bluuebunny/crossref_metadata_2025_split huggingface dataset:
Within-host adaptation alters priority effects within the phyllosphere microbiome
Authors: Debray Reena , Conover Asa , Zhang Xuening , Dewald-Wang Emily A. , Koskella Britt 
Published: August 2022

AbstractTo predict microbiome composition and function over time, it is essential to understand how evolution alters priority effects between resident and invading species. In an experimental evolution study on tomato plants, an early-colonizing bacterial species rapidly evolved to invade a new niche, altering its ecological interactions with other members of the plant microbiome, as well as its effect on the host. Prevailing models have assumed that adaptation primarily improves the efficiency of resident species within their existing niches, yet we conclude that host habitats can offer alternative evolutionary opportunities, complicating the application of existing theory to the community ecology of microbiomes.
Molecular evolution and inheritance pattern of Sox gene family among Bovidae
Authors: Akinyemi Mabel O. , Adegbaju Muyiwa S. , Grytsay Anastasia , Osaiyuwu Osamede H , Finucan Jessica , Ogunade Ibukun M. , Peters Sunday O. , Thomas Bolaji N. , Morenikeji Olanrewaju B. 
Published: August 2022

AbstractSox gene is an evolutionarily conserved family of transcription factors that play important roles in cellular differentiation and numerous complex developmental processes. In vertebrates, Sox proteins are required for cell fate decision, morphogenesis, and control self-renewal in embryonic and adult stem cells. Sox gene family has been well studied in multiple species including humans but scanty or no study in Bovidae. In this study, we conducted a detailed evolutionary analysis of this gene family in Bovidae, including their physicochemical properties, biological functions, and patterns of inheritance. We performed a genome-wide cataloguing to explore the Sox gene family using multiple bioinformatics tools. Our analysis revealed conserved motifs that are crucial to the ability of Sox genes to interact with the regulatory regions of target genes and orchestrate multiple developmental and physiological processes. Importantly, we report a unique motif being EFDQYL/ELDQYL found in SoxE and SoxF groups. Further analysis revealed that this motif sequence accounts for the binding and transactivation potential of Sox proteins. Protein-protein interaction showed significant interaction among Sox genes and related genes implicated in embryonic development and the regulation of cell differentiation. We conclude that Sox gene family uniquely evolved among Bovidae with a few exhibiting important motifs that drives several developmental and physiological processes.
Transport of Antibody into the Skin is Only Partially Dependent Upon the Neonatal Fc-Receptor
Authors: Nasir Gibran , Sinnis Photini 
Published: August 2022

AbstractThe dermis is the portal of entry for most vector-transmitted pathogens, making the host’s immune response at this site critical in mitigating the magnitude of infection. For malaria, antibody-mediated neutralization ofPlasmodiumparasites in the dermis was recently demonstrated. However, surprisingly little is known about the mechanisms that govern antibody transport into the skin. Since the neonatal Fc receptor (FcRn) has been shown to transcytose IgG into various tissues, we sought to understand its contribution to IgG transport and antibody-mediated inhibition ofPlasmodiumparasites following mosquito bite inoculation. Using confocal imaging, we show that the transport of an anti-Langerin mAb into the skin is only partially reduced in mice lacking FcRn. To understand the relevance of FcRn in the context of malaria infection, we use the rodent parasitePlasmodium bergheiand show that the protective efficacy of a passively-administered anti-malarial antibody is reduced in the skin in FcRn deficient mice, but not to the same extent that we have previously observed in wildtype mice. Overall, our data suggest that FcRn plays a role in the transport of IgG into the skin but is not the major driver of IgG transport into this tissue. These findings have implications for the rational design of antibody-based therapeutics for malaria as well as other vector-transmitted pathogens.
Genetic associations with resistance to Meloidogyne enterolobii in guava (Psidium sp.) using cross-genera SNPs and comparative genomics to Eucalyptus highlight evolutionary conservation across the Myrtaceae
Authors: Fernandes Santos Carlos Antonio , Rodrigues da Costa Soniane , Silva Boiteux Leonardo , Grattapaglia Dario , Silva-Junior Orzenil B. 
Published: August 2022

