bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genomics of ten newCaenorhabditisspecies
Authors: Stevens Lewis , Félix Marie-Anne , Beltran Toni , Braendle Christian , Caurcel Carlos , Fausett Sarah , Fitch David , Frézal Lise , Kaur Taniya , Kiontke Karin , Newton Matt D. , Noble Luke M. , Richaud Aurélien , Rockman Matthew V. , Sudhaus Walter , Blaxter Mark 
Published: August 2018

AbstractThe nematodeCaenorhabditis eleganshas been central to the understanding of metazoan biology. However,C. elegansis but one species among millions and the significance of this important model organism will only be fully revealed if it is placed in a rich evolutionary context. Global sampling efforts have led to the discovery of over 50 putative species from the genusCaenorhabditis, many of which await formal species description. Here, we present species descriptions for ten newCaenorhabditisspecies. We also present draft genome sequences for nine of these new species, along with a transcriptome assembly for one. We exploit these whole-genome data to reconstruct theCaenorhabditisphylogeny and use this phylogenetic tree to dissect the evolution of morphology in the genus. We show unexpected complexity in the evolutionary history of key developmental pathway genes. The genomic data also permit large scale analysis of gene structure, which we find to be highly variable within the genus. These new species and the associated genomic resources will be essential in our attempts to understand the evolutionary origins of theC. elegansmodel.
Origin of gibberellin-dependent transcriptional regulation by molecular exploitation of a transactivation domain in DELLA proteins
Authors: Hernández-García Jorge , Briones-Moreno Asier , Dumas Renaud , Blázquez Miguel A. 
Published: August 2018

AbstractDELLA proteins are land-plant specific transcriptional regulators known to interact through their C-terminal GRAS domain with over 150 transcription factors in Arabidopsis thaliana. Besides, DELLAs from vascular plants can interact through the N-terminal domain with the gibberellin receptor encoded by GID1, through which gibberellins promote DELLA degradation. However, this regulation is absent in non-vascular land plants, which lack active gibberellins or a proper GID1 receptor. Current knowledge indicates that DELLAs are important pieces of the signalling machinery of vascular plants, especially angiosperms, but nothing is known about DELLA function during early land plant evolution or if they exist at all in charophytan algae. We have now elucidated the evolutionary origin of DELLA proteins, showing that algal GRAS proteins are monophyletic and evolved independently from those of land plants, which explains why there are no DELLAs outside land plants. DELLA genes have been maintained throughout land plant evolution with only two major duplication events kept among plants. Furthermore, we show that the features needed for DELLA interaction with the receptor were already present in the ancestor of all land plants, and propose that these DELLA N-terminal motifs have been tightly conserved in non-vascular land plants for their function in transcriptional co-activation, which allowed subsequent exaptation for the interaction with the GID1 receptor when vascular plants developed gibberellin synthesis and the corresponding perception module.
Bayesian arrival model for Atlantic salmon smolt counts powered by environmental covariates and expert knowledge
Authors: Pulkkinen Henni , Orell Panu , Erkinaro Jaakko , Mäntyniemi Samu 
Published: August 2018

AbstractAnnual run size and timing of Atlantic salmon smolt migration was estimated using Bayesian model framework and data from six years of a video monitoring survey. The model has a modular structure. It separates sub-processes of departing, traveling and observing, of which the first two together define the arrival distribution. The sub-processes utilize biological background and expert knowledge about the migratory behavior of smolts and about the probability to observe them from the video footage under varying environmental conditions. Daily mean temperature and discharge were used as environmental covariates. The model framework does not require assuming a simple distributional shape for the arrival dynamics and thus also allows for multimodal arrival distributions. Results indicate that 20% - 43% of smolts passed the Utsjoki monitoring site unobserved during the years of study. Predictive studies were made to estimate daily run size in cases with missing counts either at the beginning or in the middle of the run, indicating good predictive performance.
PathoLive – Real-time pathogen identification from metagenomic Illumina datasets
Authors: Tausch Simon H. , Loka Tobias P. , Schulze Jakob M. , Andrusch Andreas , Klenner Jeanette , Dabrowski Piotr W. , Lindner Martin S. , Nitsche Andreas , Renard Bernhard Y. 
Published: August 2018

