bluuebunny/crossref_metadata_2025_split huggingface dataset:
On Rank Deficiency in Phenotypic Covariance Matrices
Authors: O’Keefe F. Robin , Meachen Julie A. , Polly P. David 
Published: July 2020

ABSTRACTThis paper is concerned with rank deficiency in phenotypic covariance matrices: first to establish it is a problem by measuring it, and then proposing methods to treat for it. Significant rank deficiency can mislead current measures of whole-shape phenotypic integration, because they rely on eigenvalues of the covariance matrix, and highly rank deficient matrices will have a large percentage of meaningless eigenvalues. This paper has three goals. The first is to examine a typical geometric morphometric data set and establish that its covariance matrix is rank deficient. We employ the concept of information, or Shannon, entropy to demonstrate that a sample of dire wolf jaws is highly rank deficient. The different sources of rank deficiency are identified, and include the Generalized Procrustes analysis itself, use of the correlation matrix, insufficient sample size, and phenotypic covariance. Only the last of these is of biological interest.Our second goal is to examine a test case where a change in integration is known, allowing us to document how rank deficiency affects two measures of whole shape integration (eigenvalue standard deviation and standardized generalized variance). This test case utilizes the dire wolf data set from Part 1, and introduces another population that is 5000 years older. Modularity models are generated and tested for both populations, showing that one population is more integrated than the other. We demonstrate that eigenvalue variance characterizes the integration change incorrectly, while the standardized generalized variance lacks sensitivity. Both metrics are impacted by the inclusion of many small eigenvalues arising from rank deficiency of the covariance matrix. We propose a modification of the standardized generalized variance, again based on information entropy, that considers only the eigenvalues carrying non-redundant information. We demonstrate that this metric is successful in identifying the integration change in the test case.The third goal of this paper is to generalize the new metric to the case of arbitrary sample size. This is done by normalizing the new metric to the amount of information present in a permuted covariance matrix. We term the resulting metric the ‘relative dispersion’, and it is sample size corrected. As a proof of concept we us the new metric to compare the dire wolf data set from the first part of this paper to a third data set comprising jaws of Smilodon fatalis. We demonstrate that the Smilodon jaw is much more integrated than the dire wolf jaw. Finally, this information entropy-based measures of integration allows comparison of whole shape integration in dense semilandmark environments, allowing characterization of the information content of any given shape, a quantity we term ‘latent dispersion’.
Inferring the genetic basis of sex determination from the genome of a dioecious nightshade
Authors: Wu Meng , Anderson Gregory J. , Hahn Matthew W. , Moyle Leonie C. , Guerrero Rafael F. 
Published: July 2020

ABSTRACTDissecting the genetic mechanisms underlying dioecy (i.e. separate female and male individuals) is critical for understanding the evolution of this pervasive reproductive strategy. Nonetheless, the genetic basis of sex determination remains unclear in many cases, especially in systems where dioecy has arisen recently. Within the economically important plant genusSolanum(∼2000 species), dioecy is thought to have evolved independently at least 4 times across roughly 20 species. Here, we generate the first genome sequence of a dioeciousSolanumand use it to ascertain the genetic basis of sex determination in this species. Wede novoassembled and annotated the genome ofS. appendiculatum(assembly size: ∼750 Mb; scaffold N50: 0.92 Mb; ∼35,000 genes), identified sex-specific sequences and their locations in the genome, and inferred that males in this species are the heterogametic sex. We also analyzed gene expression patterns in floral tissues of males and females, finding ∼100 genes that are differentially expressed between the sexes. These analyses, together with observed patterns of gene-family evolution specific toS. appendiculatum, consistently implicate a suite of genes from the regulatory network controlling pectin degradation and modification in the expression of sex. Furthermore, the genome of a species with a relatively young sex determination system provides the foundational resources for future studies on the independent evolution of dioecy in this speciose clade.
Bariatric surgery normalizes circulating glucocorticoid levels and lowers glucocorticoid action tissue-selectively in mice
Authors: Akalestou Elina , Lopez-Noriega Livia , Christakis Ioannis , Miras Alexander D. , Leclerc Isabelle , Rutter Guy A. 
Published: July 2020

