bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of ultracentrifugation and a commercial kit for isolation of exosomes derived from glioblastoma and breast cancer cells
Authors: Skottvoll Frøydis Sved , Berg Henriette Engen , Bjørseth Kamilla , Lund Kaja , Roos Norbert , Bekhradnia Sara , Thiede Bernd , Sandberg Cecilie , Vik-Mo Einar , Roberg-Larsen Hanne , Nyström Bo , Lundanes Elsa , Wilson Steven Ray 
Published: March 2018

ABSTRACTExosomes are small extracellular vesicles around 30-100 nm in diameter that are secreted from cells and can be found in most body fluids. Exosomes can be a vital source of biomarkers as they contain various substances (e.g. lipids, RNAs, metabolites and proteins) that can reflect the cell of origin (e.g. cancer cells). For isolation of exosomes present in biological matrices, ultracentrifugation (UC)-based procedures are most common. Other approaches exist, including commercial kits developed for easy and low sample volume isolation. In this study, differential UC and an isolation kit from a major vendor (Total Exosome Isolation Reagent from Thermo Fisher Scientific) were compared. Exosomes were isolated from cell culture media of two different cell sources (patient derived cells from glioblastoma multiforme and the breast cancer cell line MDA-MB-231). For both isolation methods, transmission electron microscopy, dynamic light scattering and western blotting indicated the presence of exosomes. The kit- and UC isolates contained similar amounts of protein measured by the bicinchoninic acid (BCA) assay with absorbance at 562 nm. Using western blot, positive exosome markers were identified in all isolates, and additional exosome markers were identified using MS-based proteomics. For the glioblastoma exosome isolates, the number of proteins identified with liquid chromatography tandem MS (LC-MS/MS) was higher for the UC isolates than the kit isolates when injecting equal protein amounts, contrary to that for the breast cancer exosome isolates. However, negative exosome markers were also found in glioblastoma isolates using LC-MS/MS. Thus, we would not use the term “exosome isolation” as impurities may be present with both isolation methods. Notably, potential biomarkers for both diseases were identified in the isolates using LS-MS/MS. In our opinion, the two isolation methods had rather similar performance, although with some minor differences based on cell of origin.
Cortical recruitment determines learning dynamics and strategy
Authors: Ceballo Sebastian , Bourg Jacques , Kempf Alexandre , Piwkowska Zuzanna , Daret Aurélie , Deneux Thomas , Rumpel Simon , Bathellier Brice 
Published: March 2018

AbstractSalience is a broad and widely used concept in neuroscience whose neuronal correlates, however, remain elusive. In behavioral conditioning, salience is used to explain various effects, such as stimulus overshadowing, and refers to how fast and strongly a stimulus can be associated with a conditioned event. Here, we show that sounds of diverse quality, but equal intensity and perceptual detectability, can recruit different levels of population activity in mouse auditory cortex. When using these sounds as cues in a Go/NoGo discrimination task, the degree of cortical recruitment matches the salience parameter of a reinforcement learning model used to analyze learning speed. We test an essential prediction of this model by training mice to discriminate light-sculpted optogenetic activity patterns in auditory cortex, and verify that cortical recruitment causally determines association or overshadowing of the stimulus components. This demonstrates that cortical recruitment underlies major aspects of stimulus salience during reinforcement learning.
MoDentify: a tool for phenotype-driven module identification in multilevel metabolomics networks
Authors: Do Kieu Trinh , Rasp David J.N.-P. , Kastenmüller Gabi , Suhre Karsten , Krumsiek Jan 
Published: March 2018

AbstractSummaryMetabolomics is an established tool to gain insights into (patho)physiological outcomes. Associations of metabolism with such outcomes are expected to span functional modules, which are defined as sets of correlating metabolites that are coordinately regulated. Moreover, these associations occur at different scales, from entire pathways to only a few metabolites, which is an aspect that has not been addressed by previous methods. Here we present MoDentify, a freely available R package to identify regulated modules in metabolomics networks at different layers of resolution. Importantly, MoDentify shows higher statistical power than classical association analysis. Moreover, the package offers direct visualization of results as interactive networks in Cytoscape. We present an application example using a complex, multifluid metabolomics dataset. Owing to its generic character, the method is widely applicable to any dataset with a phenotype variable, a data matrix, and optional pathway annotations.Availability and ImplementationMoDentify is freely available from GitHub: https://github.com/krumsiek/MoDentifyThe package vignette contains a detailed tutorial of the analysis workflow.Contactjan.krumsiek@helmholtz-muenchen.de
Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts
Authors: Kelliher Michael T. , Yue Yang , Ng Ashley , Kamiyama Daichi , Huang Bo , Verhey Kristen J. , Wildonger Jill 
Published: March 2018

