Pyruvate Decarboxylase Catalysed Formation of Terpenoid α-hydroxy Ketones

Enzyme extracts of the wild type yeast Zygosaccharomyces bisporus were applied for the pyruvate decarboxylase catalysed condensation of pyruvate and (R)-(+)-and (S)-(?)-perillyl aldehyde, (±)-citronellal, neral, geranial or (R)-(?)-myrtenal to form novel α-hydroxy ketones. Best yields were obtained when the transformation medium contained 25% (v/v) of the cosolvent N,N-dimethylformamide. Conversion of (R)-(+)-perillyl aldehyde to (1R)-1-hydroxy-1-[(4’R)-4’-isopropenyl-1-cyclohexen-1-yl]-2-propanone proceeded highly stereospecifically (>99% de), whereas the stereoselectivity was somewhat less in the transformation of (S)-(?)-perillyl aldehyde (58% de) and (R)-(?)-myrtenal (92% de). All of the new compounds imparted characteristic odour impressions as determined by means of GC-olfactometry.     

The carotid plaque imaging in acute stroke (CAPIAS) study: protocol and initial baseline data

Background

In up to 30% of patients with ischemic stroke no definite etiology can be established. A significant proportion of cryptogenic stroke cases may be due to non-stenosing atherosclerotic plaques or low grade carotid artery stenosis not fulfilling common criteria for atherothrombotic stroke. The aim of the CAPIAS study is to determine the frequency, characteristics, clinical and radiological long-term consequences of ipsilateral complicated American Heart Association lesion type VI (AHA-LT VI) carotid artery plaques in patients with cryptogenic stroke.

Methods/Design

300 patients (age >49 years) with unilateral DWI-positive lesions in the anterior circulation and non- or moderately stenosing (<70% NASCET) internal carotid artery plaques will be enrolled in the prospective multicenter study CAPIAS. Carotid plaque characteristics will be determined by high-resolution black-blood carotid MRI at baseline and 12 month follow up. Primary outcome is the prevalence of complicated AHA-LT VI plaques in cryptogenic stroke patients ipsilateral to the ischemic stroke compared to the contralateral side and to patients with defined stroke etiology. Secondary outcomes include the association of AHA-LT VI plaques with the recurrence rates of ischemic events up to 36 months, rates of new ischemic lesions on cerebral MRI (including clinically silent lesions) after 12 months and the influence of specific AHA-LT VI plaque features on the progression of atherosclerotic disease burden, on specific infarct patterns, biomarkers and aortic arch plaques.

Discussion

CAPIAS will provide important insights into the role of non-stenosing carotid artery plaques in cryptogenic stroke. The results might have implications for our understanding of stroke mechanism, offer new diagnostic options and provide the basis for the planning of targeted interventional studies.

Trial Registration

NCT01284933

     

Source pools and disharmony of the world's island floras

Island disharmony refers to the biased representation of higher taxa on islands compared to their mainland source regions and represents a central concept in island biology. Here, we develop a generalizable framework for approximating these source regions and conduct the first global assessment of island disharmony and its underlying drivers. We compiled vascular plant species lists for 178 oceanic islands and 735 mainland regions. Using mainland data only, we modelled species turnover as a function of environmental and geographic distance and predicted the proportion of shared species between each island and mainland region. We then quantified the over‐ or under‐representation of families on individual islands (representational disharmony) by contrasting the observed number of species against a null model of random colonization from the mainland source pool, and analysed the effects of six family‐level functional traits on the resulting measure. Furthermore, we aggregated the values of representational disharmony per island to characterize overall taxonomic bias of a given flora (compositional disharmony), and analysed this second measure as a function of four island biogeographical variables. Our results indicate considerable variation in representational disharmony both within and among plant families. Examples of generally over‐represented families include Urticaceae, Convolvulaceae and almost all pteridophyte families. Other families such as Asteraceae and Orchidaceae were generally under‐represented, with local peaks of over‐representation in known radiation hotspots. Abiotic pollination and a lack of dispersal specialization were most strongly associated with an insular over‐representation of families, whereas other family‐level traits showed minor effects. With respect to compositional disharmony, large, high‐elevation islands tended to have the most disharmonic floras. Our results provide important insights into the taxon‐ and island‐specific drivers of disharmony. The proposed framework allows overcoming the limitations of previous approaches and provides a quantitative basis for incorporating functional and phylogenetic approaches into future studies of island disharmony.     

New Skull Material of Taeniolabis taoensis (Multituberculata,Taeniolabididae) from the Early Paleocene (Danian) of the Denver Basin,Colorado

Journal of Mammalian Evolution - Taeniolabis taoensis is an iconic multituberculate mammal of early Paleocene (Puercan 3) age from the Western Interior of North America. Here we report the...     

Shade-Tree Rehabilitation in Vanilla Agroforests is Yield Neutral and May Translate into Landscape-Scale Canopy Cover Gains

Ecosystems - Agroforestry can contribute to an increase in tree cover in historically forested tropical landscapes with associated gains in biodiversity and ecosystem functioning, but only if...     

