bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antifungal activity of Ocotea odorifera (Vell.) Rowher, Ocotea puberula (Rich.) Nees and Cinnamodendron dinisii Schwanke essential oils
Authors: Mezzomo P. , Sausen T.L. , Paroul N. , Roman S.S. , Mielniczki A.A.P. , Cansian R.L. 
Published: December 2019

AbstractBiocompounds are promising tools with the potential to control pathogenic microorganisms. The medicinal plant species Ocotea odorifera, Ocotea puberula and Cinnamodendron dinisii, distributed along Brazilian biomes, are sources of chemical compounds of biological interest. This study aimed to evaluate the antifungal activity of the essential oils of O. odorifera, O. puberula and C. dinisii essential oils upon the mycotoxin producers Alternaria alternata, Aspergillus flavus and Penicillium crustosum. The essential oils where characterized by gas chromatography coupled to mass spectrometer (CG-MS). The majority compounds identified were: safrol (39.23%) and camphor (31.54%) in O. odorifera, Beta-caryophyllene (25.01%) and spathulenol (17.74%) in O. puberula, and bicyclogermacrene (23.19%) and spathulenol (20.21%) in C. dinisii. The Minimal Inhibitory Concentration (MIC) of antifungal activity considered diameters higher than 10 mm after 72 h of incubation at 30 ºC. A. alternata presented higher resistance to O. odorifera and C. dinisii oils. The inhibitory effect of O. odorifera on A. flavus showed stabilization at oils concentrations between 50% and 80%, increasing at 90% and 100% (pure oil) treatments. We observed that the essential oils of O. odorifera and C. dinisii have potential in the control of the analyzed fungi species. The essential oil of O. odorifera presented a better activity in all the assays, which can be related to the presence of safrole and phenylpropenes, compounds with known antifungal activity.
Polymorphic inversions underlie the shared genetic susceptibility to prevalent common diseases
Authors: González Juan R , Ruiz-Arenas Carlos , Cáceres Alejandro , Morán Ignasi , López Marcos , Alonso Lorena , Tolosana Ignacio , Guindo-Martínez Marta , Mercader Josep M , Esko Tonu , Torrents David , González Josefa , Pérez-Jurado Luis A 
Published: December 2019

AbstractThe burden of several common diseases including obesity, diabetes, hypertension, asthma, and depression is increasing in most world populations. However, the mechanisms underlying the numerous epidemiological and genetic correlations among these disorders remain largely unknown. We investigated whether common polymorphic inversions underlie the shared genetic influence of these disorders. We performed the largest inversion association analysis to date, including 21 inversions and 25 obesity-related traits, on a total of 408,898 Europeans, and validated the results in 67,299 independent individuals. Seven inversions were associated with multiple diseases while inversions at 8p23.1, 16p11.2 and 11q13.2 were strongly associated with the co-occurrence of obesity with other common diseases. Transcriptome analysis across numerous tissues revealed strong candidate genes of obesity-related traits. Analyses in human pancreatic islets indicated the potential mechanism of inversions in the susceptibility of diabetes by disrupting the cis-regulatory effect of SNPs from their target genes. Our data underscore the role of inversions as major genetic contributors to the joint susceptibility to common complex diseases.
Coinfinder: Detecting Significant Associations and Dissociations in Pangenomes
Authors: Whelan Fiona Jane , Rusilowicz Martin , McInerney James Oscar 
Published: December 2019

2.AbstractThe accessory genes of prokaryote and eukaryote pangenomes accumulate by horizontal gene transfer, differential gene loss, and the effects of selection and drift. We have developed Coinfinder, a software program that assesses whether sets of homologous genes (gene families) in pangenomes associate or dissociate with each other (i.e. are “coincident”) more often than would be expected by chance. Coinfinder employs a user-supplied phylogenetic tree in order to assess the lineage-dependence (i.e. the phylogenetic distribution) of each accessory gene, allowing Coinfinder to focus on coincident gene pairs whose joint presence is not simply because they happened to appear in the same clade, but rather that they tend to appear together more often than expected across the phylogeny. Coinfinder is implemented in C++, Python3, and R and is freely available under the GPU license fromhttps://github.com/fwhelan/coinfinder.3.Impact statementCoinfinder identifies genes that co-occur (associate) or avoid (dissociate) with each other across the accessory genomes of a pangenome of interest. Genes that associate or dissociate more often than expected by chance, suggests that those genes have a connection (attraction or repulsion) that is interesting to explore. Identification of these groups of genes will further the field’s understanding of the importance of accessory genes. Coinfinder is a freely available, open-source software which can identify gene patterns locally on a personal computer in a matter of hours.4.Data summaryCoinfinder is freely available athttps://github.com/fwhelan/coinfinder.A list of the Identifiers of the genomes used within as well as all input/output files are available athttps://github.com/fwhelan/coinfinder-manuscript.The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
A simple device to immobilize protists for electrophysiology and microinjection
Authors: Kulkarni Anirudh , Escoubet Nicolas , Pontani Léa-Laetitia , Prevost Alexis Michel , Brette Romain 
Published: December 2019

