Sclerotization and coloration of the insect cuticle

Summary Evidence indicating linkage between the processes of cuticle hardening and coloration are reviewed. Data and observations for the mutants black and ebony inDrosophila melanogaster are used to construct a possible model for the relationship between these developmental events.     

The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours

In mice, the Ter mutation causes primordial germ cell (PGC) loss in all genetic backgrounds. Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains, and markedly increases TGCT incidence in 129-Ter/Ter males. In 129-Ter/Ter mice, some of the remaining PGCs transform into undifferentiated pluripotent embryonal carcinoma cells, and after birth differentiate into various cells and tissues that compose TGCTs. Here, we report the positional cloning of Ter, revealing a point mutation that introduces a termination codon in the mouse orthologue (Dnd1) of the zebrafish dead end (dnd) gene. PGC deficiency is corrected both with bacterial artificial chromosomes that contain Dnd1 and with a Dnd1-encoding transgene. Dnd1 is expressed in fetal gonads during the critical period when TGCTs originate. DND1 has an RNA recognition motif and is most similar to the apobec complementation factor, a component of the cytidine to uridine RNA-editing complex. These results suggest that Ter may adversely affect essential aspects of RNA biology during PGC development. DND1 is the first protein known to have an RNA recognition motif directly implicated as a heritable cause of spontaneous tumorigenesis. TGCT development in the 129-Ter mouse strain models paediatric TGCT in humans. This work will have important implications for our understanding of the genetic control of TGCT pathogenesis and PGC biology.     

Chaotic electron diffusion through stochastic webs enhances current flow in superlattices

Understanding how complex systems respond to change is of fundamental importance in the natural sciences. There is particular interest in systems whose classical newtonian motion becomes chaotic as an applied perturbation grows. The transition to chaos usually occurs by the gradual destruction of stable orbits in parameter space, in accordance with the Kolmogorov-Arnold-Moser (KAM) theorem--a cornerstone of nonlinear dynamics that explains, for example, gaps in the asteroid belt. By contrast, 'non-KAM' chaos switches on and off abruptly at critical values of the perturbation frequency. This type of dynamics has wide-ranging implications in the theory of plasma physics, tokamak fusion, turbulence, ion traps, and quasicrystals. Here we realize non-KAM chaos experimentally by exploiting the quantum properties of electrons in the periodic potential of a semiconductor superlattice with an applied voltage and magnetic field. The onset of chaos at discrete voltages is observed as a large increase in the current flow due to the creation of unbound electron orbits, which propagate through intricate web patterns in phase space. Non-KAM chaos therefore provides a mechanism for controlling the electrical conductivity of a condensed matter device: its extreme sensitivity could find applications in quantum electronics and photonics.     

A low density of 0.8 g cm(-3) for the Trojan binary asteroid 617 Patroclus

The Trojan population consists of two swarms of asteroids following the same orbit as Jupiter and located at the L4 and L5 stable Lagrange points of the Jupiter-Sun system (leading and following Jupiter by 60 degrees ). The asteroid 617 Patroclus is the only known binary Trojan. The orbit of this double system was hitherto unknown. Here we report that the components, separated by 680 km, move around the system's centre of mass, describing a roughly circular orbit. Using this orbital information, combined with thermal measurements to estimate the size of the components, we derive a very low density of 0.8(- 0.1)+0.2 g cm(-3). The components of 617 Patroclus are therefore very porous or composed mostly of water ice, suggesting that they could have been formed in the outer part of the Solar System.     

