bluuebunny/crossref_metadata_2025_split huggingface dataset:
Free Energy Landscape and Conformational Kinetics of Hoogsteen Base-Pairing in DNA vs RNA
Authors: Ray D. , Andricioaei I. 
Published: January 2020

ABSTRACTGenetic information is encoded in the DNA double helix which, in its physiological milieu, is characterized by the iconical Watson-Crick nucleobase pairing. Recent NMR relaxation experiments revealed the transient presence of an alternative, Hoogsteen base pairing pattern in naked DNA duplexes and estimated its relative stability and lifetime. In contrast, HG transitions in RNA were not observed. Understanding Hoogsteen (HG) base pairing is important because the underlying "breathing" can modulate significantly DNA/RNA recognition by proteins. However, a detailed mechanistic insight into the transition pathways and kinetics is still missing. We performed enhanced sampling simulation (with combined metadynamics and adaptive force bias method) and Markov State modeling to obtain accurate free energy, kinetics and the intermediates in the transition pathway between WC and HG base pair for both naked B-DNA and A-RNA duplexes. The Markov state model constructed from our unbiased MD simulation data revealed previously unknown complex extra-helical intermediates in this seemingly simple process of base pair conformation switching in B-DNA. Extending our calculation to A-RNA, for which HG base pair is not observed experimentally, resulted in relatively unstable single hydrogen bonded distorted Hoogsteen like base pair. Unlike B-DNA the transition pathway primarily involved base paired and intra-helical intermediates with transition timescales much higher than that of B-DNA. The seemingly obvious flip-over reaction coordinate, i.e., the glycosidic torsion angle is unable to resolve the intermediates; so a multidimensional picture, involving backbone dihedral angles and distance between atoms participating in hydrogen bonds, is required to gain insight into the molecular mechanism.SIGNIFICANCEFormation of unconventional Hoogsteen (HG) base pairing is an important problem in DNA biophysics owing to its key role in facilitating the binding of DNA repairing enzymes, proteins and drugs to damaged DNA. X-ray crystallography and NMR relaxation experiments revealed the presence of HG base pair in naked DNA duplex and protein-DNA complex but no HG base pair was observed in RNA. Molecular dynamics simulations could reproduce the experimental free energy cost of HG base pairing in DNA although a detailed mechanistic insight is still missing. We performed enhanced sampling simulation and Markov state modeling to obtain accurate free energy, kinetics and the intermediates in the transition pathway between WC and HG base pair for both B-DNA and A-RNA.
Ostrea edulisat shipwrecks in the Dutch North Sea
Authors: Coolen Joop W.P. , Dongen Udo Van , Driessen Floor M.F. , Wurz Erik , Bergsma Joost H. , Olie Renate A. , Deden Brenda , Bos Oscar G. 
Published: January 2020

AbstractDuring diving expeditions in July and September 2019 two live European flat oysters (Ostrea edulis) were observed by SCUBA divers. The first oyster was found lying amongst coarse shelly material in the scour hole around shipwreck #3251, 37 nautical miles north west of Texel (NL). The second oyster was found on the Gustav Nachtigal wreck, 6 nautical miles north of Schiermonnikoog (NL). Additional shipwrecks were also inspected for O. edulis individuals but no live specimens were observed, although on 9 out of 11 inspected locations empty, fossil O. edulis shells were found. The September dive on the #3251 shipwreck revealed the presence of several large empty flat oyster shells, some of which were attached to each other, with up to three individuals in a cluster. This implies that the area around the #3251 shipwreck was a suitable location for flat oysters in the past and that oyster larvae are still capable of reaching the location. The findings suggest that shipwrecks and their surroundings are promising locations for future O. edulis restoration projects.
Pleiotropy promotes male exaggerated weapon and its associated fighting behaviour in a water strider
Authors: Toubiana William , Armisén David , Amélie Decaras , Khila Abderrahman 
Published: January 2020