ABSTRACTWe present a simple device to mechanically immobilize motile cells such as ciliates and flagellates. It can be used in particular for intracellular electrophysiology and microinjection. A transparent filter with holes smaller than the specimen is stretched over an outlet. A flow is induced by either a peristaltic pump or a depressurized tank, mechanically entraining cells to the bottom, where they immobilize against the filter. The cells swim again freely as soon as the flow is stopped. We demonstrate the device by recording action potentials in Paramecium and injecting a fluorescent dye in the cytosol.
Microbial metabolically cohesive consortia and ecosystem functioning
Authors: Pascual-García Alberto , Bonhoeffer Sebastian , Bell Thomas 
Published: December 2019

AbstractRecent theory and experiments have reported a reproducible tendency for the coexistence of microbial species under controlled environmental conditions. This observation has been explained in the context of competition for resources and metabolic complementarity given that, in microbial communities, many excreted by-products of metabolism may also be resources. Microbial communities therefore play a key role in promoting their own stability and in shaping the niches of the constituent taxa. We suggest that an intermediate level of organisation between the species and the community level may be pervasive, where tightly-knit metabolic interactions create discrete consortia that are stably maintained. We call these units Metabolically Cohesive Consortia (MeCoCos) and we discuss the environmental context in which we expect their formation, and the ecological and evolutionary consequences of their existence. We argue that the ability to identify MeCoCos would open new avenues to link the species-, community-, and ecosystem-level properties, with consequences for our understanding of microbial ecology and evolution, and an improved ability to predict ecosystem functioning in the wild.
Hardy-Weinberg Equilibrium in the Large Scale Genomic Sequencing Era
Authors: Abramovs Nikita , Brass Andrew , Tassabehji May 
Published: December 2019

AbstractHardy-Weinberg Equilibrium (HWE) is used to estimate the number of homozygous and heterozygous variant carriers based on its allele frequency in populations that are not evolving. Previously, deviation from HWE in large population databases were investigated to detect genotyping errors, which can result in extreme heterozygote excess (HetExc). However, HetExc might also be a sign of natural selection since recessive disease causing variants are expected to occur less frequently in a homozygous state in the general population, but might reach high allele frequency, especially if they are advantageous, in a heterozygote state. We developed a filtering strategy to detect these variants and applied it on genome data from 137,842 individuals. We found that the main limitations of this approach were quality of genotype calls and insufficient population sizes, whereas population structure and high level of inbreeding could reduce sensitivity, but not precision, in certain populations. Nevertheless, we identified 365 HetExc variants in 326 genes, most of which were specific to African/African American populations (~84.7%). Although the majority of them were not associated with known diseases, or were classified as “benign”, they were enriched in genes associated with autosomal recessive diseases. The resulting dataset also contained two known recessive disease causing variants with evidence of heterozygote advantage in the genes HBB and CFTR. Finally, we provide in silico evidence of a novel heterozygote advantageous variant in the CHD6 gene (involved in influenza virus replication). We anticipate that our approach will allow the detection of rare recessive disease causing variants in the future.
Volumetric Segmentation and Characterisation of the Paracingulate Sulcus on MRI Scans
Authors: Yang Junwei , Wang Duo , Rollins Colleen , Leming Matthew , Liò Pietro , Suckling John , Murray Graham , Garrison Jane , Cachia Arnaud 
Published: December 2019

