bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can a population targeted by a CRISPR-based homing gene drive be rescued?
Authors: Rode Nicolas O. , Courtier-Orgogozo Virginie , Débarre Florence 
Published: March 2020

AbstractCRISPR-based homing gene drive is a genetic control technique aiming to modify or eradicate natural populations. This technique is based on the release of individuals carrying an engineered piece of DNA that can be preferentially inherited by the progeny. Developing countermeasures is important to control the spread of gene drives, should they result in unanticipated damages. One proposed countermeasure is the introduction of individuals carrying a brake construct that targets and inactivates the drive allele but leaves the wild-type allele unaffected. Here we develop models to investigate the efficiency of such brakes. We consider a variable population size and use a combination of analytical and numerical methods to determine the conditions where a brake can prevent the extinction of a population targeted by an eradication drive. We find that a brake is not guaranteed to prevent eradication and that characteristics of both the brake and the drive affect the likelihood of recovering the wild-type population. In particular, brakes that restore fitness are more efficient than brakes that do not. Our model also indicates that threshold-dependent drives (drives that can spread only when introduced above a threshold) are more amenable to control with a brake than drives that can spread from an arbitrary low introduction frequency (threshold-independent drives). Based on our results, we provide practical recommendations and discuss safety issues.Article summary for Issue HighlightsHoming gene drive is a new genetic control technology that aims to spread a genetically engineered DNA construct within natural populations even when it impairs fitness. In case of unanticipated damages, it has been proposed to stop homing gene drives by releasing individuals carrying a genedrive brake; however, the efficiency of such brakes has been little studied. The authors develop a model to investigate the dynamics of a population targeted by a homing drive in absence or in presence of brake. The model provides insights for the design of more efficient brakes and safer gene drives.
Heterotrophic Thaumarchaeota with ultrasmall genomes are widespread in the ocean
Authors: Aylward Frank O. , Santoro Alyson E. 
Published: March 2020

AbstractThe Thaumarchaeota comprise a diverse archaeal phylum including numerous lineages that play key roles in global biogeochemical cycling, particularly in the ocean. To date, all genomically-characterized marine Thaumarchaeota are reported to be chemolithoautotrophic ammonia-oxidizers. In this study, we report a group of heterotrophic marine Thaumarchaeota (HMT) with ultrasmall genome sizes that is globally abundant in deep ocean waters, apparently lacking the ability to oxidize ammonia. We assemble five HMT genomes from metagenomic data derived from both the Atlantic and Pacific Oceans, including two that are >95% complete, and show that they form a deeply-branching lineage sister to the ammonia-oxidizing archaea (AOA). Metagenomic read mapping demonstrates the presence of this group in mesopelagic samples from all major ocean basins, with abundances reaching up to 6% that of AOA. Surprisingly, the predicted sizes of complete HMT genomes are only 837-908 Kbp, and our ancestral state reconstruction indicates this lineage has undergone substantial genome reduction compared to other related archaea. The genomic repertoire of HMT indicates a highly reduced metabolism for aerobic heterotrophy that, although lacking the carbon fixation pathway typical of AOA, includes a divergent form III-a RuBisCO that potentially functions in a nucleotide scavenging pathway. Despite the small genome size of this group, we identify 13 encoded pyrroloquinoline quinone (PQQ)-dependent dehydrogenases that are predicted to shuttle reducing equivalents to the electron transport chain, suggesting these enzymes play an important role in the physiology of this group. Our results suggest that heterotrophic Thaumarchaeota are widespread in the ocean and potentially play key roles in global chemical transformations.ImportanceIt has been known for many years that marine Thaumarchaeota are abundant constituents of dark ocean microbial communities, where their ability to couple ammonia oxidation and carbon fixation plays a critical role in nutrient dynamics. In this study we describe an abundant group of heterotrophic marine Thaumarchaeota (HMT) in the ocean with physiology distinct from their ammonia-oxidizing relatives. HMT lack the ability to oxidize ammonia and fix carbon via the 3-hydroxypropionate/4-hydroxybutyrate pathway, but instead encode a form III-a RuBisCO and diverse PQQ-dependent dehydrogenases that are likely used to generate energy in the dark ocean. Our work expands the scope of known diversity of Thaumarchaeota in the ocean and provides important insight into a widespread marine lineage.
Spatial Visualization of Cluster-Specific COVID-19 Transmission Network in South Korea During the Early Epidemic Phase
Authors: Park James Yeongjun 
Published: March 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) has been rapidly spreading throughout China and other countries including South Korea. As of March 12, 2020, a total number of 7,869 cases and 66 deaths had been documented in South Korea. Although the first confirmed case in South Korea was identified on January 20, 2020, the number of confirmed cases showed a rapid growth on February 19, 2020 with a total number of 1,261 cases with 12 deaths based on the Korea Centers for Disease Control and Prevention (KCDC).MethodUsing the data of confirmed cases of COVID-19 in South Korea that are publicly available from the KCDC, this paper aims to create spatial visualizations of COVID-19 transmission between January 20, 2020 and February 19, 2020.ResultsUsing spatial visualization, this paper identified two early transmission clusters in South Korea (Daegu cluster and capital area cluster). Using a degree-weighted centrality measure, this paper proposes potential super-spreaders of the virus in the visualized clusters.ConclusionCompared to various epidemiological measures such as the basic reproduction number, spatial visualizations of the cluster-specific transmission networks and the proposed centrality measure may be more useful to characterize super-spreaders and the spread of the virus especially in the early epidemic phase.
TMAO, a seafood-derived molecule, produces diuresis and reduces mortality in heart failure rats
Authors: Gawrys-Kopczynska Marta , Konop Marek , Maksymiuk Klaudia , Kraszewska Katarzyna , Derzsi Ladislav , Sozański Krzysztof , Holyst Robert , Pilz Marta , Samborowska Emilia , Dobrowolski Leszek , Jaworska Kinga , Mogilnicka Izabella , Ufnal Marcin 
Published: March 2020

