bluuebunny/crossref_metadata_2025_split huggingface dataset:
When species trees disagree: an approach consistent with the coalescent that quantifies phylogenomic support for contentious relationships
Authors: Hodel Richard G.J. , Walker Joseph F. , Knowles L. Lacey , Smith Stephen A. 
Published: March 2020

AbstractPhylogenies inferred using both concatenation- and coalescent-based analyses typically render highly congruent trees. However, when they disagree, they often differ with respect to historically contentious and evolutionarily important relationships. These relationships may also involve etiolated lineages where increased sampling is not possible. Recently, methods aimed at interrogating single relationships or trees have emerged as promising investigative tools to examine these cases. Although recent methods such as “Edge-based Phylogenomic Support analYsis” (EPSY) led to insights into both systematic error and real biological signal, whether they are consistent with the coalescent in cases with high Incomplete Lineage Sorting (ILS) has yet to be characterized. Here, we use simulations and an empirical dataset to test the performance of EPSY, concatenation, and coalescent-based summary analyses under high levels of ILS. We focused on high-ILS scenarios because these represent the typical difficult cases that researchers often face due to the prevalence of ILS in phylogenomic datasets. ILS is known to be a major cause of phylogenomic conflict, which confounds many biological conclusions that depend on a resolved phylogeny, such as inferring ancestral character states, biogeographic reconstructions, and domestication histories. Our study found that EPSY was consistent with the coalescent in a high-ILS empirical dataset. In high-ILS simulations EPSY infers the correct edge more than half the time, whereas coalescent based methods and concatenation methods inferred the actual tree 37.8% and 25% of the time, respectively. All methods have conditions under which they generate the most accurate inferences. Given the levels of ILS in simulations, 26.2% of the time no method recovered the true tree. This zone where no current method can infer the true topology is likely due to properties of the species tree, such as the length of internal edges adjacent to a conflict and/or the length of the shortest branch. Nevertheless, the EPSY approach proves to be a valuable complement to phylogenomic analyses for interrogating regions of the tree with conflicting hypotheses generated from past studies or alternative inference methods. Our analyses highlight that robust phylogenetic trees may not be possible under some scenarios regardless of method and data source.
Prdm8 regulates pMN progenitor specification for motor neuron and oligodendrocyte fates by modulating Shh signaling response
Authors: Scott Kayt , O’Rourke Rebecca , Gillen Austin , Appel Bruce 
Published: March 2020

AbstractSpinal cord pMN progenitors sequentially produce motor neurons and oligodendrocyte precursor cells (OPCs). Some OPCs differentiate rapidly as myelinating oligodendrocytes whereas others remain into adulthood. How pMN progenitors switch from producing motor neurons to OPCs with distinct fates is poorly understood. pMN progenitors expressprdm8, which encodes a transcriptional repressor, during motor neuron and OPC formation. To determine ifprdm8controls pMN cell fate specification, we used zebrafish as a model system to investigateprdm8function. Our analysis revealed thatprdm8mutant embryos have a deficit of motor neurons resulting from a premature switch from motor neuron to OPC production. Additionally,prdm8mutant larvae have excess oligodendrocytes and a concomitant deficit of OPCs. Notably, pMN cells of mutant embryos have elevated Shh signaling coincident with the motor neuron to OPC switch. Inhibition of Shh signaling restored the number of motor neurons to normal but did not rescue the proportion of oligodendrocytes. These data suggest that Prdm8 regulates the motor neuron-OPC switch by controlling the level of Shh activity in pMN progenitors and also regulates allocation of oligodendrocyte lineage cell fates.Summary StatementPrdm8 regulates the timing of a motor neuron-oligodendrocyte switch and oligodendrocyte lineage cell identity in the zebrafish spinal cord.
Multi-resolution imaging using bioluminescence resonance energy transfer identifies distinct biodistribution profiles of extracellular vesicles and exomeres with redirected tropism
Authors: Wu Anthony Yan-Tang , Sung Yun-Chieh , Chen Yen-Ju , Chou Steven Ting-Yu , Guo Vanessa , Chien Jasper Che-Yung , Ko John Jun-Sheng , Yang Alan Ling , Huang Hsi-Chien , Chuang Ju-Chen , Wu Syuan , Ho Meng-Ru , Ericsson Maria , Lin Wan-Wan , Cheung Chantal Hoi Yin , Juan Hsueh-Fen , Ueda Koji , Chen Yunching , Lai Charles Pin-Kuang 
Published: March 2020

