bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variation at theCyp6m2putative insecticide resistance locus inAnopheles gambiaeandAnopheles coluzzii
Authors: Wagah Martin G. , Korlević Petra , Clarkson Christopher , Miles Alistair ,   The Anopheles gambiae 1000 Genomes Consortium, Lawniczak Mara K. N. , Makunin Alex 
Published: November 2020

AbstractBackgroundThe emergence of insecticide resistance is a major threat to malaria control programmes in Africa, with many different factors contributing to insecticide resistance in its vectors,Anophelesmosquitoes.CYP6M2has previously been recognized as an important candidate in cytochrome P450-mediated detoxification inAnophelesmosquitoes. As it has been implicated in resistance against pyrethroids, organochlorines and carbamates, its broad metabolic activity makes it a potential agent in insecticide cross-resistance. Currently, allelic variation within theCyp6m2gene remains unknown.ResultsHere, we use Illumina whole-genome sequence data from Phase 2 of theAnopheles gambiae1000 Genomes Project (Ag1000G) to examine genetic variation in theCyp6m2gene across 16 populations in 13 countries comprisingAnopheles gambiaeandAnopheles coluzziimosquitoes. We find 15 missense biallelic substitutions at high frequency (defined as >5% frequency in one or more populations), that fall into five distinct haplotype groups that carry the main high frequency variants: A13T, D65A, E328Q, Y347F, I359V and A468S. We examine whether these alleles show evidence of selection either through potentially modified enzymatic function or by being linked to variants that change the transcriptional profile of the gene. Despite consistent reports ofCyp6m2upregulation and metabolic activity in insecticide resistant Anophelines, we find no evidence of directional selection occurring on these variants or on the haplotype clusters in which they are found.ConclusionOur results imply that emerging resistance associated withCyp6m2is potentially driven by distant regulatory loci such as transcriptional factors rather than by its missense variants, or that other genes are playing a more significant role in conferring metabolic resistance.
Characterization of LC-MS based urine metabolomics in healthy subjects across the life span
Authors: Liu Xiaoyan , Tian Xiaoyi , Shi Qinghong , Sun Haidan , Li Jing , Tang Xiaoyue , Guo Zhengguang , Liu Ying , Ma Jie , Ren Na , Jin Fang , He Chengyan , Song Wenqi , Sun Wei 
Published: November 2020

AbstractPrevious studies reported that gender and age could influence urine metabolomics, which should be considered in biomarker discovery. As a consequence, for the baseline of urine metabolomics characteristics, it becomes critical to avoid confounding effects in clinical cohort studies. In this study, we provided a comprehensive lifespan characterization of urine metabolomics in a cohort of 348 healthy children and 315 adults aged 1 to 70 years using liquid chromatography coupled with high resolution mass spectrometry. Our results suggested that gender-dependent urine metabolites are much greater in adults than in children. The pantothenate and CoA biosynthesis and alanine metabolism pathways were enriched in early life. Androgen and estrogen metabolism showed high activity during adolescence and youth stages. Pyrimidine metabolism was enriched in the old stage. Based on the above analysis, metabolomic characteristics of each age stage were provided. This work could help us understand the baseline of urine metabolism characteristics and contribute to further studies of clinical disease biomarker discovery.
Antisense oligonucleotide therapy forKCNT1encephalopathy
Authors: Burbano Lisseth Estefania , Li Melody , Jancovski Nikola , Jafar-Nejad Paymaan , Richards Kay , Sedo Alicia , Soriano Armand , Rollo Ben , Jia Linghan , Gazina Elena , Piltz Sandra , Adikusuma Fatwa , Thomas Paul Q. , Rigo Frank , Reid Christopher A. , Maljevic Snezana , Petrou Steven 
Published: November 2020

