bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcription profiles of age-at-maturity-associated genes suggest cell fate commitment regulation as a key factor in the Atlantic salmon maturation process
Authors: Kurko Johanna , Debes Paul V. , House Andrew , Aykanat Tutku , Erkinaro Jaakko , Primmer Craig R. 
Published: September 2019

AbstractDespite recent taxonomic diversification in studies linking genotype with phenotype, follow-up studies aimed at understanding the molecular processes of such genotype-phenotype associations remain rare. The age at which an individual reaches sexual maturity is an important fitness trait in many wild species. However, the molecular mechanisms regulating maturation timing processes remain obscure. A recent genome-wide association study in Atlantic salmon (Salmo salar) identified large-effect age-at-maturity-associated chromosomal regions including genesvgll3,akap11andsix6, which have roles in adipogenesis, spermatogenesis and the hypothalamic-pituitary-gonadal (HPG) axis, respectively. Here, we determine expression patterns of these genes during salmon development and their potential molecular partners and pathways. Using Nanostring transcription profiling technology, we show development- and tissue-specific mRNA expression patterns forvgll3,akap11andsix6. Correlated expression levels ofvgll3andakap11, which have adjacent chromosomal location, suggests they may have shared regulation. Further,vgll3correlating witharhgap6andyap1, andakap11withlats1andyap1suggests that Vgll3 and Akap11 take part in actin cytoskeleton regulation. Tissue-specific expression results indicate thatvgll3andakap11paralogs have sex-dependent expression patterns in gonads. Moreover,six6correlating withslc38a6andrtn1, and Hippo signaling genes suggests that Six6 could have a broader role in the HPG neuroendrocrine and cell fate commitment regulation, respectively. We conclude that Vgll3, Akap11 and Six6 may influence Atlantic salmon maturation timing via affecting on adipogenesis and gametogenesis by regulating cell fate commitment and the HPG axis. These results may help to unravel general molecular mechanisms behind maturation.
Towards the identification of causal genes for age-related macular degeneration
Authors: Cheng Fei-Fei , Zhuang You-Yuan , Wen Xin-Ran , Xue Angli , Yang Jian , Jin Zi-Bing 
Published: September 2019

AbstractAge-related macular degeneration (AMD) is a leading cause of visual impairment in ageing populations and has no radical treatment or prevention. Although genome-wide association studies (GWAS) have identified many susceptibility loci for AMD, the underlying causal genes remain elusive. Here, we prioritized nine putative causal genes by integrating expression quantitative trait locus (eQTL) data from blood (n = 2,765) with AMD GWAS data (16,144 cases vs. 17,832 controls) and replicated six of them using retina eQTL data (n = 523). Of the six genes, altering expression of cnn2, sarm1 and bloc1s1 led to ocular phenotype, impaired vision and retinal pigment epithelium (RPE) loss in zebrafish. Essential photoreceptor and RPE genes were downregulated in cnn2- and sarm1-knockdown zebrafishes. Through integration of GWAS and eQTL data followed by functional validation, our study reveals potential roles of CNN2, SARM1 and BLOC1S1 in AMD pathogenesis and demonstrates an efficient platform to prioritise causal genes for human complex diseases.
Hap2-Ino80 facilitated transcription promotesde novoestablishment of CENP-A chromatin
Authors: Singh Puneet P. , Shukla Manu , White Sharon A. , Tong Pin , Auchynnikava Tatsiana , Spanos Christos , Rappsilber Juri , Pidoux Alison L. , Allshire Robin C. 
Published: September 2019

SUMMARYCentromeres are maintained epigenetically by the presence of CENP-A, an evolutionarily-conserved histone H3 variant, which directs kinetochore assembly and hence, centromere function. To identify factors that promote assembly of CENP-A chromatin, we affinity selected solubilised fission yeast CENP-ACnp1chromatin. All subunits of the Ino80 complex were enriched, including the auxiliary subunit Hap2. In addition to a role in maintenance of CENP-ACnp1chromatin integrity at endogenous centromeres, Hap2 is required forde novoassembly of CENP-ACnp1chromatin on naïve centromere DNA and promotes H3 turnover on centromere regions and other loci prone to CENP-ACnp1deposition. Prior to CENP-ACnp1chromatin assembly, Hap2 facilitates transcription from centromere DNA. These analyses suggest that Hap2-Ino80 destabilises H3 nucleosomes on centromere DNA through transcription-coupled histone H3 turnover, driving the replacement of resident H3 nucleosomes with CENP-ACnp1nucleosomes. These inherent properties define centromere DNA by directing a program that mediates CENP-ACnp1assembly on appropriate sequences.
Circadian regulation of muscle growth independent of locomotor activity
Authors: Kelu Jeffrey J. , Pipalia Tapan G. , Hughes Simon M. 
Published: September 2019

