An integrated semiconductor device enabling non-optical genome sequencing

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.     

Multiple liquid crystal phases of DNA at high concentrations

DNA packaging in vivo is very tight, with volume concentrations approaching 70% w/v in sperm heads, virus capsids and bacterial nucleoids. The packaging mechanisms adopted may be related to the natural tendency of semi-rigid polymers to form liquid crystalline phases in concentrated solutions. We find that DNA forms at least three distinct liquid crystalline phases at concentrations comparable to those in vivo, with phase transitions occurring over relatively narrow ranges of DNA concentration. A weakly birefringent, dynamic, 'precholesteric' mesophase with microscopic textures intermediate between those of a nematic and a true cholesteric phase forms at the lowest concentrations required for phase separation. At slightly higher DNA concentrations, a second mesophase forms which is a strongly birefringent, well-ordered cholesteric phase with a concentration-dependent pitch varying from 2 to 10 micron. At the highest DNA concentrations, a phase forms which is two-dimensionally ordered and resembles smectic phases of thermotropic liquid crystals observed with small molecules.     

l-DOPA treatment in Parkinson's disease: Effect on dopamine and related substances in discrete brain regions

Zusammenfassung Beil-DOPA behandelten Parkinsonpatienten wird gefunden, dass Dopamin und Homovanillinsäure besonders im Striatum akkumuliert wurden. Damit wird die Möglichkeit, dass Dopamin an der Antiparkinson-Wirkung desl-DOPA entscheidend beteiligt ist, in direkter Weise gestützt.     

Cooperative tandem binding of met repressor of Escherichia coli

We present biochemical and genetic data to support the hypothesis that the Escherichia coli met repressor, MetJ, binds to synthetic and natural operator sequences in tandem arrays such that repression depends not only on the affinity of the DNA-protein interaction, but also on protein-protein contacts along the tandem array. This represents a novel form of regulatory switch. Furthermore, there seems to be homology between the organization of the met and trp operators.     

Rabbit abundance relative to rainfall and plant production in northern Chihuahuan Desert grassland and shrubland habitats

Rabbit abundance patterns in the North American Southwest are poorly known, particularly relative to the potentially important influences of rainfall and plant production. We conducted a 10-year study on the comparative densities of black-tailed jackrabbits ( Lepus californicus ) and desert cottontail rabbits ( Sylvilagus audubonii ) in relation to annual rainfall and plant production in both black grama ( Bouteloua eriopoda ) grassland and creosotebush ( Larrea tridentata ) shrubland habitats in the northern Chihuahuan Desert. We found that both species of rabbits were more abundant in black grama grassland than in creosotebush shrubland and that plant production was positively correlated with rainfall at both habitats. However, rabbit densities were not positively correlated with rainfall or plant production in either habitat. In fact, both species of rabbits exhibited gradual, multiyear changes in abundance rather than the patterns of high annual variation observed in desert rodent communities. Our findings of no significant relationship between plant production and rabbit densities indicate that rabbit abundance in the northern Chihuahuan Desert may not be strongly regulated by short-term, bottom-up effects of annual variation in plant production. Long-term trends indicate that other factors such as disease or predation may be equally or more important. We suggest that future research evaluate both top-down and bottom-up influences to elucidate the temporal dynamics of Chihuahuan Desert rabbit abundance. Se conoce poco sobre los patrones de abundancia de conejos desérticos en el suroeste de Norte America, particularmente en relación con las influencias potencialmente importantes de la precipitación y la producción de plantas. Llevamos a cabo una investigación de diez años sobre la densidad relativa de la liebre de California ( Lepus californicus ) y el conejo cola de algodón ( Sylvilagus audubonii ) en los hábitats tanto de pradera de grama negra ( Bouteloua eriopoda ) como de matorral de gobernadora ( Larrea tridentata ) en el norte del Desierto Chihuahuense, en relación con la precipitación y la producción anuales. Encontramos que ambas especies de conejo fueron más abundantes en la pradera de grama negra que en el matorral de gobernadora, y que la producción de plantas estuvo correlacionada positivamente con la precipitación en ambos hábitats. Sin embargo, las densidades de conejos no estuvieron correlacionadas positivamente con la precipitación o con la producción de plantas en ninguno de los dos hábitats. De hecho, en cuanto a la fluctuación de su abundancia, las dos especies de conejo exhibieron tendencias graduales a lo largo de varios años, en comparación con los patrones de gran variación anual que se han observado en comunidades de roedores desérticos. La falta de una relación significativa entre la producción de plantas y la abundancia de conejos, indica que la abundancia de conejos en el norte del Desierto Chihuahuense no está fuertemente regulada por los efectos ascendentes a corto plazo de la variación anual en la producción de plantas. Los cambios reflejados en las tendencias a largo plazo indican que otros factores como las enfermedades o la depredación pueden ser de igual o mayor importancia, y sugerimos que investigaciones futuras deberán evaluar tanto las influencias ascendentes como las descendentes para entender las dinámicas temporales en la abundancia de conejos del Desierto Chihuahuense.     

Comparison of bicyclic phosphorous esters with bicuculline and picrotoxin as antagonists of presynaptic inhibition in the rat cuneate nucleus

Summary The effects of 2 of a series of bicyclic phosphorous esters, the ethyl (EPTBO) and isopropyl (IPTBO) compounds, were compared with those of the GABA antagonists, picrotoxin and bicuculline, on presynaptic inhibition in the rat cuneate nucleus. Both EPTBO and IPTBO were found to be effective, reversible antagonists of presynaptic inhibition, with IPTBO approximately 10 times more potent than EPTBO and equipotent with bicuculline, EPTBO equipotent with picrotoxin.The authors are grateful to Dr J. F. Collins, Department of Chemistry, Sir John Cass School of Science and Technology, 31 Jewry Street, London, for the gift of bicyclic phosphorous esters.