bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of mitochondrial DNA copy number estimation techniques
Authors: Longchamps RJ , Castellani CA , Yang SY , Newcomb CE , Sumpter JA , Lane J , Grove ML , Guallar E , Pankratz N , Taylor KD , Rotter JI , Boerwinkle E , Arking DE 
Published: April 2019

AbstractMitochondrial DNA copy number (mtDNA-CN), a measure of the number of mitochondrial genomes per cell, is a minimally invasive proxy measure for mitochondrial function and has been associated with several aging-related diseases. Although quantitative real-time PCR (qPCR) is the current gold standard method for measuring mtDNA-CN, mtDNA-CN can also be measured from genotyping microarray probe intensities and DNA sequencing read counts. To conduct a comprehensive examination on the performance of these methods, we use known mtDNA-CN correlates (age, sex, white blood cell count, Duffy locus genotype, incident cardiovascular disease) to evaluate mtDNA-CN calculated from qPCR, two microarray platforms, as well as whole genome (WGS) and whole exome sequence (WES) data across 1,085 participants from the Atherosclerosis Risk in Communities (ARIC) study and 3,489 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). We observe mtDNA-CN derived from WGS data is significantly more associated with known correlates compared to all other methods (p < 0.001). Additionally, mtDNA-CN measured from WGS is on average more significantly associated with traits by 5.6 orders of magnitude and has effect size estimates 5.8 times more extreme than the current gold standard of qPCR. We further investigated the role of DNA extraction method on mtDNA-CN estimate reproducibility and found mtDNA-CN estimated from cell lysate is significantly less variable than traditional phenol-chloroform-isoamyl alcohol (p = 5.44×10-4) and silica-based column selection (p = 2.82×10-7). In conclusion, we recommend the field moves towards more accurate methods for mtDNA-CN, as well as re-analyze trait associations as more WGS data becomes available from larger initiatives such as TOPMed.
Scale-free Vertical Tracking Microscopy: Towards Bridging Scales in Biological Oceanography
Authors: Krishnamurthy Deepak , Li Hongquan , Benoit du Rey François , Cambournac Pierre , Larson Adam , Prakash Manu 
Published: April 2019

AbstractUnderstanding key biophysical phenomena in the ocean often requires one to simultaneously focus on microscale entities, such as motile plankton and sedimenting particles, while maintaining the macroscale context of vertical transport in a highly stratified environment. This poses a conundrum: How to measure single organisms, at microscale resolution, in the lab, while allowing them to freely move hundreds of meters in the vertical direction? We present a solution in the form of a scale-free, vertical tracking microscope based on a circular “hydrodynamic-treadmill”. Our technology allows us to transcend physiological and ecological scales, tracking organisms from marine zooplankton to single-cells over vertical scales of meters while resolving microflows and behavioral processes. We demonstrate measurements of sinking particles, including marine snow as they sediment tens of meters while capturing sub-particle-scale phenomena. We also demonstrate depth-patterned virtual-reality environments for novel behavioral analyses of microscale plankton. This technique offers a new experimental paradigm in microscale ocean biophysics by combining physiological-scale imaging with free movement in an ecological-scale patterned environment.One sentence summaryScale-free vertical tracking microscopy captures, for the first time, untethered behavioral dynamics at cellular resolution for marine plankton.
VETA: a Matlab toolbox for the collection and analysis of electromyography combined with transcranial magnetic stimulation
Authors: Jackson Nicko , Greenhouse Ian 
Published: April 2019

AbstractThe combination of electromyography (EMG) and transcranial magnetic stimulation (TMS) offers a powerful non-invasive approach for investigating corticospinal excitability in both humans and animals. Acquiring and analyzing the data produced with this combination of tools requires overcoming multiple technical hurdles. Due in part to these technical hurdles, the field lacks standard routines for EMG data collection and analysis. This poses a problem for study replication and direct comparisons. Although software toolboxes already exist that perform either online EMG data visualization or offline analysis, there currently are no openly available toolboxes that flexibly perform both and also interface directly with peripheral EMG and TMS equipment. Here, we introduce Visualize EMG TMS Analyze (VETA), a MATLAB-based toolbox that supports simultaneous EMG data collection and visualization as well as automated offline processing and is specially tailored for use with motor TMS. The VETA toolbox enables the simultaneous recording of EMG, timed administration of TMS, and presentation of behavioral stimuli from a single computer. These tools also provide a streamlined analysis pipeline with interactive data visualization. Finally, VETA offers a standard EMG data format to facilitate data sharing and open science.
FIGARO: An efficient and objective tool for optimizing microbiome rRNA gene trimming parameters
Authors: Weinstein Michael M. , Prem Aishani , Jin Mingda , Tang Shuiquan , Bhasin Jeffrey M. 
Published: April 2019

