Showing papers in "Philosophical Transactions of the Royal Society B in 2014"
TL;DR: It is argued that the magnitude of the challenge is such that action is needed throughout the food system, on moderating demand, reducing waste, improving governance and producing more food, and sustainable intensification strategies are needed.
Abstract: The coming decades are likely to see increasing pressures on the global food system, both on the demand side from increasing population and per capita consumption, and on the supply side from greater competition for inputs and from climate change. This paper argues that the magnitude of the challenge is such that action is needed throughout the food system, on moderating demand, reducing waste, improving governance and producing more food. It discusses in detail the last component, arguing that more food should be produced using sustainable intensification (SI) strategies, and explores the rationale behind, and meaning of, this term. It also investigates how SI may interact with other food policy agendas, in particular, land use and biodiversity, animal welfare and human nutrition.
778 citations
TL;DR: Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should result in a further decline in childhood mortality and development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest.
Abstract: Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.
615 citations
TL;DR: Evidence derived using optical imaging, molecular-genetic and optogenetic techniques in conjunction with appropriate behavioural analyses continues to offer support for the idea that changing the strength of connections between neurons is one of the major mechanisms by which engrams are stored in the brain.
Abstract: The synaptic plasticity and memory hypothesis asserts that activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the encoding and trace storage of the type of memory mediated by the brain area in which it is observed. Criteria for establishing the necessity and sufficiency of such plasticity in mediating trace storage have been identified and are here reviewed in relation to new work using some of the diverse techniques of contemporary neuroscience. Evidence derived using optical imaging, molecular-genetic and optogenetic techniques in conjunction with appropriate behavioural analyses continues to offer support for the idea that changing the strength of connections between neurons is one of the major mechanisms by which engrams are stored in the brain.
517 citations
TL;DR: Urgent technical, financial and institutional support is needed to improve the agricultural production and food security of Malagasy farmers and make their livelihoods resilient to climate change.
Abstract: Across the tropics, smallholder farmers already face numerous risks to agricultural production. Climate change is expected to disproportionately affect smallholder farmers and make their livelihoods even more precarious; however, there is limited information on their overall vulnerability and adaptation needs. We conducted surveys of 600 households in Madagascar to characterize the vulnerability of smallholder farmers, identify how farmers cope with risks and explore what strategies are needed to help them adapt to climate change. Malagasy farmers are particularly vulnerable to any shocks to their agricultural system owing to their high dependence on agriculture for their livelihoods, chronic food insecurity, physical isolation and lack of access to formal safety nets. Farmers are frequently exposed to pest and disease outbreaks and extreme weather events (particularly cyclones), which cause significant crop and income losses and exacerbate food insecurity. Although farmers use a variety of risk-coping strategies, these are insufficient to prevent them from remaining food insecure. Few farmers have adjusted their farming strategies in response to climate change, owing to limited resources and capacity. Urgent technical, financial and institutional support is needed to improve the agricultural production and food security of Malagasy farmers and make their livelihoods resilient to climate change.
478 citations
TL;DR: It is argued that the neuroscience of spatial cognition is emerging as an exceptionally integrative field which provides an ideal test-bed for theories linking neural coding, learning, memory and cognition.
Abstract: Over the past four decades, research has revealed that cells in the hippocampal formation provide an exquisitely detailed representation of an animal's current location and heading. These findings have provided the foundations for a growing understanding of the mechanisms of spatial cognition in mammals, including humans. We describe the key properties of the major categories of spatial cells: place cells, head direction cells, grid cells and boundary cells, each of which has a characteristic firing pattern that encodes spatial parameters relating to the animal's current position and orientation. These properties also include the theta oscillation, which appears to play a functional role in the representation and processing of spatial information. Reviewing recent work, we identify some themes of current research and introduce approaches to computational modelling that have helped to bridge the different levels of description at which these mechanisms have been investigated. These range from the level of molecular biology and genetics to the behaviour and brain activity of entire organisms. We argue that the neuroscience of spatial cognition is emerging as an exceptionally integrative field which provides an ideal test-bed for theories linking neural coding, learning, memory and cognition.
