Reflections on 40 Years of AIDS De Cock, Kevin M; Jaffe, Harold W; Curran, James W
Emerging infectious diseases,
06/2021, Volume:
27, Issue:
6
Journal Article
Peer reviewed
Open access
June 2021 marks the 40th anniversary of the first description of AIDS. On the 30th anniversary, we defined priorities as improving use of existing interventions, clarifying optimal use of HIV testing ...and antiretroviral therapy for prevention and treatment, continuing research, and ensuring sustainability of the response. Despite scientific and programmatic progress, the end of AIDS is not in sight. Other major epidemics over the past decade have included Ebola, arbovirus infections, and coronavirus disease (COVID-19). A benchmark against which to compare other global interventions is the HIV/AIDS response in terms of funding, coordination, and solidarity. Lessons from Ebola and HIV/AIDS are pertinent to the COVID-19 response. The fifth decade of AIDS will have to position HIV/AIDS in the context of enhanced preparedness and capacity to respond to other potential pandemics and transnational health threats.
Anthocyanins are secondary metabolites found in higher plants that contribute to the colors of flowers and fruits. In apples (Malus domestica Borkh.), several steps of the anthocyanin pathway are ...coordinately regulated, suggesting control by common transcription factors. A gene encoding an R2R3 MYB transcription factor was isolated from apple (cv Cripps' Pink) and designated MdMYB1. Analysis of the deduced amino acid sequence suggests that this gene encodes an ortholog of anthocyanin regulators in other plants. The expression of MdMYB1 in both Arabidopsis (Arabidopsis thaliana) plants and cultured grape cells induced the ectopic synthesis of anthocyanin. In the grape (Vitis vinifera) cells MdMYB1 stimulated transcription from the promoters of two apple genes encoding anthocyanin biosynthetic enzymes. In ripening apple fruit the transcription of MdMYB1 was correlated with anthocyanin synthesis in red skin sectors of fruit. When dark-grown fruit were exposed to sunlight, MdMYB1 transcript levels increased over several days, correlating with anthocyanin synthesis in the skin. MdMYB1 gene transcripts were more abundant in red skin apple cultivars compared to non-red skin cultivars. Several polymorphisms were identified in the promoter of MdMYB1. A derived cleaved amplified polymorphic sequence marker designed to one of these polymorphisms segregated with the inheritance of skin color in progeny from a cross of an unnamed red skin selection (a sibling of Cripps' Pink) and the non-red skin cultivar Golden Delicious. We conclude that MdMYB1 coordinately regulates genes in the anthocyanin pathway and the expression level of this regulator is the genetic basis for apple skin color.
Proanthocyanidins (PAs; or condensed tannins) can protect plants against herbivores, contribute to the taste of many fruits, and act as dietary antioxidants beneficial for human health. We have ...previously shown that in grapevine (Vitis vinifera) PA synthesis involves both leucoanthocyanidin reductase (LAR) and anthocyanidin reductase (ANR). Here we report the characterization of a grapevine MYB transcription factor VvMYBPA1, which controls expression of PA pathway genes including both LAR and ANR. Expression of VvMYBPA1 in grape berries correlated with PA accumulation during early berry development and in seeds. In a transient assay, VvMYBPA1 activated the promoters of LAR and ANR, as well as the promoters of several of the general flavonoid pathway genes. VvMYBPA1 did not activate the promoter of VvUFGT, which encodes the anthocyanin-specific enzyme UDP-glucose:flavonoid-3-O-glucosyltransferase, suggesting VvMYBPA1 is specific to regulation of PA biosynthesis in grapes. The Arabidopsis (Arabidopsis thaliana) MYB transcription factor TRANSPARENT TESTA2 (TT2) regulates PA synthesis in the seed coat of Arabidopsis. By complementing the PA-deficient seed phenotype of the Arabidopsis tt2 mutant with VvMYBPA1, we confirmed the function of VvMYBPA1 as a transcriptional regulator of PA synthesis. In contrast to ectopic expression of TT2 in Arabidopsis, constitutive expression of VvMYBPA1 resulted in accumulation of PAs in cotyledons, vegetative meristems, leaf hairs, and roots in some of the transgenic seedlings. To our knowledge, this is the first report of a MYB factor that controls genes of the PA pathway in fruit, including both LAR and ANR, and this single MYB factor can induce ectopic PA accumulation in Arabidopsis.