ABSTRACTSummaryMicrobiome studies continue to provide tremendous insight into the importance of microorganism populations to the macroscopic world. High-throughput DNA sequencing technology (i.e., Next-generation Sequencing) has enabled the cost-effective, rapid assessment of microbial populations when combined with bioinformatic tools capable of identifying microbial taxa and calculating the diversity and composition of biological and environmental samples. Ribosomal RNA gene sequencing, where 16S and 18S rRNA gene sequences are used to identify prokaryotic and eukaryotic species, respectively, is one of the most widely-used techniques currently employed in microbiome analysis. Prior to bioinformatic analysis of these sequences, trimming parameters must be set so that post-trimming sequence information is maximized while expected errors in the sequences themselves are minimized. In this application note, we present FIGARO: a Python–based application designed to maximize read retention after trimming and filtering for quality. FIGARO was designed specifically to increase reproducibility and minimize trial-and-error in trimming parameter selection for a DADA2–based pipeline and will likely be useful for optimizing trimming parameters and minimizing sequence errors in other pipelines as well where paired-end overlap is required.Availability and implementationThe FIGARO application is freely available as source code at https://github.com/Zymo-Research/figaro.
HNF4 factors control chromatin accessibility and are redundantly required for maturation of the fetal intestine
Authors: Chen Lei , Toke Natalie H. , Luo Shirley , Vasoya Roshan P. , Aita Rohit , Parthasarathy Aditya , Tsai Yu-Hwai , Spence Jason R. , Verzi Michael P. 
Published: April 2019

ABSTRACTAs an embryo matures into a fetus, cells undergo remarkable transitions, accompanied by shifts in transcription factor regulatory networks and chromatin landscapes. The mechanisms of these developmental transitions are not completely understood. The embryonic intestine transitions from a rapidly proliferating tube with pseudostratified epithelium prior to embryonic day (E) 14.5, to an exquisitely folded columnar epithelium in the fetus. We sought to define factors that drive fetal maturation of the intestine. ATAC-seq profiling revealed a dramatic restructuring of intestinal chromatin during the embryonic-to-fetal transition, with CDX2 transcription factor motifs abundant at chromatin-accessible regions of the embryo, and hepatocyte nuclear factor 4 (HNF4) transcription factor motifs the most abundant in the fetal stages. Genetic inactivation ofHnf4αand its paralog,Hnf4γ, revealed that HNF4 factors are redundantly and vitally required for fetal maturation. In the embryo, CDX2 binds to and activatesHnf4gene loci to drive HNF4 expression at fetal stages. HNF4 and CDX2 transcription factors then occupy shared genomic regulatory sites and are required for chromatin accessibility at genes expressed in the maturing fetal intestine. Thus, intestinal transcription factor regulatory networks shift to accompany changing chromatin landscapes and gene expression profiles that occur during the transition of an embryonic tissue to its mature state.
Post-saccadic face processing is modulated by pre-saccadic preview: Evidence from fixation-related potentials
Authors: Buonocore Antimo , Dimigen Olaf , Melcher David 
Published: April 2019

