Strictosidine activation in Apocynaceae: towards a "nuclear time bomb"?

Background  

The first two enzymatic steps of monoterpene indole alkaloid (MIA) biosynthetic pathway are catalysed by strictosidine synthase (STR) that condensates tryptamine and secologanin to form strictosidine and by strictosidine β-D-glucosidase (SGD) that subsequently hydrolyses the glucose moiety of strictosidine. The resulting unstable aglycon is rapidly converted into a highly reactive dialdehyde, from which more than 2,000 MIAs are derived. Many studies were conducted to elucidate the biosynthesis and regulation of pharmacologically valuable MIAs such as vinblastine and vincristine in Catharanthus roseus or ajmaline in Rauvolfia serpentina. However, very few reports focused on the MIA physiological functions.     

The ecology of Lake Myvatn and the River Laxá: Variation in space and time

Ecological features of Lake Myvatn and the outflowing River Laxá show a wide range of spatial and temporal variations. The physical division of the lake into three main basins and the variation in chemical composition and temperature of the artesian springs feeding this shallow productive lake have large spatial effects. Variation in groundwater characteristics depends on percolation time and proximity to geothermal sources. Variation in precipitation is evened out by the porous volcanic soil and bedrock and the spring-water discharge is therefore very stable. A pulse of volcanic activity in 1975–1984 (the Krafla Fires) heated the groundwater entering the North Basin of the lake and changed its chemistry. Although much reduced, these effects have not disappeared yet, but overall the impact of the volcanic activity on the biota seemed minimal. Recycling of nutrients through internal loading is important and occurs on various time scales. In winter, when the lake is ice-covered, the topmost 5-cm layer of sediment pore water has a hundredfold concentration of nutrients relative to the overlying lake water. The nutrients are released during the ice-free period by sediment resuspension, diffusion, bioturbation and recycling. In spring, resuspension events sometimes lead to spikes in dissolved phosphorus and nitrogen, but there is little evidence of any major desorption of nutrients from suspended particles during such events later in the summer. In contrast to the stable groundwater, the biota show more or less regular fluctuations with no straightforward correlation with external signals. The most prominent fluctuations, those of the chironomid Tanytarsus gracilentus seem to be driven by interactions between the species and its sediment resources. Fluctuations in other invertebrates could be a consequence of the Tanytarsus cycles due to the large impact this species has on the benthic environment of this detritus-driven ecosystem. Temporal variation in epibenthic chironomids and Cladocera translates into variable production of vertebrate predators (Arctic charr, Salvelinus alpinus, and ducks), body condition and mortality of fish and sometimes into return rates of migrating adult ducks. The waterfowl show large temporal variation on a centennial scale, e.g., the invasion of the tufted duck (Aythya fuligula) which arrived by the end of the 19th century and has by now outnumbered other species. Fluctuations of Cyanobacteria (Anabaena) and the fish Gasterosteus aculeatus (three-spined stickleback) harmonize with the cycles in the benthic community. Palaeolimnological studies indicate that primary production in the South Basin became increasingly benthic as the lake depth was reduced by sedimentation (around 2 mm year^–1). Other trends include a decrease in Tanytarsus and Daphnia and an exponential increase in green algae (Cladophorales, Pediastrum) and associated organisms.     

The biomechanics of skipping gaits: a third locomotion paradigm?

Skipping, a gait children display when they are about four- to five-years-old, is revealed to be more than a behavioural peculiarity. By means of metabolic and biomechanical measurements at several speeds, the relevance of skipping is shown to extend from links between bipedal and quadrupedal locomotion (namely galloping) to understanding why it could be a gait of choice in low-gravity conditions, and to some aspects of locomotion evolution (ground reaction forces of skipping seem to originate from pushing the walking gait to unnaturally high speeds). When the time-courses of mechanical energy and the horizontal ground reaction force are considered, a different locomotion paradigm emerges, enabling us to separate, among the bouncing gaits, the trot from the gallop (quadrupeds) and running from skipping (bipeds). The simultaneous use of pendulum-like and elastic mechanisms in skipping gaits, as shown by the energy curve analysis, helps us to understand the low cost of transport of galloping quadrupeds.     

The genome in space and time: Does form always follow function?

Recent systematic studies using newly developed genomic approaches have revealed common mechanisms and principles that underpin the spatial organization of eukaryotic genomes and allow them to respond and adapt to diverse functional demands. Genomes harbor, interpret, and propagate genetic and epigenetic information, and the three-dimensional (3D) organization of genomes in the nucleus should be intrinsically linked to their biological functions. However, our understanding of the mechanisms underlying both the topological organization of genomes and the various nuclear processes is still largely incomplete. In this essay, we focus on the functional relevance as well as the biophysical properties of common organizational themes in genomes (e.g. looping, clustering, compartmentalization, and dynamics), and examine the interconnection between genome structure and function from this angle. Present evidence supports the idea that, in general, genome architecture reflects and influences genome function, and is relatively stable. However, the answer as to whether genome architecture is a hallmark of cell identity remains elusive.     

