bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADrosophilametainflammation-blood tumor model links aspirin-triggered eicosanoid-like mediators to immune signaling
Authors: Panettieri Silvio , Paddibhatla Indira , Chou Jennifer , Rajwani Roma , Moore Rebecca S. , Goncharuk Tamara , John George , Govind Shubha 
Published: May 2019

AbstractAccumulating data from epidemiologic studies are linking aspirin’s use to a decline in chronic and metabolic inflammation that underlies many human diseases including some cancers. Aspirin reduces cyclooxygenase-mediated pro-inflammatory prostaglandins and promotes the production of pro-resolution molecules. Aspirin also triggers the production of anti-inflammatory electrophilic mono-oxygenated lipid mediators implicated in human pathologies. With the goal of developing a model system for studying the mechanisms of aspirin in reducing inflammation, we investigated aspirin’s effects in fruit fly models of chronic inflammation. Ectopic Toll/NF-κB and JAK/STAT signaling inD. melanogasterresults in an overproliferation of hematopoietic blood progenitors coupled with metabolic inflammation in adipocytes. We report that, like mammals, flies are sensitive to aspirin treatment and it modulates the Toll-NF-κB axis. Aspirin-treated mutants simultaneously experience reduction in metabolic inflammation, mitosis, ectopic immune signaling, and macrophage infiltration. Moreover, flies synthesize 13-HODE, and aspirin triggers 13-EFOX-L2 production in mutants. In such flies with ectopic immune signaling, providing 13-HODE’s precursor linoleic acid or performing targeted knockdown of transcription factor STAT in inflammatory blood cells boosts 13-EFOX-L2 levels while decreasing metabolic inflammation. Thus, hematopoietic cells regulate metabolic inflammation in flies, and their effects can be reversed by pharmaceutical or dietary intervention, suggesting deep phylogenetic conservation in animals’ ability to resolve systemic inflammation and repair tissue damage. This model system brings the power ofDrosophilagenetics to bear on immuno-metabolic mechanisms that boost systemic health and healing, with the potential to identify new targets for the treatment of chronic diseases in humans.
Legacy Data Confounds Genomics Studies
Authors: Anderson-Trocmé Luke , Farouni Rick , Bourgey Mathieu , Kamatani Yoichiro , Higasa Koichiro , Seo Jeong-Sun , Kim Changhoon , Matsuda Fumihiko , Gravel Simon 
Published: May 2019

AbstractRecent reports have identified differences in the mutational spectra across human populations. While some of these reports have been replicated in other cohorts, most have been reported only in the 1000 Genomes Project (1kGP) data. While investigating an intriguing putative population stratification within the Japanese population, we identified a previously unreported batch effect leading to spurious mutation calls in the 1kGP data and to the apparent population stratification. Because the 1kGP data is used extensively, we find that the batch effects also lead to incorrect imputation by leading imputation servers and a small number of suspicious GWAS associations. Lower-quality data from the early phases of the 1kGP thus continues to contaminate modern studies in hidden ways. It may be time to retire or upgrade such legacy sequencing data.
Robust Microfabrication of Highly Parallelized Three-Dimensional Microfluidics on Silicon
Authors: Yadavali Sagar , Lee Daeyeon , Issadore David 
Published: May 2019

AbstractWe present a new, robust three dimensional microfabrication method for highly parallel microfluidics, to improve the throughput of on-chip material synthesis by allowing parallel and simultaneous operation of many replicate devices on a single chip. Recently, parallelized microfluidic chips fabricated in Silicon and glass have been developed to increase the throughput of microfluidic materials synthesis to an industrially relevant scale. These parallelized microfluidic chips require large arrays (> 10,000) of Through Silicon Vias (TSVs) to deliver fluid from delivery channels to the parallelized devices. Ideally, these TSVs should have a small footprint to allow a high density of features to be packed into a single chip, have channels on both sides of the wafer, and at the same time minimize debris generation and wafer warping to enable permanent bonding of the device to glass. Because of these requirements and challenges, previous approaches cannot be easily applied to produce three dimensional microfluidic chips with a large array of TSVs. To address these issues, in this paper we report a fabrication strategy for the robust fabrication of three-dimensional Silicon microfluidic chips consisting of a dense array of TSVs, designed specifically for highly parallelized microfluidics. In particular, we have developed a two-layer TSV design that allows small diameter vias (d < 20 µm) without sacrificing the mechanical stability of the chip and a patterned SiO2 etch-stop layer to replace the use of carrier wafers in Deep Reactive Ion Etching (DRIE). Our microfabrication strategy allows >50,000 (d = 15 µm) TSVs to be fabricated on a single 4” wafer, using only conventional semiconductor fabrication equipment, with 100% yield (M = 16 chips) compared to 30% using previous approaches. We demonstrated the utility of these fabrication strategies by developing a chip that incorporates 20,160 flow focusing droplet generators onto a single 4” Silicon wafer, representing a 100% increase in the total number of droplet generators than previously reported. To demonstrate the utility of this chip for generating pharmaceutical microparticle formulations, we generated 5–9 µm polycaprolactone particles with a CV <5% at a rate as high as 60 g/hr (> 1 trillion particles / hour).
DNA energy constraints shape biological evolutionary trajectories
Authors: Fariselli Piero , Taccioli Cristian , Pagani Luca , Maritan Amos 
Published: May 2019

