bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiation of chromosome replication controls both division and replication cycles in E. coli through a double-adder mechanism
Authors: Witz Guillaume , van Nimwegen Erik , Julou Thomas 
Published: March 2019

AbstractLiving cells proliferate by completing and coordinating two essential cycles, a division cycle that controls cell size, and a DNA replication cycle that controls the number of chromosomal copies in the cell. Despite lacking dedicated cell cycle control regulators such as cyclins in eukaryotes, bacteria such as E. coli manage to tightly coordinate those two cycles across a wide range of growth conditions, including situations where multiple nested rounds of replication progress simultaneously. Various cell cycle models have been proposed to explain this feat, but it has been impossible to validate them so far due to a lack of experimental tools for systematically testing their different predictions. Recently new insights have been gained on the division cycle through the study of the structure of fluctuations in growth, size, and division in individual cells. In particular, it was found that cell size appears to be controlled by an adder mechanism, i.e. the added volume between divisions is held approximately constant and fluctuates independently of growth rate and cell size at birth. However, how replication initiation is regulated and coupled to cell size control remains unclear, mainly due to scarcity of experimental measurements on replication initiation at the single-cell level. Here, we used time-lapse microscopy in combination with microfluidics to directly measure growth, division and replication in thousands of single E. coli cells growing in both slow and fast growth conditions. In order to compare different phenomenological models of the cell cycle, we introduce a statistical framework which assess their ability to capture the correlation structure observed in the experimental data. Using this in combination with stochastic simulations, our data indicate that, instead of thinking of the cell cycle as running from birth to division, the cell cycle is controlled by two adder mechanisms starting at the initiation of replication: the added volume since the last initiation event controls the timing of both the next division event and the next replication initiation event. Interestingly the double-adder mechanism identified in this study has recently been found to explain the more complex cell cycle of mycobacteria, suggesting shared control strategies across species.
Augmented Interval List: a novel data structure for efficient genomic interval search
Authors: Feng Jianglin , Ratan Aakrosh , Sheffield Nathan C. 
Published: March 2019

AbstractMotivationGenomic data is frequently stored as segments or intervals. Because this data type is so common, interval-based comparisons are fundamental to genomic analysis. As the volume of available genomic data grows, developing efficient and scalable methods for searching interval data is necessary.ResultsWe present a new data structure, the augmented interval list (AIList), to enumerate intersections between a query interval q and an interval set R. An AIList is constructed by first sorting R as a list by the interval start coordinate, then decomposing it into a few approximately flattened components (sublists), and then augmenting each sublist with the running maximum interval end. The query time for AIList is O(log2N + n + m), where n is the number of overlaps between R and q, N is the number of intervals in the set R, and m is the average number of extra comparisons required to find the n overlaps. Tested on real genomic interval datasets, AIList code runs 5 - 18 times faster than standard high-performance code based on augmented interval-trees (AITree), nested containment lists (NCList), or R-trees (BEDTools). For large datasets, the memory-usage for AIList is 4% - 60% of other methods. The AIList data structure, therefore, provides a significantly improved fundamental operation for highly scalable genomic data analysis.AvailabilityAn implementation of the AIList data structure with both construction and search algorithms is available at code.databio.org/AIList.
Genome sequence of the euryhaline Javafish medaka, Oryzias javanicus: a small aquarium fish model for studies on adaptation to salinity
Authors: Takehana Yusuke , Zahm Margot , Cabau Cédric , Klopp Christophe , Roques Céline , Bouchez Olivier , Donnadieu Cécile , Barrachina Celia , Journot Laurent , Kawaguchi Mari , Yasumasu Shigeki , Ansai Satoshi , Naruse Kiyoshi , Inoue Koji , Shinzato Chuya , Schartl Manfred , Guiguen Yann , Herpin Amaury 
Published: March 2019

