bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monte Carlo Simulation of Diffusion MRI in geometries constructed from two-photon microscopy of human cortical grey matter
Authors: Gilani Nima , Hildebrand Sven , Schueth Anna , Roebroeck Alard 
Published: May 2019

AbstractPurposeNeurodegenerative diseases such as Alzheimer’s disease cause changes and disruption to cortical microstructure and architecture. Diffusion MRI (dMRI) could potentially be sensitive to such changes. There is a growing interest in modeling of human cortical areas using a combination of quantitative MRI and 3D microscopy. The purpose of this study was to quantitatively characterize the cytoarchitecture of human cortical tissue from 3D fluorescence microscopy to simulate diffusion MRI (dMRI) signal in the cortex to better understand its diffusion signal characteristics.MethodsDiffusion of water molecules and dMRI signal were simulated by an indirect geometry based method and a direct voxel based method in microstructural details extracted from microscopy of cortex. Additionally, residence times of diffusing spins inside voxel volumes were considered to set effective resolution limits. Mean diffusivity (MD) and kurtosis (MK) were calculated for variable cell and neurite densities, sizes and diffusion times under realistic values for permeability and free diffusion.ResultsBoth simulation methods could efficiently and accurately simulate dMRI signals with fractional anisotropy, diffusion coefficient and kurtosis in agreement with previous reports. Simulated MD and MK showed changes with increasing diffusion times specific to cortical cell density and sizes, with MK showing the highest sensitivity. Intra-voxel residence times with increasing diffusion times showed that the effective dMRI resolution approaches the thickness of cortical layers.ConclusionsMonte Carlo simulations based on 3D microscopy data enable estimating changes in MD and MK over diffusion times and are sensitive to cortical cytoarchitecture and its possible changes in neurodegenerative disease. When considering layer-specific cortical dMRI, effective resolution due to residence times is an important concern.
Molecular signatures of selection associated with host-plant differences in Pieris butterflies
Authors: Okamura Yu , Sato Ai , Tsuzuki Natsumi , Murakami Masashi , Heidel-Fischer Hanna , Vogel Heiko 
Published: May 2019

AbstractAdaptive traits that enable organisms to conquer novel niches and experience subsequent diversification are ecologically and evolutionarily important. The larvae of Pieris butterflies express nitrile-specifier proteins (NSPs), a key innovation for overcoming the glucosinolate (GLS)-myrosinase-based defense system of their Brassicales host-plants. NSPs are a member of the NSP-like gene family, which includes the major allergen (MA) protein, a paralog of NSP with a GLS-disarming function, and a single domain major allergen (SDMA) protein, whose function is unknown. The arms-race between a highly variable host-plant defense system and members of the NSP-like gene family is suggested to mediate diversification in both Pierid butterflies and Brassicales plants. Here, we combined feeding experiments using 25 Brassicaceae plants and five Pieris species with larval transcriptome data to investigate the evolutionary forces acting on NSP-like gene family members associated with patterns of host-plant usage. Although we observed significantly elevated nonsynonymous to synonymous substitution ratios in NSPs, no such pattern was observed in MAs or SDMAs. Furthermore, we found a signature of positive selection of NSP at a phylogenetic branch which reflects different host-plant preferences. Our data indicate that NSPs have evolved in response to shifting preferences for host plants among five Pieris butterflies, whereas MAs and SDMAs appear to have more conserved functions. Our results show that the evolution and functional differentiation of key genes used in host-plant adaptation play a crucial role in the chemical arms-race between Pieris butterflies and their Brassicales host-plants.
A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in theLPApromoter
Authors: Coassin Stefan , Hermann-Kleiter Natascha , Haun Margot , Wahl Simone , Wilson Rory , Paulweber Bernhard , Kunze Sonja , Meitinger Thomas , Strauch Konstantin , Peters Annette , Waldenberger Melanie , Kronenberg Florian , Lamina Claudia 
Published: May 2019

