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

RG-improved single-particle inclusive cross sections and forward-backward asymmetry in ttˉt\bar t production at hadron colliders

We use techniques from soft-collinear effective theory (SCET) to derive renormalization-group improved predictions for single-particle inclusive (1PI) observables in top-quark pair production at hadron colliders. In particular, we study the top-quark transverse-momentum and rapidity distributions, the forward-backward asymmetry at the Tevatron, and the total cross section at NLO+NNLL order in resummed perturbation theory and at approximate NNLO in fixed order. We also perform a detailed analysis of power corrections to the leading terms in the threshold expansion of the partonic hard-scattering kernels. We conclude that, although the threshold expansion in 1PI kinematics is susceptible to numerically significant power corrections, its predictions for the total cross section are in good agreement with those obtained by integrating the top-pair invariant-mass distribution in pair invariant-mass kinematics, as long as a certain set of subleading terms appearing naturally within the SCET formalism is included.Comment: 55 pages, 14 figures, 6 table

Ecosystem restoration strengthens pollination network resilience and function.

Land degradation results in declining biodiversity and the disruption of ecosystem functioning worldwide, particularly in the tropics. Vegetation restoration is a common tool used to mitigate these impacts and increasingly aims to restore ecosystem functions rather than species diversity. However, evidence from community experiments on the effect of restoration practices on ecosystem functions is scarce. Pollination is an important ecosystem function and the global decline in pollinators attenuates the resistance of natural areas and agro-environments to disturbances. Thus, the ability of pollination functions to resist or recover from disturbance (that is, the functional resilience) may be critical for ensuring a successful restoration process. Here we report the use of a community field experiment to investigate the effects of vegetation restoration, specifically the removal of exotic shrubs, on pollination. We analyse 64 plant-pollinator networks and the reproductive performance of the ten most abundant plant species across four restored and four unrestored, disturbed mountaintop communities. Ecosystem restoration resulted in a marked increase in pollinator species, visits to flowers and interaction diversity. Interactions in restored networks were more generalized than in unrestored networks, indicating a higher functional redundancy in restored communities. Shifts in interaction patterns had direct and positive effects on pollination, especially on the relative and total fruit production of native plants. Pollinator limitation was prevalent at unrestored sites only, where the proportion of flowers producing fruit increased with pollinator visitation, approaching the higher levels seen in restored plant communities. Our results show that vegetation restoration can improve pollination, suggesting that the degradation of ecosystem functions is at least partially reversible. The degree of recovery may depend on the state of degradation before restoration intervention and the proximity to pollinator source populations in the surrounding landscape. We demonstrate that network structure is a suitable indicator for pollination quality, highlighting the usefulness of interaction networks in environmental management

InterFace : A software package for face image warping, averaging, and principal components analysis

We describe InterFace, a software package for research in face recognition. The package supports image warping, reshaping, averaging of multiple face images, and morphing between faces. It also supports principal components analysis (PCA) of face images, along with tools for exploring the “face space” produced by PCA. The package uses a simple graphical user interface, allowing users to perform these sophisticated image manipulations without any need for programming knowledge. The program is available for download in the form of an app, which requires that users also have access to the (freely available) MATLAB Runtime environment

Is the meiofauna a good indicator for climate change and anthropogenic impacts?

Our planet is changing, and one of the most pressing challenges facing the scientific community revolves around understanding how ecological communities respond to global changes. From coastal to deep-sea ecosystems, ecologists are exploring new areas of research to find model organisms that help predict the future of life on our planet. Among the different categories of organisms, meiofauna offer several advantages for the study of marine benthic ecosystems. This paper reviews the advances in the study of meiofauna with regard to climate change and anthropogenic impacts. Four taxonomic groups are valuable for predicting global changes: foraminifers (especially calcareous forms), nematodes, copepods and ostracods. Environmental variables are fundamental in the interpretation of meiofaunal patterns and multistressor experiments are more informative than single stressor ones, revealing complex ecological and biological interactions. Global change has a general negative effect on meiofauna, with important consequences on benthic food webs. However, some meiofaunal species can be favoured by the extreme conditions induced by global change, as they can exhibit remarkable physiological adaptations. This review highlights the need to incorporate studies on taxonomy, genetics and function of meiofaunal taxa into global change impact research

ARIA-Versorgungspfade für die Allergenimmuntherapie 2019 = 2019 ARIA Care pathways for allergen immunotherapy

Allergen immunotherapy (MT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence- based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe MT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomaikers that can predict MT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate phannacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients

The Challenge of Regulation in a Minimal Photoautotroph: Non-Coding RNAs in Prochlorococcus

Prochlorococcus, an extremely small cyanobacterium that is very abundant in the world's oceans, has a very streamlined genome. On average, these cells have about 2,000 genes and very few regulatory proteins. The limited capability of regulation is thought to be a result of selection imposed by a relatively stable environment in combination with a very small genome. Furthermore, only ten non-coding RNAs (ncRNAs), which play crucial regulatory roles in all forms of life, have been described in Prochlorococcus. Most strains also lack the RNA chaperone Hfq, raising the question of how important this mode of regulation is for these cells. To explore this question, we examined the transcription of intergenic regions of Prochlorococcus MED4 cells subjected to a number of different stress conditions: changes in light qualities and quantities, phage infection, or phosphorus starvation. Analysis of Affymetrix microarray expression data from intergenic regions revealed 276 novel transcriptional units. Among these were 12 new ncRNAs, 24 antisense RNAs (asRNAs), as well as 113 short mRNAs. Two additional ncRNAs were identified by homology, and all 14 new ncRNAs were independently verified by Northern hybridization and 5′RACE. Unlike its reduced suite of regulatory proteins, the number of ncRNAs relative to genome size in Prochlorococcus is comparable to that found in other bacteria, suggesting that RNA regulators likely play a major role in regulation in this group. Moreover, the ncRNAs are concentrated in previously identified genomic islands, which carry genes of significance to the ecology of this organism, many of which are not of cyanobacterial origin. Expression profiles of some of these ncRNAs suggest involvement in light stress adaptation and/or the response to phage infection consistent with their location in the hypervariable genomic islands