AbstractExaggerated sexually selected traits, often carried by males, are characterized by the evolution of hyperallometry, resulting in their disproportionate growth relative to the rest of the body1–3. While the evolution of allometry has attracted much attention for centuries, our understanding of the developmental genetic mechanisms underlying its emergence remains fragmented4,5. Here we show that the hyperallometric legs in the males of the water striderMicrovelia longipesare associated with a specific signature of gene expression during development. Using RNAi knockdown, we demonstrate that a broadly expressed growth factor, Bone Morphogenetic Protein 11 (BMP11, also known as Growth Differentiation Factor 11), regulates leg allometries through increasing the allometric coefficient and mean body size in males. In contrast, BMP11 RNAi reduced mean body size but did not affect slope in females. Furthermore, our data show that a tissue specific factor, Ultrabithorax (Ubx), increases intercept without affecting mean body size. This indicates a genetic correlation between mean body size and variation in allometric slope, but not intercept. Strikingly, males treated with BMP11 RNAi exhibited a severe reduction in fighting frequency compared to both controls and Ubx RNAi-treated males. Overall, we demonstrate a genetic correlation between male body size, the exaggerated weapon, and the intense fighting behaviour associated with it inM. longipes. Our results provide evidence for a role of pleiotropy in the evolution of allometric slope.
Nanopore Sequencing at Mars, Europa and Microgravity Conditions
Authors: Carr Christopher E. , Bryan Noelle C. , Saboda Kendall N. , Bhattaru Srinivasa A. , Ruvkun Gary , Zuber Maria T. 
Published: January 2020

AbstractNanopore sequencing, as represented by Oxford Nanopore Technologies’ MinION, is a promising technology forin situlife detection and for microbial monitoring including in support of human space exploration, due to its small size, low mass (∼100 g) and low power (∼1W). Now ubiquitous on Earth and previously demonstrated on the International Space Station (ISS), nanopore sequencing involves translocation of DNA through a biological nanopore on timescales of milliseconds per base. Nanopore sequencing is now being done in both controlled lab settings as well as in diverse environments that include ground, air and space vehicles. Future space missions may also utilize nanopore sequencing in reduced gravity environments, such as in the search for life on Mars (Earth-relative gravito-inertial acceleration (GIA)g= 0.378), or at icy moons such as Europa (g= 0.134) or Enceladus (g= 0.012). We confirm the ability to sequence at Mars as well as near Europa or Lunar (g= 0.166) and lowerglevels, demonstrate the functionality of updated chemistry and sequencing protocols under parabolic flight, and reveal consistent performance acrossglevel, during dynamic accelerations, and despite vibrations with significant power at translocation-relevant frequencies. Our work strengthens the use case for nanopore sequencing in dynamic environments on Earth and in space, including as part of the search for nucleic-acid based life beyond Earth.
Bayesian genomic models boost prediction accuracy for resistance againstStreptococcus agalactiaein Nile tilapia (Oreochromus nilioticus)
Authors: Joshi Rajesh , Skaaurd Anders , Alvarez Alejandro Tola , Moen Thomas , Ødegård Jørgen 
Published: January 2020

AbstractStreptococcosis due to Streptococcus agalactiae is a major bacterial disease in Nile tilapia, and development of the resistant genetic strains can be a sustainable approach towards combating this problematic disease. Thus, a controlled disease trial was performed on 120 full-sib families to i) quantify and characterize the potential of genomic selection for S. agalactiae resistance in Nile tilapia and to ii) select the best genomic model and optimal SNP-chip for this trait.In total, 40 fish per family (15 fish intraperitoneally injected and 25 fish as cohabitants) were selected for the challenge test and mortalities recorded every 3 hours, until no mortalities occurred for a period of 3 consecutive days. Genotypes (50,690 SNPs) and phenotypes (0 for dead and 1 for alive) for 2472 cohabitant fish were available. The pedigree-based analysis utilized a deep pedigree, going 17 generations back in time. Genetic parameters were obtained using various genomic selection models (GBLUP, BayesB, BayesC, BayesR and BayesS) and traditional pedigree-based model (PBLUP). The genomic models were further analyzed using 10 different subsets of SNP-densities for optimum marker density selection. Prediction accuracy and bias were evaluated using 5 replicates of 10-fold cross-validation.Using an appropriate Bayesian genomic selection model and optimising it for SNP density increased prediction accuracy up to ∼71%, compared to a pedigree-based model. This result is encouraging for practical implementation of genomic selection for S. agalactiae resistance in Nile tilapia breeding programs.
mRNA localization is linked to translation regulation in theCaenorhabditis elegansgerm lineage
Authors: Parker Dylan M. , Winkenbach Lindsay P. , Boyson Samuel P. , Saxton Matthew N. , Daidone Camryn , Al-Mazaydeh Zainab A. , Nishimura Marc T. , Mueller Florian , Osborne Nishimura Erin 
Published: January 2020

