In vitro production of functional sperm in cultured neonatal mouse testes

Spermatogenesis is one of the most complex and longest processes of sequential cell proliferation and differentiation in the body, taking more than a month from spermatogonial stem cells, through meiosis, to sperm formation. The whole process, therefore, has never been reproduced in vitro in mammals, nor in any other species with a very few exceptions in some particular types of fish. Here we show that neonatal mouse testes which contain only gonocytes or primitive spermatogonia as germ cells can produce spermatids and sperm in vitro with serum-free culture media. Spermatogenesis was maintained over 2?months in tissue fragments positioned at the gas-liquid interphase. The obtained spermatids and sperm resulted in healthy and reproductively competent offspring through microinsemination. In addition, neonatal testis tissues were cryopreserved and, after thawing, showed complete spermatogenesis in vitro. Our organ culture method could be applicable through further refinements to a variety of mammalian species, which will serve as a platform for future clinical application as well as mechanistic understanding of spermatogenesis.     

Hydrous olivine unable to account for conductivity anomaly at the top of the asthenosphere

The oceanic asthenosphere is observed to have high electrical conductivity, which is highly anisotropic in some locations. In the directions parallel and normal to the plate motion, the conductivity is of the order of 10(-1) and 10(-2) S m(-1), respectively, which cannot be explained by the conductivity of anhydrous olivine. But because hydrogen can be incorporated in olivine at mantle pressures, this observation has been attributed to olivine hydration, which might cause anisotropically high conductivity by proton migration. To examine this hypothesis, here we report the effect of water on electrical conductivity and its anisotropy for hydrogen-doped and undoped olivine at 500-1,500 K and 3 GPa. The hydrous olivine has much higher conductivity and lower activation energy than anhydrous olivine in the investigated temperature range. Nevertheless, extrapolation of the experimental results suggests that conductivity of hydrous olivine at the top of the asthenosphere should be nearly isotropic and only of the order of 10(-2) S m(-1). Our data indicate that the hydration of olivine cannot account for the geophysical observations, which instead may be explained by the presence of partial melt elongated in the direction of plate motion.     

G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody

G-protein-coupled receptors are the largest class of cell-surface receptors, and these membrane proteins exist in equilibrium between inactive and active states. Conformational changes induced by extracellular ligands binding to G-protein-coupled receptors result in a cellular response through the activation of G proteins. The A(2A) adenosine receptor (A(2A)AR) is responsible for regulating blood flow to the cardiac muscle and is important in the regulation of glutamate and dopamine release in the brain. Here we report the raising of a mouse monoclonal antibody against human A(2A)AR that prevents agonist but not antagonist binding to the extracellular ligand-binding pocket, and describe the structure of A(2A)AR in complex with the antibody Fab fragment (Fab2838). This structure reveals that Fab2838 recognizes the intracellular surface of A(2A)AR and that its complementarity-determining region, CDR-H3, penetrates into the receptor. CDR-H3 is located in a similar position to the G-protein carboxy-terminal fragment in the active opsin structure and to CDR-3 of the nanobody in the active β(2)-adrenergic receptor structure, but locks A(2A)AR in an inactive conformation. These results suggest a new strategy to modulate the activity of G-protein-coupled receptors.     

Superflares on solar-type stars

Solar flares are caused by the sudden release of magnetic energy stored near sunspots. They release 10(29) to 10(32)?ergs of energy on a timescale of hours. Similar flares have been observed on many stars, with larger 'superflares' seen on a variety of stars, some of which are rapidly rotating and some of which are of ordinary solar type. The small number of superflares observed on solar-type stars has hitherto precluded a detailed study of them. Here we report observations of 365 superflares, including some from slowly rotating solar-type stars, from about 83,000 stars observed over 120 days. Quasi-periodic brightness modulations observed in the solar-type stars suggest that they have much larger starspots than does the Sun. The maximum energy of the flare is not correlated with the stellar rotation period, but the data suggest that superflares occur more frequently on rapidly rotating stars. It has been proposed that hot Jupiters may be important in the generation of superflares on solar-type stars, but none have been discovered around the stars that we have studied, indicating that hot Jupiters associated with superflares are rare.     