AbstractMost living systems rely on double-stranded DNA (dsDNA) to store their genetic information and perpetrate themselves. Thus, the biological information contained within a dsDNA molecule, in terms of a linear sequence of nucleotides, has been considered the main target of the evolution. However, in this information-centred perspective, certain DNA sequence symmetries are difficult to explain. Here we show that these patterns can emerge from the physical peculiarities of the dsDNA molecule itself and the maximum entropy principle alone, rather than from biological or environmental evolutionary pressure. Our predictions are valid for both prokaryotes and eukaryotes, and also inform the interpretation of observed codon biases and context-dependent mutation patterns in human populations. Our results suggest that the double helix energy constraints and, more generally, the physical properties of the dsDNA are the hard drivers of the overall DNA sequence architecture, whereas the biological selective processes act as soft drivers, which only under extraordinary circumstances overtake the overall entropy content of the genome.
CROSSalive: a web server for predicting the in vivo structure of RNA molecules
Authors: Ponti Riccardo Delli , Armaos Alexandros , Tartaglia Gian Gaetano 
Published: May 2019

ABSTRACTHere we introduce CROSSalive, an algorithm to predict the RNA secondary structure profile (double and single stranded regions) in vivo and without sequence length limitations. Using predictions of protein interactions CROSSalive predicts the effect of N6 adenosine methylation (m6a) on RNA structure. Trained on icSHAPE data in presence (m6a+) and absence (m6a-) of methylation CROSSalive achieves an accuracy of 0.88 on the test set. The algorithm was also applied to the murine long non-coding RNA Xist (17900 nt, not present in the training) and shows a Pearson’s correlation of 0.45 with SHAPE-map data. CROSSalive webserver is freely accessible at the following page: http://service.tartaglialab.com/new_submission/crossalive
rpoB, a promising marker for analyzing the diversity of bacterial communities by amplicon sequencing
Authors: Ogier Jean-Claude , Pagès Sylvie , Galan Maxime , Barret Mathieu , Gaudriault Sophie 
Published: May 2019

AbstractBackgroundMicrobiome composition is frequently studied by the amplification and high-throughput sequencing of specific molecular markers (metabarcoding). Various hypervariable regions of the 16S rRNA gene are classically used to estimate bacterial diversity, but other universal bacterial markers with a finer taxonomic resolution could be employed. We compared specificity and sensitivity between a portion of the rpoB gene and the V3V4 hypervariable region of the 16S rRNA gene.ResultsWe first designed universal primers for rpoB suitable for use with Illumina sequencing-based technology and constructed a reference rpoB database of 45,000 sequences. The rpoB and V3V4 markers were amplified and sequenced from (i) a mock community of 19 bacterial strains from both Gram-negative and Gram-positive lineages; (ii) bacterial assemblages associated with entomopathogenic nematodes. In metabarcoding analyses of mock communities with two analytical pipelines (FROGS and DADA2), the estimated diversity captured with the rpoB marker resembled the expected composition of these mock communities more closely than that captured with V3V4. The rpoB marker had a higher level of taxonomic affiliation, a higher sensitivity (detection of all the species present in the mock communities), and a higher specificity (low rates of spurious OTU detection) than V3V4. We applied both primers to infective juveniles of the nematode Steinernema glaseri. Both markers showed the bacterial community associated with this nematode to be of low diversity (< 50 OTUs), but only rpoB reliably detected the symbiotic bacterium Xenorhabdus poinarii.ConclusionsOur results confirm that different microbiota composition data may be obtained with different markers. We found that rpoB was a highly appropriate marker for assessing the taxonomic structure of mock communities and the nematode microbiota. Further studies on other ecosystems should be considered to evaluate the universal usefulness of the rpoB marker. Our data highlight two crucial elements that should be taken into account to ensure more reliable and accurate descriptions of microbial diversity in high-throughput amplicon sequencing analyses: i) the need to include mock communities as controls; ii) the advantages of using a multigenic approach including at least one housekeeping gene (rpoB is a good candidate) and one variable region of the 16S rRNA gene.
Achieving reproducibility and accuracy in cancer mutation detection with whole-genome and whole-exome sequencing
Authors:   The Somatic Mutation Working Group of the SEQC-II Consortium
Published: May 2019

