Centrioles: active players or passengers during mitosis?

Centrioles are cylinders made of nine microtubule (MT) triplets present in many eukaryotes. Early studies, where centrosomes were seen at the poles of the mitotic spindle led to their coining as “the organ for cell division”. However, a variety of subsequent observational and functional studies showed that centrosomes might not always be essential for mitosis. Here we review the arguments in this debate. We describe the centriole structure and its distribution in the eukaryotic tree of life and clarify its role in the organization of the centrosome and cilia, with an historical perspective. An important aspect of the debate addressed in this review is how centrioles are inherited and the role of the spindle in this process. In particular, germline inheritance of centrosomes, such as their de novo formation in parthenogenetic species, poses many interesting questions. We finish by discussing the most likely functions of centrioles and laying out new research avenues

Meiotic Regulation of TPX2 Protein Levels Governs Cell Cycle Progression in Mouse Oocytes

Formation of female gametes requires acentriolar spindle assembly during meiosis. Mitotic spindles organize from centrosomes and via local activation of the RanGTPase on chromosomes. Vertebrate oocytes present a RanGTP gradient centred on chromatin at all stages of meiotic maturation. However, this gradient is dispensable for assembly of the first meiotic spindle. To understand this meiosis I peculiarity, we studied TPX2, a Ran target, in mouse oocytes. Strikingly, TPX2 activity is controlled at the protein level through its accumulation from meiosis I to II. By RNAi depletion and live imaging, we show that TPX2 is required for spindle assembly via two distinct functions. It controls microtubule assembly and spindle pole integrity via the phosphorylation of TACC3, a regulator of MTOCs activity. We show that meiotic spindle formation in vivo depends on the regulation of at least a target of Ran, TPX2, rather than on the regulation of the RanGTP gradient itself

Selectivity control in Pt-catalyzed cinnamaldehyde hydrogenation

Chemoselectivity is a cornerstone of catalysis, permitting the targeted modification of specific functional groups within complex starting materials. Here we elucidate key structural and electronic factors controlling the liquid phase hydrogenation of cinnamaldehyde and related benzylic aldehydes over Pt nanoparticles. Mechanistic insight from kinetic mapping reveals cinnamaldehyde hydrogenation is structure-insensitive over metallic platinum, proceeding with a common Turnover Frequency independent of precursor, particle size or support architecture. In contrast, selectivity to the desired cinnamyl alcohol product is highly structure sensitive, with large nanoparticles and high hydrogen pressures favoring C=O over C=C hydrogenation, attributed to molecular surface crowding and suppression of sterically-demanding adsorption modes. In situ vibrational spectroscopies highlight the role of support polarity in enhancing C=O hydrogenation (through cinnamaldehyde reorientation), a general phenomenon extending to alkyl-substituted benzaldehydes. Tuning nanoparticle size and support polarity affords a flexible means to control the chemoselective hydrogenation of aromatic aldehydes

Mechanism of drug transport by ABC multidrug proteins in structural perspectives

ABC (ATP Binding Cassette) proteins form one of the largest protein superfamilies. Most members are active membrane transporters translocating their substrates across the lipid bilayer of the plasma membrane or intracellular organelles. Multidrug transporters exhibit broad substrate specificity, exporting molecules with diverse chemical structures to protect organisms from xenotoxic compounds, and also play an important role in influencing the efficacy of therapeutic agents. High resolution structural information is required to reveal the conformational changes associated with the transport cycle and the interaction with small molecules, with the ultimate aim to develop strategies to pharmacologically modulate function and predict substrates properties. In this chapter we review available ABC protein structures and discuss advances in using this structural information for computational approaches that are aimed at elucidating the mechanism of substrate recognition and cargo translocation in the context of the ATP catalytic cycle of human multidrug ABC transporters

Investigation of the mechanical properties of silica glasses by indentation tests

Soda lime silica glasses were investigated by continuous indentation tests. The load indentation depth curves were taken during the loading as well as the unloading period by a computer controlled MTS machine. It was found that the loading force is a quadratic function of the indentation depth during both the loading and unloading stage of the deformation. The validity of the quadratic relationship in the case of the unloading stage seems to be characteristic only for glasses. Taking into account the elastic relaxation of the indentation depth an estimation is given for the size of the hydrostatic core which is necessary to symmetrize the stress field around the indenter. Using the measured length of the radial cracks started from the corners of the Vickers indentation pattern the KIC values were calculated