ABSTRACTBackgroundThere is an ongoing debate whether trimethylamine-oxide (TMAO), a molecule present in seafood and a derivate of microbiota metabolism, is beneficial or harmful for the circulatory system. Interestingly, deep-water animals accumulate TMAO that protects proteins such as lactate dehydrogenase (LDH) against high hydrostatic pressure. We hypothesized that TMAO may benefit the circulatory system by protecting cardiac LDH exposed to hydrostatic stress (HS) produced by contracting heart.Methods and ResultsMale, 6-week-old, Sprague-Dawley (SD, n=40) and Spontaneously-Hypertensive-Heart-Failure (SHHF n=18) rats were divided into either Water or TMAO oral treatment. After 56 weeks, half of Water and TMAO SD rats were given isoprenaline (ISO) to produce catecholamine stress. In vitro, LDH with or without TMAO was exposed to HS (changes in pressure 0-250mmHg x 280min−1) and was evaluated using fluorescence correlation spectroscopy. After 58 weeks of the treatment survival was 100% in SD-Water, SD-TMAO, ISO-TMAO and 90% in ISO-Water. In SHHF-Water survival was 66% vs 100% in SHHF-TMAO. In general, TMAO-treated rats showed higher diuresis and natriuresis. In comparison to SHHF-Water, SHHF-TMAO showed significantly lower diastolic arterial blood pressure, plasma NT-proBNP and expression of angiotensinogen and AT1 receptors in the heart. In separate experiments, intravenous TMAO but not vehicle or urea significantly increased diuresis in SD. In vitro, exposure of LDH to HS with or without TMAO did not affect the protein structure.ConclusionsTMAO reduces mortality in SHHF rats that is associated with diuretic, natriuretic and hypotensive effects. HS produced by the contracting heart is neutral for cardiac LDH structure.
Pseudomonas putidachromosomal toxin-antitoxin systems carry neither clear fitness benefits nor big costs
Authors: Rosendahl Sirli , Tamman Hedvig , Brauer Age , Remm Maido , Hõrak Rita 
Published: March 2020