AbstractHumans actively sample their environment with saccadic eye movements to bring relevant information into high-acuity foveal vision. Despite being lower in resolution, peripheral information is also available prior to each saccade. How pre-saccadic extrafoveal preview of a visual object influences its post-saccadic processing is still an unanswered question. Here, we investigated this question by simultaneously recording behavior and fixation-related brain potentials while human subjects made saccades to face stimuli. We manipulated the relationship between pre-saccadic “previews” and post-saccadic images to explicitly isolate the influences of the former. Subjects performed a gender discrimination task on a newly foveated face under three preview conditions: phase-scrambled face, incongruent face (different identity from the foveated face), and congruent face (same identity). As expected, reaction times were faster after a congruent-face preview compared to the phase-scrambled and incongruent conditions. Importantly, a face preview (either incongruent or congruent) resulted in a strong reduction of post-saccadic neural responses. Specifically, we analyzed the classic face-selective N170 component at occipito-temporal EEG electrodes, which was still present in our experiments with active looking. We found that this component was strongly attenuated for face preview conditions compared to scrambled conditions. This large and long-lasting decrease in evoked activity is consistent with an active prediction mechanism influencing category-specific neural processing at the start of a new fixation. These findings constrain theories of visual stability and show that the extrafoveal preview methodology can be a useful tool to investigate its underlying mechanisms.Significance StatementNeural correlates of object recognition have traditionally been studied by flashing stimuli to the central visual field. This procedure differs in fundamental ways from natural vision, where viewers actively sample the environment with eye movements and also obtain a low-resolution preview of soon-to-be-fixated objects. Here we show that the N170, a classic electrophysiological marker of the structural processing of faces, also occurs during a more natural viewing condition but is massively reduced due to extrafoveal preprocessing (preview benefit). Our results therefore highlight the importance of peripheral vision during trans-saccadic processing in building a coherent and stable representation of the world around us.
nf-core: Community curated bioinformatics pipelines
Authors: Ewels Philip A , Peltzer Alexander , Fillinger Sven , Alneberg Johannes , Patel Harshil , Wilm Andreas , Garcia Maxime Ulysse , Di Tommaso Paolo , Nahnsen Sven 
Published: April 2019

AbstractThe standardization, portability, and reproducibility of analysis pipelines is a renowned problem within the bioinformatics community. Most pipelines are designed for execution on-premise, and the associated software dependencies are tightly coupled with the local compute environment. This leads to poor pipeline portability and reproducibility of the ensuing results - both of which are fundamental requirements for the validation of scientific findings. Here, we introduce nf-core: a framework that provides a community-driven, peer-reviewed platform for the development of best practice analysis pipelines written in Nextflow. Key obstacles in pipeline development such as portability, reproducibility, scalability and unified parallelism are inherently addressed by all nf-core pipelines. We are also continually developing a suite of tools that assist in the creation and development of both new and existing pipelines. Our primary goal is to provide a platform for high-quality, reproducible bioinformatics pipelines that can be utilized across various institutions and research facilities.
PP1 and PP2A use opposite phospho-dependencies to control distinct processes at the kinetochore
Authors: Smith Richard J , Cordeiro Marilia H , Davey Norman E , Vallardi Giulia , Ciliberto Andrea , Gross Fridolin , Saurin Adrian T 
Published: April 2019

AbstractPP1 and PP2A-B56 are major serine/threonine phosphatase families that achieve specificity by colocalising with substrates. At the kinetochore, however, both phosphatases localise to an almost identical molecular space and yet they still manage to regulate unique pathways and processes. By switching or modulating the positions of PP1/PP2A-B56 at kinetochores, we show that their unique downstream effects are not due to either the identity of the phosphatase or its precise location. Instead, these phosphatases signal differently because their kinetochore recruitment can be either inhibited (PP1) or enhanced (PP2A) by phosphorylation inputs. Mathematical modelling explains how these inverse phospho-dependencies elicit unique forms of cross-regulation and feedback, which allows otherwise indistinguishable phosphatases to produce distinct network behaviours and control different mitotic processes. Therefore, the kinetochore uses PP1 and PP2A-B56 because their binding motifs respond to kinase inputs in opposite ways. Genome-wide motif analysis suggests that many other pathways also select for these same key features, implying that these similar catalytic enzymes may have diverged during evolution to allow opposite modes of phospho-regulation.
Intronic heterochromatin prevents cryptic transcription initiation in Arabidopsis
Authors: Zhou Jincong , Liu Liangyu , Li Qin , Xu Wei , Li Kuan , Wang Zhi-Wei , Sun Qianwen 
Published: April 2019

