bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast and memory-efficient noisy read overlapping with KD-trees
Authors: Parkhomchuk Dmitri , Bremges Andreas , McHardy Alice C. 
Published: July 2017

MotivationThird-generation sequencing technologies produce long, but noisy reads with increasing sequencing throughput and decreasing per-base costs. Detecting read-to-read overlaps in such data is the most computationally intensive step inde novoassembly. Recently, efficient algorithms were developed for this task; nearly all of these utilize longk-mers (>10 bp) to compare reads, but vary in their approaches to indexing, hashing, filtering, and dimensionality reduction.ResultsWe describe an algorithm for efficient overlap detection that directly compares the full spectrum of shortk-mers, namely tetramers, through geometric embedding and approximate nearest neighbor search in multidimensional KD-trees. A proof of concept implementation detected read-to-read overlaps in bacterial PacBio and ONT datasets with notably lower memory consumption than state-of-the-art approaches and allowed downstreamde novoassembly into single contigs. We also introduce a sequence-context dependent tagging scheme that contributes to memory and computational efficiency and could be used with other aligning and overlapping algorithms.AvailabilityA C++14 implementation is available under the open source Apache License 2.0 at:https://github.com/dzif/kd-tree-overlapper
Chromatin loop anchors are associated with genome instability in cancer and recombination hotspots in the germline
Authors: Kaiser Vera B , Semple Colin A 
Published: July 2017

ABSTRACTChromatin loops form a basic unit of interphase nuclear organisation, providing contacts between regulatory regions and target promoters, and forming higher level patterns defining self interacting domains. Recent studies have shown that mutations predicted to alter chromatin loops and domains are frequently observed in tumours and can result in the upregulation of oncogenes, but the combinations of selection and mutational bias underlying these observations remains unknown. Here, we explore the unusual mutational landscape associated with chromatin loop anchor points (LAPs), which are located at the base of chromatin loops and form a kinetic trap for cohesin. We show that LAPs are strongly depleted for single nucleotide variants (SNVs) in tumours, which is consistent with their relatively early replication timing. However, despite low SNV rates, LAPs emerge as sites of evolutionary innovation showing enrichment for structural variants (SVs). They harbour an excess of SV breakpoints in cancers, are prone to double strand breaks in somatic cells, and are bound by DNA repair complex proteins. Recurrently disrupted LAPs are often associated with genes annotated with functions in cell cycle transitions. An unexpectedly large fraction of LAPs (16%) also overlap known meiotic recombination hotspot (HSs), and are enriched for the core PRDM9 binding motif, suggesting that LAPs have been foci for diversity generated during recent human evolution. We suggest that the unusual chromatin structure at LAPs underlies the elevated SV rates observed, marking LAPs as sites of regulatory importance but also genomic fragility.
BAF chromatin remodeling complex subunit diversity promotes temporally distinct gene expression programs in cardiogenesis
Authors: Hota Swetansu K. , Johnson Jeffrey R. , Verschueren Erik , Thomas Reuben , Blotnick Aaron M. , Zhu Yiwen , Sun Xin , Pennacchio Len A. , Krogan Nevan J. , Bruneau Benoit G. 
Published: July 2017

AbstractChromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. The BRG1/BRM associated factor (BAF) complexes are important for several aspects of differentiation. We show that the catalytic subunitBrg1has a specific role in cardiac precursors (CPs) to initiate cardiac gene expression programs and repress non-cardiac expression. Using immunoprecipitation with mass spectrometry (IP-MS), we determined the dynamic composition of BAF complexes during mammalian cardiac differentiation, and identified BAF60c (SMARCD3) and BAF170 (SMARCC2) as subunits enriched in CPs and cardiomyocytes (CM).Baf60candBaf170co-regulate gene expression withBrg1in CPs, but in CMs control different gene expression programs, although still promoting a cardiac-specific gene set. BRG1, BAF60, and BAF170 all modulate chromatin accessibility, to either promote accessibility at activated genes, while closing up chromatin at repressed genes. BAF60c and BAF170 are required for proper BAF complex composition and stoichiometry, and promote BRG1 occupancy in CM. Additionally, BAF170 facilitates expulsion of BRG1-containing complexes in the transition from CP to CM. Thus, dynamic interdependent BAF complex subunit assembly modulates chromatin states and thereby directs temporal gene expression programs in cardiogenesis.Significance statementBRG1/BRM associated factors (BAF) form multi-subunit protein complexes that reorganize chromatin and regulate transcription. Specific BAF complex subunits have important roles during cell differentiation and development. We systematically identify BAF subunit composition and find temporal enrichment of subunits during cardiomyocyte differentiation. We find the catalytic subunit BRG1 has important contributions in initiating gene expression programs in cardiac progenitors along with cardiac-enriched subunits BAF60c and BAF170. Both these proteins regulated BAF subunit composition and chromatin accessibility and prevent expression of non-cardiac developmental genes during precursor to cardiomyocyte differentiation. Mechanistically, we find BAF170 destabilizes the BRG1 complex and expels BRG1 from cardiomyocyte-specific genes. Thus, our data shows synergies between diverse BAF subunits in facilitating temporal gene expression programs during cardiogenesis.
Developmental transcriptomics of the brittle starAmphiura filiformisreveals gene regulatory network rewiring in echinoderm larval skeleton evolution
Authors: Dylus David , Blowes Liisa M. , Czarkwiani Anna , Elphick Maurice R. , Oliveri Paola 
Published: July 2017

ABSTRACTAmongst the echinoderms the class Ophiuroidea is of particular interest for its phylogenetic position, ecological importance, developmental and regenerative biology. However, compared to other echinoderms, notably echinoids (sea urchins), relatively little is known about developmental changes in gene expression in ophiuroids. To address this issue we have generated and assembled a large RNAseq data set of four key stages of development in the brittle starAmphiura filiformisand ade novoreference transcriptome of comparable quality to that of a model echinoderm - the sea urchinStrongyloncentrotus purpuratus. Furthermore, we provide access to the new data via a web interface:http://www.echinonet.eu/shiny/Amphiura_filiformis/. With a focus on skeleton development, we have identified highly conserved genes associated with the development of a biomineralized skeleton. We also identify important class-specific characters, including the independent duplication of themsp130class of genes in different echinoderm classes and the unique occurrence of spicule matrix (sm) genes in echinoids. Using a new quantification pipeline for ourde novotranscriptome, validated with other methodologies, we find major differences between brittle stars and sea urchins in the temporal expression of many transcription factor genes. This divergence in developmental regulatory states is more evident in early stages of development when cell specification begins, than when cells initiate differentiation. Our findings indicate that there has been a high degree of gene regulatory network rewiring in the evolution of echinoderm larval development.Data DepositionsAll sequence reads are available at Genbank SRR4436669 - SRR4436674. Any sequence alignments used are available by the corresponding author upon request.
Using MinION™to characterize dog skin microbiota through full-length 16S rRNA gene sequencing approach
Authors: Cuscó Anna , Viñes Joaquim , D’Andreano Sara , Riva Francesca , Casellas Joaquim , Sánchez Armand , Francino Olga 
Published: July 2017

AbstractThe most common strategy to assess microbiota is sequencing specific hypervariable regions of 16S rRNA gene using 2ndgeneration platforms (such as MiSeq or Ion Torrent PGM). Despite obtaining high-quality reads, many sequences fail to be classified at the genus or species levels due to their short length. This pitfall can be overcome sequencing the full-length 16S rRNA gene (1,500bp) by 3rdgeneration sequencers.We aimed to assess the performance of nanopore sequencing using MinION™on characterizing microbiota complex samples. First set-up step was performed using a staggered mock community (HM-783D). Then, we sequenced a pool of several dog skin microbiota samples previously sequenced by Ion Torrent PGM. Sequences obtained for full-length 16S rRNA with degenerated primers retrieved increased richness estimates at high taxonomic level (Bacteria and Archaea) that were missed with short-reads. Besides, we were able to obtain taxonomic assignments down to species level, although it was not always feasible due to: i) incomplete database; ii) primer set chosen; iii) low taxonomic resolution of 16S rRNA gene within some genera; and/or iv) sequencing errors. Nanopore sequencing of the full-length 16S rRNA gene using MinION™with 1D sequencing kit allowed us inferring microbiota composition of a complex microbial community to lower taxonomic levels than short-reads from 2ndgeneration sequencers.
Multiple Geographical Origins of Environmental Sex Determination enhanced the diversification of Darwin’s Favourite Orchids
Authors: Pérez-Escobar Oscar Alejandro , Chomicki Guillaume , Condamine Fabien L. , de Vos Jurriaan M. , Martins Aline C. , Smidt Eric C. , Klitgård Bente , Gerlach Günter , Heinrichs Jochen 
Published: July 2017