AbstractTropical fruit tree species constitute a yet untapped supply of outstanding diversity of taste and nutritional value, barely developed from the genetics standpoint, with scarce or no genomic resources to tackle the challenges arising in modern breeding practice. We generated a de novo genome assembly of the Psidium guajava, the super fruit “apple of the tropics”, and successfully transferred 14,268 SNP probesets from Eucalyptus to Psidium at the nucleotide level, to detect genomic loci linked to resistance to the root knot nematode (RKN) Meloidogyne enterolobii derived from the wild relative P. guineense. Significantly associated loci with resistance across alternative analytical frameworks, were detected at two SNPs on chromosome 3 in a pseudo-assembly of Psidium guajava genome built using a syntenic path approach with the Eucalyptus grandis genome to determine the order and orientation of the contigs. The P. guineense-derived resistance response to RKN and disease onset is conceivably triggered by mineral nutrients and phytohormone homeostasis or signaling with the involvement of the miRNA pathway. Hotspots of mapped resistance quantitative trait loci and functional annotation in the same genomic region of Eucalyptus provide further indirect support to our results, highlighting the evolutionary conservation of genomes across genera of Myrtaceae in the adaptation to pathogens. Marker assisted introgression of the resistance loci mapped should accelerate the development of improved guava cultivars and hybrid rootstocks.
Commensal Neisseria species share immune suppressive mechanisms with Neisseria gonorrhoeae
Authors: Zhu Weiyan , Cardenas-Alvarez Maria X. , Tomberg Joshua , Little Marguerite , Duncan Joseph A. , Nicholas Robert A. 
Published: August 2022

ABSTRACTNeisseria gonorrhoeae is a highly adapted human sexually transmitted pathogen that can cause symptomatic infections associated with localized inflammation as well as asymptomatic and subclinical infections, particularly in females. Gonococcal infection in humans does not generate an effective immune response in most cases, which contributes to both transmission of the pathogen and reinfection after treatment. Neisseria gonorrhoeae is known to evade and suppress human immune responses through a variety of mechanisms. Commensal Neisseria species that are closely related to N. gonorrhoeae, such as N. cinerea, N. lactamica, N. elongata, and N. mucosa, rarely cause disease and instead asymptomatically colonize mucosal sites for prolonged periods of time without evoking clearing immunologic responses. We have shown previously that N. gonorrhoeae inhibits the capacity of antigen-pulsed dendritic cells to induce CD4+ T cell proliferation in vitro. Much of the suppressive effects of N. gonorrhoeae on dendritic cells can be recapitulated either by outer-membrane vesicles released from the bacteria or by purified PorB, the most abundant outer-membrane protein in Neisseria gonorrhoeae. We show here that three commensal Neisseria species, N. cinerea, N. lactamica and N. mucosa, show a comparable capacity to suppress dendritic cell-induced T cell proliferation through mechanisms similar to those demonstrated previously for N. gonorrhoeae, including inhibition by purified PorB. Our findings suggest that some immune-evasive properties of pathogenic N. gonorrhoeae are shared with commensal Neisseria species and may contribute to the ability of both pathogens and commensals to cause prolonged mucosal colonization in humans.
Diversity, composition, altitude, and seasonality of high-altitude windborne migrating mosquitoes in the Sahel: Implications for disease transmission
Authors: Yaro AS , Linton Y-M , Dao A , Diallo M , Sanogo ZL , Samake D , Ousman Y , Kouam C , Krajacich BJ , Faiman R , Bamou R , Woo J , Chapman JW , Reynolds DR , Lehmann T 
Published: August 2022

