bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term co-circulation of multiple arboviruses in southeast Australia revealed by xeno-monitoring and metatranscriptomics
Authors: Julia S. P. Vieira Carla , Onn Michael B. , Shivas Martin A. , Shearman Damien , Darbro Jonathan M. , Graham Melissa , Freitas Lucas , van den Hurk Andrew F. , Frentiu Francesca D. , Wallau Gabriel L. , Devine Gregor J. 
Published: March 2024

AbstractArbovirus surveillance of wild-caught mosquitoes is an affordable and sensitive means of monitoring virus transmission dynamics at various spatial-temporal scales, and emergence and re-emergence during epidemic and interepidemic periods. A variety of molecular diagnostics for arbovirus screening of mosquitoes (known as xeno-monitoring) are available, but most provide limited information about virus diversity. PCR-based screening coupled with metatranscriptomics is an increasingly affordable and sensitive pipeline for integrating complete viral genome sequencing into surveillance programs. This enables large-scale, high-throughput arbovirus screening from diverse samples. We collected mosquitoes in CO2-baited light traps from five urban parks in Brisbane from March 2021 to May 2022. Mosquito pools of ≤200 specimens were screened for alphaviruses and flaviviruses using virus genus-specific primers and reverse transcription quantitative PCR (qRT-PCR). A subset of virus-positive samples was then processed using a mosquito-specific ribosomal RNA depletion method and then sequenced on the Illumina NextSeq. Overall, 54,670 mosquitoes, representing 26 species were screened in 382 pools. Thirty detections of arboviruses were made in 28 pools. Twenty of these positive pools were further characterised using meta-transcriptomics generating 18 full-length genomes. These full-length sequences belonged to four medically relevant arboviruses: Barmah Forest, Ross River, Sindbis-like and Stratford viruses. Phylogenetic and evolutionary analyses revealed the evolutionary progression of arbovirus lineages over the last 100 years, highlighting long-distance dispersal across the Australian continent and continuous circulation characterised by constant turnover of virus lineages.
Identification of a proteolysis regulator for an essential enzyme inMycobacterium tuberculosis
Authors: Kahne Shoshanna C. , Yoo Jin Hee , Chen James , Nakedi Kehilwe , Iyer Lakshminarayan M. , Putzel Gregory , Samhadaneh Nora M. , Pironti Alejandro , Aravind L. , Ekiert Damian C. , Bhabha Gira , Rhee Kyu Y. , Darwin K. Heran 
Published: March 2024

AbstractInMycobacterium tuberculosisproteins that are post-translationally modified with Pup, a prokaryotic ubiquitin-like protein, can be degraded by proteasomes. While pupylation is reversible, mechanisms regulating substrate specificity have not been identified. Here, we identify the first depupylation regulators: CoaX, a pseudokinase, and pantothenate, an essential, central metabolite. In a ΔcoaXmutant, pantothenate synthesis enzymes were more abundant, including PanB, a substrate of the Pup-proteasome system. Media supplementation with pantothenate decreased PanB levels in acoaXand Pup-proteasome-dependent manner.In vitro, CoaX accelerated depupylation of Pup∼PanB, while addition of pantothenate inhibited this reaction. Collectively, we propose CoaX contributes to proteasomal degradation of PanB by modulating depupylation of Pup∼PanB in response to pantothenate levels.One Sentence SummaryA pseudo-pantothenate kinase regulates proteasomal degradation of a pantothenate synthesis enzyme inM. tuberculosis.
A comprehensive two-hybrid analysis to explore theL. pneumophilaeffector-effector interactome
Authors: O’Connor Mount Harley , Urbanus Malene L. , Sheykhkarimli Dayag , Coté Atina G. , Laval Florent , Coppin Georges , Kishore Nishka , Li Roujia , Spirohn-Fitzgerald Kerstin , Petersen Morgan O. , Knapp Jennifer J. , Kim Dae-Kyum , Twizere Jean-Claude , Calderwood Michael A. , Vidal Marc , Roth Frederick P. , Ensminger Alexander W. 
Published: March 2024

