, using non-cosmological high-resolution hydrodynamic simulations with the FIRE-2 (Feedback In Realistic Environments) stellar feedback model. We specifically focus on physics present without AGN, and show that various proposed ‘non-AGN’ solution mechanisms in the literature, including Type Ia supernovae, shocked AGB winds, other forms of stellar feedback (e.g. cosmic rays), magnetic fields, Spitzer–Braginskii conduction, or ‘morphological quenching’ do not halt or substantially reduce cooling flows nor maintain ‘quenched’ galaxies in this mass range. We show that stellar feedback (including cosmic rays from SNe) alters the balance of cold/warm gas and the rate at which the cooled gas within the galaxy turns into stars, but not the net baryonic inflow. If anything, outflowing metals and dense gas promote additional cooling. Conduction is important only in the most massive haloes, as expected, but even at ∼$10^{14}\, {\rm M}_{\odot }$ reduces inflow only by a factor ∼2 (owing to saturation effects and anisotropic suppression). Changing the morphology of the galaxies only slightly alters their Toomre-Q parameter, and has no effect on cooling (as expected), so has essentially no effect on cooling flows or maintaining quenching. This all supports the idea that additional physics, e.g. AGN feedback, must be important in massive galaxies.
WashU Epigenome Browser update 2019
Authors: Li Daofeng , Hsu Silas , Purushotham Deepak , Sears Renee L , Wang Ting
Published: June 2019

The WashU Epigenome Browser (https://epigenomegateway.wustl.edu/) provides visualization, integration and analysis tools for epigenomic datasets. Since 2010, it has provided the scientific community with data from large consortia including the Roadmap Epigenomics and the ENCODE projects. Recently, we refactored the codebase, redesigned the user interface, and developed various novel features. New features include: (i) visualization using virtual reality (VR), which has implications in biology education and the study of 3D chromatin structure; (ii) expanded public data hubs, including data from the 4DN, ENCODE, Roadmap Epigenomics, TaRGET, IHEC and TCGA consortia; (iii) a more responsive user interface; (iv) a history of interactions, which enables undo and redo; (v) a feature we call Live Browsing, which allows multiple users to collaborate remotely on the same session; (vi) the ability to visualize local tracks and data hubs. Amazon Web Services also hosts the redesign at https://epigenomegateway.org/.
Unpacking the Drivers of Racial Disparities in School Suspension and Expulsion
Authors: Owens Jayanti , McLanahan Sara S
Published: June 2019

School suspension and expulsion are important forms of punishment that disproportionately affect Black students, with long-term consequences for educational attainment and other indicators of wellbeing. Prior research identifies three mechanisms that help account for racial disparities in suspension and expulsion: between-school sorting, differences in student behaviors, and differences in the treatment and support of students with similar behaviors. We extend this literature by (1) comparing the contributions of these three mechanisms in a single study, (2) assessing behavior and school composition when children enter kindergarten and before most are exposed to school discipline, and (3) using both teacher and parent reports of student behaviors. Decomposition analyses reveal that differential treatment and support account for 46 percent of the Black/White gap in suspension/expulsion, while between-school sorting and differences in behavior account for 21 percent and 9 percent of the gap respectively. Results are similar for boys and girls and robust to the use of school fixed effects and measures of school composition and student behavior at ages 5 and 9. Theoretically, our findings highlight differential treatment/support after children enter school as an important but understudied mechanism in the early criminalization of Black students.
Neural reward processing in self-reported short sleepers: examination of gambling task brain activation in the Human Connectome Project database
Authors: Curtis Brian J , Williams Paula G , Anderson Jeffrey S
Published: June 2019

Study Objectives

Much of what we assume about the effects of short sleep duration on neural reward processing derives from total sleep deprivation studies. Although total sleep deprivation appears rare, habitual short sleep is common: 30% of working US adults report habitually sleeping ≤ 6 hours/night. It remains largely unknown whether habitual short sleepers exhibit similar reward processing brain activation patterns to those observed following total sleep deprivation in prior studies. Therefore, our aim was to test objectively reward processing brain activation patterns associated with self-reported habitual short sleep duration in a large sample.