AbstractChromosomal toxin-antitoxin (TA) systems are widespread genetic elements among bacteria, yet, despite extensive studies in the last decade, their biological importance remains ambivalent. The ability of TA-encoded toxins to affect stress tolerance supports the hypothesis of TA systems being associated with stress adaptation. However, the deletion of TA genes has usually no fitness consequences, supporting the selfish elements hypothesis. Here, we aimed to evaluate the cost and benefits of chromosomal TA systems toPseudomonas putida. We show that multiple TA systems do not confer fitness benefits to this bacterium as deletion of 13 TA loci does not influence stress tolerance, persistence and biofilm formation. Our results instead show that TA loci are costly and decrease the competitive fitness ofP. putida. Still, the cost of multiple TA systems is low and detectable in certain conditions only. Construction of antitoxin deletion strains showed that only five TA systems code for toxic proteins, while other TA loci have evolved towards reduced toxicity and encode non-toxic or moderately potent proteins. Analysis ofP. putidaTA systems’ homologs among fully sequencedPseudomonadssuggests that the TA loci have been subjected to purifying selection and that TA systems spread among bacteria by horizontal gene transfer.
CRISPR/Cas9-based genome editing in the silverleaf whitefly (Bemisia tabaci)
Authors: Heu Chan C. , McCullough Francine M. , Luan Junbo , Rasgon Jason L. 
Published: March 2020

AbstractBemisia tabacicryptic species Middle East-Asia Minor I (MEAM1) is a serious agricultural polyphagous insect pest, and vector of numerous plant viruses, causing major worldwide economic losses.B. tabacicontrol is limited by lack of robust gene editing tools. Gene editing is difficult inB. tabacidue to small embryos that are technically challenging to inject, and which have high mortality post-injection. We developed a CRISPR/Cas9 gene editing protocol based on injection of vitellogenic adult females rather than embryos (“ReMOT Control”). We identified an ovary-targeting peptide ligand (“BtKV”) that, when fused to Cas9 and injected into adult females, transduced the ribonucleoprotein complex to the germline, resulting in efficient, heritable editing of the offspring genome. In contrast to embryo injection, adult injection is easy and does not require specialized equipment. Development of easy-to-use gene editing protocols forB. tabaciwill allow researchers to apply the power of reverse genetic approaches to this species and will lead to novel control methods for this devastating pest insect.
Lab-on-a-graphene-FET detection of key molecular events underpinning influenza virus infection and effect of antiviral drugs
Authors: Ono T. , Kamada K. , Hayashi R. , Piacenti A. R. , Gabbutt C. , Sriwilaijaroen N. , Hiramatsu H. , Kanai Y. , Inoue K. , Nakakita S. , Kawahara T. , Ie Y. , Watanabe Y. , Suzuki Y. , Contera S. , Matsumoto K. 
Published: March 2020

AbstractSmall solid-state devices are candidates for accelerating biomedical assays/drug discovery, however their potential remains unfulfilled. Here, we demonstrate that graphene-field effect transistors (FET) can be used to successfully detect the key molecular events underlying viral infections and the effect of antiviral drugs. Our device success is achieved by bio-mimicking the host-cell surface during an influenza infection at the graphene channel. In-situ AFM confirms the biological interactions at the sialic acid-functionalized graphene: viral hemagglutinin (HA) binds to sialic acid, and neuraminidase (NA) reacts with the sialic acid-HA complex. The graphene-FET detects HA binding to sialic acid, and NA cleavage of sialic acid. The inhibitory effect of the drug “zanamivir” on NA-sialic acid interactions is monitored in real-time; the reaction rate constant of NA-sialic acid reaction was successfully determined. We demonstrate that graphene-FETs are powerful platforms for measurement of biomolecular interactions and contribute to future deployment of solid-state devices in drug discovery/biosensing.
Ancient RNA virus epidemics through the lens of recent adaptation in human genomes
Authors: Enard David , Petrov Dmitri A. 
Published: March 2020