422 citations
TL;DR: Elevated metabolism, weakened cell-to-capillary diffusive coupling, and adaptations involving H+/H+-equivalent transporters and extracellular-facing CAs give cancer cells the means to manipulate micro-environmental acidity, a cancer hallmark.
Abstract: Cell survival is conditional on the maintenance of a favourable acid–base balance (pH). Owing to intensive respiratory CO2 and lactic acid production, cancer cells are exposed continuously to large...
401 citations
TL;DR: It is demonstrated that prey consumption can be an important exposure route as on average 46% of the pharmaceutical in ingested prey accumulated in the predator, suggesting that investigations of exposure through bioconcentration, where trophic interactions and subsequent bioaccumulation of exposed individuals are ignored, underestimate exposure.
Abstract: The study of animal behaviour is important for both ecology and ecotoxicology, yet research in these two fields is currently developing independently. Here, we synthesize the available knowledge on drug-induced behavioural alterations in fish, discuss potential ecological consequences and report results from an experiment in which we quantify both uptake and behavioural impact of a psychiatric drug on a predatory fish (Perca fluviatilis) and its invertebrate prey (Coenagrion hastulatum). We show that perch became more active while damselfly behaviour was unaffected, illustrating that behavioural effects of pharmaceuticals can differ between species. Furthermore, we demonstrate that prey consumption can be an important exposure route as on average 46% of the pharmaceutical in ingested prey accumulated in the predator. This suggests that investigations of exposure through bioconcentration, where trophic interactions and subsequent bioaccumulation of exposed individuals are ignored, underestimate exposure. Wildlife may therefore be exposed to higher levels of behaviourally altering pharmaceuticals than predictions based on commonly used exposure assays and pharmaceutical concentrations found in environmental monitoring programmes.
373 citations
TL;DR: I contrast environmental pollution due to manufacturing with that due to excretion in terms of their risks and management and highlight some recent initiatives.
Abstract: As long ago as the sixteenth century, Paracelsus recognized that 'the dose makes the poison'. Indeed, environmental concentrations of pharmaceuticals excreted by humans are limited, most importantly because a defined dose is given to just a fraction of the population. By contrast, recent studies have identified direct emission from drug manufacturing as a source of much higher environmental discharges that, in some cases, greatly exceed toxic threshold concentrations. Because production is concentrated in specific locations, the risks are not linked to usage patterns. Furthermore, as the drugs are not consumed, metabolism in the human body does not reduce concentrations. The environmental risks associated with manufacturing therefore comprise a different, wider set of pharmaceuticals compared with those associated with risks from excretion. Although pollution from manufacturing is less widespread, discharges that promote the development of drug-resistant microorganisms can still have global consequences. Risk management also differs between production and excretion in terms of accountability, incentive creation, legal opportunities, substitution possibilities and costs. Herein, I review studies about industrial emissions of pharmaceuticals and the effects associated with exposure to such effluents. I contrast environmental pollution due to manufacturing with that due to excretion in terms of their risks and management and highlight some recent initiatives.
365 citations
TL;DR: The sources, impacts and concentrations of pharmaceuticals in marine and coastal environments are reviewed to identify knowledge gaps and focused case studies are suggested as a priority for future research.
Abstract: There has been a significant investment in research to define exposures and potential hazards of pharmaceuticals in freshwater and terrestrial ecosystems. A substantial number of integrated environmental risk assessments have been developed in Europe, North America and many other regions for these situations. In contrast, comparatively few empirical studies have been conducted for human and veterinary pharmaceuticals that are likely to enter coastal and marine ecosystems. This is a critical knowledge gap given the significant increase in coastal human populations around the globe and the growth of coastal megacities, together with the increasing importance of coastal aquaculture around the world. There is increasing evidence that pharmaceuticals are present and are impacting on marine and coastal environments. This paper reviews the sources, impacts and concentrations of pharmaceuticals in marine and coastal environments to identify knowledge gaps and suggests focused case studies as a priority for future research.