AbstractNeuronal polarity relies on the selective localization of cargo to axons or dendrites. The molecular motor kinesin-1 moves cargo into axons but is also active in dendrites. This raises the question of how kinesin-1 activity is regulated to maintain the compartment-specific localization of cargo. Our in vivo structure-function analysis of endogenous Drosophila kinesin-1 reveals a novel role for autoinhibition in enabling the dendrite-specific localization of Golgi outposts. Mutations that disrupt kinesin-1 autoinhibition result in the axonal mislocalization of Golgi outposts. Autoinhibition also regulates kinesin-1 localization. Uninhibited kinesin-1 accumulates in axons and is depleted from dendrites, correlating with the change in outpost distribution and dendrite growth defects. Genetic interaction tests show that a balance of kinesin-1 inhibition and dynein activity is necessary to localize Golgi outposts to dendrites and keep them from entering axons. Our data indicate that kinesin-1 activity is precisely regulated by autoinhibition to achieve the selective localization of dendritic cargo.SummaryNeuronal polarity relies on the axon-or dendrite-specific localization of cargo by molecular motors such as kinesin-1. These studies show autoinhibition regulates both kinesin-1 activity and localization to keep dendritic cargo from entering axons.
Decomposing spatially dependent and cell type specific contributions to cellular heterogeneity
Authors: Zhu Qian , Shah Sheel , Dries Ruben , Cai Long , Yuan Guo-Cheng 
Published: March 2018

AbstractBoth the intrinsic regulatory network and spatial environment are contributors of cellular identity and result in cell state variations. However, their individual contributions remain poorly understood. Here we present a systematic approach to integrate both sequencing-and imaging-based single-cell transcriptomic profiles, thereby combining whole-transcriptomic and spatial information from these assays. We applied this approach to dissect the cell-type and spatial domain associated heterogeneity within the mouse visual cortex region. Our analysis identified distinct spatially associated signatures within glutamatergic and astrocyte cell compartments, indicating strong interactions between cells and their spatial environment. Using these signatures as a guide to analyze single cell RNAseq data, we identified previously unknown, but spatially associated subpopulations. As such, our integrated approach provides a powerful tool for dissecting the roles of intrinsic regulatory networks and spatial environment in the maintenance of cellular states.
Different inhibitory interneuron cell classes make distinct contributions to visual perception
Authors: Cone Jackson J. , Scantlen Megan D. , Histed Mark H. , Maunsell John H.R. 
Published: March 2018

SummaryWhile recent work has revealed how different inhibitory interneurons influence cortical responses to sensory stimuli, little is known about how their activity contributes to sensory perception. Here, we optogenetically stimulated different genetically defined interneurons (parvalbumin (PV), somatostatin (SST), vasoactive intestinal peptide (VIP)) in visual cortex (V1) of mice working at threshold in contrast increment or decrement detection tasks. The visual stimulus was paired with optogenetic stimulation to assess how enhancing V1 inhibitory neuron activity synchronously during cortical responses altered task performance. PV or SST activation impaired, while VIP stimulation improved, contrast increment detection. Notably, PV or SST stimulation also impaired contrast decrement detection, when opsin-evoked inhibition would exaggerate stimulus-evoked decrements in firing rate, and thus might improve performance. The impairment produced by PV or SST stimulation persisted throughout many weeks of testing. In contrast mice learned to reliably detect VIP activation in the absence of natural visual stimulation. Thus, different inhibitory signals make distinct contributions to visual contrast perception.
Transcriptional burst initiation and polymerase pause release are key control points of transcriptional regulation
Authors: Bartman Caroline , Keller Cheryl A. , Giardine Belinda , Hardison Ross C. , Blobel Gerd A. , Raj Arjun 
Published: March 2018

AbstractTranscriptional regulation occurs via changes to the rates of various biochemical processes. Sequencing-based approaches that average together many cells have suggested that polymerase binding and polymerase release from promoter-proximal pausing are two key regulated steps in the transcriptional process. However, single cell studies have revealed that transcription occurs in short, discontinuous bursts, suggesting that transcriptional burst initiation and termination might also be regulated steps. Here, we develop and apply a quantitative framework to connect changes in both Pol II ChIP-seq and single cell transcriptional measurements to changes in the rates of specific steps of transcription. Using a number of global and targeted transcriptional regulatory perturbations, we show that burst initiation rate is indeed a key regulated step, demonstrating that transcriptional activity can be frequency modulated. Polymerase pause release is a second key regulated step, but the rate of polymerase binding is not changed by any of the biological perturbations we examined. Our results establish an important role for transcriptional burst regulation in the control of gene expression.
Persistent Underrepresentation of Women’s Science in High Profile Journals
Authors: Shen Yiqin Alicia , Webster Jason M. , Shoda Yuichi , Fine Ione 
Published: March 2018

