Sur la biosynthèse des constituants amers des Simarubacées

Summary The biosynthesis of glaucarubinone (IXa) and glaucarubolone (IXb), the bitter constituents ofSimarouba glauca (Simaroubaceae), has been investigated with the help of [2-¹⁴C] mevalonic acid lactone. The results so far obtained are consistent with the scheme involving a tetracyclic triterpene of the apoeuphol type as a precursor of these bitter substances.

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Avec la collaboration technique de Mlle A.Merrien.     

Mechanisms of drug inhibition of signalling molecules

The emergence of tumour-specific, molecularly targeted agents signifies a paradigm shift in cancer therapy, with less reliance on drugs that non-discriminately kill tumour and host cells. Although the diversity of targets giving rise to this new generation of anticancer drugs has expanded, many challenges persist in the design of effective treatment regimens. The complex interplay of signal-transduction pathways further complicates the customization of cancer treatments to target single mechanisms. However, despite uncertainty over precise or dominant mechanisms of action, especially for compounds targeting multiple gene products, emerging agents are producing significant therapeutic advances against a broad range of human cancers.     

A novel self-promoted Morita-Baylis-Hillman-like dimerization

While stable in CH₂Cl₂, hexane or THF, in the presence of MeOH, self-promoted dimerization of the triarylphosphine-alkene 1, a ligand for Pd-catalyzed reactions, produced an unusual racemic bis(phosphine) 2 in high yield. The reaction of 2 with Pd(dba)₂, followed by oxidative addition of p-IC₆H₄NO₂, yielded a trans-chelated Pd(II) aryl iodide complex.     

The naturalism of the sciences

The sciences are characterized by what is sometimes called a “methodological naturalism,” which disregards talk of divine agency. In response to those who argue that this reflects a dogmatic materialism, a number of philosophers have offered a pragmatic defense. The naturalism of the sciences, they argue, is provisional and defeasible: it is justified by the fact that unsuccessful theistic explanations have been superseded by successful natural ones. But this defense is inconsistent with the history of the sciences. The sciences have always exhibited what we call a domain naturalism. They have never invoked divine agency, but have always focused on the causal structure of the natural world. It is not the case, therefore, that the sciences once employed theistic explanations and then abandoned them. The naturalism of the sciences is as old as science itself.     

Asymmetric and symmetric stem-cell divisions in development and cancer

Much has been made of the idea that asymmetric cell division is a defining characteristic of stem cells that enables them to simultaneously perpetuate themselves (self-renew) and generate differentiated progeny. Yet many stem cells can divide symmetrically, particularly when they are expanding in number during development or after injury. Thus, asymmetric division is not necessary for stem-cell identity but rather is a tool that stem cells can use to maintain appropriate numbers of progeny. The facultative use of symmetric or asymmetric divisions by stem cells may be a key adaptation that is crucial for adult regenerative capacity.     

Stoichiometry and turnover in single, functioning membrane protein complexes

Many essential cellular processes are carried out by complex biological machines located in the cell membrane. The bacterial flagellar motor is a large membrane-spanning protein complex that functions as an ion-driven rotary motor to propel cells through liquid media. Within the motor, MotB is a component of the stator that couples ion flow to torque generation and anchors the stator to the cell wall. Here we have investigated the protein stoichiometry, dynamics and turnover of MotB with single-molecule precision in functioning bacterial flagellar motors in Escherichia coli. We monitored motor function by rotation of a tethered cell body, and simultaneously measured the number and dynamics of MotB molecules labelled with green fluorescent protein (GFP-MotB) in the motor by total internal reflection fluorescence microscopy. Counting fluorophores by the stepwise photobleaching of single GFP molecules showed that each motor contains approximately 22 copies of GFP-MotB, consistent with approximately 11 stators each containing two MotB molecules. We also observed a membrane pool of approximately 200 GFP-MotB molecules diffusing at approximately 0.008 microm2 s(-1). Fluorescence recovery after photobleaching and fluorescence loss in photobleaching showed turnover of GFP-MotB between the membrane pool and motor with a rate constant of the order of 0.04 s(-1): the dwell time of a given stator in the motor is only approximately 0.5 min. This is the first direct measurement of the number and rapid turnover of protein subunits within a functioning molecular machine.     

The DNA sequence, annotation and analysis of human chromosome 3

After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.