AbstractExtracellular particles (EP) including extracellular vesicles (EVs) and exomeres have been shown to play significant roles in diseases and therapeutic applications. However, their spatiotemporal dynamicsin vivohave remained largely unresolved in detail due to the lack of a suitable method. We therefore created a bioluminescence resonance energy transfer (BRET)-based reporter, PalmGRET, to enable pan-EP labelling ranging from exomeres (< 50 nm) to small (< 200 nm) and medium and large (> 200 nm) EVs. PalmGRET emits robust, sustained signals and allows the visualization, tracking and quantification of the EPs from whole-animal to nanoscopic resolutions under different imaging modalities, including bioluminescence, BRET and fluorescence. Using PalmGRET, we show that EPs released by lung metastatic hepatocellular carcinoma (HCC) exhibit lung tropism with varying distributions to other major organs in immunocompetent mice. We further demonstrate that gene knockdown of lung-tropic membrane proteins, solute carrier organic anion transporter family member 2A1 (Slco2a1), alanine aminopeptidase (Cd13) and chloride intracellular channel (Clic1) decreases HCC-EP distribution to the lungs and yields distinct biodistribution profiles. We anticipate that EP-specific imaging, quantitative assays and detailedin vivocharacterization to be a starting point for more accurate and comprehensivein vivomodels of EP biology and therapeutic design.
Incursion pathways of the Asian tiger mosquito (Aedes albopictus) into Australia contrast sharply with those of the yellow fever mosquito (Aedes aegypti)
Authors: Schmidt Thomas L , Chung Jessica , van Rooyen Anthony R. , Sly Angus , Weeks Andrew R , Hoffmann Ary A 
Published: March 2020

AbstractBACKGROUNDUnderstanding pest incursion pathways is critical for preventing new invasions and for stopping the transfer of alleles that reduce the efficacy of local control methods. The mosquitoesAedes albopictus(Skuse) andAe. aegypti(Linnaeus) are both highly invasive disease vectors, and through a series of ongoing international incursions are continuing to colonise new regions and spread insecticide resistance alleles among established populations. This study uses high-resolution molecular markers and a set of 241 reference genotypes to trace incursion pathways ofAe. albopictusinto mainland Australia, where no successful invasions have yet been observed. We contrast these results with incursion pathways ofAe. aegypti, investigated previously.RESULTSAssignments successful identified China, Japan, Singapore and Taiwan as source locations. Incursion pathways ofAe. albopictuswere entirely different to those ofAe. aegypti, despite broad sympatry of these species throughout the Indo-Pacific region. Incursions ofAe. albopictusappeared to have come predominantly along marine routes from key trading locations, whileAe. aegyptiwas mostly linked to aerial routes from tourism hotspots.CONCLUSIONThese results demonstrate how genomics can help decipher otherwise cryptic incursion pathways. The inclusion of reference genotypes from the Americas may help resolve some unsuccessful assignments. While many congeneric taxa will share common incursion pathways, this study highlights that this is not always the case, and incursion pathways of important taxa should be specifically investigated. Species differences in aerial and marine incursion rates may reflect the efficacy of ongoing control programs such as aircraft disinsection.
Partnership between epigenetic reader BRD4 and transcription factor CEBPD
Authors: Wang Qingwei , Zhang Mengxue , Urabe Go , Wang Bowen , Ozer Hatice Gulcin , Huang Yitao , Kent K. Craig , Guo Lian-Wang 
Published: March 2020

