bluuebunny/crossref_metadata_2025 huggingface dataset:
No Evidence for Widespread Positive Selection Signatures in Common Risk Alleles Associated with Schizophrenia
Authors: Yao Yao , Yang Jia , Xie Yimin , Liao Hai , Yang Baoying , Xu Qi , Rao Shuquan
Published: April 2019

Schizophrenia poses an evolutionary-genetic paradox as it exhibits strongly negative fitness effects (early mortality and decreased fecundity), yet it persists at a prevalence of approximately 1% worldwide. Evidence from several studies have suggested that schizophrenia is evolved and maintained in part as a maladaptive byproduct of recent positive selection and adaptive evolution in human beings. However, inconsistent results have been also proposed, challenging the recent positive selection theory to explain the high population frequency of schizophrenia-associated alleles. Here, we used public domain data to locate signatures of positive selection based on genetic diversity, derived allele frequency, differentiation between populations, and long haplotypes at schizophrenia-associated single nucleotide polymorphisms (SNPs) and randomly selected SNPs (as negative controls). We found evidence for positive selection at 10 out of the 105 schizophrenia-associated SNPs, while 5 of these SNPs involved positive selection for the protective allele. Taken together, the absence of widespread positive selection signals at the schizophrenia-associated SNPs, along with the fact that half of the positive selection favored the protective allele, provide little evidence supporting the positive selection theory in schizophrenia.
Implementation of the Nagoya Protocol within the Collection of Institut Pasteur
Authors: Hurtado-Ortiz Raquel , Hébreu Alexandra , Bégaud Evelyne , Bizet-Pinson Chantal
Published: April 2019

The focus of the EU regulations on the Nagoya Protocol on Access and Benefit-Sharing leaves the control of access to genetic resources up to each member state. France has chosen to control access and is going to put in place regulations for it. All the materials received should have specific documentation regarding the accession of genetic resources, where there is a National Authority to issue them. The European commission will maintain a list of biological collections with registered status proposed by each country. The member states are responsible for considering inclusion and verification of these collections. In recent years, the Collection of Institut Pasteur (CIP) staff has expressed concern over how to interact with the implementation of the Nagoya Protocol in the collection but also at the national level with the aim that the CIP will be a registered collection. The advantage of accessing resources from a registered collection is that users of genetic resources will be considered as having exercised ‘due diligence’ if they source their genetic resources from these collections. This could facilitate the process for scientists when applying for research funding. The CIP organized the accession of new deposits and the distribution of micro-organisms in connection with it.
High-resolution 16S biogas upgrading communities: contrasting in situ and ex situ setups
Authors: FitzGerald Jamie A. , Voelklein Marcus , Claesson Marcus J , Murphy Jerry D. , Dobson Alan D.W.
Published: April 2019

As biogas from anaerobic digestion becomes an increasingly attractive biofuel, the need to improve the quality of biogas has come to the fore. Biological upgrading focuses on adding enough hydrogen to an anaerobic biogas reactor to allow methanation of the remaining carbon dioxide by methanogenic Archaea (in situ upgrading). Alternatively, biogas and hydrogen can be mixed in the absence of feedstock, in a reactor operated exclusively to facilitate methanogenesis (ex situ upgrading). This novel technology can encounter inhibition at high loading rates of hydrogen: however, in contrast to anaerobic digestion, the dynamics of this thermophilic functional microbial community are sparsely characterised. High-resolution 16S rDNA community profiles from four anaerobic biogas upgrading reactors were constructed to determine how feedstock, hydrogen, and CO2 influence biomethanation. Presence/absence of a feedstock led to large differences between in situ and ex situ communities, determining the dominant methanogen genera, and encouraging distinct populations of hydrolysing and fermenting Firmicutes. Although high hydrogen flow rates (∼37 L/day) caused a collapse in methanogenic Methanothermobacter populations in situ, ex situ hydrogen rates greatly exceeded these levels (∼400 L/day) without collapse of Methanobacterium, despite some observed instability and proliferation of likely homoacetogens. Subsequent reduction of hydrogen rates ex situ (259 L/day) appeared to create a niche for hydrogen production, indicated by increased abundance of various syntrophic fermenters known to supply biogenic hydrogen. In either upgrading setup, instability due to increased hydrogen levels manifested as a disruption of fermenting and hydrolysing populations prior to disruption of methanogens.
Identification of circular RNAs in porcine sperm and their relation to sperm motility
Authors: Gòdia Marta , Castelló Anna , Rocco Martina , Cabrera Betlem , Rodríguez-Gil Joan E. , Sánchez Armand , Clop Alex
Published: April 2019

