bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scalable cytoarchitectonic characterization of large intact human neocortex samples
Authors: Hildebrand Sven , Schueth Anna , Herrler Andreas , Galuske Ralf , Roebroeck Alard 
Published: March 2018

AbstractWe describe MASH (Multiscale Architectonic Staining of Human cortex): a simple, fast and low-cost cytoarchitectonic labeling and optical clearing approach for human cortex samples, which can be applied to large formalin fixed adult brain samples. A suite of small-molecule fluorescent nuclear and cytoplasmic dyes in combination with new refractive index matching solutions allows deep volume imaging. This enables highly scalable human neocortical cytoarchitecture characterization with a large 3D scope.
A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus
Authors: Chao Day-Yu , Shen Wen-Fan , Galula Jedhan Ucat , Liu Jiun-Hung , Liao Mei-Ying , Huang Chang-Hao , Wang Yu-Chun , Wu Han-Chung , Liang Jian-Jong , Lin Yi-Ling , Whitney Matthew T. , Chang Gwong-Jen J. , Chen Sheng-Ren , Wu Shang-Rung 
Published: March 2018

AbstractDengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. The vaccine candidates under development require a tetravalent immunogen to induce a balanced immunity against all four serotypes of dengue virus. Herein we show that mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher and broader neutralization antibodies (NtAbs) against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. The cryo-electron microscopy reconstruction showed that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes. Most importantly, maternally transferred antibodies derived from mD2VLP-vaccinated female mice protected suckling mice from lethal challenge by all four serotypes of DENV. Our results support the fact that a universal dengue vaccine that protects against all four serotypes of dengue viruses can be achieved by using an immunogen such as mD2VLP.
A protocol for single-cell transcriptomics from cryopreserved renal tissue and urine for the Accelerating Medicine Partnership (AMP) RA/SLE network
Authors: Rao Deepak A. , Berthier Celine C. , Arazi Arnon , Davidson Anne , Liu Yanyan , Browne Edward P. , Eisenhaure Thomas M. , Chicoine Adam , Lieb David J. , Smilek Dawn E. , Tosta Patti , Lederer James A. , Brenner Michael B. , Hildeman David , Woodle E. Steve , Wofsy David , Anolik Jennifer H. , Kretzler Matthias , Hacohen Nir , Diamond Betty 
Published: March 2018

ABSTRACTOBJECTIVEThere is a critical need to define the cells that mediate tissue damage in lupus nephritis. Here we aimed to establish a protocol to preserve lupus nephritis kidney biopsies and urine cell samples obtained at multiple clinical sites for subsequent isolation and transcriptomic analysis of single cells.METHODSFresh and cryopreserved kidney tissue from tumor nephrectomies and lupus nephritis kidney biopsies were disaggregated by enzymatic digestion. Cell yields and cell composition were assessed by flow cytometry. Transcriptomes of leukocytes and epithelial cells were evaluated by low-input and single cell RNA-seq.RESULTSCryopreserved kidney tissue from tumor nephrectomies and lupus nephritis biopsies can be thawed and dissociated to yield intact, viable leukocytes and epithelial cells. Cryopreservation of intact kidney tissue provides higher epithelial cell yields compared to cryopreservation of single cell suspensions from dissociated kidneys. Cell yields and flow cytometric cell phenotypes are comparable between cryopreserved kidney samples and paired kidney samples shipped overnight on wet ice. High-quality single cell and low-input transcriptomic data were generated from leukocytes from both cryopreserved lupus nephritis kidney biopsies and urine, as well as from a subset of kidney epithelial cells.CONCLUSIONThe AMP RA/SLE cryopreserved tissue analysis pipeline provides a method for centralized processing of lupus nephritis kidney biopsies and urine samples to generate robust transcriptomic analyses in multi-center studies.
Heterogeneous local dynamics revealed by classification analysis of spatially disaggregated time series data
Authors: Perkins T. Alex , Rodriguez-Barraquer Isabel , Manore Carrie , Siraj Amir S. , España Guido , Barker Christopher M. , Johansson Michael A. , Reiner Robert C. 
Published: March 2018