ABSTRACTDevelopmental and epileptic encephalopathies (DEE) are characterized by pharmacoresistant seizures with concomitant intellectual disability. Epilepsy of infancy with migrating focal seizures (EIMFS) is one of the most severe of these syndromes.De novomutations in ion channels, including gain-of-function variants inKCNT1, have been found to play a major role in the etiology of EIMFS. Here, we test a potential precision therapeutic approach inKCNT1-associated DEE using a gene silencing antisense oligonucleotide (ASO) approach. The homozygous p.P924L (L/L) mouse model recapitulates the frequent, debilitating seizures and developmental compromise that are seen in patients. After a single intracerebroventricular bolus injection of aKcnt1gapmer ASO in symptomatic mice at postnatal day 40, seizure frequency was significantly reduced, behavioral abnormalities improved, and overall survival was extended compared to mice treated with a control ASO (non-hybridizing sequence). ASO administration at neonatal age was also well-tolerated and effective in controlling seizures and extending the lifespan of treated animals. The data presented here provides a proof of concept for ASO-based gene silencing as a promising therapeutic approach inKCNT1-associated epilepsies.
Ten-year projection of white-nose syndrome disease dynamics at the southern leading-edge of infection in North America
Authors: Meierhofer Melissa B. , Lilley Thomas M. , Ruokolainen Lasse , Johnson Joseph S. , Parratt Steven , Morrison Michael L. , Pierce Brian L. , Evans Jonah W. , Anttila Jani 
Published: November 2020

AbstractPredicting the emergence and spread of infectious diseases is critical for effective conservation of biodiversity. White-nose syndrome (WNS), an emerging infectious disease of bats, has resulted in high mortality in eastern North America. Because the fungal causative agentPseudogymnoascus destructansis constrained by temperature and humidity, spread dynamics may vary greatly by geography. Environmental conditions in the southern part of the continent, where disease dynamics are typically studied, making it difficult to predict how the disease will manifest. Herein, we modeled the spread of WNS in Texas based on available cave densities and average dispersal distances of species occupying these sites, and projected these results out to 10 years. We parameterized a predictive model of WNS epidemiology and its effects on hibernatory bat populations with observed environmental data from bat hibernation sites in Texas. Our model suggests that bat populations in northern Texas will be more affected by WNS mortality than southern Texas. As such, we recommend prioritizing the preservation of large overwintering colonies of bats in north Texas through management actions. Our model further illustrates that infectious disease spread and infectious disease severity can become uncoupled over a gradient of environmental variation. Finally, our results highlight the importance of understanding host, pathogen and environmental conditions in various settings to elucidate what may happen across a breadth of environments.
Micromanipulation of amyloplasts with optical tweezers inArabidopsisstems
Authors: Abe Yoshinori , Meguriya Keisuke , Matsuzaki Takahisa , Sugiyama Teruki , Yoshikawa Hiroshi Y. , Morita Miyo Terao , Toyota Masatsugu 
Published: November 2020

AbstractIntracellular sedimentation of highly dense, starch-filled amyloplasts toward the gravity vector is likely a key initial step for gravity sensing in plants. However, recent live-cell imaging technology revealed that most amyloplasts continuously exhibit dynamic, saltatory movements in the endodermal cells ofArabidopsisstems. These complicated movements led to questions about what type of amyloplast movement triggers gravity sensing. Here we show that a confocal microscope equipped with optical tweezers can be a powerful tool to trap and manipulate amyloplasts noninvasively, while simultaneously observing cellular responses such as vacuolar dynamics in living cells. A near-infrared (λ = 1064 nm) laser that was focused into the endodermal cells at 1 mW of laser power attracted and captured amyloplasts at the laser focus. The optical force exerted on the amyloplasts was theoretically estimated to be up to 1 pN. Interestingly, endosomes and trans-Golgi networks were trapped at 30 mW but not at 1 mW, which is probably due to lower refractive indices of these organelles than that of the amyloplasts. Because amyloplasts are in close proximity to vacuolar membranes in endodermal cells, their physical interaction could be visualized in real time. The vacuolar membranes drastically stretched and deformed in response to the manipulated movements of amyloplasts by optical tweezers. Our new method provides deep insights into the biophysical properties of plant organelles in vivo and opens a new avenue for studying gravity-sensing mechanisms in plants.
GSAP Regulates Amyloid Beta Production through Modulation of Amyloid Precursor Protein Trafficking
Authors: Chang Jerry C. , Xu Peng , Wong Eitan , Flajolet Marc , Li Yue-Ming , Greengard Paul 
Published: November 2020

