On the Spatial Coherence of Magnetic Ejecta: Measurements of Coronal Mass Ejections by Multiple Spacecraft Longitudinally Separated by 0.01 AU

Measurements of coronal mass ejections (CMEs) by multiple spacecraft at small radial separations but larger longitudinal separations is one of the ways to learn about the three-dimensional structure of CMEs. Here, we take advantage of the orbit of the Wind spacecraft that ventured to distances of up to 0.012 astronomical units (au) from the Sun-Earth line during the years 2000 to 2002. Combined with measurements from ACE, which is in a tight halo orbit around L1, the multipoint measurements allow us to investigate how the magnetic field inside magnetic ejecta (MEs) changes on scales of 0.005 - 0.012 au. We identify 21 CMEs measured by these two spacecraft for longitudinal separations of 0.007 au or more. We find that the time-shifted correlation between 30-minute averages of the non-radial magnetic field components measured at the two spacecraft is systematically above 0.97 when the separation is 0.008 au or less, but is on average 0.89 for greater separations. Overall, these newly analyzed measurements, combined with 14 additional ones when the spacecraft separation is smaller, point towards a scale length of longitudinal magnetic coherence inside MEs of 0.25 - 0.35 au for the magnitude of the magnetic field but 0.06 - 0.12 au for the magnetic field components. This finding raises questions about the very nature of MEs. It also highlights the need for additional "mesoscale" multi-point measurements of CMEs with longitudinal separations of 0.01 - 0.2 au.Comment: Published in ApJL, 6 page

Hepatitis C virus-specific cellular immune responses in individuals with no evidence of infection

The detection of hepatitis C virus (HCV)-specific T cell responses in HCV-uninfected, presumably unexposed, subjects could be due to an underestimation of the frequency of spontaneously resolving infections, as most acute HCV infections are clinically silent. To address this hypothesis, HCV-specific cellular immune responses were characterized, in individuals negative for an HCV PCR assay and humoral response, with (n = 32) or without (n = 33) risk of exposure to HCV. Uninfected volunteers (n = 20) with a chronically HCV-infected partner were included as positive controls for potential exposure to HCV and HCV infection, respectively. HCV-specific T cell responses in freshly isolated peripheral blood mononuclear cells were studied ex vivo by ELISPOT and CFSE-based proliferation assays using panels of HCV Core and NS3-derived peptides. A pool of unrelated peptides was used as a negative control, and a peptide mix of human cytomegalovirus, Epstein-Bar virus and Influenza virus as a positive control. Overall, 20% of presumably HCV-uninfected subject tested had detectable T-cell responses to the virus, a rate much higher than previous estimates of HCV prevalence in developed countries. This result would be consistent with unapparent primary HCV infections that either cleared spontaneously or remained undetected by conventional serological assays

BepiColombo’s Cruise Phase: Unique Opportunity for Synergistic Observations

The investigation of multi-spacecraft coordinated observations during the cruise phase of BepiColombo (ESA/JAXA) are reported, with a particular emphasis on the recently launched missions, Solar Orbiter (ESA/NASA) and Parker Solar Probe (NASA). Despite some payload constraints, many instruments onboard BepiColombo are operating during its cruise phase simultaneously covering a wide range of heliocentric distances (0.28 AU–0.5 AU). Hence, the various spacecraft configurations and the combined in-situ and remote sensing measurements from the different spacecraft, offer unique opportunities for BepiColombo to be part of these unprecedented multipoint synergistic observations and for potential scientific studies in the inner heliosphere, even before its orbit insertion around Mercury in December 2025. The main goal of this report is to present the coordinated observation opportunities during the cruise phase of BepiColombo (excluding the planetary flybys). We summarize the identified science topics, the operational instruments, the method we have used to identify the windows of opportunity and discuss the planning of joint observations in the future

HIV-1 Nef Targets MHC-I and CD4 for Degradation Via a Final Common β-COP–Dependent Pathway in T Cells