Methods

Nine hundred and fifty-two adult participants from the Human Connectome Project database were grouped on reported habitual short (≤6 hours) vs. medium-length (7–9 hours) sleep duration using the Pittsburgh Sleep Quality Index (PSQI). Reward processing brain activation was examined using a gambling task during functional magnetic resonance imaging (fMRI). Subject-level covariates for age, sex, continuous sleep duration, daytime dysfunction, and PSQI total score are provided as supplemental analyses.

Results

Brain activation patterns revealed expected reward processing-related activation for age and sex. However, activation for sleep duration, dysfunction, and PSQI score did not correspond to those evident in previous total sleep deprivation studies.

Conclusions

Self-reported short sleep duration, perceived sleep-related dysfunction, and sleep quality via PSQI do not appear to be meaningfully associated with activation in well-described regions of the human neurobiological reward circuit. As these findings are counter to prior results using experimental sleep deprivation, future work focused on more direct comparisons between self-reported sleep variables and experimental sleep deprivation appears warranted.
Temporal Profile of Transporter mRNA Expression in the Brain after Traumatic Brain Injury in Developing Rats
Authors: Adams Solomon M. , Hagos Fanuel T. , Cheng Jeffrey P. , Clark Robert S. B. , Kochanek Patrick M. , Kline Anthony E. , Poloyac Samuel M. , Empey Philip E.
Published: June 2019

Traumatic brain injury (TBI) is a leading cause of death in children and young adults; however, new pharmacologic approaches have failed to improve outcomes in clinical trials. Transporter proteins are central to the maintenance of homeostasis within the neurovascular unit, and regulate drug penetration into the brain. Our objective was to measure transporter temporal changes in expression in the hippocampus and cortex after experimental TBI in developing rats. We also evaluated the expression of transporters in brain, liver, and kidney across the age spectrum in both pediatric and adult rats. Eighty post-natal day (PND)-17 rats and four adult rats were randomized to receive controlled cortical impact (CCI), sham surgery, or no surgery. mRNA transcript counts for 27 ATP-binding cassette and solute carrier transporters were measured in the hippocampus, cortex, choroid plexus, liver, and kidney at 3h, 12h, 24h, 72h, 7d, and 14d post injury. After TBI, the expression of many transporters (Abcc2, Slc15a2, Slco1a2) decreased significantly in the first 24 hours, with a return to baseline over 7-14 days. Some transporters (Abcc4, Abab1a/b, Slc22a4) showed a delayed increase in expression. Baseline expression of transporters was of a similar order of magnitude in brain tissues relative to liver and kidney. Findings suggest that transporter-regulated processes may be impaired in the brain early after TBI and are potentially involved in the recovery of the neurovascular unit. Our data also suggest that transport-dependent processes in the brain are of similar importance as those seen in organs involved in drug metabolism and excretion.

Significance Statement

Baseline transporter mRNA expression in the central nervous system is of similar magnitude as liver and kidney, and experimental traumatic brain injury is associated with acute decrease in expression of several transporters, while others show delayed increase or decrease in expression. Pharmacotherapy following traumatic brain injury should consider potential pharmacokinetic changes associated with transporter expression.
Exponentially few RNA structures are designable
Authors: Yao Hua-Ting , Regnier Mireille , Chauve Cedric , Ponty Yann
Published: June 2019

The problem of RNA design attempts to construct RNA sequences that perform a predefined biological function, identified by several additional constraints. One of the foremost objective of RNA design is that the designed RNA sequence should adopt a predefined target secondary structure preferentially to any alternative structure, according to a given metrics and folding model. It was observed in several works that some secondary structures are undesignable, i.e. no RNA sequence can fold into the target structure while satisfying some criterion measuring how preferential this folding is compared to alternative conformations.