AbstractIn addition to participating in γ-secretase activity, presenilin 1 (PS1) regulates trafficking and subcellular localization of β-amyloid precursor protein (APP). We previously showed that gamma-secretase activating protein (GSAP) selectively modulates γ-secretase activity by inducing conformational change in PS1. However, little is known whether and how GSAP might influence APP trafficking and consequent generation of β-amyloid (Aβ) peptides. Here, to explore whether GSAP has any role in regulating APP trafficking, and to systematically investigate the intracellular trafficking routes of APP, we paired total internal reflection fluorescence microscopy, high-speed line scanning microscopy, and 4D microscopy with comprehensive imaging analysis methodologies to depict the elusive modes of APP trafficking at a single-vesicle level. Mobility and diffusivity changes reveal the existence of two kinetically distinct pathways, classified into mobile and immobile pools, for vesicular APP trafficking, suggesting high association between immobile vesicle pool and amyloidogenic processing. GSAP knockdown significantly lowers immobile pool without overturning APP vesicle diffusivity, suggesting that GSAP affects vesicular APP trafficking by retaining APP in membrane microdomains known to favor amyloidogenic processing. Our study reveals a novel role of GSAP in the regulation of Aβ-peptide formation that modulates switching of APP vesicles between immobile and mobile pools, which may help identifying new therapeutic strategies to treat Alzheimer’s disease.
A simplified workflow for the analysis of whole-genome sequencing data fromPristionchus pacificusmutant lines
Authors: Rödelsperger Christian 
Published: November 2020

AbstractNematodes are attractive model systems to understand the genetic basis of various biological processes ranging from development to complex behaviors. In particular, mutagenesis experiments combined with whole-genome sequencing has been proven as one of the most effective methods to identify core players of multiple biological pathways. To enable experimentalists to apply such integrative genetic and bioinformatic analysis in the case of the satellite model organismPristionchus pacificus, I present a simplified workflow for the analysis of whole-genome data from mutant lines and corresponding mapping panels. Individual components are based on well-maintained and widely used software packages and are extended by 50 lines of code for the analysis and visualization of allele frequencies. The effectiveness of this workflow is demonstrated by an application to recently generated data of aP. pacificusmutant line, where it reduced the number of candidate mutations from an initial set of 3,500 single nucleotide variants to ten.
Encoding multiple virtual signals in DNA barcodes with single-molecule FRET
Authors: Kim Sung Hyun , Kim Hyunwoo , Jeong Hawoong , Yoon Tae-Young 
Published: November 2020

ABSTRACTDNA barcoding provides a way to label a huge number of different biological molecules using the extreme programmability in DNA sequence synthesis. Fluorescence imaging is an easy-to-access method to detect individual DNA barcodes, which can be scaled up to a massively high-throughput format. Large overlaps between emission spectra of fluorescence dyes, however, severely limit the numbers of DNA barcodes–and thus its signal space–that can be detected in a simultaneous manner. We here demonstrate the use of single-molecule fluorescence resonance energy transfer (FRET) to encode virtual signals in DNA barcodes using conventional two-color fluorescence microscopy. By optimizing imaging and biochemistry conditions for weak hybridization events for DNA barcodes, we markedly enhanced accuracy in our determination of the efficiency by which single-molecule FRET occurred. This allowed us to unambiguously differentiate six DNA barcodes exhibiting different FRET values without involving probe sequence exchanges. Our method can be directly incorporated with previous DNA barcode techniques, and may thus be widely adopted to expand the signal space of the DNA barcode techniques.
DarkQ: Continuous genomic monitoring using message queues
Authors: Viehweger A. , Brandt C. , Hölzer M. 
Published: November 2020

AbstractMotivationNewly sequenced genomes are often not noticed by potential stakeholders because submission to public databases is delayed, and search options are limited. However, the discovery of genomes can be vital: In pathogen outbreaks, fast updates are essential to coordinate containment efforts and prevent spread.ResultsHere we introduce DarkQ, a message queue that allows for instant sharing and discovery of genomes.AvailabilityDarkQ is released under the BSD-2 license atgithub.com/phiweger/darkq.
The population genomics of transposable element activation in the highly repressive genome of an agricultural pathogen
Authors: Pereira Danilo , Oggenfuss Ursula , McDonald Bruce A. , Croll Daniel 
Published: November 2020