ABSTRACTMany architectures of deep neural networks have been designed to solve specific biomedical problems, among which segmentation is a critical step to detect and locate the boundaries of the target object from an image. In this paper, we develop a deep learning based framework to automatically segment the paracingulate sulcus (PCS) from the MRI scan and estimate lengths for its segments. The study is the first work on segmentation and characterisation of the PCS, and the model achieves a Dice score of over 0.77 on segmentation, which demonstrates its potential for clinical use to assist human annotation. Moreover, the proposed architecture as a solution can be generalised to other problems where the object has similar patterns.
The PIWI protein Aubergine recruits eIF3 to activate translation in the germ plasm
Authors: Ramat Anne , Garcia-Silva Maria-Rosa , Jahan Camille , Naït-Saïdi Rima , Dufourt Jérémy , Garret Céline , Chartier Aymeric , Cremaschi Julie , Patel Vipul , Decourcelle Mathilde , Bastide Amandine , Juge François , Simonelig Martine 
Published: December 2019

AbstractPiwi-interacting RNAs (piRNAs) and PIWI proteins are essential in germ cells to repress transposons and regulate mRNAs. InDrosophila, piRNAs bound to the PIWI protein Aubergine (Aub) are transferred maternally to the embryo and regulate maternal mRNA stability through two opposite roles. They target mRNAs by incomplete base-pairing, leading to both their destabilization in the soma, and stabilization in the germ plasm. Here, we report a function of Aub in translation. Aub is required for translational activation ofnanosmRNA, a key determinant of the germ plasm. Aub physically interacts with the poly(A) binding protein PABP and the translation initiation factor eIF3. Polysome gradient profiling identifies Aub role at the initiation step of translation. In the germ plasm, PABP and eIF3d assemble in foci that surround Aub-containing germ granules, and Aub acts with eIF3d to promotenanostranslation. These results reveal a new mode of mRNA regulation by Aub, highlighting PIWI protein versatility in mRNA regulation.
CDK4 as a phytochemical based anticancer drug target
Authors: Chando Rony Kumer , Hussain Nazmul , Rana Mashedul Islam , Sayed Shomoita , Alam Saruar , Fakir Tawkir Ahmed , Sharma Sudip , Tanu Arifur Rahman , Mobin Faraid , Apu Ehsanul Hoque , Hasan Kamrul , Sayed Abu , Ashraf Mohammad Arif 
Published: December 2019

AbstractSuccess story of plant-based medicine had been overlooked during the advent of modern pharmaceutical industry. Despite the negligence of the multimillion-dollar drug industry, people entirely rely on medicinal plants in some part of the world. In this study, we have emphasized on going back to those traditional medicinal practices to figure out their underlying mechanism to move forward on phytochemical based drug development. We screened Medicinal Plant Database Bangladesh 1.0 (MPDB1.0) and on-going extension, MPDB2.0, of that database to find traditionally used medicinal plants and their active compounds. Here, Mangiferin, extracted from Mangifera indica, have been demonstrated to interact with cell cycle regulator Cyclin-dependent Kinase 4 (CDK4). CDK4 is differentially expressed during Glioblastoma multiforme (GBM), Brain Lower Grade Glioma (LGG), and Sarcoma (SARC). Expression of CDK4 is interlinked to the patients’ survival rate and its consistent expression throughout different stages have provided the advantage to use it as diagnostic tool and drug target. Altogether, this study demonstrated that simple mango tree extracted active compounds, mangiferin, can work as potential anticancer drug and leveraging the recent advancement of sequencing and gene expression data can accelerate the phytochemical based drug discovery process.
Variant effect predictions capture some aspects of deep mutational scanning experiments
Authors: Reeb Jonas , Wirth Theresa , Rost Burkhard 
Published: December 2019

AbstractDeep mutational scanning (DMS) studies exploit the mutational landscape of sequence variation by systematically and comprehensively assaying the effect of single amino acid variants (SAVs) for particular proteins. Different experimental protocols proxy effect through a diversity of measures. We evaluated three early prediction methods trained on traditional variant effect data (PolyPhen-2, SIFT, SNAP2) along with a regression method optimized on DMS data (Envision). On a common subset of 32,981 SAVs, all methods capture some aspects of variant effects, albeit not the same. Early effect prediction methods correlated slightly more with measurements and better classified binary states (effect or neutral), while Envision predicted better the precise degree of effect. Most surprising was that a simple approach predicting residues conserved in families (found and aligned by PSI-BLAST) in many cases outperformed other methods. All methods predicted beneficial effects (gain-of-function) significantly worse than deleterious (loss-of-function). For the few proteins with several DMS measurements, experiments agreed more with each other than predictions with experiments. Our findings highlight challenges and opportunities of DMS for improving variant effect predictions.
Primary mammary organoid model of lactation and involution
Authors: Sumbal Jakub , Chiche Aurelie , Charifou Elsa , Koledova Zuzana , Li Han 
Published: December 2019