ABSTRACTTime series data provide a crucial window into infectious disease dynamics, yet their utility is often limited by the spatially aggregated form in which they are presented. When working with time series data, violating the implicit assumption of homogeneous dynamics below the scale of spatial aggregation could bias inferences about underlying processes. We tested this assumption in the context of the 2015-2016 Zika epidemic in Colombia, where time series of weekly case reports were available at national, departmental, and municipal scales. First, we performed a descriptive analysis, which showed that the timing of departmental-level epidemic peaks varied by three months and that departmental-level estimates of the time-varying reproduction number, R(t), showed patterns that were distinct from a national-level estimate. Second, we applied a classification algorithm to six features of proportional cumulative incidence curves, which showed that variability in epidemic duration, the length of the epidemic tail, and consistency with a cumulative normal density curve made the greatest contributions to distinguishing groups. Third, we applied this classification algorithm to data simulated with a stochastic transmission model, which showed that group assignments were consistent with simulated differences in the basic reproduction number, R0. This result, along with associations between spatial drivers of transmission and group assignments based on observed data, suggests that the classification algorithm is capable of detecting differences in temporal patterns that are associated with differences in underlying drivers of incidence patterns. Overall, this diversity of temporal patterns at local scales underscores the value of spatially disaggregated time series data.
A method for simultaneous targeted mutagenesis of all nuclear rDNA repeats in Saccharomyces cerevisiae using CRISPR-Cas9
Authors: Chiou Lilly , Armaleo Daniele 
Published: March 2018

AbstractSaccharomyces cerevisiae has been the prime model to study the assembly and functionality of eukaryotic ribosomes. Within that vast landscape, the specific problem of mutagenizing all 150 nuclear rRNA genes was bypassed using strains whose chromosomal copies had been deleted and substituted by plasmid-borne rDNA. Work with these strains has produced important insights, but nucleolar structure is altered and such yeast-specific approaches are elaborate and not transferable to most other eukaryotes. We describe here a simple CRISPR-Cas9 based method to place targeted mutations in all 150 chromosomal rDNA repeats in yeast. The procedure per se is not expected to alter the nucleolus and is potentially applicable also to other eukaryotes. Yeast was transformed with a plasmid bearing the genes for Cas9 and for the guide RNA, engineered to target a site in the SSU region. Our mutagenesis plan included insertion of a spliceosomal intron in the normally intronless yeast nuclear rDNA. Despite the potential lethality of cutting all 150 rDNA repeats at the same time, yeast survived the Cas9 attack through inactivation of the cut sites either by point mutations or by inserting the intron, which was spliced out correctly from the rRNA transcript. In each mutant strain the same mutation was present in all rDNA repeats and was stably inherited even after removal of the Cas9 plasmid.
Visualizing and interpreting single-cell gene expression datasets with Similarity Weighted Nonnegative Embedding
Authors: Wu Yan , Tamayo Pablo , Zhang Kun 
Published: March 2018

SummaryHigh throughput single-cell gene expression profiling has enabled the characterization of novel cell types and developmental trajectories. Visualizing these datasets is crucial to biological interpretation, and the most popular method is t-Stochastic Neighbor embedding (t-SNE), which visualizes local patterns better than other methods, but often distorts global structure, such as distances between clusters. We developed Similarity Weighted Nonnegative Embedding (SWNE), which enhances interpretation of datasets by embedding the genes and factors that separate cell states alongside the cells on the visualization, captures local structure better than t-SNE and existing methods, and maintains fidelity when visualizing global structure. SWNE uses nonnegative matrix factorization to decompose the gene expression matrix into biologically relevant factors, embeds the cells, genes and factors in a 2D visualization, and uses a similarity matrix to smooth the embeddings. We demonstrate SWNE on single cell RNA-seq data from hematopoietic progenitors and human brain cells.
Curating clinically relevant transcripts for the interpretation of sequence variants
Authors: DiStefano Marina T. , Hemphill Sarah E. , Cushman Brandon J. , Bowser Mark J. , Hynes Elizabeth , Grant Andrew R. , Siegert Rebecca K. , Oza Andrea M. , Gonzalez Michael A. , Amr Sami S. , Rehm Heidi L. , Abou Tayoun Ahmad N. 
Published: March 2018