ABSTRACTBackgroundThe genus Oryzias is constituted of 35 medaka-fish species each exhibiting various ecological, morphological and physiological peculiarities and adaptations. Beyond of being a comprehensive phylogenetic group for studying intra-genus evolution of several traits like sex determination, behaviour, morphology or adaptation through comparative genomic approaches, all medaka species share many advantages of experimental model organisms including small size and short generation time, transparent embryos and genome editing tools for reverse and forward genetic studies. The Java medaka, Oryzias javanicus, is one of the two species of medaka perfectly adapted for living in brackish/sea-waters. Being an important component of the mangrove ecosystem, O. javanicus is also used as a valuable marine test-fish for ecotoxicology studies. Here, we sequenced and assembled the whole genome of O. javanicus, and anticipate this resource will be catalytic for a wide range of comparative genomic, phylogenetic and functional studies.FindingsComplementary sequencing approaches including long-read technology and data integration with a genetic map allowed the final assembly of 908 Mbp of the O. javanicus genome. Further analyses estimate that the O. javanicus genome contains 33% of repeat sequences and has a heterozygosity of 0.96%. The achieved draft assembly contains 525 scaffolds with a total length of 809.7 Mbp, a N50 of 6.3 Mbp and a L50 of 37 scaffolds. We identified 21454 expressed transcripts for a total transcriptome size of 57, 146, 583 bps.ConclusionsWe provide here a high-quality draft genome assembly of the euryhaline Javafish medaka, and give emphasis on the evolutionary adaptation to salinity.
Two gut microbes are necessary and sufficient for normal cognition in Drosophila melanogaster
Authors: DeNieu Michael , Mounts Kristin , Manier Mollie 
Published: March 2019

AbstractIt is widely accepted that the gut microbiome can affect various aspects of brain function, including anxiety, depression, learning, and memory. However, we know little about how individual microbial species contribute to communication along the gut-brain axis. Vertebrate microbiomes are comprised of hundreds of species, making it difficult to systematically target individual microbes and their interactions. Here, we use Drosophila melanogaster as a simple model organism to tease apart individual and combined effects of gut microbes on cognition. We used an aversive phototactic suppression assay to show that two dominant gut commensals in our lab stock, Lactobacillus and Acetobacter, are necessary and sufficient for normal learning and short-term memory relative to flies with a conventional microbiome. We also demonstrate that microbes did not affect their hosts’ ability to detect the aversive learning stimulus (quinine), suggesting that our results were due to decreased cognition and not sensory deficits. We thus establish Drosophila as a model for elucidating mechanisms of gut-brain communication at the level of individual bacterial species.
Differential impacts of the head onPlatynereis dumeriliiperipheral circadian rhythms
Authors: Arboleda Enrique , Zurl Martin , Tessmar-Raible Kristin 
Published: March 2019

AbstractBackgroundThe marine bristle wormPlatynereis dumeriliiis a useful functional model system for the study of the circadian clock and its interplay with others, e.g. circalunar clocks. The focus has so far been on the worm’s head. However, behavioral and physiological cycles in other animals typically arise from the coordination of circadian clocks located in the brain and in peripheral tissues. Here we focus on peripheral circadian rhythms and clocks, revisit and expand classical circadian work on the worm’s chromatophores, investigate locomotion as read-out and include molecular analyses.ResultsWe establish that different pieces of the trunk exhibit synchronized, robust oscillations of core circadian clock genes. These circadian core clock transcripts are under strong control of the light-dark cycle, quickly losing synchronized oscillation under constant darkness, irrespective of the absence or presence of heads. Different wavelengths are differently effective in controlling the peripheral molecular synchronization. We have previously shown that locomotor activity is under circadian clock control. Here we show that upon decapitation it still follows the light-dark cycle, but does not free-run under constant darkness. We also observe the rhythmicity of pigments in the worm’s individual chromatophores, confirming that chromatophore size changes follow a circadian pattern. These size changes continue under constant darkness, but cannot be re-entrained by light upon decapitation.ConclusionsHere we provide the first basic characterization of the peripheral circadian clock ofPlatynereis dumerilii. In the absence of the head, light is essential as a major synchronization cue for peripheral molecular and locomotor circadian rhythms. Circadian changes in chromatophore size can however continue for several days in the absence of light/dark changes and the head. Thus, the dependence on the head depends on the type of peripheral rhythm studied. These data show that peripheral circadian rhythms and clocks should be considered when investigating the interactions of clocks with different period lengths, a notion likely also true for other organisms with circadian and non-circadian clocks.
Synaptotagmin 1 oligomers clamp and regulate different modes of neurotransmitter release
Authors: Tagliatti Erica , Bello Oscar D. , Mendonça Philipe R. F. , Kotzadimitriou Dimitrios , Nicholson Elizabeth , Coleman Jeff , Timofeeva Yulia , Rothman James E. , Krishnakumar Shyam S. , Volynski Kirill E. 
Published: March 2019