AbstractMammary gland development occurs mainly after birth and is composed of three successive stages: puberty, pregnancy and lactation, and involution. These developmental stages are associated with major tissue remodeling, including extensive changes in mammary epithelium as well as surrounding stroma. Three-dimensional (3D) mammary organoid culture has become an important tool in mammary gland biology and enabled invaluable discoveries on pubertal mammary branching morphogenesis and breast cancer. However, a suitable 3D organoid model recapitulating key aspects of lactation and involution has been missing. Here, we describe a robust and straightforward mouse mammary organoid system modeling lactation and involution-like process, which can be applied to study mechanisms of physiological mammary gland lactation and involution as well as pregnancy-associated breast cancer.
Estimating brain age from structural MRI and MEG data: Insights from dimensionality reduction techniques
Authors: Xifra-Porxas Alba , Ghosh Arna , Mitsis Georgios D. , Boudrias Marie-Hélène 
Published: December 2019

AbstractBrain age prediction studies aim at reliably estimating the difference between the chronological age of an individual and their predicted age based on neuroimaging data, which has been proposed as an informative measure of disease and cognitive decline. As most previous studies relied exclusively on magnetic resonance imaging (MRI) data, we hereby investigate whether combining structural MRI with functional magnetoencephalography (MEG) information improves age prediction using a large cohort of healthy subjects (N=613, age 18-88 yrs) from the Cam-CAN repository. To this end, we examined the performance of dimensionality reduction and multivariate associative techniques, namely Principal Component Analysis (PCA) and Canonical Correlation Analysis (CCA), to tackle the high dimensionality of neuroimaging data. Using MEG features (mean absolute error (MAE) of 9.60 yrs) yielded worse performance when compared to using MRI features (MAE of 5.33 yrs), but a stacking model combining both feature sets improved age prediction performance (MAE of 4.88 yrs). Furthermore, we found that PCA resulted in inferior performance, whereas CCA in conjunction with Gaussian process regression models yielded the best prediction performance. Notably, CCA allowed us to visualize the features that significantly contributed to brain age prediction. We found that MRI features from subcortical structures were more reliable age predictors than cortical features, and that spectral MEG measures were more reliable than connectivity metrics. Our results provide an insight into the underlying processes that are reflective of brain aging, yielding promise for the identification of reliable biomarkers of neurodegenerative diseases that emerge later during the lifespan.
Systematic detection of Mendelian and non-Mendelian variants associated with retinitis pigmentosa by genome-wide association study
Authors: Nishiguchi Koji M , Miya Fuyuki , Mori Yuka , Fujita Kosuke , Akiyama Masato , Kamatani Takashi , Koyanagi Yoshito , Kota Sato , Takigawa Toru , Ueno Shinji , Tsugita Misato , Kunikata Hiroshi , Cisarova Katarina , Nishino Jo , Murakami Akira , Abe Toshiaki , Momozawa Yukihide , Terasaki Hiroko , Wada Yuko , Sonoda Koh-Hei , Rivolta Carlo , Ishibashi Tatsuro , Tsunoda Tatsuhiko , Tsujikawa Motokazu , Ikeda Yasuhiro , Nakazawa Toru 
Published: December 2019