ABSTRACTIntronic transposable elements (TEs) comprise a large proportion in eukaryotic genomes, but how they regulate the host genes remains to be explored. Our forward genetic screen disclosed the plant specific RNA polymerases IV and V in suppressing intronic TE-mediated cryptic transcription initiation of a chimeric transcripts at FLC (FLCTE). Initiation of FLCTE transcription is blocked by the locally formed intronic heterochromatin, which is directly associated with RNA Pol V to inhibit the entry of RNA Pol II and the occupancy of H3K4 methylation. Genome-wide Pol II Ser5p native elongation transcription sequencing revealed that this is a common mechanism among intronic heterochromatin-containing genes. This study sheds light on deeply understanding the function of intronic heterochromatin on host genes expression in eukaryotic genome.
Phylo-comparative analyses reveal the dual role of drift and selection in reproductive character displacement
Authors: Sağlam İsmail K. , Miller Michael R. , O’Rourke Sean , Çağlar Selim S. 
Published: April 2019

AbstractWhen incipient species meet in secondary contact, natural selection can rapidly reduce costly reproductive interactions by directly targeting reproductive traits. This process, called reproductive character displacement (RCD), leaves a characteristic pattern of geographic variation where divergence of traits between species is greater in sympatry than allopatry. However, because other forces can also cause similar patterns, care must be given in separating pattern from process. Here we show how the phylo-comparative method together with genomic data can be used to evaluate evolutionary processes at the population level in closely related species. Using this framework, we test the role of RCD in speciation of two cricket species endemic to Anatolian mountains by quantifying patterns of character displacement, rates of evolution and adaptive divergence. Our results show differing patterns of character displacement between species for reproductive vs. non-reproductive characters and strong patterns of asymmetric divergence. We demonstrate diversification results from rapid divergence of reproductive traits towards multiple optima under the dual influence of strong drift and selection. These results present the first solid evidence for RCD in Anatolian mountains, quantify the amount of drift and selection necessary for RCD to lead to speciation, and demonstrate the utility of phylo-comparative methods for quantifying evolutionary parameters at the population level.
An unusual amino acid substitution within hummingbird cytochromecoxidase alters a key proton-conducting channel
Authors: Dunn Cory D. , Akpınar Bala Anı , Sharma Vivek 
Published: April 2019

ABSTRACTHummingbirds in flight exhibit the highest metabolic rate of all vertebrates. The bioenergetic requirements associated with sustained hovering flight raise the possibility of unique amino acid substitutions that would enhance aerobic metabolism. Here, we have identified a non-conservative substitution within the mitochondria-encoded cytochromecoxidase subunit I (COI) that is fixed within hummingbirds, but not among other vertebrates. This unusual change is also rare among metazoans, but can be identified in several clades with diverse life histories. We performed atomistic molecular dynamics simulations using bovine and hummingbird COI models, thereby bypassing experimental limitations imposed by the inability to modify mtDNA in a site-specific manner. Intriguingly, our findings suggest that COI amino acid position 153 (bovine numbering system) provides control over the hydration and activity of a key proton channel in COX. We discuss potential phenotypic outcomes linked to this alteration encoded by the hummingbird mitochondrial genome.
Environmental Assessment of Cytotoxic Drugs in the Oncology Center of Cyprus
Authors: Soteriades Elpidoforos S. , Economidou Sofia C. , Tsivitanidou Artemis , Polyviou Petros , Lorimer Amanda , Katodritis Nikos , Theophanous-Kitiri Stavroula 
Published: April 2019