AbstractLegionella pneumophilauses over 300 translocated effector proteins to rewire host cells during infection and create a replicative niche for intracellular growth. To date, several studies have identifiedL. pneumophilaeffectors that indirectly and directly regulate the activity of other effectors, providing an additional layer of regulatory complexity. Amongst these are “metaeffectors” – a special class of effectors that regulate the activity of other effectors once inside the host. A defining feature of metaeffectors is direct, physical interaction with a target effector. Metaeffector identification to date has depended on phenotypes in heterologous systems and experimental serendipity. Using a multiplexed, recombinant-barcode-based yeast two-hybrid technology we screened for protein-protein interactions amongst allL. pneumophilaeffectors and several components of the Dot/Icm type IV secretion system (>167,000 protein combinations). Of the 52 protein interactions identified by this approach, 44 are novel protein interactions, including ten novel effector-effector interactions (doubling the number of known effector-effector interactions).
Sex-Specific Cardiovascular Adaptations to Simulated Microgravity in Sprague-Dawley Rats
Authors: Elsangeedy Ebrahim , Yamaleyeva Dina N. , Edenhoffer Nicholas P. , Deak Allyson , Soloshenko Anna , Ray Jonathan , Sun Xuming , Shaltout Omar H. , Diaz Nildris Cruz , Westwood Brian , Kim-Shapiro Daniel , Diz Debra I. , Soker Shay , Pulgar Victor M. , Ronca April , Willey Jeffrey S. , Yamaleyeva Liliya M. 
Published: April 2024

AbstractMen and women have different cardiovascular responses to spaceflight; however few studies have focused on direct comparisons between sexes. Therefore, we investigated cardiovascular system differences, including arterial stiffness between socially and sexually mature 20-week-old male and female Sprague Dawley (SD) rats exposed to hindlimb unloading (HLU) - an analogue for spaceflight-induced microgravity. Two weeks of HLU had no effect on body weight in either male or female rats. The index of arterial stiffness determined by ultrasound, pulse wave velocity (PWV), was greater in the aortic arch and carotid artery of females after HLU versus control females. HLU had no effect on arterial PWV in males. α smooth muscle actin, myosin, collagen, elastin, and collagen-to-elastin ratio were not different in rats of either sex in response to HLU. HLU exposure did not alter individual collagen fiber characteristics in studied groups. The levels of G protein-coupled estrogen receptor (GPER) were lower in the aorta of SD females exposed to HLU compared with female controls but not in males. These changes were associated with lower PPAR γ and increased oxidative stress markers (8-hydroxy-2’-deoxyguanosine and p47phox) in the females. Diastolic cardiac function was altered in females after HLU versus control females. GPER agonist, G1 prevented the increase in pulse wave velocity and 8-hydroxy-2’-deoxyguanosine, without altering PPAR γ or p47phox. Our data revealed that lower GPER in the HLU females contributes to the development of arterial stiffness, and that the SD rat is a suitable model to study the cardiovascular response of females to HLU.
Prophages express a type IV pilus component to provide anti-phage defence
Authors: Sztanko Kristina M. , Javorčík P. Nathael , Fitzpatrick Alexa D. , Lenskaia Tatiana , Maxwell Karen L. , Davidson Alan R. 
Published: March 2024

AbstractPhage genomes integrated within bacterial genomes, known as prophages, frequently encode proteins that provide defence against further phage infection. These proteins often function at the cell surface and prevent phages from attaching to their host receptor. Here, we describe the discovery of prophage-encoded proteins that resemble FimU, a component of thePseudomonas aeruginosatype IV pilus. These phage FimU proteins are incorporated into the pilus without altering its function, yet they mediate robust protection against infection by phages that bind to the tip of the pilus, where FimU is likely located. The phage FimU proteins and the phage tail proteins that interact with FimU are highly diverse, suggesting that evolution in this system is driven by phage versus phage competition. To our knowledge, this is the first example of anti-phage defence mediated by replacement of a bacterial cell surface component with a phage-encoded protein.
p300/CBP degradation is required to disable the active AR enhanceosome in prostate cancer
Authors: Luo Jie , Chen Zhixiang , Qiao Yuanyuan , Tien Jean Ching-Yi , Young Eleanor , Mannan Rahul , Mahapatra Somnath , He Tongchen , Eyunni Sanjana , Zhang Yuping , Zheng Yang , Su Fengyun , Cao Xuhong , Wang Rui , Cheng Yunhui , Seri Rithvik , George James , Shahine Miriam , Miner Stephanie J. , Vaishampayan Ulka , Wang Mi , Wang Shaomeng , Parolia Abhijit , Chinnaiyan Arul M. 
Published: March 2024