AbstractTo uncover genetic basis of autosomal recessive retinitis pigmentosa (ARRP), we applied 2-step genome-wide association study (GWAS) in 640 Japanese patients prescreened with targeted re-sequencing. Meta-GWAS identified three independent peaks atP< 5.0×10-8, all within the major ARRP geneEYS. Two were each tagged by a low frequency variant (allele frequency < 0.05); a known founder Mendelian mutation (c.4957dupA, p.S1653Kfs*2) and a presumably hypomorphic non-synonymous variant (c.2528G>A, p.G843E). c.2528G>A newly solved 7.0% of Japanese ARRP cases, improving genetic diagnosis by 26.8% and simultaneously serving as a new attractive target for genome editing gene therapy. The third peak was tagged by an intronic common variant, representing a novel disease-susceptibility signal. GWAS successfully unraveled genetic causes of a rare “monogenic” disorder for the first time, which provided unexpected insights into significant contribution of non-Mendelian genetic factors and identified a novel high frequency variant directly linked to development of local genome therapeutics.
Adaptation of plasticity to predicted climates in Australian rainbowfishes (Melanotaenia) across climatically defined bioregions
Authors: Sandoval-Castillo Jonathan , Gates Katie , Brauer Chris J. , Smith Steve , Bernatchez Louis , Beheregaray Luciano B. 
Published: December 2019

AbstractResilience to environmental stressors due to climate warming is influenced by local adaptations, including the capacity for plastic responses. The recent literature has focussed on genomic signatures of climatic adaptation, however little work has been done to address how plastic capacity may be influenced by biogeographic history and evolutionary processes. Here, we investigate phenotypic plasticity as a target of climatic selection, hypothesising that lineages that evolved under warmer climate will exhibit greater plastic adaptive resilience to thermal stress. This was tested using common garden experiments to compare gene expression regulation within and among a temperate, a subtropical and a desert ecotype of Australian rainbowfish. Individuals from each ecotype were subjected to contemporary and projected summer thermal conditions for 2070, and their global patterns of gene expression were characterized using liver transcriptomes. Critical thermal maximums were also determined for each ecotype to assess thermal tolerance. A comparative phylogenetic expression variance and evolution model framework was used to assess plastic and evolved changes in gene expression. Similar changes in both the direction and the magnitude of expressed genes were found within ecotypes. Although most expressed genes were identified in all ecotypes, 532 genes were identified as candidates subject to ecotype-specific directional selection. Twenty-three of those genes showed signal of adaptive (i.e. genetic-based) plastic response to future increases in temperature. Network analyses demonstrated centrality of these genes in thermal response pathways, along with several highly conserved hub genes thought to be integral for heat stress responses. The greatest adaptive resilience to warming was shown by the subtropical ecotype, followed by the desert and temperate ecotypes. Our findings indicate that vulnerability to climate change will be highly influenced by biogeographic factors, and we stress the need for integrative assessments of climatic adaptive traits for accurate estimations of population and ecosystem responses.
Mapping Human Pluripotent Stem Cell-Derived Erythroid Differentiation by Single-Cell Transcriptome Analysis
Authors: Xin Zijuan , Zhang Wei , Gong Shangjin , Zhu Junwei , Li Yanming , Zhang Zhaojun , Fang Xiangdong 
Published: December 2019

AbstractThere is an imbalance between the supply and demand of functional red blood cells (RBCs) in clinical applications. This imbalance can be addressed by regenerating RBCs using several in vitro methods. Induced pluripotent stem cells (iPSCs) can handle the low supply of cord blood and the ethical issues in embryonic stem cell research and provide a promising strategy to eliminate immune rejection. However, no complete single-cell level differentiation pathway exists for the iPSC-derived RBC differentiation system. In this study, we used iPSC line BC1 to establish a RBCs regeneration system. The 10× genomics single-cell transcriptome platform was used to map the cell lineage and differentiation trajectories on day 14 of the regeneration system. We observed that iPSCs differentiation was not synchronized during embryoid body (EB) culture. The cells (day 14) mainly consisted of mesodermal and various blood cells, similar to the yolk sac hematopoiesis. We identified six cell classifications and characterized the regulatory transcription factors (TFs) networks and cell-cell contacts underlying the system. iPSCs undergo two transformations during the differentiation trajectory, accompanied by the dynamic expression of cell adhesion molecules and estrogen-responsive genes. We identified different stages of erythroid cells such as burst-forming unit erythroid (BFU-E) and orthochromatic erythroblasts (ortho-E) and found that the regulation of TFs (e.g., TFDP1 and FOXO3) is erythroid-stage specific. Immune erythroid cells were identified in our system. This study provides systematic theoretical guidance for optimizing the iPSCs-derived RBCs differentiation system, and this system is a useful model for simulating in vivo hematopoietic development and differentiation.