bluuebunny/crossref_metadata_2025_split huggingface dataset:
Halophilic microbial community compositional shift after a rare rainfall in the Atacama Desert
Authors: Uritskiy Gherman , Getsin Samantha , Munn Adam , Gomez-Silva Benito , Davila Alfonso , Glass Brian , Taylor James , DiRuggiero Jocelyne 
Published: October 2018

ABSTRACTUnderstanding the mechanisms underlying microbial resistance and resilience to perturbations is essential to predict the impact of climate change on Earth’s ecosystems. However, the resilience and adaptation mechanisms of microbial communities to natural perturbations remain relatively unexplored, particularly in extreme environments. The response of an extremophile community inhabiting halite (salt rocks) in the Atacama Desert to a catastrophic rainfall provided the opportunity to characterize and de-convolute the temporal response of a highly specialized community to a major disturbance. With shotgun metagenomic sequencing, we investigated the halite microbiome taxonomic composition and functional potential over a 4-year longitudinal study, uncovering the dynamics of the initial response and of the recovery of the community after a rainfall event. The observed changes can be recapitulated by two general modes of community shifts – a rapidType 1shift and a more gradualType 2adjustment. In the initial response, the community entered an unstable intermediate state after stochastic niche re-colonization, resulting in broad predicted protein adaptations to increased water availability. In contrast, during recovery, the community returned to its former functional potential by a gradual shift in abundances of the newly acquired taxa. The general characterization and proposed quantitation of these two modes of community response could potentially be applied to other ecosystems, providing a theoretical framework for prediction of taxonomic and functional flux following environmental changes.
A prognostic signature for lower-grade gliomas based on expression of long noncoding RNAs
Authors: Kiran Manjari , Chatrath Ajay , Tang Xiwei , Keenan Daniel Macrae , Dutta Anindya 
Published: October 2018

AbstractDiffuse low-grade and intermediate-grade gliomas (together known as lower-grade gliomas, WHO grade II and III) develop in the supporting glial cells of brain and are the most common types of primary brain tumor. Despite a better prognosis for lower-grade gliomas, 70% of patients undergo high-grade transformation within 10 years, stressing the importance of better prognosis. Long non-coding RNAs (lncRNAs) are gaining attention as potential biomarkers for cancer diagnosis and prognosis. We have developed a computational model, UVA8, for prognosis of lower-grade gliomas by combining lncRNA expression, Cox regression and L1-LASSO penalization. The model was trained on a subset of patients in TCGA. Patients in TCGA, as well as a completely independent validation set (CGGA) could be dichotomized based on their risk score, a linear combination of the level of each prognostic lncRNA weighted by its multivariable cox regression coefficient. UVA8 is an independent predictor of survival and outperforms standard epidemiological approaches and previous published lncRNA-based predictors as a survival model. Guilt-by-association studies of the lncRNAs in UVA8, all of which predict good outcome, suggest they have a role in suppressing interferon stimulated response and epithelial to mesenchymal transition. The expression levels of 8 lncRNAs can be combined to produce a prognostic tool applicable to diverse populations of glioma patients. The 8 lncRNA (UVA8) based score can identify grade II and grade III glioma patients with poor outcome and thus identify patients who should receive more aggressive therapy at the outset.
The History, Advocacy and Efficacy of Data Management Plans
Authors: Smale Nicholas , Unsworth Kathryn , Denyer Gareth , Barr Daniel 
Published: October 2018

