Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within ...resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.
Diet as a whole, encompassing food composition, calorie intake, and the length and frequency of fasting periods, affects the time span in which health and functional capacity are maintained. Here, we ...analyze aging and nutrition studies in simple organisms, rodents, monkeys, and humans to link longevity to conserved growth and metabolic pathways and outline their role in aging and age-related disease. We focus on feasible nutritional strategies shown to delay aging and/or prevent diseases through epidemiological, model organism, clinical, and centenarian studies and underline the need to avoid malnourishment and frailty. These findings are integrated to define a longevity diet based on a multi-pillar approach adjusted for age and health status to optimize lifespan and healthspan in humans.
Longo and Anderson synthesize and weigh the literature, from molecular mechanisms to epidemiology and spanning yeast to people, about what you should eat, how much you should eat, and when should you eat it to live a long and healthy life.
Astrocyte dysfunction in Alzheimer disease Acosta, Crystal; Anderson, Hope D.; Anderson, Christopher M.
Journal of neuroscience research,
December 2017, Letnik:
95, Številka:
12
Journal Article
There is a growing interest in controlling the synthesis of colloidal metal nanocrystals and thus tailoring their properties toward various applications. In this context, choosing an appropriate ...combination of reagents (e.g., salt precursor, reductant, capping agent, and stabilizer) plays a pivotal role in enabling the synthesis of metal nanocrystals with diversified sizes, shapes, and structures. Here we present a comprehensive review that highlights one of the key reagents for the synthesis of metal nanocrystals via chemical reduction: the reductants. We start with a brief introduction to the compounds commonly employed as reductants in the colloidal synthesis of metal nanocrystals by showing their oxidation half‐reactions and the corresponding oxidation potentials. Then we offer specific examples pertaining to the controlled synthesis of metal nanocrystals, followed by some fundamental aspects covering the general mechanisms of metal ion reduction based on the Marcus Theory. Afterwards, we present a case‐by‐case discussion on a wide variety of reductants, including their major properties, reduction mechanisms, and additional effects on the final products. We illustrate these aspects by selecting key examples from the literature and paying close attention to the underlying mechanism in each case. At the end, we conclude by summarizing the highlights of the review and providing some perspectives on future directions.
Reductants play a pivotal role in controlling the shapes and surface structures of noble‐metal nanocrystals, which affect both the reaction kinetics and thermodynamics significantly. By choosing an appropriate reductant, one is able to produce various noble metal nanocrystals with a variety of shapes, with typical examples including Pd, Pt, Au, Ag, and Rh.
The public health, tourism, fisheries, and ecosystem impacts from harmful algal blooms (HABs) have all increased over the past few decades. This has led to heightened scientific and regulatory ...attention, and the development of many new technologies and approaches for research and management. This, in turn, is leading to significant paradigm shifts with regard to, e.g., our interpretation of the phytoplankton species concept (strain variation), the dogma of their apparent cosmopolitanism, the role of bacteria and zooplankton grazing in HABs, and our approaches to investigating the ecological and genetic basis for the production of toxins and allelochemicals. Increasingly, eutrophication and climate change are viewed and managed as multifactorial environmental stressors that will further challenge managers of coastal resources and those responsible for protecting human health. Here we review HAB science with an eye toward new concepts and approaches, emphasizing, where possible, the unexpected yet promising new directions that research has taken in this diverse field.
Summary Background Artemisinin resistance in Plasmodium falciparum lengthens parasite clearance half-life during artemisinin monotherapy or artemisinin-based combination therapy. Absence of in-vitro ...and ex-vivo correlates of artemisinin resistance hinders study of this phenotype. We aimed to assess whether an in-vitro ring-stage survival assay (RSA) can identify culture-adapted P falciparum isolates from patients with slow-clearing or fast-clearing infections, to investigate the stage-dependent susceptibility of parasites to dihydroartemisinin in the in-vitro RSA, and to assess whether an ex-vivo RSA can identify artemisinin-resistant P falciparum infections. Methods We culture-adapted parasites from patients with long and short parasite clearance half-lives from a study done in Pursat, Cambodia, in 2010 (registered with ClinicalTrials.gov , number NCT00341003 ) and used novel in-vitro survival assays to explore the stage-dependent susceptibility of slow-clearing and fast-clearing parasites to dihydroartemisinin. In 2012, we implemented the RSA in prospective parasite clearance studies in Pursat, Preah Vihear, and Ratanakiri, Cambodia ( NCT01736319 ), to measure the ex-vivo responses of parasites from patients with malaria. Continuous variables were compared with the Mann-Whitney U test. Correlations were analysed with the Spearman correlation test. Findings In-vitro survival rates of culture-adapted parasites from 13 slow-clearing and 13 fast-clearing infections differed significantly when assays were done on 0–3 h ring-stage parasites (10·88% vs 0·23%; p=0·007). Ex-vivo survival rates significantly correlated with in-vivo parasite clearance half-lives (n=30, r =0·74, 95% CI 0·50–0·87; p<0·0001). Interpretation The in-vitro RSA of 0–3 h ring-stage parasites provides a platform for the molecular characterisation of artemisinin resistance. The ex-vivo RSA can be easily implemented where surveillance for artemisinin resistance is needed. Funding Institut Pasteur du Cambodge and the Intramural Research Program, NIAID, NIH.
Pursuit of the triple bottom line of economic, community and ecological sustainability has increased the complexity of fishery management; fisheries assessments require new types of data and analysis ...to guide science-based policy in addition to traditional biological information and modeling. We introduce the Fishery Performance Indicators (FPIs), a broadly applicable and flexible tool for assessing performance in individual fisheries, and for establishing cross-sectional links between enabling conditions, management strategies and triple bottom line outcomes. Conceptually separating measures of performance, the FPIs use 68 individual outcome metrics--coded on a 1 to 5 scale based on expert assessment to facilitate application to data poor fisheries and sectors--that can be partitioned into sector-based or triple-bottom-line sustainability-based interpretative indicators. Variation among outcomes is explained with 54 similarly structured metrics of inputs, management approaches and enabling conditions. Using 61 initial fishery case studies drawn from industrial and developing countries around the world, we demonstrate the inferential importance of tracking economic and community outcomes, in addition to resource status.
The efficiency of generating electricity from heat using concentrated solar power plants (which use mirrors or lenses to concentrate sunlight in order to drive heat engines, usually involving ...turbines) may be appreciably increased by operating with higher turbine inlet temperatures, but this would require improved heat exchanger materials. By operating turbines with inlet temperatures above 1,023 kelvin using closed-cycle high-pressure supercritical carbon dioxide (sCO
) recompression cycles, instead of using conventional (such as subcritical steam Rankine) cycles with inlet temperatures below 823 kelvin
, the relative heat-to-electricity conversion efficiency may be increased by more than 20 per cent. The resulting reduction in the cost of dispatchable electricity from concentrated solar power plants (coupled with thermal energy storage
) would be an important step towards direct competition with fossil-fuel-based plants and a large reduction in greenhouse gas emissions
. However, the inlet temperatures of closed-cycle high-pressure sCO
turbine systems are limited
by the thermomechanical performance of the compact, metal-alloy-based, printed-circuit-type heat exchangers used to transfer heat to sCO
. Here we present a robust composite of ceramic (zirconium carbide, ZrC) and the refractory metal tungsten (W) for use in printed-circuit-type heat exchangers at temperatures above 1,023 kelvin
. This composite has attractive high-temperature thermal, mechanical and chemical properties and can be processed in a cost-effective manner. We fabricated ZrC/W-based heat exchanger plates with tunable channel patterns by the shape-and-size-preserving chemical conversion of porous tungsten carbide plates. The dense ZrC/W-based composites exhibited failure strengths of over 350 megapascals at 1,073 kelvin, and thermal conductivity values two to three times greater than those of iron- or nickel-based alloys at this temperature. Corrosion resistance to sCO
at 1,023 kelvin and 20 megapascals was achieved
by bonding a copper layer to the composite surface and adding 50 parts per million carbon monoxide to sCO
. Techno-economic analyses indicate that ZrC/W-based heat exchangers can strongly outperform nickel-superalloy-based printed-circuit heat exchangers at lower cost.
We present the discovery of a nuclear transient with the Caltech–NRAO Stripe 82 Survey (CNSS), a dedicated radio transient survey carried out with the Karl G.Jansky Very Large Array (VLA). This ...transient, CNSS J001947.3+003527, exhibited a turn-on over a timescale of <~1 yr, increasing in flux density at 3 GHz from <0.14 mJy in 2014 February to 4.4 ± 0.1 mJy in 2015 March, reaching a peak luminosity of 5 x 10^28 erg s-1 Hz-1 around 2015 October. The association of CNSS J0019+00 with the nucleus (Gaia and
our very-long baseline interferometry positions are consistent to within 1 pc) of a nearby S0 Seyfert galaxy at 77 Mpc, together with the radio spectral evolution, implies that this transient is most likely a tidal disruption event (TDE). Our equipartition analysis indicates the presence of a ∼15,000 km s−1 outflow, having energy ∼1049 erg. We derive the radial density profile for the circumnuclear material in the host galaxy to be proportional to R−2.5. All of these properties suggest resemblance with radio-detected thermal TDEs like ASASSN-14li and XMMSL1 J0740-85. No significant X-ray or optical emission is detected from CNSS J0019+00, although this may simply be due to the thermal emission being weak during our late-time follow-up observations. From the CNSS survey we have obtained the first unbiased measurement of the rate of radio TDEs, R(>500μJy) of about 2 × 10−3 deg−2, or equivalently a volumetric rate of about 10 Gpc−3 yr−1. This rate implies that all-sky radio surveys such as the VLA Sky Survey and those planned with ASKAP, will find many tens of radio TDEs over the next few years.
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