Deciphering the Leishmania exoproteome: what we know and what we can learn

Parasitic protozoa of the genus Leishmania are the causative agents of leishmaniasis. Survival and transmission of these parasites in their different hosts require membrane-bound or extracellular factors to interact with and modify their host environments. Over the last decade, several approaches have been applied to study all the extracellular proteins exported by an organism at a particular time or stage in its life cycle and under defined conditions, collectively termed the secretome or the exoproteome. In this review, we focus on emerging data shedding light on the secretion mechanisms involved in the production of the Leishmania exoproteome. We also describe other methodologies currently available that could be used to analyse the Leishmania exoproteome. Understanding the complexity of the Leishmania exoproteome is a key component to elucidating the mechanisms used by these parasites for exporting proteins to the extracellular space during its life cycle. Given the importance of extracellular factors, a detailed knowledge of the Leishmania exoproteome may provide novel targets for rational drug design and/or a source of antigens for vaccine development.     

Mechanisms of testicular immune privilege

The testis exhibits a distinctive form of immune privilege to protect the germ cells from the host immune attack. The property of testicular immune privilege was originally attributed to the blood-testis barrier in the seminiferous epithelium, which sequesters antigens. Recent studies have uncovered several levels of immune control besides the blood-testis barrier involved in the privilege of the testis, including the mechanisms of immune tolerance, reduced immune activation, localized active immunosuppression and antigen-specific immunoregulation. The somatic cells of the testis, especially Sertoli cells, play a key role in regulating the testicular immune privileged status. The constitutive expression of anti-inflammatory factors in the testis by somatic cells is essential for local immunosuppression. Growing evidence shows that androgens orchestrate the inhibition of proinflammatory factors and shift cytokine balance toward a tolerogenic environment. Disruption of these protective mechanisms, which may be caused by trauma, infection and genetic factors, can lead to orchitis and infertility. This review article highlights the unique immune environment of the testis, particularly focuses on the regulation of testicular immune privilege.     

Amphibian decline and extinction: what we know and what we need to learn

For over 350 million yr, thousands of amphibian species have lived on Earth. Since the 1980s, amphibians have been disappearing at an alarming rate, in many cases quite suddenly. What is causing these declines and extinctions? In the modern era (post 1500) there are 6 leading causes of biodiversity loss in general, and all of these acting alone or together are responsible for modern amphibian declines: commercial use; introduced/exotic species that compete with, prey on, and parasitize native frogs and salamanders; land use change; contaminants; climate change; and infectious disease. The first 3 causes are historical in the sense that they have been operating for hundreds of years, although the rate of change due to each accelerated greatly after about the mid-20th century. Contaminants, climate change, and emerging infectious diseases are modern causes suspected of being responsible for the so-called 'enigmatic decline' of amphibians in protected areas. Introduced/exotic pathogens, land use change, and infectious disease are the 3 causes with a clear role in amphibian decline as well as extinction; thus far, the other 3 causes are only implicated in decline and not extinction. The present work is a review of the 6 causes with a focus on pathogens and suggested areas where new research is needed. Batrachochytrium dendrobatidis (Bd) is a chytrid fungus that is an emerging infectious disease causing amphibian population decline and species extinction. Historically, pathogens have not been seen as a major cause of extinction, but Bd is an exception, which is why it is such an interesting, important pathogen to understand. The late 20th and early 21st century global biodiversity loss is characterized as a sixth extinction event. Amphibians are a striking example of these losses as they disappear at a rate that greatly exceeds historical levels. Consequently, modern amphibian decline and extinction is a lens through which we can view the larger story of biodiversity loss and its consequences.     

Highly unsaturated fatty acids in nature: what we know and what we need to learn

The supply and demand of omega‐3 highly unsaturated fatty acids (ω‐3 HUFA) in natural ecosystems may lead to resource limitation in a diverse array of animal taxa. Here, we review why food quality in terms of ω‐3 HUFAs is important, particularly for neural tissue, across a diversity of animal taxa ranging from invertebrate zooplankton to vertebrates (including humans). Our review is focused on ω‐3 HUFAs rather than other unsaturated fatty acids because these compounds are especially important biochemically, but scarce in nature. We discuss the dichotomy between ω‐3 HUFA availability between aquatic primary producers, which are often rich in these compounds, and terrestrial primary producers, which are contain little to none of them. We describe the use of fatty acids as qualitative and quantitative tracers for reconstructing animal diets in natural ecosystems. Next, we discuss both direct and indirect ecological implications of ω‐3 HUFA limitation at the individual, population, food web, and ecosystem scales, which include: changes in behavior, species composition, secondary production rates, trophic transfer efficiency and cross‐ecosystem subsidies. We finish by highlighting future research priorities including a need for more research on ω‐3 HUFAs in terrestrial systems, more research their importance for higher order consumers, and more research on the food web and ecosystem‐scale effects of ω‐3 HUFA limitation. Synthesis Mismatches between the supply of and demand for omega‐3 highly unsaturated fatty acids (ω‐3 HUFA) in natural ecosystems have the potential to result in resource limitation across a diverse array of ecosystems. We combined perspectives from ecology and nutritional science to develop a unified synthesis of ω‐3 HUFA ecology. We reviewed the importance of ω‐3 HUFAs for animals, the striking differences in ω‐3 HUFA availability at the base of terrestrial versus aquatic food webs, and the implications of ω‐3 HUFA limitation for food webs. We finished by highlighting research priorities in the field including more research on ω‐3 HUFAs in terrestrial systems, on higher order consumers, and at the food web and ecosystem‐scales.     

Polyploidy and the sexual system: what can we learn from Mercurialis annua?

The evolutionary success of polyploidy most directly requires the ability of polyploid individuals to reproduce and transmit their genes to subsequent generations. As a result, the sexual system (i.e. the mating system and the sex allocation of a species) will necessarily play a key role in determining the fate of a new polyploid lineage. The effects of the sexual system on the evolution of polyploidy are complex and interactive. They include both aspects of the genetic system, the genetic load maintained in a population and the ecological context in which selection takes place. Here, we explore these complexities and review the empirical evidence for several potentially important genetic and ecological interactions between ploidy and the sexual system in plants. We place particular emphasis on work in our laboratory on the European annual plant Mercurialis annua , which offers promising scope for detailed investigations on this topic. M. annua forms a polyploid complex that varies in its sexual system from dioecy (separate sexes) through androdioecy (males and hermaphrodites) to functional hermaphroditism.  © 2004 The Linnean Society of London, Biological Journal of the Linnean Society , 2004, 82 , 547–560.     

Insights from linked single nucleotide polymorphisms: what we can learn from linkage disequilibrium

New methods for analyzing sequence polymorphism data have uncovered some striking patterns of linkage disequilibrium in both humans and fruitflies. These methods have revealed examples where the observed amount of linkage disequilibrium is either much more or much less than expected, and have led to advances in our understanding of the forces that affect naturally occurring genetic variation. With the recent explosion of sequence polymorphism data, the prospects for further progress from these methods are quite promising.     

Primeval conditions – what can we learn from them?

In this paper I argue that prehistoric British forests and their avifauna were similar to those persisting in a near-primeval condition in the Białowieża Forest (Polish/Belarussian border). Therefore, observations in the Białowieża Forest may serve as a baseline against which effects of changes in the British woods can be assessed. The results of long-term (30 years) studies of the breeding birds in the Białowieża National Park are summarized. They reveal that the local avifauna shows some features (high species richness, low population densities, high nest predation and low production of young) regarded as typical for undisturbed tropical forests. It is proposed that high productivity, high population densities and sedentary habits found in many British populations are to a large extent a recent phenomenon, due to forest fragmentation, reduction of predator diversity and changes in forest structure. The necessity to preserve the whole Białowieża Forest – currently seriously threatened by ongoing logging – as a benchmark for future biological studies is underlined.     

Metabolic rate and genomic GC: what we can learn from teleost fish

Teleosts are a highly diverse group of animals occupying all kind of aquatic environment. Data on routine mass specific metabolic rate were re-examined correcting them for the Boltzmann's factor. Teleostean fish were grouped in five broad groups, corresponding to major environmental classifications: polar, temperate, sub-tropical, tropical and deep-water. The specific routine metabolic rate, temperature-corrected using the Boltzmann's factor (MR), and the average base composition of genomes (GC%) were calculated in each group. Fish of the polar habitat showed the highest MR. Temperate fish displayed a significantly higher MR than tropical fish, which had the lowest average value. These results were apparently in agreement with the cold adaptation hypothesis. In contrast with this hypothesis, however, the MR of fish living in deep-water environment turned out to be not significantly different from that of fish living in tropical habitats. Most probably, the amount of oxygen dissolved in the water directly affects MR adaptation. Regarding the different habitats, the genomic GC levels showed a decreasing trend similar to that of MR. Indeed, both polar and temperate fish showed a GC level significantly higher than that of both sub-tropical and tropical fish. Plotting the genomic GC levels versus the MR a significant positive correlation was found, supporting the hypothesis that metabolic rate can explain not only the compositional transition mode (e.g. amphibian/mammals), but also the compositional shifting mode (e.g. fish/fish) of evolution observed for vertebrate genomes.     