Regulation of intestinal epithelial permeability by tight junctions

The gastrointestinal epithelium forms the boundary between the body and external environment. It effectively provides a selective permeable barrier that limits the permeation of luminal noxious molecules, such as pathogens, toxins, and antigens, while allowing the appropriate absorption of nutrients and water. This selective permeable barrier is achieved by intercellular tight junction (TJ) structures, which regulate paracellular permeability. Disruption of the intestinal TJ barrier, followed by permeation of luminal noxious molecules, induces a perturbation of the mucosal immune system and inflammation, and can act as a trigger for the development of intestinal and systemic diseases. In this context, much effort has been taken to understand the roles of extracellular factors, including cytokines, pathogens, and food factors, for the regulation of the intestinal TJ barrier. Here, I discuss the regulation of the intestinal TJ barrier together with its implications for the pathogenesis of diseases.     

No high-mass protostars in the silhouette young stellar object M17-SO1

The birth of very massive stars is not well understood, in contrast to the formation process of low-mass stars like our Sun. It is not even clear that massive stars can form as single entities; rather, they might form through the mergers of smaller ones born in tight groups. The recent claim of the discovery of a massive protostar in M17 (a nearby giant ionized region) forming through the same mechanism as low-mass stars has therefore generated considerable interest. Here we show that this protostar has an intermediate mass of only 2.5 to 8 solar masses (M(o), contrary to the earlier claim of 20M(o) (ref. 8). The surrounding circumstellar envelope contains only 0.09M(o) and a much more extended local molecular cloud has 4-9M(o).     

An early extrasolar planetary system revealed by planetesimal belts in beta Pictoris

beta Pictoris (beta Pic) is a main-sequence star with an edge-on dust disk that might represent a state of the early Solar System. The dust does not seem to be a remnant from the original protoplanetary disk, but rather is thought to have been generated from large bodies like planetesimals and/or comets. The history and composition of the parent bodies can therefore be revealed by determining the spatial distribution, grain size, composition and crystallinity of the dust through high-resolution mid-infrared observations. Here we report that the sub-micrometre amorphous silicate grains around beta Pic have peaks in their distribution around 6, 16 and 30 au (1 au is the Sun-Earth distance), whereas the crystalline and micrometre-sized amorphous silicate grains are concentrated in the disk centre. As sub-micrometre grains are blown quickly out from the system by radiation pressure from the central star, the peaks indicate the locations of ongoing dust replenishment, which originates from ring-like distributions of planetesimals or 'planetesimal belts'.     

Dry mantle transition zone inferred from the conductivity of wadsleyite and ringwoodite

The Earth's mantle transition zone could potentially store a large amount of water, as the minerals wadsleyite and ringwoodite incorporate a significant amount of water in their crystal structure. The water content in the transition zone can be estimated from the electrical conductivities of hydrous wadsleyite and ringwoodite, although such estimates depend on accurate knowledge of the two conduction mechanisms in these minerals (small polaron and proton conductions), which early studies have failed to distinguish between. Here we report the electrical conductivity of these two minerals obtained by high-pressure multi-anvil experiments. We found that the small polaron conductions of these minerals are substantially lower than previously estimated. The contributions of proton conduction are small at temperatures corresponding to the mantle transition zone and the conductivity of wadsleyite is considerably lower than that of ringwoodite for both mechanisms. The dry model mantle shows considerable conductivity jumps associated with the olivine-wadsleyite, wadsleyite-ringwoodite and post-spinel transitions. Such a dry model explains well the currently available conductivity-depth profiles obtained from geoelectromagnetic studies. We therefore conclude that there is no need to introduce a significant amount of water in the mantle transition to satisfy electrical conductivity constraints.