AbstractYiqin Alicia Shen, Jason M. Webster, Yuichi Shoda, and Ione Fine Department of Psychology, University of Washington Past research has demonstrated an under-representation of female editors and reviewers in top scientific journals, but less is known about the representation of women authors within original research articles. We collected research article publication records from 15 high-profile multidisciplinary and neuroscience journals for 2005-2017 and analyzed the representation of women over time, as well as its relationship with journal impact factor. We find that women authors have been persistently underrepresented in high-profile journals. This under-representation has persisted over more than a decade, with glacial improvement over time. Even within our limited group of high profile journals, the percent of female first and last authors is negatively associated with journal impact factor. Since publishing in high-profile journals is a gateway to academic success, this underrepresentation of women may contribute to the lack of women at the top of the academic ladder.
Orthogonal dietary niche enables reversible engraftment of a gut bacterial commensal
Authors: Kearney Sean M. , Gibbons Sean M. , Erdman SE , Alm EJ 
Published: March 2018

ABSTRACTInterest in manipulating the gut microbiota to treat disease has led to a need for understanding how organisms can establish themselves when introduced into a host with an intact microbial community. While probiotic or prebiotic approaches typically lead to a transient pulse in an organism’s abundance, persistent establishment of an introduced species may require alternative strategies. Here, we introduce the concept of orthogonal niche engineering in the gut, where we include a resource typically absent from the diet, seaweed, to establish a customized niche for an introduced organism. We show that in the short term, co-introduction of this resource at 1% in the diet along with an organism with exclusive access to this resource,B. plebeiusDSM 17135, enables it to colonize at a median abundance of 1%, frequently increasing in abundance to 10 or more percent. We construct a mathematical model of the system to infer thatB. plebeiuscompetitively acquires endogenous resources. We provide evidence that it competes with native commensals to achieve its observed abundance. We observe a diet-dependent loss in seaweed responsiveness ofB. plebeiusin the long term and show the potential for IgA-mediated control of putative invaders by the immune system. These results point to the potential for diet-based intervention as a means to introduce target organisms, but also indicate potential modes for failure of this strategy in the long term.
A dense linkage map of Lake Victoria cichlids improved the Pundamilia genome assembly and revealed a major QTL for sex-determination
Authors: Feulner Philine G.D. , Schwarzer Julia , Haesler Marcel P. , Meier Joana I. , Seehausen Ole 
Published: March 2018

AbstractGenetic linkage maps are essential for comparative genomics, high quality genome sequence assembly and fine scale quantitative trait locus (QTL) mapping. In the present study we identified and genotyped markers via restriction-site associated DNA (RAD) sequencing and constructed a genetic linkage map based on 1,597 SNP markers of an interspecific F2 cross of two closely related Lake Victoria cichlids (Pundamilia pundamilia and P. sp. “red head”). The SNP markers were distributed on 22 linkage groups and the total map size was 1,594 cM with an average marker distance of 1.01 cM. This high-resolution genetic linkage map was used to anchor the scaffolds of the Pundamilia genome and estimate recombination rates along the genome. Via QTL mapping we identified a major QTL for sex in a ∼1.9 Mb region on Pun-LG10, which is homologous to Oreochromis niloticus LG 23 (Ore-LG23) and includes a well-known vertebrate sex-determination gene (amh).
Dynamic control of hippocampal spatial coding resolution by local visual cues
Authors: Bourboulou Romain , Marti Geoffrey , Michon FranÇois-Xavier , Nouguier Morgane , Robbe David , Koenig Julie , Epsztein Jérôme 
Published: March 2018

AbstractThe ability to flexibly navigate an environment relies on a hippocampal-dependent internal cognitive map. Explored space can be internally mapped at different spatial resolutions. However, whether hippocampal spatial coding resolution can be dynamically controlled within and between environments is unknown. In this work we recorded the firing of hippocampal principal cells in mice navigating virtual reality environments, which differed by the presence of local visual cues (virtual 3D objects). Objects improved spatial coding resolution globally with a higher proportion of place cells, smaller place fields, increased spatial selectivity and stability. Spatial coding resolution was notably enhanced locally near objects and could be rapidly tuned by their manipulations. In the presence of objects, place cells also displayed improved theta phase precession and theta timescale spike coordination. These results suggest that local visual cues can rapidly tune the resolution of the hippocampal mapping system within and between environments.
Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen binding affinity
Authors: Dosenovic Pia , Kara Ervin E. , Pettersson Anna-Klara , McGuire Andrew , Gray Matthew , Hartweger Harald , Thientosapol Eddy S. , Stamatatos Leonidas , Nussenzweig Michel C. 
Published: March 2018