AbstractMotivationOver the past years, NGS has become a crucial workhorse for open-view pathogen diagnostics. Yet, long turnaround times result from using massively parallel high-throughput technologies as the analysis can only be performed after sequencing has finished. The interpretation of results can further be challenged by contaminations, clinically irrelevant sequences, and the sheer amount and complexity of the data.ResultsWe implemented PathoLive, a real-time diagnostics pipeline for the detection of pathogens from clinical samples hours before sequencing has finished. Based on real-time alignment with HiL-ive2, mappings are scored with respect to common contaminations, low-entropy areas, and sequences of widespread, non-pathogenic organisms. The results are visualized using an interactive taxonomic tree that provides an easily interpretable overview of the relevance of hits. For a human plasma sample that was spiked in vitro with six pathogenic viruses, all agents were clearly detected after only 40 of 200 sequencing cycles. For a real-world sample from Sudan the results correctly indicated the presence of Crimean-Congo hemorrhagic Fever Virus. In a second real-world dataset from the 2019 SARS-CoV-2 outbreak in Wuhan, we found the presence of a SARS Coronavirus as the most relevant hit without the novel virus reference genome being included in the database. For all samples, clinically irrelevant hits were correctly de-emphasized. Our approach is valuable to obtain fast and accurate NGS-based pathogen identifications and correctly prioritize and visualize them based on their clinical significance.AvailabilityPathoLive is open source and available on GitLab (https://gitlab.com/rkibioinformatics/PathoLive) and BioConda (conda install –c bioconda patholive).ContactBernhard.Renard@hpi.de, NitscheA@rki.de
Effect of cadmium accumulation on the performance of plants and of herbivores that cope differently with organic defences
Authors: Godinho Diogo Prino , Serrano Helena Cristina , Silva Anabela , Branquinho Cristina , Magalhães Sara 
Published: August 2018

AbstractSome plants can accumulate in their shoots metals that are toxic to most other organisms. This ability may serve as a defence against herbivores. Although both metal accumulation and the production of organic defences may be costly to the plant, the two mechanisms may interact on their effect on herbivores. However, this interplay between metal-based and ‘classical’ organic defences remains overlooked.To fill this gap, we studied the interactions between tomato (Solanum lycopersicum), a plant that accumulates cadmium, and two spider-mites,Tetranychus urticaeandT. evansithat respectively induce and suppress organic plant defences, measurable via the activity of trypsin inhibitors. We exposed plants to different concentrations of cadmium and measured their effect on mites and plants. The oviposition of both spider-mite species was higher on plants exposed to low concentrations of Cd than on control plants but decreased at concentrations above 0.5 mM. Therefore, herbivores with contrasting responses to organic defences responded similarly to metal accumulation by the plants. On the plant, despite clear evidence for Cd accumulation, we did not detect any effect of Cd on traits that reflect the general response of the plant, such as biomass, water content and carbon/nitrogen ratio. Still, we found an effect of Cd supply upon the quantity of soluble sugars and leaf reflectance changes that may reflect structural modifications in the cells. In turn, these changes in plant traits interfered with the performance of spider mites feeding on those plants.Additionally, we show that the induction and suppression of plant defences by spider mites was not affected by Cd supply to the plants. Furthermore, the effect of metal supply on spider-mite performance was not affected by previous infestation. Together, our results suggest no interaction between metal-based and organic plant defences, on our system. This may be useful for plants living in heterogeneous environments, as they may use one or the other defence mechanism, depending on their relative performance in each environment. This may be relevant to studies on the interactions between herbivores and plants, from physiology to ecology.
Formation of periodic pigment spots by the reaction-diffusion mechanism
Authors: Ding Baoqing , Patterson Erin L. , Holalu Srinidhi V. , Li Jingjian , Johnson Grace A. , Stanley Lauren E. , Greenlee Anna B. , Peng Foen , Bradshaw H. D. , Blackman Benjamin K. , Yuan Yao-Wu 
Published: August 2018