A laser frequency comb that enables radial velocity measurements with a precision of 1 cm s(-1)

Searches for extrasolar planets using the periodic Doppler shift of stellar spectral lines have recently achieved a precision of 60 cm s(-1) (ref. 1), which is sufficient to find a 5-Earth-mass planet in a Mercury-like orbit around a Sun-like star. To find a 1-Earth-mass planet in an Earth-like orbit, a precision of approximately 5 cm s(-1) is necessary. The combination of a laser frequency comb with a Fabry-Pérot filtering cavity has been suggested as a promising approach to achieve such Doppler shift resolution via improved spectrograph wavelength calibration, with recent encouraging results. Here we report the fabrication of such a filtered laser comb with up to 40-GHz (approximately 1-A) line spacing, generated from a 1-GHz repetition-rate source, without compromising long-term stability, reproducibility or spectral resolution. This wide-line-spacing comb, or 'astro-comb', is well matched to the resolving power of high-resolution astrophysical spectrographs. The astro-comb should allow a precision as high as 1 cm s(-1) in astronomical radial velocity measurements.     

Corneal avascularity is due to soluble VEGF receptor-1

Corneal avascularity-the absence of blood vessels in the cornea-is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders. But the molecular underpinnings of the avascular phenotype have until now remained obscure and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6+/- mice and Pax6+/- patients with aniridia are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6+/- mice. Manatees, the only known creatures uniformly to have vascularized corneas, do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.     

Saccadic oscillations facilitate ocular perfusion from the avian pecten

THE evolution of the eye is constrained by two conflicting requirements--good vascular perfusion of the retina, and an optical path through the retina that is unobstructed by blood vessels. Birds are interesting in that they have higher metabolic rates and thicker retinas than mammals, but have no retinal blood vessels. Nutrients and oxygen must thus reach the neurons of the inner retina either from the choroid through 300 micron of metabolically very active retina, or from the pecten, a pleated vascular structure protruding from the head of the optic nerve into the vitreous chamber, and more than a centimetre away from some retinal neurons. Despite the diffusional distance involved, several lines of evidence indicate that the pecten is the primary source of nutrients for the inner retina: the presence of an oxygen gradient from pecten to retina, the large surface area produced by macroscopic folds and by microscopic infoldings of the luminal and external surfaces of the capillary endothelium, extrusion of circulating fluorescein, high content of carbonic anhydrase and alkaline phosphatase, and retinal impairments after pecten ablation. Another peculiarity of birds, their saccadic oscillations, occur with a large cyclotor-sional component during every saccadic eye movement. In different species, saccades, which occur at intervals of 0.5-40 s, have up to 13 oscillations with frequencies of 15-30 Hz and ampliá-tudes of about 10 degrees. Therefore, as much as 12% of some birds' total viewing time may be subject to the image instability caused by the oscillations. Using fluorescein angiography, we show here that during every saccade, the pecten acts as an agitator which propels perfusate towards the central retina much more effectively than is observed during intersaccadic intervals.     

Senescence surveillance of pre-malignant hepatocytes limits liver cancer development

Upon the aberrant activation of oncogenes, normal cells can enter the cellular senescence program, a state of stable cell-cycle arrest, which represents an important barrier against tumour development in vivo. Senescent cells communicate with their environment by secreting various cytokines and growth factors, and it was reported that this 'secretory phenotype' can have pro- as well as anti-tumorigenic effects. Here we show that oncogene-induced senescence occurs in otherwise normal murine hepatocytes in vivo. Pre-malignant senescent hepatocytes secrete chemo- and cytokines and are subject to immune-mediated clearance (designated as 'senescence surveillance'), which depends on an intact CD4(+) T-cell-mediated adaptive immune response. Impaired immune surveillance of pre-malignant senescent hepatocytes results in the development of murine hepatocellular carcinomas (HCCs), thus showing that senescence surveillance is important for tumour suppression in vivo. In accordance with these observations, ras-specific Th1 lymphocytes could be detected in mice, in which oncogene-induced senescence had been triggered by hepatic expression of Nras(G12V). We also found that CD4(+) T cells require monocytes/macrophages to execute the clearance of senescent hepatocytes. Our study indicates that senescence surveillance represents an important extrinsic component of the senescence anti-tumour barrier, and illustrates how the cellular senescence program is involved in tumour immune surveillance by mounting specific immune responses against antigens expressed in pre-malignant senescent cells.