Circular RNAs (circRNAs) are emerging as a novel class of noncoding RNAs which potential role as gene regulators is quickly gaining interest. Although circRNAs have been studied in several tissues and cell types across several animal species, the characterization of the circRNAome in ejaculated sperm remains unexplored. In this study, we profiled the sperm circRNA catalogue in 40 boar samples. A complex population of 1,598 circRNAs was shared in at least 30 samples. The predicted circRNAs presented in general low abundances and were highly tissue-specific. Circa 80% of the circRNAs identified in the boar sperm were reported as novel. We also constructed a circRNA-miRNA interaction network based on experimental and predictive microRNA (miRNA) binding sites. Moreover, we found significant correlation between the abundance of some circRNAs and sperm motility parameters and confirmed two of these correlations by RT-qPCR in 36 samples with extreme sperm quality. Our study provides a thorough characterization of a novel cell type for the circRNA encyclopedia collection and suggests that circRNAs are potential noninvasive biomarkers for male sperm quality and thus, might also hold potential to predict male fertility.
Body mass index, earnings and partnership: genetic instrumental variable analysis in two nationally representative UK samples
Authors: Hughes Amanda , Bao Yanchun , Smart Melissa , Kumari Meena
Published: April 2019

In high-income countries there is an established link between high body mass index (BMI) and low income, but the direction of this association is unclear. Recent analyses in a large UK population using genetically-instrumented BMI supported a causal influence of BMI on household income, educational attainment and job class. Since analyses were based on an age-restricted and relatively wealthy population, it is unclear whether results are generalizable, and limited income data precluded decomposition of household income effects into own-income and partnership effects. Investigation is therefore warranted in more representative UK populations where associations may differ, and where individual and partner-based mechanisms can be studied separately.

Data came from two nationally-representative samples, the UK Household Longitudinal Survey (UKHLS) and the English Longitudinal Study of Ageing (ELSA). Analysis was conducted in each sample, with results then pooled by meta-analysis. We used externally-weighted polygenic scores based on the latest genome-wide association study for BMI to examine the influence of genetically-instrumented BMI on earnings, probability of employment, job class conditional on working, likelihood of partnership, and partner’s earnings.

A one-unit (kg/m2) increase in genetically-instrumented BMI was associated with a roughly 9% decrease in own monthly earnings (pooled coefficient: 0.91, CI:0.86, 0.97) and lower probability of employment (OR: 0.89, CI:0.83, 0.96) or having a university degree (OR: 0.95, CI:0.90, 0.99). Employed individuals with higher genetically-instrumented BMI were less likely to have professional or managerial occupations (OR: 0.91, CI:0.86, 0.96). No associations were seen with partnership. A one-unit increase in BMI was associated with a 5% decrease in partners’ earnings, but estimates were imprecise (pooled coefficient: 0.95, CI:0.88,1.01).

Results are consistent with a negative influence of body mass index on a range of labour market and educational outcomes for both men and women.

Key Messages

Higher genetically-instrumented BMI was associated with lower earnings and odds of working

Also with lower odds of holding a managerial/professional occupation or a degree

No associations were seen with probability of cohabiting partnership
A 3D molecular atlas of the chick embryonic heart
Authors: Anderson Claire , Hill Bill , Lu Hui-Chun , Moverley Adam , Yang Youwen , Oliveira Nidia M.M. , Baldock Richard A. , Stern Claudio D.
Published: April 2019

We present a detailed analysis of gene expression in the 2-day (HH12) embryonic chick heart. RNA-seq of 13 micro-dissected regions reveals regionalised expression of 15,570 genes. Of these, 132 were studied byin situhybridisation and a subset (38 genes) was mapped by Optical Projection Tomography or serial sectioning to build a detailed 3-dimensional atlas of expression. We display this with a novel interactive 3-D viewer and as stacks of sections, revealing the boundaries of expression domains and regions of overlap. Analysis of the expression domains also defines some sub-regions distinct from those normally recognised by anatomical criteria at this stage of development, such as a previously undescribed subdivision of the atria into two orthogonal sets of domains (dorsoventral and left-right). We also include a detailed comparison of expression in the chick with the mouse and other species.
Methods for the generation of heritable germline mutations in the disease vector Culex quinquefasciatus using CRISPR/Cas9
Authors: Li Ming , Li Ting , Liu Nannan , Raban Robyn , Wang Xuegui , Akbari Omar S.
Published: April 2019