350 citations
TL;DR: In this paper, a review of the use of graph analysis in translational neuroscience has been presented, which provides practical indications to make sense of brain network analysis and contrast counterproductive attitudes.
Abstract: The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective, communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires the know-how of all the methodological steps of the pipeline that manipulate the input brain signals and extract the functional network properties. On the other hand, knowledge of the neural phenomenon under study is required to perform physiologically relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes.
342 citations
TL;DR: A refinement of the MEC and LEC model is proposed, which is more complex than the simple spatial–non-spatial dichotomy and provides the hippocampus with information about the content of an experience.
Abstract: The hippocampus receives its major cortical input from the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). It is commonly believed that the MEC provides spatial input to the hippocampus, whereas the LEC provides non-spatial input. We review new data which suggest that this simple dichotomy between ‘where’ versus ‘what’ needs revision. We propose a refinement of this model, which is more complex than the simple spatial–non-spatial dichotomy. MEC is proposed to be involved in path integration computations based on a global frame of reference, primarily using internally generated, self-motion cues and external input about environmental boundaries and scenes; it provides the hippocampus with a coordinate system that underlies the spatial context of an experience. LEC is proposed to process information about individual items and locations based on a local frame of reference, primarily using external sensory input; it provides the hippocampus with information about the content of an experience.
TL;DR: Even across markedly different task states, central tendencies dominate the coupling configurations of network configurations, suggesting anatomical connectivity provides constraints that act as attractors pulling network configurations towards a limited number of robust states.
Abstract: Functional coupling across distributed brain regions varies across task contexts, yet there are stable features. To better understand the range and central tendencies of network configurations, coupling patterns were explored using functional MRI (fMRI) across 14 distinct continuously performed task states ranging from passive fixation to increasingly demanding classification tasks. Mean global correlation profiles across the cortex ranged from 0.69 to 0.82 between task states. Network configurations from both passive fixation and classification tasks similarly predicted task coactivation patterns estimated from meta-analysis of the literature. Thus, even across markedly different task states, central tendencies dominate the coupling configurations. Beyond these shared components, distinct task states displayed significant differences in coupling patterns in response to their varied demands. One possibility is that anatomical connectivity provides constraints that act as attractors pulling network configurations towards a limited number of robust states. Reconfigurable coupling modes emerge as significant modifications to a core functional architecture.
TL;DR: A holistic, global view of environmental exposure to pharmaceuticals encompassing terrestrial, freshwater and marine ecosystems in high- and low-income countries is taken, and studies on uptake, trophic transfer and indirect effects of pharmaceuticals acting via food webs are presented.
Abstract: Global pharmaceutical consumption is rising with the growing and ageing human population and more intensive food production Recent studies have revealed pharmaceutical residues in a wide range of ecosystems and organisms Environmental concentrations are often low, but pharmaceuticals typically are designed to have biological effects at low doses, acting on physiological systems that can be evolutionarily conserved across taxa This Theme Issue introduces the latest research investigating the risks of environmentally relevant concentrations of pharmaceuticals to vertebrate wildlife We take a holistic, global view of environmental exposure to pharmaceuticals encompassing terrestrial, freshwater and marine ecosystems in high- and low-income countries Based on both field and laboratory data, the evidence for and relevance of changes to physiology and behaviour, in addition to mortality and reproductive effects, are examined in terms of the population- and community-level consequences of pharmaceutical exposure on wildlife Studies on uptake, trophic transfer and indirect effects of pharmaceuticals acting via food webs are presented Given the logistical and ethical complexities of research in this area, several papers focus on techniques for prioritizing which compounds are most likely to harm wildlife and how modelling approaches can make predictions about the bioavailability, metabolism and toxicity of pharmaceuticals in non-target species This Theme Issue aims to help clarify the uncertainties, highlight opportunities and inform ongoing scientific and policy debates on the impacts of pharmaceuticals in the environment
TL;DR: The P-chain is introduced, an emerging framework for theory in psycholinguistics that unifies research on comprehension, production and acquisition that proposes that language processing involves incremental prediction, which is carried out by the production system.
