bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extreme genetic structure and dynamic range evolution in a montane passerine bird: implications for tropical diversification
Authors: Cadena Carlos Daniel , Pérez-Emán Jorge L. , Cuervo Andrés M. , Céspedes Laura N. , Epperly Kevin L. , Klicka John T. 
Published: July 2018

AbstractAimEmploy phylogeographic analyses of a widespread species complex to examine the role of historical and evolutionary processes in the origin and maintenance of high species diversity in the Neotropical montane region.LocationNeotropical highlands.TaxonHenicorhinawood-wrens (Aves, Troglodytidae).MethodsWe collected mtDNA sequence data for 288 individuals thoroughly covering the range of theHenicorhina leucophryscomplex from Mexico to Bolivia. Sequences were employed to characterize population structure, infer phylogenetic relationships among populations and their divergence times, examine lineage accumulation through time, and identify presumptive species using coalescent methods. We also explored the origin of elevational and latitudinal replacements involved in spatial changes in species assemblages in the Andes.ResultsWe found remarkable genetic structure within the complex, which consists of numerous lineages reaching >12% sequence divergence; most divergent populations occur in areas separated by topographic barriers but several of them, typically not sister to each other, co-occur with elevational segregation on mountain slopes or replace each other with latitude along the Andes. Some close relatives occur in areas separated by thousands of kilometers, with more distant relatives occupying intervening areas. The complex likely originated in the Mexican highlands and expanded extensively in South America while diverging rapidly at a constant rate into many different lineages which have persisted for millions of years. Coalescent analyses consistently revealed that the complex may comprise more than 30 species; while we do not suggest these presumptive species should be recognized by taxonomists in the absence of additional data,H. leucophrysis a distant outlier among New World birds in terms of high lineage diversity within a single recognized species.Main ConclusionsOur study captured wood-wren lineages in the act of building up diversity via divergence and persistence in allopatry, achievement of secondary sympatry, and coexistence at the landscape scale mediated by ecological and evolutionary divergence. Although dispersal by wood-wrens is restricted at present and this likely accounts for strong population structure across topographic barriers, their ranges have been dynamic, managing to disperse over much of the montane Neotropics. Phases of expansion and contraction of ranges and localized extinctions of populations likely account for phylogeographic patterns which are precursors to the origin of new species and the accumulation of diversity in tropical mountains.
Microscale light management and inherent optical properties of intact corals studied with optical coherence tomography
Authors: Wangpraseurt Daniel , Jacques Steven , Lyndby Niclas , Holm Jacob Boiesen , Pages Christine Ferrier , Kühl Michael 
Published: July 2018

AbstractCoral reefs are highly productive photosynthetic systems and coral optics studies suggest that such high efficiency is due to optimised light scattering by coral tissue and skeleton. Here, we characterise the inherent optical properties, i.e., the scattering coefficient, μs, and the anisotropy of scattering, g, of 8 intact coral species using optical coherence tomography (OCT). Specifically, we describe light scattering by coral skeletons, coenoarc tissues, polyp tentacles and areas covered by fluorescent pigments (FP). Our results reveal that light scattering between coral species ranges from μs = 3 mm−1 (Stylophora pistillata) to μs= 25 mm−1 (Echinopora lamelosa). For Platygyra pini, μs was 10-fold higher for tissue vs skeleton, while in other corals (e.g. Hydnophora pilosa) no difference was found between tissue and skeletal scattering. Tissue scattering was 3-fold enhanced in coenosarc tissues (μs = 24.6 mm−1) vs polyp tentacles (μs = 8.3 mm−1) in Turbinaria reniformis. FP scattering was almost isotropic when FP were organized in granule chromatophores (g=0.34) but was forward directed when FP were distributed diffusely in the tissue (g=0.96). Our study provides detailed measurements of coral scattering and establishes a rapid approach for characterising optical properties of photosynthetic soft tissues via OCT in vivo.
A subfunctionalization epistasis model to evaluate homeologous gene interactions in allopolyploid wheat
Authors: Santantonio Nicholas , Jannink Jean-Luc , Sorrells Mark E. 
Published: July 2018