The evolving epidemiology of HIV/AIDS De Cock, Kevin M; Jaffe, Harold W; Curran, James W
AIDS (London),
06/2012, Volume:
26, Issue:
10
Journal Article
Peer reviewed
Open access
Following its recognition in 1981, the HIV/AIDS epidemic has evolved to become the greatest challenge in global health, with some 34 million persons living with HIV worldwide. Early epidemiologic ...studies identified the major transmission routes of the virus before it was discovered, and enabled the implementation of prevention strategies. Although the first identified cases were in MSM in the United States and western Europe, the greatest impact of the epidemic has been in sub-Saharan Africa, where most of the transmission occurs between heterosexuals. Nine countries in southern Africa account for less than 2% of the world's population but now they represent about one third of global HIV infections. Where broadly implemented, HIV screening of donated blood and antiretroviral treatment (ART) of pregnant women have been highly effective in preventing transfusion-associated and perinatally acquired HIV, respectively. Access to sterile equipment has also been a successful intervention for injection drug users. Prevention of sexual transmission has been more difficult. Perhaps the greatest challenge in terms of prevention has been in the global community of MSM in which HIV remains endemic at high prevalence. The most promising interventions are male circumcision for prevention of female-to-male transmission and use of ART to reduce infectiousness, but the extent to which these interventions can be brought to scale will determine their population-level impact.
Aims. We aim to find torus models that explain the observed high-resolution mid-infrared (MIR) measurements of active galactic nuclei (AGN). Our goal is to determine the general properties of the ...circumnuclear dusty environments. Methods. We used the MIR interferometric data of a sample of AGNs provided by the instrument MIDI/VLTI and followed a statistical approach to compare the observed distribution of the interferometric measurements with the distributions computed from clumpy torus models. We mainly tested whether the diversity of Seyfert galaxies can be described using the Standard Model idea, where differences are solely due to a line-of-sight (LOS) effect. In addition to the LOS effects, we performed different realizations of the same model to include possible variations that are caused by the stochastic nature of the dusty models. Results. We find that our entire sample of AGNs, which contains both Seyfert types, cannot be explained merely by an inclination effect and by including random variations of the clouds. Instead, we find that each subset of Seyfert type can be explained by different models, where the filling factor at the inner radius seems to be the largest difference. For the type 1 objects we find that about two thirds of our objects could also be described using a dusty torus similar to the type 2 objects. For the remaining third, it was not possible to find a good description using models with high filling factors, while we found good fits with models with low filling factors. Conclusions. Within our model assumptions, we did not find one single set of model parameters that could simultaneously explain the MIR data of all 21 AGN with LOS effects and random variations alone. We conclude that at least two distinct cloud configurations are required to model the differences in Seyfert galaxies, with volume-filling factors differing by a factor of about 5–10. A continuous transition between the two types cannot be excluded.
Context. Protoplanetary disks show large diversity regarding their morphology and dust composition. With mid-infrared interferometry the thermal emission of disks can be spatially resolved, and the ...distribution and properties of the dust within can be studied. Aims. Our aim is to perform a statistical analysis on a large sample of 82 disks around low- and intermediate-mass young stars, based on mid-infrared interferometric observations. We intend to study the distribution of disk sizes, variability, and the silicate dust mineralogy. Methods. Archival mid-infrared interferometric data from the MIDI instrument on the Very Large Telescope Interferometer are homogeneously reduced and calibrated. Geometric disk models are used to fit the observations to get spatial information about the disks. An automatic spectral decomposition pipeline is applied to analyze the shape of the silicate feature. Results. We present the resulting data products in the form of an atlas, containing N band correlated and total spectra, visibilities, and differential phases. The majority of our data can be well fitted with a continuous disk model, except for a few objects, where a gapped model gives a better match. From the mid-infrared size–luminosity relation we find that disks around T Tauri stars are generally colder and more extended with respect to the stellar luminosity than disks around Herbig Ae stars. We find that in the innermost part of the disks (r ≲ 1 au) the silicate feature is generally weaker than in the outer parts, suggesting that in the inner parts the dust is substantially more processed. We analyze stellar multiplicity and find that in two systems (AB Aur and HD 72106) data suggest a new companion or asymmetric inner disk structure. We make predictions for the observability of our objects with the upcoming Multi-AperTure mid-Infrared SpectroScopic Experiment (MATISSE) instrument, supporting the practical preparations of future MATISSE observations of T Tauri stars.