AbstractMuscle tissue shows circadian variation, but whether and how the intracellular circadian clock per se regulates muscle growth remains unclear. By measuring muscle growth over 12 h periods, here we show that muscle grows more during the day than at night. Inhibition of muscle contraction reduces growth to a similar extent in day and night, but does not ablate the circadian variation in growth. Muscle protein synthesis is higher during the day compared to night, whereas markers of protein degradation are higher at night. Mechanistically, the TORC1 inhibitor rapamycin inhibits the extra daytime growth, but no effect on muscle growth at night was detected. Conversely, the proteasomal inhibitor MG132 increases muscle growth at night, but has no effect during the day, irrespective of activity. Ablation of contractile activity rapidly reduces muscle protein synthesis both during the day and at night and leads to a gradual increase in Murf gene expression without ablating circadian variation in growth. Removal of circadian input by exposure to either permanent light or permanent darkness reduces muscle growth. We conclude that circadian variation in muscle growth is independent of the presence of, or changes in, physical activity and affects both protein synthesis and degradation in distinct circadian phases.
Molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolates with focus on antimicrobial resistance
Authors: Yu Xiaoling , Zhang Wen , Zhao Zhiping , Ye Chengsong , Zhou Shuyan , Wu Shaogui , Han Lifen , Han Zhaofang , Ye Hanhui 
Published: September 2019

AbstractThe enhancing incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP)-mediated infections in Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017 is the motivation behind this investigation to study gene phenotypes and resistance-associated genes of emergence regarding the CRKP strains. In current study, seven inpatients are enrolled in the hospital with complete treatments. The carbapenem-resistant K. pneumoniae whole genome is sequenced using MiSeq short-read and Oxford Nanopore long-read sequencing technology. Prophages are identified to assess genetic diversity within CRKP genomes. The investigation encompassed eight CRKP strains that collected from the patients enrolled as well as the environment, which illustrate that blaKPC-2 is responsible for phenotypic resistance in six CRKP strains that K. pneumoniae sequence type (ST11) is informed. The plasmid with IncR, ColRNAI and pMLST type with IncF[F33:A-:B-] co-exist in all ST11 with KPC-2-producing CRKP strains. Along with carbapenemases, all K. pneumoniae strains harbor two or three extended spectrum β-lactamase (ESBL)-producing genes. fosA gene is detected amongst all the CRKP strains. The single nucleotide polymorphisms (SNP) markers are indicated and validated among all CRKP strains, providing valuable clues for distinguishing carbapenem-resistant strains from conventional K. pneumoniae. In conclusion, ST11 is the main CRKP type, and blaKPC-2 is the dominant carbapenemase gene harbored by clinical CRKP isolates from current investigations.
Describing macroecological patterns in microbes: Approaches for comparative analyses of operational taxonomic unit read number distribution with a case study of global oceanic bacteria
Authors: Nakadai Ryosuke , Okazaki Yusuke , Matsuoka Shunsuke 
Published: September 2019

