bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioblastoma utilizes fatty acids and ketone bodies for growth allowing progression during ketogenic diet therapy
Authors: Sperry Jantzen , Condro Michael C. , Guo Lea , Braas Daniel , Vanderveer-Harris Nathan , Kim Kristen K.O. , Pope Whitney B. , Divakaruni Ajit S. , Lai Albert , Christofk Heather , Castro Maria G. , Lowenstein Pedro R. , Le Belle Janel E. , Kornblum Harley I. 
Published: June 2019

SummaryGlioblastoma (GBM) metabolism has traditionally been characterized by a primary dependence on aerobic glycolysis, prompting the use of the ketogenic diet (KD) as a potential therapy. In this study we evaluated the effectiveness of the KD in GBM and assessed the role of fatty acid oxidation (FAO) in promoting GBM propagation. In vitro assays revealed FA utilization throughout the GBM metabolome, and growth inhibition in nearly every cell line in a broad spectrum of patient-derived glioma cells treated with FAO inhibitors. In vivo assessments revealed that knockdown of carnitine palmitoyltransferase 1A (CPT1A), the rate limiting enzyme for FAO, reduced the rate of tumor growth and increased survival. However, the unrestricted ketogenic diet did not reduce tumor growth, and for some models significantly reduced survival. Altogether, these data highlight important roles for FA and ketone body metabolism that could serve to improve targeted therapies in GBM.
Developmental myelination is modified by microglial pruning
Authors: Hughes Alexandria N. , Appel Bruce 
Published: June 2019

AbstractDuring development, oligodendrocytes contact and wrap neuronal axons with myelin. Similar to neurons and synapses, excess myelin sheaths are produced and selectively eliminated. However, unlike these other structures, almost nothing is known about myelin sheath elimination. Microglia, the resident immune cells of the CNS, refine the developing CNS by engulfing surplus neurons and synapses. To determine if microglia also prune myelin sheaths, we used zebrafish to visualize and manipulate interactions between microglia, oligodendrocytes, and neurons during development. We found that microglia closely associate with oligodendrocytes and specifically phagocytose myelin sheaths. Silencing neuronal activity with botulinum toxin (BoNT/B) increased myelin engulfment by microglia. Furthermore, oligodendrocytes maintained excessive myelin sheaths following microglial ablation. Our work reveals a neuronal activity-regulated role for microglia in regulating myelination by oligodendrocytes.
Y-chromosome haplotypes of varying differentiation to the X are not associated with male fitness in common frogs
Authors: Veltsos Paris , Rodrigues Nicolas , Studer Tania , Ma Wen-Juan , Sermier Roberto , Leuenberger Julien , Perrin Nicolas 
Published: June 2019

AbstractThe canonical model of sex-chromosome evolution assigns a key role to sexually antagonistic (SA) genes on the arrest of recombination and ensuing degeneration of Y chromosomes. This assumption cannot be tested in organisms with highly differentiated sex chromosomes, such as mammals or birds, owing to the lack of polymorphism. Fixation of SA alleles, furthermore, might be the consequence rather than the cause of recombination arrest. Here we focus on a population of common frogs (Rana temporaria) where XY males with genetically differentiated Y chromosomes (non-recombinant Y haplotypes) coexist with both XY° males with proto-Y chromosomes (only differentiated from X chromosomes in the immediate vicinity of the candidate sex-determining locus Dmrt1) and XX males with undifferentiated sex chromosomes (genetically identical to XX females). Our study shows no effect of sex-chromosome differentiation on male phenotype, mating success or fathering success. Our conclusions rejoin genomic studies that found no differences in gene expression between XY, XY° and XX males. Sexual dimorphism in common frogs seems to result from the differential expression of autosomal genes rather than sex-linked SA genes. Among-male variance in sex-chromosome differentiation is better explained by a polymorphism in the penetrance of alleles at the sex locus, resulting in variable levels of sex reversal (and thus of X-Y recombination in XY females), independent of sex-linked SA genes.Impact SummaryHumans, like other mammals, present highly differentiated sex chromosomes, with a large, gene-rich X chromosome contrasting with a small, gene-poor Y chromosome. This differentiation results from a process that started approximately 160 Mya, when the Y first stopped recombining with the X. How and why this happened, however, remain controversial. According to the canonical model, the process was initiated by sexually antagonistic selection; namely, selection on the proto-Y chromosome for alleles that were beneficial to males but detrimental to females. The arrest of XY recombination then allowed such alleles to be only transmitted to sons, not to daughters. Although appealing and elegant, this model can no longer be tested in mammals, as it requires a sex-chromosome system at an incipient stage of evolution. Here we focus on a frog that displays within-population polymorphism is sex-chromosome differentiation, where XY males with differentiated chromosomes coexist with XX males lacking Y chromosomes. We find no effect of sex-chromosome differentiation on male phenotype or mating success, opposing expectations from the standard model. Sex linked genes do not seem to have a disproportionate effect on sexual dimorphism. From our results, sexually antagonistic genes show no association with sex-chromosome differentiation in frogs, which calls for alternative models of sex-chromosome evolution.
Fungal Feature Tracker (FFT): A tool for quantitatively characterizing the morphology and growth of filamentous fungi
Authors: de Ulzurrun Guillermo Vidal-Diez , Huang Tsung-Yu , Chang Ching-Wen , Lin Hung-Che , Hsueh Yen-Ping 
Published: June 2019