AbstractEnvironmental sex determination (ESD) – a change in sexual function during an individual life span driven by environmental cues – is an exceedingly rare sexual system among angiosperms. Because ESD can directly affect reproduction success, it could influence diversification rate as compared with lineages that have alternative mating systems. Here we test this hypothesis using a solid phylogenetic framework of Neotropical Catasetinae, the angiosperm lineage richest in taxa with ESD. We assess whether gains of ESD are associated with higher diversification rates compared to lineages with alternative systems while considering additional traits known to positively affect diversification rates in orchids. We found that ESD has evolved asynchronously three times during the last ~5 Myr. Lineages with ESD have consistently higher diversification rates than related lineages with other sexual systems. Habitat fragmentation due to mega-wetlands extinction, and climate instability are suggested as the driving forces for ESD evolution.
Understanding the dynamics of scaffold-mediated signaling
Authors: Suderman Ryan , Schauer Addison , Deeds Eric J. 
Published: July 2017

AbstractMany signaling networks involve scaffold proteins that bind multiple kinases in kinase cascades. While scaffolds play a fundamental role in regulating signaling, few hypotheses regarding their function have been rigorously examined. Here, we used dynamical models of scaffold signaling to investigate the impact scaffolds have on network behavior. We considered two paradigms of scaffold assembly: as either the nucleation point for assembly of discrete multi-subunit proteins (the machine paradigm) or a platform upon which kinases independently associate (the ensemble paradigm). We found that several well-accepted hypotheses regarding the role of scaffolds in regulating signal response either do not hold or depend critically on the assembly paradigm employed. In addition to providing novel insights into the function of scaffold proteins, our work suggests experiments that could distinguish between assembly paradigms. Our findings should also inform attempts to target scaffold proteins for therapeutic intervention and the design of scaffolds for synthetic biology.
Distinct antibody-mediated selection in a narrow-source HIV-1 outbreak among Chinese former plasma donors
Authors: Andrews Sophie M. , Zhang Yonghong , Dong Tao , Rowland-Jones Sarah L. , Gupta Sunetra , ESBJÖRNSSON Joakim 
Published: July 2017

ABSTRACTThe HIV-1 envelope protein mutates rapidly to evade recognition and killing, and is a major target of the humoral immune response and in vaccine development. Identification of common antibody epitopes for vaccine development have been complicated by large variations on both virus (different infecting founder strains) and host genetic levels. We studied HIV-1 envelopegp120evolution in 12 Chinese former plasma donors infected with a purportedly single founder virus, with the aim of identifying common antibody epitopes under immune selection. We found five amino acid sites to be under significant positive selection in ≥50% of the patients, and 22 sites housing mutations consistent with antibody-mediated selection. Despite strong selection pressure, some sites housed a limited repertoire of amino acids. Structural modelling revealed that most sites were located on the exposed distal edge of the Gp120 trimer, whilst wholly invariant sites clustered within the centre of the protein complex. Four sites, flanking the V3 hypervariable loop of the Gp120, represent novel antibody epitopes that may be suitable as vaccine candidates.
The Correlation between MicroRNA-199a and White Adipose Tissue in C57/BL6J Mice with High-Fat Diet
Authors: Liu Dan , Wang Xia , Lin Xinying , Zhang Baihui , Wang Shue , Bao Wei 
Published: July 2017

