Induction of antibody-mediated neutralization in SIVmac239 by a naturally acquired V3 mutation

AbstractAchieving humoral immunity against human immunodeficiency virus (HIV) is a major obstacle in AIDS vaccine development. Despite eliciting robust humoral responses to HIV, exposed hosts rarely produce broadly neutralizing antibodies. The present study utilizes simian immunodeficiency virus (SIV) to identify viral epitopes that conferred antibody neutralization to clone SIV/17E-CL, an in vivo variant derived from neutralization resistant SIVmac239. Neutralization assays using rhesus macaque monoclonal antibodies were performed on viruses engineered to express single or multiple amino acid mutations. Results identified a single amino acid mutation, P334R, in the carboxy-terminal half of the V3 loop as a critical residue that induced neutralization while retaining normal glycoprotein expression on the surface of the virus. Furthermore, the R334 residue yielded neutralization sensitivity by antibodies recognizing diverse conformational and linear epitopes of gp120, suggesting that neutralization phenotype was a consequence of global structural changes of the envelope protein rather than a specific site epitope

First Constraints on Source Counts at 350 Microns

We have imaged a $\sim$6 arcminute$^2$ region in the Bo\"otes Deep Field using the 350 $\mu$m-optimised second generation Submillimeter High Angular Resolution Camera (SHARC II), achieving a peak 1$\sigma$ sensitivity of $\sim$5 mJy. We detect three sources above 3$\sigma$, and determine a spurious source detection rate of 1.09 in our maps. In the absence of $5\sigma$ detections, we rely on deep 24 $\mu$m and 20 cm imaging to deduce which sources are most likely to be genuine, giving two real sources. From this we derive an integral source count of 0.84$^{+1.39}_{-0.61}$ sources arcmin$^{-2}$ at $S>13$ mJy, which is consistent with 350 $\mu$m source count models that have an IR-luminous galaxy population evolving with redshift. We use these constraints to consider the future for ground-based short-submillimetre surveys.Comment: accepted for publication in The Astrophysical Journa

The Canada-UK Deep Submillimetre Survey: The Survey of the 14-hour field

We have used SCUBA to survey an area of 50 square arcmin, detecting 19 sources down to a 3sigma sensitivity limit of 3.5 mJy at 850 microns. We have used Monte-Carlo simulations to assess the effect of source confusion and noise on the SCUBA fluxes and positions, finding that the fluxes of sources in the SCUBA surveys are significantly biased upwards and that the fraction of the 850 micron background that has been resolved by SCUBA has been overestimated. The radio/submillmetre flux ratios imply that the dust in these galaxies is being heated by young stars rather than AGN. We have used simple evolution models based on our parallel SCUBA survey of the local universe to address the major questions about the SCUBA sources: (1) what fraction of the star formation at high redshift is hidden by dust? (2) Does the submillimetre luminosity density reach a maximum at some redshift? (3) If the SCUBA sources are proto-ellipticals, when exactly did ellipticals form? However, we show that the observations are not yet good enough for definitive answers to these questions. There are, for example, acceptable models in which 10 times as much high-redshift star formation is hidden by dust as is seen at optical wavelengths, but also acceptable ones in which the amount of hidden star formation is less than that seen optically. There are acceptable models in which very little star formation occurred before a redshift of three (as might be expected in models of hierarchical galaxy formation), but also ones in which 30% of the stars have formed by this redshift. The key to answering these questions are measurements of the dust temperatures and redshifts of the SCUBA sources.Comment: 41 pages (latex), 17 postscript figures, to appear in the November issue of the Astronomical Journa

Implications of the 2019–2020 megafires for the biogeography and conservation of Australian vegetation

Australia's 2019–2020 'Black Summer' bushfires burnt more than 8 million hectares of vegetation across the south-east of the continent, an event unprecedented in the last 200 years. Here we report the impacts of these fires on vascular plant species and communities. Using a map of the fires generated from remotely sensed hotspot data we show that, across 11 Australian bioregions, 17 major native vegetation groups were severely burnt, and up to 67–83% of globally significant rainforests and eucalypt forests and woodlands. Based on geocoded species occurrence data we estimate that >50% of known populations or ranges of 816 native vascular plant species were burnt during the fires, including more than 100 species with geographic ranges more than 500 km across. Habitat and fire response data show that most affected species are resilient to fire. However, the massive biogeographic, demographic and taxonomic breadth of impacts of the 2019–2020 fires may leave some ecosystems, particularly relictual Gondwanan rainforests, susceptible to regeneration failure and landscape-scale decline

State of Type 1 Diabetes Management and Outcomes from the T1D Exchange in 2016–2018

Objective: To provide a snapshot of the profile of adults and youth with type 1 diabetes (T1D) in the United States and assessment of longitudinal changes in T1D management and clinical outcomes in the T1D Exchange registry. Research Design and Methods: Data on diabetes management and outcomes from 22,697 registry participants (age 1–93 years) were collected between 2016 and 2018 and compared with data collected in 2010–2012 for 25,529 registry participants. Results: Mean HbA1c in 2016–2018 increased from 65 mmol/mol at the age of 5 years to 78 mmol/mol between ages 15 and 18, with a decrease to 64 mmol/mol by age 28 and 58–63 mmol/mol beyond age 30. The American Diabetes Association (ADA) HbA1c goal of 10-fold in children <12 years old. HbA1c levels were lower in CGM users than nonusers. Severe hypoglycemia was most frequent in participants ≥50 years old and diabetic ketoacidosis was most common in adolescents and young adults. Racial differences were evident in use of pumps and CGM and HbA1c levels. Conclusions: Data from the T1D Exchange registry demonstrate that only a minority of adults and youth with T1D in the United States achieve ADA goals for HbA1c