AbstractFilamentous fungi are ubiquitous in nature and serve as important biological models in various scientific fields including genetics, cell biology, ecology, evolution, and chemistry. A significant obstacle in studying filamentous fungi is the lack of tools for characterizing their growth and morphology in an efficient and quantitative manner. Consequently, assessments of the growth of filamentous fungi are often subjective and imprecise. In order to remedy this problem, we developed Fungal Feature Tracker (FFT), a user-friendly software comprised of different image analysis tools to automatically quantify different fungal characteristics, such as spore number, spore morphology, and measurements of total length, number of hyphal tips and the area covered by the mycelium. In addition, FFT can recognize and quantify specialized structures such as the traps generated by nematode-trapping fungi, which could be tuned to quantify other distinctive fungal structures in different fungi. We present a detailed characterization and comparison of a few fungal species as a case study to demonstrate the capabilities and potential of our software. Using FFT, we were able to quantify various features at strain and species level, such as mycelial growth over time and the length and width of spores, which would be difficult to track using classical approaches. In summary, FFT is a powerful tool that enables quantitative measurements of fungal features and growth, allowing objective and precise characterization of fungal phenotypes.Author SummaryOne of the main obstacles to study filamentous fungi is the lack of tools for characterizing fungal phenotypes in an efficient and quantitative manner. Assessment of cell growth and numbers rely on tedious manual techniques that often result in subjective and imprecise measurements. In response to those limitations, we developed Fungal Feature Tracker (FFT), a user-friendly software that allows researchers to characterize different phenotypic features of filamentous fungi such as sporulation, spore morphology and mycelial growth. In addition, FFT can recognize and quantify other fungal structures including the fungal traps developed by nematode-trapping fungi. In order to show the capabilities and potential of our software, we conducted a detailed characterization and comparison of different fungal species. Our comparison relies on a series of experimental set-ups using standard and easily accessible equipment to ensure reproducibility in other laboratories. In summary, FFT is an easy to use and powerful tool that can quantitatively characterize fungal morphology, cell number and quantitatively measures the filamentous growth, which will allow advance our understanding of the growth and biology of filamentous fungi.
Biophysical principles of choanoflagellate self-organization
Authors: Larson Ben T. , Ruiz-Herrero Teresa , Lee Stacey , Kumar Sanjay , Mahadevan L. , King Nicole 
Published: June 2019

AbstractInspired by the patterns of multicellularity in choanoflagellates, the closest living relatives of animals, we quantify the biophysical processes underlying the morphogenesis of rosette colonies in the choanoflagellateSalpingoeca rosetta. We find that rosettes reproducibly transition from an early stage of 2D growth to a later stage of 3D growth, despite the underlying stochasticity of the cell lineages. We postulate that the extracellular matrix (ECM) exerts a physical constraint on the packing of proliferating cells, thereby sculpting rosette morphogenesis. Our perturbative experiments coupled with biophysical simulations demonstrates the fundamental importance of a basally-secreted ECM for rosette morphogenesis. In addition, this yields a morphospace for the shapes of these multicellular colonies, consistent with observations of a range of choanoflagellates. Overall, our biophysical perspective on rosette development complements previous genetic perspectives and thus helps illuminate the interplay between cell biology and physics in regulating morphogenesis.Significance statementComparisons among animals and their closest living relatives, the choanoflagellates, have begun to shed light on the origin of animal multicellularity and development. Here we complement previous genetic perspectives on this process by focusing on the biophysical principles underlying colony morphology and morphogenesis. Our study reveals the crucial role of the extracellular matrix in shaping the colonies and leads to a phase diagram that delineates the range of morphologies as a function of the biophysical mechanisms at play.
Yeast growth responses to environmental perturbations are associated with rewiring of large epistatic networks
Authors: Zan Yanjun , Carlborg Örjan 
Published: June 2019

