Accelerated Evolution of the ASPM Gene Controlling Brain Size Begins Prior to Human Brain Expansion

Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size

Proton transfer or hemibonding? The structure and stability of radical cation clusters

The basin hopping search algorithm in conjunction with second-order Moller-Plesset perturbation theory is used to determine the lowest energy structures of the radical cation clusters (NH_3)_n^+, (H_2O)_n^+, (HF)_n^+, (PH_3)_n^+, (H_2S)_n^+ and (HCl)_n^+, where n=2-4. The energies of the most stable structures are subsequently evaluated using coupled cluster theory in conjunction with the aug-cc-pVTZ basis set. These cationic clusters can adopt two distinct structural types, with some clusters showing an unusual type of bonding, often referred to as hemibonding, while other clusters undergo proton transfer to give an ion and radical. It is found that proton transfer based structures are preferred by the (NH_3)_n+, (H_2O)_n^+, and (HF)_n^+ clusters while hemibonded structures are favoured by (PH_3)_n^+, (H_2S)_n^+ and (HCl)_n^+. These trends can be attributed to the relative strengths of the molecules and molecular cations as Brønsted bases and acids, respectively, and the strength of the interaction between the ion and radical in the ion-radical clusters

Role of heavy-meson exchange in pion production near threshold

Recent calculations of $s$-wave pion production have severely underestimated the accurately known $pp\rightarrow pp\pi^0$\ total cross section near threshold. In these calculations, only the single-nucleon axial-charge operator is considered. We have calculated, in addition to the one-body term, the two-body contributions to this reaction that arise from the exchange of mesons. We find that the inclusion of the scalar $\sigma$-meson exchange current (and lesser contributions from other mesons) increases the cross section by about a factor of five, and leads to excellent agreement with the data. The results are neither very sensitive to changes in the distorting potential that generates the $NN$ wave function, nor to different choices for the meson-nucleon form factors. We argue that $pp\rightarrow pp\pi^0$\ data provide direct experimental evidence for meson-exchange contributions to the axial current.Comment: 28 Pages, IU-NTC #93-0

Semantic mutation testing

This is the Pre-print version of the Article. The official published version can be obtained from the link below - Copyright @ 2011 ElsevierMutation testing is a powerful and flexible test technique. Traditional mutation testing makes a small change to the syntax of a description (usually a program) in order to create a mutant. A test suite is considered to be good if it distinguishes between the original description and all of the (functionally non-equivalent) mutants. These mutants can be seen as representing potential small slips and thus mutation testing aims to produce a test suite that is good at finding such slips. It has also been argued that a test suite that finds such small changes is likely to find larger changes. This paper describes a new approach to mutation testing, called semantic mutation testing. Rather than mutate the description, semantic mutation testing mutates the semantics of the language in which the description is written. The mutations of the semantics of the language represent possible misunderstandings of the description language and thus capture a different class of faults. Since the likely misunderstandings are highly context dependent, this context should be used to determine which semantic mutants should be produced. The approach is illustrated through examples with statecharts and C code. The paper also describes a semantic mutation testing tool for C and the results of experiments that investigated the nature of some semantic mutation operators for C

Primary Care Staff's Views and Experiences Related to Routinely Advising Patients about Physical Activity. A Questionnaire Survey