AbstractVariant interpretation depends on accurate annotations using biologically relevant transcripts. We have developed a systematic strategy for designating primary transcripts, and applied it to 109 hearing loss-associated genes that were divided into 3 categories. Category 1 genes (n=38) had a single transcript, Category 2 genes (n=32) had multiple transcripts, but a single transcript was sufficient to represent all exons, and Category 3 genes (n=38) had multiple transcripts with unique exons. Transcripts were curated with respect to gene expression reported in the literature and the Genotype-Tissue Expression Project. In addition, high frequency loss of function variants in the Genome Aggregation Database, and disease-causing variants in ClinVar and the Human Gene Mutation Database across the 109 genes were queried. These data were used to classify exons as "clinically relevant", "uncertain significance", or "clinically insignificant". Interestingly, 7% of all exons, containing >124 "clinically significant" variants, were of “uncertain significance”. Finally, we used exon-level next generation sequencing quality metrics generated at two clinical labs, and identified a total of 43 technically challenging exons in 20 different genes that had inadequate coverage and/or homology issues which might lead to false variant calls. We have demonstrated that transcript analysis plays a critical role in accurate clinical variant interpretation.
An improved method for fitting gamma distribution to substitution rate variation among sites
Authors: Xia Xuhua 
Published: March 2018

AbstractGamma distribution has been used to fit substitution rate variation over site. One simple method to estimate the shape parameter of the gamma distribution is to 1) reconstruct a phylogenetic tree and the ancestral states of internal nodes, 2) perform pairwise comparison between nodes on each side of each branch to count the number of “observed” substitutions for each site, and apply correction of multiple hits to derive the estimated number of substitutions for each site, and 3) fit the site-specific substitution data to gamma distribution to obtain the shape parameter α This method is fast but its accuracy depends much on the accuracy of the estimated site-specific number of substitutions. The existing method has three shortcomings. First, it uses Poisson correction which is inadequate for almost any nucleotide sequences. Second, it does independent estimation for the number of substitutions at each site without making use of information at all sites. Third, the program implementing the method has never been made publically available. I have implemented in DAMBE software a new method based on the F84 substitution model with simultaneous estimation that uses information from all sites in estimating the number of substitutions at each site. DAMBE is freely available at available athttp://dambe.bio.uottawa.ca
The marked diversity of unique cortical enhancers enables neuron-specific tools by Enhancer-Driven Gene Expression
Authors: Blankvoort Stefan , Witter Menno P. , Noonan James , Cotney Justin , Kentros Cliff 
Published: March 2018

SUMMARYUnderstanding neural circuit function requires individually addressing their component parts: specific neuronal cell types. However, not only do the precise genetic mechanisms specifying neuronal cell types remain obscure, access to these neuronal cell types by transgenic techniques also remains elusive. While most genes are expressed in the brain, the vast majority are expressed in many different kinds of neurons, suggesting that promoters alone are not sufficiently specific to distinguish cell types. However, there are orders of magnitude more distal genetic cis-regulatory elements controlling transcription (i.e. enhancers), so we screened for enhancer activity in microdissected samples of mouse cortical subregions. This identified thousands of novel putative enhancers, many unique to particular cortical subregions. Pronuclear injection of expression constructs containing such region-specific enhancers resulted in transgenic lines driving expression in distinct sets of cells specifically in the targeted cortical subregions, even though the parent gene’s promoter was relatively nonspecific. These data showcase the promise of utilizing the genetic mechanisms underlying the specification of diverse neuronal cell types for the development of genetic tools potentially capable of targeting any neuronal circuit of interest, an approach we call Enhancer-Driven Gene Expression (EDGE).HighlightsEnhancer ChIP-seq of cortical subregions reveals 59372 putative enhancers.3740 of these are specific to particular cortical subregions.This reflects the remarkable anatomical diversity of the adult cortex.Unique enhancers provide a means to make targeted cell-type specific genetic tools.
Cryo-EM structure of alpha-synuclein fibrils
Authors: Guerrero-Ferreira Ricardo , Taylor Nicholas M. I. , Mona Daniel , Ringler Philippe , Lauer Matthias E. , Riek Roland , Britschgi Markus , Stahlberg Henning 
Published: March 2018