AbstractThe activity of transposable elements (TEs) can be an important driver of genetic diversity with TE-mediated mutations having a wide range of fitness consequences. To avoid deleterious effects of TE activity, some fungi evolved highly sophisticated genomic defences to reduce TE proliferation across the genome. Repeat-induced point (RIP) mutations is a fungal-specific TE defence mechanism efficiently targeting duplicated sequences. The rapid accumulation of RIP mutations is expected to deactivate TEs over the course of a few generations. The evolutionary dynamics of TEs at the population level in a species with highly repressive genome defences is poorly understood. Here, we analyze 366 whole-genome sequences ofParastagonospora nodorum, a fungal pathogen of wheat with efficient RIP. A global population genomics analysis revealed high levels of genetic diversity and signs of frequent sexual recombination. Contrary to expectations for a species with RIP, we identified recent TE activity in multiple populations. The TE composition and copy numbers showed little divergence among global populations regardless of the demographic history. Miniature inverted-repeat transposable elements (MITEs) and terminal repeat retrotransposons in miniature (TRIMs) were largely underlying recent intra-species TE expansions. We inferred RIP footprints in individual TE families and found that recently active, high-copy TEs have possibly evaded genomic defences. We find no evidence that recent positive selection acted on TE-mediated mutations rather that purifying selection maintained new TE insertions at low insertion frequencies in populations. Our findings highlight the complex evolutionary equilibria established by the joint action of TE activity, selection and genomic repression.Data SummaryAll Illumina sequence data is available from the NCBI SRA BioProject numbers PRJNA606320, PRJNA398070 and PRJNA476481 (https://www.ncbi.nlm.nih.gov/bioproject). The Methods and Supplementary Figures S1-S11 and Supplementary Tables S1-S4 provide all information on strain locations and outcomes of genome analyses.
Modelling Citrus Huanglongbing Spread in Scenarios involving Alternative Hosts, Vector Populations and Removal of Symptomatic Plants
Authors: Ternes Sônia , Vilamiu Raphael G. d’A. , Moreira Alécio S. , Rossi Marcelo , de C. Santos Tâmara T. , Laranjeira Francisco F. 
Published: November 2020

AbstractHuanglongbing (HLB, ex-greening) is the most devastating citrus disease around the world. We modelled HLB spread in scenarios with different populational levels of the main alternative host (Murraya paniculata) andDiaphorina citriKuwayama, vector of HLB associated bacteria; and removal of HLB-symptomatic plants. A compartmental deterministic mathematical model was built for representing the HLB dynamics in the Reconcavo Baiano, Bahia State, Brazil. The model encompasses delays on latency and incubation disease periods and on theD. citrinymphal stages. The simulations indicated that the presence of alternative hosts at low proportion would not play a crucial role in HLB dynamics in situations of poorD. citrimanagement, regardless of HLB-symptomatic plants eradication. Symptomatic citrus plants contribute more to increase the HLB-incidence than the alternative host in scenarios without a suitableD. citrimanagement.
MetamORF: A repository of unique short Open Reading Frames identified by both experimental and computational approaches for gene-level and meta-analysis
Authors: Choteau Sebastien A. , Wagner Audrey , Pierre Philippe , Spinelli Lionel , Brun Christine 
Published: November 2020

ABSTRACTThe development of high-throughput technologies revealed the existence of non-canonical short open reading frames (sORFs) on most eukaryotic RNAs. They are ubiquitous genetic elements highly conserved across species and suspected to be involved in numerous cellular processes. MetamORF (http://metamorf.hb.univ-amu.fr/) aims to provide a repository of unique sORFs identified in the human and mouse genomes with both experimental and computational approaches. By gathering publicly available sORF data, normalizing it and summarizing redundant information, we were able to identify a total of 1,162,675 unique sORFs. Despite the usual characterization of ORFs as short, upstream or downstream, there is currently no clear consensus regarding the definition of these categories. Thus, the data has been reprocessed using a normalized nomenclature. MetamORF enables new analyses at loci, gene, transcript and ORF levels, that should offer the possibility to address new questions regarding sORF functions in the future. The repository is available through an user-friendly web interface, allowing easy browsing, visualization, filtering over multiple criteria and export possibilities. sORFs could be searched starting from a gene, a transcript, an ORF ID, or looking in a genome area. The database content has also been made available through track hubs at UCSC Genome Browser.
Compensation Strategies for Bioelectric Signal Changes in Chronic Selective Nerve Cuff Recordings: A Simulation Study
Authors: Sammut Stephen , Koh Ryan G.L. , Zariffa José 
Published: November 2020