AbstractLipoprotein(a) [Lp(a)] is a major cardiovascular risk factor, which is largely genetically determined by one major gene locus, theLPAgene. Many aspects of the transcriptional regulation ofLPAare poorly understood and the role of epigenetics has not been addressed yet. Therefore, we conducted an epigenome-wide analysis of DNA methylation on Lp(a) levels in two population-based studies (total n=2208). We identified a CpG site in theLPApromoter which was significantly associated with Lp(a) concentrations. Surprisingly, the identified CpG site was found to overlap the SNP rs76735376. We genotyped this SNP de-novo in three studies (total n=7512). The minor allele of rs76735376 (1.1% minor allele frequency) was associated with increased Lp(a) values (p=1.01e-59) and explained 3.5% of the variation of Lp(a). Statistical mediation analysis showed that the effect on Lp(a) is rather originating from the base change itself and is not mediated by DNA methylation levels. This finding is supported by eQTL data from 153 liver tissue samples from the GTEx project, which shows a significant association of the rs76735376 minor allele with increasedLPAexpression. In summary, our data supports a functional role of rs76735376 in the regulation ofLPAexpression.
2D or 3D? How in vitro cell motility is conserved across dimensions, and predicts in vivo invasion
Authors: Galarza Sualyneth , Kim Hyuna , Atay Naciye , Peyton Shelly R , Munson Jennifer M 
Published: May 2019

AbstractCell motility is a critical aspect of wound healing, the immune response, and is deregulated in cancer. Current limitations in imaging tools make it difficult to study cell migration in vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D and 3D tissue model systems in which to study cell motility in vitro, with the aim of mimicking the environments in which cells move in vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries/systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, in vitro models are predictive of in vivo cell motility. To our surprise, many metrics of cell movement on 2D surfaces significantly and positively correlate with cell migration in 3D environments, and cell invasion in 3D is negatively correlated with glioblastoma invasion in vivo. Finally, to best compare across complex model systems, in vivo data, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility.
PureseqTM: efficient and accurate prediction of transmembrane topology from amino acid sequence only
Authors: Wang Qing , Ni Chong-ming , Li Zhen , Li Xiu-feng , Han Ren-min , Zhao Feng , Xu Jinbo , Gao Xin , Wang Sheng 
Published: May 2019

AbstractMotivationRapid and accurate identification of transmembrane (TM) topology is well suited for the annotation of the entire membrane proteome. It is the initial step of predicting the structure and function of membrane proteins. However, existing methods that utilize only amino acid sequence information suffer from low prediction accuracy, whereas methods that exploit sequence profile or consensus need too much computational time.MethodHere we propose a deep learning framework DeepCNF that predicts TM topology from amino acid sequence only. Compared to previous sequence-based approaches that use hidden Markov models or dynamic Bayesian networks, DeepCNF is able to incorporate much more contextual information by a hierarchical deep neural network, while simultaneously modeling the interdependency between adjacent topology labels.ResultExperimental results show that PureseqTM not only outperforms existing sequence-based methods, but also reaches or even surpasses the profile/consensus methods. On the 39 newly released membrane proteins, our approach successfully identifies the correct TM segments and boundaries for at least 3 cases while all existing methods fail to do so. When applied to the entire human proteome, our method can identify the incorrect annotations of TM regions by UniProt and discover the membrane-related proteins that are not manually curated as membrane proteins.Availabilityhttp://pureseqtm.predmp.com/
Patterns of putative gene loss suggest rampant developmental system drift in nematodes
Authors: Woodruff Gavin C. 
Published: May 2019

AbstractGene loss often contributes to the evolution of adaptive traits. Conversely, null mutations frequently reveal no obvious phenotypic consequences. How pervasive is gene loss, what kinds of genes are dispensable, and what are the consequences of gene loss? The nematodeCaenorhabditis eleganshas long been at the forefront of genetic research, yet only recently have genomic resources become available to situate this species in its comparative phylogenetic and evolutionary context. Here, patterns of gene loss withinCaenorhabditisare evaluated using 28 nematode genomes (most of them sequenced only in the past few years). Orthologous genes detected in every species except one were defined as being lost within that species. Putative functional roles of lost genes were determined using phenotypic information fromC. elegansWormBase ontology terms as well as using existingC. eleganstranscriptomic datasets. All species have lost multiple genes in a species-specific manner, with a genus-wide average of several dozen genes per species. Counterintuitively, nearly all species have lost genes that perform essential functions inC. elegans(an average of one third of the genes lost within a species). Retained genes reveal no differences from lost genes inC. eleganstranscriptional abundance across all developmental stages when considering all 28Caenorhabitisgenomes. However, when considering only genomes in the subgenericElegansgroup, lost genes tend to have lower expression than retained genes. Taken together, these results suggest that the genetics of developmental processes are evolving rapidly despite a highly conserved adult morphology and cell lineage in this group, a phenomenon known as developmental system drift. These patterns highlight the importance of the comparative approach in interpreting findings in model systems genetics.
Quantitative evaluation of a high resolution lipidomics platform
Authors: Liu Juan , Liu Xiaojing , Xiao Zhengtao , Locasale Jason W. 
Published: May 2019

AbstractGiven the general importance of lipids in health and disease, there is a need for efficient technology that broadly profiles and quantitates the lipid composition of complex mixtures. In this study, we developed and quantitatively evaluated a platform that simultaneously profiles both lipids and polar metabolites from the same sample. This method was achieved by using a methyl tert-butyl ether (MTBE) extraction and employing two liquid chromatography methods coupled with high resolution mass spectrometry (LC-HRMS). This workflow enabled detection and semi-quantitation of over 300 polar metabolites as well as over 300 lipids with comprehensive coverage of diverse chemical classes. Using cultured mammalian cells as an example, we report the quantitative properties of the platform including the sensitivity and linear range. The lipidomics strategy was further applied to characterize changes to lipid metabolism upon treatment with metformin to human ovarian cancer cells. Of the 256 detected lipids, 99 lipids (39%) significantly increased, 11 lipids (4%) were significantly reduced and 146 lipids (57%) remain unchanged in metformin-treated cells. Stable isotope tracing of carbon into lipids using [13C6]-glucose further measured the contribution of de novo fatty acid synthesis to the total fatty acid pool. In summary, the platform enabled the semi-quantitative assessment of hundreds of lipid species and associated carbon incorporation from glucose in a high throughput manner.
Sex classification by resting state brain connectivity
Authors: Weis Susanne , Patil Kaustubh , Hoffstaedter Felix , Nostro Alessandra , Yeo B.T. Thomas , Eickhoff Simon B. 
Published: May 2019

1AbstractA large amount of brain imaging research has focused on group studies delineating differences between males and females with respect to both cognitive performance as well as structural and functional brain organization. To supplement existing findings, the present study employed a machine learning approach to assess how accurately participants’ sex can be classified based on spatially specific resting state (RS) brain-connectivity, using two samples from the Human Connectome Project (n1 = 434, n2 = 310) and one fully independent sample from the 1000BRAINS study (n=941). The classifier, which was trained on one sample and tested on the other two, was able to reliably classify sex, both within sample and across independent samples, differing both with respect to imaging parameters and sample characteristics. Brain regions displaying highest sex classification accuracies were mainly located along the cingulate cortex, medial and lateral frontal cortex, temporo-parietal regions, insula and precuneus. These areas were stable across samples and match well with previously described sex differences in functional brain organization. While our data show a clear link between sex and regionally specific brain connectivity, they do not support a clear-cut dimorphism in functional brain organization that is driven by sex alone.
Characterisation of gastrointestinal helminths and their impact in commercial small-scale chicken flocks in the Mekong Delta of Vietnam
Authors: Van Nguyen T.B. , Cuong Nguyen V , Yen Nguyen T. Phuong , Nhi Nguyen T.H. , Kiet Bach Tuan , Hoang Nguyen V. , Hien Vo B. , Thwaites Guy , Carrique-Mas Juan J. , Ribas Alexis 
Published: May 2019

