bluuebunny/crossref_metadata_2025_split huggingface dataset:
An lp17-encoded small non-coding RNA with a potential regulatory role in mammalian host adaptation by the Lyme disease spirochete
Authors: Crowley Michael A. , Bankhead Troy 
Published: November 2020

AbstractThe bacterial agent of Lyme disease,Borrelia burgdorferi,relies on an intricate gene regulatory network to transit between the disparateIxodestick vector and mammalian host environments. We recently reported that aB. burgdorferimutant lacking an intergenic region of lp17 displayed attenuated murine tissue colonization and pathogenesis due to altered antigen expression. In this study, a more detailed characterization of the putative regulatory factor encoded by the region was pursued through genetic complementation of the mutant with variants of the intergenic sequence.In ciscomplemented strains featuring mutations aimed at eliminating potential BBD07 protein translation were capable of full tissue colonization, suggesting that the region encodes an sRNA.In transcomplementation resulted in elevated transcription levels and was found to completely abolish infectivity in both immunocompetent and immunodeficient mice. Quantitative analysis of transcription of the putative sRNA by wild typeB. burgdorferishowed it to be highly induced during murine infection. Lastly, targeted deletion of this region resulted in significant changes to the transcriptome, including genes with potential roles in transmission and host adaptation. The findings reported herein strongly suggest that this lp17 intergenic region encodes for an sRNA with a critical role in the gene regulation required for adaptation and persistence of the pathogen in the mammalian host.Author SummaryLyme disease continues to emerge as a devastating infection that afflicts hundreds of thousands of people annually in the United States and abroad, highlighting the need for new approaches and targets for intervention. Successful development of these therapies relies heavily on an improved understanding of the biology of the causative agent,Borrelia burgdorferi.This is particularly true for the critical points in the life cycle of the pathogen where it must transition between ticks and mammals. Variation in the levels of bacterial gene expression is the lynchpin of this transition and is known to be driven partly by the activity of regulatory molecules known as small non-coding RNAs (sRNAs). In this work, we characterize one of these sRNAs by providing experimental evidence that the transcribed product does not code for a protein, by testing the effects of its overproduction on infectivity, and by interrogating whether its activity causes changes in expression levels of genes at the level of transcription. The findings of this study provide further evidence that regulatory sRNA activity is critical for transmission and optimal infectivity ofB. burgdorferiand contribute to the recently growing effort to attribute specific roles to these important molecules in the context of Lyme disease.
Rapid adaptation to human protein kinase R by a unique genomic rearrangement in rhesus cytomegalovirus
Authors: Child Stephanie J. , Greninger Alexander L. , Geballe Adam P. 
Published: November 2020

ABSTRACTCytomegaloviruses (CMVs) are generally unable to cross species barriers, in part because prolonged coevolution with one host species limits their ability to evade restriction factors in other species. However, the limitation in host range is incomplete. For example, rhesus CMV (RhCMV) can replicate in human cells, albeit much less efficiently than in rhesus cells. Previously we reported that the protein kinase R (PKR) antagonist encoded by RhCMV, rTRS1, has limited activity against human PKR but is nonetheless necessary and sufficient to enable RhCMV replication in human fibroblasts (HF). We now show that knockout of PKR in human cells or treatment with the eIF2B agonist ISRIB, which overcomes the translational inhibition resulting from PKR activation, augments RhCMV replication in HF, indicating that human PKR contributes to the inefficiency of RhCMV replication in HF. Serial passage of RhCMV in HF reproducibly selected for viruses with improved fitness in human cells. The evolved viruses contain an inverted duplication of the terminal 6.8 kb of the genome, including rTRS1. The duplication replaces ~11.8 kb just downstream of an internal sequence element,pac1-like, which is very similar to thepac1 cleavage and packaging signal found near the terminus of the genome. Plaque-purified evolved viruses produced at least twice as much rTRS1 as the parental RhCMV and blocked the PKR pathway more effectively in HF. Southern blots revealed that unlike the parental RhCMV, viruses with the inverted duplication isomerize in a manner similar to HCMV and other herpesviruses that have internal repeat sequences. The apparent ease with which this duplication event occurs raises the possibility that thepac1-like site, which is conserved in Old World monkey CMV genomes, may serve a function in facilitating rapid adaptation to evolutionary obstacles.AUTHOR SUMMARYRhesus macaque CMV (RhCMV) is an important model for human CMV (HCMV) pathogenesis and vaccine development. Therefore, it is important to understand the similarities and differences in infectivity and interaction of these viruses with their host species. In contrast to the strict species-specificity of HCMV, RhCMV is able to cross species barriers to replicate in human cells. We know from past work that a component of this broader host range is RhCMV’s ability to counteract both the rhesus and human versions of a key antiviral factor. Here we delve further into the mechanisms by which RhCMV can adapt to counteract human cellular defenses. We find that RhCMV appears to be poised to undergo a specific genomic rearrangement that facilitates increased replication efficiency in human cells. Besides providing insights into CMV species-specificity and host barriers to cross-species transmission, this work also provides more generalized clues about viral adaptative mechanisms.
Interspecies variation of larval locomotion kinematics in the genusDrosophilaand its relation to habitat temperature
Authors: Matsuo Yuji , Nose Akinao , Kohsaka Hiroshi 
Published: November 2020