To facilitate viral infection and spread, HIV-1 Nef disrupts the surface expression of the viral receptor (CD4) and molecules capable of presenting HIV antigens to the immune system (MHC-I). To accomplish this, Nef binds to the cytoplasmic tails of both molecules and then, by mechanisms that are not well understood, disrupts the trafficking of each molecule in different ways. Specifically, Nef promotes CD4 internalization after it has been transported to the cell surface, whereas Nef uses the clathrin adaptor, AP-1, to disrupt normal transport of MHC-I from the TGN to the cell surface. Despite these differences in initial intracellular trafficking, we demonstrate that MHC-I and CD4 are ultimately found in the same Rab7+ vesicles and are both targeted for degradation via the activity of the Nef-interacting protein, β-COP. Moreover, we demonstrate that Nef contains two separable β-COP binding sites. One site, an arginine (RXR) motif in the N-terminal α helical domain of Nef, is necessary for maximal MHC-I degradation. The second site, composed of a di-acidic motif located in the C-terminal loop domain of Nef, is needed for efficient CD4 degradation. The requirement for redundant motifs with distinct roles supports a model in which Nef exists in multiple conformational states that allow access to different motifs, depending upon which cellular target is bound by Nef

A critical appraisal of appendage disparity and homology in fishes

Fishes are both extremely diverse and morphologically disparate. Part of this disparity can be observed in the numerous possible fin configurations that may differ in terms of the number of fins as well as fin shapes, sizes and relative positions on the body. Here, we thoroughly review the major patterns of disparity in fin configurations for each major group of fishes and discuss how median and paired fin homologies have been interpreted over time. When taking into account the entire span of fish diversity, including both extant and fossil taxa, the disparity in fin morphologies greatly complicates inferring homologies for individual fins. Given the phylogenetic scope of this review, structural and topological criteria appear to be the most useful indicators of fin identity. We further suggest that it may be advantageous to consider some of these fin homologies as nested within the larger framework of homologous fin‐forming morphogenetic fields. We also discuss scenarios of appendage evolution and suggest that modularity may have played a key role in appendage disparification. Fin modules re‐expressed within the boundaries of fin‐forming fields could explain how some fins may have evolved numerous times independently in separate lineages (e.g., adipose fin), or how new fins may have evolved over time (e.g., anterior and posterior dorsal fins, pectoral and pelvic fins). We favour an evolutionary scenario whereby median appendages appeared from a unique field of competence first positioned throughout the dorsal and ventral midlines, which was then redeployed laterally leading to paired appendages.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151971/1/faf12402_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151971/2/faf12402.pd

Endoskeletal structure in Cheirolepis (Osteichthyes, Actinopterygii), An early ray-finned fish

As the sister lineage of all other actinopterygians, the Middle to Late Devonian (Eifelian–Frasnian) Cheirolepis occupies a pivotal position in vertebrate phylogeny. Although the dermal skeleton of this taxon has been exhaustively described, very little of its endoskeleton is known, leaving questions of neurocranial and fin evolution in early ray‐finned fishes unresolved. The model for early actinopterygian anatomy has instead been based largely on the Late Devonian (Frasnian) Mimipiscis, preserved in stunning detail from the Gogo Formation of Australia. Here, we present re‐examinations of existing museum specimens through the use of high‐resolution laboratory‐ and synchrotron‐based computed tomography scanning, revealing new details of the neuro‐cranium, hyomandibula and pectoral fin endoskeleton for the Eifelian Cheirolepis trailli. These new data highlight traits considered uncharacteristic of early actinopterygians, including an uninvested dorsal aorta and imperforate propterygium, and corroborate the early divergence of Cheirolepis within actinopterygian phylogeny. These traits represent conspicuous differences between the endoskeletal structure of Cheirolepis and Mimipiscis. Additionally, we describe new aspects of the parasphenoid, vomer and scales, most notably that the scales display peg‐and‐socket articulation and a distinct neck. Collectively, these new data help clarify primitive conditions within ray‐finned fishes, which in turn have important implications for understanding features likely present in the last common ancestor of living osteichthyans