AbstractVascular smooth muscle cell (SMC) state/phenotype transitions underlie neointimal hyperplasia (IH) predisposing to cardiovascular diseases. Bromodomain protein BRD4 is a histone acetylation reader and enhancer mark that co-activates transcription elongation. CCAAT enhancer binding protein delta (CEBPD) is a transcription factor typically studied in adipogenesis and immune cell differentiation. Here we investigated the association between BRD4 and CEBPD in SMC state transition.Chromatin immunoprecipitation sequencing (ChIPseq) showed enrichment of BRD4 and histone acetylation (H3K27ac) atCebpdand enhancer in rat carotid arteries undergoing IH. In vitro, BRD4 silencing with siRNA reduced SMC expression of CEBPD. Bromodomain-1 but not bromodoamin-2 accounted for this BRD4 function. Endogenous BRD4 co-IP’ed with CEBPD;Cebpdpromoter and enhancer DNA fragments co-IP’ed with CEBPD or endogenous BRD4 (ChIP-qPCR). These co-IPs were abolished by the BRD4 bromodomain blocker JQ1. TNFα upregulated both BRD4 and CEBPD. Silencing CEBPD averted TNFα-induced inflammatory SMC state transition (heightened IL-1β, IL6, and MCP-1 mRNA levels), so did JQ1. CEBPD overexpression increased PDGFRα preferentially over PDGFRβ; so did TNFα, and JQ1 abolished TNFα’s effect.Our data reveal a BRD4/CEBPD partnership that promotes CEBPD’s own transcription and inflammatory SMC state transition, thus shedding new light on epigenetic reader and transcription factor cooperative actions in SMC pathobiology.
Evidence of Presence and Activation of the two Cell Cycle Kinases Nek6 and Nek7 in the ciliated Neuroretina
Authors: Janisch Kerstin M , Kasanuki J Mie , Davis Richard J , Tsang Stephen H 
Published: March 2020

AbstractThe serine/threonine NIMA kinases are widely found in eukaryotes. They are cell-cycle kinases that are associated with centrosomes and spindle apparatus and cilia. In cilia, NIMA kinases are reported to play a role in cilia length maintenance and deflagelation. Here we focus on the two Nek homologs, Nek6 and Nek7, and their potential role in retina. We report for the first-time expression ofnek6andnek7mRNA and protein in retinal tissue. In particular, we detect localisation of these kinases to photoreceptors outer segments. Moreover, we are able to show a light-dependent phosphorylation of the activation loop (serine 206) of Nek6/7 in rod outer segments, suggesting activation of these kinases is downstream of the phototransduction pathway. Indeed, we demonstrate that Nek6/7 phosphorylation in the retina is dependent onGrk1function. Furthermore, Nek6/7 phosphorylation can be stimulated in the brain by opiate drugs, suggesting that activation of Nek6/7 lies downstream of G protein coupled receptors activation, in general. Nek6/7 may couple photoreception with outer segment biogenesis through phosphorylation of downstream substrates, which may affect the microtubules of the axoneme.
RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses
Authors: Rangan Ramya , Zheludev Ivan N. , Das Rhiju 
Published: March 2020

AbstractAs the COVID-19 outbreak spreads, there is a growing need for a compilation of conserved RNA genome regions in the SARS-CoV-2 virus along with their structural propensities to guide development of antivirals and diagnostics. Using sequence alignments spanning a range of betacoronaviruses, we rank genomic regions by RNA sequence conservation, identifying 79 regions of length at least 15 nucleotides as exactly conserved over SARS-related complete genome sequences available near the beginning of the COVID-19 outbreak. We then confirm the conservation of the majority of these genome regions across 739 SARS-CoV-2 sequences reported to date from the current COVID-19 outbreak, and we present a curated list of 30 ‘SARS-related-conserved’ regions. We find that known RNA structured elements curated as Rfam families and in prior literature are enriched in these conserved genome regions, and we predict additional conserved, stable secondary structures across the viral genome. We provide 106 ‘SARS-CoV-2-conserved-structured’ regions as potential targets for antivirals that bind to structured RNA. We further provide detailed secondary structure models for the 5’ UTR, frame-shifting element, and 3’ UTR. Last, we predict regions of the SARS-CoV-2 viral genome have low propensity for RNA secondary structure and are conserved within SARS-CoV-2 strains. These 59 ‘SARS-CoV-2-conserved-unstructured’ genomic regions may be most easily targeted in primer-based diagnostic and oligonucleotide-based therapeutic strategies.
The transcriptional aftermath in two independently formed hybrids of the opportunistic pathogenCandida orthopsilosis
Authors: Hovhannisyan Hrant , Saus Ester , Ksiezopolska Ewa , Gabaldón Toni 
Published: March 2020