AbstractSpeed and trajectory of locomotion are characteristic traits of individual species. During evolution, locomotion kinematics is likely to have been tuned for survival in the habitats of each species. Although kinematics of locomotion is thought to be influenced by habitats, the quantitative relation between the kinematics and environmental factors has not been fully revealed. Here, we performed comparative analyses of larval locomotion in 11Drosophilaspecies. We found that larval locomotion kinematics are divergent among the species. The diversity is not correlated to the body length but is correlated instead to the habitat temperature of the species. Phylogenetic analyses using Bayesian inference suggest that the evolutionary rate of the kinematics is diverse among phylogenetic trees. The results of this study imply that the kinematics of larval locomotion has diverged in the evolutionary history of the genusDrosophilaand evolved under the effects of the ambient temperature of habitats.
The host exocyst complex is targeted by a conserved bacterial type III effector protein that promotes virulence
Authors: Michalopoulou Vassiliki A. , Kotsaridis Konstantinos , Mermigka Glykeria , Kotsifaki Dina , Kokkinidis Michael , Celie Patrick H. N. , Jones Jonathan D.G. , Sarris Panagiotis F. 
Published: November 2020

ABSTRACTFor most Gram-negative bacteria, pathogenicity largely depends on the type-III secretion system that delivers virulence effectors into eukaryotic cells. The subcellular targets for the majority of these effectors remain unknown. Here, we show thatXanthomonas campestris, the causal agent of black rot disease, delivers the highly conserved effector XopP that interacts with host’s EXO70 protein. EXO70 is an essential component of the exocyst complex with a role in plant immunity. The XopP/EXO70 interaction is specific and inhibits exocyst-dependent exocytosis without activating a specific plant NLR receptor that guards EXO70. In this way,Xanthomonasefficiently inhibits the host’s PAMP-triggered immunity (PTI) by blocking exocytosis of PR1, callose deposition and the FLS2 immunity-receptor translocation to the plasma membrane, promoting successful infection.
Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination
Authors: Tsai Shang Jui , Guo Chenxu , Sedgwick Alanna , Kanagavelu Saravana , Nice Justin , Shetty Sanjana , Landaverde Connie , Atai Nadia A. , Gould Stephen J. 
Published: November 2020

AbstractExpression-dependent, Spike-only vaccines have been developed, deployed, and shown to be effective in the fight against SARS-CoV-2. However, additional approaches to vaccine development may be needed to meet existing and future challenges posed by emerging Spike variant strains, as well as a likely need for different antigen-delivery systems that are safe and effective for regular, periodic re-administration. We report here the development of mRNA-loaded exosomes, demonstrate that they can mediate the functional expression of heterologous proteinsin vitroandin vivo, and have fewer adverse effects than comparable doses of lipid nanoparticles. Furthermore, we applied this approach to the development of an exosome-based, multiplexed mRNA vaccine that drives expression of immunogenic SARS-CoV-2 Nucleocapsid and Spike proteins. This vaccine elicited long-lasting cellular and humoral responses to Nucleocapsid and to Spike, demonstrating that exosome-based mRNA formulations represent a previously unexplored platform in the fight against COVID-19 and other infectious diseases.
Immunoregulatory effects of Imuno TF®(transfer factors) on Th1/Th2/Th17/Treg cytokines
Authors: Oliveira Carlos Rocha , Vieira Rodolfo Paula , de Oliveira Ferreira Anderson , de Souza Schmidt Gonçalves Any Elisa , Polonini Hudson 
Published: November 2020

