A bacteriolytic agent that detects and kills Bacillus anthracis

The dormant and durable spore form of Bacillus anthracis is an ideal biological weapon of mass destruction. Once inhaled, spores are transported by alveolar macrophages to lymph nodes surrounding the lungs, where they germinate; subsequent vegetative expansion causes an overwhelming flood of bacteria and toxins into the blood, killing up to 99% of untreated victims. Natural and genetically engineered antibiotic-resistant bacilli amplify the threat of spores being used as weapons, and heighten the need for improved treatments and spore-detection methods after an intentional release. We exploited the inherent binding specificity and lytic action of bacteriophage enzymes called lysins for the rapid detection and killing of B. anthracis. Here we show that the PlyG lysin, isolated from the gamma phage of B. anthracis, specifically kills B. anthracis isolates and other members of the B. anthracis 'cluster' of bacilli in vitro and in vivo. Both vegetative cells and germinating spores are susceptible. The lytic specificity of PlyG was also exploited as part of a rapid method for the identification of B. anthracis. We conclude that PlyG is a tool for the treatment and detection of B. anthracis.     

Mineralogy of the mid-ocean-ridge basalt source from neodymium isotopic composition of abyssal peridotites

Inferring the melting process at mid-ocean ridges, and the physical conditions under which melting takes place, usually relies on the assumption of compositional similarity between all mid-ocean-ridge basalt sources. Models of mantle melting therefore tend to be restricted to those that consider the presence of only one lithology in the mantle, peridotite. Evidence from xenoliths and peridotite massifs show that after peridotite, pyroxenite and eclogite are the most abundant rock types in the mantle. But at mid-ocean ridges, where most of the melting takes place, and in ophiolites, pyroxenite is rarely found. Here we present neodymium isotopic compositions of abyssal peridotites to investigate whether peridotite can indeed be the sole source for mid-ocean-ridge basalts. By comparing the isotopic compositions of basalts and peridotites at two segments of the southwest Indian ridge, we show that a component other than peridotite is required to explain the low end of the (143)Nd/(144)Nd variations of the basalts. This component is likely to have a lower melting temperature than peridotite, such as pyroxenite or eclogite, which could explain why it is not observed at mid-ocean ridges.     

Identification of the platelet ADP receptor targeted by antithrombotic drugs

Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.     

The impact of cyclin-dependent kinase 5 depletion on poly(ADP-ribose) polymerase activity and responses to radiation

Cyclin-dependent kinase 5 (Cdk5) has been identified as a determinant of sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. Here, the consequences of its depletion on cell survival, PARP activity, the recruitment of base excision repair (BER) proteins to DNA damage sites, and overall DNA single-strand break (SSB) repair were investigated using isogenic HeLa stably depleted (KD) and Control cell lines. Synthetic lethality achieved by disrupting PARP activity in Cdk5-deficient cells was confirmed, and the Cdk5^KD cells were also found to be sensitive to the killing effects of ionizing radiation (IR) but not methyl methanesulfonate or neocarzinostatin. The recruitment profiles of GFP-PARP-1 and XRCC1-YFP to sites of micro-irradiated Cdk5^KD cells were slower and reached lower maximum values, while the profile of GFP-PCNA recruitment was faster and attained higher maximum values compared to Control cells. Higher basal, IR, and hydrogen peroxide-induced polymer levels were observed in Cdk5^KD compared to Control cells. Recruitment of GFP-PARP-1 in which serines 782, 785, and 786, potential Cdk5 phosphorylation targets, were mutated to alanines in micro-irradiated Control cells was also reduced. We hypothesize that Cdk5-dependent PARP-1 phosphorylation on one or more of these serines results in an attenuation of its ribosylating activity facilitating persistence at DNA damage sites. Despite these deficiencies, Cdk5^KD cells are able to effectively repair SSBs probably via the long patch BER pathway, suggesting that the enhanced radiation sensitivity of Cdk5^KD cells is due to a role of Cdk5 in other pathways or the altered polymer levels.     

Direct observation of Anderson localization of matter waves in a controlled disorder

In 1958, Anderson predicted the localization of electronic wavefunctions in disordered crystals and the resulting absence of diffusion. It is now recognized that Anderson localization is ubiquitous in wave physics because it originates from the interference between multiple scattering paths. Experimentally, localization has been reported for light waves, microwaves, sound waves and electron gases. However, there has been no direct observation of exponential spatial localization of matter waves of any type. Here we observe exponential localization of a Bose-Einstein condensate released into a one-dimensional waveguide in the presence of a controlled disorder created by laser speckle. We operate in a regime of pure Anderson localization, that is, with weak disorder-such that localization results from many quantum reflections of low amplitude-and an atomic density low enough to render interactions negligible. We directly image the atomic density profiles as a function of time, and find that weak disorder can stop the expansion and lead to the formation of a stationary, exponentially localized wavefunction-a direct signature of Anderson localization. We extract the localization length by fitting the exponential wings of the profiles, and compare it to theoretical calculations. The power spectrum of the one-dimensional speckle potentials has a high spatial frequency cutoff, causing exponential localization to occur only when the de Broglie wavelengths of the atoms in the expanding condensate are greater than an effective mobility edge corresponding to that cutoff. In the opposite case, we find that the density profiles decay algebraically, as predicted in ref. 13. The method presented here can be extended to localization of atomic quantum gases in higher dimensions, and with controlled interactions.     

Relations phénétiques entre les familles d'Hamamelididae

Summary The phenetic relationships between the families of the Hamamelididae subclass were studied by using the following multifactorial analytical methods: principal components analysis (PCA) and reciprocal averaging (RA). The results obtained agree appreciably with Takhtajan's classification system.

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Remerciements. Nous remercions Mlle Sylvie Laliberté, Institut botanique de l'Université de Montréal, pour sa révision du manuscrit; M. Michel Labrecque, Institut botanique de l'Université de Montréal, pour avoir dessiné les figures; de même que M. André Bouchard, Jardin Botanique de Montréal et Institut botanique de l'Université de Montréal, de nous avoir permis d'utiliser les programmes dont il se sert pour ses travaux d'écologie.     

Prostaglandin-like substances inPropionibacterium acnes. IV. Effect on isolated human vessels

Summary The present study demonstrates a powerful vasoconstrictor activity of prostaglandin-like substances (PLS), extracted fromP. acnes, on human blood vessels. PLS is about equipotent to PGE₂ in its effect on human umbilical vessels, but the contractile response pattern is different. PLS therefore seems to have specific and different physiological characteristics.     

Rate of tryptophan hydroxylation in vivo in brain nuclei of genetically hypertensive rats of the Lyon strain

The rate of tryptophan hydroxylation in vivo is unaltered in brain areas of 5, 9 and 21 week-old Lyon genetically Hypertensive (LH) rats as compared to both Lyon Normotensive (LN) and Low Blood Pressure (LL) rats, except for a decrease in the C1 area of the medulla oblongata in 9 week-old animals.