AbstractData management plans (DMPs) have increasingly been encouraged as a key component of institutional and funding body policy. Although DMPs necessarily place administrative burden on researchers, proponents claim that DMPs have myriad benefits, including enhanced research data quality, increased rates of data sharing, and institutional planning and compliance benefits.In this manuscript, we explore the international history of DMPs and describe institutional and funding body DMP policy. We find that economic and societal benefits from presumed increased rates of data sharing was the original driver of mandating DMPs by funding bodies. Today, 86% of UK Research Councils and 63% of US funding bodies require submission of a DMP with funding applications. Given that no major Australian funding bodies require DMP submission, it is of note that 37% of Australian universities have taken the initiative to internally mandate DMPs.Institutions both within Australia and internationally frequently promote the professional benefits of DMP use, and endorse DMPs as ‘best practice’. We analyse one such typical DMP implementation at a major Australian institution, finding that DMPs have low levels of apparent translational value. Indeed, an extensive literature review suggests there is very limited published systematic evidence that DMP use has any tangible benefit for researchers, institutions or funding bodies.We are therefore led to question why DMPs have become the go-to tool for research data professionals and advocates of good data practice. By delineating multiple use-cases and highlighting the need for DMPs to be fit for intended purpose, we question the view that a good DMP is necessarily that which encompasses the entire data lifecycle of a project. Finally, we summarise recent developments in the DMP landscape, and note a positive shift towards evidence-based research management through more researcher-centric, educative, and integrated DMP services.
Longitudinal Visual Analytics for Unpacking the Cancer Journey
Authors: Yuan Zhou , Finan Sean , Warner Jeremy , Savova Guergana , Hochheiser Harry 
Published: October 2018

AbstractRetrospective cancer research requires identification of patients matching both categorical and temporal inclusion criteria, often based on factors exclusively available in clinical notes. Although natural language processing approaches for inferring higher-level concepts have shown promise for bringing structure to clinical texts, interpreting results is often challenging, involving the need to move between abstracted representations and constituent text elements. We discuss qualitative inquiry into user tasks and goals, data elements and models resulting in an innovative natural language processing pipeline and a visual analytics tool designed to facilitate interpretation of patient summaries and identification of cohorts for retrospective research.
Contribution of sensory encoding to measured bias
Authors: Jin Miaomiao , Glickfeld Lindsey L. 
Published: October 2018

AbstractPerceptual decision-making is a complex process that involves sensory integration followed by application of a cognitive threshold. Signal detection theory (SDT) provides a mathematical framework for attributing the underlying neurobiological processes to these distinct phases of perceptual decision-making. In particular, SDT reveals the sensitivity (d’) of the neuronal response distributions and the bias (c) of the decision criterion, which are commonly thought to reflect sensory and cognitive processes, respectively. However, neuronal representations of bias have been observed in sensory areas, suggesting that some changes in bias are due to effects on sensory encoding. To directly test whether sensory encoding can influence bias, we optogenetically manipulated neuronal excitability in primary visual cortex (V1) during a detection task. Increasing excitability in V1 significantly decreased behavioral bias, while decreasing excitability had the opposite effect. To determine whether this change in bias is consistent with the effects on sensory encoding, we made extracellular recordings from V1 neurons in passively viewing mice. Indeed, we found that optogenetic manipulation of excitability shifted the neuronal bias in the same direction as the behavioral bias, despite using a fixed artificial decision criterion to predict hit and false alarm rates from the neuronal firing rates. To test the generality these effects, we also manipulated the quality of V1 encoding by changing stimulus contrast or inter-stimulus interval. These stimulus manipulations also resulted in consistent changes in bias measured both behaviorally and neuronally. Thus, changes in sensory encoding are sufficient to drive changes in bias measured using SDT.
Geometric principles of second messenger dynamics in dendritic spines
Authors: Cugno Andrea , Bartol Thomas M. , Sejnowski Terrence J. , Iyengar Ravi , Rangamani Padmini 
Published: October 2018

