bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key features of pneumococcal isolates recovered in Central and Northwestern Russia in 2011–2018 determined through whole-genome sequencing
Authors: Egorova Ekaterina , Kumar Narender , Gladstone Rebecca A. , Urban Yulia , Voropaeva Elena , Chaplin A.V. , Rumiantseva Elena , Svistunova T. S. , Hawkins Paulina A. , Klugman Keith P. , Breiman Robert F. , McGee Lesley , Bentley Stephen D. , Lo Stephanie W. 
Published: September 2022

Invasive pneumococcal disease remains one of the leading causes of morbidity and mortality worldwide. In Russia, 13- valent pneumococcal conjugate vaccine (PCV13) was introduced into the childhood immunization programme nationwide in 2014. As part of the Global Pneumococcal Sequencing Project (GPS), we used genome data to characterize 179 pneumococcal isolates collected from Russia in 2011–2018 to investigate the circulating pneumococcal strains using a standardized genomic definition of pneumococcal lineages (global pneumococcal sequence clusters, GPSCs), prevalent serotypes and antimicrobial resistance profiles.
We observed high serotype and lineage diversity among the 179 isolates recovered from cerebrospinal fluid (n=77), nasopharyngeal swabs (n=99) and other non-sterile site swabs (n=3). Overall, 60 GPSCs were identified, including 48 clonal complexes (CCs) and 14 singletons, and expressed 42 serotypes (including non-typable). Among PCV13 serotypes, 19F, 6B and 23F were the top three serotypes while 11A, 15B/C and 8 were the top three among non-PCV13 serotypes in the collection. Two lineages (GPSC6 and GPSC47) expressed both PCV13 and non-PCV13 serotypes that caused invasive disease, and were penicillin- and multidrug-resistant (MDR), highlighting their potential to adapt and continue to cause infections under vaccine and antibiotic selective pressure. PCV13 serotypes comprised 92 % (11/12) of the CSF isolates from the children aged below 5 years; however, the prevalence of PCV13 serotype isolates dropped to 53 % (31/58) among the nasopharyngeal isolates. Our analysis showed that 59 % (105/179) of the isolates were predicted to be non-susceptible to at least one class of antibiotics and 26 % (46/179) were MDR. Four MDR lineages (GPSC1, GPSC6, GPSC10 and GPSC47) accounted for 65 % (30/46) of the MDR isolates and expressed PCV13 serotypes (93 %, 28/30).
This study provides evidence of high genetic and serotype diversity contributed by a mix of globally spreading and regionally circulating lineages in Russia. The observations suggest that the PCV13 vaccine could be important in reducing both invasive disease and antimicrobial resistance. We also identify potential lineages (GPSC6 and GPSC47) that may evade the vaccine.
Origins of monkeypox viruses and their strains circulating in 2022
Authors: Chen Ji-Ming , Gong Huan-Yu , Chen Rui-Xu , Sun Ming-Hui , Ji Yu-Fei , Li Guo-Hui , Tan Su-Mei , Sun Ying-Xue 
Published: September 2022

AbstractMonkeypox has spread unprecedentedly to nearly 100 countries and infected more than 51,000 people since 1 May 2022. This large-scale outbreak constituted a public health emergency of international concern (PHEIC), as declared by the World Health Organization. To better recognize and control this outbreak, we explore here through phylogenetic analysis the origins of MPXVs and their strains circulating in 2022, which remain unclear so far. Our results suggest that MPXVs possibly originated from some cowpox viruses and three lineages of MPXVs within Clade IIb circulated in 2022. Our results also suggest that two MPXVs respectively similar to the two MPXVs exported from Nigeria to the USA in 2021, ON676708/USA/2021 and ON676707/USA/2021, evolved into two lineages and sparked the large-scale outbreak in 2022, after their unknown evolutionary and epidemiological journeys possibly in Nigeria, the USA, or other countries before May 2022. This view does not stigmatize any country, because monkeypox is an endemic zoonosis in west Africa with wildlife reservoirs, and its large-scale outbreak in 2022 also resulted from the global decline of population immunity against smallpox due to the cease of vaccination against smallpox decades ago.
BRAin-wide Neuron quantification Toolkit reveals strong sexual dimorphism in the evolution of fear memory
Authors: Franceschini Alessandra , Mazzamuto Giacomo , Checcucci Curzio , Chicchi Lorenzo , Fanelli Duccio , Costantini Irene , Passani Maria Beatrice , Silva Bianca Ambrogina , Pavone Francesco Saverio , Silvestri Ludovico 
Published: September 2022

