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     

Consequences of Environmental Fluctuations on Taylor’s Power Law and Implications for the Dynamics and Persistence of Populations

Conservation Biologists have found that demographic stochasticity causes the mean time to extinction to increase exponentially with population size. This has proved helpful in analyses determining extinction times and characterizing the pathway to extinction. The aim of this investigation is to explore the possible interactions between environmental/demographic noises and the scaling effect of the mean population size with its variance, which is expected to follow Taylor’s power law relationship. We showed that the combined effects of environmental/demographic noises and the scaling of population size variability interact with the population dynamics and affect the mean time to extinction.     

Dead or gone? Bayesian inference on mortality for the dispersing sex

Estimates of age‐specific mortality are regularly used in ecology, evolution, and conservation research. However, estimating mortality of the dispersing sex, in species where one sex undergoes natal dispersal, is difficult. This is because it is often unclear whether members of the dispersing sex that disappear from monitored areas have died or dispersed. Here, we develop an extension of a multievent model that imputes dispersal state (i.e., died or dispersed) for uncertain records of the dispersing sex as a latent state and estimates age‐specific mortality and dispersal parameters in a Bayesian hierarchical framework. To check the performance of our model, we first conduct a simulation study. We then apply our model to a long‐term data set of African lions. Using these data, we further study how well our model estimates mortality of the dispersing sex by incrementally reducing the level of uncertainty in the records of male lions. We achieve this by taking advantage of an expert's indication on the likely fate of each missing male (i.e., likely died or dispersed). We find that our model produces accurate mortality estimates for simulated data of varying sample sizes and proportions of uncertain male records. From the empirical study, we learned that our model provides similar mortality estimates for different levels of uncertainty in records. However, a sensitivity of the mortality estimates to varying uncertainty is, as can be expected, detectable. We conclude that our model provides a solution to the challenge of estimating mortality of the dispersing sex in species with data deficiency due to natal dispersal. Given the utility of sex‐specific mortality estimates in biological and conservation research, and the virtual ubiquity of sex‐biased dispersal, our model will be useful to a wide variety of applications.     

How Large is the Probability for the Estimate of a Variance Component to be Negative?

For a balanced one-way classification, where the normally distributed observations obey a random model y_ij=μ+b_i+c_ij with two variance components var (b_i) = δ and var (c_ij) = δ, the probability is given that the analysis of variance estimate of δ will be negative. This probability depends on δ/δ and the degrees of freedom in the ANOVA table. Tables for this probability are given. If the normally distributed observations obey an intra-class correlation model, the probability that the Mean Square between groups is smaller than the Mean Square within groups can also be evaluated from the given tables.     

Control of Dead end localization and activity – Implications for the function of the protein in antagonizing miRNA function

Dead end (dnd) is a vertebrate-specific component of the germ plasm and germ-cell granules that is crucial for germ-cell development in zebrafish and mouse. Dnd counteracts the inhibitory function of miRNAs, thereby facilitating the expression of proteins such as Nanos and Tdrd7 in the germ cells. Here, we show that cis-acting elements within dnd mRNA and the RNA recognition motive (RRM) of the protein are essential for targeting protein expression to the germ cells and to the perinuclear granules, respectively. We demonstrate that as it executes its function, Dnd translocates between the germ-cell nucleus and germ-cell granules. This phenomenon is not observed in proteins mutated in the RRM motif, correlating with loss of function of Dnd. Based on molecular modeling, we identify the putative RNA binding domain of Dnd as a canonical RRM and propose that this domain is important for protein subcellular localization and function.     