AbstractDendritic spines are small, bulbous protrusions along dendrites in neurons and play a critical role in synaptic transmission. Dendritic spines come in a variety of shapes that depend on their developmental state. Additionally, roughly 14−19% of mature spines have a specialized endoplasmic reticulum called the spine apparatus. How does the shape of a postsynaptic spine and its internal organization affect the spatio-temporal dynamics of short timescale signaling? Answers to this question are central to our understanding the initiation of synaptic transmission, learning, and memory formation. In this work, we investigated the effect of spine and spine apparatus size and shape on the spatio-temporal dynamics of second messengers using mathematical modeling using reaction-diffusion equations in idealized geometries (ellipsoids, spheres, and mushroom-shaped). Our analyses and simulations showed that in the short timescale, spine size and shape coupled with the spine apparatus geometries govern the spatiotemporal dynamics of second messengers. We show that the curvature of the geometries gives rise to pseudo-harmonic functions, which predict the locations of maximum and minimum concentrations along the spine head. Furthermore, we showed that the lifetime of the concentration gradient can be fine-tuned by localization of fluxes on the spine head and varying the relative curvatures and distances between the spine apparatus and the spine head. Thus, we have identified several key geometric determinants of how the spine head and spine apparatus may regulate the short timescale chemical dynamics of small molecules that control synaptic plasticity.
The COMA complex is required for positioning Ipl1 activity proximal to Cse4 nucleosomes in budding yeast
Authors: Halwachs Josef Fischböck , Singh Sylvia , Potocnjak Mia , Hagemann Götz , Solis Victor , Woike Stephan , Steger Medini Ghodgaonkar , Feuillet Jessica Andreani , Herzog Franz 
Published: October 2018

AbstractKinetochores are macromolecular protein complexes assembled on centromeric chromatin that ensure accurate chromosome segregation by linking DNA to spindle microtubules and integrating safeguard mechanisms. A kinetochore-associated pool of Ipl1Aurora B kinase, a subunit of the chromosomal passenger complex (CPC), was previously implicated in feedback control mechanisms. To study the kinetochore subunit connectivity built on budding yeast point centromeres and its CPC interactions we performed crosslink-guided in vitro reconstitution. The Ame1/Okp1CENP-U/Q heterodimer, forming the COMA complex with Ctf19/Mcm21CENP-P/O, selectively bound Cse4CENP-A nucleosomes through the Cse4 N-terminus and thereby establishes a direct link to the outer kinetochore MTW1 complex. The Sli15/Ipl1INCENP/Aurora B core-CPC interacted with COMA through the Ctf19 C-terminus, and artificial tethering of Sli15 to Ame1/Okp1 rescued synthetic lethality upon Ctf19/Mcm21 deletion in a Sli15 centromere-targeting deficient mutant. This study reveals characteristics of the inner kinetochore architecture assembled at point centromeres and the relevance of its Sli15/Ipl1 interaction for CPC function.
A direct comparison of genome alignment and transcriptome pseudoalignment
Authors: Yi Lynn , Liu Lauren , Melsted Páll , Pachter Lior 
Published: October 2018

AbstractMotivationGenome alignment of reads is the first step of most genome analysis workflows. In the case of RNA-Seq, transcriptome pseudoalignment of reads is a fast alternative to genome alignment, but the different “coordinate systems” of the genome and transcriptome have made it difficult to perform direct comparisons between the approaches.ResultsWe have developed tools for converting genome alignments to transcriptome pseudoalignments, and conversely, for projecting transcriptome pseudoalignments to genome alignments. Using these tools, we performed a direct comparison of genome alignment with transcriptome pseudoalignment. We find that both approaches produce similar quantifications. This means that for many applications genome alignment and transcriptome pseudoalignment are interchangeable.Availability and Implementationbam2tcc is a C++14 software for converting alignments in SAM/BAM format to transcript compatibility counts (TCCs) and is available at https://github.com/pachterlab/bam2tcc. kallisto genomebam is a user option of kallisto that outputs a sorted BAM file in genome coordinates as part of transcriptome pseudoalignment. The feature has been released with kallisto v0.44.0, and is available at https://pachterlab.github.io/kallisto/.Supplementary MaterialN/AContactLior Pachter (lpachter@caltech.edu)
High throughput droplet single-cell Genotyping of Transcriptomes (GoT) reveals the cell identity dependency of the impact of somatic mutations
Authors: Nam Anna S. , Kim Kyu-Tae , Chaligne Ronan , Izzo Franco , Ang Chelston , Abu-Zeinah Ghaith , Omans Nathaniel D. , Taylor Justin , Pastore Alessandro , Alonso Alicia , Mariani Marisa , Cubillos-Ruiz Juan R. , Tam Wayne , Hoffman Ronald , Scandura Joseph M. , Rabadan Raul , Abdel-Wahab Omar , Smibert Peter , Landau Dan A. 
Published: October 2018