AbstractInterspecific hybridization can drive evolutionary adaptation to novel environments. TheSaccharomycotinaclade of budding yeasts includes many hybrid lineages, and hybridization has been proposed as a source for new pathogenic species.Candida orthopsilosisis an emerging opportunistic pathogen for which most clinical isolates are hybrids, each derived from one of at least four independent crosses between the same two parental lineages. To gain insight on the transcriptomic aftermath of hybridization in these pathogens, we analyzed allele-specific gene expression in two independently formed hybrid strains, and in a homozygous strain representative of one parental lineage. Our results show that the effect of hybridization on overall gene expression is rather limited, affecting ~4% of the studied genes. However, we identified a larger effect in terms of imbalanced allelic expression, affecting ~9.5% of the heterozygous genes in the hybrids. Some of these altered genes have functions related to pathogenicity, including zinc transport and superoxide dismutase activities. Additionally, the number of shared genes with imbalanced expression in the two independently formed hybrids was higher than random expectation, suggesting selective retention. While it remains unclear whether the observed imbalanced genes play a role in virulence, our results suggest that differences in allele-specific expression may add an additional layer of phenotypic plasticity to traits related to virulence inC. orthopsilosishybrids.ImportanceHow new pathogens emerge is an important question that remains largely unanswered. Some emerging yeast pathogens are hybrids originated through the crossing of two different species, but how hybridization contributes to a higher virulence is unclear. Here we show that hybrids selectively retain gene regulation plasticity inherited from the two parents, and that this plasticity affects genes involved in virulence.
APOBEC3C tandem domain proteins create super restriction factors against HIV-1
Authors: McDonnell Mollie M. , Crawford Kate H.D. , Dingens Adam S. , Bloom Jesse D. , Emerman Michael 
Published: March 2020

AbstractHumans encode proteins, called restriction factors, that inhibit replication of viruses like HIV-1. One family of antiviral proteins,apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3, shortened to A3) acts by deaminating cytidines to uridines during the reverse transcription reaction of HIV-1. TheA3locus encodes seven genes, namedA3A-A3H. These genes either have one or two cytidine deaminase domains and several of these A3s potently restrict HIV-1. A3C, which has only a single cytidine deaminase domain, however, inhibits HIV-1 only very weakly. We tested novel double domain protein combinations by genetically linking twoA3Cgenes to make a synthetic tandem domain protein. This protein created a “super restriction factor” that had more potent antiviral activity than the native A3C protein, which correlated with increased packaging into virions. Furthermore, disabling one of the active sites of the synthetic tandem domain protein results in an even greater increase in the antiviral activity—recapitulating a similar evolution seen in A3F and A3G (double domain A3s that only use a single catalytically active deaminase domain). These A3C tandem domain proteins do not have an increase in mutational activity, but instead inhibit formation of reverse transcription products which correlates with their ability to form large higher order complexes in cells. Finally, the A3C-A3C super restriction factor largely escaped antagonism by the HIV-1 viral protein, Vif.ImportanceAs a part of the innate immune system, humans encode proteins that inhibit viruses like HIV-1. These broadly acting antiviral proteins do not protect humans from viral infections because viruses encode proteins that antagonize the host antiviral proteins to evade the innate immune system. One such example of a host antiviral protein is APOBEC3C (A3C), which weakly inhibits HIV-1. Here, we show that we can improve the antiviral activity of A3C by duplicating the DNA sequence to create a synthetic tandem domain, and furthermore, are relatively resistant to the viral antagonist, Vif. Together, these data give insights about how nature has evolved a defense against viral pathogens like HIV.
Determining structures of biomacromolecular complexes from ambiguous NMR restraints and cryoEM data
Authors: Walser Reto , Milbradt Alexander G. 
Published: March 2020

AbstractIntegrated structural biology aims at combining different techniques to tackle challenging systems. Where individual techniques are not delivering structures of suitable quality, harnessing the strengths of various methods can often overcome this problem. X-ray crystallography and NMR have been the two most widely applied structural biology disciplines. In recent years cryoelectron microscopy (cryoEM) has become ever more powerful and is now capable of providing structures at resolutions comparable to those common in X-ray crystallography. Unfortunately, both NMR and cryoEM have inherent limitations on the system under study. However, the two techniques can be considered somewhat complementary as NMR has an upper and cryoEM a lower molecular weight (MW) limit. Here, we present a joint NMR and cryoEM methodology for the determination of biomacromolecular structures at the boundary region between the MW limits of the two techniques. The method relies on measuring chemical shift perturbations, which is the most readily accessible NMR parameter for characterizing the interaction of biomacromolecular complexes. Low-resolution cryoEM information yields global information on the shape of the complex and is used for complementing the local NMR data. We have successfully applied this method to the model system histidine-containing phosphoprotein (HPr) in complex with the glucose-specific acceptor protein IIAGlcfromEscherichia coli.
Recombination and sterility in inversion homo- and heterokaryotypes under a general counting model of chiasma interference
Authors: Kapperud Øystein 
Published: March 2020