Culex quinquefasciatus is vector of many diseases that adversely impact human and animal health; however, compared to other mosquito vectors limited genome engineering technologies have been characterized for this vector. CRISPR-Cas9 based technologies are a powerful tool for genome engineering and functional genomics and consequently have transformed genomics studies in many organisms. Our objective was to improve upon the limited technologies available for genome editing in Cx. quinquefasciatus to create a reproducible and straightforward method for CRISPR-Cas9-targeted mutagenesis in this vector. Here we describe methods to both improve embryo survival rates as well as mutagenesis rates by optimizing injection supplies and equipment, embryo injection procedures, embryo handling and gRNA target design. Through these efforts, we achieved embryo survival rates and germline mutagenesis rates that greatly exceed any previously reported rates in this vector. This work was also the first characterize the white gene marker, which is a valuable phenotypic marker for future transgenesis or mutagenesis of this vector. In the end, these tools provide the framework for future functional genomic studies in this important disease vector and may support the development of future gene drive and genetic technologies that can be used to control this vector.
RNA-seq analysis of transcriptomes for assessing stress tolerance of S. cerevisiae strain, NCIM3186
Authors: Goud Burragoni Sravanthi , Ulaganathan Kandasamy
Published: April 2019

We have previously sequenced the draft genome of high ethanol producing S. cerevisiae strain, NCIM3186. Towards assessing the stress tolerance by this strain transcriptomes from control and in response to glucose, ethanol and furfural stress were sequenced. Comparative RNA-seq analysis of these transcriptomes identified 573 differentially expressed genes of which thiamine biosynthesis genes under furfural stress, TDH1, heat shock proteins and hexose transporter gene under ethanol stress were observed to be highly differentially expressed. Apart from thiamine biosynthesis genes and TDH1, 2 other proteins of unknown function were highly differentially expressed under glucose stress. Most importantly, TAR1 gene was highly down-regulated under all the stress conditions compared to control. Among 93 fermentome genes, 7 (TPS1, TPS2, SIN3, PTK2, SSQ1, ZAP1, DOA4) out of 9 stuck genes are found to be differentially expressed. Several stress-related genes like PHO4, SOD2, STR3, GRE2, GLR1, MEP1,3, MLH3, SNF1, MSN2, ATG1, GLC7 were differentially expressed.
Microtubules control cellular shape and coherence in amoeboid migrating cells
Authors: Kopf Aglaja , Renkawitz Jörg , Hauschild Robert , Girkontaite Irute , Tedford Kerry , Merrin Jack , Thorn-Seshold Oliver , Trauner Dirk , Häcker Hans , Fischer Klaus-Dieter , Kiermaier Eva , Sixt Michael
Published: April 2019

Cells navigating through tissues face a fundamental challenge: while multiple cellular protrusions explore different paths through the complex geometry of an interstitial matrix the cell needs to avoid becoming too long or ramified, which might ultimately lead to a loss of physical coherence. How a cell surveys its own shape to inform the actomyosin system to retract entangled or stretched protrusions is not understood. Here, we demonstrate that spatially distinct microtubule (MT) dynamics regulate amoeboid cell migration by locally specifying the retraction of explorative protrusions. In migrating dendritic cells (DCs), the microtubule organizing center (MTOC) guides the path through a three dimensional (3D) interstitium and local MT depolymerization in protrusions remote from the MTOC triggers myosin II dependent contractility via the RhoA exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: i) impaired cell edge coordination during path-finding and ii) defective adhesion-resolution. Such compromised cell shape control is particularly hindering when cells navigate through geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. Our data demonstrate that MTs control cell shape and coherence by locally controlling protrusion-retraction dynamics of the actomyosin system.
Lineage specific core-regulatory circuits determine gene essentiality in cancer cells
Authors: Rauscher Benedikt , Henkel Luisa , Heigwer Florian , Boutros Michael
Published: April 2019