AbstractDefining the transcriptomic identity of clonally related malignant cells is challenging in the absence of cell surface markers that distinguish cancer clones from one another or from admixed non-neoplastic cells. While single-cell methods have been devised to capture both the transcriptome and genotype, these methods are not compatible with droplet-based single-cell transcriptomics, limiting their throughput. To overcome this limitation, we present single-cell Genotyping of Transcriptomes (GoT), which integrates cDNA genotyping with high-throughput droplet-based single-cell RNA-seq. We further demonstrate that multiplexed GoT can interrogate multiple genotypes for distinguishing subclonal transcriptomic identity. We apply GoT to 26,039 CD34+ cells across six patients with myeloid neoplasms, in which the complex process of hematopoiesis is corrupted by CALR-mutated stem and progenitor cells. We define high-resolution maps of malignant versus normal hematopoietic progenitors, and show that while mutant cells are comingled with wildtype cells throughout the hematopoietic progenitor landscape, their frequency increases with differentiation. We identify the unfolded protein response as a predominant outcome of CALR mutations, with significant cell identity dependency. Furthermore, we identify that CALR mutations lead to NF-κB pathway upregulation specifically in uncommitted early stem cells. Collectively, GoT provides high-throughput linkage of single-cell genotypes with transcriptomes and reveals that the transcriptional output of somatic mutations is heavily dependent on the native cell identity.
Response of Australian pied oystercatchersHaematopus longirostristo increasing abundance of the beach bivalve preyDonax deltoides
Authors: Totterman Stephen L. 
Published: October 2018

AbstractThis study measured the response of Australian pied oystercatchersHaematopus longirostrison South Ballina Beach, New South Wales, Australia during a recovery in the stock of the primary prey speciesDonax deltoides, a large beach clam and commonly known as the ‘pipi’. It was predicted that oystercatcher counts would increase when pipi abundance increased (numerical response) and that oystercatcher feeding rates would also increase (functional response). Between Oct 2009 and Mar 2015, mean pipi density increased from c. zero to 30 pipis/m2. Mean oystercatcher feeding rates increased to an asymptote of c. 0.26 pipis/min. Breeding season mean counts of adult-plumage oystercatchers increased from 23 to 43, largely driven by non-territorial birds. Prey size selection was absent, both among different prey types and among pipis > 20 mm. This report provides some insights into the feeding ecology of oystercatchers on sandy ocean beaches that should be valuable in planning future studies.
Identifying stationary phases in multivariate time-series for highlighting behavioural modes and home range settlements
Authors: Patin Rémi , Étienne Marie-Pierre , Lebarbier Émilie , Chamaillé-Jammes Simon , Benhamou Simon 
Published: October 2018

AbstractRecent advances in bio-logging open promising perspectives in the study animal movements at numerous scales. It is now possible to record time-series of animal locations and ancillary data (e.g. activity level derived from on-board accelerometers) over extended areas and long durations with a high spatial and temporal resolution. Such time-series are often piecewise stationary, as the animal may alternate between different stationary phases (i.e. characterised by a specific mean and variance of some key parameter for limited periods). Identifying when these phases start and end is a critical first step to understand the dynamics of the underlying movement processes.We introduce a new segmentation-clustering method we called segclust2d. It can segment bi-(or more generally multi-) variate time-series and possibly cluster the various segments obtained, corresponding to phases assumed to be stationary. It is easy to use, as it only requires specifying the minimum length of a segment (to prevent over-segmentation) based on biological considerations.Although this method can be applied to time-series of any nature, we focus here on two-dimensional piecewise time-series whose phases correspond at small scale to the expressions of different behavioural modes such as transit, feeding and resting, as characterised by two joint metrics such as speed and turning angles or, at larger scale, to temporary home ranges, characterised by stationary distributions of bivariate coordinates.Using computer simulations, we show that segcust2d can rival and even outperform previous, more complex methods, which were specifically developed to highlight changes in movement modes or home range shifts (based on Hidden Markov or Ornstein-Uhlenbeck modelling, respectively), which, contrary to our method, require truly informative initial guesses to be efficient. Furthermore we demonstrate it on actual examples involving a zebra’s small scale movements and an elephant’s large scale movements, to illustrate the identification of various movement modes and of home range shifts, respectively.
MicroRNAs buffer genetic variation at specific temperatures during embryonic development
Authors: Amourda Christopher , Chong Jeronica , Saunders Timothy E. 
Published: October 2018

