The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site

BAK/BAX-mediated mitochondrial outer-membrane permeabilization (MOMP) drives cell death during development and tissue homeostasis from zebrafish to humans. In most cancers, this pathway is inhibited by BCL-2 family antiapoptotic members, which bind and block the action of proapoptotic BCL proteins. We report the 1.5 A crystal structure of calpain-proteolysed BAK, cBAK, to reveal a zinc binding site that regulates its activity via homodimerization. cBAK contains an occluded BH3 peptide binding pocket that binds a BID BH3 peptide only weakly . Nonetheless, cBAK requires activation by truncated BID to induce cytochrome c release in mitochondria isolated from bak/bax double-knockout mouse embryonic fibroblasts. The BAK-mediated MOMP is inhibited by low micromolar zinc levels. This inhibition is alleviated by mutation of the zinc-coordination site in BAK. Our results link directly the antiapoptotic effects of zinc to BAK.     

Influence of nebivolol and metoprolol on inflammatory mediators in human coronary endothelial or smooth muscle cells. Effects on neointima formation after balloon denudation in carotid arteries of rats treated with nebivolol.

OBJECTIVE AND BACKGROUND: Inflammation plays a critical role in all stages of atherogenesis. Proliferating vascular smooth muscle cells (SMC) and endothelial cells (EC) enhancing the inflammatory response, both contribute to the progression of atherosclerosis. Anti-proliferative, anti-inflammatory and anti-oxidative therapy seems to be a promising therapeutic strategy. The aim of this study was to assess the anti-proliferative and anti-inflammatory effect of the beta-blocker nebivolol in comparison to metoprolol in vitro and to find out whether nebivolol inhibits neointima formation in vivo. METHODS AND RESULTS: Real-time-RT-PCR revealed a decrease in VCAM-1, ICAM-1, PDGF-B, E-selectin and P-selectin mRNA expression in human coronary artery EC and SMC incubated with nebivolol for 72 hours while metoprolol did not have this effect. Nebivolol reduced MCP-1 and PDGF-BB protein in the culture supernatant of SMC and EC, respectively. Sprague-Dawley rats were treated with nebivolol for 0 or 35 days before and 28 days after carotid balloon injury. Immunohistological analyses showed that pre-treatment with nebivolol was associated with a decreased number of SMC layers and macrophages and an increased lumen area at the site of the arterial injury. The intima area was reduced by 43% after pre-treatment. CONCLUSION: We found that nebivolol reduced the expression of proinflammatory genes in endothelial cells and vascular smooth muscle cells in vitro whereas metoprolol did not. In vivo, nebivolol inhibited neointima formation by reducing SMC proliferation and macrophage accumulation.     

The multi-mode polarization modulation spectrometer: part 1: simultaneous detection of absorption, turbidity, and optical activity

Circular dichroism (CD) is an important spectroscopic technique for monitoring chirality and biological macromolecule conformation. However, during a CD measurement, absorbance, light scattering/turbidity, and fluorescence can also be detected. The simultaneous measurement of these different spectral features for a single sample is the basis of a multi-mode optical spectrometer. This allows time-efficient gathering of complementary information and provides a scheme to ensure that CD measurements are reliable. Aspects of circular polarization differential light scattering, pH, and temperature variation of a protein (antibody) solution are described. A procedure to help ensure that CD measurements are reliable is described.     

Constructing black Jews: genetic tests and the Lemba--the 'black Jews' of South Africa

This commentary examines the use of Y-chromosome testing to reconstruct a genetic ancestry for the Lemba, a group in southern Africa that has long considered itself Jewish. The commentary looks especially at the reasons why this project drew such attention from the mainstream media.     

IMP,GTP, and 6-phosphoryl-IMP complexes of recombinant mouse muscle adenylosuccinate synthetase

Prokaryotes have a single form of adenylosuccinate synthetase that controls the committed step of AMP biosynthesis, but vertebrates have two isozymes of the synthetase. The basic isozyme, which predominates in muscle, participates in the purine nucleotide cycle, has an active site conformation different from that of the Escherichia coli enzyme, and exhibits significant differences in ligand recognition. Crystalline complexes presented here of the recombinant basic isozyme from mouse show the following. GTP alone binds to the active site without inducing a conformational change. IMP in combination with an acetate anion induces major conformational changes and organizes the active site for catalysis. IMP, in the absence of GTP, binds to the GTP pocket of the synthetase. The combination of GTP and IMP results in the formation of a stable complex of 6-phosphoryl-IMP and GDP in the presence or absence of hadacidin. The response of the basic isozyme to GTP alone differs from that of synthetases from plants, and yet the conformation of the mouse basic and E. coli synthetases in their complexes with GDP, 6-phosphoryl-IMP, and hadacidin are nearly identical. Hence, reported differences in ligand recognition among synthetases probably arise from conformational variations observed in partially ligated enzymes.     

