From exotic spice to modern drug?

The global demand for more affordable therapeutics and concerns about side effects of commonly used drugs are refocusing interest on Eastern traditional medicines, particularly those of India and China.     

Seeing the trees for the wood: random walks or bounded fluctuations of population size?

Summary It is often claimed that the fluctuation of numbers in field populations is fundamentally different from random walks of densities, in that population size is kept between certain positive limits. To test this hypothesis patterns of fluctuation in field populations were compared with random walks of density of about the same duration. It was found that the boundaries (Log-Range) between which numbers fluctuate in field populations increase with time to about the same extent as in comparable random walks of density. Moreover, deviations of the trend of numbers over years (Average lnR) from zero trend in populations of 62 (carabid) species were just those expected for simulated random walk runs, with the median value of Var(lnR), and different values for mean population size that cover the possible range of survival times for these species. This means that the null hypothesis that in the field numbers would fluctuate as random walks of densities could not be rejected. Although it is not very probable that field populations fluctuate exactly like random walks of densities, random walk models appear to mimic the fluctuation patterns of field populations sufficiently closely to explain what happens in nature, and to deny the need for regulation. The same conclusion was drawn in earlier studies where statistical tests were applied to fluctuation patterns of field populations (Den Boer and Reddingius 1989; Den Boer 1990a). Random walks of densities do not exclude the possibility that local populations can persist for some centuries.Communication No. 435 of the Biological Station Wijster     

Primary aldosteronism: are we missing the wood for the trees?

The prevalence of primary aldosteronism (PA) is around 10% of hypertensives, with markedly increased risk of cardiovascular damage compared with age-, sex- and BP-matched essential hypertension (EH). Currently, if hypertension is present in 20% of the population, PA will account for 2%; of these PA patients only 1% are ever screened, let alone diagnosed and treated, and the remaining 99% suboptimally treated, if at all. Mineralocorticoid receptor (MR) antagonists are effective in lowering BP, uniquely vasoprotective and safe when titrated to effect in EH. In resistant hypertension (BP elevated despite 3 or more conventional agents, including a diuretic), which constitutes 20-30% of EH, addition of a low dose MR antagonist reproducibly produces BP lowering of 20-30 mm Hg. Two thirds of PA is unilateral, and normally treated by MR antagonists; in unilateral PA surgery is recommended, but there are also studies reporting MR antagonist therapy to be noninferior over the longer term. There thus seems to be a very strong case for including a low dose MR antagonist in first-line therapy for new hypertension, given its utility and safety across EH, its particular efficacy in resistant hypertension, and its specific benefits for the 99% of subjects with occult PA. We do not have the resources to diagnose PA, but we do have the wherewithal to treat it.     

Making the Baruya great again: From glorified great men to modern suffering subjects?

This paper explores avenues for prestige‐making now available to and championed by the Baruya, the archetypal ‘Great Man’ people of Papua New Guinea, who I recently studied following previous work by Maurice Godelier. Amid critiques by Robbins and Ortner of anthropologists’ drive to document and empathise with “suffering subjects”, I suggest that being ‘left behind’ and ‘forgotten’ is an important part of Baruya social life that reinterprets previous ways of ‘making great men.’ Baruya exposure to material and institutional modernity remains very limited. Local rhetorics of being ‘last place’ (las ples) are both concomitant and discordant with Baruya assumptions and assertions of being ‘the greatest people’ of their region. Unable to revive traditional contexts for producing great men through warriorship, shamanism, cassowary hunting, and salt‐making, Baruya turn to the very modernity they cannot quite reach for their own pursuit of masculinity and prestige—which paradoxically now lies within domains also open to women. Desirous to both establish continuity with their glorified past and to depart from it, Baruya's local modernity itself constrains their newly‐shaped desire for prestige—and dramatically changes gender relations in the process. Though the concrete impossibility to ‘be great’ reinforces Baruya perceptions of enduring what we might call a ‘suffering slot’, the larger issue is how concrete experiences sediment into socio‐cultural change over time. This process is informed by a tension between a quest for modernity and its larger failure, resulting in a drive to reignite longer standing values of morality, spirituality, and ultimately, greatmanship.     

From stem cell to T cell: one route or many?