AbstractIntracellular inclusions of alpha-synuclein are the neuropathological hallmark of progressive disorders called synucleinopathies. Alpha-synuclein fibrils are associated with transmissive cell-to-cell propagation of pathology. We report the structure of an alpha-synuclein fibril (residues 1-121) determined by cryo-electron microscopy at 3.4Å resolution. Two protofilaments form a polar fibril composed of staggered β-strands. The backbone of residues 38 to 95, including the fibril core and the non-amyloid component region, are well resolved in the EM map. Residues 50-57, containing three mutation sites associated with familial synucleinopathies, form the interface between the two protofilaments and contribute to fibril stability. A hydrophobic cleft may have implications for fibril elongation, and inform the rational design of molecules for diagnosis and treatment of synucleinopathies.
WAVES: a Web Application for Versatile Enhanced bioinformatic Services
Authors: Chakiachvili Marc , Milanesi Sylvain , Arigon Chifolleau Anne-Muriel , Lefort Vincent 
Published: March 2018

AbstractSummary: WAVES is a web application dedicated to bioinformatic tool integration. It provides an efficient way to implement a service for any bioinformatic software. Such services are automatically made available in three ways: web pages, web forms to include in remote websites, and a RESTful web services API to access remotely from applications. In order to fulfill the service’s computational needs, WAVES can perform computation on various resources and environments, such as Galaxy instances.Availability and implementation: WAVES was developed with Django, a Python-based web framework. It was designed as a reusable web application. It is fully portable, as only a Python installation is required to run Django. It is licensed under GNU General Public License. Source code, documentation with examples and demo are available from http://www.atgc-montpellier.fr/waves/.Contact:lefort@lirmm.fr
Interplay between the paradox of enrichment and nutrient cycling in food webs
Authors: Quévreux Pierre , Barot Sébastien , Thébault Élisa 
Published: March 2018

AbstractNutrient cycling is fundamental to ecosystem functioning. Despite recent major advances in the understanding of complex food web dynamics, food web models have so far generally ignored nutrient cycling. However, nutrient cycling is expected to strongly impact food web stability and functioning. To make up for this gap, we built an allometric and size structured food web model including nutrient cycling. By releasing mineral nutrients, recycling increases the availability of limiting resources for primary producers and links each trophic level to the bottom of food webs. We found that nutrient cycling can provide a significant part of the total nutrient supply of the food web, leading to a strong enrichment effect that promotes species persistence in nutrient poor ecosystems but leads to a paradox of enrichment at high nutrient inputs. The presence of recycling loops linking each trophic level to the basal resources weakly affects species biomass temporal variability in the food web. Recycling loops tend to slightly dampen the destabilising effect of nutrient enrichment on consumer temporal variability while they have opposite effects for primary producers. By considering nutrient cycling, this new model improves our understanding of the response of food webs to nutrient availability and opens perspectives to better link studies on food web dynamics and ecosystem functioning.
MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size
Authors: Lewis Tommy L. , Kwon Seok-Kyu , Lee Annie , Shaw Reuben , Polleux Franck 
Published: March 2018