AbstractSynaptotagmin1 (Syt1) synchronises neurotransmitter release to action potentials acting as the fast Ca2+ release sensor and as the inhibitor (clamp) of spontaneous and delayed asynchronous release. Whilst the Syt1 Ca2+ activation mechanism has been well characterised, how Syt1 clamps transmitter release remains enigmatic. Here we show that C2B domain-dependent oligomerisation provides the molecular basis for the Syt1 clamping function. This follows from the investigation of a designed mutation (F349A), which selectively destabilises Syt1 oligomerisation. Using combination of fluorescence imaging and electrophysiology in neocortical synapses we show that Syt1F349A is more efficient than wild type Syt1 (Syt1WT) in triggering synchronous transmitter release but fails to clamp spontaneous and Synaptotagmin7 (Syt7)-mediated asynchronous release components both in rescue (Syt1−/− knock-out background) and dominant-interference (Syt1+/+ background) conditions. Thus we conclude that Ca2+-sensitive Syt1 oligomers, acting as an exocytosis clamp, are critical for maintaining the balance among the different modes of neurotransmitter release.
Crosstalk and Ultrasensitivity in Protein Degradation Pathways
Authors: Mallela Abhishek , Nariya Maulik K. , Deeds Eric J. 
Published: March 2019

AbstractProtein turnover is vital to protein homeostasis within the cell. Many proteins are degraded efficiently only after they have been post-translationally “tagged” with a polyubiquitin chain. Ubiquitylation is a form of Post-Translational Modification (PTM): addition of a ubiquitin to the chain is catalyzed by E3 ligases, and removal of ubiquitin is catalyzed by a De-UBiquitylating enzyme (DUB). Over three decades ago, Goldbeter and Koshland discovered that reversible PTM cycles function like on-off switches when the substrates are at saturating concentrations. Although this finding has had profound implications for the understanding of switch-like behavior in biochemical networks, the general behavior of PTM cycles subject to synthesis and degradation has not been studied. Using a mathematical modeling approach, we found that simply introducing protein turnover to a standard modification cycle has profound effects, including significantly reducing the switch-like nature of the response. Our findings suggest that many classic results on PTM cycles may not holdin vivowhere protein turnover is ubiquitous. We also found that proteins sharing an E3 ligase can have closely related changes in their expression levels. These results imply that it may be difficult to interpret experimental results obtained from either overexpressing or knocking down protein levels, since changes in protein expression can be coupled via E3 ligase crosstalk. Understanding crosstalk and competition for E3 ligases will be key to ultimately developing a global picture of protein homeostasis.
Patterns and potential drivers of intraspecific variability in the body elemental composition of a terrestrial consumer, the snowshoe hare (Lepus americanus)
Authors: Rizzuto Matteo , Leroux Shawn J. , Wal Eric Vander , Wiersma Yolanda F. , Heckford Travis R. , Balluffi-Fry Juliana 
Published: March 2019

