A Cure for HIV Infection: "Not in My Lifetime" or "Just Around the Corner"?

With the advent and stunning success of combination antiretroviral therapy (ART) to prolong and improve quality of life for persons with HIV infection, HIV research has been afforded the opportunity to pivot towards studies aimed at finding "a cure." The mere idea that cure of HIV might be possible has energized researchers and the community towards achieving this goal. Funding agencies, both governmental and private, have targeted HIV cure as a high priority; many in the field have responded to these initiatives and the cure research agenda is robust. In this "salon" two editors of Pathogens and Immunity, Michael Lederman and Daniel Douek ask whether curing HIV is a realistic, scalable objective. We start with an overview perspective and have asked a number of prominent HIV researchers to add to the discussion

A method for finding new sets of axioms for classes of semigroups

We introduce a general technique for finding sets of axioms for a given class of semigroups. To illustrate the technique, we provide new sets of defining axioms for groups of exponent n, bands, and semilattices

Sampling a Littoral Fish Assemblage: Comparison of Small-Mesh Fyke Netting and Boat Electrofishing

We compared small-mesh (4-mm) fyke netting and boat electrofishing for sampling a littoral fish assemblage in Muskegon Lake, Michigan. We hypothesized that fyke netting selects for small-bodied fishes and electrofishing selects for large-bodied fishes. Three sites were sampled during May (2004 and 2005), July (2005 only), and September (2004 and 2005). We found that the species composition of captured fish differed considerably between fyke netting and electrofishing based on nonmetric multidimensional scaling (NMDS). Species strongly associated with fyke netting (based on NMDS and relative abundance) included the brook silverside Labidesthes sicculus, banded killifish Fundulus diaphanus, round goby Neogobius melanostomus, mimic shiner Notropis volucellus, and bluntnose minnow Pimephales notatus, whereas species associated with electrofishing included the Chinook salmon Oncorhynchus tshawytscha, catostomids (Moxostoma spp. and Catostomus spp.), freshwater drum Aplodinotus grunniens, walleye Sander vitreus, gizzard shad Dorosoma cepedianum, and common carp Cyprinus carpio. The total length of fish captured by electrofishing was 12.8 cm (95% confidence interval ¼ 5.5– 17.2 cm) greater than that of fish captured by fyke netting. Size selectivity of the gears contributed to differences in species composition of the fish captured, supporting our initial hypothesis. Thus, small-mesh fyke nets and boat electrofishers provided complementary information on a littoral fish assemblage. Our results support use of multiple gear types in monitoring and research surveys of fish assemblages. Copyright by the American Fisheries Society 2007, Originally published in the North American Journal of Fisheries Management 27: 825-831, 2007

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

Are Cattle Surrogate Wildlife? Savanna Plant Community Composition Explained by Total Herbivory more than Herbivore Type

The widespread replacement of wild ungulate herbivores by domestic livestock in African savannas is composed of two interrelated phenomena: (1) loss or reduction in numbers of individual wildlife species or guilds and (2) addition of livestock to the system. Each can have important implications for plant community dynamics. Yet very few studies have experimentally addressed the individual, combined, and potentially interactive effects of wild vs. domestic herbivore species on herbaceous plant communities within a single system. Additionally, there is little information about whether, and in which contexts, livestock might functionally replace native herbivore wildlife or, alternatively, have fundamentally different effects on plant species composition. The Kenya Long-term Exclosure Experiment, which has been running since 1995, is composed of six treatment combinations of mega-herbivores, mesoherbivore ungulate wildlife, and cattle. We sampled herbaceous vegetation 25 times between 1999 and 2013. We used partial redundancy analysis and linear mixed models to assess effects of herbivore treatments on overall plant community composition and key plant species. Plant communities in the six different herbivore treatments shifted directionally over time and diverged from each other substantially by 2013. Plant community composition was strongly related (R2 = 0.92) to residual plant biomass, a measure of herbivore utilization. Addition of any single herbivore type (cattle, wildlife, or mega-herbivores) caused a shift in plant community composition that was proportional to its removal of plant biomass. These results suggest that overall herbivory pressure, rather than herbivore type or complex interactions among different herbivore types, was the main driver of changes in plant community composition. Individual plant species, however, did respond most strongly to either wild ungulates or cattle. Although these results suggest considerable functional similarity between a suite of native wild herbivores (which included grazers, browsers, and mixed feeders) and cattle (mostly grazers) with respect to understory plant community composition, responses of individual plant species demonstrate that at the plant-population-level impacts of a single livestock species are not functionally identical to those of a diverse group of native herbivores

Plant genotype influences aquatic-terrestrial ecosystem linkages through timing and composition of insect emergence