AbstractThe phenotypic effects of genetic polymorphisms often depend on the genetic and environmental context. Here, we explore how polymorphic loci in large interaction networks contribute to complex trait variation and in particular how genetic effects and network topologies are influenced by environmental perturbations. This was done by reanalysing a dataset of >4,000 haploid yeast segregants grown on 20 different media. In total, 130 epistatic loci were associated with growth in at least one environment. The across-environment interaction network defined by these loci explained 69 - 100% of the narrow sense heritability in the individual environments. Environmental changes often resulted in network hubs being connected and disconnected from their interactors, leading to changes in additive effects of individual loci, epistatic effects of multi-locus interactions and the total level of genetic variance in growth. The largest variation in genetic effects across environments was found for epistatic loci that were highly connected network hubs in some environments but not in others. In environments where loci were highly connected, the segregating alleles epistatically suppressed or released genetic effects from their interactors. In environments where they were lowly connected, the same alleles made small or no contributions to growth. Hub-loci thus often serve as modulators, influencing the phenotypic effects of environmentally specific sets of interacting effector genes, rather than being effectors themselves. These findings illustrate the importance of the interplay between large genetic interactions networks and the living environment, both for individual phenotypes and population level metrics of genetic variation.
Isolation and characterization of toxic Cyanobacterial Communities distribution in Lake Tana, Amhara Regional state, Ethiopia
Authors: Admas Adugnaw , Agida Aklilue , Melese Smegnew , Genetu Amare 
Published: June 2019

AbstractLake Tana is the second largest lake next to Victoria Lake in Africa. This Lake is exsposed to agriculture run off, industrial and Urban waste since it has not buffer zone to protect any invading materials to the water body. The accumulation and growth of blue-green algae in water body call public attention because of its health concern. Some cyanobacterial species produce toxin microcystins and anatoxin molecules can affect the liver, kideney and nervous system of animals because the toxic molecules of released from some toxic cyanobacteria may lead the organs to fail the metabolice system. The major exposure pathways of these toxins are through drinking water and recreations including swimming. In addition, these problems happen through food web. Those cyanobacteria’a are spread and growth in diffrent water body via agriculture run off, industrial and urban wastes and other nutrient source of N and P. The main goal of this scientific study was to assess the distribution of potential toxic cyanobacteria in Lake Tana. Cyano bacterial distributions were studied in different water bodies of Lake Tana. From the water bodies that have visible algal blooms and not observed algal blooms were investigated. Identification of cyano bacteria was conducted using microscope by following appropriate procedures. In the present studied area Anabaena sp, Nostoc sp., Chlorella sp., and Microcystis aeruginosa sp. were dominantly exist. Therefore, Maybe the numbers of fishe depleted in Lake Tana due to the presence of microcystine molcule source, those are Anabaena sp.,Nostoc sp. and Microcystis aeruginosa sp.
Host carbon dioxide concentration is an independent stress for Cryptococcus neoformans that affects virulence and antifungal susceptibility
Authors: Krysan Damian J. , Zhai Bing , Beattie Sarah R. , Misel Kara M. , Wellington Melanie , Lin Xiaorong 
Published: June 2019

AbstractThe ability of Cryptococcus neoformans to cause disease in humans varies significantly among strains with highly related genotypes. In general, environmental isolates of pathogenic species such as C. neoformans var. grubii have reduced virulence relative to clinical isolates, despite having no differences in the expression of the canonical virulence traits (high temperature growth, melanization and capsule formation). In this observation, we report that environmental isolates of C. neoformans tolerate host CO2 concentrations poorly compared to clinical isolates and that CO2 tolerance correlates well with the ability of the isolates to cause disease in mammals. Initial experiments also suggest that CO2 tolerance is particularly important for dissemination of C. neoformans from the lung to the brain. Furthermore, CO2 concentrations affect the susceptibility of both clinical and environmental C. neoformans isolates to the azole class of antifungal drugs, suggesting that antifungal testing in the presence of CO2 may improve the correlation between in vitro azole activity and patient outcome.ImportanceA number of studies comparing either patient outcomes or model system virulence across large collections of Cryptococcus isolates have found significant heterogeneity in virulence even among strains with highly related genotypes. Because this heterogeneity cannot be explained by variations in the three well-characterized virulence traits (growth at host body temperature; melanization; and polysaccharide capsule formation), it has been widely proposed that additional C. neoformans virulence traits must exist. C. neoformans natural niche is in the environment where the carbon dioxide concentration is very low (∼0.04%); in contrast, mammalian host tissue carbon dioxide concentrations are 125-fold higher (5%). We have found that the ability to grow in the presence of 5% carbon dioxide distinguishes low virulence strains from high virulence strains, even those with a similar genotype. Our findings suggest that carbon dioxide tolerance is a previously un-recognized virulence trait for C. neoformans.
TaAPO-A1, an ortholog of riceABERRANT PANICLE ORGANIZATION 1, is associated with total spikelet number per spike in elite hexaploid winter wheat varieties (Triticum aestivumL.)
Authors: Muqaddasi Quddoos H. , Brassac Jonathan , Koppolu Ravi , Plieske Jörg , Ganal Martin W. , Röder Marion S. 
Published: June 2019