How reliable are the Powell–Wetherall plot method and the maximum-length approach? Implications for length-based studies of growth and mortality

Length-based methods are the cornerstone of many population studies and stock assessments. This study tested two widely used methods: the Powell–Wetherall (P–W) plot and the L_max approach (i.e., estimating L_∞ directly from L_max). In most simulations, P–W estimates of the ratio total mortality/growth (Z/K ratio) were biased beyond acceptable limits (bias?>?30%). Bias in Z/K showed a complex behavior, without possible corrections. Estimates of asymptotic length (L_∞) were less biased than Z/K, but were very sensitive to intra-cohort variability in growth and to changes in the occurrence of large individuals in the sample. Exclusion of the largest size classes during the regression procedure or weighing by abundance does not solve these issues. Perfect linearization of the data and extremely narrow confidence intervals for Z/K will lead users to erroneous overconfidence in outputs. Clearly, the P–W method is not suitable for the assessment of Z/K ratios of natural populations. Estimation of L_∞ may be tentatively possible under very specific conditions, with necessary external verifications. Also, this study demonstrates that there is no way to estimate L_∞ directly from L_max, since there is no particular relationship to expect a priori between L_∞ and L_max. Errors in estimating L_∞ directly affect the estimate of the growth constant K and all other subsequent calculations in population studies, stock assessments and ecosystem models. New approaches are urgently needed for length-based studies of body growth (e.g., unconstrained curve fit with subsequent bootstrapping), that consider the inherent uncertainty regarding the underlying data and processes.     

How Does Connectivity Between Cortical Areas Depend on Brain Size? Implications for Efficient Computation

A formula for an average connectivity between cortical areas in mammals is derived. Based on comparative neuroanatomical data, it is found, surprisingly, that this connectivity is either only weakly dependent or independent of brain size. It is discussed how this formula can be used to estimate the average length of axons in white matter. Other allometric relations, such as cortical patches and area sizes vs. brain size, are also provided. Finally, some functional implications, with an emphasis on efficient cortical computation, are discussed as well.     

How Useful are Ant Assemblages for Monitoring Habitat Disturbance on Grasslands in South Eastern Australia?

Native grasslands are one of the most endangered ecosystems in south eastern Australia. Conservation of grassland remnants and development of effective indicator groups to monitor their quality is a high priority. Recent surveys of epigaeic invertebrates have revealed several candidate groups for this. Ants are a popular focal group for invertebrate surveys in the region. The ant species richness and functional groups on four series of grassland sites in Victoria suggest that small scale heterogeneity is sufficiently high that the predictive indicator values of ants are limited, and that ants may not be sufficiently sensitive to floristic change to employ them alone in monitoring grassland condition in the region.     

Coiled-Coil Formation on Lipid Bilayers—Implications for Docking and?Fusion Efficiency

Coiled-coil formation of four different oligopeptides was characterized in solution, on hydrogels, and on membranes by employing circular dichroism spectroscopy, surface plasmon resonance spectroscopy, attenuated total reflection infrared spectroscopy, and ellipsometry. Peptide sequences rich in either glutamic acid (E: E3Cys, i-E3Cys) or lysine (K: K3Cys, i-K3Cys) were used to represent minimal mimics of eukaryotic SNARE motifs. Half of the peptides were synthesized in reverse sequence, so that parallel and antiparallel heptad coiled-coil structures were formed. Either E-peptides or K-peptides were attached covalently to phospholipid anchors via maleimide chemistry, and served as receptors for the recognition of the corresponding binding partners added to solution. Attenuated total reflection infrared spectroscopy of single bilayers confirmed the formation of coiled-coil complexes at the membrane interface. Coiled-coil formation in solution, as compared with association at the membrane surface, displays considerably larger binding constants that are largely attributed to loss of translational entropy at the interface. Finally, the fusogenicity of the various coiled-coil motifs was explored, and the results provide clear evidence that hemifusion followed by full fusion requires a parallel orientation of α-helices, whereas antiparallel oriented coiled-coil motifs display only docking.     