AbstractDescribing the variation in commonness and rarity in a community is a fundamental method of evaluating biodiversity. Such patterns have been studied in the context of species abundance distributions (SADs) among macroscopic organisms in numerous communities. Recently, models for analyzing variation in local SAD shapes along environmental gradients have been constructed. The recent development of high-throughput sequencing enables evaluation of commonness and rarity in local communities of microbes using operational taxonomic unit (OTU) read number distributions (ORDs), which are conceptually similar to SADs. However, few studies have explored the variation in local microbial ORD shapes along environmental gradients. Therefore, the similarities and differences between SADs and ORDs are unclear, clouding any universal rules of global biodiversity patterns. We investigated the similarities and differences in ORD shapes vs. SADs, and how well environmental variables explain the variation in ORDs along latitudinal and depth gradients. Herein, we integrate ORDSinto recent comparative analysis methods for SAD shape using datasets generated on the Tara Oceans expedition. About 56% of the variance in skewness of ORDs among global oceanic bacterial communities was explained with this method. Moreover, we confirmed that the parameter combination constraints of Weibull distributions were shared by ORDs of bacterial communities and SADs of tree communities, suggesting common long-term limitation processes such as adaptation and community persistence acting on current abundance variation. On the other hand, skewness was significantly greater for bacterial communities than tree communities, and many ecological predictions did not apply to bacterial communities, suggesting differences in the community assembly rules for microbes and macroscopic organisms. Approaches based on ORDs provide opportunities to quantify macroecological patterns of microbes under the same framework as macroscopic organisms.
Neurocognitive and Functional Heterogeneity in Depressed Youth
Authors: Baller Erica B. , Kaczkurkin Antonia N. , Sotiras Aristeidis , Adebimpe Azeez , Bassett Danielle S. , Calkins Monica E. , Cui Zaizu , Gur Raquel E. , Gur Ruben C. , Linn Kristin A. , Moore Tyler , Roalf David. R. , Varol Erdem , Wolf Daniel H. , Xia Cedric H. , Davatzikos Christos , Satterthwaite Theodore D. 
Published: September 2019

ABSTRACTOBJECTIVEDepression is a common psychiatric illness that often begins in youth, and is associated with cognitive symptoms. However, there is significant variability in the cognitive burden, likely reflecting biological heterogeneity. This study sought to identify neurocognitive subtypes in a large sample of depressed youth, and evaluated the neural signatures of these subtypes.METHODSParticipants were drawn from the Philadelphia Neurodevelopmental Cohort, including 712 youth with a lifetime history of a major depressive episode and 712 typically developing (TD) youth matched on age and sex. A subset (n=368, TD=200) also completed neuroimaging. Cognition was assessed with the Penn Computerized Neurocognitive Battery. A semi-supervised machine-learning algorithm, HYDRA (Heterogeneity through Discriminative Analysis), was used to delineate neurocognitive subtypes. Subtypes were evaluated for differences in both clinical psychopathology and brain activation during ann-back working memory fMRI task.RESULTSHYDRA identified three neurocognitive subtypes in the depressed group. Overall, Subtype 1 had better performance than TD comparators across many cognitive tasks (high accuracy, moderate speed), Subtype 2 was cognitively impaired (low accuracy, slow speed), whereas Subtype 3 was impulsive (low accuracy, fast speed). While subtypes did not differ in clinical psychopathology, they diverged in their activation profiles in regions critical for executive function, which mirrored differences in cognition.CONCLUSIONSUsing a data-driven approach, three neurocognitive subtypes of depression were identified that differed in neural signatures despite similar clinical psychopathology. These data suggest disparate mechanisms of cognitive vulnerability and resilience in depression, which may inform the identification of biomarkers for prognosis and treatment response.
Long-lasting effects of transient, perinatal fluoxetine exposure on cell proliferation in the dentate gyrus of mice
Authors: Spanswick Simon C. , Chrusch Michael J. , Kiryanova Veronika , Dyck Richard H. 
Published: September 2019

AbstractIn the adult mammalian brain, up-regulation of serotonin via the selective serotonin reuptake inhibitor fluoxetine increases hippocampal neurogenesis. However, research assessing the long-term effects of modulating serotonin during the developmental period on hippocampal neurogenesis, is sparse. Here we evaluated hippocampal neurogenesis early (postnatal day 12), and later in life (postnatal day 60), in the offspring of mouse dams that were administered fluoxetine in their drinking water from embryonic day 15 (E15) through postnatal day 12 (P12). Fluoxetine-exposed mice had significantly higher levels of neuronal proliferation at P12, and P60, despite cessation of fluoxetine on P12. These effects were limited to proliferation, as survival of postnatal-born hippocampal neurons was unaltered. Mice exposed to fluoxetine also showed significantly higher levels of cell death, suggesting that homeostatic mechanisms present within the hippocampus may limit integration of adult-born neurons into the existing neuronal network. These findings demonstrate modulation of serotonin during development may be sufficient to induce long-lasting changes in hippocampal neurogenesis.
Photoswitchable microtubule stabilisers optically control tubulin cytoskeleton structure and function
Authors: Müller-Deku Adrian , Loy Kristina , Kraus Yvonne , Heise Constanze , Bingham Rebekkah , Ahlfeld Julia , Trauner Dirk , Thorn-Seshold Oliver 
Published: September 2019