Cancer cells rely on dysregulated gene expression programs to maintain their malignant phenotype. A cell’s transcriptional state is controlled by a small set of interconnected transcription factors that form its core-regulatory circuit (CRC). Previous work in pediatric cancers has shown, that disruption of the CRC by genetic alterations causes tumor cells to become highly dependent on its components creating new opportunities for therapeutic intervention. However, the role of CRCs and the mechanisms by which they are controlled remain largely unknown for most tumor types. Here, we developed a method that infers lineage dependency scores to systematically predict functional CRCs and associated biological processes from context-dependent essentiality data sets. Analysis of genome-scale CRISPR-Cas9 screens in 558 cancer cell lines showed that most tumor types specifically depend on a small number of transcription factors for proliferation. We found that these transcription factors compose the CRCs in these tumor types. Moreover, they are frequently altered in patient tumor samples indicating their oncogenic potential. Finally, we show that biological processes associated with each CRC are revealed by analyzing codependency between lineage-specific essential genes. Our results demonstrate that genetic addiction to lineage-specific core transcriptional mechanisms occurs across a broad range of tumor types. We exploit this phenomenon to systematically infer CRCs from lineage specific gene essentiality. Furthermore, our findings shed light on the selective genetic vulnerabilities that arise as the consequence of transcriptional dysregulation in different tumor types and show how the plasticity of regulatory circuits might influence drug resistance and metastatic potential.
Caenorhabditis eleganssensory neurons modulate pathogen specific responses via HLH-30/TFEB transcription factor and FSHR-1 GPCR axes of immunity
Authors: Gupta Anjali , Varma Manoj , Singh Varsha
Published: April 2019

Pattern recognition receptors allow animals to sense microbe associated molecular patterns and mount effective immune responses. It is not clear howCaenorhabditis elegansrecognizes pathogenic microbes in absence of classical pattern recognition pathways. Here, we asked if sensory neurons ofC. elegansallow it to distinguish between pathogens. Exposure ofC. elegansto a Gram positive bacteriumEnterococcus faecalisor to a Gram negative bacteriumPseudomonas aeruginosashowed predominantly pathogen-specific signatures. Using nematodes defective in sensory perception, we show that neuronal sensing is essential to mount pathogen specific immune response. OSM-6 expressing, ciliated neurons exert non-cell autonomous control of immune effector production via an OSM-6-FSHR-1 GPCR axis as well as an OSM-6-HLH-30/TFEB transcription factor axis duringE. faecalisinfection. OSM-6-FSHR-1 axis also controls immune response toP. aeruginosa. In all, this study delineates essential role of sensory perception in the regulation of pathogen-specific immunity inC. elegans.
Relationship between Dynamic Instability of Individual Microtubules and Flux of Subunits into and out of Polymer
Authors: Mauro Ava J. , Jonasson Erin M. , Goodson Holly V.
Published: April 2019

Behaviors of dynamic polymers such as microtubules and actin are frequently assessed at one or both of two scales: (i) net assembly or disassembly of bulk polymer, (ii) growth and shortening of individual filaments. Previous work has derived various forms of an equation to relate the rate of change in bulk polymer mass (i.e., flux of subunits into and out of polymer, often abbreviated as “J”) to individual filament behaviors. However, these versions of this “Jequation” differ in the variables used to quantify individual filament behavior, which correspond to different experimental approaches. For example, some variants of theJequation use dynamic instability parameters, obtained by following particular individuals for long periods of time. Another form of the equation uses measurements from many individuals followed over short time steps. We use a combination of derivations and computer simulations that mimic experiments to (i) relate the various forms of theJequation to each other; (ii) determine conditions under which theseJequation forms are and are not equivalent; and (iii) identify aspects of the measurements that can affect the accuracy of each form of theJequation. Improved understanding of theJequation and its connections to experimentally measurable quantities will contribute to efforts to build a multi-scale understanding of steady-state polymer behavior.
Rapid characterisation of hERG channel kinetics II: temperature dependence
Authors: Lei Chon Lok , Clerx Michael , Beattie Kylie A. , Melgari Dario , Hancox Jules C. , Gavaghan David J. , Polonchuk Liudmila , Wang Ken , Mirams Gary R.
Published: April 2019

Ion channel behaviour can depend strongly on temperature, with faster kinetics at physiological temperatures leading to considerable changes in currents relative to room temperature. These temperature-dependent changes in voltage-dependent ion channel kinetics (rates of opening, closing and inactivating) are commonly represented with Q10coefficients or an Eyring relationship. In this paper we assess the validity of these representations by characterising channel kinetics at multiple temperatures. We focus on the hERG channel, which is important in drug safety assessment and commonly screened at room temperature, so that results require extrapolation to physiological temperature. In Part I of this study we established a reliable method for high-throughput characterisation of hERG1a (Kv11.1) kinetics, using a 15 second information-rich optimised protocol. In this Part II, we use this protocol to study the temperature dependence of hERG kinetics using CHO cells over-expressing hERG1a on the Nanion SyncroPatch 384PE, a 384-well automated patch clamp platform, with temperature control. We characterise the temperature dependence of hERG gating by fitting the parameters of a mathematical model of hERG kinetics to data obtained at five distinct temperatures between 25 and 37 °C, and validate the models using different protocols. Our models reveal that activation is far more temperature sensitive than inactivation, and we observe that the temperature dependency of the kinetic parameters is not represented well by Q10coefficients: it broadly follows a generalised, but not the standardly-used, Eyring relationship. We also demonstrate that experimental estimations of Q10coefficients are protocol-dependent. Our results show that a direct fit using our 15 second protocol best represents hERG kinetics at any given temperature, and suggests that predictions from the Generalised Eyring theory may be preferentially used if no experimentally-derived data are available.