AbstractMany organisms exhibit visually striking spotted or striped pigmentation patterns. Turing’s reaction-diffusion model postulates that such periodic pigmentation patterns form when a local autocatalytic feedback loop and a long-range inhibitory feedback loop interact. At its simplest, this network only requires one self-activating activator that also activates a repressor, which inhibits the activator and diffuses to neighboring cells. However, the molecular activators and repressors fully fitting this versatile model remain elusive. Here, we characterize an R2R3-MYB activator and an R3-MYB repressor in monkeyflowers that correspond to Turing’s model and explain how periodic anthocyanin spots form. Notably, disrupting this pattern impacts pollinator visitation. Thus, subtle changes in simple reaction-diffusion networks are likely essential contributors to the evolution of the remarkable diversity of periodic pigmentation patterns in flowers.
Leave-One-Trial-Out (LOTO): A general approach to link single-trial parameters of cognitive models to neural data
Authors: Gluth Sebastian , Meiran Nachshon 
Published: August 2018

AbstractIt has become a key goal of model-based neuroscience to estimate trial-by-trial fluctuations of cognitive model parameters for linking these fluctuations to brain signals. However, previously developed methods were limited by being difficulty to implement, time-consuming, or model-specific. Here, we propose an easy, efficient and general approach to estimating trial-wise changes in parameters: Leave-One-Trial-Out (LOTO). The rationale behind LOTO is that the difference between the parameter estimates for the complete dataset and for the dataset with one omitted trial reflects the parameter value in the omitted trial. We show that LOTO is superior to estimating parameter values from single trials and compare it to previously proposed approaches. Furthermore, the method allows distinguishing true variability in a parameter from noise and from variability in other parameters. In our view, the practicability and generality of LOTO will advance research on tracking fluctuations in latent cognitive variables and linking them to neural data.
Oscillatory infrasonic modulation of the cochlear amplifier by selective attention
Authors: Dragicevic Constantino D. , Marcenaro Bruno , Navarrete Marcela , Robles Luis , Delano Paul H. 
Published: August 2018

AbstractEvidence shows that selective attention to visual stimuli modulates the gain of cochlear responses, probably through auditory-cortex descending pathways. At the cerebral cortex level, amplitude and phase changes of neural oscillations have been proposed as a correlate of selective attention. However, whether sensory receptors are also influenced by the oscillatory network during attention tasks remains unknown. Here, we searched for oscillatory attention-related activity at the cochlear receptor in humans. We used an alternating visual/auditory selective attention task and measured electroencephalographic activity simultaneously to distortion product otoacoustic emissions (a measure of cochlear receptor-cell activity). In order to search for cochlear oscillatory activity, the otoacoustic emission signal, was included as an additional channel in the electroencephalogram analyses. This method allowed us to study dynamic changes of cochlear oscillations in the same range of frequencies (1-35 Hz) in which cognitive effects are commonly observed in electroencephalogram works. We found the presence of low frequency (<10 Hz) brain and cochlear amplifier oscillations during periods of selective attention to visual and auditory stimuli. Notably, switching between auditory and visual attention modulates the amplitude and the temporal order of brain and inner ear oscillations. These results extend the role of the oscillatory activity network during cognition in neural systems to the receptor level.
Sex-Specific Protection Against Diet-Induced Non-Alcoholic Fatty Liver Disease in TRPV1 Null Mice
Authors: Connell Patrick J. , Bratz Ian N. , Andrei Spencer R. , Eusebio Luke , DelloStritto Daniel J. , Fahmy Joseph N. , Ferrell Jessica M. , Pathak Preeti , Chiang John Y.L. , Damron Derek S. 
Published: August 2018