AbstractCaenorhabditis elegansearly embryos generate cell-specific transcriptomes despite lacking active transcription. This presents an opportunity to study mechanisms of post-transcriptional regulatory control. In seeking the mechanisms behind this patterning, we discovered that some cell-specific mRNAs accumulate non-homogenously within cells, localizing to membranes, P granules (associated with progenitor germ cells in the P lineage), and P-bodies (associated with RNA processing). Transcripts differed in their dependence on 3’UTRs and RNA Binding Proteins, suggesting diverse regulatory mechanisms. Notably, we found strong but imperfect correlations between low translational status and P granule localization within the progenitor germ lineage. By uncoupling these, we untangled a long-standing question: Are mRNAs directed to P granules for translational repression or do they accumulate there as a downstream step? We found translational repression preceded P granule localization and could occur independent of it. Further, disruption of translation was sufficient to send homogenously distributed mRNAs to P granules. Overall, we show transcripts important for germline development are directed to P granules by translational repression, and this, in turn, directs their accumulation in the progenitor germ lineage where their repression can ultimately be relieved.SummaryMaternally loaded mRNAs localize non-homogeneously withinC. elegansearly embryos correlating with their translational status and lineage-specific fates.
The neural computations for stimulus presence and modal identity diverge along a shared circuit
Authors: Tovar David A. , Noel Jean-Paul , Ishizawa Yumiko , Patel Shaun R. , Eskandar Emad N. , Wallace Mark T. 
Published: January 2020

AbstractThe brain is comprised of neural circuits that are able to flexibly represent the complexity of the external world. In accomplishing this feat, one of the first attributes the brain must code for is whether a stimulus is present and subsequently what sensory information that stimulus contains. One of the core characteristics of that information is which sensory modality(ies) are being represented. How information regarding both the presence and modal identity of a given stimulus is represented and transformed within the brain remains poorly understood. In this study, we investigated how the brain represents the presence and modal identity of a given stimulus while tactile, audio, and audio-tactile stimuli were passively presented to non-human primates. We recorded spiking activity from primary somatosensory (S1) and ventral pre-motor (PMv) cortices, two areas known to be instrumental in transforming sensory information into motor commands for action. Using multivariate analyses to decode stimulus presence and identity, we found that information regarding stimulus presence and modal identity were found in both S1 and PMv and extended beyond the duration of significant evoked spiking activity, and that this information followed different time-courses in these two areas. Further, we combined time-generalization decoding with cross-area decoding to demonstrate that while signaling the presence of a stimulus involves a feedforward-feedback coupling between S1-PMv, the processing of modal identity is largely restricted to S1. Together, these results highlight the differing spatiotemporal dynamics of information flow regarding stimulus presence and modal identity in two nodes of an important cortical sensorimotor circuit.Significance StatementIt is unclear how the structure and function of the brain support differing sensory functions, such as detecting the presence of a stimulus in the environment vs. identifying it. Here, we used multivariate decoding methods on monkey neuronal data to track how information regarding stimulus presence and modal identity flow within a sensorimotor circuit. Results demonstrate that while neural patterns in both primary somatosensory (S1) and ventral pre-motor (PMv) cortices can be used to detect and discriminate between stimuli, they follow different time-courses. Importantly, findings suggest that while information regarding the presence of a stimulus flows reciprocally between S1 and PMv, information regarding stimulus identity is largely contained in S1.
A New Tree-Based Methodological Framework to Infer the Evolutionary History of Mesopolyploid Lineages: An Application to the Brassiceae Tribe (Brassicaceae)
Authors: Hénocq Laura , Gallina Sophie , Schmitt Eric , Castric Vincent , Vekemans Xavier , Poux Céline 
Published: January 2020