AbstractTransfer factors are known since 1955 due to their activities on the immune system. Although the reports on the effects on diverse immune mechanisms, their role on Th1, Th2, Th17 and Treg responses was still not described. In this sense, the present work focused on the evaluation of such immune responses. For that, human lymphocytes, and mice thymic, splenic and Peyer’s cells were stimulated with Lipopolysaccharides and Concanavalin A, and then treated with isolated transfer factors (Imuno TF®). The culture medium was harvested and the quantification of Th1 cytokines (IL-2 and IFN-γ), Th2 cytokines (IL-4, IL-5, and IL-13), Th17 cytokine (IL- 17), Treg cytokine (IL-35), inflammatory cytokines (IL-6 and TNF-α), and anti-inflammatory cytokine (IL-10) was performed, as well as the quantification of mRNA levels. Imuno TF®positively regulated Th1 cytokines, while decreased Th2 cytokines. It also increased levels of mRNA and secretion of the anti-inflammatory cytokine IL-10, whereas it reduced levels of mRNA and the secretion of pro-inflammatory cytokines IL-6 and TNF-α. Finally, it reversed the hypersecretion of IL-17 and did not promote significant changes in IL-35 secretion. This highlights the role of Imuno TF®in the regulation of the immune responses.
The impact ofStaphylococcus aureuscell wall glycosylation on langerin recognition and Langerhans cell activation
Authors: Hendriks A , van Dalen R , Ali S , Gerlach D , van der Marel GA , Fuchsberger FF , Aerts P , de Haas CJC , Peschel A , Rademacher C , van Strijp JAG , Codée JDC , van Sorge NM 
Published: November 2020

AbstractStaphylococcus aureusis the leading cause of skin and soft tissue infections. It remains incompletely understood how skin-resident immune cells respond toS. aureusinvasion and contribute to an effective immune response. Langerhans cells (LCs), the only professional antigen-presenting cell type in the epidermis, senseS. aureusthrough their pattern-recognition receptor langerin, triggering a pro-inflammatory response. Langerin specifically recognizes the β-1,4-linkedN-acetylglucosamine (β-GlcNAc) modification, which requires the glycosyltransferase TarS, on the cell wall glycopolymer Wall Teichoic Acid (WTA). Recently, an alternative WTA glycosyltransferase, TarP, was identified in methicillin-resistantS. aureusstrains belonging to clonal complexes (CC) 5 and CC398. TarP also modifies WTA with β-GlcNAc but at the C-3 position of the WTA ribitol phosphate (RboP) subunit. Here, we aimed to unravel the impact of β-GlcNAc linkage position for langerin binding and LC activation. In addition, we performed structure-binding studies using a small panel of unique chemically-synthesized WTA molecules to assess langerin-WTA binding requirements. Using FITC-labeled recombinant human langerin and genetically-modifiedS. aureusstrains, we observed that langerin similarly recognized bacteria that produce either TarS- or TarP-modified WTA. Furthermore, using chemically-synthesized WTA, representative of the differentS. aureusWTA glycosylation patterns, established that β-GlcNAc is sufficient to confer langerin binding. Functionally,tarP-expressingS. aureusinduce increased cytokine production and maturation ofin vitro-generated LCs compared totarSexpressingS. aureus. Overall, our data suggest that LCs are able to sense all β-GlcNAc-WTA producingS. aureusstrains, likely performing an important role as first responders uponS. aureusskin invasion.
Persistence of SARS-CoV-2 specific B- and T-cell responses in convalescent COVID-19 patients 6-8 months after the infection
Authors: Sherina Natalia , Piralla Antonio , Du Likun , Wan Hui , Kumagai-Braesh Makiko , Andréll Juni , Braesch-Andersen Sten , Cassaniti Irene , Percivalle Elena , Sarasini Antonella , Bergami Federica , Di Martino Raffaella , Colaneri Marta , Vecchia Marco , Sambo Margherita , Zuccaro Valentina , Bruno Raffaele , Oggionni Tiberio , Meloni Federica , Abolhassani Hassan , Bertoglio Federico , Schubert Maren , Byrne-Steele Miranda , Han Jian , Hust Michael , Xue Yintong , Hammarström Lennart , Baldanti Fausto , Marcotte Harold , Pan-Hammarström Qiang 
Published: November 2020