Abstract: This article introduces the P-chain, an emerging framework for theory in psycholinguistics that unifies research on comprehension, production and acquisition. The framework proposes that language processing involves incremental prediction, which is carried out by the production system. Prediction necessarily leads to prediction error, which drives learning, including both adaptive adjustment to the mature language processing system as well as language acquisition. To illustrate the P-chain, we review the Dual-path model of sentence production, a connectionist model that explains structural priming in production and a number of facts about language acquisition. The potential of this and related models for explaining acquired and developmental disorders of sentence production is discussed.
TL;DR: The possible mechanisms underlying the importance of potassium channels in cell-cycle control are summarized and some of the identified channels are reviewed that illustrate the multiple ways in which this group of proteins can influence cell proliferation and modulate cell- cycle progression.
Abstract: Normal cell-cycle progression is a crucial task for every multicellular organism, as it determines body size and shape, tissue renewal and senescence, and is also crucial for reproduction. On the other hand, dysregulation of the cell-cycle progression leading to uncontrolled cell proliferation is the hallmark of cancer. Therefore, it is not surprising that it is a tightly regulated process, with multifaceted and very complex control mechanisms. It is now well established that one of those mechanisms relies on ion channels, and in many cases specifically on potassium channels. Here, we summarize the possible mechanisms underlying the importance of potassium channels in cell-cycle control and briefly review some of the identified channels that illustrate the multiple ways in which this group of proteins can influence cell proliferation and modulate cell-cycle progression.
TL;DR: This review uses selected examples to show how LED can mimic natural light to ensure the growth and development of photosynthetic organisms, and how changes in intensity and wavelength can manipulate the plant metabolism with the aim to produce functionalized foods.
Abstract: Providing an adequate quantity and quality of food for the escalating human population under changing climatic conditions is currently a great challenge. In outdoor cultures, sunlight provides energy (through photosynthesis) for photosynthetic organisms. They also use light quality to sense and respond to their environment. To increase the production capacity, controlled growing systems using artificial lighting have been taken into consideration. Recent development of light-emitting diode (LED) technologies presents an enormous potential for improving plant growth and making systems more sustainable. This review uses selected examples to show how LED can mimic natural light to ensure the growth and development of photosynthetic organisms, and how changes in intensity and wavelength can manipulate the plant metabolism with the aim to produce functionalized foods.
TL;DR: The different mechanisms by which centrosome amplification could contribute to tumour progression and the new advances in the development of therapies that target cells with extra centrosomes are discussed.
Abstract: Centrosome amplification is a hallmark of cancer. However, despite significant progress in recent years, we are still far from understanding how centrosome amplification affects tumorigenesis. Boveri's hypothesis formulated more than 100 years ago was that aneuploidy induced by centrosome amplification promoted tumorigenesis. Although the hypothesis remains appealing 100 years later, it is also clear that the role of centrosome amplification in cancer is more complex than initially thought. Here, we review how centrosome abnormalities are generated in cancer and the mechanisms cells employ to adapt to centrosome amplification, in particular centrosome clustering. We discuss the different mechanisms by which centrosome amplification could contribute to tumour progression and the new advances in the development of therapies that target cells with extra centrosomes.
TL;DR: In this paper, the authors propose a multi-modal view of conceptualization, which combines neuropsychology, neuroscience and computational models, offering evidence that conceptualization follows from a combination of modality-specific sources of information plus a transmodal representational system that is supported primarily by regions within the anterior temporal lobe, bilaterally.