AbstractWe dissected the genetic basis of total spikelet number (TSN) along with other traits, namely spike length (SL) and flowering time (FT) in a panel of 518 elite European winter wheat varieties. Genome-wide association studies based on 39,908 SNP markers revealed highly significant quantitative trait loci (QTL) for TSN on chromosomes 2D, 7A, and 7B, for SL on 5A, and FT on 2D, with 2D-QTL being the functional marker for the genePpd-D1. The physical region of the 7A-QTL for TSN revealed the presence of an ortholog toAPO1– a rice gene that positively controls spikelet number on panicles. Interspecific analyses ofTaAPO-A1orthologs showed that it is a highly conserved gene important for floral development, and present in a wide range of terrestrial plants. Intraspecific studies of the wheat orthologTaAPO-A1across wheat genotypes revealed a polymorphism in the highly conserved F-box domain, defining two haplotypes. A KASP maker developed on the polymorphic site showed a highly significant association ofTaAPO-A1with TSN, explaining 23.2% of the genotypic variance. Also, theTaAPO-A1alleles showed weak but significant differences for SL and grain yield. Our results demonstrate the importance of wheat sequence resources to identify candidate genes for important traits based on genetic analyses.
GSEA-InContext Explorer: An interactive visualization tool for putting gene set enrichment analysis results into biological context
Authors: Powers Rani K. , Sun Anthony , Costello James C. 
Published: June 2019

AbstractSummaryGSEA-InContext Explorer is a Shiny app that allows users to perform two methods of gene set enrichment analysis (GSEA). The first, GSEAPreranked, applies the GSEA algorithm in which statistical significance is estimated from a null distribution of enrichment scores generated for randomly permuted gene sets. The second, GSEA-InContext, incorporates a user-defined set of background experiments to define the null distribution and calculate statistical significance. GSEA-InContext Explorer allows the user to build custom background sets from a compendium of over 5,700 curated experiments, run both GSEAPreranked and GSEA-InContext on their own uploaded experiment, and explore the results using an interactive interface. This tool will allow researchers to visualize gene sets that are commonly enriched across experiments and identify gene sets that are uniquely significant in their experiment, thus complementing current methods for interpreting gene set enrichment results.Availability and implementationThe code for GSEA-InContext Explorer is available at: https://github.com/CostelloLab/GSEA-InContext_Explorer and the interactive tool is at: http://gsea-incontext_explorer.ngrok.io
Gravity highlights a dual role of the insula in internal models
Authors: Rousseau Célia , Barbiero Marie , Pozzo Thierry , Papaxanthis Charalambos , White Olivier 
Published: June 2019

AbstractMovements rely on a mixture of predictive and reactive mechanisms. With experience, the brain builds internal representations of actions in different contexts. Many factors are taken into account in this process among which the immutable presence of gravity. Any displacement of a massive body in the gravitational field generates forces and torques that must be predicted and compensated by appropriate motor commands. Studies have shown that the insular cortex is a key brain area for graviception. However, none attempted to address whether the same internal representation of gravity is shared between reactive and predictive mechanisms. Here, participants either mentally simulated (only predictive) or performed (predictive and reactive) vertical movements of the hand. We found that the posterior part of the insular cortex was engaged when feedback was processed. The anterior insula, however, was activated only in mental simulation of the action. A psychophysical experiment shows participants’ ability to integrate the effects of gravity. Our results demonstrate a dual internal representation of gravity within the insula and discuss how they can conceptually be linked.
Deciphering the metabolic capabilities of Bifidobacteria using genome-scale metabolic models
Authors: Devika N. T. , Raman Karthik 
Published: June 2019

ABSTRACTBifidobacteria, the initial colonisers of breastfed infant guts, are considered as the key commensals that promote a healthy gastrointestinal tract. However, little is known about the key metabolic differences between different strains of these bifidobacteria, and consequently, their suitability for their varied commercial applications. In this context, the present study applies a constraint-based modelling approach to differentiate between 36 important bifidobacterial strains, enhancing their genome-scale metabolic models obtained from the AGORA (Assembly of Gut Organisms through Reconstruction and Analysis) resource. By studying various growth and metabolic capabilities in these enhanced genome-scale models across 30 different nutrient environments, we classified the bifidobacteria into three specific groups. We also studied the ability of the different strains to produce short chain fatty acids, finding that acetate production is niche- and strain-specific, unlike lactate. Further, we captured the role of critical enzymes from the bifid shunt pathway, which was found to be essential for a subset of bifidobacterial strains. Our findings underline the significance of analysing metabolic capabilities as a powerful approach to explore distinct properties of the gut microbiome. Overall, our study presents several insights into the nutritional lifestyles of bifidobacteria and could potentially be leveraged to design species/strain-specific probiotics or prebiotics.