AbstractBackgroundGlucocorticoids produced by the adrenal cortex are essential for the maintenance of metabolic homeostasis. Glucocorticoid activation is catalyzed by 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and signalling is achieved through the glucocorticoid receptor (GR), a ligand-dependent transcription factor. Excess glucocorticoids are associated with insulin resistance and hyperglycaemia. A small number of studies have investigated the effects of bariatric surgery, a gastrointestinal procedure known to improve insulin sensitivity, on glucocorticoid metabolism, but the hypothesised mechanism is assumed to be via weight loss.AimTo investigate the effect of bariatric surgery on glucocorticoid metabolism in lean and obese mice.MethodsLean mice and HFD mice underwent Vertical Sleeve Gastrectomy (VSG) or sham surgery. Glucose and insulin tolerance tests were performed at four and ten weeks post operatively and circulating corticosterone was measured. Liver and adipose tissues were harvested from fed mice and 11β-HSD1 and GR levels were measured by quantitative RT-PCR or Western (immuno-) blotting, respectively.ResultsVSG did not cause excess weight loss in lean mice when compared to sham operated mice. However, both lean and HFD VSG mice displayed significantly improved glucose clearance and insulin sensitivity. Remarkably, VSG restores physiological corticosterone production in HFD mice and reduces11β-HSD1 levels at four and ten weeks post-surgery. Additionally, lean mice displayed significantly lowered mRNA levels of 11β-HSD1 in subcutaneous adipose tissue and GR in liver.ConclusionsBariatric surgery improves insulin sensitivity and reduces glucocorticoid activation at tissular level, under physiological and pathophysiological (obesity) conditions, irrespective of weight loss. The reduction of glucocorticoid exposure may represent an additional contribution to the health benefits of bariatric surgery. These findings point towards a physiologically relevant gut-adrenal axis.
Balancing selection maintains hyper-divergent haplotypes inC. elegans
Authors: Lee Daehan , Zdraljevic Stefan , Stevens Lewis , Wang Ye , Tanny Robyn E. , Crombie Timothy A. , Cook Daniel E. , Webster Amy K. , Chirakar Rojin , Baugh L. Ryan , Sterken Mark G. , Braendle Christian , Félix Marie-Anne , Rockman Matthew V. , Andersen Erik C. 
Published: July 2020

AbstractAcross diverse taxa, selfing species have evolved independently from outcrossing species thousands of times. The transition from outcrossing to selfing significantly decreases the effective population size, effective recombination rate, and heterozygosity within a species. These changes lead to a reduction in genetic diversity, and therefore adaptive potential, by intensifying the effects of random genetic drift and linked selection. Within the nematode genusCaenorhabditis, selfing has evolved at least three times and all three species, including in the model organismCaenorhabditis elegans, show substantially reduced genetic diversity relative to outcrossing species. Selfing and outcrossingCaenorhabditisspecies are often found in the same niches, but we still do not know how selfing species with limited genetic diversity can adapt to these environments. Here, we examine the whole-genome sequences from 609 wildC. elegansstrains isolated worldwide and show that genetic variation is concentrated in punctuated hyper-divergent regions that cover 20% of theC. elegansreference genome. These regions are enriched in environmental response genes that mediate sensory perception, pathogen response, and xenobiotic stress response. Population genomic evidence suggests that genetic diversity in these regions has been maintained by long-term balancing selection. Using long-read genome assemblies for 15 wild strains, we show that hyper-divergent haplotypes contain unique sets of genes and show levels of divergence comparable to levels found betweenCaenorhabditisspecies that diverged millions of years ago. These results provide an example for how species can avoid the evolutionary “dead end” associated with selfing.
Dielectrophoretic separation of randomly shaped protein particles
Authors: Kwak Tae Joon , Jung Huihun , Allen Benjamin D , Demirel Melik C , Chang Woo-Jin 
Published: July 2020