ABSTRACTFear responses are functionally adaptive behaviors that are strengthened as memories. Indeed, a detailed knowledge of the neural circuitry modulating fear and fear memory could be the turning point for the comprehension of this emotion and its pathological states.A comprehensive understading of the neural circuits mediating memory encoding, consolidation, and retrieval over time presents the fundamental technological challenge of analyzing activity in the entire brain with single-neuron resolution. In this context, we developed the BRAin-wide Neuron quantification Toolkit (BRANT) for mapping whole-brain neuronal activation at micron-scale resolution, combining tissue clearing, high-resolution light-sheet microscopy, and automated 3D image analysis. The robustness and scalability of this method allowed us to quantify the evolution of neuronal activation patterns across multiple phases of memory in mice. This approach highlighted a strong sexual dimorphism in the circuits recruited during memory recall, which had no counterpart in the behaviour. The methodology presented here paves the way for a comprehensive functional characterization of the evolution of fear memory.
Developmental rate displays effects of inheritance but not of sex in inter-population hybrids ofTigriopus californicus
Authors: Healy Timothy M. , Hargadon Alexis Cody , Burton Ronald S. 
Published: September 2022

AbstractCoevolved interactions between mitochondrial-encoded and nuclear-encoded genes within populations can be disrupted by inter-population hybridization resulting in reduced hybrid fitness. This hybrid breakdown may be an important factor contributing to reproductive isolation between populations or species, and strong selection among hybrids to maintain compatible mitonuclear genotypes occurs in at least some species. Despite potentially differential consequences of mitonuclear incompatibilities in females and males due to maternal inheritance of the mitochondrial genome, the extent to which phenotypic variation associated with hybrid breakdown is sex-specific and heritable remains unresolved. Here we present two experiments investigating variation in developmental rate among reciprocal inter-population hybrids of the intertidal copepodTigriopus californicus. Developmental rate is a proxy for fitness in this species that is substantially influenced by variation in mitonuclear compatibility among hybrids. First, we show that F2hybrid developmental rate is the same in females and males, suggesting that effects of mitonuclear incompatibilities on this trait are likely experienced equally by the two sexes. Second, we demonstrate that variation in developmental rate among F3hybrids is heritable; times to copepodid metamorphosis of F4offspring of fast-developing F3parents (12.25 ± 0.05 d, μ ± SEM) were significantly faster than those of F4offspring of slow-developing parents (14.58 ± 0.05 d). Taken together, these results provide evidence for strong effects of mitonuclear interactions across generations of hybrid eukaryotes with no differences between the sexes, and support key roles of mitonuclear incompatibility in hybrid breakdown and reproductive isolation.
Single-nuclei transcriptomics of mammalian prion diseases identifies dynamic gene signatures shared between species
Authors: Dimitriadis Athanasios , Zhang Fuquan , Murphy Thomas , Trainer Thomas , Jaunmuktane Zane , Schmidt Christian , Nazari Tamsin , Linehan Jacqueline , Brandner Sebastian , Collinge John , Mead Simon , Viré Emmanuelle 
Published: September 2022

ABSTRACTMammalian prion diseases are fatal and transmissible neurological conditions caused by the propagation of prions, self-replicating multimeric assemblies of misfolded forms of host cellular prion protein (PrP). The most common human form of the disease, sporadic Creutzfeldt-Jakob disease (sCJD), typically presents as a rapidly progressive dementia and has no effective treatments. Prion diseases are transmissible to laboratory rodents affording unprecedented opportunities to understand neurodegeneration in its evolving stages. Murine models are especially useful in prion research as they develop bona fide prion disease and recapitulate all biochemical and neuropathological hallmarks of human prion disease. Despite extensive studies investigating the changes in transcriptional profiles in prion diseases the mechanisms by which prion diseases induce cellular toxicity, including changes in gene expression profiles are yet to be fully characterized. This is at least in part because confounding effects related to brain cellular heterogeneity have not been resolved. Here, we took advantage of the recent developments in single-cell technologies and performed an unbiased whole-transcriptome single-nucleus transcriptomic analysis in prion disease.
Platelet phosphatidylserine is the critical mediator of thrombosis in heparin-induced thrombocytopenia
Authors: Zlamal Jan , Singh Anurag , Weich Karoline , Jaffal Hisham , Uzun Günalp , Althaus Karina , Bakchoul Tamam 
Published: September 2022