Abstract: Conceptual knowledge reflects our multi-modal ‘semantic database’. As such, it brings meaning to all verbal and non-verbal stimuli, is the foundation for verbal and non-verbal expression and provides the basis for computing appropriate semantic generalizations. Multiple disciplines (e.g. philosophy, cognitive science, cognitive neuroscience and behavioural neurology) have striven to answer the questions of how concepts are formed, how they are represented in the brain and how they break down differentially in various neurological patient groups. A long-standing and prominent hypothesis is that concepts are distilled from our multi-modal verbal and non-verbal experience such that sensation in one modality (e.g. the smell of an apple) not only activates the intramodality long-term knowledge, but also reactivates the relevant intermodality information about that item (i.e. all the things you know about and can do with an apple). This multi-modal view of conceptualization fits with contemporary functional neuroimaging studies that observe systematic variation of activation across different modality-specific association regions dependent on the conceptual category or type of information. A second vein of interdisciplinary work argues, however, that even a smorgasbord of multi-modal features is insufficient to build coherent, generalizable concepts. Instead, an additional process or intermediate representation is required. Recent multidisciplinary work, which combines neuropsychology, neuroscience and computational models, offers evidence that conceptualization follows from a combination of modality-specific sources of information plus a transmodal ‘hub’ representational system that is supported primarily by regions within the anterior temporal lobe, bilaterally.
TL;DR: The sound symbolism bootstrapping hypothesis is proposed, claiming that pre-verbal infants are sensitive to sound symbolism, due to a biologically endowed ability to map and integrate multi-modal input, and that sound symbolism helps infants gain referential insight for speech sounds.
Abstract: Sound symbolism is a non-arbitrary relationship between speech sounds and meaning. We review evidence that, contrary to the traditional view in linguistics, sound symbolism is an important design feature of language, which affects online processing of language, and most importantly, language acquisition. We propose the sound symbolism bootstrapping hypothesis, claiming that (i) pre-verbal infants are sensitive to sound symbolism, due to a biologically endowed ability to map and integrate multi-modal input, (ii) sound symbolism helps infants gain referential insight for speech sounds, (iii) sound symbolism helps infants and toddlers associate speech sounds with their referents to establish a lexical representation and (iv) sound symbolism helps toddlers learn words by allowing them to focus on referents embedded in a complex scene, alleviating Quine's problem. We further explore the possibility that sound symbolism is deeply related to language evolution, drawing the parallel between historical development of language across generations and ontogenetic development within individuals. Finally, we suggest that sound symbolism bootstrapping is a part of a more general phenomenon of bootstrapping by means of iconic representations, drawing on similarities and close behavioural links between sound symbolism and speech-accompanying iconic gesture.
TL;DR: Five aspects of the fight against infection beyond 2015 are highlighted, including exploiting the biological links between infectious and non-infectious diseases; controlling infections among the new urban majority; enhancing the response to international health threats; expanding childhood immunization programmes to prevent acute and chronic diseases in adults; and working towards universal health coverage.
Abstract: Running over timescales that span decades or centuries, the epidemiological transition provides the central narrative of global health. In this transition, a reduction in mortality is followed by a reduction in fertility, creating larger, older populations in which the main causes of illness and death are no longer acute infections of children but chronic diseases of adults. Since the year 2000, the Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment to low-income countries. Despite the successes of the MDGs era, the inhabitants of low-income countries still suffer an enormous burden of disease owing to diarrhoea, pneumonia, HIV/AIDS, tuberculosis, malaria and other pathogens. Adding to the predictable burden of endemic disease, the threat of pandemics is ever-present and global. With a view to the future, this review spotlights five aspects of the fight against infection beyond 2015, when the MDGs will be replaced by a new set of goals for poverty reduction and sustainable development. These aspects are: exploiting the biological links between infectious and non-infectious diseases; controlling infections among the new urban majority; enhancing the response to international health threats; expanding childhood immunization programmes to prevent acute and chronic diseases in adults; and working towards universal health coverage. By scanning the wider horizon now, infectious disease specialists have the chance to shape the post-2015 era of health and development.