How do stone knappers predict and control the outcome of flaking? Implications for understanding early stone tool technology

The aim of the current study was to provide detailed data on the skill at controlling conchoidal fracture, data that may be used to help infer the processes responsible for generating the technological diversity observed in Early Stone Age sites. We conducted an experiment with modern stone knappers with different skill levels and systematically analyzed not only the products of flaking (i.e., detached flakes) but also the intentions prior to flaking, as well as the actions taken to control the shape of a flake through direct hard-hammer percussion. Only modern stone knappers with extensive knapping experience proved capable of predicting and controlling the shape of a flake, which indicated the significant difficulty of controlling the shape of flakes. Evidence was found that knowing the consequence of a strike given to a core at hand requires the acute exploration of the properties of the core and hammerstone to comply with the higher-order relationship among potential platform variables, kinetic energy of the hammerstone at impact, and flake dimension that reflects the constraints of conchoidal fracture. We argue that without this ability, controlling the shape of a flake or the organized débitage of flakes observed in some of the Early Stone Age sites may not have been possible. We further suggest that, given the difficulty and the nature of the skill, the evidence of precise control of conchoidal fracture in the Early Stone Age record may be indicative of the recurrence of a learning situation that allows the transmission of the skill, possibly through providing the opportunities for first-hand experience.     

Altered Community Flammability in Florida’s Apalachicola Ravines and Implications for the Persistence of the Endangered Conifer Torreya taxifolia

Plant species and communities often reflect historic fire regimes via ecological and evolutionary responses to recurrent fires. Plant communities of the southeastern USA experience a wide array of fire regimes, perhaps nowhere more marked than the juxtaposition of fire-prone uplands and adjacent mesic ravines along Florida’s Apalachicola River. The ravines contain many endemic and disjunct species, most notably the endangered endemic conifer Torreya taxifolia. A rapid decline in T. taxifolia over the past 60 years has been associated with widespread replacement by other tree species. To understand the changes accompanying the shift in ravine composition, we compared leaf litter flammability of nine historic and contemporary species. We measured maximum flame height, flame duration, smoldering duration, mass loss, absorptive capacity, and drying rate. Ordination and perMANOVA suggest the nine species segregated into three distinct groups: the fire-impeding T. taxifolia and Taxus floridana; an intermediate group of three deciduous angiosperms; and a mixed cluster of four flammable species. Results suggest T. taxifolia and T. floridana were fire-impeding species in these communities, while contemporary dominants burn similarly to the upslope pyric species. The increasing presence of fire-facilitating species may portend a shifting fire regime that further imperils T. taxifolia and other rare species in the formerly fire-safe ravines.     

Germinal and Somatic Trisomy 21 Mosaicism: How Common is it,What are the Implications for Individual Carriers and How Does it Come About?

It is well known that varying degrees of mosaicism for Trisomy 21, primarily a combination of normal and Trisomy 21 cells within individual tissues, may exist in the human population. This involves both Trisomy 21 mosaicism occurring in the germ line and Trisomy 21 mosaicism documented in different somatic tissues, or indeed a combination of both in the same subjects. Information on the incidence of Trisomy 21 mosaicism in different tissue samples from people with clinical features of Down syndrome as well as in the general population is, however, still limited. One of the main reasons for this lack of detailed knowledge is the technological problem of its identification, where in particular low grade/cryptic Trisomy 21 mosaicism, i.e. occurring in less than 3-5% of the respective tissues, can only be ascertained by fluorescence in situ hybridization (FISH) methods on large cell populations from the different tissue samples.In this review we summarize current knowledge in this field with special reference to the question on the likely incidence of germinal and somatic Trisomy 21 mosaicism in the general population and its mechanisms of origin. We also highlight the reproductive and clinical implications of this type of aneuploidy mosaicism for individual carriers. We conclude that the risk of begetting a child with Trisomy 21 Down syndrome most likely is related to the incidence of Trisomy 21 cells in the germ line of any carrier parent. The clinical implications for individual carriers may likewise be dependent on the incidence of Trisomy 21 in the relevant somatic tissues. Remarkably, for example, there are indications that Trisomy 21 mosaicism will predispose carriers to conditions such as childhood leukemia and Alzheimer's Disease but there is on the other hand a possibility that the risk of solid cancers may be substantially reduced.     