AbstractHeparin-induced thrombocytopenia (HIT) is a severe immune-mediated prothrombotic disorder caused by antibodies reactive to complexes of platelet factor 4 and heparin. Platelets (PLTs) and their interaction with different immune cells contribute to prothrombotic conditions in HIT. However, the exact mechanisms and the role of different PLT subpopulations to this prothrombotic enviroment remain poorly understood. In this study, we observed that HIT patient antibodies (Abs) induce relevant changes in PLT phenotype, with the key features being increased P-Selectin expression and procoagulant phosphatidylserine (PS) externalization. Formation of procoagulant PLTs was dependent on engagement of PLT Fc-gamma-RIIA by HIT Abs and resulted in significant increase of thrombin generation on the PLT surface. Using an ex vivo thrombosis model and multi-parameter assessment of thrombus formation, we observed that HIT Ab-induced procoagulant PLTs propagated formation of large PLT aggregates, leukocyte recruitment and most importantly, fibrin network generation. These prothrombotic conditions were prevented via the upregulation of PLTs intracellular cAMP with Iloprost, a clinically approved prostacyclin analogue. Additionally, the functional relevance of high P-Selectin and PS levels on procoagulant PLTs was dissected. While inhibition of P-Selectin did not affect thrombus formation, the specific blockade of PS with Lactadherin prevented HIT Ab-mediated thrombin generation and most importantly procoagulant PLT-mediated thrombus formation ex vivo. Taken together, our findings indicate that procoagulant PLTs are critical mediators of prothrombotic conditions in HIT. Upregulation of cAMP with Iloprost or PS targeting specifc therapeutics could be a promising approach to prevent thromboembolic events in HIT patients.Key points- HIT immune complexes drive procoagulant platelet formation- Phosphatidylserine blockade prevents HIT antibody-induced thrombus formation
A climate-driven compartmental model for fungal diseases in fruit orchards: The impacts of climate change on a brown rot-peach system
Authors: Bevacqua Daniele , Vanalli Chiara , Casagrandi Renato , Gatto Marino 
Published: September 2022

AbstractAs a well-known driving force of diseases in crops, climate change is likely to impact future crop yields. In the present work, we account for climate-related influences on the key parameters of a SIR-type epidemiological model for fungal diseases in stone fruit aimed at simulating different observed epidemic patterns, and, eventually, evaluating the possible impacts of climate change on the disease-induced yield loss. Brown rot disease in peach orchards is used here as a study system. We contrasted simulation results with epidemiological measures collected from an experimental orchard in Avignon (southern France) in two consecutive years, characterized by dissimilar brown rot outbreaks. The capacity of our climate-driven model to adequately reproduce the observed disease patterns suggests temperature and precipitation as key drivers of brown rot epidemics. Overall, the model predicts a potential decrease of brown rot severity under warmer and drier climatic conditions. To comprehensively understand the effect of future climate change on peach yield, alterations of crop phenology must also be accounted for. We thus build a model that considers the synergism between the two factors: vulnerability to the pathogen and varying phenology. Using plausible climate change scenarios, we find that the peach yield in the considered Mediterranean region will be considerably impaired: although brown rot-related yield losses are expected to decrease in warmer and drier climatic conditions, climate change will hinder fruit blooming and consequently the yield because milder winters will impede the achievement of dormancy. By deepening our understanding of climatic impacts on crop fungal infections, the present study may serve as a useful tool to plan and implement suitable adaptation strategies for peach cultivation.
DEGoldS: a workflow to assess the accuracy of differential expression analysis pipelines through gold-standard construction
Authors: Hurtado Mikel , Mora-Márquez Fernando , Soto Álvaro , Marino Daniel , Goicoechea Pablo G. , López de Heredia Unai 
Published: September 2022

