Bacteriophage (phage) taxonomy has been in flux since its inception over four decades ago. Genome sequencing has put pressure on the classification system and recent years have seen significant ...changes to phage taxonomy. Here, we reflect on the state of phage taxonomy and provide a roadmap for the future, including the abolition of the order
and the families
,
and
. Furthermore, we specify guidelines for the demarcation of species, genus, subfamily and family-level ranks of tailed phage taxonomy.
Microbiomes from every environment contain a myriad of uncultivated archaeal and bacterial viruses, but studying these viruses is hampered by the lack of a universal, scalable taxonomic framework. We ...present vConTACT v.2.0, a network-based application utilizing whole genome gene-sharing profiles for virus taxonomy that integrates distance-based hierarchical clustering and confidence scores for all taxonomic predictions. We report near-identical (96%) replication of existing genus-level viral taxonomy assignments from the International Committee on Taxonomy of Viruses for National Center for Biotechnology Information virus RefSeq. Application of vConTACT v.2.0 to 1,364 previously unclassified viruses deposited in virus RefSeq as reference genomes produced automatic, high-confidence genus assignments for 820 of the 1,364. We applied vConTACT v.2.0 to analyze 15,280 Global Ocean Virome genome fragments and were able to provide taxonomic assignments for 31% of these data, which shows that our algorithm is scalable to very large metagenomic datasets. Our taxonomy tool can be automated and applied to metagenomes from any environment for virus classification.
The loading of chemical pollutants into stream systems can result in isolation of aquatic communities upstream of the discharge. Ecological theory suggests that isolation will result in species ...richness losses, but this potential indirect effect of stream pollution is not widely studied. Here, I present a study of fish assemblage structure in watersheds that have been longitudinally fragmented by abandoned mine drainage. A number of headwater streams in the Clarion River watershed of the upper Ohio River Basin, Pennsylvania, USA, have escaped any direct effects of abandoned mine drainage but have been isolated by severe pollution lower in the watershed. I evaluated the effects of watershed fragmentation on fish species richness, composition, and abundance by comparing the fish assemblages of 22 headwater streams embedded in watersheds receiving mine effluent with the assemblages of 34 reference streams with no apparent blockages to dispersal. I used a general linear model to evaluate the effect of isolation on species richness while accounting for stream size and water quality. I also used non-metric multidimensional scaling and permutational analysis of variance to evaluate differences in fish species composition between isolated and reference streams. Controlling for the effect of stream size, reference streams had a mean richness of 3.63 species (±0.27 SE), but isolated streams had a mean species richness of just 1.02 (±0.33), a 3.5× difference. Species occupying isolated stream systems were a nested subset of fish species in reference streams. Species composition also differed between isolated and reference streams, with higher relative abundance of Creek Chubs (Semotilus atromaculatus Mitchill, 1818) and lower relative abundances of Mottled Sculpin (Cottus bairdii Girard, 1850) and Brook Trout (Salvelinus fontinalis Mitchill, 1814) in isolated streams. These results illustrate an important indirect effect of water pollution in dendritic watersheds and provide evidence for the importance of connectivity in maintaining aquatic biodiversity.