AbstractIntraspecific variability in ecological traits is widespread in nature. Recent evidence, mostly from aquatic ecosystems, shows individuals differing at the most fundamental level, that of their chemical composition. Age, sex, or body size may be key drivers of intraspecific variability in the body concentrations of carbon (C), nitrogen (N), and phosphorus (P). However, we still have a rudimentary understanding of the patterns and drivers of intraspecific variability in chemical composition of terrestrial consumers, particularly vertebrates.Here, we investigate the whole-body chemical composition of snowshoe hareLepus americanus, providing one of the few studies of patterns of stoichiometric variability and its potential drivers for a terrestrial vertebrate. Based on snowshoe hare ecology, we expected higher P and N concentrations in females, as well as in larger and older individuals.We obtained whole-body C, N, and P concentrations and C:N, C:P, N:P ratios from a sample of 50 snowshoe hares. We then used general linear models to test for evidence of a relationship between age, sex, or body size and stoichiometric variability in hares.We found considerable variation in the C, N, and P concentrations and elemental ratios within our sample. Contrary to our predictions, we found evidence of N content decreasing with age. As expected, we found evidence of P content increasing with body size. As well, we found no support for a relationship between sex and N or P content, nor for variability in C content and any of our predictor variables.Despite finding considerable stoichiometric variability in our sample, we found no substantial support for age, sex, or body size to relate to this variation. The weak relationship between body N concentration and age may suggest varying nutritional requirements of individuals at different ages. Conversely, P’s weak relationship to body size appears in line with recent evidence of the potential importance of P in terrestrial systems. Snowshoe hares are a keystone herbivore in the boreal forest of North America. The substantial stoichiometric variability we find in our sample could have important implications for nutrient dynamics in both boreal and adjacent ecosystems.
FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy
Authors: Díaz Osterman Carlos J. , Ozmadenci Duygu , Kleinschmidt Elizabeth G. , Taylor Kristin N. , Barrie Allison M. , Jiang Shulin , Bean Lisa M. , Sulzmaier Florian J. , Jean Christine , Tancioni Isabelle , Anderson Kristen , Uryu Sean , Cordasco Edward A. , Li Jian , Chen Xiao Lei , Fu Guo , Ojalill Marjaana , Rappu Pekka , Heino Jyrki , Mark Adam M. , Xu Guorong , Fisch Kathleen M. , Kolev Vihren N. , Weaver David T. , Pachter Jonathan A. , Győrffy Balázs , McHale Michael T. , Connolly Denise C. , Molinolo Alfredo , Stupack Dwayne G. , Schlaepfer David D. 
Published: March 2019

AbstractGene copy number changes, cancer stem cell (CSC) increases, and platinum chemotherapy resistance contribute to poor prognosis in patients with recurrent high grade serous ovarian cancer (HGSOC). CSC phenotypes involving Wnt-β-catenin and aldehyde dehydrogenase activities, platinum resistance, and tumor initiating frequency are here associated with spontaneous genetic gains, including genes encodingKRAS,MYCandFAK, in a new murine model of ovarian cancer (KMF). Noncanonical FAK signaling was sufficient to sustain human and KMF tumorsphere proliferation, CSC survival, and platinum resistance. Increased FAK tyrosine phosphorylation occurred in HGSOC patient tumors surviving neo-adjuvant platinum and paclitaxel chemotherapy and platinum resistant tumorspheres acquired FAK dependence for growth. Importantly, combining a pharmacologic FAK inhibitor with platinum overcame chemoresistance and triggered apoptosisin vitroandin vivo. Knockout, rescue, genomic and transcriptomic analyses collectively identified more than 400 genes regulated along a FAK/β-catenin/Myc axis impacting stemness and DNA repair in HGSOC, with 66 genes gained in a majority of Cancer Genome Atlas samples. Together, these results support combinatorial testing of FAK inhibitors for the treatment of recurrent ovarian cancer.Graphical SummaryKey PointsHigh grade serous ovarian carcinoma tumors containPTK2(FAK) 8q24.3 gains associated with prognostic differences.KMF, a new murine ovarian cancer model withK-Ras,Myc, andFAK gene gains and intrinsic platinum resistance.FAK activation in tumors surviving platinum chemotherapy promotes cancer stem cell survival.FAK facilitates a β-catenin-Myc signaling axis controlling gene expression supporting platinum resistance.FAK activity is essential for KMF tumor growth and is a targetable cellular adaptation of platinum resistance.
Feature overlap modulates rapid semantic but not lexical integration of novel associations by means of fast mapping
Authors: Zaiser Ann-Kathrin , Meyer Patric , Bader Regine 
Published: March 2019