AbstractObjectivesTRPV1 channels have been linked to the development and progression of diabetes at multiple levels, including control of appetite and weight, regulation of pancreatic function, thermogenesis, metabolism and energy homeostasis. Despite this, little information is known regarding its role in liver homeostasis and nonalcoholic fatty liver disease (NAFLD).Methods and ResultsTo better understand the role of TRPV1 in liver metabolism, we explored the effects of a high fat/sugar diet (Western, 24-week regimen) in male and female wild type (WT) and TRPV1-null (V1KO) mice. Our data reveal that loss of the TRPV1 gene makes mice susceptible to diet-induced obesity and induces NAFLD. V1KO mice displayed gross phenotypic and gross morphological changes including insulin resistance, glucose intolerance, increased body mass and central adiposity on a western diet compared to WT counterparts. Western fed V1KO mice exhibited gross changes in liver morphology and size compared to western fed WT mice, which were supported with histological H&E and Oil Red O staining. Accompanying the liver changes, Western fed V1KO mice exhibited altered lipid profiles as demonstrated by elevated hepatic triglyceride, cholesterol and free fatty acid levels compared to western fed WT mice. Interestingly, female V1KO mice fed a western diet displayed significant protection against diet-induced obesity and the progression of NAFLD compared to their male counterparts. Taken together, these data suggest that loss of TRPV1 promotes fat accumulation, NAFLD development and changes in liver lipid profiles in male mice, the extent to which is less severe in female V1KO mice.ConclusionIn conclusion, TRPV1 may be a protective therapeutic target for the prevention of NAFLD development in diet-induced obesity.
Chiral DNA sequences as commutable reference standards for clinical genomics
Authors: Deveson Ira W. , Madala Bindu Swapna , Blackburn James , Barker Chris , Wong Ted , Barton Kirston M. , Smith Martin A. , Watkins D. Neil , Mercer Tim R. 
Published: August 2018

ABSTRACTChirality is a geometric property describing any object that is inequivalent to a mirror image of itself. Due to its 5’-3’ directionality, a DNA sequence is distinct from a mirrored sequence arranged in reverse nucleotide order, and is therefore chiral. A given sequence and its opposing chiral partner sequence share many properties, such as nucleotide composition and sequence entropy. Here we demonstrate that chiral DNA sequence pairs also perform equivalently during molecular and bioinformatic techniques that underpin modern genetic analysis, including PCR amplification, hybridization, whole-genome, target-enriched and nanopore sequencing, sequence alignment and variant detection. Given these shared properties, synthetic DNA sequences that directly mirror clinically relevant and/or analytically challenging regions of the human genome are ideal reference standards for clinical genomics. We show how the addition of chiral DNA standards to patient tumor samples can prevent false-positive and false-negative mutation detection and, thereby, improve diagnosis. Accordingly, we propose that chiral DNA standards can fulfill the unmet need for commutable internal reference standards in precision medicine.
The capsule regulatory network ofKlebsiella pneumoniaedefined by density-TraDISort
Authors: Dorman Matthew J. , Feltwell Theresa , Goulding David A. , Parkhill Julian , Short Francesca L. 
Published: August 2018