AbstractRecent studies have reported Anopheles mosquitoes captured at high-altitude (40–290 m above ground) in the Sahel. Here, we describe this migration modality across genera and species of African Culicidae and examine its implications for disease transmission and control. As well as Anopheles, six other genera—Culex, Aedes, Mansonia, Mimomyia, Lutzia, and Eretmapodites comprised 90% of the 2,340 mosquitoes captured at altitude. Of the 50 molecularly confirmed species (N=2,107), 33 species represented by multiple specimens were conservatively considered high-altitude windborne migrants, suggesting it is a common migration modality in mosquitoes (31–47% of the known species in Mali), and especially in Culex (45–59%). Overall species abundance varied between 2 and 710 specimens/species (in Ae. vittatus and Cx. perexiguus, respectively). At altitude, females outnumbered males 6:1, and 93% of the females have taken at least one blood meal on a vertebrate host prior to their departure. Most taxa were more common at higher sampling altitudes, indicating that total abundance and diversity are underestimated. High-altitude flight activity was concentrated between June and November coinciding with availability of surface waters and peak disease transmission by mosquitoes. These hallmarks of windborne mosquito migration bolster their role as carriers of mosquito-borne pathogens (MBPs). Screening 921 mosquitoes using pan-Plasmodium assays revealed that thoracic infection rate in these high-altitude migrants was 2.4%, providing a proof of concept that vertebrate pathogens are transported by windborne mosquitoes at altitude. Fourteen of the 33 windborne mosquito species had been reported as vectors to 25 MBPs in West Africa, which represent 32% of the MBPs known in that region and include those that inflict the heaviest burden on human and animal health, such as malaria, yellow fever, dengue, and Rift Valley fever. We highlight five arboviruses that are most likely affected by windborne mosquitoes in West Africa: Rift Valley fever, O’nyong’nyong, Ngari, Pangola, and Ndumu. We conclude that the study of windborne spread of diseases by migrating insects and the development of surveillance to map the sources, routes, and destinations of vectors and pathogens is key to understand, predict, and mitigate existing and new threats of public health.
Discovery, Structure, and Function of Filamentous 3-Methylcrotonyl-CoA Carboxylase
Authors: Hu Jason J. , Lee Jane K.J. , Liu Yun-Tao , Yu Clinton , Huang Lan , Aphasizheva Inna , Aphasizhev Ruslan , Zhou Z. Hong 
Published: August 2022

SUMMARY3-methylcrotonyl-CoA carboxylase (MCC) is a biotin-dependent enzyme necessary for leucine catabolism in most organisms. While the crystal structure of recombinant bacterial MCC has been characterized, the structure and potential polymerization of native MCC remain elusive. Here, we discovered that native MCC fromLeishmania tarentolae(LtMCC) forms filaments and determined its structure at near-atomic resolution using cryoEM. α6β6LtMCC dodecamers assemble in a twisted-stacks architecture, manifesting as supramolecular rods extending up to approximately 400 nanometers. LtMCCs in filaments bind biotin but are not covalently biotinylated and lack coenzyme A. Filaments elongate by stacking α6β6LtMCCs onto the exterior α-trimer of the terminal α6β6dodecamer. This stacking immobilizes the biotin carboxylase domains, sequestering the enzyme in an inactive state within the mitochondrial matrix. Our results support a new model for LtMCC catalysis, termed the dual-swinging-domains model, and cast new light on the functional significance of polymerization in the carboxylase superfamily and beyond.
Function and structure of FlaK, a master regulator of the polar flagellar genes in marine Vibrio
Authors: Homma Michio , Kobayakawa Tomoya , Hao Yuxi , Nishikino Tatsuro , Kojima Seiji 
Published: August 2022

ABSTRACTVibrio alginolyticus has a flagellum at the cell pole, and the fla genes, involved in its formation, are hierarchically regulated in several classes. FlaK (also called FlrA) is an ortholog of Pseudomonas aeruginosa FleQ, an AAA+ ATPase that functions as a master regulator for all later fla genes. In this study, we conducted mutational analysis of FlaK to examine its ATPase activity, ability to form a multimeric structure, and function in flagellation. We cloned flaK and confirmed that its deletion caused a non-flagellated phenotype. We substituted amino acids at the ATP binding/hydrolysis site and performed putative subunit interfaces in a multimeric structure. Mutations in the aforementioned sites abolished both ATPase activity and the ability of FlaK to induce downstream flagellar gene expression. The L371E mutation, at the putative subunit interface, abolished flagellar gene expression but retained ATPase activity, suggesting that ATP hydrolysis is not sufficient for flagellar gene expression. We also found that FlhG, a negative flagellar biogenesis regulator, suppressed the ATPase activity of FlaK. The 20 FlhG C-terminal residues are critical for reducing FlaK ATPase activity. Chemical crosslinking and size exclusion chromatography revealed that FlaK mostly exists as a dimer in solution and can form multimers, independent of ATP. However, ATP induced the interaction between FlhG and FlaK to form a large complex. The in vivo effects of FlhG on FlaK, such as multimer formation and/or DNA binding, are important for gene regulation.IMPORTANCEFlaK is an NtrC-type activator of the AAA+ ATPase subfamily of σ54-dependent promoters of flagellar genes. FlhG, a MinD-like ATPase, negatively regulates the polar flagellar number by collaborating with FlhF, an FtsY-like GTPase. We found that FlaK and FlhG interact in the presence of ATP, to form a large complex. Mutational analysis revealed the importance of FlaK ATPase activity in flagellar gene expression and provided a model of the Vibrio molecular mechanism that regulates the flagellar number.
Partial EMT and associated changes in cellular plasticity in oncovirus-positive samples
Authors: Sehgal Manas , Ray Ritoja , Vaz Joel Markus , Kanikar Shrihar , Somarelli Jason A. , Jolly Mohit Kumar 
Published: August 2022