Directional female preference for an exaggerated male trait in canary (Serinus canaria) song

Motor constraints on vocal production impose a trade-off between trill rate and frequency bandwidth within birdsong. We tested whether domesticated canary (Serinus canaria) females, reared either in acoustic isolation or in aviary conditions, had a preference for broad bandwidth songs with artificially increased syllable rates. The copulation solicitation display (CSD) was used as an index of female preference. As predicted, both naive and experienced females were especially responsive to syllables with a broad bandwidth emitted at an artificially increased rate. Female preference for supernormal stimuli provide support for the honest-signalling hypothesis and our results are consistent with recent findings indicating that production of song phrases maximizing both bandwidth and syllable rate may be a reliable indicator of male physical or behavioural qualities. We suggest that female preference for vocal emissions, which simultaneously maximize these two parameters, could be a widespread pattern within songbirds.     

Functional symmetries in the schmelzmuster and morphology of rootless rodent molars

Morphology and schmelzmuster of rootless cheek teeth of 25 extant rodent genera were studied in relation to jaw movement. A differentiation between leading and trailing edges is observed regularly in enamel thickness and schmelzmuster. Similarities between antagonists are interpreted as 'functional symmetries'. Differences in the enamel thickness, the schmelzmuster and orientation of cutting edges are controlled by functional and phylogenetic constraints. The heterogenous sample allows discrimination between these two constraints. The most obvious functional constraint leads to the almost regular occurrence of radial enamel on the push sides of cutting edges. The degree of functional symmetry seems to be determined by phylogenetic limitations.     

Micropropagation of wild beet (Beta maritima) from inflorescence pieces

In order to investigate the regeneration of wild beet (Beta maritima) from inflorescence pieces, the effects of growth regulator, genotype, explant source and stage of plant development on adventitious shoot formation and rooting in vitro and subsequent transplanting in the glasshouse were tested. Inflorescence tips produced more adventitious shoots than sub-apical segments and the best micropropagation was achieved on a Murashige and Skoog (MS) medium supplemented with 1.0 mg l^–1 BAP. Addition of auxin was not beneficial. The induction rate of adventitious shoots was genotype-dependent and influenced by the stage of plant development. Adventitious shoots were produced from the base of the flower buds, i.e. from the receptacle, not from axils or stalks and only a few buds on inflorescence tip explants produced adventitious shoots. Rooting was increased by using a MS medium with 3% sucrose supplemented with 1.0 mg l^–1 NAA. There was no variation in leaf morphology of the transplants. This work shows that inflorescence tips can be used successfully as explants for in vitro multiplication of sugar beet and wild beet.Abbreviations BAP benzylaminopurine - IBA indole-3-butyric acid - GA₃ gibberellic acid - MS Murashige and Skoog medium - NAA naphthaleneacetic acid Author for correspondence     

Responses of florence fennel (Foeniculum vulgare azoricum) seeds to light,temperature and gibberellin A4/7

The percentage and the rate of germination of seeds of three varieties of Florence fennel was higher in the dark than in the light, the high temperature cut-off points being between 27.2 and 29.4°C. The optimum temperature for germination was between 20 and 25°C. Seeds of all three varieties responded to incubation in solutions containing gibberellin A_4/7 mixture (GA_4/7; Regulex), giving higher germination in the light at temperatures from 20 to 30°C. Seeds steeped for 4 h at 25°C or for 24 h at 5°C in GA_4/7 solutions gave a higher percentage and increased rate of emergence as compared with untreated dry seeds, when sown in compost at 25°C; steeping in water alone was also beneficial. In general, drying the treated seeds before sowing reduced the rate but sometimes increased the percentage of germination as compared with seeds sown when still moist. Seeds harvested from secondary umbels of var. Zefa fino germinated better both in the light and dark than those taken from primary umbels.Abbreviations GA_4/7 a commercial mixture of the gibberellins A₄ and A₇ (trade name Regulex)