Dogfish hair cells sense hydrostatic pressure

Many marine invertebrates and fish respond to hydrostatic pressure in order to regulate their depth and synchronize their behaviour to tidal cycles. Here we investigate the effect of hydrostatic pressure on the vestibular hair cells located in the labyrinth of the dogfish Scyliorhinus canicula, and find that it modulates their spontaneous activity and response to angular acceleration. This may explain not only the low resting activity of vertebrate hair cells but also how fish that do not have swim bladders can sense hydrostatic cues.     

Massive gene decay in the leprosy bacillus

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.     

Effect of blood pH on anionic ferritin transport through rat aortic endothelium

Summary Acute lowering of blood pH between 7.4 and 6.9 in rats by ventilation with 10 or 20% CO₂ does not increase the passage of ferritin molecules across the aortic endothelium. These results do not rule out alteration of endothelial permeability to anionic macromolecules in local circulatory disturbances when blood pH drops to levels much lower than 6.9.Supported by The Medical Research Council of Canada grant No. MA-5958.Dr J.R. Fraser was a recipient of a Summer Research Scholarship from McGill University during the completion of this study.The authors thank Colin Bier for the statistical analysis.     

Effects of tricaine methane sulphonate (M.S. 222) on the blood glucose levels in adult salamanders (Diemicytlus viridescens)

Summary Exposure to M. S. 222 results in hyperglycemia in adult newts (Diemicytlus viridescens). A combination of higher anesthetic concentrations with reduced exposure periods reduces the magnitude of this form of stress response.This work was supported by National Research Council of Canada Grant No. A9753 to S. Vethamany-Globus and No. A6933 to M. Globus.     

Host immunity and synchronized epidemics of syphilis across the United States

A central question in population ecology is the role of 'exogenous' environmental factors versus density-dependent 'endogenous' biological factors in driving changes in population numbers. This question is also central to infectious disease epidemiology, where changes in disease incidence due to behavioural or environmental change must be distinguished from the nonlinear dynamics of the parasite population. Repeated epidemics of primary and secondary syphilis infection in the United States over the past 50 yr have previously been attributed to social and behavioural changes. Here, we show that these epidemics represent a rare example of unforced, endogenous oscillations in disease incidence, with an 8-11-yr period that is predicted by the natural dynamics of syphilis infection, to which there is partially protective immunity. This conclusion is supported by the absence of oscillations in gonorrhoea cases, where a protective immune response is absent. We further demonstrate increased synchrony of syphilis oscillations across cities over time, providing empirical evidence for an increasingly connected sexual network in the United States.     

Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution

Influenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality. The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 'Spanish' flu, one of the most deadly outbreaks in recorded history, which killed 30-50 million people worldwide, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu. Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives.     

Dishevelled controls cell polarity during Xenopus gastrulation

Although cell movements are vital for establishing the normal architecture of embryos, it is unclear how these movements are regulated during development in vertebrates. Inhibition of Xenopus Dishevelled (Xdsh) function disrupts convergent extension movements of cells during gastrulation, but the mechanism of this effect is unclear, as cell fates are not affected. In Drosophila, Dishevelled controls both cell fate and cell polarity, but whether Dishevelled is involved in controlling cell polarity in vertebrate embryos has not been investigated. Here we show, using time-lapse confocal microscopy, that the failure of cells lacking Xdsh function to undergo convergent extension results from defects in cell polarity. Furthermore, Xdsh mutations that inhibit convergent extension correspond to mutations in Drosophila Dishevelled that selectively perturb planar cell polarity. Finally, the localization of Xdsh at the membrane of normal dorsal mesodermal cells is consistent with Xdsh controlling cell polarity. Our results show that polarized cell behaviour is essential for convergent extension and is controlled by vertebrate Dishevelled. Thus, a vertebrate equivalent of the Drosophila planar cell polarity signalling cascade may be required for normal gastrulation.     

Functional genomic analysis of C. elegans chromosome I by systematic RNA interference

Complete genomic sequence is known for two multicellular eukaryotes, the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster, and it will soon be known for humans. However, biological function has been assigned to only a small proportion of the predicted genes in any animal. Here we have used RNA-mediated interference (RNAi) to target nearly 90% of predicted genes on C. elegans chromosome I by feeding worms with bacteria that express double-stranded RNA. We have assigned function to 13.9% of the genes analysed, increasing the number of sequenced genes with known phenotypes on chromosome I from 70 to 378. Although most genes with sterile or embryonic lethal RNAi phenotypes are involved in basal cell metabolism, many genes giving post-embryonic phenotypes have conserved sequences but unknown function. In addition, conserved genes are significantly more likely to have an RNAi phenotype than are genes with no conservation. We have constructed a reusable library of bacterial clones that will permit unlimited RNAi screens in the future; this should help develop a more complete view of the relationships between the genome, gene function and the environment.