Rapamycin and Ageing: When,for How Long,and How Much?

正The mechanistic target of rapamycin(mTOR)is a nutrient and growth factor responsive kinase that modulates lifespan in species from yeast to mice(Johnson et al.,2013b).mTOR exists in two complexes within cells,mTOR complexⅠ(mTORC1)and mTOR complex 2(mTORC2)(Laplante and Sabatini,2012).Abundant evidence suggests that mTORC1is the primary mTOR complex involved in regulating longevity:mutations that reduce the     

How Much Ecology Do We Need to Know to Restore Mediterranean Ecosystems?

Despite important advances in ecological knowledge of Mediterranean‐type ecosystems, advances in restoration ecology have not seen a parallel increase in these systems. Although some concepts such as positive plant–plant interaction (facilitation) have received attention in the restoration ecology community, others such as phenotypic plasticity have not. Some concepts (e.g., environmental heterogeneity) are mature enough for a wide use in restoration, whereas available knowledge on others (e.g., facilitation, plasticity) is less conclusive. However, the scientific knowledge is in general enough to significantly improve the guidelines for restoration of Mediterranean ecosystems. Our review suggests that (1) the extent of facilitation in dry ecosystems is partially understood, with supporting, but somewhat contradictory empirical evidence for its potential use in restoration; (2) the influence of habitat heterogeneity on plant performance and plasticity is only beginning to be understood, with a strong bias toward patterns of structural heterogeneity and negligible information on functional heterogeneity; and (3) sound evaluations of phenotypic plasticity might be useful to increase the success of restoration practices in patchy Mediterranean environments. Future global change scenarios involving temperature rise, reduced precipitation, increased frequency of extreme climatic events, and important land use changes and fragmentation must be particularly considered when restoring Mediterranean ecosystems. Further research on how to incorporate results on facilitation, environmental heterogeneity, and plasticity within a global change framework is clearly needed.     

From Habits to Self-Regulation: How Do We Change?

The Yale Cognitive Science department hosted the conference “From Habits to Self-Regulation: How Do We Change?” on November 4 and 5, 2011, to showcase current research on self-control in cognitive science, psychology, and neuroscience. The conference included a panel discussion by four philosophers who gave context for the scope and limitations of research on self-control. The common theme concerning the best method to attain lasting change included becoming aware of what one wants to change, increasing commitment to the goal of change, and imagining all of the potential problems and solutions to those problems.     

Culture and Panic Disorder: How Far Have We Come?

Culture, Medicine, and Psychiatry -     

Vaccines against Tuberculosis: Where Are We and Where Do We Need to Go?

In this review we discuss recent progress in the development, testing, and clinical evaluation of new vaccines against tuberculosis (TB). Over the last 20 years, tremendous progress has been made in TB vaccine research and development: from a pipeline virtually empty of new TB candidate vaccines in the early 1990s, to an era in which a dozen novel TB vaccine candidates have been and are being evaluated in human clinical trials. In addition, innovative approaches are being pursued to further improve existing vaccines, as well as discover new ones. Thus, there is good reason for optimism in the field of TB vaccines that it will be possible to develop better vaccines than BCG, which is still the only vaccine available against TB.     

Integrated Surveys of Neglected Tropical Diseases in Southern Sudan: How Much Do They Cost and Can They Be Refined?

Background

Increasing emphasis on integrated control of neglected tropical diseases (NTDs) requires identification of co-endemic areas. Integrated surveys for lymphatic filariasis (LF), schistosomiasis and soil-transmitted helminth (STH) infection have been recommended for this purpose. Integrated survey designs inevitably involve balancing the costs of surveys against accuracy of classifying areas for treatment, so-called implementation units (IUs). This requires an understanding of the main cost drivers and of how operating procedures may affect both cost and accuracy of surveys. Here we report a detailed cost analysis of the first round of integrated NTD surveys in Southern Sudan.