BepiColombo's Cruise Phase : Unique Opportunity for Synergistic Observations

The investigation of multi-spacecraft coordinated observations during the cruise phase of BepiColombo (ESA/JAXA) are reported, with a particular emphasis on the recently launched missions, Solar Orbiter (ESA/NASA) and Parker Solar Probe (NASA). Despite some payload constraints, many instruments onboard BepiColombo are operating during its cruise phase simultaneously covering a wide range of heliocentric distances (0.28 AU-0.5 AU). Hence, the various spacecraft configurations and the combined in-situ and remote sensing measurements from the different spacecraft, offer unique opportunities for BepiColombo to be part of these unprecedented multipoint synergistic observations and for potential scientific studies in the inner heliosphere, even before its orbit insertion around Mercury in December 2025. The main goal of this report is to present the coordinated observation opportunities during the cruise phase of BepiColombo (excluding the planetary flybys). We summarize the identified science topics, the operational instruments, the method we have used to identify the windows of opportunity and discuss the planning of joint observations in the future.Peer reviewe

HSV-2 glycoprotein gD targets the CC domain of tetherin and promotes tetherin degradation via lysosomal pathway.

BACKGROUND: HSV-2 is the major cause of genital herpes. We previously demonstrated that the host viral restriction factor tetherin restricts HSV-2 release and is antagonized by several HSV-2 glycoproteins. However, the mechanisms underlying HSV-2 glycoproteins mediated counteraction of tetherin remain unclear. In this study, we investigated whether tetherin restricts the cell-to-cell spread of HSV-2 and the mechanisms underlying HSV-2 gD mediated antagonism of tetherin. METHODS: Infectious center assays were used to test whether tetherin could affect cell-to-cell spread of HSV-2. Coimmunoprecipitation assays were performed to map the tetherin domains required for HSV-2 gD-mediated downregulation. Immunoflurence assays were performed to detect the accumulation of tetherin in lysosomes or proteasomes. All experiments were repeated for at least three times and the data were performed statistical analysis. RESULTS: 1) Tetherin restricts cell-to-cell spread of HSV-2; 2) HSV-2 gD specifically interacts with the CC domain of tetherin; 3) HSV-2 gD promotes tetherin to the lysosomal degradation pathway. CONCLUSIONS: Tetherin not only restricts HSV-2 release but also its cell-to-cell spread. In turn, HSV-2 gD targets the CC domain of tetherin and promotes its degradation in the lysosome. Findings in this study have increased our understanding of tetherin restriction and viral countermeasures

Rab7A Is Required for Efficient Production of Infectious HIV-1

Retroviruses take advantage of cellular trafficking machineries to assemble and release new infectious particles. Rab proteins regulate specific steps in intracellular membrane trafficking by recruiting tethering, docking and fusion factors, as well as the actin- and microtubule-based motor proteins that facilitate vesicle traffic. Using virological tests and RNA interference targeting Rab proteins, we demonstrate that the late endosome-associated Rab7A is required for HIV-1 propagation. Analysis of the late steps of the HIV infection cycle shows that Rab7A regulates Env processing, the incorporation of mature Env glycoproteins into viral particles and HIV-1 infectivity. We also show that siRNA-mediated Rab7A depletion induces a BST2/Tetherin phenotype on HIV-1 release. BST2/Tetherin is a restriction factor that impedes HIV-1 release by tethering mature virus particles to the plasma membrane. Our results suggest that Rab7A contributes to the mechanism by which Vpu counteracts the restriction factor BST2/Tetherin and rescues HIV-1 release. Altogether, our results highlight new roles for a major regulator of the late endocytic pathway, Rab7A, in the late stages of the HIV-1 replication cycle

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance:Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives:To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants:A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures:Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures:Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results:A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-β A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance:In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies