Animal cellulases

Previous dogma has maintained that cellulose, ingested by xylophagous or herbivorous animals, is digested by cellulolytic symbiotes. The first evidence in conflict with this contention involved the demonstration of cellulolytic activities in symbiote-free secreting organs (e.g., the salivary glands of termites) or defaunated guts. Following these demonstrations, possible endogenous cellulase components were purified from several cellulose-digesting invertebrates, but this research did little to change the general view concerning animal cellulose digestion. Thanks to recent developments in molecular biology, the existence of cellulases of animal origin has been firmly established. To date, cellulase genes have been reported from arthropods (insects and a crayfish) and nematodes. This paper describes and discusses the presence and nature of endogenous cellulases in higher animals. Received 19 December 2000; received after revision 5 March 2001; accepted 6 March 2001     

Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2

Ataxia-ocular apraxia 2 (AOA2) was recently identified as a new autosomal recessive ataxia. We have now identified causative mutations in 15 families, which allows us to clinically define this entity by onset between 10 and 22 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia and elevated alpha-fetoprotein (AFP). Ten of the fifteen mutations cause premature termination of a large DEAxQ-box helicase, the human ortholog of yeast Sen1p, involved in RNA maturation and termination.     

The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis

Meiosis comprises a pair of specialized nuclear divisions that produce haploid germ cells. To accomplish this, sister chromatids must segregate together during the first meiotic division (meiosis I), which requires that sister chromatid cohesion persists at centromeres. The factors that protect centromeric cohesion during meiosis I have remained elusive. Here we identify Sgo1 (shugoshin), a protector of the centromeric cohesin Rec8 in fission yeast. We also identify a homologue of Sgo1 in budding yeast. We provide evidence that shugoshin is widely conserved among eukaryotes. Moreover, we identify Sgo2, a paralogue of shugoshin in fission yeast, which is required for faithful mitotic chromosome segregation. Localization of Sgo1 and Sgo2 at centromeres requires the kinase Bub1, identifying shugoshin as a crucial target for the kinetochore function of Bub1. These findings provide insights into the evolution of meiosis and kinetochore regulation during mitosis and meiosis.     

Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus

The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA. Thus, to identify properties of the 1918 pandemic influenza A strain that might be related to its extraordinary virulence, viruses were produced containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. The HA of this strain supports the pathogenicity of a mouse-adapted virus in this animal. Here we demonstrate that the HA of the 1918 virus confers enhanced pathogenicity in mice to recent human viruses that are otherwise non-pathogenic in this host. Moreover, these highly virulent recombinant viruses expressing the 1918 viral HA could infect the entire lung and induce high levels of macrophage-derived chemokines and cytokines, which resulted in infiltration of inflammatory cells and severe haemorrhage, hallmarks of the illness produced during the original pandemic.     

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'.     

Circulating plasma kinin in patients with bronchial asthma

Zusammenfassung Bei 33 Patienten mit Asthma bronchiale von verschiedenem Erkrankungsgrade wurde der Kiningehalt im zirkulierenden Blut bestimmt. Erhöhte Blutkininwerte wurden in den Patienten gefunden, und zwar im allgemeinen mit der Schwere der Krankheit korrelierbar. Daraus folgt, dass das «Kinin» aetiologisch mit Asthma bronchiale verknüpft ist.     

Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus

Hassall's corpuscles-first described in the human thymus over 150 years ago-are groups of epithelial cells within the thymic medulla. The physical nature of these structures differs between mammalian species. Although Hassall's corpuscles have been proposed to act in both the removal of apoptotic thymocytes and the maturation of developing thymocytes within the thymus, the function of Hassall's corpuscles has remained an enigma. Here we report that human Hassall's corpuscles express thymic stromal lymphopoietin (TSLP). Human TSLP activates thymic CD11c-positive dendritic cells to express high levels of CD80 and CD86. These TSLP-conditioned dendritic cells are then able to induce the proliferation and differentiation of CD4(+)CD8(-)CD25(-) thymic T cells into CD4(+)CD25(+)FOXP3(+) (forkhead box P3) regulatory T cells. This induction depends on peptide-major histocompatibility complex class II interactions, and the presence of CD80 and CD86, as well as interleukin 2. Immunohistochemistry studies reveal that CD25(+)CTLA4(+) (cytotoxic T-lymphocyte-associated protein 4) regulatory T cells associate in the thymic medulla with activated or mature dendritic cells and TSLP-expressing Hassall's corpuscles. These findings suggest that Hassall's corpuscles have a critical role in dendritic-cell-mediated secondary positive selection of medium-to-high affinity self-reactive T cells, leading to the generation of CD4(+)CD25(+) regulatory T cells within the thymus.     

Repeated injections of energy in the first 600 ms of the giant flare of SGR 1806-20

The massive flare of 27 December 2004 from the soft gamma-ray repeater SGR 1806-20, a possible magnetar, saturated almost all gamma-ray detectors, meaning that the profile of the pulse was poorly characterized. An accurate profile is essential to determine physically what was happening at the source. Here we report the unsaturated gamma-ray profile for the first 600 ms of the flare, with a time resolution of 5.48 ms. The peak of the profile (of the order of 10(7) photons cm(-2) s(-1)) was reached approximately 50 ms after the onset of the flare, and was then followed by a gradual decrease with superposed oscillatory modulations possibly representing repeated energy injections with approximately 60-ms intervals. The implied total energy is comparable to the stored magnetic energy in a magnetar (approximately 10(47) erg) based on the dipole magnetic field intensity (approximately 10(15) G), suggesting either that the energy release mechanism was extremely efficient or that the interior magnetic field is much stronger than the external dipole field.     

Experimental investigation of geologically produced antineutrinos with KamLAND

The detection of electron antineutrinos produced by natural radioactivity in the Earth could yield important geophysical information. The Kamioka liquid scintillator antineutrino detector (KamLAND) has the sensitivity to detect electron antineutrinos produced by the decay of 238U and 232Th within the Earth. Earth composition models suggest that the radiogenic power from these isotope decays is 16 TW, approximately half of the total measured heat dissipation rate from the Earth. Here we present results from a search for geoneutrinos with KamLAND. Assuming a Th/U mass concentration ratio of 3.9, the 90 per cent confidence interval for the total number of geoneutrinos detected is 4.5 to 54.2. This result is consistent with the central value of 19 predicted by geophysical models. Although our present data have limited statistical power, they nevertheless provide by direct means an upper limit (60 TW) for the radiogenic power of U and Th in the Earth, a quantity that is currently poorly constrained.