AbstractIt has long been known that chiasmata are not independently generated along the chromosome, a phenomenon known aschiasma interference. In this paper, I suggest a model of chiasma interference that generalizes thePoisson model, thecounting model, thePoisson-skip modeland thetwo-pathway counting modelinto a single framework, and use it to derive infinite series expressions for the sterility and recombination pattern probabilities in inversion homo- and heterokaryotypes, and a closed-form expression for the special case of the two-pathway counting model in homokaryotypes.
Secreted TAL effectors protect symbiotic bacteria from entrapment within fungal hyphae
Authors: Richter Ingrid , Uzum Zerrin , Stanley Claire E. , Moebius Nadine , Stinear Timothy P. , Pidot Sacha J. , Ferling Iuliia , Hillmann Falk , Hertweck Christian 
Published: March 2020

AbstractThe association of the agriculturally significant phytopathogenic fungusRhizopus microsporuswith the bacterial endosymbiontBurkholderia rhizoxinicais a remarkable example of bacteria controlling host physiology and reproduction. Here, we show that a group of transcription activator-like effectors (TALEs) calledBurkholderiaTALE-like proteins (BATs) fromB. rhizoxinicaare essential for the establishment of the symbiosis. Mutants lacking BAT proteins are unable to induce host sporulation. Utilising novel microfluidic devices in combination with fluorescence microscopy we observed the accumulation of BAT-deficient mutants in specific fungal side-hyphae with accompanying increased fungal re-infection. High-resolution live imaging revealed septa biogenesis at the base of infected hyphae leading to compartmental trapping of BATdeficient endobacteria. Trapped endosymbionts showed reduced intracellular survival, suggesting a protective response from the fungal host against bacteria lacking specific effectors. These findings underscore the involvement of BAT proteins in maintaining a balance between mutualism and antagonism in bacterial-fungal interactions and provide deeper insights into the dynamic interactions between bacteria and eukaryotes.
Melatonin Protects T-2 toxin-induced neuronal stress through Acetylcholinesterase & Cytochrome P450 receptor-mediated signaling
Authors: Maroli Nikhil 
Published: March 2020

AbstractT-2 toxin is one of the potent mycotoxins responsible for several pathological conditions in humans and animals. This nonvolatile low molecular weight toxin compound shows strong resistance to degradation at room temperature as well as at autoclaving temperature. The inhibition of acetylcholinesterase and cytochrome P450 receptor by T-2 toxin leads to many pathological conditions as these two receptors involved in many pathways. Here, we have used melatonin as a protection agent against T-2 toxin in both receptor systems. Using molecular docking, molecular dynamics simulation and free energy calculations we have shown that melatonin can act as a potent inhibitor of T-2 toxin in acetylcholinesterase and cytochrome P450.
Bacterial envelope damage inflicted by bioinspired nanospikes grown in a hydrogel
Authors: Arias Sandra L. , Devorkin Joshua , Spear Jessica C. , Civantos Ana , Allain Jean Paul 
Published: March 2020

AbstractDevice-associated infections are one of the deadliest complications accompanying the use of biomaterials, and despite recent advances in the development of anti-biofouling strategies, biomaterials that exhibit both functional tissue restoration and antimicrobial activity have been challenging to achieve. Here, we report the fabrication of bio-inspired bactericidal nanospikes in bacterial cellulose and investigate the mechanism underlying this phenomenon. We demonstrate these structures affects preferentially stiff membranes like those in Gram-positive bacteria, but exhibit cytocompatibility towards mammalian cells, a requisite for tissue restoration. We also reveal the bactericidal activity of the nanospikes is due to a pressure-induced mechanism, which depends on the cell’s adherence time, nanospike’s geometry and spacing, cell shape, and mechanical properties of the cell wall. Our findings provide a better understanding of the mechanobiology of bacterial cells at the interface with nanoscale structures, which is fundamental for the rational design bactericidal topographies.