A peptide deformylase-ribosome complex reveals mechanism of nascent chain processing

Messenger-RNA-directed protein synthesis is accomplished by the ribosome. In eubacteria, this complex process is initiated by a specialized transfer RNA charged with formylmethionine (tRNA(fMet)). The amino-terminal formylated methionine of all bacterial nascent polypeptides blocks the reactive amino group to prevent unfavourable side-reactions and to enhance the efficiency of translation initiation. The first enzymatic factor that processes nascent chains is peptide deformylase (PDF); it removes this formyl group as polypeptides emerge from the ribosomal tunnel and before the newly synthesized proteins can adopt their native fold, which may bury the N terminus. Next, the N-terminal methionine is excised by methionine aminopeptidase. Bacterial PDFs are metalloproteases sharing a conserved N-terminal catalytic domain. All Gram-negative bacteria, including Escherichia coli, possess class-1 PDFs characterized by a carboxy-terminal alpha-helical extension. Studies focusing on PDF as a target for antibacterial drugs have not revealed the mechanism of its co-translational mode of action despite indications in early work that it co-purifies with ribosomes. Here we provide biochemical evidence that E. coli PDF interacts directly with the ribosome via its C-terminal extension. Crystallographic analysis of the complex between the ribosome-interacting helix of PDF and the ribosome at 3.7 A resolution reveals that the enzyme orients its active site towards the ribosomal tunnel exit for efficient co-translational processing of emerging nascent chains. Furthermore, we have found that the interaction of PDF with the ribosome enhances cell viability. These results provide the structural basis for understanding the coupling between protein synthesis and enzymatic processing of nascent chains, and offer insights into the interplay of PDF with the ribosome-associated chaperone trigger factor.     

The human chorionic gonadotrophin bio-assay by seminal vesicles in mice

Zusammenfassung Biologische Methode zur Bestimmung von Choriogonadotrophin (HCG) im Harn, welche auf Gewichtszunahme von Samenblasen juveniler Mäuse basiert.     

Some pharmacological properties of [4-Leucine]-arginine-vasotocin

Zusammenfassung Die pharmakologischen Eigenschaften von [Leu⁴]-Arginin-vasotocin sind in der Tabelle zusammengefasst. Am isolierten Rattenuterus in magnesiumfreiem Medium wirkt das Peptid als Oxytocinantagonist.     

Anthropic Fluctuations vs. Weak Anthropic Principle

A modern assessment of the classical Boltzmann-Schuetz argument for large-scale entropy fluctuations as the origin of our observable cosmological domain is given.The emphasis is put on the central implication of this picture which flatly contradicts the weak anthropic principle as an epistemological statement about the universe. Therefore, to associate this picture with the anthropic principle as it is usually done is unwarranted. In particular, Feynman's criticism of theanthropic principle based on the entropy-fluctuation picture is a product of this semantic confusion.     

Role of 1,25-dihydroxyvitamin D3 in the generation of the acute-phase response in rats with talc-induced granulomatosis

Subcutaneous injection of nonspecific irritants such as magnesium silicate (talc) provokes granulomatous inflammation in the rat. Part of the acute phase response (APR) in these animals is the loss of trabecular bone at sites distant from the site of inflammation. To assess the possible involvement of vitamin D in the bone loss, we studied the development of the acute phase response in vitamin D-deprived rats. The serum APR provoked by subcutaneous inflammation in rachitic rats consisted of hypozincemia, hypercupremia, increased, alkaline phosphatase activity and adrenocorticotropic hormone (ACTH) concentration, and was similar to that in control animals except for the absence of hypoferremia. Control rats with talc-induced subcutaneous inflammation also had splenomegaly and decreased total and mononuclear peripheral blood cell counts, while subcutaneous inflammation did not induce spleen changes in rachitic rats. Subcutaneous inflammation induced the loss of trabecular bone and decreased the osteoblastic cell count in tibial metaphyses in control animals. Rachitic rats had abundant osteoid on trabecular surfaces, and the number of osteoblasts and osteoclasts was comparable to that of the controls. Subcutaneous inflammation did not affect any of the bone parameters in rachitic rats. These results indicate that vitamin D plays an important role in the generation of the acute phase response during inflammation, particularly in the induction of spleen and bone cell changes. The discrepancy of the blood on one hand and bone and spleen indices of the APR on the other, indicate that there may be divergent pathways in the generation of the inflammatory response, some of which may be dependent on vitamin D.     

Single mimivirus particles intercepted and imaged with an X-ray laser

X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000?K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.     

Systematic variation of the stellar initial mass function in early-type galaxies

Much of our knowledge of galaxies comes from analysing the radiation emitted by their stars, which depends on the present number of each type of star in the galaxy. The present number depends on the stellar initial mass function (IMF), which describes the distribution of stellar masses when the population formed, and knowledge of it is critical to almost every aspect of galaxy evolution. More than 50 years after the first IMF determination, no consensus has emerged on whether it is universal among different types of galaxies. Previous studies indicated that the IMF and the dark matter fraction in galaxy centres cannot both be universal, but they could not convincingly discriminate between the two possibilities. Only recently were indications found that massive elliptical galaxies may not have the same IMF as the Milky Way. Here we report a study of the two-dimensional stellar kinematics for the large representative ATLAS(3D) sample of nearby early-type galaxies spanning two orders of magnitude in stellar mass, using detailed dynamical models. We find a strong systematic variation in IMF in early-type galaxies as a function of their stellar mass-to-light ratios, producing differences of a factor of up to three in galactic stellar mass. This implies that a galaxy's IMF depends intimately on the galaxy's formation history.