AbstractClinical applications of precision oncology require accurate tests that can distinguish tumor-specific mutations from errors introduced at each step of next generation sequencing (NGS). For NGS to successfully improve patient lives, discriminating between true mutations and artifacts is crucial.We systematically interrogated somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy. Different types of samples with varying input amount and tumor purity were processed using multiple library construction protocols. Whole-genome and whole-exome sequencing were carried out at six sequencing centers followed by processing with nine bioinformatics pipelines to evaluate their reproducibility. We identified artifacts due to sample and library processing and evaluated the capabilities and limitations of bioinformatics tools for artifact detection and removal.By examining the interaction and effect of various wet lab and computational parameters concomitantly, here we recommend actionable best practices for mutation detection in clinical applications using NGS technologies.
Extensive and diverse patterns of cell death sculpt neural networks in insects
Authors: Pop Sinziana , Chen Chin-Lin , Sproston Connor J , Kondo Shu , Ramdya Pavan , Williams Darren W 
Published: May 2019

ABSTRACTChanges to the structure and function of neural networks are thought to underlie the evolutionary adaptation of animal behaviours. Among the many developmental phenomena that generate change programmed cell death appears to play a key role. We show that cell death occurs continuously throughout insect neurogenesis and happens soon after neurons are born. Focusing on two dipterans which have lost flight during evolution we reveal that reductions in populations of flight interneurons are likely caused by increased cell death during development.Mimicking an evolutionary role for increasing cell numbers, we artificially block programmed cell death in the medial neuroblast lineage inDrosophila melanogaster, which results in the production of ‘undead’ neurons with complex arborisations and distinct neurotransmitter identities. Activation of these ‘undead’ neurons and recordings of neural activity in behaving animals demonstrate that they are functional. Our findings suggest that the evolutionary modulation of death-based patterning could generate novel network configurations.
Competing Fluid Forces Control Endothelial Sprouting in a 3-D Microfluidic Vessel Bifurcation Model
Authors: Akbari Ehsan , Spychalski Griffin B. , Rangharajan Kaushik K. , Prakash Shaurya , Song Jonathan W. 
Published: May 2019

AbstractSprouting angiogenesis, the infiltration and extension of endothelial cells from pre-existing blood vessels, helps orchestrate vascular growth and remodeling. It is now agreed that fluid forces, such as laminar shear stress due to unidirectional flow in straight vessel segments, are important regulators of angiogenesis. However, regulation of angiogenesis by the different flow dynamics that arise due to vessel branching, such as impinging flow stagnation at the base of a bifurcating vessel, are not well understood. Here we used a recently developed 3-D microfluidic model to investigate the role of the flow conditions that occur due to vessel bifurcations on endothelial sprouting. We observed that bifurcating fluid flow located at the vessel bifurcation point suppresses the formation of angiogenic sprouts. Similarly, laminar shear stress at a magnitude of ∼3 dyn/cm2 applied in the branched vessels downstream of the bifurcation point, inhibited the formation of angiogenic sprouts. In contrast, co-application of ∼1 µm/s average transvascular flow across the endothelial monolayer with bifurcating fluid flow and laminar shear stress induced the formation of angiogenic sprouts. These results suggest that transvascular flow imparts a competing effect against bifurcating fluid flow and laminar shear stress in regulating endothelial sprouting. To our knowledge, these findings are the first report on the stabilizing role of bifurcating fluid flow on endothelial sprouting. These results also demonstrate the importance of local flow dynamics due to branched vessel geometry in determining the location of sprouting angiogenesis.
Identifying Brain Region Connectivity using Steiner Minimal Tree Approximation and a Genetic Algorithm
Authors: Islam Syed , Sarwar Dewan M. 
Published: May 2019