AbstractOncoviruses exploit diverse host mechanisms to survive and proliferate. These adaptive strategies overlap with mechanisms employed by malignant cells during their adaptation to dynamic micro-environments and for evasion of immune attack. While the role of individual oncoviruses in mediating cancer progression has been extensively characterized, little is known about the common gene regulatory features of oncovirus-induced cancers. Here, we focus on defining the interplay between several cancer hallmarks, including Epithelial-Mesenchymal Transition (EMT), metabolic alterations, and immune evasion across major oncoviruses by examining publicly available transcriptomics data sets containing both oncovirus-positive and oncovirus-negative samples. We observe that oncovirus-positive samples display varying degrees of EMT and metabolic reprogramming. While the progression of EMT generally associated with an enriched glycolytic metabolic program and suppressed fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS), partial EMT correlated well with glycolysis. Furthermore, oncovirus-positive samples had higher activity and/or expression levels of immune checkpoint molecules, such as PD-L1, which was associated with a partial EMT program. These analyses thus decode common pathways in oncovirus-positive samples that may be used in pinpointing new therapeutic vulnerabilities for oncovirus-associated cancer cell plasticity.
The Drosophila AWP1 ortholog Doctor No regulates JAK/STAT signaling for left-right asymmetry in the gut by promoting receptor endocytosis
Authors: Lai Yi-Ting , Takeshi Sasamura , Kuroda Junpei , Maeda Reo , Nakamura Mitsutoshi , Hatori Ryo , Ishibashi Tomoki , Taniguchi Kiichiro , Ooike Masashi , Taguchi Tomohiro , Nakazawa Naotaka , Hozumi Shunya , Okumura Takashi , Aigaki Toshiro , Inaki Mikiko , Matsuno Kenji 
Published: August 2022

ABSTRACTMany internal Drosophila organs show stereotypical left-right (LR) asymmetry, for which the underlying mechanisms remain elusive. Here, we identified an evolutionarily conserved ubiquitin-binding protein, AWP1/Doctor no (Drn), as a novel factor required for the LR asymmetry of the embryonic anterior gut in Drosophila. We showed that drn is essential in the circular visceral muscle cells of the midgut for JAK/STAT signaling, which contributes to the first known cue for anterior gut lateralization via LR-asymmetric nuclear rearrangement. Embryos homozygous for drn and lacking its maternal contribution showed phenotypes similar to that of depleted JAK/STAT signaling, suggesting that Drn is a general component of JAK/STAT signaling. The absence of Drn resulted in the specific accumulation of Domeless (Dome), the receptor of JAK/STAT signaling, in intracellular compartments. Thus, Drn is required for the endocytic trafficking of Dome, which is subsequently degraded in lysosomes. Our results suggest that the endocytosis of Dome is a critical step in activating JAK/STAT signaling. The roles of AWP1/Drn in activating JAK/STAT signaling and in LR-asymmetric development may be conserved in various organisms.Summary StatementDr. No, a Drosophila ortholog of AWP1, activates JAK/STAT signaling via Dome receptor endocytosis in a crucial step for left-right asymmetry in the developing gut.
Extracellular vesicle-mediated promotion of myogenic differentiation is dependent on dose, collection media composition, and isolation method
Authors: Hanson Britt , Conceição Mariana , Lomonsova Yulia , Mäger Imre , Puri Pier Lorenzo , Andaloussi Samir EL , Wood Matthew J.A. , Roberts Thomas C. 
Published: August 2022