AbstractThere is evidence that rapid integration of novel associations into cortical networks is possible if associations are acquired through a learning procedure called fast mapping (FM). FM requires precise visual discrimination of sometimes highly similar pictures of a previously unknown and a known item, and linking an unfamiliar label to the unknown item. In order to shed light on the mechanisms underlying learning through FM, we manipulated feature overlap between the two items as potential modulating factor. In Experiment 1, we found that labels of the unknown items generally evoked instantaneous lexical competition when encoded through FM, indicating rapid integration into lexical networks. In Experiment 2, we observed semantic priming immediately after FM encoding but only if the items shared many features. This indicates that whereas feature overlap leaves item-level lexical integration unaffected, it might mediate semantic integration of arbitrary picture-label associations, which could explain contradictory findings in the literature.HighlightsWe examined cortical integration of associations using implicit memory measures.Fast mapping enables immediate integration of associations into cortical networks.Semantic integration requires the discrimination between items sharing many features.Item-level lexical integration is unaffected by feature overlap.
Do El Niño events beget generations of reproductively deficient adults?
Authors: Ortega Santiago , Rodríguez Cristina , Drummond Hugh 
Published: March 2019

AbstractWarm ocean waters during El Niño events deplete primary productivity, with cascading effects through the food chain that profoundly affect many marine and terrestrial species, commonly increasing adult mortality and offspring starvation. With global warming, events will double and increasingly threaten the depletion or extinction of some animal populations.Because adverse environments experienced during infancy generally induce reproductive deficits in adulthood, El Niño events are also expected to affect animals born during them, engendering generations of adults with reduced reproductive potential and exacerbating demographic impacts.We made the first test of this idea, using the blue-footed booby, a piscivorous apex predator of the eastern tropical Pacific Ocean. Surprisingly, detailed monitoring of 18 generations over a 27-year period detected no deficits in the annual breeding success, offspring viability, lifespan or lifetime reproductive success of generations of adults born during El Niño years.These results testify to remarkable developmental resilience extending across the lifespan. However, there was evidence that this resilience was supported by two mechanisms of quality control of adult generations from El Niño years.First, viability selection on nestlings and fledglings was more severe for El Niño birth cohorts than ordinary cohorts.Second, in El Niño years, adult boobies self-selected for breeding. There was no increase in the proportional representation of either high quality breeders or breeders in their peak years (middle-age), but there was an increase in old-young adult pairings, which in this population produce the most viable fledglings.The blue-footed booby appears to be immune to the expected developmental impact of El Niño on the reproductive value of adult generations. The susceptibilities and resilience of other species need to be explored, to better predict the demographic impacts of this accelerating climatic oscillation.
Ligands, receptors and transcription factors that mediate inter-cellular and intra-cellular communication during ovarian follicle development
Authors: Bernabé Beatriz Peñalver , Woodruff Teresa , Broadbelt Linda J , Shea Lonnie D 
Published: March 2019

SUMMARYReliably producing a competent oocyte entails a deeper comprehension of ovarian follicle maturation, a very complex process that includes meiotic maturation of the female gamete, the oocyte, together with the mitotic divisions of the hormone-producing somatic cells. In this report, we investigate mice ovarian folliculogenesis in vivo using publically available time-series microarrays from primordial to antral stage follicles. Manually curated protein interaction networks were employed to identify autocrine and paracrine signaling between the oocyte and the somatic cells (granulosa and theca cells) and the oocyte and cumulus and mural cells at multiple stages of follicle development. We established protein binding interactions between expressed genes that encoded secreted factors and expressed genes that encoded cellular receptors. Some of computationally identified signaling interactions are well established, such as the paracrine signaling from the oocyte to the somatic cells through the secreted oocyte growth factor Gdf9; while others are novel connections in term of ovarian folliculogenesis, such as the possible paracrine connection from somatic secreted factor Ntn3 to the oocyte receptor Neo1. Additionally, we identify several of the likely transcription factors that might control the dynamic transcriptome during ovarian follicle development, noting that the YAP/TAP signaling is very active in vivo. This novel dynamic model of signaling and regulation can be employed to generate testable hypotheses regarding follicle development, guide the improvement of culture media to enhance in vitro ovarian follicle maturation and possibly as novel therapeutic targets for reproductive diseases.