The severity of marine heatwaves (MHWs) that are increasingly impacting ocean ecosystems, including vulnerable coral reefs, has primarily been assessed using remotely sensed sea-surface temperatures ...(SSTs), without information relevant to heating across ecosystem depths. Here, using a rare combination of SST, high-resolution in-situ temperatures, and sea level anomalies observed over 15 years near Moorea, French Polynesia, we document subsurface MHWs that have been paradoxical in comparison to SST metrics and associated with unexpected coral bleaching across depths. Variations in the depth range and severity of MHWs was driven by mesoscale (10s to 100s of km) eddies that altered sea levels and thermocline depths and decreased (2007, 2017 and 2019) or increased (2012, 2015, 2016) internal-wave cooling. Pronounced eddy-induced reductions in internal waves during early 2019 contributed to a prolonged subsurface MHW and unexpectedly severe coral bleaching, with subsequent mortality offsetting almost a decade of coral recovery. Variability in mesoscale eddy fields, and thus thermocline depths, is expected to increase with climate change, which, along with strengthening and deepening stratification, could increase the occurrence of subsurface MHWs over ecosystems historically insulated from surface ocean heating by the cooling effects of internal waves.
Modified vaccinia virus Ankara (MVA) is the leading poxvirus vector for development of vaccines against diverse infectious diseases. This distinction is based on high expression of proteins and good ...immunogenicity despite an inability to assemble infectious progeny in human cells, which together promote efficacy and safety. Nevertheless, the basis for the host-range restriction is unknown despite past systematic attempts to identify the relevant missing viral gene(s). The search for host-range factors is exacerbated by the large number of deletions, truncations and mutations that occurred during the long passage history of MVA in chicken embryo fibroblasts. By whole genome sequencing of a panel of recombinant host-range extended (HRE) MVAs generated by marker rescue with 40 kbp segments of vaccinia virus DNA, we identified serine protease inhibitor 1 (SPI-1) as one of several candidate host-range factors present in those viruses that gained the ability to replicate in human cells. Electron microscopy revealed that the interruption of morphogenesis in human cells infected with MVA occurred at a similar stage as that of a vaccinia virus strain WR SPI-1 deletion mutant. Moreover, the introduction of the SPI-1 gene into the MVA genome led to more than a 2-log enhancement of virus spread in human diploid MRC-5 cells, whereas deletion of the gene diminished the spread of HRE viruses by similar extents. Furthermore, MRC-5 cells stably expressing SPI-1 also enhanced replication of MVA. A role for additional host range genes was suggested by the restoration of MVA replication to a lower level relative to HRE viruses, particularly in other human cell lines. Although multiple sequence alignments revealed genetic changes in addition to SPI-1 common to the HRE MVAs, no evidence for their host-range function was found by analysis thus far. Our finding that SPI-1 is host range factor for MVA should simplify use of high throughput RNAi or CRISPR/Cas single gene methods to identify additional viral and human restriction elements.
We present nebular phase optical and near-infrared spectroscopy of the Type Ia supernova (SN) 2017cbv. The early light curves of SN 2017cbv showed a prominent blue bump in the U, B, and g bands ...lasting for ∼5 days. One interpretation of the early light curve is that the excess blue light is due to shocking of the SN ejecta against a nondegenerate companion star-a signature of the single degenerate scenario. If this is the correct interpretation, the interaction between the SN ejecta and the companion star could result in significant H (or helium) emission at late times, possibly along with other species, depending on the companion star and its orbital separation. A search for H emission in our +302 d spectrum yields a nondetection, with a LH < 8.0 × 1035 erg s−1 (given an assumed distance of D = 12.3 Mpc), which we verified by implanting simulated H emission into our data. We make a quantitative comparison to models of swept-up material stripped from a nondegenerate companion star and limit the mass of hydrogen that might remain undetected to MH < 1 × 10−4 M . A similar analysis of helium star related lines yields a MHe < 5 × 10−4 M . Taken at face value, these results argue against a nondegenerate H- or He-rich companion in Roche lobe overflow as the progenitor of SN 2017cbv. Alternatively, there could be weaknesses in the envelope-stripping and radiative transfer models necessary to interpret the strong H and He flux limits.
Objective
In preterm infants, white matter (WM) abnormalities detected on magnetic resonance imaging (MRI) at term‐age are associated with early developmental delay. We set out to study this ...association in adolescents born pre‐term, by examining intellectual outcome in relation to markers of brain injury, focusing on the effects of WM reduction.
