Molecular machines: nanomotor rotates microscale objects

Nanomachines of the future will require molecular-scale motors that can perform work and collectively induce controlled motion of much larger objects. We have designed a synthetic, light-driven molecular motor that is embedded in a liquid-crystal film and can rotate objects placed on the film that exceed the size of the motor molecule by a factor of 10,000. The changes in shape of the motor during the rotary steps cause a remarkable rotational reorganization of the liquid-crystal film and its surface relief, which ultimately causes the rotation of submillimetre-sized particles on the film.     

Flagellar motility is required for the viability of the bloodstream trypanosome

The 9 + 2 microtubule axoneme of flagella and cilia represents one of the most iconic structures built by eukaryotic cells and organisms. Both unity and diversity are present among cilia and flagella on the evolutionary as well as the developmental scale. Some cilia are motile, whereas others function as sensory organelles and can variously possess 9 + 2 and 9 + 0 axonemes and other associated structures. How such unity and diversity are reflected in molecular repertoires is unclear. The flagellated protozoan parasite Trypanosoma brucei is endemic in sub-Saharan Africa, causing devastating disease in humans and other animals. There is little hope of a vaccine for African sleeping sickness and a desperate need for modern drug therapies. Here we present a detailed proteomic analysis of the trypanosome flagellum. RNA interference (RNAi)-based interrogation of this proteome provides functional insights into human ciliary diseases and establishes that flagellar function is essential to the bloodstream-form trypanosome. We show that RNAi-mediated ablation of various proteins identified in the trypanosome flagellar proteome leads to a rapid and marked failure of cytokinesis in bloodstream-form (but not procyclic insect-form) trypanosomes, suggesting that impairment of flagellar function may provide a method of disease control. A postgenomic meta-analysis, comparing the evolutionarily ancient trypanosome with other eukaryotes including humans, identifies numerous trypanosome-specific flagellar proteins, suggesting new avenues for selective intervention.     

Structure of eEF3 and the mechanism of transfer RNA release from the E-site

Elongation factor eEF3 is an ATPase that, in addition to the two canonical factors eEF1A and eEF2, serves an essential function in the translation cycle of fungi. eEF3 is required for the binding of the aminoacyl-tRNA-eEF1A-GTP ternary complex to the ribosomal A-site and has been suggested to facilitate the clearance of deacyl-tRNA from the E-site. Here we present the crystal structure of Saccharomyces cerevisiae eEF3, showing that it consists of an amino-terminal HEAT repeat domain, followed by a four-helix bundle and two ABC-type ATPase domains, with a chromodomain inserted in ABC2. Moreover, we present the cryo-electron microscopy structure of the ATP-bound form of eEF3 in complex with the post-translocational-state 80S ribosome from yeast. eEF3 uses an entirely new factor binding site near the ribosomal E-site, with the chromodomain likely to stabilize the ribosomal L1 stalk in an open conformation, thus allowing tRNA release.     

Mast cells are essential intermediaries in regulatory T-cell tolerance

Contrary to the proinflammatory role of mast cells in allergic disorders, the results obtained in this study establish that mast cells are essential in CD4+CD25+Foxp3+ regulatory T (T(Reg))-cell-dependent peripheral tolerance. Here we confirm that tolerant allografts, which are sustained owing to the immunosuppressive effects of T(Reg) cells, acquire a unique genetic signature dominated by the expression of mast-cell-gene products. We also show that mast cells are crucial for allograft tolerance, through the inability to induce tolerance in mast-cell-deficient mice. High levels of interleukin (IL)-9--a mast cell growth and activation factor--are produced by activated T(Reg) cells, and IL-9 production seems important in mast cell recruitment to, and activation in, tolerant tissue. Our data indicate that IL-9 represents the functional link through which activated T(Reg) cells recruit and activate mast cells to mediate regional immune suppression, because neutralization of IL-9 greatly accelerates allograft rejection in tolerant mice. Finally, immunohistochemical analysis clearly demonstrates the existence of this novel T(Reg)-IL-9-mast cell relationship within tolerant allografts.     

Early maize agriculture and interzonal interaction in southern Peru

Over the past decade, increasing attention to the recovery and identification of plant microfossil remains from archaeological sites located in lowland South America has significantly increased knowledge of pre-Columbian plant domestication and crop plant dispersals in tropical forests and other regions. Along the Andean mountain chain, however, the chronology and trajectory of plant domestication are still poorly understood for both important indigenous staple crops such as the potato (Solanum sp.) and others exogenous to the region, for example, maize (Zea mays). Here we report the analyses of plant microremains from a late preceramic house (3,431 +/- 45 to 3,745 +/- 65 14C bp or approximately 3,600 to 4,000 calibrated years bp) in the highland southern Peruvian site of Waynuna. Our results extend the record of maize by at least a millennium in the southern Andes, show on-site processing of maize into flour, provide direct evidence for the deliberate movement of plant foods by humans from the tropical forest to the highlands, and confirm the potential of plant microfossil analysis in understanding ancient plant use and migration in this region.     

Efficient auditory coding

The auditory neural code must serve a wide range of auditory tasks that require great sensitivity in time and frequency and be effective over the diverse array of sounds present in natural acoustic environments. It has been suggested that sensory systems might have evolved highly efficient coding strategies to maximize the information conveyed to the brain while minimizing the required energy and neural resources. Here we show that, for natural sounds, the complete acoustic waveform can be represented efficiently with a nonlinear model based on a population spike code. In this model, idealized spikes encode the precise temporal positions and magnitudes of underlying acoustic features. We find that when the features are optimized for coding either natural sounds or speech, they show striking similarities to time-domain cochlear filter estimates, have a frequency-bandwidth dependence similar to that of auditory nerve fibres, and yield significantly greater coding efficiency than conventional signal representations. These results indicate that the auditory code might approach an information theoretic optimum and that the acoustic structure of speech might be adapted to the coding capacity of the mammalian auditory system.