ABSTRACTSmall molecule inhibitors provide a versatile method for studies in microtubule cytoskeleton research, since tubulin is not readily amenable to functional control using genetics. However, traditional chemical inhibitors do not allow spatiotemporally precise applications on the length and time scales appropriate for selectively modulating microtubule-dependent processes. We have synthesised a panel of taxane-based light-responsive microtubule stabilisers, whose tubulin hyperpolymerisation activity can be induced by photoisomerisation to their thermodynamically metastable state. These reagents can be isomerised in live cells, optically controlling microtubule network integrity, cell cycle repartition, and cell survival, and offering biological response on the timescale of seconds and spatial precision to the level of individual cells. These azobenzene-based microtubule stabilisers offer the possibility of noninvasive, highly spatiotemporally precise modulation of the microtubule cytoskeleton in live cells, and can prove powerful reagents for studies of intracellular transport, cell motility, and neurodegeneration.Abstract Figure
ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL
Authors: Wutz Gordana , Ladurner Rene , St. Hilaire Brian , Stocsits Roman , Nagasaka Kota , Pignard Benoit , Sanborn Adrian , Tang Wen , Várnai Csilla , Ivanov Miroslav , Schoenfelder Stefan , van der Lelij Petra , Huang Xingfan , Dürnberger Gerhard , Roitinger Elisabeth , Mechtler Karl , Davidson Iain F. , Fraser Peter , Aiden Erez Lieberman , Peters Jan-Michael 
Published: September 2019

AbstractEukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin’s chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesinSTAG1 which binds chromatin for hours, whereas cohesinSTAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesinSTAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesinSTAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesinSTAG2 extrusion activity.
The speed of GTP hydrolysis determines GTP cap size and controls microtubule stability
Authors: Roostalu Johanna , Thomas Claire , Cade Nicholas I. , Kunzelmann Simone , Taylor Ian A. , Surrey Thomas 
Published: September 2019

ABSTRACTMicrotubules are bistable cytoskeletal polymers whose function depends on their property to switch between states of growth and shrinkage1. Growing microtubules are thought to be stabilized by a GTP cap at their ends2-5. The nature of this cap, however, is still poorly understood. How GTP hydrolysis determines the properties of the GTP cap and hence microtubule stability is unclear. End Binding proteins (EBs) recruit a diverse range of regulators of microtubule function to growing microtubule ends6. Whether these regulatory platforms at growing microtubule ends are identical to the GTP cap is not known. Using mutated human tubulin with blocked GTP hydrolysis, we demonstrate in microscopy-basedin vitroreconstitutions that EB proteins bind with high affinity to the GTP conformation of microtubules. Slowing-down GTP hydrolysis leads to extended GTP caps and consequently hyper-stable microtubules. Single molecule experiments reveal that the microtubule conformation gradually changes in the cap as GTP is hydrolyzed. These results demonstrate the critical importance of the kinetics of GTP hydrolysis for microtubule stability; and establish that the GTP cap coincides with the EB-binding regulatory hub that modulates microtubule cytoskeleton function in cells.
Efficiently summarizing relationships in large samples: a general duality between statistics of genealogies and genomes
Authors: Ralph Peter , Thornton Kevin , Kelleher Jerome 
Published: September 2019