Methods
Seventy‐nine participants were recruited and assessed at a mean age of 16 years: 49 adolescents born preterm (<32 weeks' gestation) with a wide spectrum of brain injuries (including 22 with no identifiable brain injury at birth) and 30 term‐born controls. Data collected included: brain MRI scans, full‐scale intelligence quotient (IQ) scores, educational attainments, and behavioral scores. Measures of WM reduction included total volume, cross‐sectional area of the corpus callosum (CC), and ventricular dilatation. Cerebellar volumes and neuroradiological ratings were also included.
Results
WM volume and IQ were reduced in the preterm groups (both with and without brain injury). Total WM volume and CC area jointly explained 70% of IQ variance in the adolescents born preterm, irrespective of the presence or severity of brain abnormalities detected at birth or on follow‐up MRI. This relationship was not seen in controls. Importantly, correlations were also found with real‐world measures of academic achievement and behavioral difficulties.
Interpretation
Preterm birth has a long‐term effect on cognition, behavior, and future academic success primarily as a consequence of global brain WM reduction. This emphasizes the need for early therapeutic efforts to prevent WM injury and promote or optimize its development in preterm neonates. Ann Neurol 2011
Poxvirus replication involves synthesis of double-stranded RNA (dsRNA), which can trigger antiviral responses by inducing phosphorylation-mediated activation of protein kinase R (PKR) and stimulating ...2′5′-oligoadenylate synthetase (OAS). PKR inactivates the translation initiation factor eIF2α via phosphorylation, while OAS induces the endonuclease RNase L to degrade RNA. We show that poxvirus decapping enzymes D9 and D10, which remove caps from mRNAs, inhibit these antiviral responses by preventing dsRNA accumulation. Catalytic site mutations of D9 and D10, but not of either enzyme alone, halt vaccinia virus late protein synthesis and inhibit virus replication. Infection with the D9-D10 mutant was accompanied by massive mRNA reduction, cleavage of ribosomal RNA, and phosphorylation of PKR and eIF2α that correlated with a ∼15-fold increase in dsRNA compared to wild-type virus. Additionally, mouse studies show extreme attenuation of the mutant virus. Thus, vaccinia virus decapping, in addition to targeting mRNAs for degradation, prevents dsRNA accumulation and anti-viral responses.
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•Catalytic site mutations were introduced in vaccinia virus decapping enzymes, D9 and D10•D9 and D10 catalytic mutant virus exhibits replication defects and attenuation in mice•Mutant virus increases dsRNA, activates RNase L, and induces PKR phosphorylation•Protein synthesis is inhibited and RNA degraded in absence of functional D9 and D10
Double-stranded RNA is an important viral pathogen-associated molecular pattern that is synthesized during various virus infections. Liu et al. (2015) show that vaccinia virus decapping enzymes prevent double-strand RNA accumulation and activation of innate anti-viral response pathways.
Modified vaccinia virus Ankara (MVA) is an approved smallpox vaccine and a promising vaccine vector for other pathogens as well as for cancer therapeutics with more than 200 current or completed ...clinical trials. MVA was derived by passaging the parental Ankara vaccine virus hundreds of times in chick embryo fibroblasts during which it lost the ability to replicate in human and most other mammalian cells. Although this replication deficiency is an important safety feature, the genetic basis of the host restriction is not understood. Here, an unbiased human genome-wide RNAi screen in human A549 cells revealed that the zinc-finger antiviral protein (ZAP), previously shown to inhibit certain RNA viruses, is a host restriction factor for MVA, a DNA virus. Additional studies demonstrated enhanced MVA replication in several human cell lines following knockdown of ZAP. Furthermore, CRISPR-Cas9 knockout of ZAP in human A549 cells increased MVA replication and spread by more than one log but had no effect on a non-attenuated strain of vaccinia virus. The intact viral C16 protein, which had been disrupted in MVA, antagonized ZAP by binding and sequestering the protein in cytoplasmic punctate structures. Studies aimed at exploring the mechanism by which ZAP restricts MVA replication in the absence of C16 showed that knockout of ZAP had no discernible effect on viral DNA or individual mRNA or protein species as determined by droplet digital polymerase chain reaction, deep RNA sequencing and mass spectrometry, respectively. Instead, inactivation of ZAP reduced the number of aberrant, dense, spherical particles that typically form in MVA-infected human cells, suggesting that ZAP has a novel role in interfering with a late step in the assembly of infectious MVA virions in the absence of the C16 protein.