AbstractOver the course of the last several million years of evolution, humans likely have been plagued by hundreds or perhaps thousands of epidemics. Little is known about such ancient epidemics and a deep evolutionary perspective on current pathogenic threats is lacking. The study of past epidemics has typically been limited in temporal scope to recorded history, and in physical scope to pathogens that left sufficient DNA behind, such asYersinia pestisduring the Great Plague.Host genomes however offer an indirect way to detect ancient epidemics beyond the current temporal and physical limits. Arms races with pathogens have shaped the genomes of the hosts by driving a large number of adaptations at many genes, and these signals can be used to detect and further characterize ancient epidemics.Here, we detect the genomic footprints left by ancient viral epidemics that took place in the past ~50,000 years in the 26 human populations represented in the 1,000 Genomes Project. By using the enrichment in signals of adaptation at ~4,500 host loci that interact with specific types of viruses, we provide evidence that RNA viruses have driven a particularly large number of adaptive events across diverse human populations. These results suggest that different types of viruses may have exerted different selective pressures during human evolution. Knowledge of these past selective pressures will provide a deeper evolutionary perspective on current pathogenic threats.
Single-cell transcriptomics reveals zone-specific alterations of liver sinusoidal endothelial cells in cirrhosis
Authors: Su Tingting , Yang Yilin , Lai Sanchuan , Jeong Jain , Jung Yirang , McConnell Matthew , Utsumi Teruo , Iwakiri Yasuko 
Published: March 2020

AbstractDysfunction of liver endothelial cells (ECs), particularly sinusoidal endothelial cells (LSECs), is permissive for the progression of liver fibrosis/cirrhosis and responsible for its clinical complications. Here, we have mapped the spatial distribution of heterogeneous liver ECs in normal versus cirrhotic mouse livers and identified zone-specific transcriptomic changes of LSECs associated with liver cirrhosis using single-cell RNA sequencing technology. We identified 6 clusters of liver EC populations including 3 clusters of LSECs, 2 clusters of vascular ECs and 1 cluster of lymphatic ECs. To add finer detail, we mapped the 3 clusters of LSECs to Zones 1 to 3. We found that heterogeneous liver EC identities are conserved even in liver cirrhosis and that Zone 3 LSECs are most susceptible to damage associated with liver cirrhosis, demonstrating increased capillarization and decreased ability to regulate endocytosis. Altogether, this study deepens our knowledge of the pathogenesis of liver cirrhosis at a spatial, cell-specific level, which is indispensable for the development of novel therapeutic strategies to target the most highly dysfunctional liver ECs.
Fear, Access, and the Real-Time Estimation of Etiological Parameters for Outbreaks of Novel Pathogens
Authors: Fefferman Nina H. , Lofgren Eric T. , Li Nianpeng , Blue Pieter , Weber David J. , Yakubu Abdul-Aziz 
Published: March 2020

AbstractEarly analysis of outbreaks of novel pathogens to evaluate their likely public health impact depends on fitting predictive models to data gathered and updated in real-time. Both transmission rates and the criticalR0threshold (i.e. the pathogen’s ‘reproductive number’) are inferred by finding the values that provide the best model fit to reported case incidence. These models and inferred results are then the basic tools used for public health planning: how many people expected to be infected, at what scales of time and space, and whether potential intervention strategies impact disease transmission and spread. An underlying assumption, however, is that the ability to observe new cases is either constant, or at least constant relative to diagnostic test availability.We present a demonstration, discussion, and mathematical analysis of how this assumption of predictable observability in disease incidence can drastically impact model accuracy. We also demonstrate how to tailor estimations of these parameters to a few examples of different types of shifting influences acting on detection, depending on the likely sensitivity of surveillance systems to errors from sources such as clinical testing rates and differences in healthcare-seeking behavior from the public over time. Finally, we discuss the implications of these corrections for both historical and current outbreaks.
Age profile of susceptibility, mixing, and social distancing shape the dynamics of the novel coronavirus disease 2019 outbreak in China
Authors: Zhang Juanjuan , Litvinova Maria , Liang Yuxia , Wang Yan , Wang Wei , Zhao Shanlu , Wu Qianhui , Merler Stefano , Viboud Cecile , Vespignani Alessandro , Ajelli Marco , Yu Hongjie 
Published: March 2020

AbstractStrict interventions were successful to control the novel coronavirus (COVID-19) outbreak in China. As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection and disease, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-9 fold during the COVID-19 social distancing period, with most interactions restricted to the household. Children 0-14 years were 59% (95% CI 7-82%) less susceptible than individuals 65 years and over. A transmission model calibrated against these data indicates that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they reduce peak incidence by half and delay the epidemic. These findings can help guide global intervention policies.
Chromosomal resolution reveals symbiotic virus colonization of parasitic wasp genomes
Authors: Gauthier Jérémy , Boulain Hélène , van Vugt Joke J.F.A. , Baudry Lyam , Persyn Emma , Aury Jean-Marc , Noel Benjamin , Bretaudeau Anthony , Legeai Fabrice , Warris Sven , Chebbi Mohamed Amine , Dubreuil Géraldine , Duvic Bernard , Kremer Natacha , Gayral Philippe , Musset Karine , Josse Thibaut , Bigot Diane , Bressac Christophe , Moreau Sébastien , Periquet Georges , Harry Myriam , Montagné Nicolas , Boulogne Isabelle , Sabeti-Azad Mahnaz , Maïbèche Martine , Chertemps Thomas , Hilliou Frédérique , Siaussat David , Amselem Joëlle , Luyten Isabelle , Capdevielle-Dulac Claire , Labadie Karine , Merlin Bruna Laís , Barbe Valérie , de Boer Jetske G. , Marbouty Martial , Cônsoli Fernando Luis , Dupas Stéphane , Hua Van Aurélie , Le Goff Gaëlle , Bézier Annie , Jacquin-Joly Emmanuelle , Whitfield James B. , Vet Louise E.M. , Smid Hans M. , Kaiser-Arnault Laure , Koszul Romain , Huguet Elisabeth , Herniou Elisabeth A. , Drezen Jean-Michel 
Published: March 2020

AbstractMost endogenous viruses, an important proportion of eukaryote genomes, are doomed to slowly decay. Little is known, however, on how they evolve when they confer a benefit to their host. Bracoviruses are essential for the parasitism success of parasitoid wasps, whose genomes they integrated ~103 million years ago. Here we show, from the assembly of a parasitoid wasp genome, for the first time at a chromosomal scale, that symbiotic bracovirus genes spread to and colonized all the chromosomes. Moreover, large viral clusters are stably maintained suggesting strong evolutionary constraints. Genomic comparison with another wasps revealed that this organization was already established ~53 mya. Transcriptomic analyses highlight temporal synchronization of viral gene expression, leading to particle production. Immune genes are not induced, however, indicating the virus is not perceived as foreign by the wasp. This recognition suggests that no conflicts remain between symbiotic partners when benefits to them converge.
Social interaction and network structure in groups ofDrosophilamales are shaped by prior social experience and group composition
Authors: Bentzur Assa , Ben-Shaanan Shir , Benishou Jennifer , Costi Eliezer , Ilany Amiyaal , Shohat-Ophir Galit 
Published: March 2020

SummaryLiving in a group creates a complex and dynamic environment in which the behavior of the individual is influenced by and affects the behavior of others. Although social interactions and group living are fundamental adaptations exhibited by many organisms, relatively little is known about how prior social experience, internal states and group composition shape behavior in a group, and the neuronal and molecular mechanisms that mediate it. Here we present a practical framework for studying the interplay between social experience and group interaction inDrosophila melanogasterand show that the structure of social networks and group interactions are sensitive to group composition and individuals’ social experience. We simplified the complexity of interactions in a group using a series of experiments in which we controlled the social experience and motivational states of individuals to dissect patterns that represent distinct structures and behavioral responses of groups under different social conditions. Using high-resolution data capture, machine learning and graph theory, we analyzed 60 distinct behavioral and social network features, generating a comprehensive representation (“group signature”) for each condition. We show that social enrichment promotes the formation of a distinct group structure that is characterized by high network modularity, high inter-individual and inter-group variance, high inter-individual coordination, and stable social clusters. Using environmental and genetic manipulations, we show that this structure requires visual and pheromonal cues, and that cVA sensing neurons are necessary for the expression of different aspects of social interaction in a group. Finally, we explored the formation of group behavior and structure in heterogenous groups composed of flies with distinct internal states, and discovered evidence suggesting that group structure and dynamics reflect a level of complexity that cannot be explained as a simple average of the individuals that constitute it. Our results demonstrate that fruit flies exhibit complex and dynamic social structures that are modulated by the experience and composition of different individuals within the group. This paves the path for using simple model organisms to dissect the neurobiology of behavior in complex social environments.