Statement of Significance

Ion channel currents are highly sensitive to temperature changes. Yet because many experiments are performed more easily at room temperature, it is common to extrapolate findings to physiological temperatures through the use of Q10coefficients or Eyring rate theory. By applying short, information-rich protocols that we developed in Part I of this study we identify how kinetic parameters change over temperature. We find that the commonly-used Q10and Eyring formulations are incapable of describing the parameters’ temperature dependence, a more Generalised Eyring relationship works well, but remeasuring kinetics and refitting a model is optimal. The findings have implications for the accuracy of the many applications of Q10coefficients in electrophysiology, and suggest that care is needed to avoid misleading extrapolations in their many scientific and industrial pharmaceutical applications.
Longevity Relatives Count score identifies heritable longevity carriers and suggests case improvement in genetic studies
Authors: van den Berg Niels , Rodríguez-Girondo Mar , Mandemakers Kees , Janssens Angelique A.P.O. , Beekman Marian , Slagboom P. Eline
Published: April 2019

Abstract

Longevity loci represent key mechanisms of a life-long decreased mortality and decreased/compressed morbidity. However, identifying such loci is challenging. One of the most plausible reasons is the uncertainty in defining long-lived cases with the heritable longevity trait amongst long-living phenocopies. To avoid phenocopies, family selection scores have been constructed but these have not yet been adopted as state of the art in longevity research. Here we aim to identify individuals with the heritable longevity trait by using current insights and a novel family score based on these insights. We use a unique dataset connecting living study participants to their deceased ancestors covering 37,825 persons from 1,326 five-generational families, living between 1788 and 2019. Our main finding suggests that longevity is transmitted for at least 2 subsequent generations only when at least 20% of all relatives are long-lived. This proves the importance of family data to avoid phenocopies in genetic studies.
Brown adipocyte NOSEMPE promotes nonmitochondrial thermogenesis and improves systemic metabolism through ATF4 activation
Authors: Paulo Esther , Zhang Yun , Masand Ruchi , Huynh Tony L. , Seo Youngho , Swaney Danielle L. , Soucheray Margaret , Jimenez-Morales David , Krogan Nevan J. , Wang Biao
Published: April 2019

Mitochondrial transcription factor A (Tfam)-mediated mtDNA maintenance and transcription, as well as leucine-rich PPR motif-containing protein (Lrpprc)-mediated mtRNA maturation and translation are essential steps of mtDNA-encoded electron transport chain (ETC) protein expression. ETC is essential for mitochondrial thermogenesis, the process of oxygen-dependent heat production inside the mitochondria in brown adipocytes. Here we describe that Tfam or Lrpprc deficiency in brown adipocytes cause non-synchronized ETC mRNA and protein expression (NOSEMPE) and mitochondrial ETC imbalance, ultimately abolish mitochondrial thermogenesis. However, mice with NOSEMPE in brown adipocytes are cold resistant upon an acute 4°C cold challenge, because of augmented nonmitochondrial thermogenesis driven by the “NOSEMPE→ATF4→proteome turnover” pathway. Importantly, mice with either NOSEMPE or ATF4 overexpression in brown adipocytes are protected against high-fat-diet-induced metabolic abnormalities, indicating a positive association between nonmitochondrial thermogenesis in brown adipocytes and metabolic fitness. Thus, although brown adipocytes are defined by their unique ability to produce heat through mitochondrial respiration, our study demonstrates a novel cytosolic nonmitochondrial thermogenesis in brown adipocytes. Targeting this ATF4-dependent nonmitochondrial thermogenesis in brown adipocytes may represent a new therapeutic strategy for combating metabolic disorders.
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

Mitochondrial 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

Understanding 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 summary

Scale-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

The 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

Microbiome 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 implementation

The 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

As 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

Humans 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 Statement

Neural 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

The 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

PP1 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

Intronic 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

When 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

Hummingbirds 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

Background

Cytotoxic 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.

Methods

Wipe 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.

Results

Wipe 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.

Conclusions

The 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

Introduction

Khalwa 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.

Methods

A 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.

Results

The 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).

Discussion

The 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.