Interpretation of stable isotope ratios of carbon and nitrogen (δ(13)C and δ(15)N) is generally based on the assumption that with each trophic level there is a constant enrichment in the heavier ...isotope, leading to diet-tissue discrimination factors of 3.4‰ for (15)N (ΔN) and ∼0.5‰ for (13)C (ΔC). Diet-tissue discrimination factors determined from paired tissue and gut samples taken from 152 individuals from 26 fish species at Ningaloo Reef, Western Australia demonstrate a large amount of variability around constant values. While caution is necessary in using gut contents to represent diet due to the potential for high temporal variability, there were significant effects of trophic position and season that may also lead to variability in ΔN under natural conditions. Nitrogen enrichment increased significantly at higher trophic levels (higher tissue δ(15)N), with significantly higher ΔN in carnivorous species. Changes in diet led to significant changes in ΔN, but not tissue δ(15)N, between seasons for several species: Acanthurus triostegus, Chromis viridis, Parupeneus signatus and Pomacentrus moluccensis. These results confirm that the use of meta-analysis averages for ΔN is likely to be inappropriate for accurately determining diets and trophic relationships using tissue stable isotope ratios. Where feasible, discrimination factors should be directly quantified for each species and trophic link in question, acknowledging the potential for significant variation away from meta-analysis averages and, perhaps, controlled laboratory diets and conditions.
The oral mucosa is an attractive site for mucosal vaccination, however the thick squamous epithelium limits antigen uptake. Here we utilize a modified needle-free injector to deliver immunizations to ...the sublingual and buccal (SL/B) tissue of rhesus macaques. Needle-free SL/B vaccination with modified vaccinia Ankara (MVA) and a recombinant trimeric gp120 protein generates strong vaccine-specific IgG responses in serum as well as vaginal, rectal and salivary secretions. Vaccine-induced IgG responses show a remarkable breadth against gp70-V1V2 sequences from multiple clades of HIV-1. In contrast, topical SL/B immunizations generates minimal IgG responses. Following six intrarectal pathogenic SHIV-SF162P3 challenges, needle-free but not topical immunization results in a significant delay of acquisition of infection. Delay of infection correlates with non-neutralizing antibody effector function, Env-specific CD4
T-cell responses, and gp120 V2 loop specific antibodies. These results demonstrate needle-free MVA/gp120 oral vaccination as a practical and effective route to induce protective immunity against HIV-1.
In contrast to trophodynamic variations, the marked zonation in physical and biological processes across coral reefs and the concomitant changes in habitat and community structure are well ...documented. In this study, we demonstrate consistent spatial changes in the community-level trophodynamics of 46 species of fish across the fringing Ningaloo Reef, Western Australia, using tissue stable isotope and fatty acid analyses. Increasing nitrogen (δ
15
N) and decreasing carbon (δ
13
C) isotope ratios in the tissues of herbivores, planktivores and carnivores with increasing proximity to the ocean were indicative of increased reliance on oceanic productivity. In contrast, detritivores and corallivores displayed no spatial change in δ
15
N or δ
13
C, indicative of the dependence on reef-derived material across the reef. Higher δ
13
C, as well as increased benthic- and bacterial-specific fatty acids, suggested reliance on reef-derived production increased in back-reef habitats. Genus-level analyses supported community- and trophic group-level trends, with isotope modelling of species from five genera (
Abudefduf sexfasciatus
,
Chromis viridis
,
Dascyllus
spp.,
Pomacentrus
spp. and
Stegastes
spp.), demonstrating declining access to oceanic zooplankton and, in the case of
Pomacentrus
spp. and
Stegastes
spp., a switch to herbivory in the back-reef. The spatial changes in fish trophodynamics suggest that the relative roles of oceanic and reef-derived nutrients warrant more detailed consideration in reef-level community ecology.
Cryptic species that are morphologically similar co-occur because either the rate of competitive exclusion is very slow, or because they are not, in fact, ecologically similar. The processes that ...maintain cryptic local diversity may, therefore, be particularly subtle and difficult to identify. Here, we uncover differences among several cryptic species in their relative abundance across a depth gradient within a dominant and ecologically important genus of hard coral,
Pocillopora
. From extensive sampling unbiased toward morphological characters, at multiple depths on the fore reef around the island of Mo’orea, French Polynesia, we genetically identified 673 colonies in the
Pocillopora
species complex. We identified 14 mitochondrial Open Reading Frame haplotypes (mtORFs, a well-studied and informative species marker used for pocilloporids), which included at least six nominal species, and uncovered differences among haplotypes in their relative abundance at 5, 10, and 20 m at four sites around the island. Differences in relative haplotype abundance across depths were greater than differences among sites separated by several kilometers. The four most abundant species are often visibly indistinguishable at the gross colony level, yet they exhibited stark differences in their associations with light irradiance and daily water temperature variance. The pattern of community composition was associated with frequent cooling in deeper versus shallower water more than warmer temperatures in shallow water. Our results indicate that these cryptic species are not all ecologically similar. The differential abundance of
Pocillopora
cryptic species across depth should promote their coexistence at the reef scale, as well as promote resilience through response diversity.
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