AbstractUnderstanding is emerging about microRNAs as mediators in the regulation of white adipose tissue (WAT) and obesity. The expression level of miR-199a in mice was investigated to test our hypothesis: miR-199a might be related to fat accumulation and try to find its target mRNA, which perhaps could propose strategies with a therapeutic potential affecting the fat storage. C57/BL6J mice were randomly assigned to either a control group or an obesity model group (n=10 in both groups). Control mice were fed a normal diet (fat: 10 kcal %)ad libitumfor 12 weeks, and model mice were fed a high-fat diet (fat: 30 kcal %)ad libitumfor 12 weeks to induce obesity. At the end of the experiment, body fat mass and the free fatty acids (FFAs) and triglycerides (TGs) in WAT were tested. Fat cell size was measured by hematoxylin-eosin (H&E) staining method. The fat mass of the model group was higher than that of the control group (P<0.05). In addition, the concentrations of the FFAs and TGs were higher (P<0.05) and the adipocyte count was lower (P<0.05) in the model group. We tested the expression levels of miR-199a and key adipogenic transcription factors, including peroxisome proliferator activated receptor gamma2 (PPARγ2), CCAAT/enhancer binding proteins alpha (C/EBPα), adipocyte fatty acid-binding protein (aP2), and sterol regulatory element binding protein-1c (SREBP-1c). Up-regulated expression of miR-199a was observed in model group. Increased levels of miR-199a was accompanied by high expression levels of SREBP-1c. We found that the 3’-UTR of SREBP-1c mRNA has a predicted binding site for miR-199a. Based on the current discoveries, we suggest that miR-199a may exert its action by binding to its target mRNA and cooperate with SREBP-1c to induce obesity. Therefore, if the predicted binding site is confirmed by further research, miR-199a may have therapeutic potential for obesity.AbbreviationsWAT, white adipose tissue; PPARγ2, peroxisome proliferator, activated receptor γ2; C/EBP αCCAAT/enhancer binding proteins α; aP2, adipocyte fatty acid-binding protein; SREBP-1c, sterol regulatory element binding protein-1c; HFD, high-fat diet.
Operating regimes of covalent modification cycles at high enzyme concentrations
Authors: Straube Ronny 
Published: July 2017

AbstractThe Goldbeter-Koshland model has been a paradigm for ultrasensitivity in biological networks for more than 30 years. Despite its simplicity the validity of this model is restricted to conditions when the substrate is in excess over the converter enzymes − a condition that is easy to satisfyin vitro, but which is rarely satisfiedin vivo. Here, we analyze the Goldbeter-Koshland model by means of the total quasi-steady state approximation which yields a comprehensive classification of the steady state operating regimes under conditions when the enzyme concentrations are comparable to or larger than that of the substrate. Where possible we derive simple expressions characterizing the input-output behavior of the system. Our analysis suggests that enhanced sensitivity occurs if the concentration of at least one of the converter enzymes is smaller (but not necessarily much smaller) than that of the substrate and if that enzyme is saturated. Conversely, if both enzymes are saturated and at least one of the enzyme concentrations exceeds that of the substrate the system exhibits concentration robustness with respect to changes in that enzyme concentration. Also, depending on the enzyme’s saturation degrees and the ratio between their maximal reaction rates the total fraction of phosphorylated substrate may increase, decrease or change nonmonotonically as a function of the total substrate concentration. The latter finding may aid the interpretation of experiments involving genetic manipulations of enzyme and substrate abundances.
Capturing the diversity of biological tuning curves using generative adversarial networks
Authors: Arakaki Takafumi , Barello G. , Ahmadian Yashar 
Published: July 2017