AbstractRecently, insoluble protein particles have been increasingly investigated for artificial drug delivery systems due to their favorable properties, including programmability for active drug targeting of diseases as well as their biocompatibility and biodegradability after administration. One of the biggest challenges is selectively collecting monodisperse particles in desirable morphologies and sizes to enable consistent levels and rates of drug loading and release. Therefore, technology that allows sorting of protein particles with respect to size and morphology will enhance the design and production of next-generation drug delivery materials. Here, we introduce a dielectrophoretic (DEP) separation technique to selectively isolate spherical protein particles from a mixture of randomly shaped particles. We tested this approach by applying it to a mixture of precipitated squid ring teeth inspired tandem repeat protein particles with diverse sizes and morphologies. The DEP trapping system enabled us to isolate specific-sized, spherical protein particles out of this mixture: after separation, the fraction of 2 μm and 4 μm spherical particles was increased from 28.64% of mixture to 80.53% and 74.02% with polydispersity indexes (PDIs) decreased from 0.93 of mixture to 0.19 and 0.09, respectively. The protein particles show high aqueous swelling capability (up to 74% by mass) that could enable delivery of drug solutions. This work is intended to inspire the future development of biocompatible drug-delivery systems.
Synergistic Effects of the DRD2/3 Antagonist ONC201 and Radiation in Glioblastoma
Authors: He Ling , Bhat Kruttika , Ioannidis Angeliki , Zhang Le , Nguyen Nhan T. , Allen Joshua E. , Nghiemphu Phioanh Leia , Cloughesy Timothy F. , Liau Linda M. , Kornblum Harley I. , Pajonk Frank 
Published: July 2020

AbstractBackgroundGlioblastoma (GBM) is the deadliest of all brain cancers in adults. The current standard-of-care is surgery followed by radiotherapy and temozolomide, leading to a median survival time of only 15 months. GBM are organized hierarchically with a small number of glioma-initiating cells, responsible for therapy resistance and tumor recurrence, suggesting that targeting glioma-initiating cells could improve treatment response. ONC201 is a first-in-class anti-tumor agent with clinical efficacy in some forms of high-grade gliomas. Here we test its efficacy against GBM in combination with radiation.MethodsUsing patient-derived GBM lines and mouse models of GBM we test the effects of radiation and ONC201 on GBM self - renewalin vitroand survivalin vivo. A possible resistance mechanism is investigated using RNA-Sequencing.ResultsTreatment of GBM cells with ONC201 reduced self-renewal, clonogenicity and cell viabilityin vitro. ONC201 exhibited anti-tumor effects on radioresistant GBM cells indicated by reduced self-renewal in secondary and tertiary glioma spheres. Combined treatment with ONC201 and radiation prolonged survival in syngeneic and patient-derived orthotopic xenograft mouse models of GBM. Subsequent transcriptome analyses after combined treatment revealed shifts in gene expression signatures related to quiescent GBM populations, GBM plasticity, and GBM stem cells.ConclusionsOur findings suggest that combined treatment with the DRD2/3 antagonist ONC201 and radiation improves the efficacy of radiation against GBMin vitroandin vivothrough suppression of GICs without increasing toxicity in mouse models of GBM. A clinical assessment of this novel combination therapy against GBM is further warranted.Key points- Combined treatment of ONC201 and radiation exhibit anti-tumor effects on cells from primary and recurrent GBM- Combined treatment significantly prolongs survival in vivo- Combined treatment potentially targets the quiescent GBM cell populationImportance of the StudyThe survival rates for patients with GBM are unacceptably low and novel treatment approaches are needed. This study provides evidence that a combination of radiation and the dopamine receptor antagonist ONC201 significantly prolongs survival in mouse models of glioma.
Metabarcoding reveals different zooplankton communities in northern and southern areas of the North Sea
Authors: Macher Jan Niklas , van der Hoorn Berry B. , Peijnenburg Katja T. C. A. , van Walraven Lodewijk , Renema Willem 
Published: July 2020