1AbstractHybridization between related species results in the formation of an allopolyploid with multiple subgenomes. These subgenomes will each contain complete, yet evolutionarily divergent, sets of genes. Like a diploid hybrid, allopolyploids will have two versions, or homeoalleles, for every gene. Partial functional redundancy between homeologous genes should result in a deviation from additivity. These epistatic interactions between homeoalleles are analogous to dominance effects, but are fixed across subgenomes through self pollination. An allopolyploid can be viewed as an immortalized hybrid, with the opportunity to select and fix favorable homeoallelic interactions within inbred varieties. We present a subfunctionalization epistasis model to estimate the degree of functional redundancy between homeoallelic loci and a statistical framework to determine their importance within a population. We provide an example using the homeologous dwarfing genes of allohexaploid wheat,Rht-1, and search for genome-wide patterns indicative of homeoallelic subfunctionalization in a breeding population. Using the IWGSC RefSeq vl.0 sequence, 23,796 homeoallelic gene sets were identified and anchored to the nearest DNA marker to form 10,172 homeologous marker sets. Interaction predictors constructed from products of marker scores were used to fit the homeologous main and interaction effects, as well as estimate whole genome genetic values. Some traits displayed a pattern indicative of homeoallelic subfunctionalization, while other traits showed a less clear pattern or were not affected. Using genomic prediction accuracy to evaluate importance of marker interactions, we show that homeologous interactions explain a portion of the non-additive genetic signal, but are less important than other epistatic interactions.
Probabilities of tree topologies with temporal constraints and diversification shifts
Authors: Didier Gilles 
Published: July 2018

AbstractDating the tree of life is a task far more complicated that only determining the evolutionary relationships between species. It is therefore of interest to develop approaches able to deal with undated phylogenetic trees.The main result of this work is a method to compute probabilities of undated phylogenetic trees under piecewiseconstant-birth-death-sampling models by constraining some of the divergence times to belong to given time intervals and by allowing diversification shifts on certain clades. The computation is quite fast since its time complexity is quadratic with the size of the tree topology and linear with the number of time constraints and of “pieces” in the model.The interest of this computation method is illustrated with three applications, namely,to compute the exact distribution of the divergence times of a tree topology with temporal constraints,to directly sample the divergence times of a tree topology, andto test for a diversification shift at a given clade.
Targeting a Therapy-Resistant Cancer Cell State Using Masked Electrophiles as GPX4 Inhibitors
Authors: Eaton John K. , Furst Laura , Ruberto Richard A. , Moosmayer Dieter , Hillig Roman C. , Hilpmann André , Zimmermann Katja , Ryan Matthew J. , Niehues Michael , Badock Volker , Kramm Anneke , Chen Sixun , Clemons Paul A. , Gradl Stefan , Montagnon Claire , Lazarski Kiel E. , Christian Sven , Bajrami Besnik , Neuhaus Roland , Eheim Ashley L. , Viswanathan Vasanthi S. , Schreiber Stuart L. 
Published: July 2018

SUMMARYWe recently discovered that inhibition of the lipid peroxidase GPX4 can selectively kill cancer cells in a therapy-resistant state through induction of ferroptosis. Although GPX4 lacks a conventional druggable pocket, covalent small-molecule inhibitors are able to overcome this challenge by reacting with the GPX4 catalytic selenocysteine residue to eliminate enzymatic activity. Unfortunately, all currently-reported GPX4 inhibitors achieve their activity through reactive chloroacetamide groups. We demonstrate that such chloroacetamide-containing compounds are poor starting points for further advancement given their promiscuity, instability, and low bioavailability. Development of improved GPX4 inhibitors, including those with therapeutic potential, requires the identification of new electrophilic chemotypes and mechanisms of action that do not suffer these shortcomings. Here, we report our discovery that nitrile oxide electrophiles, and a set of remarkable chemical transformations that generates them in cells from masked precursors, provide an effective strategy for selective targeting of GPX4. Our results, which include structural insights, target engagement assays, and diverse GPX4-inhibitor tool compounds, provide critical insights that may galvanize development of improved compounds that illuminate the basic biology of GPX4 and therapeutic potential of ferroptosis induction. In addition, our discovery that nitrile oxide electrophiles engage in highly selective cellular interactions and are bioavailable in their masked forms may be relevant for targeting other currently undruggable proteins, such as those revealed by recent proteome-wide ligandability studies.
Yeast Chd1p remodels nucleosomes with unique DNA unwrapping and translocation dynamics
Authors: Kirk Jaewon , Lee Ju Yeon , Lee Yejin , Kang Chanshin , Shin Soochul , Lee Eunhye , Song Ji-Joon , Hohng Sungchul 
Published: July 2018

