The importance of regional geology in the geological theories of Abraham Gottlob Werner: a contrary opinion

It has been and still is commonly believed by geologists and historians of geology alike that geological theory is an extrapolation from the empirical knowledge of the geology of a region. Abraham Gottlob Werner (1749–1817), whose theory concerning the origin of basalt and the minor role of volcanoes and the major role of water in the history of the earth's crust was eventually proven wrong in some respects, is usually cited as the prime example of a geologist who had not ventured beyond the confines of his native region, Saxony, and had developed a universal geological theory based almost entirely on his observations of that region. In this essay I show that the geology of Saxony played a relatively unimportant role in the development of Werner's universal geological theory; that he became a neptunist before he had closely examined the geology of Saxony; and that his explanation of the history of the earth's crust was as reasonable, if not more reasonable, than the explanations brought forth by those of his contemporaries who opposed his views.     

Substrate ambiguity among the nudix hydrolases: biologically significant, evolutionary remnant, or both?

Many members of the nudix hydrolase family exhibit considerable substrate multispecificity and ambiguity, which raises significant issues when assessing their functions in vivo and gives rise to errors in database annotation. Several display low antimutator activity when expressed in bacterial tester strains as well as some degree of activity in vitro towards mutagenic, oxidized nucleotides such as 8-oxo-dGTP. However, many of these show greater activity towards other nucleotides such as ADP-ribose or diadenosine tetraphosphate (Ap₄A). The antimutator activities have tended to gain prominence in the literature, whereas they may in fact represent the residual activity of an ancestral antimutator enzyme that has become secondary to the more recently evolved major activity after gene duplication. Whether any meaningful antimutagenic function has also been retained in vivo requires very careful assessment. Then again, other examples of substrate ambiguity may indicate as yet unexplored regulatory systems. For example, bacterial Ap₄A hydrolases also efficiently remove pyrophosphate from the 5′ termini of mRNAs, suggesting a potential role for Ap₄A in the control of bacterial mRNA turnover, while the ability of some eukaryotic mRNA decapping enzymes to degrade IDP and dIDP or diphosphoinositol polyphosphates (DIPs) may also be indicative of new regulatory networks in RNA metabolism. DIP phosphohydrolases also degrade diadenosine polyphosphates and inorganic polyphosphates, suggesting further avenues for investigation. This article uses these and other examples to highlight the need for a greater awareness of the possible significance of substrate ambiguity among the nudix hydrolases as well as the need to exert caution when interpreting incomplete analyses.     

Structure of the ESCRT-II endosomal trafficking complex

The multivesicular-body (MVB) pathway delivers transmembrane proteins and lipids to the lumen of the endosome. The multivesicular-body sorting pathway has crucial roles in growth-factor-receptor downregulation, developmental signalling, regulation of the immune response and the budding of certain enveloped viruses such as human immunodeficiency virus. Ubiquitination is a signal for sorting into the MVB pathway, which also requires the functions of three protein complexes, termed ESCRT-I, -II and -III (endosomal sorting complex required for transport). Here we report the crystal structure of the core of the yeast ESCRT-II complex, which contains one molecule of the Vps protein Vps22, the carboxy-terminal domain of Vps36 and two molecules of Vps25, and has the shape of a capital letter 'Y'. The amino-terminal coiled coil of Vps22 and the flexible linker leading to the ubiquitin-binding NZF domain of Vps36 both protrude from the tip of one branch of the 'Y'. Vps22 and Vps36 form nearly equivalent interactions with the two Vps25 molecules at the centre of the 'Y'. The structure suggests how ubiquitinated cargo could be passed between ESCRT components of the MVB pathway through the sequential transfer of ubiquitinated cargo from one complex to the next.     

Stable isotopes of lithium: dissimilar biochemical and behavioral effects

Summary Lithium, which is used routinely in the treatment of mania, is composed of two stable isotopes, lithium-7 (92.58%) and lithium-6 (7.42%). Usually there is minimal physiological or biochemical differentiation between isotopes of an element, but lithium is an exception. Data derived from a variety of biochemical and behavioral experiments are reviewed to support this idea. Additionally, the clinical implications of this work are presented.     

The reactivity of anti-peptide antibodies is a function of the atomic mobility of sites in a protein

To study the nature of antigenic recognition, antibodies have been prepared against a set of peptide sequences representing both highly mobile and well-ordered regions of myohaemerythrin, based on X-ray crystallographic temperature factors. Anti-peptide antibodies against highly mobile regions react strongly with the native protein; anti-peptide antibodies from well-ordered regions do not. Mobility is a major factor in the recognition of the native protein by anti-peptide antibodies; this may be of general significance in protein-protein interactions.