Chemistry and meteorology, 1700–1825

In 1639–1640 Benedetto Castelli (1577–1643) wrote a treatise on the loadstone which is quite unlike any of its contemporaries. In it are the origins of the notion of elementary magnets sharing a common alignment, the idea that all materials are magnetic in different ways, and the first intimation of the conception of magnetic domains. Castelli did not publish his treatise. Nevertheless his work was noted during his life-time, and may have exerted an influence on the development of magnetic theory in the 17th century. The treatise was published in 1883. Since then, however, it has either been neglected or not appreciated. It deserves being rescued from the neglect of more than three centuries.     

The American Philosophical Society and the rise of astronomy in the United States in the middle of the nineteenth century

Early geological investigations in the St David's area (Pembrokeshire) are described, particularly the work of Murchison. In a reconnaissance survey in 1835, he regarded a ridge of rocks at St David's as intrusive in unfossiliferous Cambrian; and the early Survey mapping (chiefly the work of Aveline and Ramsay) was conducted on that assumption, leading to the publication of maps in 1845 and 1857. The latter represented the margins of the St David's ridge as ‘Altered Cambrian’. So the supposedly intrusive ‘syenite’ was regarded as younger, and there was no Precambrian. These views were challenged by a local doctor, Henry Hicks, who developed an idea of the ex-Survey palaeontologist John Salter that the rocks of the ridge were stratified and had formed a Precambrian island, round which Cambrian sediments (now confirmed by fossil discoveries) had been deposited. Hicks subsequently proposed subdivision of his Precambrian into ‘Dimetian’, ‘Pebidian’, and (later) ‘Arvonian’, and he attempted correlations with rocks in Shropshire, North Wales, and even North America, seeking to develop the neo-Neptunist ideas of Sterry Hunt. The challenge to the Survey's work was countered in the 1880s by the Director General, Geikie, who showed that Hicks's idea of stratification in the Dimetian was mistaken. A heated controversy developed, several amateur geologists, supported by a group of Cambridge Sedgwickians, forming a coalition of ‘Archaeans’ against the Survey. Geikie was supported by Lloyd Morgan. Attention focused particularly on Ogof Lle-sugn Cave and St Non's Arch, with theory/controversy-ladenness of observations evident on both sides. Evidence from an eyewitness student record of a Geological Society meeting reveals the ‘sanit`ized’ nature of the official summary of the debate in QJGS. Field mapping early in the twentieth century by J. F. N. Green allowed a compromise consensus to be achieved, but Green's evidence for unconformity between the Cambrian and the Dimetian, obtained by excavation, can no longer be verified, and his consensual history of the area may need revision. Unconformity between the Cambrian and the Pebidian tuffs is not in doubt, however, and Precambrian at St David's is accepted. The study exhibits features of geological controversy and the British geological community in the nineteenth century. It also furnishes a further instance of the great influence of Murchison in nineteenth-century British geology and the side-effects of his controversy with Sedgwick.     

Multiple paths to aquatic specialisation in four species of Central American Anolis lizards

Aquatic anoles present an interesting ecomorphological puzzle. On the one hand, the link between habitat use and morphology is well established as convergent within the Caribbean anole radiation. On the other hand, aquatic anoles do not appear to form an ecomorphological group – rather, it appears that there may be several ways to adapt to aquatic habitats. We explore this issue by examining the ecology, morphology and performance of four species of Central American aquatic anoles belonging to two different lineages. Overall, we find that aquatic anoles overlap in multiple ecological and morphological dimensions. However, we do find some differences in substrate use, claw and limb morphology, and bite force that distinguish Anolis aquaticus from the other three species (A. lionotus, A. oxylophus and A. poecilopus). Our results suggest that A. aquaticus is adapted to climb on boulders, whereas the other species utilise vegetation in streamside habitats.     

Forecasting VaR models under Different Volatility Processes and Distributions of Return Innovations

This paper provides clear‐cut evidence that the out‐of‐sample VaR (value‐at‐risk) forecasting performance of alternative parametric volatility models, like EGARCH (exponential general autoregressive conditional heteroskedasticity) or GARCH, and Markov regime‐switching models, can be considerably improved if they are combined with skewed distributions of asset return innovations. The performance of these models is found to be similar to that of the EVT (extreme value theory) approach. The performance of the latter approach can also be improved if asset return innovations are assumed to be skewed distributed. The performance of the Markov regime‐switching model is considerably improved if this model allows for EGARCH effects, for all different volatility regimes considered. Copyright © 2014 John Wiley & Sons, Ltd.     

Mechanisms of cellular invasion by intracellular parasites

Numerous disease-causing parasites must invade host cells in order to prosper. Collectively, such pathogens are responsible for a staggering amount of human sickness and death throughout the world. Leishmaniasis, Chagas disease, toxoplasmosis, and malaria are neglected diseases and therefore are linked to socio-economical and geographical factors, affecting well-over half the world’s population. Such obligate intracellular parasites have co-evolved with humans to establish a complexity of specific molecular parasite–host cell interactions, forming the basis of the parasite’s cellular tropism. They make use of such interactions to invade host cells as a means to migrate through various tissues, to evade the host immune system, and to undergo intracellular replication. These cellular migration and invasion events are absolutely essential for the completion of the lifecycles of these parasites and lead to their for disease pathogenesis. This review is an overview of the molecular mechanisms of protozoan parasite invasion of host cells and discussion of therapeutic strategies, which could be developed by targeting these invasion pathways. Specifically, we focus on four species of protozoan parasites Leishmania, Trypanosoma cruzi, Plasmodium, and Toxoplasma, which are responsible for significant morbidity and mortality.     

Transient dynamics of Aβ contribute to toxicity in Alzheimer’s disease

The aggregation and deposition of the amyloid-β peptide (Aβ) in the brain has been linked with neuronal death, which progresses in the diagnostic and pathological signs of Alzheimer’s disease (AD). The transition of an unstructured monomeric peptide into self-assembled and more structured aggregates is the crucial conversion from what appears to be a harmless polypeptide into a malignant form that causes synaptotoxicity and neuronal cell death. Despite efforts to identify the toxic form of Aβ, the development of effective treatments for AD is still limited by the highly transient and dynamic nature of interconverting forms of Aβ. The variability within the in vivo “pool” of different Aβ peptides is another complicating factor. Here we review the dynamical interplay between various components that influence the heterogeneous Aβ system, from intramolecular Aβ flexibility to intermolecular dynamics between various Aβ alloforms and external factors. The complex dynamics of Aβ contributes to the causative role of Aβ in the pathogenesis of AD.     

Key role of integrin αIIbβ3 signaling to Syk kinase in tissue factor-induced thrombin generation

The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.