AbstractPeripheral nerve interfaces (PNIs) allow us to extract motor, sensory and autonomic information from the nervous system and use it as control signals in neuroprosthetic and neuromodulation applications. Recent efforts have aimed to improve the recording selectivity of PNIs, including by using spatiotemporal patterns from multi-contact nerve cuff electrodes as input to a convolutional neural network (CNN). Before such a methodology can be translated to humans, its performance in chronic implantation scenarios must be evaluated. In this simulation study, approaches were evaluated for maintaining selective recording performance in the presence of two chronic implantation challenges: the growth of encapsulation tissue and rotation of the nerve cuff electrode. Performance over time was examined in three conditions: training the CNN at baseline only, supervised re-training with explicitly labeled data at periodic intervals, and a semi-supervised self-learning approach. This study demonstrated that a selective recording algorithm trained at baseline will likely fail over time due to changes in signal characteristics resulting from the chronic challenges. Results further showed that periodically recalibrating the selective recording algorithm can maintain its performance over time, and that a self-learning approach has the potential to reduce the frequency of recalibration.
Protein-Protein Interactions Shape Genomic Autoimmunity in the Adaptively-Evolving Rhino-Deadlock-Cutoff (RDC) Complex
Authors: Kelleher Erin S. 
Published: November 2020

ABSTRACTThe piRNA pathway is a genomic defense system that controls the movement of transposable elements (TEs) through transcriptional and post-transcriptional silencing. While TE defense is critical to ensuring germline genome integrity, it is equally critical that the piRNA pathway avoids autoimmunity in the form of silencing host genes. Ongoing cycles of selection for expanded control of invading TEs, followed by selection for increased specificity to reduce impacts on host genes, are proposed to explain the frequent signatures of adaptive evolution among piRNA pathway proteins. However, empirical tests of this model remain limited, particularly with regards to selection against genomic autoimmunity.I examined three adaptively evolving piRNA proteins, Rhino, Deadlock and Cutoff, for evidence of interspecific divergence in autoimmunity betweenDrosophila melanogasterandD. simulans. I tested a key prediction of the autoimmunity hypothesis: that foreign heterospecific piRNA proteins will exhibit enhanced autoimmunity, due to the absence of historical selection against off-target effects. Consistent with this prediction, full-lengthD. simulansCutoff, as well as theD. simulanshinge domain of Rhino, exhibit expanded regulation ofD. melanogastergenes. I further demonstrate that this autoimmunity is dependent on known incompatibilities betweenD. simulansproteins or domains and their interacting partners inD. melanogaster. My observations reveal that the same protein-protein interaction domains that are interfaces of adaptive evolution in Rhino and Cutoff also determine their potential for autoimmunity.
Functional phenomics and genetics of the root economics space in winter wheat using high-throughput phenotyping of respiration and architecture
Authors: Guo Haichao , Ayalew Habtamu , Seethepalli Anand , Dhakal Kundan , Griffiths Marcus , Ma Xue-Feng , York Larry M. 
Published: November 2020

SummaryThe root economics space is a useful framework for plant ecology, but rarely considered for crop ecophysiology. In order to understand root trait integration in winter wheat, we combined functional phenomics with trait economic theory utilizing genetic variation, high-throughput phenotyping, and multivariate analyses.We phenotyped a diversity panel of 276 genotypes for root respiration and architectural traits using a novel high-throughput method for CO2flux and the open-source software RhizoVision Explorer for analyzing scanned images.We uncovered substantial variation for specific root respiration (SRR) and specific root length (SRL), which were primary indicators of root metabolic and construction costs. Multiple linear regression estimated that lateral root tips had the greatest SRR, and the residuals of this model were used as a new trait. SRR was negatively correlated with plant mass. Network analysis using a Gaussian graphical model identified root weight, SRL, diameter, and SRR as hub traits. Univariate and multivariate genetic analyses identified genetic regions associated with aspects of the root economics space, with underlying gene candidates.Combining functional phenomics and root economics is a promising approach to understand crop ecophysiology. We identified root traits and genomic regions that could be harnessed to breed more efficient crops for sustainable agroecosystems.