The neuronal ceroid-lipofuscinoses: from past to present

The neuronal ceroid-lipofuscinoses (NCLs) are inherited lysosomal storage diseases and constitute the most common group of children's progressive encephalopathies. Most childhood forms of NCL are clinically characterized by progressive loss of vision as well as mental and motor deterioration, epileptic seizures, and premature death, while the rare adult forms are dominated by dementia. All forms of NCL share common pathomorphological features. Autofluorescent, periodic acid-Schiff- and Sudan black B-positive granules, resistant to lipid solvents, accumulate in the cytoplasm of most nerve cells, and there is progressive and remarkably selective neuronal degeneration and loss. For a long time, the NCLs were grouped under the heading of the "amaurotic family idiocies" and conceived as lipidoses. However, in the late 1980s and 1990s the NCL storage cytosomes were shown to consist largely of two hydrophobic proteins: either subunit c of mitochondrial ATP synthase or sphingolipid activator proteins A and D. Since 1995 numerous mutations in at least seven different genes have been shown to underlie the multiple human and animal forms of NCL. This review discusses the historical evolution of the NCL concept and the impact of the recent biochemical and molecular genetic findings on our views on the classification and pathogenesis of these devastating brain disorders.     

Extrapolating feedback processes from the present to the past

Extant terrestrial vegetation alters its physical environment via its albedo, and its influence on immediate temperature via stomatal and boundary-layer influences of energy dissipation as sensible and latent heat; aquatic vegetation also controls albedo (e.g. coccolithophorids) and, by competing with water for electromagnetic energy absorption, the depth of the mixed layer and hence the quantity of nutrients trapped for the spring bloom. Both aquatic and terrestrial vegetation have had, together with microbial and geological processes, an influence on O₂ and CO₂ levels, and hence on the availability and biological functioning of Fe, Mn, Cu, Zn, Se and P, and the relative competitive advantage of C₃ versus C₄, crassulacean acid metabolism (CAM) and carbon concentration mechanism (CCM) organisms. Less directly, changes in primary productivity impact on the production of CH₄ and N₂O which, like CO₂, are greenhouse gases, while some (marine) primary producers yield dimethyl sulphide (and hence cloud condensation nuclei, with effects on cloudiness) and halocarbons (via, in part, O₂-dependent processes), partly negating the O₃ attenuation of UV-B radiation. These effects can be related to the terrestrial embryophytic vegetation back to ca. 450 Ma, and to eukaryotic marine vegetation back to at least 1.7, and probably 2.1 Ga, with implications for inter alia C₃ versus C4, CAM and CCM photosynthesis, and Fe acquisition mechanisms. Even earlier (3.8 Ga onwards) prokaryotes may have influenced CO₂ levels and hence controlled (as they did later) surface temperature. By producing O₂, they led to decreasing availability of Fe, Mn and P (and utility of Se?), and increasing availability of Cu (and Zn?) that shaped the biochemistry on which later biogeochemistry was based.     

Dynamic distribution modelling: predicting the present from the past

Confidence in projections of the future distributions of species requires demonstration that recently-observed changes could have been predicted adequately. Here we use a dynamic model framework to demonstrate that recently-observed changes at the expanding northern boundaries of three British butterfly species can be predicted with good accuracy. Previous work established that the distributions of the study species currently lag behind climate change, and so we presumed that climate is not currently a major constraint at the northern range margins of our study species. We predicted 1970–2000 distribution changes using a colonisation model, MIGRATE, superimposed on a high-resolution map of habitat availability. Thirty-year rates and patterns of distribution change could be accurately predicted for each species (κ goodness-of-fit of models >0.64 for all three species, corresponding to >83% of grid cells correctly assigned), using a combination of individual species traits, species-specific habitat associations and distance-dependent dispersal. Sensitivity analyses showed that population productivity was the most important determinant of the rate of distribution expansion (variation in dispersal rate was not studied because the species are thought to be similar in dispersal capacity), and that each species' distribution prior to expansion was critical in determining the spatial pattern of the current distribution. In future, modelling approaches that combine climate suitability and spatially-explicit population models, incorporating demographic variables and habitat availability, are likely to be valuable tools in projecting species' responses to climatic change and hence in anticipating management to facilitate species' dispersal and persistence.     

Schistosomiasis in Indonesia: past and present

Schistosomiasis is endemic in Indonesia in two isolated areas, Lindu valley and Napu valley, both located in the Province of Central Sulawesi. In 1940, a prevalence survey was initiated in Lake Lindu, which indicated a Schistosoma japonicum infection prevalence of 56% among the population of Anca, Tomado and Langko villages. Another survey was conducted in 1973 in Napu valley and very high infection prevalences of up to 72% were found among the population in Winowanga village. Since then, comprehensive studies on the epidemiology and the effects of control have been carried out in 24 endemic villages in both areas. Over the past six decades, schistosomiasis control has been implemented and the average prevalence is now much lower than before the control programme was launched. In 2006, it was 0.49% in 7 villages in Lindu valley. In Napu valley, the average infection prevalence among the population of 17 villages was 1.08% in the same year. Again in 2006, the prevalence of infection in snails ranged from 0 to 13.4% and from 0 to 9.1% in Napu and Lindu valleys, respectively. The highest prevalence among snails was found in Dodolo village. The prevalence of S. japonicum in the reservoir host Rattus spp. ranged from 0 to 20% and the highest prevalence was again found in Dodolo village. Contemporary data suggest that transmission of schistosomiasis is still ongoing in Indonesia despite regular surveillance and control activities covering the whole endemic area.     

Ecology of congruence: past meets present

Phylogenetic congruence is governed by various macroevolutionary events, including cospeciation, host switching, sorting, duplication, and failure to speciate. The relative frequency of these events may be influenced by factors that govern the distribution and abundance of the interacting groups; i.e., ecological factors. If so, it may be possible to predict the degree of phylogenetic congruence between two groups from information about their ecology. Unfortunately, adequate comparative ecological data are not available for many of the systems that have been subjected to cophylogenetic analysis. An exception is provided by chewing lice (Insecta: Phthiraptera), which parasitize birds and mammals. For a few genera of these lice, enough data have now been published to begin exploring the relationship between ecology and congruence. In general, there is a correspondence between important ecological factors and the degree of phylogenetic congruence. Careful comparison of these genera suggests that dispersal is a more fundamental barrier to host switching among related hosts than is establishment. Transfer experiments show that host-specific lice can survive and reproduce on novel hosts that are similar in size to the native host as long as the lice can disperse to these hosts. To date, studies of parasite dispersal have been mainly inferential. A better understanding of the role of dispersal will require more direct data on dispersal frequency and distances.     

Formation of peroxisomes: present and past

Eukaryotic cells contain functionally distinct, membrane enclosed compartments called organelles. Here we like to address two questions concerning this architectural lay out. How did this membrane complexity arise during evolution and how is this collection of organelles maintained in multiplying cells to ensure that new cells retain a complete set of them. We will try to address these questions with peroxisomes as a focal point of interest.     

Making the past serve the present

Botany has been successfully introduced to environmental design students, as a foundation for ecology and horticulture, in the form of extracts from an 18th century text which students are asked to criticise and update. This historical introduction demonstrates something of both the development ofthe subject and the students ' range of knowledge in it; and is a useful prompt for study. It encourages precision in the use of words, and emphasizes the provisional nature of scientific explanations. Suggestions for the use of this approach in other subjects and more advanced studies are made.     

The evolutionary diversification of seed size: using the past to understand the present

The Devonian origin of seed plants and subsequent morphological diversification of seeds during the late Paleozoic represents an adaptive radiation into unoccupied ecological niche space. A plant's seed size is correlated with its life-history strategy, growth form, and seed dispersal syndrome. The fossil record indicates that the oldest seed plants had relatively small seeds, but the Mississippian seed size envelope increased significantly with the diversification of larger seeded lineages. Fossil seeds equivalent to the largest extant gymnosperm seeds appeared by the Pennsylvanian, concurrent with morphological diversification of growth forms and dispersal syndromes as well as the clade's radiation into new environments. Wang's Analysis of Skewness indicates that the evolutionary trend of increasing seed size resulted from primarily passive processes in Pennsylvanian seed plants. The distributions of modern angiosperms indicate a more diverse system of active and some passive processes, unbounded by Paleozoic limits; multiple angiosperm lineages independently evolved though the upper and lower bounds. Quantitative measures of preservation suggest that, although our knowledge of Paleozoic seeds is far from complete, the evolutionary trend in seed size is unlikely to be an artifact of taphonomy.     

Chitosomes: past, present and future

José Ruiz-Herrera's discovery that chitin microfibrils could be made by a fungal extract paved the way for elucidating the intracellular location of chitin synthetase. In collaboration with Charles Bracker, chitosomes were identified as the major reservoir of chitin synthetase in fungi. Unique in size, buoyant density, and membrane thickness, chitosomes were found in a wide range of fungi. Their reversible dissociation into 16S subunits is another unique property of chitosomes. These 16S subunits are the smallest molecular entities known to retain chitin synthetase activity. Further dissociation leads to complete loss of activity. From studies with secretory mutants, yeast researchers concluded that chitosomes were components of the endocytosis pathway. However, key structural and enzymatic characteristics argue in favor of the chitosome being poised for exocytotic delivery rather than endocytotic recycling. The chitosome represents the main vehicle for delivering chitin synthetase to the cell surface. An immediate challenge is to elucidate chitosome ontogeny and the role of proteins encoded by the reported chitin synthetase genes in the structure or function of chitosomes. The ultimate challenge would be to understand how the chitosome integrates with the cell surface to construct the organized microfibrillar skeleton of the fungal cell wall.     

Growth hormone-releasing hormone: past and present

The discovery of hypothalamic hypophysiotropic factors confirmed the hypothesis of Green and Harris in the late 1940s. These hormones were isolated from their eutopic site of production (the hypothalamus) with the exception of growth hormone (GH)-releasing hormone (GHRH), which was isolated from an ectopic, tumoral site of production and found to be responsible for acromegaly. Following the isolation, characterization and synthesis of human GHRH, clinical studies were performed and are described below. Circulating levels of GHRH can be measured and provide the basis for the diagnosis of acromegaly related to the ectopic, tumoral production of GHRH. At present, GHRH is used as a test of GH secretion mainly as an adjunct to other agents which modify somatostatin status, or to GH-releasing peptides. Its therapeutic potential in children and the elderly is still under investigation. The role of GHRH in the pulsatile secretion of GH is described.     

Life: past, present and future

Molecular methods of taxonomy and phylogeny have changed the way in which life on earth is viewed; they have allowed us to transition from a eukaryote-centric (five-kingdoms) view of the planet to one that is peculiarly prokarote-centric, containing three kingdoms, two of which are prokaryotic unicells. These prokaryotes are distinguished from their eukaryotic counterparts by their toughness, tenacity and metabolic diversity. Realization of these features has, in many ways, changed the way we feel about life on earth, about the nature of life past and about the possibility of finding life elsewhere. In essence, the limits of life on this planet have expanded to such a degree that our thoughts of both past and future life have been altered. The abilities of prokaryotes to withstand many extreme conditions has led to the term extremophiles, used to describe the organisms that thrive under conditions thought just a few years ago, to be inconsistent with life. Perhaps the most extensive adaptation to extreme conditions, however, is represented by the ability of many bacteria to survive nutrient conditions not compatible with eukaryotic life. Prokaryotes have evolved to use nearly every redox couple that is in abundance on earth, filling the metabolic niches left behind by the oxygen-using, carbon-eating eukaryotes. This metabolic plasticity leads to a common feature in physically stratified environments of layered microbial communities, chemical indicators of the metabolic diversity of the prokaryotes. Such 'metabolic extremophily' forms a backdrop by which we can view the energy flow of life on this planet, think about what the evolutionary past of the planet might have been, and plan ways to look for life elsewhere, using the knowledge of energy flow on earth.