In this paper, we show that the proportion of designable secondary structures decreases exponentially with the size of the target secondary structure, for various popular combinations of energy models and design objectives. This exponential decay is, at least in part, due to the existence of undesignable motifs, which can be generically constructed, and jointly analyzed to yield asymptotic upper-bounds on the number of designable structures.
A Versatile Robotic Platform for the Design of Natural, Three-Dimensional Reaching and Grasping Tasks in Monkeys
Authors: Barra B , Badi M , Perich MG , Conti S , Salehian SS Mirrazavi , Moreillon F , Wurth S , Kaeser M , Passeraub P , Milekovic T , Billard A , Micera S , Capogrosso M
Published: June 2019

Translational studies on motor control and neurological disorders require detailed monitoring of sensorimotor components of natural limb movements in relevant animal models. However, available experimental tools do not provide a sufficiently rich repertoire of behavioral signals. Here, we developed a robotic platform that enables the monitoring of kinematics, interaction forces, and neurophysiological signals during user-definable upper limb tasks for monkeys. We configured the platform to position instrumented objects in a three-dimensional workspace and provide an interactive dynamic force-field. We show the relevance of our platform for fundamental and translational studies with three example applications. First, we study the kinematics of natural grasp in response to variable interaction forces. We then show simultaneous and independent encoding of kinematic and forces in single unit intra-cortical recordings from sensorimotor cortical areas. Lastly, we demonstrate the relevance of our platform to develop clinically relevant brain computer interfaces in a kinematically unconstrained motor task
Decoding the development of the blood and immune systems during human fetal liver haematopoiesis
Authors: Popescu Dorin-Mirel , Botting Rachel A. , Stephenson Emily , Green Kile , Jardine Laura , Calderbank Emily F. , Efremova Mirjana , Acres Meghan , Maunder Daniel , Vegh Peter , Goh Issac , Gitton Yorick , Park Jongeun , Polanski Krzysztof , Vento-Tormo Roser , Miao Zhichao , Rowell Rachel , McDonald David , Fletcher James , Dixon David , Poyner Elizabeth , Reynolds Gary , Mather Michael , Moldovan Corina , Mamanova Lira , Greig Frankie , Young Matthew , Meyer Kerstin , Lisgo Steven , Bacardit Jaume , Fuller Andrew , Millar Ben , Innes Barbara , Lindsay Susan , Stubbington Michael J. T. , Kowalczyk Monika S. , Li Bo , Ashenbrg Orr , Tabaka Marcin , Dionne Danielle , Tickle Timothy L. , Slyper Michal , Rozenblatt-Rosen Orit , Filby Andrew , Villani Alexandra-Chloe , Roy Anindita , Regev Aviv , Chedotal Alain , Roberts Irene , Göttgens Berthold , Laurenti Elisa , Behjati Sam , Teichmann Sarah A. , Haniffa Muzlifah
Published: June 2019

Definitive haematopoiesis in the fetal liver supports self-renewal and differentiation of haematopoietic stem cells/multipotent progenitors (HSC/MPPs), yet remains poorly defined in humans. Using single cell transcriptome profiling of ~133,000 fetal liver and ~65,000 fetal skin and kidney cells, we identify the repertoire of blood and immune cells in first and early second trimesters of development. From this data, we infer differentiation trajectories from HSC/MPPs, and evaluate the impact of tissue microenvironment on blood and immune cell development. We predict coupling of mast cell differentiation with erythro-megakaryopoiesis and identify physiological erythropoiesis in fetal skin. We demonstrate a shift in fetal liver haematopoietic composition during gestation away from being erythroid-predominant, accompanied by a parallel change in HSC/MPP differentiation potential, which we functionally validate. Our integrated map of fetal liver haematopoiesis provides a blueprint for the study of paediatric blood and immune disorders, and a valuable reference for understanding and harnessing the therapeutic potential of HSC/MPPs.
A feedback loop of conditionally stable circuits drives the cell cycle from checkpoint to checkpoint
Authors: Deritei Dávid , Rozum Jordan , Regan Erzsébet Ravasz , Albert Réka
Published: June 2019