SummaryProstate cancer is an exemplar of an enhancer-binding transcription factor-driven disease. The androgen receptor (AR) enhanceosome complex comprised of chromatin and epigenetic coregulators assembles at enhancer elements to drive disease progression. The paralog lysine acetyltransferases p300 and CBP deposit histone marks that are associated with enhancer activation. Here, we demonstrate that p300/CBP are determinant cofactors of the active AR enhanceosome in prostate cancer. Histone H2B N-terminus multisite lysine acetylation (H2BNTac), which is exclusively reliant on p300/CBP catalytic function, marked active enhancers and was notably elevated in prostate cancer lesions relative to the adjacent benign epithelia. Degradation of p300/CBP rapidly depleted acetylation marks associated with the active AR enhanceosome, which was only partially phenocopied by inhibition of their reader bromodomains. Notably, H2BNTac was effectively abrogated only upon p300/CBP degradation, which led to a stronger suppression of p300/CBP-dependent oncogenic gene programs relative to bromodomain inhibition or the inhibition of its catalytic domain.In vivoexperiments using an orally active p300/CBP proteolysis targeting chimera (PROTAC) degrader (CBPD-409) showed that p300/CBP degradation potently inhibited tumor growth in preclinical models of castration-resistant prostate cancer and synergized with AR antagonists. While mouse p300/CBP orthologs were effectively degraded in host tissues, prolonged treatment with the PROTAC degrader was well tolerated with no significant signs of toxicity. Taken together, our study highlights the pivotal role of p300/CBP in maintaining the active AR enhanceosome and demonstrates how target degradation may have functionally distinct effects relative to target inhibition, thus supporting the development of p300/CBP degraders for the treatment of advanced prostate cancer.
An old inversion polymorphism involving giant mobile elements in an invasive fungal pathogen
Authors: Hartmann Fanny E. , Rodriguez de la Vega Ricardo C. , Demené Arthur , Badet Thomas , Vernadet Jean-Philippe , Rougemont Quentin , Labat Amandine , Snirc Alodie , Stauber Lea , Croll Daniel , Prospero Simone , Dutech Cyril , Giraud Tatiana 
Published: March 2024

AbstractRecombination suppression can evolve in sex or mating-type chromosomes, or in autosomal supergenes, with different haplotypes being maintained by balancing selection. In the invasive chestnut blight fungusCryphonectria parasitica, a genomic region was suggested to lack recombination and to be partially linked to the mating-type (MAT) locus based on segregation analyses. Using hundreds of availableC. parasiticagenomes and generating new high-quality genome assemblies, we show that a ca. 1.2 Mb genomic region proximal to the mating-type locus lacks recombination, with the segregation of two highly differentiated haplotypes in balanced proportions in invasive populations. High-quality genome assemblies further revealed an inversion in one of the haplotypes in the invaded range. The two haplotypes were estimated to have diverged 1.5 million years ago, and each harboured specific genes, some of which likely belonging toStarshipelements, that are large mobile elements, mobilized by tyrosine recombinases, able to move accessory genes, and involved in adaptation in multiple fungi. The MAT-proximal region carried genes upregulated under virus infection or vegetative incompatibility reaction. In the native range, the MAT-proximal region also appeared to have a different evolutionary history than the rest of the genome. In all continents, the MAT-Proximal region was enriched in non-synonymous substitutions, in gene presence/absence polymorphism, in tyrosine recombinases and in transposable elements. This study thus sheds light on a case of a large non-recombining region partially linked to a mating compatibility locus, with likely balancing selection maintaining differentiated haplotypes, possibly involved in adaptation in a devastating tree pathogen.
Loss of Paneth cells dysregulates gut ILC subsets and enhances weight gain response to high fat diet in a mouse model
Authors: Joldrichsen Marisa R. , Kim Eunsoo , Steiner Haley E. , Jeong Yea Ji , Premanandan Christopher , Hsueh Willa , Ziouzenkova Ouliana , Cormet-Boyaka Estelle , Boyaka Prosper N. 
Published: April 2024