AbstractThe discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination, and instead that it would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin knock-in mice. Sequential immunization with a series of specifically designed immunogens was required to shepherd the development of bNAbs. However, knock-in mice contain super-physiologic numbers of bNAb precursor expressing B cells and therefore how these results can be translated to a more physiologic setting remains to be determined. Here we make use of adoptive transfer experiments using knock-in B cells that carry a synthetic intermediate in the pathway to anti-HIV-1 bNAb development to examine how the relationship between B cell receptor affinity and precursor frequency affects germinal center B cell recrutiment and clonal expansion. Immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the germinal center when there are as few as 10 such cells per mouse. However, at low precursor frequencies the extent of clonal expansion is directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to germinal centers is variable and dependent on re-circulation.Significance statementAn essential requirement for an HIV-vaccine is to elicit antibodies to conserved regions of the spike protein (Env) becasue these antibodies can protect against infection. Although broadly neutralizing antibodies develop naturally in rare individuals after prolongued HIV infection, eliciting them by vaccination has only been possible in artificial knock-in mouse models wherein the number of B cells expressing the antibody precursor is super-physiologic. To understand the relationship between precursor frequency, antigen affinity and germinal center recruitment we have performed adoptive transfer experiments in which fixed numbers of precursor cells are engrafted in wild type mice. Our results provide a framework for understanding how precursor frequency and antigen affinity shape humoral immunity to HIV.
Bayesian and likelihood placement of fossils on phylogenies from quantitative morphometries
Authors: Parins-Fukuchi Caroline 
Published: March 2018

AbstractJointly developing a comprehensive tree of life from living and fossil taxa has long been a fundamental goal in evolutionary biology. One major challenge has stemmed from difficulties in merging evidence from extant and extinct organisms. While these efforts have resulted in varying stages of synthesis, they have been hindered by their dependence on qualitative descriptions of morphology. Though rarely applied to phylogenetic inference, traditional and geometric morphometric data can improve these issues by generating more rigorous ways to quantify variation in morphological structures. They may also facilitate the rapid and objective aggregation of large morphological datasets. I describe a new Bayesian method that leverages quantitative trait data to reconstruct the positions of fossil taxa on fixed reference trees composed of extant taxa. Unlike most formulations of phylogenetic Brownian motion models, this method expresses branch lengths in units of morphological disparity, suggesting a new framework through which to construct Bayesian node calibration priors for molecular dating and explore comparative patterns in morphological disparity. I am hopeful that the approach described here will help to facilitate a deeper integration of neo- and paleontological data to move morphological phylogenetics further into the genomic era.
BIC Defacing Algorithm
Authors: Fonov Vladimir S. , Collins Louis D. 
Published: March 2018

AbstractPublic distribution of imaging information from several MRI data processing projects at the BIC has lead to the development of this DEFACING algorithm that is used as part of anonymisation process. Key features of the algorithm include: the defacing should modify voxels associated with face of the subject, making a rendering of the face unrecognisable, it should work on data in the native scanner space and it should not significantly affect subsequent data processing outcome (model based registration, brain extraction, brain tissue classification and brain segmentation). The algorithm is implemented using the MINC library and source code is publicly available. The effect of the defacing algorithm on the data processing was verified using the ICBM database of 152 scans of young adults.
Rapid and Accurate Interpretation of Clinical Exomes Using Phenoxome: a Computational Phenotype-driven Approach
Authors: Wu Chao , Devkota Batsal , Zhao Xiaonan , Baker Samuel W , Niazi Rojeen , Cao Kajia , Gonzalez Michael A , Jayaraman Pushkala , Conlin Laura K , Krock Bryan L , Deardorff Matthew A , Spinner Nancy B , Krantz Ian D , Santani Avni B , Tayoun Ahmad N Abou , Sarmady Mahdi 
Published: March 2018

AbstractClinical exome sequencing (CES) has become the preferred diagnostic platform for complex pediatric disorders with suspected monogenic etiologies, solving up to 20%-50% of cases depending on indication. Despite rapid advancements in CES analysis, the major challenge still resides in identifying the casual variants among the thousands of variants detected during CES testing, and thus establishing a molecular diagnosis. To improve the clinical exome diagnostic efficiency, we developed Phenoxome, a robust phenotype-driven model that adopts a network-based approach to facilitate automated variant prioritization and subsequent classification. Phenoxome dissects the phenotypic manifestation of a patient in conjunction with their genomic profile to filter and then prioritize putative pathogenic variants. To validate our method, we have compiled a clinical cohort of 105 positive patient samples (i.e. at least one reported ‘pathogenic’ variant) that represent a wide range of genetic heterogeneity from The Children’s Hospital of Philadelphia. Our approach identifies the causative variants within the top 5, 10, or 25 candidates in more than 50%, 71%, or 88% of these patient samples respectively. Furthermore, we show that our method is optimized for clinical testing by yielding superior ranking of the pathogenic variants compared to current state-of-art methods. The web application of Phenoxome is available to the public at http://phenoxome.chop.edu/.