Background: United Kingdom public health policy has recently re-emphasised the role of primary health care professionals in tackling increasing levels of physical inactivity within the general population. However, little is known about the impact that this has had in practice. This study explores Scottish primary care staff's knowledge, attitudes and experiences associated with advising patients about physical activity during routine consultations. Methods: A cross-sectional questionnaire survey of general practitioners (or family physicians), practice nurses and health visitors based in four health regions was conducted during 2004. The main outcome measures included: i) health professionals' knowledge of the current physical activity recommendations; (ii) practice related to routine physical activity advising; and (iii) associated attitudes. Results: Questionnaires were returned by 757 primary care staff (response rate 54%). Confidence and enthusiasm for giving advice was generally high, but knowledge of current physical activity recommendations was low. In general, respondents indicated that they routinely discuss and advise patients about physical activity regardless of the presenting condition. Health visitors and practice nurses were more likely than general practitioners to offer routine advice. Lack of time and resources were more likely to be reported as barriers to routine advising by general practitioners than other professional groups. However, health visitors and practice nurses were also more likely than general practitioners to believe that patients would follow their physical activity advice giving. Conclusion: If primary health care staff are to be fully motivated and effective in encouraging and supporting the general population to become more physically active, policymakers and health professionals need to engage in efforts to: (1) improve knowledge of current physical activity recommendations and population trends amongst frontline primary care staff; and (2) consider the development of tools to support individual assessment and advice giving to suit individual circumstances. Despite the fact that this study found that system barriers to routine advising were less of a problem than other previous research has indicated, this issue still remains a challenge

Chapter 11 - Agriculture, forestry and other land use (AFOLU)

Agriculture, Forestry, and Other Land Use (AFOLU) plays a central role for food security and sustainable development. Plants take up carbon dioxide (CO2) from the atmosphere and nitrogen (N) from the soil when they grow, re-distributing it among different pools, including above and below-ground living biomass, dead residues, and soil organic matter. The CO2 and other non-CO2 greenhouse gases (GHG), largely methane (CH4) and nitrous oxide (N2O), are in turn released to the atmosphere by plant respiration, by decomposition of dead plant biomass and soil organic matter, and by combustion. Anthropogenic land-use activities (e.g., management of croplands, forests, grasslands, wetlands), and changes in land use / cover (e.g., conversion of forest lands and grasslands to cropland and pasture, afforestation) cause changes superimposed on these natural fluxes. AFOLU activities lead to both sources of CO2 (e.g., deforestation, peatland drainage) and sinks of CO2 (e.g., afforestation, management for soil carbon sequestration), and to non-CO2 emissions primarily from agriculture (e.g., CH4 from livestock and rice cultivation, N2O from manure storage and agricultural soils and biomass burning. The main mitigation options within AFOLU involve one or more of three strategies: reduction / prevention of emissions to the atmosphere by conserving existing carbon pools in soils or vegetation that would otherwise be lost or by reducing emissions of CH4 and N2O; sequestration - enhancing the uptake of carbon in terrestrial reservoirs, and thereby removing CO2 from the atmosphere; and reducing CO2 emissions by substitution of biological products for fossil fuels or energy-intensive products. Demand-side options (e.g., by lifestyle changes, reducing losses and wastes of food, changes in human diet, changes in wood consumption), though known to be difficult to implement, may also play a role. Land is the critical resource for the AFOLU sector and it provides food and fodder to feed the Earth's population of ~7 billion, and fibre and fuel for a variety of purposes. It provides livelihoods for billions of people worldwide. It is finite and provides a multitude of goods and ecosystem services that are fundamental to human well-being. Human economies and quality of life are directly dependent on the services and the resources provided by land. Figure 11.1 shows the many provisioning, regulating, cultural and supporting services provided by land, of which climate regulation is just one. Implementing mitigation options in the AFOLU sector may potentially affect other services provided by land in positive or negative ways. In the Intergovernmental Panel on Climate Change (IPCC) Second Assessment Report (SAR) and in the IPCC Fourth Assessment Report (AR4), agricultural and forestry mitigation were dealt with in separate chapters. In the IPCC Third Assessment Report (TAR), there were no separate sectoral chapters on either agriculture or forestry. In the IPCC Fifth Assessment Report (AR5), for the first time, the vast majority of the terrestrial land surface, comprising agriculture, forestry and other land use (AFOLU), is considered together in a single chapter, though settlements (which are important, with urban areas forecasted to triple in size from 2000 global extent by 2030), are dealt with in Chapter 12. This approach ensures that all land-based mitigation options can be considered together; it minimizes the risk of double counting or inconsistent treatment (e.g., different assumptions about available land) between different land categories, and allows the consideration of systemic feedbacks between mitigation options related to the land surface. Considering AFOLU in a single chapter allows phenomena common across land-use types, such as competition for land and water, co-benefits, adverse side-effects and interactions between mitigation and adaptation to be considered consistently. The complex nature of land presents a unique range of barriers and opportunities, and policies to promote mitigation in the AFOLU sector need to take account of this complexity. In this chapter, we consider the competing uses of land for mitigation and for providing other services. Unlike the chapters on agriculture and forestry in AR4, impacts of sourcing bioenergy from the AFOLU sector are considered explicitly in a dedicated appendix. Also new to this assessment is the explicit consideration of food / dietary demand-side options for GHG mitigation in the AFOLU sector, and some consideration of freshwater fisheries and aquaculture, which may compete with the agriculture and forestry sectors, mainly through their requirements for land and / or water, and indirectly, by providing fish and other products to the same markets as animal husbandry. This chapter deals with AFOLU in an integrated way with respect to the underlying scenario projections of population growth, economic growth, dietary change, land-use change (LUC), and cost of mitigation. We draw evidence from both "bottom-up" studies that estimate mitigation potentials at small scales or for individual options or technologies and then scale up, and multi-sectoral "top-down" studies that consider AFOLU as just one component of a total multi-sector system response. In this chapter, we provide updates on emissions trends and changes in drivers and pressures in the AFOLU sector, describe the practices available in the AFOLU sector, and provide refined estimates of mitigation costs and potentials for the AFOLU sector, by synthesising studies that have become available since AR4. We conclude the chapter by identifying gaps in knowledge and data, providing a selection of Frequently Asked Questions, and presenting an Appendix on bioenergy to update the IPCC Special Report on Renewable Energy Sources and Climate Change Mitigation (SRREN)