AbstractZooplankton are key players in marine ecosystems, linking primary production to higher trophic levels. The high abundance and high taxonomic diversity renders zooplankton ideal for biodiversity monitoring. However, taxonomic identification of the zooplankton assemblage is challenging due to its high diversity, subtle morphological differences and the presence of many meroplanktonic species, especially in coastal seas. Molecular techniques such as metabarcoding can help with rapid processing and identification of taxa in complex samples, and are therefore promising tools for identifying zooplankton communities. In this study, we applied metabarcoding of the mitochondrial cytochrome c oxidase I gene to zooplankton samples collected along a latitudinal transect in the North Sea, a shelf sea of the Atlantic Ocean. Northern regions of the North Sea are influenced by inflow of oceanic Atlantic waters, whereas the southern parts are characterised by more coastal waters. Our metabarcoding results indicated strong differences in zooplankton community composition between northern and southern areas of the North Sea, particularly in the classes Copepoda, Actinopterygii (ray-finned fishes) and Polychaeta. We compared these results to the known distributions of species reported in previous studies, and by comparing the abundance of copepods to data obtained from the Continuous Plankton Recorder (CPR). We found that our metabarcoding results are mostly congruent with the reported distribution and abundance patterns of zooplankton species in the North Sea. Our results highlight the power of metabarcoding to rapidly assess complex zooplankton samples, and we suggest that the technique could be used in future monitoring campaigns and biodiversity assessments.HighlightsZooplankton communities are different in northern and southern areas of the North SeaMetabarcoding results are consistent with known species distributions and abundanceMetabarcoding allows for fast identification of meroplanktonic species
PecanPy: a fast, efficient, and parallelized Python implementation ofnode2vec
Authors: Liu Renming , Krishnan Arjun 
Published: July 2020

AbstractLearning low-dimensional representations (embeddings) of nodes in large graphs is key to applying machine learning on massive biological networks.Node2vecis the most widely used method for node embedding. However, its original Python and C++ implementations scale poorly with network density, failing for dense biological networks with hundreds of millions of edges. We have developed PecanPy, a new Python implementation ofnode2vecthat uses cache-optimized compact graph data structures and precomputing/parallelization to result in fast, high-quality node embeddings for biological networks of all sizes and densities. PecanPy software and documentation are available athttps://github.com/krishnanlab/pecanpy.
A Feedback Mechanism RegulatesOdorant ReceptorExpression in the Malaria Mosquito,Anopheles gambiae
Authors: Maguire Sarah E. , Afify Ali , Goff Loyal A. , Potter Christopher J. 
Published: July 2020

ABSTRACTMosquitoes locate and approach humans (‘host-seek’) when specific Olfactory Neurons (ORNs) in the olfactory periphery activate a specific combination of glomeruli in the mosquito Antennal Lobe (AL). We hypothesize that dysregulating proper glomerular activation in the presence of human odor will prevent host-seeking behavior. In experiments aimed at ectopically activating most ORNs in the presence of human odor, we made a surprising finding: ectopic expression of anAgOr (AgOr2)inAnopheles gambiaeORNs dampens the activity of the expressing neuron. This contrasts studies inDrosophila melanogaster, the typical insect model of olfaction, in which ectopic expression of non-native ORs in ORNs confers ectopic neuronal responses without interfering with native olfactory physiology. To gain insight into this dysfunction in mosquitoes, RNA-seq analyses were performed comparing wild-type antennae to those ectopically expressingAgOr2in ORNs. Remarkably, almost allOrtranscripts were significantly downregulated (except forAgOr2), and additional experiments suggest that it is AgOR2 protein rather than mRNA that mediates this downregulation. Our study shows that ORNs ofAnophelesmosquitoes (in contrast toDrosophila) employ a currently unexplored regulatory mechanism of OR expression, which may be adaptable as a vector-control strategy.SIGNIFICANCE STATEMENTStudies inDrosophila melanogastersuggest that insect Olfactory Receptor Neurons (ORNs) do not contain mechanisms by which Odorant Receptors (ORs) regulate OR expression. This has proved useful in studies where ectopic expression of an OR inDrosophilaORNs confers responses to the odorants that activate the newly expressed OR. In experiments inAnopheles gambiaemosquitoes, we found that ectopic expression of an OR in mostAnophelesORNs dampened the activity of the expressing neurons. RNA-seq analyses demonstrated that ectopic OR expression inAnophelesORNs leads to downregulation of endogenousOrtranscripts. Additional experiments suggest that this downregulation required ectopic expression of a functional OR protein. These findings reveal thatAnophelesmosquitoes, in contrast toDrosophila, contain a feedback mechanism to regulate OR expression. Mosquito ORNs might employ regulatory mechanisms of OR expression previously thought to occur only in non-insect olfactory systems.
Kilohertz retinal FF-SS-OCT and flood imaging with hardware-based adaptive optics
Authors: Valente Denise , Vienola Kari V. , Zawadzki Robert J. , Jonnal Ravi S. 
Published: July 2020