ABSTRACTNeurons display extreme degrees of polarization, including compartment-specific organelle morphology. In cortical pyramidal neurons, dendritic mitochondria are long and tubular whereas axonal mitochondria display uniformly short length. Here, we explored the functional significance of maintaining small mitochondria for axonal developmentin vitroandin vivo. We report that the Drp1 ‘receptor’ Mitochondrial fission factor (MFF) is required for determining the size of mitochondria entering the axon and then for maintenance of their size along the distal portions of the axon without affecting their trafficking properties, presynaptic capture, membrane potential or capacity for ATP production. Strikingly, this increase in presynaptic mitochondrial size upon MFF downregulation augments their capacity for Ca2+([Ca2+]m) uptake during neurotransmission, leading to reduced presynaptic [Ca2+]caccumulation, decreased presynaptic release and terminal axon branching. Our results uncover a novel mechanism controlling neurotransmitter release and axon branching through fission-dependent regulation of presynaptic mitochondrial size.
A balance index for phylogenetic trees based on quartets
Authors: Coronado Tomás M. , Mir Arnau , Rosselló Francesc , Valiente Gabriel 
Published: March 2018

AbstractWe define a new balance index for phylogenetic trees based on the symmetry of the evolutive history of every quartet of leaves. This index makes sense for polytomic trees and it can be computed in time linear in the number of leaves. We compute its maximum and minimum values for arbitrary and bifurcating trees, and we provide exact formulas for its expected value and variance for bifurcating trees under Ford’sα-model and Aldous’ β-model and for arbitrary trees under the α-γ-model.
Paradata and dashboards in PIAAC
Authors: Mohadjer Leyla , Edwards Brad 
Published: March 2018

Purpose
This paper aims to provides a brief review of the dashboard literature, an account of the development of performance dashboards for field data collection at Westat, and more specifically for the first cycle of the Programme for the International Assessment of Adult Competencies (PIAAC). A brief concluding section offers suggestions for improvements in survey dashboards for PIAAC’s next cycle.

Design/methodology/approach
To manage field work at Westat, the authors create views into various paradata databases and present them in a dashboard, showing key performance indicators at a glance. Users can drill down from the dashboard into underlying databases to investigate potential problems. The US PIAAC dashboard is a monitoring system that supports daily review of many activities. For example, it provides overnight alerts to the field supervisor when global positioning system (GPS) data from an interviewer’s smartphone shows the interview occurred far from the respondent’s home.

Findings
Performance dashboards may represent best practice for monitoring field activities. Paradata sources and systems vary greatly across the PIAAC countries, but a multitude of process data exists in every country and can be used to create quality indicators and a monitoring system. PIAAC can establish standards/guidelines to improve visualization of quality metrics and management data, regardless of the local survey infrastructure.

Originality/value
The core of the paper is a case study of the experiences on the US PIAAC implementation of dashboards to monitor survey quality, production and costs, with special attention to the issue of fabrication.
Heterogeneity of functional outcomes in patients with bipolar disorder: a cluster‐analytic approach
Authors: Solé B. , Bonnin C. M. , Jiménez E. , Torrent C. , Torres I. , Varo C. , Valls E. , Montejo L. , Gómez‐Ocaña C. , Tomioka Y. , Vieta E. , Martinez‐Aran A. , Reinares M. 
Published: March 2018

ObjectiveThe aim was to examine the heterogeneity of psychosocial outcomes in euthymic bipolar disorder (BD) patients and analyse the potential influence of distinct variables on functioning.MethodUsing a hierarchical cluster exploratory analysis, 143 euthymic patients with diagnosis of BD were grouped according to their functional performance based on domains scores of the Functioning Assessment Short Test (FAST). The resulting groups were compared on sociodemographic, clinical and neurocognitive variables to find factors associated with each functional cluster.ResultsPatients were grouped in three functional profiles: patients with good functioning in all the FAST areas, patients with an intermediate profile showing great difficulties in the occupational domain and milder difficulties in most of the rest domains, and a third group with serious difficulties in almost all functional areas. Both functionally impaired groups were characterized by higher subthreshold symptoms (depressive and manic) and higher unemployment rates. The most functionally impaired group also showed lower scores on some measures of processing speed.ConclusionTwo of three functional profiles showed some kind of impairment which was associated with subsyndromal symptoms and cognitive performance. These patterns should be taken into consideration to develop more individualized interventions to restore, or improve, psychosocial outcomes.