AbstractBackgroundComputation and visualization of connectivity among the brain regions is vital for tasks such as disease identification and drug discovery. An effective visualization can aid clinicians and biologists to perform these tasks addressing a genuine research and industrial need. In this paper, we present SMT-Neurophysiology, a web-based tool in a form of an approximation to the Steiner Minimal Tree (SMT) algorithm to search neurophysiology partonomy and connectivity graph in order to find biomedically-meaningful paths that could explain, to neurologists and neuroscientists, the mechanistic relationship, for example, among specific neurophysiological examinations. We also present SMT-Genetic, a web-based tool in a form of a Genetic Algorithm (GA) to find better paths than SMT-Neurophysiology.ResultsWe introduce an approximation to the SMT algorithm to identify the most parsimonious connectivity among the brain regions of interest. We have implemented our algorithm as a highly interactive web application called SMT-Neurophysiology that enables such computation and visualization. It operates on brain region connectivity dataset curated from the Neuroscience Information Framework (NIF) for four species – human, monkey, rat and bird. We present two case studies on finding the most biomedically-meaningful solutions that identifies connections among a set of brain regions over a specific route. The case studies demonstrate that SMT-Neurophysiology is able to find connection among brain regions of interest. Furthermore, SMT-Neurophysiology is modular and generic in nature allowing the underlying connectivity graph to model any data on which the tool can operate. In order to find better connections among a set of brain regions than SMT-Neurophysiology, we have implemented a web-based tool in a form of a GA called SMT-Genetic. We present further three case studies where SMT-Genetic finds better connections among a set of brain regions than SMT-Neurophysiology. SMT-Genetic gives better connections because SMT-Genetic finds global optimum whereas SMT-Neurophysiology finds local optimum although execution time of SMT-Genetic is higher than SMT-Neurophysiology.ConclusionOur analysis would provide key insights to clinical investigators about potential mechanisms underlying a particular neurological disease. The web-based tools and the underlying data are useful to clinicians and scientists to understand neurological disease mechanisms; discover pharmacological or surgical targets; and design diagnostic or therapeutic clinical trials. The source codes and links to the live tools are available at https://github.com/dewancse/connected-brain-regions and https://github.com/dewancse/SMT-Genetic.
All of gene expression (AOE): an integrated index for public gene expression databases
Authors: Bono Hidemasa 
Published: May 2019

AbstractGene expression data have been archived as microarray and RNA-seq datasets in two public databases, Gene Expression Omnibus (GEO) and ArrayExpress (AE). In 2018, the DNA DataBank of Japan started a similar repository called the Genomic Expression Archive (GEA). These databases are useful resources for the functional interpretation of genes, but have been separately maintained and may lack RNA-seq data, while the original sequence data are available in the Sequence Read Archive (SRA).We constructed an index for those gene expression data repositories, called All Of gene Expression (AOE), to integrate publicly available gene expression data. The web interface of AOE can graphically query data in addition to the application programming interface. By collecting gene expression data from RNA-seq in the SRA, AOE also includes data not included in GEO and AE.AOE is accessible as a search tool from the GEA website and is freely available at https://aoe.dbcls.jp/.
The Australian Genetics of Depression Study: Study Description and Sample Characteristics
Authors: Byrne Enda M , Kirk Katherine M , Medland Sarah E , McGrath John J , Parker Richard , Cross Simone , Sullivan Lenore , Statham Dixie J , Levinson Douglas F , Licinio Julio , Wray Naomi R , Hickie Ian B , Martin Nicholas G 
Published: May 2019

AbstractObjectivesDepression is the most common psychiatric disorder and the largest contributor to global disability. The Australian Genetics of Depression study was established to recruit a large cohort of individuals who have been diagnosed with depression, and to investigate genetic and environmental risk factors for depression and response to commonly prescribed antidepressants. This paper describes the recruitment and characteristics of the sample.MethodsParticipants completed an online questionnaire that consisted of a compulsory module that assessed self-reported psychiatric history, clinical depression using the Composite Interview Diagnostic Interview Short Form, and experiences of using commonly prescribed antidepressants. Further voluntary modules assessed a wide range of traits of relevance to psychopathology. Participants who reported they were willing to provide a DNA sample were sent a saliva kit in the mail.ResultsA total of 20,689 participants, 75% of whom were female, enrolled in the study. The average age of participants was 43 years ± 15 years. 15,807 participants (76% of the participant group) returned saliva kits. The overwhelming majority of participants reported being given a diagnosis of depression by a medical practitioner and 88% met the criteria for a depressive episode. Rates of comorbidity with other psychiatric disorders were high. Two-thirds of the sample reported having taken more than one type of antidepressant during treatment for their depression.ConclusionsThis study was effective in recruiting a large community sample of people with a history of clinical depression, highlighting the willingness of Australians to engage with medical research. A combination of recruitment through health records and media as well as use of an online questionnaire made it feasible to recruit the large sample needed for investigating the genetics of common diseases. It will be a valuable resource for investigating risk factors for depression, treatment response to antidepressants and susceptibility to side effects.
Photoactivation of silicon rhodamines via a light-induced protonation
Authors: Frei Michelle S. , Hoess Philipp , Lampe Marko , Nijmeijer Bianca , Kueblbeck Moritz , Ellenberg Jan , Ries Jonas , Pitsch Stefan , Reymond Luc , Johnsson Kai 
Published: May 2019

AbstractWe present a new type of photoactivatable fluorophore that forms a bright silicon rhodamine derivative through a light-dependent isomerization followed by protonation. In contrast to other photoactivatable fluorophores, no caging groups are required, nor are there any undesired side-products released. Using this photoactivatable fluorophore, we created probes for HaloTag and actin for live-cell single-molecule localization microscopy and single-particle tracking experiments. The unusual mechanism of photoactivation and the fluorophore’s outstanding spectroscopic properties make it a powerful tool for live-cell super-resolution microscopy.