How Much is Enough? Estimating the Minimum Sampling Required for Effective Monitoring of African Reserves

Effective biological monitoring in developing countries requires a balance of rigour and practicality. Unfortunately, there exist few general guidelines to help practitioners design monitoring programs that reach this balance. Here, we analyse a 33-year monitoring program from Ghana, West Africa, to provide both specific and general suggestions for monitoring in developing countries. Since the late 1960s the Ghana Wildlife Division has monitored more than 40 wildlife species with monthly surveys at sites throughout Ghana's nature reserves. These data present unparalleled opportunities to illuminate the scale and pattern of changes in animal abundance over time and the forces that drive these changes. We used sub-sampling of the Ghana monitoring data for four species in two savanna reserves to identify the minimum level of monitoring necessary to reliably detect changes in wildlife populations over 5-year intervals. We used a similar approach to estimate the minimum sampling needed to infer changes in abundance of hunters in reserves. Our results highlight the relative importance of comprehensive spatial and temporal sampling and suggest a requirement of no less than one monitoring site per every 285 km² in large reserves and 65 km² in smaller reserves. We discuss briefly the cost of effective monitoring and the relevance of our results to other regions of Africa and the world.     

Do We Feel the Same Empathy for Loved and Hated Peers?

Empathy allows us to understand and react to other people''s feelings and sensations; we can more accurately judge another person’s situation when we are aware of his/her emotions. Empathy for pain is a good working model of the behavioral and neural processes involved in empathy in general. Although the influence of perspective-taking processes (notably "Self" vs. "Other") on pain rating has been studied, the impact of the degree of familiarity with the person representing the “Other” perspective has not been previously addressed. In the present study, we asked participants to adopt four different perspectives: "Self", "Other-Most-Loved-Familiar", "Other-Most-Hated-Familiar" and "Other-Stranger". The results showed that higher pain ratings were attributed to the Other-Most-Loved-Familiar perspective than to the Self, Other-Stranger and Other-Most-Hated-Familiar perspectives. Moreover, participants were quicker to rate pain for the Other-Most-Loved-Familiar perspective and the Self-perspective than for the other two perspectives. These results for a perspective-taking task therefore more clearly define the role of familiarity in empathy for pain.     

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.     

How Long and Low Can You Go? Effect of Conformation on the Risk of Thoracolumbar Intervertebral Disc Extrusion in Domestic Dogs

Intervertebral disc extrusion (IVDE) is a common neurological disorder in certain dog breeds, resulting in spinal cord compression and injury that can cause pain and neurological deficits. Most disc extrusions are reported in chondrodystrophic breeds (e.g. Dachshunds, Basset Hounds, Pekingese), where selection for ‘long and low’ morphologies is linked with intervertebral discs abnormalities that predispose dogs to IVDE. The aim of this study was to quantify the relationship between relative thoracolumbar vertebral column length and IVDE risk in diverse breeds. A 14 month cross-sectional study of dogs entering a UK small animal referral hospital for diverse disorders including IVDE was carried out. Dogs were measured on breed-defining morphometrics, including back length (BL) and height at the withers (HW). Of 700 dogs recruited from this referral population, measured and clinically examined, 79 were diagnosed with thoracolumbar IVDE following diagnostic imaging ± surgery. The BL:HW ratio was positively associated with IVDE risk, indicating that relatively longer dogs were at increased risk, e.g. the probability of IVDE was 0.30 for Miniature Dachshunds when BL:HW ratio equalled 1.1, compared to 0.68 when BL:HW ratio equalled 1.5. Additionally, both being overweight and skeletally smaller significantly increased IVDE risk. Therefore, selection for longer backs and miniaturisation should be discouraged in high-risk breeds to reduce IVDE risk. In higher risk individuals, maintaining a lean body shape is particularly important to reduce the risk of IVDE. Results are reported as probabilities to aid decision-making regarding breed standards and screening programmes reflecting the degree of risk acceptable to stakeholders.