Rapid phospho-turnover by receptor tyrosine kinases impacts downstream signaling and drug binding

Epidermal growth factor receptors (ErbB1-4) are oncogenic receptor tyrosine kinases (RTKs) that regulate diverse cellular processes. In this study, we combine measurement and mathematical modeling to quantify phospho-turnover at ErbB receptors in human cells and to determine the consequences for signaling and drug binding. We find that phosphotyrosine residues on ErbB1 have half-lives of a few seconds and therefore turn over 100-1000 times in the course of a typical immediate-early response to ligand. Rapid phospho-turnover is also observed for EGF-activated ErbB2 and ErbB3, unrelated RTKs, and multiple intracellular adaptor proteins and signaling kinases. Thus, the complexes formed on the cytoplasmic tail of active receptors and the downstream signaling kinases they control are highly dynamic and antagonized by potent phosphatases. We develop a kinetic scheme for binding of anti-ErbB1 drugs to receptors and show that rapid phospho-turnover significantly impacts their mechanisms of action.     

The roads and bridges of science. Research infrastructures are key components of Europe's future research, but their funding is not guaranteed

Research infrastructures are a crucial component of modern biological research, but the EU has not yet figured out how to fund and maintain them.The development of recombinant gene technology in the 1970s heralded a new era of application-oriented research for molecular biology, with a huge economic impact. During the decades that have followed, biological research and development have become a major enterprise, with an increasing demand for sophisticated technologies, databases, tissue banks and other tools that range from microscopes and DNA sequencers to bioinformatics services and mutant collections. Biology has followed in the footsteps of physics and astronomy, which share costly instrumentation such as particle accelerators, observatories and satellites. A key difference is that biological research infrastructures are often distributed across several sites and are less costly to establish. Nevertheless, they are expensive to operate and maintain, and need long-term financial support.There is no doubt among scientists that research infrastructures are essential for biomedicine and the life sciencesThe European Union (EU) regards biomedical research as an important component of its future economic and social development as part of its ''Innovation Union'' strategy (EC, 2010), but the necessary creation and operation of research infrastructures is not keeping pace. European biologists have been highlighting the problem for years (van Dyck, 2005), to the effect that some pan-European infrastructures for biomedical research and the life sciences have been created, such as the European Bioinformatics Institute (EBI; Hinxton, UK). The European Commission (EC) also established the European Strategy Forum on Research Infrastructures (ESFRI) in 2002, to define the infrastructures required for international research (ESFRI, 2006, 2011). However, most of the planned projects for the biomedical and life sciences (ESFRI, 2011)

Biology of the sauropod dinosaurs: the evolution of gigantism

The herbivorous sauropod dinosaurs of the Jurassic and Cretaceous periods were the largest terrestrial animals ever, surpassing the largest herbivorous mammals by an order of magnitude in body mass. Several evolutionary lineages among Sauropoda produced giants with body masses in excess of 50 metric tonnes by conservative estimates. With body mass increase driven by the selective advantages of large body size, animal lineages will increase in body size until they reach the limit determined by the interplay of bauplan, biology, and resource availability. There is no evidence, however, that resource availability and global physicochemical parameters were different enough in the Mesozoic to have led to sauropod gigantism. We review the biology of sauropod dinosaurs in detail and posit that sauropod gigantism was made possible by a specific combination of plesiomorphic characters (phylogenetic heritage) and evolutionary innovations at different levels which triggered a remarkable evolutionary cascade. Of these key innovations, the most important probably was the very long neck, the most conspicuous feature of the sauropod bauplan. Compared to other herbivores, the long neck allowed more efficient food uptake than in other large herbivores by covering a much larger feeding envelope and making food accessible that was out of the reach of other herbivores. Sauropods thus must have been able to take up more energy from their environment than other herbivores. The long neck, in turn, could only evolve because of the small head and the extensive pneumatization of the sauropod axial skeleton, lightening the neck. The small head was possible because food was ingested without mastication. Both mastication and a gastric mill would have limited food uptake rate. Scaling relationships between gastrointestinal tract size and basal metabolic rate (BMR) suggest that sauropods compensated for the lack of particle reduction with long retention times, even at high uptake rates. The extensive pneumatization of the axial skeleton resulted from the evolution of an avian‐style respiratory system, presumably at the base of Saurischia. An avian‐style respiratory system would also have lowered the cost of breathing, reduced specific gravity, and may have been important in removing excess body heat. Another crucial innovation inherited from basal dinosaurs was a high BMR. This is required for fueling the high growth rate necessary for a multi‐tonne animal to survive to reproductive maturity. The retention of the plesiomorphic oviparous mode of reproduction appears to have been critical as well, allowing much faster population recovery than in megaherbivore mammals. Sauropods produced numerous but small offspring each season while land mammals show a negative correlation of reproductive output to body size. This permitted lower population densities in sauropods than in megaherbivore mammals but larger individuals. Our work on sauropod dinosaurs thus informs us about evolutionary limits to body size in other groups of herbivorous terrestrial tetrapods. Ectothermic reptiles are strongly limited by their low BMR, remaining small. Mammals are limited by their extensive mastication and their vivipary, while ornithsichian dinosaurs were only limited by their extensive mastication, having greater average body sizes than mammals.