AbstractRNA sequencing (RNA-seq) is a high throughput sequencing method that has become one the most employed tools in transcriptomics. The implementation of optimal bioinformatic analyses required in RNA-seq experiments may be complicated due to the large amounts of data generated by the sequencing platforms, along with the intrinsic nature of these data types. In the last years many programs and pipelines have been developed for differential expression (DE) analyses, but their effectiveness can be reduced when working with non-model species lacking public genomic resources. Moreover, there is not a universal recipe for all the experiments and datasets and the modification of standard RNA-seq bioinformatic pipelines through parameter tuning and the use of alternative software may have a strong impact in the outcome of DE analysis. Therefore, although the selection of the most accurate DE pipeline configuration and the evaluation of how these changes could affect the final DE results in RNA-seq experiments is mandatory to reduce bias, the lack of gold-standard datasets with known expression patterns hampers its implementation. In the present manuscript we present DEGoldS, a workflow consisting on sequential Bash and R scripts to construct gold-standards for simulation-based benchmarking of user selected pipelines for DE analysis and the computation of the accuracy of the pipelines. We validated the workflow with a case study consisting on real RNA-seq libraries of radiata pine, an important forest tree species with no publicly available reference genome. The results showed that slight pipeline modifications produced remarkable differences in the outcome of DE analysis.
A High throughput method for egg size measurement inDrosophila
Authors: Barghi Neda , Ramirez-Lanzas Claudia 
Published: September 2022

AbstractLife-history traits are used as proxies of fitness in insects includingDrosophila. Egg size is an adaptive and ecologically important trait potentially with genetic variation across different populations. However, the low throughput of manual measurement of egg size has hampered the widespread use of this trait in evolutionary biology and population genetics. We established a method for accurate and high throughput measurement ofDrosophilaegg size using large particle flow cytometry (LPFC). The size estimates using LPFC are accurate and highly correlated with the manual measurements. The measurement of egg size is high throughput (average of 214 eggs measured per minute) and viable eggs of a specific size can be sorted rapidly (average of 70 eggs per minute). Sorting by LPFC does not reduce the survival of eggs making it a suitable approach for sorting eggs for downstream analyses. This protocol can be applied to any organism within the detectable size range (10-1500 μm) of the large particle flow cytometers. We discuss the potential applications of this method and provide recommendations for optimizing the protocol for other organisms.
Sounding the alarm: sex differences in rat ultrasonic vocalizations during Pavlovian fear conditioning and extinction
Authors: Laine MA , Mitchell JR , Rhyner J , Clark R , Kannan A , Keith J , Pikus MC , Bergeron E , Ravaglia I. , Ulgenturk E , Shinde A , Shansky RM 
Published: September 2022

AbstractPavlovian fear conditioning is a prevalent tool in the study of aversive learning, which is a key component of stress-related psychiatric disorders. Adult rats can exhibit various threat-related behaviors, including freezing, motor responses and ultrasonic vocalizations (USVs). While these responses can all signal aversion, we know little about how they relate to one another. Here we characterize USVs emitted by male and female rats during cued fear acquisition and extinction and assess the relationship between different threat-related behaviors. To probe the effects of aversive stimulus intensity, we exposed the rats to mild (0.3 mA), moderate (0.5 mA) or strong (1 mA) foot shocks. We found that males consistently emitted more alarm calls than females, and male alarm calls were more closely contingent on shock intensity than were female alarm calls. Furthermore, 25 % of males and 45 % of females did not emit alarm calls. Males that made alarm calls had significantly higher levels of freezing than males who did not, while no differences in freezing were observed between female alarm callers and non-callers. Alarm call emission was also affected by the predictability of the shock; when unpaired from a tone cue, both males and females started emitting alarm calls significantly later. Some rats continued to alarm-call during extinction learning (90% of males, 30% of females) and retrieval (65% of males, 20% of females). Collectively these data suggest sex-dependence in how behavioral readouts relate to innate and conditioned threat responses. Importantly, we suggest that the same behaviors can signal sex-dependent features of aversion.Significance statementBehavioral neuroscientists can access various outputs during behavioral tests to draw conclusions about internal states of animals. While freezing is the most common index of rodents feeling threatened, these animals also emit specific ultrasonic vocalizations during aversive situations. Here we record several motor and vocal behaviors to assess how they relate to each other as threat responses, and how such relationships vary across sex. We found robust differences in how much male and female rats engaged in so-called alarm vocalizations. These vocalizations were subject to extinction in both sexes, but correlated with freezing only in males. As the field advances to include more females in preclinical research, it is crucial that we understand how similar-appearing outputs may reflect sex-biased features.
The Evolution of Dynamic and Flexible Courtship Displays That Reveal Individual Quality
Authors: Hollon Sam H. , Ruiz Irene García , Veen Thor , Fawcett Tim W. 
Published: September 2022