AbstractWhole genome duplication events are notably widespread in plants and this poses particular challenges for phylogenetic inference in allopolyploid lineages, i.e. lineages that result from the merging of two or more diverged genomes after interspecific hybridization. The nuclear genomes resulting from allopolyploidization contain homologous gene copies from different evolutionary origins called homoeologs, whose orthologs must be sorted out in order to reconstruct the evolutionary history of polyploid clades. In this study, we propose a methodological approach to resolve the phylogeny of allopolyploid clades focusing on mesopolyploid genomes, which experienced some level of genome reshuffling and gene fractionation across their subgenomes. To illustrate our methodological framework we applied it to a clade belonging to the model Brassicaceae plant family, the Brassiceae tribe, that experienced a mesohexaploidy event. The dataset analysed consists of both publically available genomic sequences and new transcriptomic data according to taxa. The present methodology requires a well-annotated reference genome, for which the identification of the parental subgenome fragments has been performed (e.g. Brassica rapa and Brassica oleracea). Focusing on fully retained genes (i.e. genes for which all homoeologous gene copies inherited from the parental lineages are still present in the reference genome), the method constructs multi-labelled gene trees that allow subsequent assignment of each gene copy to its diploid parental lineage. Once the orthologous copies are identified, genes from the same parental origin are concatenated and tree-building methods are used to reconstruct the species tree. This method allows resolving the phylogenetic relationships (i) among extant species within a mesopolyploid clade, (ii) among the parental lineages of a mesopolyploid lineage, and (iii) between the parental lineages and closely related extant species. We report here the first well-resolved nuclear-based phylogeny of the Brassiceae tribe.
Identification of a novel breathing circuit that controls pain and anxiety
Authors: Liu Shijia , Ye Mao , Pao Gerald M. , Song Samuel Myeongsup , Jhang Jinho , Han Sung 
Published: January 2020

AbstractAlleviating pain with controlled breathing has been practiced throughout human history. Despite its wide use and long history, a neural circuit-based understanding of the pain-breathing interaction is largely lacking. Here we report a novel breathing circuit that regulates non-homeostatic breathing rhythm, as well as pain and anxiety. We identify that a cluster of neurons expressing theOprm1gene, which encodes the μ-opioid receptor (MOR) in the lateral subdivision of parabrachial nucleus (PBLOprm1), directly regulates breathing rate in mice by conveying signals from the limbic areas to respiratory rhythm generating neurons in the medullary preBötzinger Complex (preBötC). In addition, we found that pain signals rapidly increase breathing rate by activating these neurons in both awake and anesthetized mice. Inactivating these neurons not only decreases the breathing rate, but it also substantially decreases anxiety-like behaviors and induces strong appetitive behaviors. Furthermore, PBLOprm1inactivation alleviates pain by attenuating the perception of the affective-motivational aspect of pain. These results suggest that PBLOprm1neurons play a critical role in the non-homeostatic regulation of breathing and in the regulation of pain and anxiety through breathing.
Quantifying the spatiotemporal dynamics of IRES versus Cap translation with single-molecule resolution in living cells
Authors: Koch Amanda , Aguilera Luis , Morisaki Tatsuya , Munsky Brian , Stasevich Timothy J. 
Published: January 2020