T cells developing in the adult thymus ultimately derive from haematopoietic stem cells in the bone marrow. Here, we summarize research into the identity of the haematopoietic progenitors that leave the bone marrow, migrate through the blood and settle in the thymus to generate T cells. Accumulating data indicate that various different bone-marrow progenitors are T-cell-lineage competent and might contribute to intrathymic T-cell development. Such developmental flexibility implies a mechanism of T-cell-lineage commitment that can operate on a range of T-cell-lineage-competent progenitors, and further indicates that only those T-cell-lineage-competent progenitors able to migrate to, and settle in, the thymus should be considered physiological T-cell progenitors.     

Oxidative stress in Alzheimer's disease: Primary villain or physiological by-product?

Abstract

The prevalence of Alzheimer's disease (AD) is increasing rapidly worldwide due to an ageing population and largely ineffective treatments. In AD cognitive decline is due to progressive neuron loss that begins in the medial temporal lobe and spreads through many brain regions. Despite intense research the pathogenesis of the common sporadic form of AD remains largely unknown. The popular amyloid cascade hypothesis suggests that the accumulation of soluble oligomers of beta amyloid peptides (Aβ) initiates a series of events that cause neuronal loss. Among their putative toxic effects, Aβ oligomers are thought to act as pro-oxidants combining with redox-active metals to produce excessive reactive oxygen and nitrogen species. However, to date the experimental therapies that reduce Aβ load in AD have failed to halt cognitive decline. Another hypothesis proposed by the late Mark Smith and colleagues is that oxidative stress, rather than Aβ, precipitates the pathogenesis of AD. That is, Aβ and microtubule-associated protein tau are upregulated to address the redox imbalance in the AD brain. As the disease progresses, excess Aβ and tau oligomerise to further accelerate the disease process. Here, we discuss redox balance in the human brain and how this balance is affected by ageing. We then discuss where oxidative stress is most likely to act in the disease process and the potential for intervention to reduce its effects.     

Genetic design automation: engineering fantasy or scientific renewal?

The aim of synthetic biology is to make genetic systems more amenable to engineering, which has naturally led to the development of computer-aided design (CAD) tools. Experimentalists still primarily rely on project-specific ad hoc workflows instead of domain-specific tools, which suggests that CAD tools are lagging behind the front line of the field. Here, we discuss the scientific hurdles that have limited the productivity gains anticipated from existing tools. We argue that the real value of efforts to develop CAD tools is the formalization of genetic design rules that determine the complex relationships between genotype and phenotype.     

Temporal pollen pattern in temperate trees: expedience or fate?

European forests are populated with a variety of wind‐pollinated tree species. Their pollen productivity and spatio‐temporal pattern are largely unknown. Long‐term data (17 years) collected at 22 sites across Austria were presented and the pollen production of 12 tree genera was analysed. We ranked the tree genera according to their pollen productivity taking actual tree abundances of the Austrian Forestry Inventory into account. The productivity varied strongly among tree genera with a maximum for Betula. Pollen production in Larix, Abies and Picea amounted to approximately 1/20, while in increasing order Salix, Quercus, Alnus, Populus and Fraxinus produced approximately 1/3 to 1/4 of the respective Betula estimate. In general, pollen quantity in broadleaves was higher than in conifers. We analysed the temporal pollen production pattern by means of hierarchical cluster analysis and identified three major groups: [(Fagus, Larix, Picea, Abies), (Alnus, Betula, Fraxinus)], [Carpinus],[Populus, Salix, Pinus, Quercus]. Distance matrices based on life‐history traits as well as molecular phylogeny were also constructed; they correlated significantly with each other by means of Mantel‐tests. However, there was no significant relationship between the distances on temporal pollen production with the other matrices. Intermittent or idiosyncratic pollen production was studied by means of deviation from expected means, skewness and spindle diagrams. We proposed that Fagus, Carpinus, Larix, Picea and Abies belong to ‘masting pollen producers’, while the remaining genera idiosyncratically produced pollen over the monitored period. Moreover we correlated the distance matrix of pollen production for each tree genus at each sampling site with respective ‘ecological distance matrices’ based on aerial and altitudinal distance among sites. Significant correlations were detected for tree genera (Fagus, Larix, Picea) which were also prone to pollen masting, thus indicating a Moran effect.     

From animal communication to the human language and cognition: evolution or revolution?

The paper discusses the problem of language and cognitive specificity in humans as compared to other species. The main hypotheses of human evolution and the emergence of language seem to be well researched on genetic basis of higher functions. Cognitive abilities of other animals and their communication signals and the main views on basic principles of brain underlying these functions are described.     

Explaining patterns in modern ruminant diversity: contingency or constraint?

Bovid species outnumber those of cervids by over two and half to one. The present study attempts to explain this difference using two principle concepts: contingency and constraint. The concept of contingency considers the role of biogeography and the distributions and timings of major dispersals seen in the two families. Although this historical context is considered vital for understanding the problem, cervids are also characterized by their global absence from open and arid grassland habitats. This is explained in terms of phylogenetic constraint. One proposal considers the deciduous antlers of cervids as constraining the group to higher quality forage that is not generally associated with open habitats. Alternatively and more generally applicable to all ruminants is the ‘cusp fusion hypothesis’, presented here for the first time. The hypothesis seeks to explain how the primitive ruminant molar state, as seen in modern cervids and giraffids, prevents the attainment of very high molar crowns and, with it, the ability to cope with high rates of dietary tooth wear. Conversely, the derived condition of precocial cusp fusion seen in the Bovidae and Antilocapridae has enabled higher tooth crowns, their expansion into open habitats, and an increased diversity potential. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 99 , 657–672.     

Antiprion immunotherapy: to suppress or to stimulate?

Although human prion diseases are rare, they are invariably fatal, and treatments remain elusive. Hundreds of iatrogenic prion transmissions have occurred in the past two decades, and the bovine spongiform encephalopathy epidemic has raised concerns about prion transmission from cattle to humans. Research into therapeutics for prion disease is being pursued in several centres and prominently includes immunological strategies. Currently, the options that are being explored aim either to mobilize the innate and adaptive immune systems towards prion destruction or to suppress or dedifferentiate the lymphoreticular compartments that replicate prions. This article reviews the pathophysiology of prion diseases in mouse models and discusses their relevance to immunotherapeutic and immunoprophylactic antiprion strategies.     

The use of fetal bovine serum: ethical or scientific problem?

Fetal bovine serum (FBS) is a common component of animal cell culture media. It is harvested from bovine fetuses taken from pregnant cows during slaughter. FBS is commonly harvested by means of a cardiac puncture without any form of anaesthesia. Fetuses are probably exposed to pain and/or discomfort, so the current practice of fetal blood harvesting is inhumane. Apart from moral concerns, several scientific and technical problems exist with regard to the use of FBS in cell culture. Efforts should be made to reduce the use of FBS or, preferably, to replace it with synthetic alternatives.     

Ecology of Caribbean Sponges: Are Top-Down or Bottom-Up Processes More Important?

Benthic-pelagic coupling and the role of bottom-up versus top-down processes are recognized as having a major impact on the structure of marine communities. While the roles of bottom-up processes are better appreciated they are still viewed as principally affecting the outcome of top-down processes. Sponges on coral reefs are important members of the benthic community and provide a critically important functional linkage between water-column productivity and the benthos. As active suspension feeders sponges utilize the abundant autotrophic and heterotrophic picoplankton in the water column. As a result sponges across the Caribbean basin exhibit a consistent and significant pattern of greater biomass, tube extension rate, and species numbers with increasing depth. Likewise, the abundance of their food supply also increases along a depth gradient. Using experimental manipulations it has recently been reported that predation is the primary determinant of sponge community structure. Here we provide data showing that the size and growth of the sponge Callyspongia vaginalis are significantly affected by food availability. Sponges increased in size and tube extension rate with increasing depth down to 46 m, while simultaneously exposed to the full range of potential spongivores at all depths. Additionally, we point out important flaws in the experimental design used to demonstrate the role of predation and suggest that a resolution of this important question will require well-controlled, multi-factorial experiments to examine the independent and interactive effects of predation and food abundance on the ecology of sponges.     

Atrial fibrillation: to map or not to map?

Isolation of the pulmonary veins may be an effective treatment modality for eliminating atrial fibrillation (AF) episodes but unfortunately not for all patients. When ablative therapy fails, it is assumed that AF has progressed from a trigger-driven to a substrate-mediated arrhythmia. The effect of radiofrequency ablation on persistent AF can be attributed to various mechanisms, including elimination of the trigger, modification of the arrhythmogenic substrate, interruption of crucial pathways of conduction, atrial debulking, or atrial denervation. This review discusses the possible effects of pulmonary vein isolation on the fibrillatory process and the necessity of cardiac mapping in order to comprehend the mechanisms of AF in the individual patient and to select the optimal treatment modality.