Dung in the dumps: what we can learn from multi-proxy studies of archaeological dung pellets

Vegetation History and Archaeobotany - A key question in archaeobotany concerns the role of herbivore dung in contributing plant remains to archaeobotanical assemblages. This issue has been...     

Mechanisms of atrial fibrillation in athletes: what we know and what we do not know

Exercise is an emerging cause of atrial fibrillation (AF) in young individuals without coexisting cardiovascular risk factors. The causes of exercise-induced atrial fibrillation remain largely unknown, and conclusions are jeopardised by apparently conflicting data. Some components of the athlete’s heart are known to be arrhythmogenic in other settings. Bradycardia, atrial dilatation and, possibly, atrial premature beats are therefore biologically plausible contributors to exercise-induced AF. Challenging findings in an animal model suggest that exercise might also prompt the development of atrial fibrosis, possibly due to cumulative minor structural damage after each exercise bout. However, there is very limited, indirect data supporting this hypothesis in athletes. Age, sex, the presence of comorbidities and cardiovascular risk factors, and genetic individual variability might serve to flag those athletes who are at the higher risk of exercise-induced AF. In this review, we will critically address current knowledge on the mechanisms of exercise-induced AF.     

The category of roots and the roots of categories: what we learn from selection in derivation

Selection—the tendency of derivational affixes to choose the category of their base—has most often been couched in terms of syntactic categories such as Noun, Verb, and Adjective. In recent years several theories have claimed, however, that roots are categoryless, and receive category only by virtue of being merged with functional projections of various sorts. This article examines three such theories—Distributed Morphology, Borer’s Exo-Skeletal model, and DiSciullo’s Asymmetrical Morphology, and determines that none of them can handle the phenomenon of affixal selection. We may, however, maintain the claim that roots lack syntactic category if we make use of a system of lexical semantic categorization that allows us to state selection in terms of semantic categories. It is shown that the framework of Lieber (2004) allows for such categorization, and moreover that semantic categorization permits us to make generalizations that are not available in a theory in which selection is purely on the basis of syntactic category. I am grateful to the faculty and students of the University of Patras, Greece for discussion and comments on an earlier version of this work. Thanks also to Sergio Scalise, Antonietta Bisetto, Chiara Melloni, and three anonymous reviewers for useful comments.     

Intercontinental biotic invasions: what can we learn from native populations and habitats?

The effectiveness of management strategies for invasive species is often hampered by a lack of clear understanding of the factors that limit species distributions. The distribution of exotic species, especially those that are invasive, are often so dynamic that limiting factors are difficult to identify. Comparisons of exotic species between their native ranges, where they are presumably close to equilibrium with controlling factors, and their ranges in areas of introduction can circumvent this difficulty. Such studies would help identify (1) limiting factors for distributions in native ranges, (2) factors associated with a high degree of invasiveness, (3) changes in genetics and morphology since introduction, which also might contribute to invasiveness, and (4) future directions and rates of invasion as a basis for developing detection/warning systems. Findings from such comparative studies would be highly valuable for understanding the dynamics of biological invasions and for improving the effectiveness of management to prevent or control invasives.     

Mouse models of human diseases: what can we learn?

Heightened interest in disease models is one very clear outcome of the Human Genome Project. Teams are now racing to identify the genes that cause disease, enabling the study of their function in mouse models for subsequent research into prevention and therapy. The simultaneous evolution of gene knockout and mutation technology in mice has provided the prime opportunity to facilitate the elucidation of genetic etiology of inherited disorders in humans. In this online supplement, leading scientists review such work by disease type, from Alzheimer's disease to DiGeorge syndrome. This valuable collection provides readers with timely, comprehensive reviews of mouse knockout and mutation research, including focus on single candidate gene knockouts to complex transgenics. We hope that you will find this supplement enjoyable and informative reading.