ABSTRACTViruses use IRES sequences within their RNA to hijack translation machinery and thereby rapidly replicate in host cells. While this process has been extensively studied in bulk assays, the dynamics of hijacking at the single-molecule level remain unexplored in living cells. To achieve this, we developed a bicistronic biosensor encoding complementary repeat epitopes in two ORFs, one translated in a Cap-dependent manner and the other translated in an IRES-mediated manner. Using a pair of complementary probes that bind the epitopes co-translationally, our biosensor lights up in different colors depending on which ORF is being translated. In combination with single-molecule tracking and computational modeling, we measured the relative kinetics of Cap versus IRES translation and show: (1) Two non-overlapping ORFs can be simultaneously translated within a single mRNA; (2) EMCV IRES-mediated translation sites recruit ribosomes less efficiently than Cap-dependent translation sites but are otherwise nearly indistinguishable, having similar mobilities, sizes, spatial distributions, and ribosomal initiation and elongation rates; (3) Both Cap-dependent and IRES-mediated ribosomes tend to stretch out translation sites; (4) Although the IRES recruits two to three times fewer ribosomes than the Cap in normal conditions, the balance shifts dramatically in favor of the IRES during oxidative and ER stresses that mimic viral infection; and (5) Translation of the IRES is enhanced by translation of the Cap, demonstrating upstream translation can positively impact the downstream translation of a non-overlapping ORF. With the ability to simultaneously quantify two distinct translation mechanisms in physiologically relevant live-cell environments, we anticipate bicistronic biosensors like the one we developed here will become powerful new tools to dissect both canonical and non-canonical translation dynamics with single-molecule precision.Graphical Abstract
Designing flow regimes to support entire river ecosystems
Authors: Tonkin Jonathan D. , Olden Julian D. , Merritt David. M. , Reynolds Lindsay V. , Rogosch Jane S. , Lytle David A. 
Published: January 2020

AbstractOvercoming the challenges of water scarcity will require creative approaches to flow management and modeling approaches that forecast the effects of management actions on multiple ecosystem components simultaneously. Using a mechanistic multispecies modeling approach, we investigated the cross-ecosystem effects of environmental flow regimes designed for specific ecosystem outcomes. We reveal tradeoffs associated with flow regimes targeting riparian vegetation, fishes, and invertebrates. The different frequencies associated with each flow regime in some cases caused non-target ecosystem components to become locally extirpated within short (decadal) timespans. By incorporating multiple flow frequencies (from intraannual-scale pulses to large decadal-scale floods), the natural flow regime enabled a balanced but sub-optimal response of the three ecosystem components (mean 72% of designer flow). Although returning to a natural flow regime may not be possible in highly managed rivers, novel flow regimes must incorporate diverse frequencies inherent to such a regime and accommodate the sometimes conflicting requirements of different taxa at different times.
Cooperative and non-cooperative behaviour in the exploitation of a common renewable resource with environmental stochasticity
Authors: Hackney Michael , James Alex , Plank Michael J. 
Published: January 2020

AbstractClassical fisheries biology aims to optimise fisheries-level outcomes, such as yield or profit, by controlling the fishing effort. This can be adjusted to allow for the effects of environmental stochasticity, or noise, in the population dynamics. However, when multiple fishing entities, which could represent countries, commercial organisations, or individual vessels, can autonomously determine their own fishing effort, the the optimal action for one fishing entity depends on the actions of others. Coupled with noise in the population dynamics, and with decisions about fishing effort made repeatedly, this becomes an iterated stochastic game. We tackle this problem using the tools of stochastic optimisation, first for the monopolist’s problem and then for the duopolist’s problem. In each case, we derive optimal policies that specify the best level of fishing effort for a given stock biomass. Under these optimal policies, we can calculate the equilibrium stock biomass, the expected long-term return from fishing and the probability of stock collapse. We also show that there is a threshold stock biomass below which it is optimal to stop fishing until the stock recovers. We then develop an agent-based model to test the effectiveness of simple strategies for responding to deviations by an opponent from a cooperative fishing level. Our results show that the economic value of the fishery to a monopolist, or to a consortium of fishing agents, is robust to a certain level of noise. However, without the means of making agreements about fishing effort, even low levels of noise make sustained cooperation between autonomous fishing agents difficult.