The influence of the atmospheric boundary layer on nocturnal layers of noctuids and other moths migrating over southern Britain

Insects migrating at high altitude over southern Britain have been continuously monitored by automatically-operating, vertical-looking radars over a period of several years. During some occasions in the summer months, the migrants were observed to form well-defined layer concentrations, typically at heights of 200-400 m, in the stable night-time atmosphere. Under these conditions, insects are likely to have control over their vertical movements and are selecting flight heights which are favourable for long-range migration. We therefore investigated the factors influencing the formation of these insect layers by comparing radar measurements of the vertical distribution of insect density with meteorological profiles generated by the UK Met. Office’s Unified Model (UM). Radar-derived measurements of mass and displacement speed, along with data from Rothamsted Insect Survey light traps provided information on the identity of the migrants. We present here three case studies where noctuid and pyralid moths contributed substantially to the observed layers. The major meteorological factors influencing the layer concentrations appeared to be: (a) the altitude of the warmest air, (b) heights corresponding to temperature preferences or thresholds for sustained migration and (c), on nights when air temperatures are relatively high, wind-speed maxima associated with the nocturnal jet. Back-trajectories indicated that layer duration may have been determined by the distance to the coast. Overall, the unique combination of meteorological data from the UM and insect data from entomological radar described here show considerable promise for systematic studies of high-altitude insect layering

The Effects of the SSRI Paroxetine on Feeding Rates of the Larval Mosquito Aedes aegypti

Paroxetine is an antidepressant drug that is found in aquatic habitats. It is a serotonin specific reuptake inhibitor (SSRI) that increases the amount of serotonin in synapses, mimicking increased activity of serotonergic pathways. Studying the effects of the SSRI paroxetine in freshwater animals such as Aedes aegypti larvae (mosquito larva) may help us see what physical and behavioral impact the drug may have on these animals and how it may affect the ecosystem. The testing of feeding rates of mosquito larvae exposed to paroxetine was conducted because of the known influence of serotonin on appetite. In order to see the influence of serotonin on appetite Aedes aegypti were exposed to different concentrations of paroxetine (1x10-5, 1x10-6, and 1x10-7 mmol/L). The effect of paroxetine on feeding rates are expected to affect growth and development of mosquitoes, suggesting ways that paroxetine and other SSRIs in the environment will likely alter the ecosystem

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions