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Cell extrusion is a mechanism of cell elimination that is used by organisms as diverse as sponges, nematodes, insects and mammals

Peripheral mechanisms preventing autoimmunity and maintaining tolerance to commensal microbiota involve CD4(+) Foxp3(+) regulatory T (Treg) cells generated in the thymus or extrathymically by induction of naive CD4(+) Foxp3(-) T cells. Previous studies suggested that the T-cell receptor repertoires of thymic Treg cells and induced Treg cells are biased towards self and non-self antigens, respectively, but their relative contribution in controlling immunopathology, such as colitis and other untoward inflammatory responses triggered by different types of antigens, remains unresolved. The intestine, and especially the colon, is a particularly suitable organ to study this question, given the variety of self-, microbiota- and food-derived antigens to which Treg cells and other T-cell populations are exposed. Intestinal environments can enhance conversion to a regulatory lineage and favour tolerogenic presentation of antigens to naive CD4(+) T cells, suggesting that intestinal homeostasis depends on microbiota-specific induced Treg cells. Here, to identify the origin and antigen-specificity of intestinal Treg cells, we performed single-cell and high-throughput sequencing of the T-cell receptor repertoires of CD4(+) Foxp3(+) and CD4(+) Foxp3(-) T cells, and analysed their reactivity against specific commensal species. We show that thymus-derived Treg cells constitute most Treg cells in all lymphoid and intestinal organs, including the colon, where their repertoire is heavily influenced by the composition of the microbiota. Our results suggest that thymic Treg cells, and not induced Treg cells, dominantly mediate tolerance to antigens produced by intestinal commensals.

The elimination of unnecessary or defective cells from metazoans occurs during normal development and tissue homeostasis, as well as in response to infection or cellular damage. Although many cells are removed through caspase-mediated apoptosis followed by phagocytosis by engulfing cells, other mechanisms of cell elimination occur, including the extrusion of cells from epithelia through a poorly understood, possibly caspase-independent, process. Here we identify a mechanism of cell extrusion that is caspase independent and that can eliminate a subset of the Caenorhabditis elegans cells programmed to die during embryonic development. In wild-type animals, these cells die soon after their generation through caspase-mediated apoptosis. However, in mutants lacking all four C. elegans caspase genes, these cells are eliminated by being extruded from the developing embryo into the extra-embryonic space of the egg. The shed cells show apoptosis-like cytological and morphological characteristics, indicating that apoptosis can occur in the absence of caspases in C. elegans. We describe a kinase pathway required for cell extrusion involving PAR-4, STRD-1 and MOP-25.1/-25.2, the C. elegans homologues of the mammalian tumour-suppressor kinase LKB1 and its binding partners STRADα and MO25α. The AMPK-related kinase PIG-1, a possible target of the PAR-4–STRD-1–MOP-25 kinase complex, is also required for cell shedding. PIG-1 promotes shed-cell detachment by preventing the cell-surface expression of cell-adhesion molecules. Our findings reveal a mechanism for apoptotic cell elimination that is fundamentally distinct from that of canonical programmed cell death.

THE concentration of carbon dioxide in the atmosphere is increasing, largely because of fossil-fuel combustion, but the rate of increase is only about half of the total emission rate1. The balance of the carbon must be taken up in the oceans and the terrestrial biosphere, but the relative importance of each of these sinks—as well as their geographical distribution and the uptake mechanisms involved—are still a matter of debate1-4. Measurements of CO2 concentrations at remote marine sites5-9 have been used with numerical models of atmospheric transport to deduce the location, nature and magnitude of these carbon sinks2,10-19. One of the most important constraints on such estimates is the observed interhemispheric gradient in atmospheric CO2 concentration. Published models that simulate the transport of trace gases suggest that the gradient is primarily due to interhemispheric differences in fossil-fuel emissions, with small contributions arising from natural exchange of CO2 with the various carbon reservoirs. Here we use a full atmospheric general circulation model with a more realistic representation of turbulent mixing near the ground to investigate CO2 transport. We find that the latitudinal (meridional) gradient imposed by the seasonal terrestrial biota is nearly half as strong as that imposed by fossil-fuel emissions. Such a contribution implies that the sinks of atmospheric CO2 in the Northern Hemisphere must be stronger than previously suggested.

Cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane Cl- channel regulated by cyclic AMP-dependent phosphorylation and by intracellular ATP. Mutations in CFTR cause cystic fibrosis partly through loss of cAMP-regulated Cl- permeability from the plasma membrane of affected epithelia. The most common mutation in cystic fibrosis is deletion of phenylalanine at residue 508 (CFTR delta F508) (ref. 10). Studies on the biosynthesis and localization of CFTR delta F508 indicate that the mutant protein is not processed correctly and, as a result, is not delivered to the plasma membrane. These conclusions are consistent with earlier functional studies which failed to detect cAMP-stimulated Cl- channels in cells expressing CFTR delta F508 (refs 16, 17). Chloride channel activity was detected, however, when CFTR delta F508 was expressed in Xenopus oocytes, Vero cells and Sf9 insect cells. Because oocytes and Sf9 cells are typically maintained at lower temperatures than mammalian cells, and because processing of nascent proteins can be sensitive to temperature, we tested the effect of temperature on the processing of CFTR delta F508. Here we show that the processing of CFTR delta F508 reverts towards that of wild-type as the incubation temperature is reduced. When the processing defect is corrected, cAMP-regulated Cl- channels appear in the plasma membrane. These results reconcile previous contradictory observations and suggest that the mutant most commonly associated with cystic fibrosis is temperature-sensitive.