The earliest history of the deuterostomes: the importance of the Chengjiang Fossil-Lagerst?tte

While the broad framework of deuterostome evolution is now clear, the remarkable diversity of extant forms within this group has rendered the nature of the ancestral types problematic: what, for example, does the common ancestor of a sea urchin and lamprey actually look like? The answer to such questions can be addressed on the basis of remarkably well-preserved fossils from Cambrian Lagerstätten, not least the celebrated Chengjiang Lagerstätte (Yunnan, China). This deposit is particularly important because of its rich diversity of deuterostomes. These include some of the earliest known representatives, among which are the first vertebrates, as well as more enigmatic groups, notably the vetulicolians and yunnanozoans. The latter groups, in particular, have been the subject of some radical divergences in opinion as to their exact phylogenetic placements. Here, we both review the known diversity of Chengjiang deuterostomes and in particular argue that the vetulicolians and yunnanozoans represent very primitive deuterostomes. Moreover, in the latter case we present new data to indicate that the yunnanozoans are unlikely to be any sort of chordate.     

Role of autophagy in the clearance of mutant huntingtin: a step towards therapy?

Macroautophagy (henceforth referred to simply as autophagy) is a bulk degradation process involved in the clearance of long-lived proteins, protein complexes and organelles. A portion of the cytosol, with its contents to be degraded, is enclosed by double-membrane structures called autophagosomes/autophagic vacuoles, which ultimately fuse with lysosomes where their contents are degraded. In this review, we will describe how induction of autophagy is protective against toxic intracytosolic aggregate-prone proteins that cause a range of neurodegenerative diseases. Autophagy is a key clearance pathway involved in the removal of such proteins, including mutant huntingtin (that causes Huntington’s disease), mutant ataxin-3 (that causes spinocerebellar ataxia type 3), forms of tau that cause tauopathies, and forms of alpha-synuclein that cause familial Parkinson’s disease. Induction of autophagy enhances the clearance of both soluble and aggregated forms of such proteins, and protects against toxicity of a range of these mutations in cell and animal models. Interestingly, the aggregates formed by mutant huntingtin sequester and inactivate the mammalian target of rapamycin (mTOR), a key negative regulator of autophagy. This results in induction of autophagy in cells with these aggregates.     

Current advances in the phylogenetic reconstruction of metazoan evolution. A new paradigm for the Cambrian explosion?

The study of metazoan evolution has fascinated biologists for centuries, and it will certainly keep doing so. Recent interest on the origin of metazoan body plans, early metazoan evolution, genetic mechanisms generating disparity and diversity, molecular clock information, paleontology, and biogeochemistry is contributing to a better understanding of the current phyletic diversity. Unfortunately, the pattern of the metazoan tree of life still shows some important gaps in knowledge. It is the aim of this article to review some of the most important issues related to the inference of the metazoan tree, and point towards possible ways of solving certain obscure aspects in the history of animal evolution. A new hypothesis of the metazoan diversification during the Cambrian explosion is proposed by synthesizing ideas from phylogenetics, molecular evolution, paleontology, and developmental biology.     

The phylogenetic system of primates—character evolution in the light of a consolidated tree

Molecular analyses of the last decades helped solving the major open questions on the external and internal phylogenetic relationships of primates. The present review uses these data for the inference of character evolution along the branches of the primate tree. Altogether, more than 200 evolutionary changes in hard and soft tissue anatomy/morphology, behavior, physiology, and protein constitution are presented in the context of their functional relevance and adaptive value. The compilation focuses on primates as a whole and on the higher-ranked primate subtaxa with living representatives: Strepsirhini: Lorisiformes, Galagidae, Lorisidae, Lemuriformes; Haplorhini: Tarsioidea, Anthropoidea, Platyrrhini, Atelidae + Cebidae, Atelidae, Cebidae, Aotinae, Callithrichinae, Cebinae, Pitheciidae, Pithecinae, Catarrhini, Cercopithecoidea, Cercopithecinae, Colobinae, Colobini, and Hominoidea. Within Hominoidea character evolution is traced down to more peripheral branches: Hylobatidae, Hominidae, Pongo, Homininae, Gorilla, Pan + Homo, Pan, and modern humans. Character states in extinct representatives of Plesiadapiformes, Omomyoidea, Propliopithecidae, Hominini, etc. are always taken into account; they are presented in detail whenever character-state distribution in living species is ambiguous or misleading. The taxonomic sample and the characters included combine to a phylogenetic system that illustrates primate evolution and diversity. The data presented additionally provide a detailed picture of the evolutionary steps and trends involved in hominization. Reflections on the frequently underestimated role of polymorphisms in phylogenetic analyses complete the survey.     

Role of motor cortex in coordinating multi-joint movements: is it time for a new paradigm?