AbstractAs a genetic mutation is passed down across generations, it distinguishes those genomes that have inherited it from those that have not, providing a glimpse of the genealogical tree relating the genomes to each other at that site. Statistical summaries of genetic variation therefore also describe the underlying genealogies. We use this correspondence to define a general framework that efficiently computes single-site population genetic statistics using the succinct tree sequence encoding of genealogies and genome sequence. The general approach accumulates “sample weights” within the genealogical tree at each position on the genome, which are then combined using a “summary function”; different statistics result from different choices of weight and function. Results can be reported in three ways: bysite,which corresponds to statistics calculated as usual from genome sequence; bybranch,which gives the expected value of the dual site statistic under the infinite-sites model of mutation, and bynode,which summarizes the contribution of each ancestor to these statistics. We use the framework to implement many currently-defined statistics of genome sequence (making the statistics’ relationship to the underlying genealogical trees concrete and explicit), as well as the corresponding “branch” statistics of tree shape. We evaluate computational performance using simulated data, and show that calculating statistics from tree sequences using this general framework is several orders of magnitude more efficient than optimized matrix-based methods in terms of both run time and memory requirements. We also explore how well the duality between site and branch statistics holds in practice on trees inferred from the 1000 Genomes Project dataset, and discuss ways in which deviations may encode interesting biological signals.
Hackflex: low cost Illumina Nextera Flex sequencing library construction
Authors: Gaio Daniela , Anantanawat Kay , To Joyce , Liu Michael , Monahan Leigh , Darling Aaron E. 
Published: September 2019

ABSTRACTWe developed a low-cost method for the production of Illumina-compatible sequencing libraries that allows up to 14 times more libraries for high-throughput Illumina sequencing to be generated for the same cost. We call this new method Hackflex. Quality of library preparation was tested by constructing libraries fromE. coliMG1655 genomic DNA using either Hackflex, standard Nextera Flex or a variation of standard Nextera Flex in which the bead-linked transposase is diluted prior to use. In order to test the library quality for genomes with a higher and a lower GC content, library construction methods were also tested onP. aeruginosaPAO1 andS. aureusATCC25923, respectively. We demonstrated that Hackflex can produce high quality libraries and yields a highly uniform coverage, equivalent to the standard Nextera Flex kit. We show that strongly size selected libraries produce sufficient yield and complexity to supportde novomicrobial genome assembly, and that assemblies of the large insert libraries can be much more contiguous than standard libraries without strong size selection. We introduce a new set of sample barcodes that are distinct from standard Illumina barcodes, enabling Hackflex samples to be multiplexed with samples barcoded using standard Illumina kits. Using Hackflex, we were able to achieve a per sample reagent cost for library prep of A$7.22 (USD$5.60), which is 9.87 times lower than the Standard Nextera Flex protocol at advertised retail price. An additional simple modification and further simplification of the protocol by omitting the wash step enables a further price reduction to reach an overall 14-fold cost saving. This method will allow researchers to construct more libraries within a given budget, thereby yielding more data and facilitating research programs where sequencing large numbers of libraries is beneficial.
Anatomy-guided Inverse-phase-encoding Registration Method for Correcting Susceptibility Artifacts in Sub-millimeter fMRI
Authors: Duong Soan T. M. , Phung Son L. , Bouzerdoum Abdesselam , Boyd Taylor Harriet G. , Puckett Alexander M. , Schira Mark M. 
Published: September 2019

AbstractEcho planar imaging (EPI) is a fast and non-invasive magnetic resonance imaging (MRI) technique that supports data acquisition at spatial and temporal resolutions suitable for brain function studies. However, susceptibility artifacts are unavoidable distortions in EPI. These distortions are especially strong in high spatial resolution images and can lead to misrepresentation of brain function in fMRI experiments. A common method for correcting susceptibility artifacts is based on a registration scheme which uses two EPI images acquired using identical sequences but with inverse phase-encoding (PE) directions. In this paper, we present a new method for correcting susceptibility artifacts by integrating a T1-weighted (T1w) image into the inverse-PE based registration, since the T1w structural image is considered as a ground-truth measurement of the brain. Furthermore, the T1w image is used as a criterion to select automatically the regularization parameters of the proposed image registration. Evaluations on two high-resolution EPI-fMRI datasets, acquired at 3T and 7T scanners, confirm that the proposed method provides more robust and sharper corrections and runs faster compared with two other state-of-the-art inverse-PE based susceptibility artifact correction methods, i.e. HySCO and TOPUP.