AbstractExtracellular vesicles (EVs) have been implicated in the regulation of myogenic differentiation. We observed that treatment of C2C12 murine myoblasts with either GW4869 (to inhibit exosome biogenesis) or heparin (to inhibit EV uptake) reduced myogenic differentiation. Conversely, conditioned media collected from differentiated C2C12 myotubes enhanced myogenic differentiation. Ultrafiltration-size exclusion liquid chromatography (UF-SEC) was used to isolate pure EV preparations and extracellular protein from C2C12 myoblast- and myotube-conditioned media in parallel. UF-SEC purified EVs promoted myogenic differentiation at low doses (≤2×108 particles/ml), had no effect at 2×1010 particles/ml, and inhibited myo<genic differentiation at the highest dose tested (2×1011 particles/ml). Similar effects were observed with both myoblast- and myotube-derived EVs. Given that muscle-enriched miRNAs (myomiRs) are largely absent in myoblast cultures, these findings are indicative of a myomiR-independent mechanism underlying the observed pro-myogenic effects. Indeed, individual myomiRs were found to be scarce in EVs (e.g. the most abundant myomiR, miR-133a-3p, was present at 1 copy per 195 EVs). UF-SEC-purified extracellular protein had no effect on myogenic differentiation when collected in serum-free DMEM. However, a potent pro-myogenic effect was observed when Opti-MEM was used as EV harvest media. Opti-MEM contains insulin, which was sufficient to recapitulate the pro-myogenic effect. Similarly, when EVs were isolated by polymer-based precipitation, a pro-myogenic effect was observed, but only when Opti-MEM was used as a collection media. These findings highlight Opti-MEM as a potential confounding factor, and provide further evidence that polymer-based precipitation techniques should be avoided in EV research.
Murine cytomegalovirus downregulates ERAAP & induces an unconventional T cell response to self
Authors: Geiger Kristina M. , Manoharan Michael , Coombs Rachel , Park Chan-su , Lee Angus Y. , Shastri Nilabh , Robey Ellen A. , Coscoy Laurent 
Published: August 2022

SummaryThe endoplasmic reticulum aminopeptidase associated with antigen presentation (ERAAP) plays a crucial role in shaping the peptide-MHC I repertoire and maintaining immune surveillance. While murine cytomegalovirus (MCMV) has multiple strategies for manipulating the antigen processing pathway to evade immune responses, the host has also developed ways to counter viral immune evasion. In this study, we found that MCMV modulates ERAAP and induces an IFN-γ producing CD8+T cell effector response that targets uninfected ERAAP deficient cells. We also observed that ERAAP downregulation during infection led to presentation of the self-peptide FL9 on non-classical Qa-1b, thereby eliciting Qa-1b restricted QFL T cells to proliferate in the liver and spleen of infected mice. QFL T cells upregulated effector markers upon MCMV infection and were sufficient to reduce viral load after transfer to immunodeficient mice. Our study highlights the consequences of ERAAP dysfunction during viral infection and provides potential targets for antiviral therapies.
COVID-19 pandemic, global advisories and the imperatives of strengthening the public healthcare system: Nigeria in context
Authors: Shodunke Aliu Oladimeji , Oladipupo Sodiq Abiodun , Tayo-Ladega Oluwadamisi Toluwalase , Alowolodu Adebusayo Joel , Adebayo Yusuf Olalekan 
Published: August 2022

PurposeGiven the efficacy of a robust public healthcare system in handling public health emergencies, the rapid rate of COVID-19 pandemic infection in early-hit (advanced) countries with competent healthcare system is intriguing. The popular public health argument supports the strengthening of the healthcare system as a significant response strategy to minimize infection. Hence, this paper examines the catalysts that exacerbated the pandemic’s rapid spread in these countries despite the sound state of their healthcare system. Also, it assesses the condition of Nigerian public healthcare system in the lights of the novel COVID-19 pandemic and suggests the need for improvement and effective functioning.Design/methodology/approachThis paper uses a documentary approach to establish the authors’ opinion on the subject matter under investigation.FindingsFactors such as climate, temperature, and humidity levels played a key role in infection in the winter of 2020. These factors facilitated for the pandemic’s rapid spread in advanced countries. In peripheral countries like Nigeria, the public healthcare system is burdened by a lack of funding, an insufficiency in welfare and training for healthcare staff and facilities and other operational challenges. Hence, the effective management of COVID-19 outbreak in Nigeria relative to advanced countries was hindered by the inadequacies mentioned above.Originality/valueThis paper provides an understanding on the condition of public healthcare system in peripheral nations in relation to the healthcare system advisories from the World Health Organization (WHO) in the context of handling the pandemic outbreak. Also, it explains the catalysts that heightened the pandemic’s rapid spread in advanced countries despite the higher capacity of their healthcare system to manage health emergencies.