A deep ATCA 20cm radio survey of the AKARI Deep Field South near the South Ecliptic Pole

The results of a deep 20 cm radio survey at 20 cm are reported of the AKARI Deep Field South (ADF-S) near the South Ecliptic Pole (SEP), using the Australia Telescope Compact Array telescope, ATCA. The survey has 1 sigma detection limits ranging from 18.7--50 microJy per beam over an area of ~1.1 sq degrees, and ~2.5 sq degrees to lower sensitivity. The observations, data reduction and source count analysis are presented, along with a description of the overall scientific objectives, and a catalogue containing 530 radio sources detected with a resolution of 6.2" x 4.9". The derived differential source counts show a pronounced excess of sources fainter than ~1 mJy, consistent with an emerging population of star forming galaxies. Cross-correlating the radio with AKARI sources and archival data we find 95 cross matches, with most galaxies having optical R-magnitudes in the range 18-24 mag, and 52 components lying within 1" of a radio position in at least one further catalogue (either IR or optical). We have reported redshifts for a sub-sample of our catalogue finding that they vary between galaxies in the local universe to those having redshifts of up to 0.825. Associating the radio sources with the Spitzer catalogue at 24 microns, we find 173 matches within one Spitzer pixel, of which a small sample of the identifications are clearly radio loud compared to the bulk of the galaxies. The radio luminosity plot and a colour-colour analysis suggest that the majority of the radio sources are in fact luminous star forming galaxies, rather than radio-loud AGN. There are additionally five cross matches between ASTE or BLAST submillimetre galaxies and radio sources from this survey, two of which are also detected at 90 microns, and 41 cross-matches with submillimetre sources detected in the Herschel HerMES survey Public Data release.Comment: MNRAS accepted and in press 9 July 2012: 28 pages, 15 Figures, 17 Table

Coordinated Regulation of SIV Replication and Immune Responses in the CNS

Central nervous system (CNS) invasion during acute-stage HIV-infection has been demonstrated in a small number of individuals, but there is no evidence of neurological impairment at this stage and virus infection in brain appears to be controlled until late-stage disease. Using our reproducible SIV macaque model to examine the earliest stages of infection in the CNS, we identified immune responses that differentially regulate inflammation and virus replication in the brain compared to the peripheral blood and lymphoid tissues. SIV replication in brain macrophages and in brain of SIV-infected macaques was detected at 4 days post-inoculation (p.i.). This was accompanied by upregulation of innate immune responses, including IFNβ, IFNβ-induced gene MxA mRNA, and TNFα. Additionally, IL-10, the chemokine CCL2, and activation markers in macrophages, endothelial cells, and astrocytes were all increased in the brain at four days p.i. We observed synchronous control of virus replication, cytokine mRNA levels and inflammatory markers (MHC Class II, CD68 and GFAP) by 14 days p.i.; however, control failure was followed by development of CNS lesions in the brain. SIV infection was accompanied by induction of the dominant-negative isoform of C/EBPβ, which regulates SIV, CCL2, and IL6 transcription, as well as inflammatory responses in macrophages and astrocytes. This synchronous response in the CNS is in part due to the effect of the C/EBPβ on virus replication and cytokine expression in macrophage-lineage cells in contrast to CD4+ lymphocytes in peripheral blood and lymphoid tissues. Thus, we have identified a crucial period in the brain when virus replication and inflammation are controlled. As in HIV-infected individuals, though, this control is not sustained in the brain. Our results suggest that intervention with antiretroviral drugs or anti-inflammatory therapeutics with CNS penetration would sustain early control. These studies further suggest that interventions should target HIV-infected individuals with increased CCL2 levels or HIV RNA in the CNS

Mean-atom-trajectory model for the velocity autocorrelation function of monatomic liquids

We present a model for the motion of an average atom in a liquid or supercooled liquid state and apply it to calculations of the velocity autocorrelation function $Z(t)$ and diffusion coefficient $D$. The model trajectory consists of oscillations at a distribution of frequencies characteristic of the normal modes of a single potential valley, interspersed with position- and velocity-conserving transits to similar adjacent valleys. The resulting predictions for $Z(t)$ and $D$ agree remarkably well with MD simulations of Na at up to almost three times its melting temperature. Two independent processes in the model relax velocity autocorrelations: (a) dephasing due to the presence of many frequency components, which operates at all temperatures but which produces no diffusion, and (b) the transit process, which increases with increasing temperature and which produces diffusion. Because the model provides a single-atom trajectory in real space and time, including transits, it may be used to calculate all single-atom correlation functions.Comment: LaTeX, 8 figs. This is an updated version of cond-mat/0002057 and cond-mat/0002058 combined Minor changes made to coincide with published versio

Herschel-ATLAS: Evolution of the 250 μm luminosity function out to z = 0.5

We have determined the luminosity function of 250 μm-selected galaxies detected in the ~14 deg2 science demonstration region of the Herschel-ATLAS project out to a redshift of z = 0.5. Our findings very clearly show that the luminosity function evolves steadily out to this redshift. By selecting a sub-group of sources within a fixed luminosity interval where incompleteness effects are minimal, we have measured a smooth increase in the comoving 250 μm luminosity density out to z = 0.2 where it is 3.6-0.9+1.4 times higher than the local value.S.D. Acknowledges the UK STFC for support