TL;DR: The strategies for isolation of exosomes from human blood serum and urine, characterization of their RNA cargo by sequencing, and the initial data on exosome labelling and uptake tracing in a cell culture model are described.
Abstract: Exosomes are tiny vesicles (30–150 nm) constantly secreted by all healthy and abnormal cells, and found in abundance in all body fluids. These vesicles, loaded with unique RNA and protein cargo, have a wide range of biological functions, including cell-to-cell communication and signalling. As such, exosomes hold tremendous potential as biomarkers and could lead to the development of minimally invasive diagnostics and next generation therapies within the next few years. Here, we describe the strategies for isolation of exosomes from human blood serum and urine, characterization of their RNA cargo by sequencing, and present the initial data on exosome labelling and uptake tracing in a cell culture model. The value of exosomes for clinical applications is discussed with an emphasis on their potential for diagnosing and treating neurodegenerative diseases and brain cancer.
TL;DR: This review article addresses the psychological processes and brain mechanisms that enable rhythmic interpersonal coordination and highlights musical ensemble performance as an ecologically valid yet readily controlled domain for investigating rhythm in joint action.
Abstract: Human interaction often requires simultaneous precision and flexibility in the coordination of rhythmic behaviour between individuals engaged in joint activity, for example, playing a musical duet or dancing with a partner. This review article addresses the psychological processes and brain mechanisms that enable such rhythmic interpersonal coordination. First, an overview is given of research on the cognitive-motor processes that enable individuals to represent joint action goals and to anticipate, attend and adapt to other's actions in real time. Second, the neurophysiological mechanisms that underpin rhythmic interpersonal coordination are sought in studies of sensorimotor and cognitive processes that play a role in the representation and integration of self- and other-related actions within and between individuals' brains. Finally, relationships between social–psychological factors and rhythmic interpersonal coordination are considered from two perspectives, one concerning how social-cognitive tendencies (e.g. empathy) affect coordination, and the other concerning how coordination affects interpersonal affiliation, trust and prosocial behaviour. Our review highlights musical ensemble performance as an ecologically valid yet readily controlled domain for investigating rhythm in joint action.
Journal Article•
TL;DR: It is proposed that the irrational threat beliefs (obsessions) characteristic of OCD may be a consequence, rather than an instigator, of compulsive behaviour in these patients, laying the foundation for a potential shift in both clinical and neuropsychological conceptualization of OCD and related disorders.
Abstract: Obsessive–compulsive disorder (OCD) has become a paradigmatic case of goal-directed dysfunction in psychiatry. In this article, we review the neurobiological evidence, historical and recent, that originally led to this supposition and continues to support a habit hypothesis of OCD. We will then discuss a number of recent studies that have directly tested this hypothesis, using behavioural experiments in patient populations. Based on this research evidence, which suggests that rather than goal-directed avoidance behaviours, compulsions in OCD may derive from manifestations of excessive habit formation, we present the details of a novel account of the functional relationship between these habits and the full symptom profile of the disorder. Borrowing from a cognitive dissonance framework, we propose that the irrational threat beliefs (obsessions) characteristic of OCD may be a consequence, rather than an instigator, of compulsive behaviour in these patients. This lays the foundation for a potential shift in both clinical and neuropsychological conceptualization of OCD and related disorders. This model may also prove relevant to other putative disorders of compulsivity, such as substance dependence, where the experience of ‘wanting’ drugs may be better understood as post hoc rationalizations of otherwise goal-insensitive, stimulus-driven behaviour.
TL;DR: New on-farm field trials show that using the locally commercial brachiaria cv mulato and greenleaf desmodium in adapted push–pull technology provides effective control of stemborers and striga weeds, resulting in significant grain yield increases.