AbstractSexual selection is a major force shaping morphological and behavioral diversity. Existing theory focuses on courtship display traits such as morphological ornaments whose costs and benefits are assumed be to fixed across individuals’ lifetimes. In contrast, empirically observed displays are often inherently dynamic, as vividly illustrated by the acrobatic dances, loud vocalizations, and vigorous motor displays involved in courtship behavior across a broad range of taxa. One empirically observed form of display flexibility occurs when signalers adjust their courtship investment based on the number of rival signalers. The predictions of established sexual selection theory cannot readily be extended to such displays because display expression varies between courtship events, such that any given display may not reliably reflect signaler quality. Thus, we lack an understanding of how dynamic displays coevolve with sexual preferences and how signalers should tactically adjust their display investment across multiple courtship opportunities. To address these questions, we extended an established model of the coevolution of a female sexual preference and a male display trait to allow for dynamic, flexible displays. We find that a dynamic display can coevolve with a sexual preference away from their naturally selected optima, though display intensity is a weaker signal of male quality than for static ornaments. Furthermore, we find that males evolve to decrease their display investment when displaying alongside more rivals. This research represents a first step towards generalizing the findings of sexual selection theory to account for the ubiquitous dynamism of animal courtship.Significance StatementAnimal courtship displays are typically costly for survival: songs attract predators; dances are exhausting; extravagant plumage is cumbersome. Because of the trade-off between mating benefits and survival costs, displaying individuals often vary their displays across time, courting more intensely when the potential benefit is higher or the cost is lower. Despite the ubiquity of such adjustment in nature, existing theory cannot account for how this flexibility might affect the coevolution of displays with sexual preferences, nor for the patterns of tactical display adjustment that might result, because those models treat displays as static, with fixed costs and benefits. Generalizing a well-studied model of sexual selection, we find that a static display and a flexible display can evolve under similar conditions. Our model predicts that courtship should be less intense when more competitors are present.
Loss of H3.1K27me1 in Arabidopsis confers resistance to Geminivirus by sequestering DNA repair proteins onto rDNA and defense-related genes
Authors: Wang Zhen , Castillo Gonzalez Claudia M. , Zhao Changjiang , Tong Chun-Yip , Li Changhao , Liu Zhiyang , Xie Kaili , Zhu Jiaying , Wu Zhongshou , Peng Xu , Jacob Yannick , Michaels Scott D. , Jacobsen Steven E. , Zhang Xiuren 
Published: September 2022

AbstractThe H3 methyltransferases ATXR5 and ATXR6 deposit H3.1K27me1 to heterochromatin to prevent genomic instability and transposon reactivation. Here, we report that atxr5 atxr6 mutants displayed robust resistance to Geminivirus. The viral resistance correlated with activation of DNA repair pathways, but not with transposon reactivation or heterochromatin amplification. We identified RAD51 and RPA1A as partners of virus-encoded Rep protein. The two DNA repair proteins showed increased binding to heterochromatic regions and defense-related genes in atxr5 atxr6 vs wild type plants. Consequently, the proteins had reduced interactions to viral DNA in the mutant, thus hampering viral replication. Additionally, RAD51 recruitment to the host genome arose via BRCA1, HOP2 and CYCB1, and this recruitment was essential for viral resistance in atxr5 atxr6. Thus, Geminiviruses adapt to healthy plants by hijacking its DNA repairing pathways for replication, but the host could retain DNA repairing proteins via sacrificing its genome stability to suppress viral infection.