We perform logic-based network analysis on a model of the mammalian cell cycle. This model is composed of a Restriction Switch driving cell cycle commitment and a Phase Switch driving mitotic entry and exit. By generalizing the concept of stable motif, i.e., a self-sustaining positive feedback loop that maintains an associated state, we introduce the concept of conditionally stable motif, the stability of which is contingent on external conditions. We show that the stable motifs of the Phase Switch are contingent on the state of three nodes through which it receives input from the rest of the network. Biologically, these conditions correspond to cell cycle checkpoints. Holding these nodes locked (akin to a checkpoint-free cell) transforms the Phase Switch into an autonomous oscillator that robustly toggles through the cell cycle phases G1, G2 and mitosis. The conditionally stable motifs of the Phase Switch Oscillator are organized into an ordered sequence, such that they serially stabilize each other but also cause their own destabilization. Along the way they channel the dynamics of the module onto a narrow path in state space, lending robustness to the oscillation. Self-destabilizing conditionally stable motifs suggest a general negative feedback mechanism leading to sustained oscillations.
micrIO: An Open-Source Autosampler and Fraction Collector for Automated Microfluidic Input-Output
Authors: Longwell Scott A. , Fordyce Polly M.
Published: June 2019

Microfluidic devices are an empowering technology for many labs, enabling a wide range of applications spanning high-throughput encapsulation, molecular separations, and long-term cell culture. In many cases, however, their utility is limited by a ‘world-to-chip’ barrier that makes it difficult to serially interface samples with these devices. As a result, many researchers are forced to rely on low-throughput, manual approaches for managing device input and output (IO) of samples, reagents, and effluent. Here, we present a hardware-software platform for automated microfluidic IO (micrIO). The platform, which is uniquely compatible with positive-pressure microfluidics, comprises an ‘AutoSipper’ for input and a Fraction Collector for output. To facilitate wide-spread adoption, both are open-source builds constructed from components that are readily purchased online or fabricated from included design files. The software control library, written in Python, allows the platform to be integrated with existing experimental setups and to coordinate IO with other functions such as valve actuation and assay imaging. We demonstrate these capabilities by coupling both the AutoSipper and Fraction Collector to a microfluidic device that produces beads with distinct spectral codes, and an analysis of the collected bead fractions establishes the ability of the platform to draw from and output to specific wells of multiwell plates with no detectable cross-contamination between samples.
The Mastery Rubric for Bioinformatics: supporting design and evaluation of career-spanning education and training
Authors: Tractenberg Rochelle E. , Lindvall Jessica M. , Attwood Teresa K. , Via Allegra
Published: June 2019

As the life sciences have become more data intensive, the pressure to incorporate the requisite training into life-science education and training programs has increased. To facilitate curriculum development, various sets of (bio)informatics competencies have been articulated; however, these have proved difficult to implement in practice. Addressing this issue, we have created a curriculum-design and -evaluation tool to support the development of specific Knowledge, Skills and Abilities (KSAs) that reflect the scientific method and promote both bioinformatics practice and the achievement of competencies. Twelve KSAs were extracted via formal analysis, and stages along a developmental trajectory, from uninitiated student to independent practitioner, were identified. Demonstration of each KSA by a performer at each stage was initially described (Performance Level Descriptors, PLDs), evaluated, and revised at an international workshop. This work was subsequently extended and further refined to yield the Mastery Rubric for Bioinformatics (MR-Bi). The MR-Bi was validated by demonstrating alignment between the KSAs and competencies, and its consistency with principles of adult learning. The MR-Bi tool provides a formal framework to support curriculum building, training, and self-directed learning. It prioritizes the development of independence and scientific reasoning, and is structured to allow individuals (regardless of career stage, disciplinary background, or skill level) to locate themselves within the framework. The KSAs and their PLDs promote scientific problem formulation and problem solving, lending the MR-Bi durability and flexibility. With its explicit developmental trajectory, the tool can be used by developing or practicing scientists to direct their (and their team’s) acquisition of new, or to deepen existing, bioinformatics KSAs. The MR-Bi can thereby contribute to the cultivation of a next generation of bioinformaticians who are able to design reproducible and rigorous research, and to critically analyze results from their own, and others’, work.
Low Abundance of Circulating Tumor DNA in Localized Prostate Cancer
Authors: Hennigan S. Thomas , Trostel Shana Y. , Terrigino Nicholas T. , Voznesensky Olga S. , Schaefer Rachel J. , Whitlock Nichelle C. , Wilkinson Scott , Carrabba Nicole V. , Atway Rayann , Shema Steven , Lake Ross , Sweet Amalia R. , Einstein David J. , Karzai Fatima , Gulley James L. , Chang Peter , Bubley Glenn J. , Balk Steven P. , Ye Huihui , Sowalsky Adam G.
Published: June 2019

