Arbuscular mycorrhizal fungi as mediators of ecosystem responses to nitrogen deposition: A trait-based predictive framework

Anthropogenic nitrogen (N) deposition is exposing plants and their arbuscular mycorrhizal fungi (AMFs) to elevated N availability, often leading to shifts in communities of AMF. However, physiological trade-offs among AMF taxa in their response to N enrichment vs the ability to acquire other soil nutrients could have negative effects on plant and ecosystem productivity. It follows that information on the functional traits of AMF taxa can be used to generate predictions of their potential role in mediating ecosystem responses to N enrichment. Arbuscular mycorrhizal fungi taxa that produce extensive networks of external hyphae should forage for N and phosphorus (P) more effectively, but these services incur greater carbon (C) costs to the plant. If N enrichment ameliorates plant nutrient limitation, then plants may reduce C available for AMF, which in turn could eliminate AMF taxa with large extensive external hyphae from the soil community. As a result, the remaining AMF taxa may confer less P benefit to their host plants. Using a synthesis of data from the literature, we found that the ability of a taxon to persist in the face of increasing soil N availability was particularly high in isolates from the genus Glomus, but especially low among the Gigasporaceae. Across AMF genera, our data support the prediction that AMF with a tolerance for high soil N may confer a lower P benefit to their host plant. Relationships between high N tolerance and production of external hyphae were mixed. Synthesis. If the relationship between N tolerance and plant P benefit is widespread, then shifts in arbuscular mycorrhizal fungi communities associated with N deposition could have negative consequences for the ability of plants to acquire P and possibly other nutrients via a mycorrhizal pathway. Based on this relationship, we predict that arbuscular mycorrhizal fungi responses could constrain net primary productivity in P-limited ecosystems exposed to N enrichment. This prediction could be tested in future empirical and modelling studies

Recombinant factorVIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A

This work was supported by funding from Biogen, including funding for the editorial and writing support in the the development of this paper

Heritability of Lumbar Trabecular Bone Mechanical Properties in Baboons

Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6–32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h2) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h2 = 0.58), toughness (h2 = 0.64), and BV/TV (h2 = 0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p> <p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p> <p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p&gt

Molecular Genetics of T Cell Development

T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment

Tailoring Therapeutic Responses via Engineering Microenvironments with a Novel Synthetic Fluid Gel

This study reports the first fully synthetic fluid gel (SyMGels) using a simple poly(ethylene glycol) polymer. Fluid gels are an interesting class of materials: structured during gelation via shear-confinement to form microparticulate suspensions, through a bottom-up approach. Structuring in this way, when compared to first forming a gel and subsequently breaking it down, results in the formation of a particulate dispersion with particles “grown” in the shear flow. Resultantly, systems form a complex microstructure, where gelled particles concentrate remaining non-gelled polymer within the continuous phase, creating an amorphous-like interstitial phase. As such, these materials demonstrate mechanical characteristics typical of colloidal glasses, presenting solid-like behaviors at rest with defined yielding; likely through intrinsic particle-particle and particle-polymer interactions. To date, fluid gels have been fabricated using polysaccharides with relatively complex chemistries, making further modifications challenging. SyMGels are easily functionalised, using simple click-chemistry. This chemical flexibility, allows the creation of microenvironments with discrete biological decoration. Cellular control is demonstrated using MSC (mesenchymal stem cells)/chondrocytes and enables the regulation of key biomarkers such as aggrecan and SOX9. These potential therapeutic platforms demonstrate an important advancement in the biomaterial field, underpinning the mechanisms which drive their mechanical properties, and providing a versatile delivery system for advanced therapeutics

Time to go global: a consultation on global health competencies for postgraduate doctors

BACKGROUND: Globalisation is having profound impacts on health and healthcare. We solicited the views of a wide range of stakeholders in order to develop core global health competencies for postgraduate doctors. METHODS: Published literature and existing curricula informed writing of seven global health competencies for consultation. A modified policy Delphi involved an online survey and face-to-face and telephone interviews over three rounds. RESULTS: Over 250 stakeholders participated, including doctors, other health professionals, policymakers and members of the public from all continents of the world. Participants indicated that global health competence is essential for postgraduate doctors and other health professionals. Concerns were expressed about overburdening curricula and identifying what is 'essential' for whom. Conflicting perspectives emerged about the importance and relevance of different global health topics. Five core competencies were developed: (1) diversity, human rights and ethics; (2) environmental, social and economic determinants of health; (3) global epidemiology; (4) global health governance; and (5) health systems and health professionals. CONCLUSIONS: Global health can bring important perspectives to postgraduate curricula, enhancing the ability of doctors to provide quality care. These global health competencies require tailoring to meet different trainees' needs and facilitate their incorporation into curricula. Healthcare and global health are ever-changing; therefore, the competencies will need to be regularly reviewed and updated

Laguerre-Gaussian wave propagation in parabolic media

We report a new set of Laguerre-Gaussian wave-packets that propagate with periodical self-focusing and finite beam width in weakly guiding inhomogeneous media. These wave-packets are solutions to the paraxial form of the wave equation for a medium with parabolic refractive index. The beam width is defined as a solution of the Ermakov equation associated to the harmonic oscillator, so its amplitude is modulated by the strength of the medium inhomogeneity. The conventional Laguerre-Gaussian modes, available for homogenous media, are recovered as a particular case.Comment: 11 pages, 5 figure