AbstractCommercial small-scale chicken farms using all-in-all-out production but operating with low standards of hygiene/biosecurity are increasingly common in Vietnam. These conditions facilitate transmission of gastrointestinal helminths. However there are no published data on these parasites in these systems. The aims were: (1) to determine the prevalence/burden of gastrointestinal helminths in small-scale commercial flocks in commercial small-scale flocks in the Mekong Delta region; and (2) to investigate the association between worm burdens and birds’ weight and disease status. Randomly selected chickens (n=120) (‘normal’ flocks) were investigated at the end of their production cycle (∼18 weeks), as well as 90 chickens with signs of respiratory and/or severe disease. The gastrointestinal tract of chickens was dissected and all visible helminths were identified. 54.2% and 54.4% healthy and diseased chickens contained helminths. Diseased, colonized chickens harboured a higher mass of helminth worms (3.8 ±SD 8.6g) than colonized, healthy chickens (1.9 ±6.3g). Eight species were identified, three nematodes (Ascaridia galli, Cheilospirura hamulosa and Heterakis gallinarum), four cestodes (Hymenolepis, Raillietina cesticillus, Raillietina echinobothrida, Raillietina tetragona,) and one trematode (Echinostomatidae). Heterakis gallinarum was the most prevalent helminth (43.3% and 42.2% in healthy and sick chickens, respectively), followed by A. galli (26.7% and 41.1%). Colonized chickens weighed 101.5g less than non-colonized birds. Colonisation was significantly higher during the rainy months (May-November) for both H. gallinarum and A. galli. Anthelminthic usage was not associated with reduced helminth burdens. We recommend upgrading cleaning and disinfection and limiting access to ranging areas to control helminth infections in small-scale commercial chicken flocks.
Investigating Fibroblast-Induced Collagen Gel Contraction Using a Dynamic Microscale Platform
Authors: Zhang Tianzi , Day John H. , Su Xiaojing , Guadarrama Arturo G. , Sandbo Nathan K. , Esnault Stephane , Denlinger Loren C. , Berthier Erwin , Theberge Ashleigh B. 
Published: May 2019

AbstractMechanical forces have long been recognized as fundamental drivers in biological processes, such as embryogenesis, tissue formation and disease regulation. The collagen gel contraction (CGC) assay has served as a classic tool in the field of mechanobiology to study cell-induced contraction of extracellular matrix (ECM), which plays an important role in inflammation and wound healing. In a conventional CGC assay, cell-laden collagen is loaded into a cell culture vessel (typically a well plate) and forms a disk-shaped gel adhering to the bottom of the vessel. The decrement in diameter or surface area of the gel is used as a parameter to quantify the degree of cell contractility. In this study, we developed a microscale CGC assay with an engineered well plate insert that uses surface tension forces to load and manipulate small volumes (14 µL) of cell-laden collagen. The system is easily operated with two pipetting steps and the microscale device moves dynamically as a result of cellular forces. We used a straightforward one-dimensional measurement as the gel contraction readout. We adapted a conventional lung fibroblast CGC assay to demonstrate the functionality of the device, observing significantly more gel contraction when human lung fibroblasts were cultured in serum-containing media versus serum-free media (p≤0.01). We further cocultured eosinophils and fibroblasts in the system, two important cellular components that lead to fibrosis in asthma, and observed that soluble factors from eosinophils significantly increase fibroblast-mediated gel contraction (p≤0.01). Our microscale CGC device provides a new method for studying downstream ECM effects of intercellular cross talk using 7-35 fold less cell-laden gel than traditional CGC assays.
Efficient small-world and scale-free functional brain networks at rest using k-nearest neighbors thresholding
Authors: Forlim Caroline Garcia , Haghiri Siavash , Düzel Sandra , Kühn Simone 
Published: May 2019