AbstractBackgroundCytotoxic drugs constitute an important workplace hazard in the hospital environment. Our aim was to conduct an environmental assessment of hazardous drugs in the Oncology center of Cyprus.MethodsWipe samples were obtained from 42 workplace areas of the Oncology Center including two pairs of gloves in an initial assessment, while 10 samples were obtained at follow-up 3 years later. Potential contamination with cyclophosphamide (CP), ifosphamide (IF) and 5-fluorouracil (5-FU) and other cytotoxic medications was examined using the GC-MSMS system (CP, IF) and the HPLC system with UV detection (5-FU) method, respectively.ResultsWipe sample contamination was detected at 11.9% and 15% in the initial and follow-up assessment, respectively. Both pairs of gloves assessed were free from contamination. The results showed contamination with cyclophosphamide on the work space inside the isolator, on a day-care office phone and on the central pharmacy bench. Ifosphamide was only detected on the floor of a patient’s room. Contamination with 5-fluorouracil was found only on the surface of a prepared IV infusion bag. The levels of contamination in the positive samples ranged from 0.05 to 10.12 ng/cm2.ConclusionsThe overall percentage of sample contamination at the Oncology Center was very low compared to other centers around the world. In addition, the detected levels of contamination with cytotoxic drugs were relatively low with the exception of the workspace inside the biological safety cabinet.These results in both assessments may reflect the implementation of comprehensive control measures including employee training, technological equipment and effective cleaning procedures.
Nutritional Status and its Related Factors in Khalwa Residents, Khartoum state, Sudan
Authors: Giha Israa Hassan , Shaddad Mahasin Ibrahim , Yusuf Abdulrahman , Paga Ibrahim Abba , Noma Mounkaila , Homeida Mamoun 
Published: April 2019

AbstractIntroductionKhalwa is an Islamic educational institution, known as such in Sudan and called elsewhere Koranic institution. Our research aimed to assess the nutritional status and its related factors among Khalwa residents in Khartoum State.MethodsA facility-based cross-sectional study was implemented in two localities of Khartoum State. A multistage sampling technique was used to selected 1273 residents. At first level, four khalwa were selected in the seven localities of Khartoum State through a stratified random sampling technique. At second level, in each of the khalwa selected, all the residents fulfilling the inclusion and exclusion criteria were included in the study. The collected data were firstly summarized numerically and graphically. Then, associations/differences among variables were determined through chi-square tests and ANOVA. A multinomial logistic regression established the relationship between the nutritional status of the residents and its related factors. All statistical tests were considered statistically significant whenp< 0.05.ResultsThe age of 1273 residents varied from 6 to 60 years with an average age of 15 years. Their mean body mass index (BMI) of 16.6±3.4 ranged from 7.8 to 34.0. 73.8% (939/1272) of the residents were undernourished, 23.9% (23.9%, 309/1272) were well nourished and 2.3% (29/1272) were overweight/obese. The statistically significant factors related to the nutritional status of the residents were age (under-nourishedp=0.000; well-nourishedp=0.004), status in the khalwa (p=0.001 vsp=0.075), resting time (p=0.002 vsp=0.038), practices of hand washing (p=0.165 vsp=0.011) and exercising (p=0.032 vsp=0.027). The food practices, despite their contributions to the model, were not statistically significant (p > 0.05).DiscussionThe nutritional status of khalwa should be translated urgently in a community-directed intervention based on a partnership involving the affected communities, political and administrative authorities, national, bilateral and international donors to overcome the burden of malnutrition.
Beta-caryophyllene enhances wound healing through multiple routes
Authors: Koyama Sachiko , Purk Anna , Kaur Manpreet , Soini Helena A. , Novotny Milos V. , Davis Keith , Kao C. Cheng , Matsunami Hiroaki , Mescher Anthony 
Published: April 2019

AbstractBeta-caryophyllene is an odoriferous bicyclic sesquiterpene found in various herbs and spices. Recently, it was found that beta-caryophyllene is a ligand of the cannabinoid receptor 2 (CB2). Activation of CB2 will decrease pain, a major signal for inflammatory responses. We hypothesized that beta-caryophyllene can affect wound healing by decreasing inflammation. Here we show that cutaneous wounds of mice treated with beta-caryophyllene had enhanced re-epithelialization. The treated tissue showed increased cell proliferation and cells treated with beta-caryophyllene showed enhanced cell migration, suggesting that the higher re-epithelialization is due to enhanced cell proliferation and cell migration. The treated tissues also had up-regulated gene expression for hair follicle bulge stem cells. Olfactory receptors were not involved in the enhanced wound healing. Transient Receptor Potential channel genes were up-regulated in the injured skin exposed to beta-caryophyllene. Interestingly, there were sex differences in the impact of beta-caryophyllene as only the injured skin of female mice had enhanced re-epithelialization after exposure to beta-caryophyllene. Our study suggests that chemical compounds included in essential oils have the capability to improve wound healing, an effect generated by synergetic impacts of multiple pathways.