Abstract: Food insecurity is a chronic problem in Africa and is likely to worsen with climate change and population growth. It is largely due to poor yields of the cereal crops caused by factors including stemborer pests, striga weeds and degraded soils. A platform technology, ‘push–pull’, based on locally available companion plants, effectively addresses these constraints resulting in substantial grain yield increases. It involves intercropping cereal crops with a forage legume, desmodium, and planting Napier grass as a border crop. Desmodium repels stemborer moths (push), and attracts their natural enemies, while Napier grass attracts them (pull). Desmodium is very effective in suppressing striga weed while improving soil fertility through nitrogen fixation and improved organic matter content. Both companion plants provide high-value animal fodder, facilitating milk production and diversifying farmers’ income sources. To extend these benefits to drier areas and ensure long-term sustainability of the technology in view of climate change, drought-tolerant trap and intercrop plants are being identified. Studies show that the locally commercial brachiaria cv mulato (trap crop) and greenleaf desmodium (intercrop) can tolerate long droughts. New on-farm field trials show that using these two companion crops in adapted push–pull technology provides effective control of stemborers and striga weeds, resulting in significant grain yield increases. Effective multi-level partnerships have been established with national agricultural research and extension systems, non-governmental organizations and other stakeholders to enhance dissemination of the technology with a goal of reaching one million farm households in the region by 2020. These will be supported by an efficient desmodium seed production and distribution system in eastern Africa, relevant policies and stakeholder training and capacity development.
TL;DR: It is argued that the pool of individuals at high risk of progression may be significantly smaller than the 2.33 billion thought to be immune sensitized by Mycobacterium tuberculosis and that identifying and targeting this group will be an important strategy in the road to elimination.
Abstract: The global health community has set itself the task of eliminating tuberculosis (TB) as a public health problem by 2050. Although progress has been made in global TB control, the current decline in incidence of 2% yr−1 is far from the rate needed to achieve this. If we are to succeed in this endeavour, new strategies to reduce the reservoir of latently infected persons (from which new cases arise) would be advantageous. However, ascertainment of the extent and risk posed by this group is poor. The current diagnostics tests (tuberculin skin test and interferon-gamma release assays) poorly predict who will develop active disease and the therapeutic options available are not optimal for the scale of the intervention that may be required. In this article, we outline a basis for our current understanding of latent TB and highlight areas where innovation leading to development of novel diagnostic tests, drug regimens and vaccines may assist progress. We argue that the pool of individuals at high risk of progression may be significantly smaller than the 2.33 billion thought to be immune sensitized by Mycobacterium tuberculosis and that identifying and targeting this group will be an important strategy in the road to elimination.
TL;DR: A centrosome consists of two barrel-shaped centrioles embedded in a matrix of proteins known as the pericentriolar material, which serves as a platform for protein complexes that regulate organelle trafficking, protein degradation and spindle assembly.
Abstract: A centrosome consists of two barrel-shaped centrioles embedded in a matrix of proteins known as the pericentriolar material (PCM). The PCM serves as a platform for protein complexes that regulate organelle trafficking, protein degradation and spindle assembly. Perhaps most important for cell division, the PCM concentrates tubulin and serves as the primary organizing centre for microtubules in metazoan somatic cells. Thus, similar to other well-described organelles, such as the nucleus and mitochondria, the cell has compartmentalized a multitude of vital biochemical reactions in the PCM. However, unlike these other organelles, the PCM is not membrane bound, but rather a dynamic collection of protein complexes and nucleic acids that constitute the organelle's interior and determine its boundary. How is the complex biochemical machinery necessary for the myriad centrosome functions concentrated and maintained in the PCM? Recent advances in proteomics and RNAi screening have unveiled most of the key PCM components and hinted at their molecular interactions ( table 1). Now we must understand how the interactions between these molecules contribute to the mesoscale organization and the assembly of the centrosome. Among outstanding questions are the intrinsic mechanisms that determine PCM shape and size, and how it functions as a biochemical reaction hub.
TL;DR: Biological concepts and analytical methods for characterizing patterns of variation and for comparing across levels are reviewed, clear that research using this approach can take advantage of an abundance of new possibilities that are so far largely unexplored.