Reaching movements to spatial targets require motor patterns at the shoulder to be coordinated carefully with those at the elbow to smoothly move the hand through space. While the motor cortex is involved in this volitional task, considerable debate remains about how this cortical region participates in planning and controlling movement. This article reviews two opposing interpretations of motor cortical function during multi-joint movements. On the one hand, studies performed predominantly on single-joint movement generally support the notion that motor cortical activity is intimately involved in generating motor patterns at a given joint. In contrast, studies on reaching demonstrate correlations between motor cortical activity and features of movement related to the hand, suggesting that the motor cortex may be involved in more global features of the task. Although this latter paradigm involves a multi-joint motor task in which neural activity is correlated with features of movement related to the hand, this neural activity is also correlated to other movement variables. Therefore it is difficult to assess if and how the motor cortex contributes to the coordination of motor patterns at different joints. In particular, present paradigms cannot assess whether motor cortical activity contributes to the control of one joint or multiple joints during whole-arm tasks. The final point discussed in this article is the development of a new experimental device (KINARM) that can both monitor and manipulate the mechanics of the shoulder and elbow independently during multi-joint motor tasks. It is hoped that this new device will provide a new approach for examining how the motor cortex is involved in motor coordination.     

The cost of disturbance: a waste of time and energy?

Quantifying the effect of disturbance is a central issue in conservation. Using time and energy budgets, we obtain a range of ways to assess the importance of disturbance. One measure is the time that must be spent foraging in order to balance the energy budget. From this we derive critical levels of wastage (rate of disturbance multiplied by duration of disturbance) at which the animal runs out of time or reaches a limit on energy expenditure. In the case of the time constraint, the critical wastage is the net rate of energetic gain while foraging divided by the rate of energetic expenditure during a disturbance. The associated critical rate of disturbance is the net rate of energetic gain while foraging divided by the energy spent during a disturbance. The model is illustrated using data from the African wild dog, which suffers disturbance from lions and kleptoparasitism from hyenas. Findings suggest that disturbance imposes significant costs on wild dog time and energy budgets. We show how alternative environments can be evaluated in terms of their effective rate of gain, which is the net rate of gain from foraging minus the rate of energy expenditure as a result of disturbance.     

The importance of willow thickets for ptarmigan and hares in shrub tundra: the more the better?

In patchy habitats, the relationship between animal abundance and cover of a preferred habitat may change with the availability of that habitat, resulting in a functional response in habitat use. Here, we investigate the relationship of two specialized herbivores, willow ptarmigan (Lagopus lagopus) and mountain hare (Lepus timidus), to willows (Salix spp.) in three regions of the shrub tundra zone-northern Norway, northern European Russia and western Siberia. Shrub tundra is a naturally patchy habitat where willow thickets represent a major structural element and are important for herbivores both as food and shelter. Habitat use was quantified using feces counts in a hierarchical spatial design and related to several measures of willow thicket configuration. We document a functional response in the use of willow thickets by ptarmigan, but not by hares. For hares, whose range extends into forested regions, occurrence increased overall with willow cover. The occurrence of willow ptarmigan showed a strong positive relationship to willow cover and a negative relationship to thicket fragmentation in the region with lowest willow cover at landscape scale, where willow growth may be limited by reindeer browsing. In regions with higher cover, in contrast, such relationships were not observed. Differences in predator communities among the regions may contribute to the observed pattern, enhancing the need for cover where willow thickets are scarce. Such region-specific relationships reflecting regional characteristics of the ecosystem highlight the importance of large-scale investigations to understand the relationships of habitat availability and use, which is a critical issue considering that habitat availability changes quickly with climate change and human impact.     

The interference of flexible working times with the utility of time: a predictor of social impairment?

Periodic components inherent in actual schedules of flexible working hours and their interference with social rhythms were measured using spectrum analysis. The resulting indicators of periodicity and interference were then related to the reported social impairments of workers. The results show that a suppression of the 24 and the 168 h (seven-day) components (absence of periodicity) in the work schedules predicts reported social impairment. However, even if there are relatively strong 24 and 168 h components left in the work schedules, their interference with the social rhythm (using the phase difference between working hours and the utility of time) further predicts impairment. The results thus indicate that the periodicity of working hours and the amount of (social) desynchronization induced by flexible work schedules can be used both for predicting the impairing effects of the specific work schedules on social well-being as well as for the design of socially acceptable flexible work hours.     

Quantitative genetics of Aedes aegypti vector competence for dengue viruses: towards a new paradigm?

Similar to many other host-pathogen interactions, the vector competence of Aedes aegypti for dengue viruses appears to be determined by genotype-by-genotype interactions, whereby the outcome of infection depends on the specific combination of mosquito and virus genotypes. This can complicate efforts to dissect the genetic basis of vector competence in nature because it obscures mapping between genotype and phenotype and brings into question the notion of universal mosquito resistance or susceptibility. Conversely, it offers novel opportunities to better define compatible vector-pathogen associations based on integration of both vector and pathogen genomics, which should eventually improve understanding of pathogen transmission dynamics and the risk of vector-borne disease emergence.