AbstractTuning curves characterizing the response selectivities of biological neurons often exhibit large degrees of irregularity and diversity across neurons. Theoretical network models that feature heterogeneous cell populations or random connectivity also give rise to diverse tuning curves. However, a general framework for fitting such models to experimentally measured tuning curves is lacking. We address this problem by proposing to view mechanistic network models as generative models whose parameters can be optimized to fit the distribution of experimentally measured tuning curves. A major obstacle for fitting such models is that their likelihood function is not explicitly available or is highly intractable to compute. Recent advances in machine learning provide ways for fitting generative models without the need to evaluate the likelihood and its gradient. Generative Adversarial Networks (GAN) provide one such framework which has been successful in traditional machine learning tasks. We apply this approach in two separate experiments, showing how GANs can be used to fit commonly used mechanistic models in theoretical neuroscience to datasets of measured tuning curves. This fitting procedure avoids the computationally expensive step of inferring latent variables,e.g., the biophysical parameters of individual cells or the particular realization of the full synaptic connectivity matrix, and directly learns model parameters which characterize thestatisticsof connectivity or of single-cell properties. Another strength of this approach is that it fits the entire, joint distribution of experimental tuning curves, instead of matching a few summary statistics pickeda prioriby the user. More generally, this framework opens the door to fitting theoretically motivated dynamical network models directly to simultaneously or non-simultaneously recorded neural responses.
Metabolism constrains bird and mammal ranges and predicts shifts in response to climate change
Authors: Buckley Lauren B. , Khaliq Imran , Swanson David L. , Hof Christian 
Published: July 2017

AbstractAimWe test whether physiological constraints on maximum metabolic rate and the factor by which endotherms can elevate their metabolism (metabolic expansibility) govern cold range limits for mammal and bird species.LocationGlobalMethodsWe examine metabolic expansibility at the cold range boundary (MEcrb) and its trait predictors and then use MEcrbto project range shifts for 210 mammal and 61 bird species.ResultsWe find evidence for metabolic constraints: the distributions of metabolic expansibility at the cold range boundary peak at similar values for birds (2.7) and mammals (3.2). The right skewed distributions suggest some species have adapted to elevate or evade metabolic constraints. Mammals exhibit greater skew than birds, consistent with their diverse thermoregulatory adaptations and behaviors. Mammal and bird species that are small and occupy low trophic levels exhibit high levels of MEcrb. Mammals with high MEcrbtend to hibernate or use torpor. Predicted metabolic rates at the cold range boundaries represent large energetic expenditures (>50% of maximum metabolic rates). We project species to shift their cold range boundaries poleward by an average of 3.9° latitude by 2070.Main conclusionsOur analysis suggests that metabolic constraints provide a viable mechanism for projecting cold range boundaries and range shifts in response to climate change for endotherms.
Corporate boards, monitoring and securities class actions: a pitch
Authors: Clout Victoria J. 
Published: July 2017

Purpose
The purpose of this paper is to apply Faff’s (2015) pitch template to a regulatory financial accounting research topic. The author describes her personal reflections on completing the pitch template for this project by investigating corporate boards, monitoring and securities class actions (SCAs) in Australia. The author builds on prior research in this area (Chapple et al., 2014). This study is set within prior literature examining capital markets, corporate governance, continuous disclosure regime and regulatory changes. The market reaction to corporate board changes pre- and post-SCAs is the focus of the examination within the pitch template. The pitch letter contributes to prior literature, as it demonstrates a team with established researchers using the pitch template, while prior papers have documented PhD student usage of the pitch template.

Design/methodology/approach
The author uses the Faff (2015) pitch template to focus the research team’s ideas into a concisely focused research idea. An earlier version of this pitch was presented at the Centre for International Finance and Regulation Pitching Research Symposium on 29 May 2015 in Sydney to a panel of distinguished professors and participants from market regulators including the Australian Securities and Investments Commission, Reserve Bank of Australia, Australian Prudential Regulation Authority and the financial sector including Colonial First State.

Findings
It was found that there are benefits to using the pitch template for both established and emerging researchers. Prior pitch papers have primarily been authored by PhD students. This paper’s aim was to provide evidence that established as well as emerging scholars can benefit from completing the Faff pitch template.

Originality/value
This pitch letter contributes to the research community, as it shows the process and personal reflections on undertaking the pitch exercise by a team including established and emerging researchers. Within this pitch letter there is a documentation of how the research team for the underlying project was formed and the prior experiences of the team.