Despite decreased screening-based detection of clinically insignificant tumors, most diagnosed prostate cancers are still indolent, indicating a need for better strategies for detection of clinically significant disease prior to treatment. We hypothesized that patients with detectable circulating tumor DNA (ctDNA) were more likely to harbor aggressive disease. We applied ultra-low pass whole genome sequencing to profile cell-free DNA from 112 patients diagnosed with localized prostate cancer and performed targeted resequencing of plasma DNA for somatic mutations previously identified in matched solid tumor in nine cases. We also performed similar analyses on patients with metastatic prostate cancer. In all cases of localized disease, even in clinically high-risk patients who subsequently recurred, we did not detect ctDNA by either method in plasma acquired before surgery or before recurrence. In contrast, ctDNA was detected from patients with metastatic disease. Our findings demonstrate clear differences between localized and advanced prostate cancer with respect to the dissemination and detectability of ctDNA. Because allele-specific alterations in ctDNA are below the threshold for detection in localized prostate cancer, other approaches to identify cell-free nucleic acids of tumor origin may demonstrate better specificity for aggressive disease.
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

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.
OptiJ: Open-source optical projection tomography of large organ samples
Authors: Vallejo Ramirez Pedro P. , Zammit Joseph , Vanderpoorten Oliver , Riche Fergus , Blé François-Xavier , Zhou Xiao-Hong , Spiridon Bogdan , Valentine Christopher , Spasov Simeon P. , Oluwasanya Pelumi W. , Goodfellow Gemma , Fantham Marcus J. , Siddiqui Omid , Alimagham Farah , Robbins Miranda , Stretton Andrew , Simatos Dimitrios , Hadeler Oliver , Rees Eric J. , Ströhl Florian , Laine Romain F. , Kaminski Clemens F.
Published: June 2019

The three-dimensional imaging of mesoscopic samples with Optical Projection Tomography (OPT) has become a powerful tool for biomedical phenotyping studies. OPT uses visible light to visualize the 3D morphology of large transparent samples. To enable a wider application of OPT, we present OptiJ, a low-cost, fully open-source OPT system capable of imaging large transparent specimens up to 13 mm tall and 8 mm deep with 50 μm resolution. OptiJ is based on off-the-shelf, easy-to-assemble optical components and an ImageJ plugin library for OPT data reconstruction. The software includes novel correction routines for uneven illumination and sample jitter in addition to CPU/GPU accelerated reconstruction for large datasets. We demonstrate the use of OptiJ to image and reconstruct cleared lung lobes from adult mice. We provide a detailed set of instructions to set up and use the OptiJ framework. Our hardware and software design are modular and easy to implement, allowing for further open microscopy developments for imaging large organ samples.
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

Species 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

RNA-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

Many 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

Plant 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

Background

Sexual 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.

Methods

Twenty-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.

Results

The 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.

Conclusion

To 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

Much 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

Cryogenic 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

Measurements 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 summary

We 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

Cyanobacteria 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

Transmission 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

Despite 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

Drug 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

Mass 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.