AbstractIn recent years, there has been a massive effort to analyze the topological properties of brain networks. Yet, one of the challenging questions in the field is how to construct brain networks based on the connectivity values derived from neuroimaging methods. From a theoretical point of view, it is plausible that the brain would have evolved to minimize energetic costs of information processing, and therefore, maximizes efficiency as well as to redirect its function in an adaptive fashion, that is, resilience. A brain network with such features, when characterized using graph analysis, would present small-world and scale-free properties.In this paper, we focused on how the brain network is constructed by introducing and testing an alternative method: k-nearest neighbor (kNN). In addition, we compared the kNN method with one of the most common methods in neuroscience: namely the density threshold. We performed our analyses on functional connectivity matrices derived from resting state fMRI of a big imaging cohort (N=434) of young and older healthy participants. The topology of networks was characterized by the graph measures degree, characteristic path length, clustering coefficient and small world. In addition, we verified whether kNN produces scale-free networks. We showed that networks built by kNN presented advantages over traditional thresholding methods, namely greater values for small-world (linked to efficiency of networks) than those derived by means of density thresholds and moreover, it presented also scale-free properties (linked to the resilience of networks), where density threshold did not. A brain network with such properties would have advantages in terms of efficiency, rapid adaptive reconfiguration and resilience, features of brain networks that are relevant for plasticity and cognition as well as neurological diseases as stroke and dementia.HighlightsA novel thresholding method for brain networks based on k-nearest neighbors (kNN)kNN applied on resting state fMRI from a big cohort of healthy subjects BASE-IIkNN built networks present greater small world properties than density thresholdkNN built networks present scale-free properties whereas density threshold did not
The persimmon genome reveals clues to the evolution of a lineage-specific sex determination system in plants
Authors: Akagi Takashi , Shirasawa Kenta , Nagasaki Hideki , Hirakawa Hideki , Tao Ryutaro , Comai Luca , Henry Isabelle M. 
Published: May 2019

AbstractMost angiosperms bear hermaphroditic flowers, but a few species have evolved outcrossing strategies, such as dioecy, the presence of separate male and female individuals. We previously investigated the mechanisms underlying dioecy in diploid persimmon (D. lotus) and found that male flowers are specified by repression of the autosomal gene MeGI by its paralog, the Y-encoded pseudo-gene OGI. This mechanism is thought to be lineage-specific, but its evolutionary path remains unknown. Here, we developed a full draft of the diploid persimmon genome (D. lotus), which revealed a lineage-specific genome-wide paleoduplication event. Together with a subsequent persimmon-specific duplication(s), these events resulted in the presence of three paralogs, MeGI, OGI and newly identified Sister of MeGI (SiMeGI), from the single original gene. Evolutionary analysis suggested that MeGI underwent adaptive evolution after the paleoduplication event. Transformation of tobacco plants with MeGI and SiMeGI revealed that MeGI specifically acquired a new function as a repressor of male organ development, while SiMeGI presumably maintained the original function. Later, local duplication spawned MeGI’s regulator OGI, completing the path leading to dioecy. These findings exemplify how duplication events can provide flexible genetic material available to help respond to varying environments and provide interesting parallels for our understanding of the mechanisms underlying the transition into dieocy in plants.Author summaryPlant sexuality has fascinated scientists for decades. Most plants can self-reproduce but not all. For example, a small subset of species have evolved a system called dioecy, with separate male and female individuals. Dioecy has evolved multiple times independently and, while we do not understand the molecular mechanisms underlying dioecy in many of these species yet, a picture is starting to emerge with recent progress in several dioecious species. Here, we focused on the evolutionary events leading to dioecy in persimmon. Our previous work had identified a pair of genes regulating sex in this species, called OGI and MeGI. We drafted the whole genome sequence of diploid persimmon to investigate their evolutionary history. We discovered a lineage-specific genome duplication event, and observed that MeGI underwent adaptive evolution after this duplication. Transgenic analyses validated that MeGI newly acquired a male-suppressor function, while the other copy of this gene, SiMeGI, did not. The regulator of MeGI, OGI, resulted from a second smaller-scale duplication event, finalizing the system. This study sheds light on the role of duplication as a mechanism that promote flexible genes functions, and how it can affect important biological functions, such as the establishment of a new sexual system.