AbstractA retinal imaging system was designed for full-field (FF) swept-source (SS) optical coherence tomography (OCT) with cellular resolution. The system incorporates a real-time adaptive optics (AO) subsystem and a very high speed CMOS sensor, and is capable of acquiring volumetric images of the retina at rates up to 1 kHz. While digital aberration correction (DAC) is an attractive potential alternative to AO, it has not yet been shown to provide resolution of cones in the fovea, where early detection of functional deficits is most critical. Here we demonstrate that FF-SS-OCT with hardware AO permits resolution of foveal cones, with volume rates adequate to measure light-evoked changes in photoreceptors. With the reference arm blocked, the system can operate as kilohertz AO flood illumination fundus camera with adjustable temporal coherence and is expected to allow measurement of light-evoked changes caused by common path interference in photoreceptor outer segments (OS). In this work, we describe the system’s optical design, characterize its performance, and demonstrate its ability to produce images of the human photoreceptor mosaic.
Multi-Platform Assessment of DNA Sequencing Performance using Human and Bacterial Reference Genomes in the ABRF Next-Generation Sequencing Study
Authors: Foox Jonathan , Tighe Scott W. , Nicolet Charles M. , Zook Justin M. , Byrska-Bishop Marta , Clarke Wayne E. , Khayat Michael M. , Mahmoud Medhat , Laaguiby Phoebe K. , Herbert Zachary T. , Warner Derek , Grills George S. , Jen Jin , Levy Shawn , Xiang Jenny , Alonso Alicia , Schroth Gary P. , Sedlazeck Fritz J. , Narzisi Giuseppe , Farmerie William , Baldwin Don A. , Mason Christopher E. 
Published: July 2020

AbstractMassively parallel DNA sequencing is a critical tool for genomics research and clinical diagnostics. Here, we describe the Association of Biomolecular Resource Facilities (ABRF) Next-Generation Sequencing Phase II Study to measure quality and reproducibility of DNA sequencing. Replicates of human and bacterial reference DNA samples were generated across multiple sequencing platforms, including well-established technologies such as Illumina, ThermoFisher Ion Torrent, and Pacific Biosciences, as well as emerging technologies such as BGI, Genapsys, and Oxford Nanopore. A total of 202 datasets were generated to investigate the performance of a total of 16 sequencing platforms, including mappability of reads, coverage and error rates in difficult genomic regions, and detection of small-scale polymorphisms and large-scale structural variants. This study provides a comprehensive baseline resource for continual benchmarking as chemistries, methods, and platforms evolve for DNA sequencing.
Novel rabies virus variant for bi-directional optical control reveals modulatory influence of the pulvinar on visual cortex in rat
Authors: Scholl LR , Zhang L , Foik AT , Lyon DC 
Published: July 2020

AbstractOptogenetic tools have become of great utility in the causal analysis of systems in the brain. However, current optogenetic techniques do not reliably support both excitation and suppression of the same cells in vivo, limiting analysis and slowing research. Here we developed a novel glycoprotein-deleted rabies virus expressing two channelrhodopsin proteins, GtACR2 and Chrimson, in order to independently manipulate excitatory and inhibitory transmembrane potentials, respectively. Using this approach, we demonstrated that rodent pulvinar neurons modulate cortical size tuning and suppress flash responses, but do not drive activity in visual cortex. While our goal was primarily to develop this novel method to study the structure-function organization of thalamocortical circuits, this technique is readily applicable to study any brain region.