Conspectus This Account presents recent advances in our understanding on the formation pathways of complex organic molecules (COMs) within interstellar analog ices on ice-coated interstellar ...nanoparticles upon interaction with ionizing radiation exploiting reflectron time-of-flight mass spectrometry (ReTOF-MS) coupled with tunable vacuum ultraviolet (VUV) single photon ionization (PI) and resonance enhanced multiphoton ionization (REMPI) of the subliming molecules during the temperature-programmed desorption (TPD) phase. Laboratory simulation experiments provided compelling evidence that key classes of complex organics (aromatic hydrocarbons, alcohols, ethers, aldehydes, enols, ketones, and carboxylic acids) can be synthesized upon exposure of astrophysically relevant model ices to ionizing radiation within and throughout the ices at temperatures as low as 5 K. Molecular mass growth processes can be initiated by suprathermal or electronically excited reactants along with barrierless radical–radical recombination if both radicals hold a proper recombination geometry. Methyl (CH3), amino (NH2), hydroxyl (OH), ethyl (C2H5), vinyl (C2H3), ethynyl (C2H), formyl (HCO), hydroxycarbonyl (HOCO), hydroxymethyl (CH2OH), methoxy (CH3O), and acetyl (CH3CO) represent readily available reactants for radical–radical recombination within the ices. Reactive singlet species were found to insert without barrier into carbon–hydrogen and carbon–carbon single bonds (carbene) leading to an extension of the carbon chain and may add to carbon–carbon double bonds (carbene, atomic oxygen) forming cyclic reaction products. These galactic cosmic ray-triggered nonequilibrium pathways overcome previous obstacles of hypothesized thermal grain-surface processes and operate throughout the ice at 5 K. Our investigations discriminate between multiple structural isomers such as alcohols/ethers, aldehydes/enols, and cyclic/acyclic carbonyls. These data provide quantitative, isomer selective input parameters for a cosmic ray-dictated formation of complex organics in interstellar ices and are fully able to replicate the astronomical observations of complex organics over typical lifetimes of molecular clouds of a few 106 to 107 years. Overall, PI-ReTOF-MS revealed that the processing of astrophysically relevant ices can lead to multifaceted mixtures of organics reaching molecular weights of up to 200 amu. Further advances in laboratory techniques beyond the FTIR-QMS limit are clearly desired not only to confidently assign detection in laboratory ice analog experiments of increasingly more complex molecules of interest but also from the viewpoint of future astronomical searches in the age of the Atacama Large Millimeter/submillimeter Array (ALMA).
A cobalt-phosphate based oxygen evolution catalyst (Co-Pi OEC) was electrochemically deposited onto the surface of a porous bismuth vanadate electrode doped with 2 atom% Mo (BiV0.98Mo0.02O4). The ...porous BiV0.98Mo0.02O4 electrode was prepared using a surfactant assisted metal-organic decomposition technique at 500 degreeC. The comparison of the photocurrent-voltage characteristics of the BiV0.98Mo0.02O4 electrodes with and without the presence of Co-Pi catalyst demonstrated that the Co-Pi catalyst enhanced the anodic photocurrent of the BiV0.98Mo0.02O4 electrode with its effect more pronounced at lower potentials. A stable photocurrrent density of 1.0 mA cm-2 at 1.0 V vs. Ag/AgCl was achieved under standard AM 1.5 illumination using 0.5M Na2SO4 aqueous solution in phosphate buffer at pH7. Relative to the BiV0.98Mo0.02O4 electrode, a sustained enhancement, nearly doubled photocurrent density was observed at 1.0 V vs. Ag/AgCl for Co-Pi/BiV0.98Mo0.02O4 composite photoelectrode. Significant performance gains are obtained on BiV0.98Mo0.02O4 electrodes upon modification with Co-Pi water oxidation catalyst.
Hepatic stellate cells (HSCs) drive hepatic fibrosis. Therapies that inactivate HSCs have clinical potential as antifibrotic agents. We previously identified acid ceramidase (aCDase) as an ...antifibrotic target. We showed that tricyclic antidepressants (TCAs) reduce hepatic fibrosis by inhibiting aCDase and increasing the bioactive sphingolipid ceramide. We now demonstrate that targeting aCDase inhibits YAP/TAZ activity by potentiating its phosphorylation-mediated proteasomal degradation via the ubiquitin ligase adaptor protein β-TrCP. In mouse models of fibrosis, pharmacologic inhibition of aCDase or genetic knockout of aCDase in HSCs reduces fibrosis, stromal stiffness, and YAP/TAZ activity. In patients with advanced fibrosis, aCDase expression in HSCs is increased. Consistently, a signature of the genes most down-regulated by ceramide identifies patients with advanced fibrosis who could benefit from aCDase targeting. The findings implicate ceramide as a critical regulator of YAP/TAZ signaling and HSC activation and highlight aCDase as a therapeutic target for the treatment of fibrosis.