Abstract: Although most studies on integration and modularity have focused on variation among individuals within populations or species, this is not the only level of variation for which integration and modularity exist. Multiple levels of biological variation originate from distinct sources: genetic variation, phenotypic plasticity resulting from environmental heterogeneity, fluctuating asymmetry from random developmental variation and, at the interpopulation or interspecific levels, evolutionary change. The processes that produce variation at all these levels can impart integration or modularity on the covariance structure among morphological traits. In turn, studies of the patterns of integration and modularity can inform about the underlying processes. In particular, the methods of geometric morphometrics offer many advantages for such studies because they can characterize the patterns of morphological variation in great detail and maintain the anatomical context of the structures under study. This paper reviews biological concepts and analytical methods for characterizing patterns of variation and for comparing across levels. Because research comparing patterns across level has only just begun, there are relatively few results, generalizations are difficult and many biological and statistical questions remain unanswered. Nevertheless, it is clear that research using this approach can take advantage of an abundance of new possibilities that are so far largely unexplored.
TL;DR: More general and integrative steps of regulation, legislation and research have been developed and are presented and should aim to improve the existing legislation for pharmaceuticals, prioritize pharmaceuticals in the environment and improve the availability and collection of pharmaceutical data.
Abstract: During the past two decades scientists, regulatory agencies and the European Commission have acknowledged pharmaceuticals to be an emerging environmental problem. In parallel, a regulatory framework for environmental risk assessment (ERA) of pharmaceutical products has been developed. Since the regulatory guidelines came into force the German Federal Agency (UBA) has been evaluating ERAs for human and veterinary pharmaceutical products before they are marketed. The results show that approximately 10% of pharmaceutical products are of note regarding their potential environmental risk. For human medicinal products, hormones, antibiotics, analgesics, antidepressants and antineoplastics indicated an environmental risk. For veterinary products, hormones, antibiotics and parasiticides were most often discussed as being environmentally relevant. These results are in good correlation with the results within the open scientific literature of prioritization approaches for pharmaceuticals in the environment. UBA results revealed that prospective approaches, such as ERA of pharmaceuticals, play an important role in minimizing problems caused by pharmaceuticals in the environment. However, the regulatory ERA framework could be improved by (i) inclusion of the environment in the risk–benefit analysis for human pharmaceuticals, (ii) improvement of risk management options, (iii) generation of data on existing pharmaceuticals, and (iv) improving the availability of ERA data. In addition, more general and integrative steps of regulation, legislation and research have been developed and are presented in this article. In order to minimize the quantity of pharmaceuticals in the environment these should aim to (i) improve the existing legislation for pharmaceuticals, (ii) prioritize pharmaceuticals in the environment and (iii) improve the availability and collection of pharmaceutical data.
TL;DR: The authors showed that phenotypic integration can produce both more and less disparate organisms than would be expected under random walk models by repartitioning variance in preferred directions, which can also be expected to favour homoplasy and convergent evolution.
Abstract: Phenotypic integration is a pervasive characteristic of organisms. Numerous analyses have demonstrated that patterns of phenotypic integration are conserved across large clades, but that significant variation also exists. For example, heterochronic shifts related to different mammalian reproductive strategies are reflected in postcranial skeletal integration and in coordination of bone ossification. Phenotypic integration and modularity have been hypothesized to shape morphological evolution, and we extended simulations to confirm that trait integration can influence both the trajectory and magnitude of response to selection. We further demonstrate that phenotypic integration can produce both more and less disparate organisms than would be expected under random walk models by repartitioning variance in preferred directions. This effect can also be expected to favour homoplasy and convergent evolution. New empirical analyses of the carnivoran cranium show that rates of evolution, in contrast, are not strongly influenced by phenotypic integration and show little relationship to morphological disparity, suggesting that phenotypic integration may shape the direction of evolutionary change, but not necessarily the speed of it. Nonetheless, phenotypic integration is problematic for morphological clocks and should be incorporated more widely into models that seek to accurately reconstruct both trait and organismal evolution.