How is information distributed across large neuronal populations within a given brain area? Information may be distributed roughly evenly across neuronal populations, so that total information scales ...linearly with the number of recorded neurons. Alternatively, the neural code might be highly redundant, meaning that total information saturates. Here we investigate how sensory information about the direction of a moving visual stimulus is distributed across hundreds of simultaneously recorded neurons in mouse primary visual cortex. We show that information scales sublinearly due to correlated noise in these populations. We compartmentalized noise correlations into information-limiting and nonlimiting components, then extrapolate to predict how information grows with even larger neural populations. We predict that tens of thousands of neurons encode 95% of the information about visual stimulus direction, much less than the number of neurons in primary visual cortex. These findings suggest that the brain uses a widely distributed, but nonetheless redundant code that supports recovering most sensory information from smaller subpopulations.
Aims. The aim of this paper is to understand the relation in active galactic nuclei (AGNs) between the small obscuring torus and dusty structures at larger scales (5−10 pc). Methods. The dusty ...structures in AGNs are best observed in the mid-infrared. To achieve the necessary spatial resolution (20−100 millarcsec) we use ESO’s Mid-Infrared Interferometer (MIDI) with the 1.8 m Auxiliary Telescopes. We use the chromatic phases in the data to improve the spatial fidelity of the analysis. Results. We present interferometric data for NGC 1068 obtained in 2007 and 2012. We find no evidence of source variability. Many (u,v) points show non-zero chromatic phases indicating significant asymmetries. Gaussian model fitting of the correlated fluxes and chromatic phases provides a three-component best fit with estimates of sizes, temperatures, and positions of the components. A large, warm, offcenter component is required at a distance approximately 90 mas to the northwest at a position angle (PA) of ~−18°. Conclusions. The dust at 5−10 pc in the polar region contributes four times more to the mid-infrared flux at 12 μm than the dust located at the center. This dust may represent the inner wall of a dusty cone. If similar regions are heated by the direct radiation from the nucleus, then they will contribute substantially to the classification of many Seyfert galaxies as Type 2. Such a region is also consistent in other Seyfert galaxies (the Circinus galaxy, NGC 3783, and NGC 424).
A diversity of dusty AGN tori Burtscher, L; Meisenheimer, K; Tristram, K R W ...
Astronomy and astrophysics (Berlin),
10/2013, Volume:
558
Journal Article
Peer reviewed
Open access
The AGN-heated dust distribution is increasingly recognized not only as the absorber required in unifying models, but as a tracer for the reservoir that feeds the nuclear super-massive black hole. ...Yet, even its most basic structural properties are unknown for all but a few archetypical objects. In order to understand how the properties of AGN tori are related to feeding and obscuration, we need to resolve the matter distribution on parsec scales. Since most AGNs are unresolved in the mid-IR, even with the largest telescopes, we utilize the MID-infrared interferometric Instrument (MIDI) at the Very Large Telescope Interferometer (VLTI) that is sensitive to structures as small as a few milli-arcseconds. Variations in the relative contribution of extended dust in the narrow line region or heated by star formation vs. compact AGN-heated dust and non-thermal emission also have to be taken into account.
Summary Globally, men who have sex with men (MSM) continue to bear a high burden of HIV infection. In sub-Saharan Africa, same-sex behaviours have been largely neglected by HIV research up to now. ...The results from recent studies, however, indicate the widespread existence of MSM groups across Africa, and high rates of HIV infection, HIV risk behaviour, and evidence of behavioural links between MSM and heterosexual networks have been reported. Yet most African MSM have no safe access to relevant HIV/AIDS information and services, and many African states have not begun to recognise or address the needs of these men in the context of national HIV/AIDS prevention and control programmes. The HIV/AIDS community now has considerable challenges in clarifying and addressing the needs of MSM in sub-Saharan Africa; homosexuality is illegal in most countries, and political and social hostility are endemic. An effective response to HIV/AIDS requires improved strategic information about all risk groups, including MSM. The belated response to MSM with HIV infection needs rapid and sustained national and international commitment to the development of appropriate interventions and action to reduce structural and social barriers to make these accessible.
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