AbstractChromodomain-helicase-DNA-binding protein 1 (CHD1) remodels chromatin by translocating nucleosomes along DNA, but its mechanism remains poorly understood. Here, we employ a single-molecule fluorescence approach to characterize nucleosome remodeling by yeast CHD1 (Chd1p). We show that Chd1p translocates nucleosomes in steps of multiple base pairs per ATP. ATP binding to Chd1p induces a transient unwrapping of the exit-side DNA, and facilitates nucleosome translocation. ATP hydrolysis induces nucleosome translocation, which is followed by the rewrapping upon the release of the hydrolyzed nucleotide. Multiple Chd1ps binding to a single nucleosome sequentially moves a histone octamer with a preference to the center of DNA fragments, suggesting a new mechanism for regularly spaced nucleosome generation by Chd1p. Our results reveal the unique mechanism by which Chd1p remodels nucleosomes.Significance StatementThere are four major ATP-dependent chromatin remodeler families: SWI/SNF, ISWI, CHD, and INO80/SWR1. The remodeling mechanisms of SWI/SNF and ISWI chromatin remodelers have been elucidated through extensive single-molecule studies, but it remains poorly understood how CHD chromatin remodeler operate. We use single-molecule FRET techniques, and show that Yeast CHD1 uses unique mechanisms to remodel a nucleosome.
Metagenomic screening of global microbiomes identifies pathogen-enriched environments
Authors: Li Xiaofang 
Published: July 2018

AbstractBackgroundHuman pathogens are widespread in the environment, and examination of pathogen-enriched environments in a rapid and high-throughput fashion is important for development of pathogen-risk precautionary measures.MethodsIn this study, a Local BLASTP procedure for metagenomic screening of pathogens in the environment was developed using a toxin-centered database. A total of 27 microbiomes derived from ocean water, freshwater, soil, feces, and wastewater were screened using the Local BLASTP procedure. Bioinformatic analysis and Canonical Correspondence Analysis were conducted to examine whether the toxins included in the database were taxonomically associated.ResultsThe specificity of the Local BLASTP method was tested with known and unknown toxin sequences. Bioinformatic analysis indicated that most toxins were phylum-specific but not genus-specific. Canonical Correspondence Analysis implied that almost all of the toxins were associated with the phyla ofProteobacteria,NitrospiraeandFirmicutes. Local BLASTP screening of the global microbiomes showed that pore-forming RTX toxin and adenylate cyclase Cya were most prevalent globally in terms of relative abundance, while polluted water and feces samples were the most pathogen-enriched.ConclusionsA Local BLASTP procedure was established for rapid detection of toxins in environmental samples. Screening of global microbiomes in this study provided a quantitative estimate of the most prevalent toxins and most pathogen-enriched environment.
High-density extracellular probes reveal dendritic backpropagation and facilitate neuron classification
Authors: Jia Xiaoxuan , Siegle Josh , Bennett Corbett , Gale Sam , Denman Daniel R , Koch Christof , Olsen Shawn R. 
Published: July 2018

AbstractDifferent neuron types serve distinct roles in neural processing. Extracellular electrical recordings are extensively used to study brain function but are typically blind to cell identity. Morpho-electric properties of neurons measured on spatially dense electrode arrays might be useful for distinguishing neuron types. Here we used Neuropixels probes to record from cortical and subcortical regions of the mouse brain. Extracellular waveforms of each neuron were detected across many channels and showed distinct spatiotemporal profiles among brain regions. Classification of neurons by brain region was improved with multi-channel compared to single-channel waveforms. In visual cortex, waveform clustering identified the canonical regular spiking (RS) and fast spiking (FS) classes, but also uncovered a subclass of RS units with unidirectional backpropagating action potentials (BAPs). Moreover, BAPs were observed in many hippocampal RS cells. Overall, waveform analysis of spikes from high-density probes aids neuron identification and can reveal dendritic backpropagation.
Genetics & the Geography of Health, Behavior, and Attainment
Authors: Belsky Daniel W , Caspi Avshalom , Arseneault Louise , Corcoran David L , Domingue Benjamin W , Harris Kathleen Mullan , Houts Renate M , Mill Jonathan S , Moffitt Terrie E , Prinz Joseph , Sugden Karen , Wertz Jasmin , Williams Benjamin , Odgers Candice L 
Published: July 2018

AbstractPeople’s life chances can be predicted by their neighborhoods. This observation is driving efforts to improve lives by changing neighborhoods. Some neighborhood effects may be causal, supporting neighborhood-level interventions. Other neighborhood effects may reflect selection of families with different characteristics into different neighborhoods, supporting interventions that target families/individuals directly. To test how selection affects different neighborhood-linked problems, we linked neighborhood data with genetic, health, and social-outcome data for >7,000 European-descent UK and US young people in the E-Risk and Add Health Studies. We tested selection/concentration of genetic risks for obesity, schizophrenia, teen-pregnancy, and poor educational outcomes in high-risk neighborhoods, including genetic analysis of neighborhood mobility. Findings argue against genetic selection/concentration as an explanation for neighborhood gradients in obesity and mental-health problems, suggesting neighborhoods may be causal. In contrast, modest genetic selection/concentration was evident for teen-pregnancy and poor educational outcomes, suggesting neighborhood effects for these outcomes should be interpreted with care.
PhISCS - A Combinatorial Approach for Sub-perfect Tumor Phylogeny Reconstruction via Integrative use of Single Cell and Bulk Sequencing Data
Authors: Malikic Salem , Ciccolella Simone , Mehrabadi Farid Rashidi , Ricketts Camir , Rahman Khaledur , Haghshenas Ehsan , Seidman Daniel , Hach Faraz , Hajirasouliha Iman , Cenk Sahinalp S. 
Published: July 2018

AbstractRecent technological advances in single cell sequencing (SCS) provide high resolution data for studying intra-tumor heterogeneity and tumor evolution. Available computational methods for tumor phylogeny inference via SCS typically aim to identify the most likelyperfect phylogeny treesatisfyinginfinite sites assumption(ISA). However limitations of SCS technologies such as frequent allele dropout or highly variable sequence coverage, commonly result in mutational call errors and prohibit a perfect phylogeny. In addition, ISA violations are commonly observed in tumor phylogenies due to the loss of heterozygosity, deletions and convergent evolution. In order to address such limitations, we, for the first time, introduce a new combinatorial formulation that integrates single cell sequencing data with matching bulk sequencing data, with the objective of minimizing a linear combination of (i) potential false negatives (due to e.g. allele dropout or variance in sequence coverage) and (ii) potential false positives (due to e.g. read errors) among mutation calls, as well as (iii) the number of mutations that violate ISA - to define theoptimal sub-perfect phylogeny.Our formulation ensures that several lineage constraints imposed by the use of variant allele frequencies (VAFs, derived from bulk sequence data) are satisfied. We express our formulation both in the form of an integer linear program (ILP) and - for the first time in the context of tumor phylogeny reconstruction - a boolean constraint satisfaction problem (CSP) and solve them by leveraging state-of-the-art ILP/CSP solvers. The resulting method, which we name PhISCS, is the first to integrate SCS and bulk sequencing data under the finite sites model. Using several simulated and real SCS data sets, we demonstrate that PhISCS is not only more general but also more accurate than the alternative tumor phylogeny inference tools. PhISCS is very fast especially when its CSP based variant is used returns the optimal solution, except in rare instances for which it provides an optimality gap. PhISCS is available athttps://github.com/haghshenas/PhISCS.
M3C: Monte Carlo reference-based consensus clustering
Authors: John Christopher R. , Watson David , Russ Dominic , Goldmann Katriona , Ehrenstein Michael , Pitzalis Costantino , Lewis Myles , Barnes Michael 
Published: July 2018