SummaryBackgroundThe longevity of the immune response against SARS-CoV-2 is currently debated. We thus profiled the serum anti-SARS-CoV-2 antibody levels and virus specific memory B- and T-cell responses over time in convalescent COVID-19 patients.MethodsA cohort of COVID-19 patients from the Lombardy region in Italy who experienced mild to critical disease and Swedish volunteers with mild symptoms, were tested for the presence of elevated anti-spike and anti-receptor binding domain antibody levels over a period of eight months. In addition, specific memory B- and T-cell responses were tested in selected patient samples.ResultsAnti-SARS-CoV-2 antibodies were present in 85% samples collected within 4 weeks after onset of symptoms in COVID-19 patients. Levels of specific IgM or IgA antibodies declined after 1 month while levels of specific IgG antibodies remained stable up to 6 months after diagnosis. Anti-SARS-CoV-2 IgG antibodies were still present, though at a significantly lower level, in 80% samples collected at 6-8 months after symptom onset. SARS-CoV-2-specific memory B- and T-cell responses were developed in vast majority of the patients tested, regardless of disease severity, and remained detectable up to 6-8 months after infection.ConclusionsAlthough the serum levels of anti-SARS-CoV-2 IgG antibodies started to decline, virus-specific T and/or memory B cell responses increased with time and maintained during the study period (6-8 months after infection).FundingEuropean Union’s Horizon 2020 research and innovation programme (ATAC), the Italian Ministry of Health, CIMED, the Swedish Research Council and the China Scholarship Council.
Resuscitation of soil microbiota after > 70-years of desiccation
Authors: Zhao Jun , Chen Dongfeng , Gao Wei , Guo Zhiying , Jia Zhongjun , Hernández Marcela 
Published: November 2020

AbstractThe abundance and diversity of bacteria in 24 historical soil samples under air-dried storage conditions for more than 70 years were assessed by quantification and high-throughput sequencing analysis of 16S rRNA genes. All soils contained a measurable abundance of bacteria varying from 103to 108per gram of soil and contrasting community compositions were observed in different background soils, suggesting that the bacteria detected were indigenous to the soil. Following a 4-week soil rewetting event, the bacterial abundance significantly increased in soils, indicating strong adaptation of soil bacteria to extreme osmotic change and high resuscitation potential of some bacteria over long periods of desiccation.Paenibacillus, Cohnellaand two unclassifiedBacillalesgenera within the phylumFirmicutesrepresented the most ubiquitously active taxa, which showed growth in the highest number of soils (≥12 soils), while generaTumebacillus, AlicyclobacillusandBrevibacillusin the phylumFirmicutesdisplayed the highest growth rates in soils (with >1000-fold average increase) following rewetting. Additionally, someActinobacteriaandProteobacteriagenera showed relatively high activity following rewetting, suggesting that the resilience to long-term desiccation and rewetting is a common trait across phylogenetically divergent microbes. The present study thus demonstrated that diversified groups of microbes are present and potentially active in historically desiccated soils, which might be of importance in the context of microbial ecology.
Cryo-EM structure of the mature and infective Mayaro virus at 4.4 Å resolution reveals new features of arthritogenic alphaviruses
Authors: Filho Helder Ribeiro , Coimbra Lais D. , Cassago Alexandre , Rocha Rebeca P. F. , Padilha Antonio Cláudio , da Silva Guerra João Victor , Leme Luiza , Trivella Daniela B. B. , Portugal Rodrigo V. , Lopes-de-Oliveira Paulo Sérgio , Marques Rafael Elias 
Published: November 2020