Terrestrial leaf litter provides aquatic insects with an energy source and habitat structure,and species differences in litter can influence aquatic insect emergence. Emerging insects also provide energy to riparian predators. We hypothesized that plant genetics would influence the composition and timing of emerging insect communities among individual genotypes of Populus angustifolia varying in litter traits. We also compared the composition and timing of emerging insect communities on litter from mixed genotypes of three cross types of a hybridizing cottonwood complex: P. angustifolia, P. fremontii, and their F1 hybrids. Using litter harvested from an experimental common garden, we measured emerging insect community composition, abundance, and production for 12 weeks in large litter packs affixed with emergence traps. Five major findings emerged. (1) In support of the genetic similarity hypothesis, we found that, among P. angustifolia tree genotypes, litter from more closely related genotypes had more similar litter thickness, nitrogen concentrations, decomposition rates, and emerging insect communities. (2) Genetic similarity was not correlated with other litter traits, although the litter fungal community was a strong predictor of emerging insect communities. (3) Litter decomposition rate, which was the strongest predictor of emerging aquatic insect communities, was influenced by litter thickness, litter N, and the litter fungal community. (4) In contrast to strong community composition differences among P. angustifolia genotypes, differences in community composition between P. fremontii and P. angustifolia were only marginally significant, and communities on F1 hybrids were indistinguishable from P. angustifolia despite genetic and litter trait differences. (5) Mixed litter packs muted the genetic effects observed in litter packs con- sisting of single genotypes. These results demonstrate that the genetic structure of riparian forests can affect the composition and timing of aquatic insect emergence. Because many riparian trees are clonal, including P. angustifolia, large clone size is likely to result in patches of genetically structured leaf litter that may influence the timing and composition of insect emergence within watersheds. Riparian restoration efforts incorporating different tree genotypes could also influence the biodiversity of emerging aquatic insects. Our work illustrates the importance of plant genes for community and ecosystem processes in riparian corridors

Wigs, disguises and child's play : solidarity in teacher education

It is generally acknowledged that much contemporary education takes place within a dominant audit culture, in which accountability becomes a powerful driver of educational practices. In this culture both pupils and teachers risk being configured as a means to an assessment and target-driven end: pupils are schooled within a particular paradigm of education. The article discusses some ethical issues raised by such schooling, particularly the tensions arising for teachers, and by implication, teacher educators who prepare and support teachers for work in situations where vocational aims and beliefs may be in in conflict with instrumentalist aims. The article offers De Certeau’s concept of ‘la perruque’ to suggest an opening to playful engagement for human ends in education, as a way of contending with and managing the tensions generated. I use the concept to recover a concept of solidarity for teacher educators and teachers to enable ethical teaching in difficult times

DMPP-4: Candidate sub-Neptune mass planets orbiting a naked-eye star

We present radial velocity measurements of the very bright ($V\sim5.7$) nearby F star, DMPP-4 (HD 184960). The anomalously low Ca II H&K emission suggests mass loss from planets orbiting a low activity host star. Periodic radial velocity variability with $\sim 10$ ms$^{-1}$ amplitude is found to persist over a $>4$ year timescale. Although the non-simultaneous photometric variability in four TESS sectors supports the view of an inactive star, we identify periodic photometric signals and also find spectroscopic evidence for stellar activity. We used a posterior sampling algorithm that includes the number of Keplerian signals, $N_\textrm{p}$, as a free parameter to test and compare (1) purely Keplerian models (2) a Keplerian model with linear activity correlation and (3) Keplerian models with Gaussian processes. A preferred model, with one Keplerian and quasi-periodic Gaussian process indicates a planet with a period of $P_\textrm{b} = 3.4982^{+0.0015}_{-0.0027}$ d and corresponding minimum mass of $m_\textrm{b}\,\textrm{sin}\,i = 12.2^{+1.8}_{-1.9}$ M$_\oplus$. Without further high time resolution observations over a longer timescale, we cannot definitively rule out the purely Keplerian model with 2 candidates planets with $P_\textrm{b} = 2.4570^{+0.0026}_{-0.0462}$ d, minimum mass $m_\textrm{b}\,\textrm{sin}\,i = 8.0^{+1.1}_{-1.5}$ M$_\oplus$ and $P_\textrm{c} = 5.4196^{+0.6766}_{-0.0030}$ d and corresponding minimum mass of $m_\textrm{b}\,\textrm{sin}\,i = 12.2^{+1.4}_{-1.6}$ M$_\oplus$. The candidate planets lie in the region below the lower-envelope of the Neptune Desert. Continued mass loss may originate from the highly irradiated planets or from an as yet undetected body in the system.Comment: 19 pages, 11 figures. Accepted for publication in MNRA