The genomics of advanced breast cancer (ABC) has been described through tumour tissue biopsy sequencing, although these approaches are limited by geographical and temporal heterogeneity. Here we use ...plasma circulating tumour DNA sequencing to interrogate the genomic profile of ABC in 800 patients in the plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment of HER2 mutations in HER2 positive disease, co-occurring ESR1 and MAP kinase pathway mutations in HR + HER2- disease that associate with poor overall survival (p = 0.0092), and multiple PIK3CA mutations in HR + disease that associate with short progression free survival on fulvestrant (p = 0.0036). The fraction of cancer with a mutation, the clonal dominance of a mutation, varied between genes, and within hotspot mutations of ESR1 and PIK3CA. In ER-positive breast cancer subclonal mutations were enriched in an APOBEC mutational signature, with second hit PIK3CA mutations acquired subclonally and at sites characteristic of APOBEC mutagenesis. This study utilises circulating tumour DNA analysis in a large clinical trial to demonstrate the subclonal diversification of pre-treated advanced breast cancer, identifying distinct mutational processes in advanced ER-positive breast cancer, and novel therapeutic opportunities.
The acquisition of sensory information by animals is central to species interactions. In aquatic environments, most taxa use chemical cues to assess predation risk and other key ecological factors. A ...number of laboratory studies suggest that anthropogenic pollutants can disrupt chemoreception, even when at low, non-toxic concentrations, but there are few tests of whether real-world variation in water quality affects chemoreception. Here we investigate whether chemosensory perception of predators by the gray treefrog, Hyla versicolor, depends on water quality. We evaluated the anti-predator response of anuran tadpoles housed in water collected from three sites that represent strong contrasts in the concentration and types of dissolved solids: de-chlorinated tap water, water from an impaired stream, and treated wastewater effluent. Behavioral assays were conducted in laboratory aquaria. Chemical cues associated with predation were generated by feeding tadpoles to dragonfly predators held in containers, and then transferring aliquots of water from dragonfly containers to experimental aquaria. Tadpoles housed in tap water responded to predator cues with an activity reduction of 49%. Tadpoles housed in stream water and wastewater effluent responded to predator cues by reducing activity by 29% and 24% respectively. The results of factorial ANOVA support the hypothesis that the response to predator cues depended on water type. These results show that alteration of the chemical environment can mediate chemical perception of predators in aquatic ecosystems. Because most aquatic species rely on chemoreception to gather information on the location of food and predators, any impairment of sensory perception likely has important ecological consequences.
Carboxylic acid reductase (CAR) catalyzes the ATP- and NADPH-dependent reduction of carboxylic acids to the corresponding aldehydes. The enzyme is related to the nonribosomal peptide synthetases, ...consisting of an adenylation domain fused via a peptidyl carrier protein (PCP) to a reductase termination domain. Crystal structures of the CAR adenylation-PCP didomain demonstrate that large-scale domain motions occur between the adenylation and thiolation states. Crystal structures of the PCP-reductase didomain reveal that phosphopantetheine binding alters the orientation of a key Asp, resulting in a productive orientation of the bound nicotinamide. This ensures that further reduction of the aldehyde product does not occur. Combining crystallography with small-angle X-ray scattering (SAXS), we propose that molecular interactions between initiation and termination domains are limited to competing PCP docking sites. This theory is supported by the fact that (R)-pantetheine can support CAR activity for mixtures of the isolated domains. Our model suggests directions for further development of CAR as a biocatalyst.
For the last century, the source of sulfur in Earth's very first organisms has remained a fundamental, unsolved enigma. While sulfates and their organic derivatives with sulfur in the S(+VI) ...oxidation state represent core nutrients in contemporary biochemistry, the limited bioavailability of sulfates during Earth's early Archean period proposed that more soluble S(+IV) compounds served as the initial source of sulfur for the first terrestrial microorganisms. Here, we reveal via laboratory simulation experiments that the three simplest alkylsulfonic acids-water soluble organic S(+IV) compounds-can be efficiently produced in interstellar, sulfur-doped ices through interaction with galactic cosmic rays. This discovery opens a previously elusive path into the synthesis of vital astrobiological significance and untangles fundamental mechanisms of a facile preparation of sulfur-containing, biorelevant organics in extraterrestrial ices; these molecules can be eventually incorporated into comets and asteroids before their delivery and detection on Earth such as in the Murchison, Tagish Lake, and Allende meteorites along with the carbonaceous asteroid Ryugu.
PDF