AbstractSuccessful embryogenesis requires the coordination of developmental events. Perturbations, such as environmental changes, must be buffered to ensure robust development. However, how such buffering occurs is currently unknown in most developmental systems. Here, we demonstrate that seven miRNAs are differentially expressed duringDrosophilaembryogenesis at varying temperatures within natural physiological ranges. Lack of miR-3-309, -31a, -310c, -980 or -984c causes developmental delays specifically at a given temperature. Detailed analysis on miR-310c and -984c shows that their targets are typically mis-expressed in mutant backgrounds, with phenotypes more pronounced at temperatures where miRNAs show highest expression in wild-type embryos. Our results show that phenotypes may arise at specific temperatures while remaining silent at others, even within typical temperature ranges. Our work uncovers that miRNAs mask genetic variation at specific temperatures to increase embryonic robustness, highlighting another layer of complexity in miRNA expression.
Haplotype assignment of longitudinal viral deep-sequencing data using co-variation of variant frequencies
Authors: Pang Juanita , Venturini Cristina , Tamuri Asif U. , Roy Sunando , Breuer Judith , Goldstein Richard A. 
Published: October 2018

ABSTRACTLongitudinal deep sequencing of viruses can provide detailed information about intra-host evolutionary dynamics including how viruses interact with and transmit between hosts. Many analyses require haplotype reconstruction, identifying which variants are co-located on the same genomic element. Most current methods to perform this reconstruction are based on a high density of variants and cannot perform this reconstruction for slowly evolving viruses. We present a new approach, HaROLD (HAplotype Reconstruction Of Longitudinal Deep sequencing data), which performs this reconstruction based on identifying co-varying variant frequencies using a probabilistic framework. We test this method with synthetic data sets of mixed cytomegalovirus and norovirus genomes, demonstrating high accuracy when longitudinal samples are available.
DNA replication initiation in Bacillus subtilis; Structural and functional characterisation of the essential DnaA-DnaD interaction
Authors: Martin Eleyna , Williams Huw E. L. , Pitoulias Matthaios , Stevens Daniel , Winterhalter Charles , Craggs Timothy D. , Murray Heath , Searle Mark S. , Soultanas Panos 
Published: October 2018

AbstractThe homotetrameric DnaD protein is essential in low G+C content gram positive bacteria and is involved in replication initiation at oriC and re-start of collapsed replication forks. It interacts with the ubiquitously conserved bacterial master replication initiation protein DnaA at the oriC but structural and functional details of this interaction are lacking, thus contributing to our incomplete understanding of the molecular details that underpin replication initiation in bacteria. DnaD comprises N-terminal (DDBH1) and C-terminal (DDBH2) domains, with contradicting bacterial two-hybrid and yeast two-hybrid studies suggesting that either the former or the latter interact with DnaA, respectively. Using Nuclear Magnetic Resonance (NMR) we show that both DDBH1 and DDBH2 interact with the N-terminal domain I of DnaA and studied the DDBH2 interaction in structural detail by NMR. We revealed two families of conformations for the DDBH2-DnaA domain I complex and showed that the DnaA-interaction patch of DnaD is distinct from the DNA-interaction patch, suggesting that DnaD can bind simultaneously DNA and DnaA. Using sensitive single-molecule FRET techniques we revealed that DnaD remodels DnaA-DNA filaments consistent with stretching and/or untwisting. Furthermore, the DNA binding activity of DnaD is redundant for this filament remodelling. This in turn suggests that DnaA and DnaD are working collaboratively in the oriC to locally melt the DNA duplex during replication initiation.