THE potential development of optoelectronic devices based on the nonlinear polarization of molecular materials has aroused much recent interest1,2. The search for large second-order electric susceptibilities (that is, proportional to the square of an applied electric field) has concentrated on acentric organic or organometallic chromophores with an organic π-electron system coupling electron donor and acceptor groups3–6. It is conceivable that mixed-valence compounds characterized by an intervalence charge-transfer (IVCT) transition7, in which the donor and acceptor centres are both metal atoms, might also have the potential to provide a large second-order response8, but this possibility has not been widely explored. Here we report the first hyperpolarizability, β, of a bimetallic complex ion, [(CN)5Ru-μCN-Ru(NH3)5]- (I in Fig. 1), and a novel organometallic analogue, [(η5-C5H5)Ru(PPh3)2-μ-CN-Ru(NH3)5]3+ (II). Measurements of β (which is related to the bulk second-order response) in solution at a wavelength of 1,064 nm using the newly developed hyper-Rayleigh scattering technique9,10 give values greater than 10–27 e.s.u., which are among the largest reported for solution species. The ease with which the energy of the IVCT transition can be modified suggests that there may be considerable potential for this class of chromophore in nonlinear optical devices.

AFTER heavy storms of hail on January 30, the sky cleared and the night was exceptionally fine. I observed Jupiter with my 10-inch reflector about 11h. 30m., and watched the chief markings pass the central meridian of the planet. The well-known equatorial white spot came to transit at 11h. 44m., and it was followed 5 minutes later—at 11h. 49m.—by the great red spot. These objects, therefore, must have been in conjunction on January 30, at 2h. 47m., as the greater velocity of the white spot enables it to gain 13m. 24s. on the red spot daily.

THE labour done by astronomical amateurs has had no little influence upon the progress of this science. The work achieved by them has indeed often been of the utmost value, and a long list of names might be adduced of those who in past years attained a most honourable position either as discoverers, as systematic observers, or as both. Seeing therefore that amateurs, whose efforts are purely disinterested and the natural outcome of a love for the subject, have contributed so largely to place our knowledge of astronomy in its present high place, their efforts should be encouraged and utilised by their contemporaries, who hold official positions, and who may find it convenient to assist them by some of that practical advice and instruction which they are eminently qualified to afford.

WITH Mars, Jupiter, and Saturn so favourably visible in the sky during the ensuing autumn and winter months, we think it may be interesting to call attention to some of their more prominent features, and to ask amateurs and others who devote themselves to the attractive field of planetary observation to make a combined effort, not only to substantiate such facts as are already known with regard to the physical appearances of these bodies, but to endeavour to glean something new concerning them. For, notwithstanding the diligence with which these planets have been scrutinised in past years and the many curious facts that have been brought to light, it must still be confessed that there remains much to be done. Our knowledge is admitted to be extremely incomplete. The powerful instruments of the present day do not seem capable of rendering us efficient aid in this respect; indeed we shall find by a comparison of results that we owe most of our discoveries to telescopes of moderate aperture. The real explanation probably is that, with increase of aperture, definition, especially of the brighter planets, becomes less perfect. Faint markings are obliterated or seen unsteadily and uncertainly in large instruments owing to glare, the difficulty of getting a sharp, hard disk with so much light, and the constant undulations of the atmosphere. With moderately small instruments the conditions are in many respects more favourable. The image is sharply defined, and though the quantity of light may be some-what deficient, there is an absence of glare and of that atmospheric interference which are inseparable from large apertures. Moreover, the eye is more capable of prolonged observation and is enabled to glimpse the faintest details on an image of moderate intensity. The deficiency of light in small instruments is therefore to some extent a recommendation when it is accompanied with extreme sharpness of definition and when the amount collected by the object-glass or speculum is sufficient to allow a power to be used which displays a fairly large disk without destroying the quality of the definition. Indeed one great desiderative in such cases is to utilise light and power in agreeable proportion, for this is a very essential requirement, which is, however, often neglected, and is frequently the source of disappointing experiences. Amateurs who are careful to consider these matters will be enabled, though their instruments may be of comparatively small reach, to do much useful work in many departments of observation, and particularly in that relating to planetary markings.

WELL may Mr. Greg, in his catalogue of meteoric radiants, published in 1876, affix a remark indicating the all-surpassing character of the mid-November meteors. For if there is one star shower more striking than all the rest, it is assuredly the Leonids. Every one who has seen the phenomenon at its best, is prepared to admit that it furnishes a grander spectacle than any other system, and will have realised that, once seen, it impresses itself indelibly upon the memory. There can be very few people living now who witnessed the great shower in America on the morning of November 14, 1833, but there are many Englishmen who vividly remember the fine but less splendid exhibition of 1860. With a swiftness unsurpassed among meteor streams, and with a brilliancy quite their own, the Leonids belong to the most striking class of these bodies, and offer a great distinction to the slow and gentle flights of the Andro-inedes, or meteors of Biela's comet which present themselves about a fortnight later. It is true the Leonids are only manifested, in vast abundance, once in a generation, and that, considered as an annual display, they usually fall below the strength of the August Perseids. But, considering all things, the November shower is undoubtedly entitled to precedence. The writer saw the Leonids in 1866, he also observed the rich displays of Andromedes in 1872 and 1885, and has been fortunate enough to witness many bright returns of the Perseids and of other prominent systems; but, of all such spectacles, one only, by its surpassing splendour, created an impression which still lives fresh in the memory, and that was the Leonids of November 1866.