AbstractKlebsiella pneumoniaeinfections affect infants and the immunocompromised, and the recent emergence of hypervirulent and multi-drug resistantK. pneumoniaelineages is a critical healthcare concern. Hypervirulence inK. pneumoniaeis mediated by several factors, including the overproduction of extracellular capsule. However, the full details of howK. pneumoniaecapsule biosynthesis is achieved or regulated are not known. We have developed a robust and sensitive procedure to identify genes influencing capsule production, density-TraDISort, which combines density gradient centrifugation with transposon-insertion sequencing. We have used this method to explore capsule regulation in two clinically-relevantKlebsiellastrains;K. pneumoniaeNTUH-K2044 (capsule type K1), andK. pneumoniaeATCC43816 (capsule type K2). We identified multiple genes required for full capsule production inK. pneumoniae, as well as putative suppressors of capsule in NTUH-K2044, and have validated the results of our screen with targeted knockout mutants. Further investigation of several of theK. pneumoniaecapsule regulators identified – ArgR, MprA/KvrB, SlyA/KvrA and the Sap ABC transporter – revealed effects on capsule amount and architecture, serum resistance and virulence. We show that capsule production inK. pneumoniaeis at the centre of a complex regulatory network involving multiple global regulators and environmental cues, and that the majority of capsule regulatory genes are located in the core genome. Overall our findings expand our understanding of how capsule is regulated in this medically-important pathogen, and provide a technology that can be easily implemented to study capsule regulation in other bacterial species.ImportanceCapsule production is essential forK. pneumoniaeto cause infections, but its regulation and mechanism of synthesis are not fully understood in this organism. We have developed and applied a new method for genome-wide identification of capsule regulators. Using this method, many genes that positively or negatively affect capsule production inK. pneumoniaewere identified, and we use these data to propose an integrated model for capsule regulation in this species. Several of the genes and biological processes identified have not previously been linked to capsule synthesis. We also show that the methods presented here can be applied to other species of capsulated bacteria, providing the opportunity to explore and compare capsule regulatory networks in other bacterial strains and species.
A tunable dual-input system for ‘on-demand’ dynamic gene expression regulation
Authors: Pedone Elisa , Rocca Dan L. , Postiglione Lorena , Aulicino Francesco , Montes-Olivas Sandra , Bernardo Diego di , Cosma Maria Pia , Marucci Lucia 
Published: August 2018

AbstractCellular systems have evolved numerous mechanisms to finely control signalling pathway activation and properly respond to changing environmental stimuli. This is underpinned by dynamic spatiotemporal patterns of gene expression. Indeed, in addition to gene transcription and translation regulation, modulation of protein levels, dynamics and localization are also essential checkpoints that govern cell functions. The introduction of tetracycline-inducible promoters has allowed gene expression control using orthogonal small molecules, facilitating rapid and reversible manipulation to study gene function in biological systems. However, differing protein stabilities means this solely transcriptional regulation is insufficient to allow precise ON-OFF dynamics, thus hindering generation of temporal profiles of protein levels seenin vivo. We developed an improved Tet-On based system augmented with conditional destabilising elements at the post-translational level that permits simultaneous control of gene expression and protein stability. Integrating these properties to control expression of a fluorescent protein in mouse Embryonic Stem Cells (mESCs), we found that adding protein stability control allows faster response times to changes in small molecules, fully tunable and enhanced dynamic range, and vastly improved microfluidic-basedin-silicofeedback control of gene expression. Finally, we highlight the effectiveness of our dual-input system to finely modulate levels of signalling pathway components in stem cells.
Mitotic chromosome binding predicts transcription factor properties in interphase
Authors: Raccaud Mahé , Alber Andrea B. , Friman Elias T. , Agarwal Harsha , Deluz Cédric , Kuhn Timo , Gebhardt J. Christof M. , Suter David M. 
Published: August 2018

SummaryMammalian transcription factors (TFs) differ broadly in their nuclear mobility and sequence-specific/non-specific DNA binding affinity. How these properties affect the ability of TFs to occupy their specific binding sites in the genome and modify the epigenetic landscape is unclear. Here we combined live cell quantitative measurements of mitotic chromosome binding (MCB) of 502 TFs, measurements of TF mobility by fluorescence recovery after photobleaching, single molecule imaging of DNA binding in live cells, and genome-wide mapping of TF binding and chromatin accessibility. MCB scaled with interphase properties such as association with DNA-rich compartments, mobility, as well as large differences in genome-wide specific site occupancy that correlated with TF impact on chromatin accessibility. As MCB is largely mediated by electrostatic, non-specific TF-DNA interactions, our data suggests that non-specific DNA binding of TFs enhances their search for specific sites and thereby their impact on the accessible chromatin landscape.