ABSTRACTMayaro virus (MAYV) is an emerging arbovirus of the Americas that may cause a debilitating arthritogenic disease. The biology of MAYV is not fully understood and largely inferred from related arthritogenic alphaviruses. Here we present the structure of MAYV at 4.4 Å resolution, obtained from a preparation of mature, infective virions. MAYV presents typical alphavirus features and organization. Interactions between viral proteins that lead to particle formation are described together with a hydrophobic pocket formed between E1 and E2 spike proteins and conformational epitopes specific of MAYV. We also describe MAYV glycosylation residues in E1 and E2 that may affect MXRA8 host receptor binding, and a molecular “handshake” between MAYV spikes formed by N262 glycosylation in adjacent E2 proteins. The structure of MAYV is suggestive of structural and functional complexity among alphaviruses, which may be targeted for specificity or antiviral activity.
In-The-Wild Interference Characterization and Modelling for Electro-Quasistatic-HBC with Miniaturized Wearables
Authors: Mehrotra Parikha , Yang David , Weigand Scott , Sen Shreyas 
Published: November 2020

AbstractThe emergence of Human Body Communication (HBC) as an alternative to wireless body area networks (WBAN) has led to the development of small sized, energy efficient and more secure wearable and implantable devices forming a network in and around the body. Previous studies claim that though HBC is comparatively more secure than WBAN, nevertheless, the electromagnetic (EM) radiative nature of HBC in >10MHz region makes the information susceptible to eavesdropping. Furthermore, interferences may be picked up by the body due to the human body antenna effect in the 40-400MHz range. Alternatively, electro-quasistatic (EQS) mode of HBC forms an attractive way for covert data transmission in the sub 10MHz region by allowing the signal to be contained within the body. However, there is a gap in the knowledge about the mechanism and sources of interference in this region (crucial in allowing for proper choice of data transmission band). In this paper, the interference coupling modality in the EQS region is explained along with its possible sources. Interferences seen by the wearable in the actual scenario is a non-trivial problem and a suitable measurement EQS HBC setup is designed to recreate it by employing a wearable sized measurement setup having a small ground plane. For the first time, a human biophysical interference pickup model is proposed and interference measurement results using a wearable device are presented up to 250kHz in different environmental settings.
Darwinian dynamics over recurrent neural computations for combinatorial problem solving
Authors: Czégel Dániel , Giaffar Hamza , Csillag Márton , Futó Bálint , Szathmáry Eörs 
Published: November 2020

AbstractEfficient search in enormous combinatorial spaces is an essential component of intelligence. Humans, for instance, are often found searching for optimal action sequences, linguistic structures and causal explanations. Is there any computational domain that provides good-enough and fast-enough solutions to such a diverse set of problems, yet can be robustly implemented over neural substrates? Based on previous accounts, we propose that a Darwinian process, operating over sequential cycles of imperfect copying and selection of informational patterns, is a promising candidate. It is, in effect, a stochastic parallel search that i) does not need local gradient-like information and ii) redistributes its computational resources from globally bad to globally good solution candidates automatically. Here we demonstrate these concepts in a proof-of-principle model based on dynamical output states of reservoir computers as units of evolution. We show that a population of reservoir computing units, arranged in one or two-dimensional topologies, is capable of maintaining and continually improving upon existing solutions over rugged combinatorial reward landscapes. We also provide a detailed analysis of how neural quantities, such as noise and topology, translate to evolutionary ones, such as mutation rate and population structure. We demonstrate the existence of a sharp error threshold, a neural noise level beyond which information accumulated by an evolutionary process cannot be maintained. We point at the importance of neural representation, akin to genotype-phenotype maps, in determining the efficiency of any evolutionary search in the brain. Novel analysis methods are developed, including neural firing pattern phylogenies that display the unfolding of the process.
A commercial antibody to the human condensin II subunit NCAPH2 cross-reacts with a SWI/SNF complex component
Authors: Cutts Erin E. , Taylor Gillian C , Pardo Mercedes , Yu Lu , Wills Jimi C , Choudhary Jyoti S. , Vannini Alessandro , Wood Andrew J 
Published: November 2020

SummaryCondensin complexes compact and disentangle chromosomes in preparation for cell division. Commercially available antibodies raised against condensin subunits have been widely used to characterise their cellular interactome. Here we have assessed the specificity of a polyclonal antibody (Bethyl A302-276A) that is commonly used as a probe for NCAPH2, the kleisin subunit of condensin II, in mammalian cells. We find that, in addition to its intended target, this antibody cross-reacts with one or more components of the SWI/SNF family of chromatin remodelling complexes in an NCAPH2-independent manner. This cross-reactivity with an abundant chromatin-associated factor is likely to affect the interpretation of protein and chromatin immunoprecipitation experiments that make use of this antibody probe.