Solution structure of a protein denatured state and folding intermediate

The most controversial area in protein folding concerns its earliest stages. Questions such as whether there are genuine folding intermediates, and whether the events at the earliest stages are just rearrangements of the denatured state or progress from populated transition states, remain unresolved. The problem is that there is a lack of experimental high-resolution structural information about early folding intermediates and denatured states under conditions that favour folding because competent states spontaneously fold rapidly. Here we have solved directly the solution structure of a true denatured state by nuclear magnetic resonance under conditions that would normally favour folding, and directly studied its equilibrium and kinetic behaviour. We engineered a mutant of Drosophila melanogaster Engrailed homeodomain that folds and unfolds reversibly just by changing ionic strength. At high ionic strength, the mutant L16A is an ultra-fast folding native protein, just like the wild-type protein; however, at physiological ionic strength it is denatured. The denatured state is a well-ordered folding intermediate, poised to fold by docking helices and breaking some non-native interactions. It unfolds relatively progressively with increasingly denaturing conditions, and so superficially resembles a denatured state with properties that vary with conditions. Such ill-defined unfolding is a common feature of early folding intermediate states and accounts for why there are so many controversies about intermediates versus compact denatured states in protein folding.     

Indirect effect of ultrasound on water permeability of the connective tissue

Zusammenfassung Die Durchlässigkeit des Rattenmesenteriums für demineralisiertes Wasser wird durch Ultraschallbehandlung des Wassers signifikant erhöht.     

Biosynthesis of plant sterols. Conversion of cholesterol to pregnenolone in Digitalis purpurea

Zusammenfassung Der bei der Bestrahlung mit ionisierenden Strahlen auftretende Sättigungseffekt, d.h. die Abweichung von der Linearität des Verhältnisses zwischen der Strahlendosis und der Zahl der geschädigten Molekeln bei höheren Dosisleistungen, wird unter Zugrundelegung eines einfachen Modells, welches sowohl die Erzeugung als auch die Rekombination der Strahlenschäden berücksichtigt, mathematisch beschrieben.     

Effect of hepatectomy on the growth of the foetal rat liver

Résumé Les auteurs ont utilisé deux lots des Rates portantes. L'un d'eux a été soumis à la laparotomie et l'autre à une hépatectomie partielle le 16ème jour de la gestation. Les animaux ont été sacrifiés à des dates échelonnées après l'intervention. Le poids des embryons et celui de leur foie, ainsi que la teneur en DNA du foie ont été mésurés.L'hépatectomie de la mère ralentit la croissance des embryons sans aucun effet spécifique sur le foie embryonnaire.     

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.     

South-polar features on Venus similar to those near the north pole

Venus has no seasons, slow rotation and a very massive atmosphere, which is mainly carbon dioxide with clouds primarily of sulphuric acid droplets. Infrared observations by previous missions to Venus revealed a bright 'dipole' feature surrounded by a cold 'collar' at its north pole. The polar dipole is a 'double-eye' feature at the centre of a vast vortex that rotates around the pole, and is possibly associated with rapid downwelling. The polar cold collar is a wide, shallow river of cold air that circulates around the polar vortex. One outstanding question has been whether the global circulation was symmetric, such that a dipole feature existed at the south pole. Here we report observations of Venus' south-polar region, where we have seen clouds with morphology much like those around the north pole, but rotating somewhat faster than the northern dipole. The vortex may extend down to the lower cloud layers that lie at about 50 km height and perhaps deeper. The spectroscopic properties of the clouds around the south pole are compatible with a sulphuric acid composition.