AbstractGenome-wide data is used to stratify patients into classes for precision medicine using clustering algorithms. A common problem in this area is selection of the number of clusters (K). The Monti consensus clustering algorithm is a widely used method which uses stability selection to estimate K. However, the method has bias towards higher values of K and yields high numbers of false positives. As a solution, we developed Monte Carlo reference-based consensus clustering (M3C), which is based on this algorithm. M3C simulates null distributions of stability scores for a range of K values thus enabling a comparison with real data to remove bias and statistically test for the presence of structure. M3C corrects the inherent bias of consensus clustering as demonstrated on simulated and real expression data from The Cancer Genome Atlas (TCGA). For testing M3C, we developed clusterlab, a new method for simulating multivariate Gaussian clusters.
Platypus Induced Pluripotent Stem Cells: the Unique Pluripotency Signature of a Monotreme
Authors: Whitworth DJ , Limnios IJ , Gauthier M-E , Weeratunga P , Ovchinnikov DA , Baillie G , Grimmond SM , Marshall Graves JA , Wolvetang EJ 
Published: July 2018

Summary StatementThe generation and transcriptome analysis of the first induced pluripotent stem cells from the platypus reveals SOX2 has been a key driver of the expanded pluripotency regulatory network in placental mammals.ABSTRACTThe mechanisms by which pluripotency has evolved remain unclear. To gain insight into the evolution of mammalian pluripotency we have generated induced pluripotent stem cells (piPSCs) from the platypus. Deep sequencing of the piPSC transcriptome revealed that piPSCs robustly express the core eutherian pluripotency factorsOCT4, SOX2andNANOG. Given the more extensive role ofSOX3overSOX2in avian pluripotency, our data indicate that between 315 million years and 166 million years ago primitive mammals replaced the role ofSOX3in the vertebrate pluripotency network withSOX2. DAX1/NR0B1is not expressed in piPSCs and an analysis of the platypusDAX1promoter revealed the absence of a proximal SOX2-binding DNA motif known to be critical forDAX1expression in eutherian pluripotent stem cells, suggesting that the acquisition of SOX2 responsiveness byDAX1has facilitated its recruitment into the pluripotency network of eutherians. We further show that the expression ratio of X chromosomes to autosomes (X1-5X1-5:AA) is approximately equal to 1 indicating that there is no upregulation of X-linked genes and that there is no preference for silencing of maternal or paternal alleles (ie imprinting).
A robust image registration interface for large volume brain atlas
Authors: Ni Hong , Tan Chaozhen , Feng Zhao , Chen Shangbin , Zhang Zoutao , Li Wenwei , Guan Yue , Gong Hui , Luo Qingming , Li Anan 
Published: July 2018

AbstractMapping the brain structures in three-dimensional accurately is critical for an in-depth understanding of the brain functions. By using the brain atlas as a hub, mapping detected datasets into a standard brain space enables efficiently use of various datasets. However, because of the heterogeneous and non-uniform characteristics of the brain structures at cellular level brought with the recently developed high-resolution whole-brain microscopes, traditional registration methods are difficult to apply to the robust mapping of various large volume datasets. Here, we proposed a robust Brain Spatial Mapping Interface (BrainsMapi) to address the registration of large volume datasets at cellular level by introducing the extract regional features of the anatomically invariant method and a strategy of parameter acquisition and large volume transformation. By performing validation on model data and biological images, BrainsMapi can not only achieve robust registration on sample tearing and streak image datasets, different individual and modality datasets accurately, but also are able to complete the registration of large volume dataset at cellular level which dataset size reaches 20 TB. Besides, it can also complete the registration of historical vectorized dataset. BrainsMapi would facilitate the comparison, reuse and integration of a variety of brain datasets.