AbstractObesity has been associated with dysbiosis, but innate mechanisms linking intestinal epithelial cell subsets and obesity remain poorly understood. Using mice lacking Paneth cells (Sox9ΔIECmice), small intestinal epithelial cells specialized in the production of antimicrobial products and cytokines, we show that dysbiosis alone does not induce obesity or metabolic disorders. Loss of Paneth cells reduced ILC3 and increased ILC2 numbers in the intestinal lamina propria. High-fat diet (HFD) induced higher weight gain and more severe metabolic disorders in Sox9ΔIECmice. Further, HFD enhances the number of ILC1 in the intestinal lamina propria of Sox9ΔIECmice and increases intestinal permeability and the accumulation of immune cells (inflammatory macrophages and T cells, and B cells) in abdominal fat tissues of obese Sox9ΔIEC. Transplantation of fecal materials from Sox9ΔIECmice in germ-free mice before HFD further confirmed the regulatory role of Paneth cells for gut ILC subsets and the development of obesity.
The Evolution of Microbiome-Mediated Traits
Authors: Week Bob , Morris Andrew H. , Bohannan Brendan J. M. 
Published: March 2024

AbstractThe role of host-associated microbiomes in shaping host fitness is becoming increasingly recognized, and may have important evolutionary consequences. The degree to which microbiomes contribute to host evolution depends on how they are inherited. To understand the conditions under which host evolution is mediated by microbiome inheritance, we introduce a simple mathematical model. Our model tracks the evolution of a quantitative host trait that is mediated by host genotype and host microbiome. Unlike host genotype, the host microbiome may have several routes of transmission, including social contact and environmental acquisition. Our model takes a breeding-value approach to formally generalize classical quantitative genetic theory to account for these various modes of microbiome inheritance. A key prediction of our model is that, as long as microbiomes are transmitted between host generations, their mode of transmission has no effect on host trait dynamics. To understand the conditions required for this result, we analyze microbiome-explicit simulations that break important model assumptions. We then discuss avenues to generalize our model and connections with related concepts. Taken together, this work provides novel insights into the dynamics of non-Mendelian populations, and makes first steps towards establishing a theory of microbiome-mediated trait evolution.
Detection of known and novel virus sequences in the black solider fly and expression of host antiviral pathways
Authors: Walt Hunter K. , Jordan Heather R. , Meyer Florencia , Hoffmann Federico G. 
Published: March 2024

ABSTRACTMass rearing of animals in close quarters can be highly conducive to microbe transmission, including pathogens. This has been shown multiple times in the case of important industrial insects such as crickets, silkworms, and honeybees. One industrial insect of increasing importance is the black soldier fly (Diptera:Hermetia illucens), as it can convert organic waste into high quality protein and fatty acids. Along with this, they take up far less space than traditional protein sources, as millions of black soldier flies can be reared in a relatively small facility. Because of this, there is a growing interest in the pathogens that could impact black soldier fly rearing efforts. So far, only three black soldier fly-associated viruses have been identified. We used metatranscriptomic sequencing to survey black soldier fly guts, frass, and diet for viruses. We detected sequences from two novel viruses. One, which we nameHermetia illucenssigma-like virus 1, is phylogenetically related to viruses of the genus Sigmavirus, which have been highly studied inDrosophila. The other novel virus, which we nameHermetia illucenstoti-like virus 2, is the second toti-like virus to be described in the black soldier fly. We also detected two black soldier fly-associated viruses previously identified by our group: BSF nairo-like virus, and BSF uncharacterized bunya-like virus. Consistent with our previous study, these two viruses are found primarily in frass samples and occur together more often than expected at random. When analyzing host transcription, we found significant differences in gene expression for eight candidate antiviral genes in black soldier fly when comparing samples with and without viral sequences. Our results suggest that black soldier fly-virus interactions are ongoing, and they could be of interest to black soldier fly producers.
Co-Essentiality Analysis Identifies PRR12 as a Regulator of Cohesin and Genome Integrity
Authors: Nguyen Alexandra L. , Smith Eric , Cheeseman Iain M. 
Published: March 2024

