Detailed molecular comparison between the inhibition mode of A/B-type carboxypeptidases in the zymogen state and by the endogenous inhibitor latexin

Treatment of advanced stages of prostate carcinoma with histone-deacetylase inhibitors entails expression of human procarboxypeptidase-A4 (hPCPA4). The three-dimensional structure of hPCPA4 has been solved and shows the features of related metallocarboxypeptidase zymogens, with a preformed α/β/-hydrolase active-enzyme moiety (hCPA4) and an inhibiting pro-domain (PD). The protease moiety recalls a sphere, out of which a spherical cone has been cut. This results in a funnel-like structure, at the bottom of which the active-site cleft resides. The border of this funnel is shaped by loops, which are responsible for the interaction with the PD, characterised by a large interface area and relatively few contacts. Such an inhibitory mode is evocative of the recently reported structure of the human inhibitor latexin in its complex with hCPA4. The main contacting structure of latexin is similar to the one employed for PD inhibition. In both cases, active-site blocking relies mainly on a loop provided by the central part of a β sheet.R. Garcia-Castellanos and R. Bonet-Figueredo contributed equally to this study and share first authorship.Received 28 April 2005; received after revision 1 June 2005; accepted 29 June 2005     

World Year of Physics: a direct test of E=mc2

One of the most striking predictions of Einstein's special theory of relativity is also perhaps the best known formula in all of science: E=mc(2). If this equation were found to be even slightly incorrect, the impact would be enormous--given the degree to which special relativity is woven into the theoretical fabric of modern physics and into everyday applications such as global positioning systems. Here we test this mass-energy relationship directly by combining very accurate measurements of atomic-mass difference, Delta(m), and of gamma-ray wavelengths to determine E, the nuclear binding energy, for isotopes of silicon and sulphur. Einstein's relationship is separately confirmed in two tests, which yield a combined result of 1-Delta(mc2)/E=(-1.4+/-4.4)x10(-7), indicating that it holds to a level of at least 0.00004%. To our knowledge, this is the most precise direct test of the famous equation yet described.     

Follicles development in the foetal human ovary

Summary In the foetal human ovary, diameters of oocyte and follicle, as well as those of oocyte and nucleus, are found to be positively and linearly correlated with each other. Follicle diameter and number of granulosa cells also show a positive and linear relationship. Finally, in all ovaries examined, from 5 months after conception onwards, small antral follicles were assessed.     

Translating tissue-engineered tracheal replacement from bench to bedside

There are a variety of airway diseases with different clinical settings, which may extend from a surgical approach to total organ replacement. Tissue engineering involves modifying cells or tissues in order to repair, regenerate, or replace tissue in the body and seems to be a promising approach for airway replacement. The successful implantation of stem-cell-based tissue-engineered trachea in a young woman with end-stage post-tuberculosis left main bronchus collapse serves as a prototype for the airway tissue-engineered-based approach. The trachea indeed could represent a perfect model system to investigate the translational aspects of tissue engineering, largely due to its low-oxygen needs. This review highlights the anatomy of the airways, the various disease conditions that cause damage to the airways, elaborates on the essential components of the tissue-engineering approach, and discusses the success of the revolutionary trachea transplantation approach.     

Submillimetre galaxies reside in dark matter haloes with masses greater than 3 × 10(11) solar masses

The extragalactic background light at far-infrared wavelengths comes from optically faint, dusty, star-forming galaxies in the Universe with star formation rates of a few hundred solar masses per year. These faint, submillimetre galaxies are challenging to study individually because of the relatively poor spatial resolution of far-infrared telescopes. Instead, their average properties can be studied using statistics such as the angular power spectrum of the background intensity variations. A previous attempt at measuring this power spectrum resulted in the suggestion that the clustering amplitude is below the level computed with a simple ansatz based on a halo model. Here we report excess clustering over the linear prediction at arcminute angular scales in the power spectrum of brightness fluctuations at 250, 350 and 500?μm. From this excess, we find that submillimetre galaxies are located in dark matter haloes with a minimum mass, M(min), such that log(10)[M(min)/M(⊙)] = 11.5(+0.7)(-0.2) at 350?μm, where M(⊙) is the solar mass. This minimum dark matter halo mass corresponds to the most efficient mass scale for star formation in the Universe, and is lower than that predicted by semi-analytical models for galaxy formation.