Methods and Findings

Financial and economic costs were estimated from financial expenditure records and interviews with survey staff using an ingredients approach. The main outcome was cost per IU surveyed. Uncertain variables were subjected to univariate sensitivity analysis and the effects of modifying standard operating procedures were explored. The average economic cost per IU surveyed was USD 40,206 or USD 9,573, depending on the size of the IU. The major cost drivers were two key categories of recurrent costs: i) survey consumables, and ii) personnel.

Conclusion

The cost of integrated surveys in Southern Sudan could be reduced by surveying larger administrative areas for LF. If this approach was taken, the estimated economic cost of completing LF, schistosomiasis and STH mapping in Southern Sudan would amount to USD 1.6 million. The methodological detail and costing template provided here could be used to generate cost estimates in other settings and readily compare these to the present study, and may help budget for integrated and single NTDs surveys elsewhere.     

Bifurcation Analysis of Models with Uncertain Function Specification: How Should We Proceed?

When we investigate the bifurcation structure of models of natural phenomena, we usually assume that all model functions are mathematically specified and that the only existing uncertainty is with respect to the parameters of these functions. In this case, we can split the parameter space into domains corresponding to qualitatively similar dynamics, separated by bifurcation hypersurfaces. On the other hand, in the biological sciences, the exact shape of the model functions is often unknown, and only some qualitative properties of the functions can be specified: mathematically, we can consider that the unknown functions belong to a specific class of functions. However, the use of two different functions belonging to the same class can result in qualitatively different dynamical behaviour in the model and different types of bifurcation. In the literature, the conventional way to avoid such ambiguity is to narrow the class of unknown functions, which allows us to keep patterns of dynamical behaviour consistent for varying functions. The main shortcoming of this approach is that the restrictions on the model functions are often given by cumbersome expressions and are strictly model-dependent: biologically, they are meaningless. In this paper, we suggest a new framework (based on the ODE paradigm) which allows us to investigate deterministic biological models in which the mathematical formulation of some functions is unspecified except for some generic qualitative properties. We demonstrate that in such models, the conventional idea of revealing a concrete bifurcation structure becomes irrelevant: we can only describe bifurcations with a certain probability. We then propose a method to define the probability of a bifurcation taking place when there is uncertainty in the parameterisation in our model. As an illustrative example, we consider a generic predator–prey model where the use of different parameterisations of the logistic-type prey growth function can result in different dynamics in terms of the type of the Hopf bifurcation through which the coexistence equilibrium loses stability. Using this system, we demonstrate a framework for evaluating the probability of having a supercritical or subcritical Hopf bifurcation.     

Volatiles and Nonvolatiles in Flourensia campestris Griseb. (Asteraceae), How Much Do Capitate Glandular Trichomes Matter?

The distribution and ultrastructure of capitate glandular trichomes (GTs) in Flourensia species (Asteraceae) have been recently elucidated, but their metabolic activity and potential biological function remain unexplored. Selective nonvolatile metabolites from isolated GTs were strikingly similar to those found on leaf surfaces. The phytotoxic allelochemical sesquiterpene (–)‐hamanasic acid A ((–)‐HAA) was the major constituent (ca. 40%) in GTs. Although GTs are quaternary ammonium compounds (QACs)‐accumulating species, glycine betaine was not found in GTs; it was only present in the leaf mesophyll. Two (–)‐HAA accompanying surface secreted products: compounds 4‐hydroxyacetophenone (piceol; 1 ) and 2‐hydroxy‐5‐methoxyacetophenone ( 2 ), which were isolated and fully characterized (GC/MS, NMR), were present in the volatiles found in GTs. The essential oils of fresh leaves revealed ca. 33% monoterpenes, 26% hydrocarbon‐ and 30% oxygenated sesquiterpenes, most of them related to cadinene and bisabolene derivatives. Present results suggest a main role of GTs in determining the volatile and nonvolatile composition of F. campestris leaves. Based on the known activities of the compounds identified, it can be suggested that GTs in F. campestris would play key ecological functions in plant‐pathogen and plant‐plant interactions. In addition, the strikingly high contribution of compounds derived from cadinene and bisabolene pathways, highlights the potential of this species as a source of high‐valued bioproducts.