SummaryThe cohesin complex is critical for genome regulation, relying on specialized co-factors to mediate its diverse functional activities. Here, by analyzing patterns of similar gene requirements across cell lines, we identify PRR12 as a regulator of cohesin and genome integrity. We show that PRR12 interacts with cohesin and PRR12 loss results in a reduction of nuclear-localized cohesin and an accumulation of DNA lesions. We find that different cell lines across human and mouse exhibit significant variation in their sensitivity to PRR12 loss. Unlike the modest phenotypes observed in human cell lines, PRR12 depletion in mouse cells results in substantial genome instability. Despite a modest requirement in human cell lines, mutations in PRR12 lead to severe developmental defects in human patients, suggesting context-specific roles in cohesin regulation. By harnessing comparative studies across species and cell lines, our work reveals critical insights into how cohesin is regulated across diverse cellular contexts.
A next generation of hierarchical Bayesian analyses of hybrid zones enables direct quantification of variation in introgression in R
Authors: Gompert Zachariah , DeRaad Devon A. , Alex Buerkle C. 
Published: March 2024

AbstractHybrid zones, where genetically distinct groups of organisms meet and interbreed, offer valuable insights into the nature of species and speciation. Here, we present a new R package bgchm, for population genomic analyses of hybrid zones. This R package extends and updates the existing bgc software and combines Bayesian analyses of hierarchical genomic clines with Bayesian methods for estimating hybrid indexes, interpopulation ancestry proportions, and geographic clines. Compared to existing software, bgchm offers enhanced efficiency through Hamiltonian Monte Carlo sampling and the ability to work with genotype likelihoods combined with a hierarchical Bayesian approach, enabling accurate inference for diverse types of genetic datasets. The package also facilitates the quantification of introgression patterns across genomes, which is crucial for understanding reproductive isolation and speciation genetics. We first describe the models underlying bgchm and then provide an overview of the R package and illustrate its use through the analysis of simulated and empirical data sets. We show that bgchm generates accurate estimates of model parameters under a variety of conditions, especially when the genetic loci analyzed are highly ancestry informative. This includes relatively robust estimates of genome-wide variability in clines, which has not been the focus of previous models and methods. We also illustrate how both selection and genetic drift contribute to variability in introgression among loci and how additional information can be used to help distinguish these contributions. We conclude by describing the promises and limitations of bgchm, comparing bgchm to other software for genomic cline analyses, and identifying areas for fruitful future development.
Multispecies interactions and the community context of the evolution of virulence
Authors: Evensen Claire , White Andy , Boots Mike 
Published: March 2024

AbstractIn nature, host-parasite/pathogen relationships are embedded in a network of ecological interactions that have the potential to shape the evolutionary trajectories of shared pathogens. Understanding this community context of infectious disease evolution is important for wildlife, agricultural, and human systems alike – illustrated, for example, by the increasing risk of zoonotic disease emergence. We introduce an eco-evolutionary model that examines ecological feedbacks across a range of host-host interactions. Specifically, we analyze a model of the evolution of virulence of a pathogen infecting hosts who themselves exhibit competitive, mutualistic, or exploitative relationships. We find that pathogen specialism is necessary for inter-host interactions to impact parasite evolution. An important general result is that increasing competition between hosts leads to higher shared pathogen virulence, while increasing mutualism leads to lower virulence. Across a range of scenarios, the nature of pathogen specialization is critical to the outcome – for instance, if hosts only differ in initial susceptibility to infection, there is no impact of host-host interactions on virulence evolution. In contrast, specialization in terms of onward transmission, host tolerance, or intra-host pathogen growth rate critically impact the evolution of virulence. For example, stronger specialism in transmission selects for lower virulence, while stronger specialism in tolerance and growth rate selects for higher virulence. Our work provides testable hypotheses for multi-host disease systems, predicts how changing interaction networks may impact the evolution of virulence, and broadly demonstrates the importance of looking beyond pairwise relationships to understand evolution in realistic natural contexts.