cdx4 mutants fail to specify blood progenitors and can be rescued by multiple hox genes

Organogenesis is dependent on the formation of distinct cell types within the embryo. Important to this process are the hox genes, which are believed to confer positional identities to cells along the anteroposterior axis. Here, we have identified the caudal-related gene cdx4 as the locus mutated in kugelig (kgg), a zebrafish mutant with an early defect in haematopoiesis that is associated with abnormal anteroposterior patterning and aberrant hox gene expression. The blood deficiency in kgg embryos can be rescued by overexpressing hoxb7a or hoxa9a but not hoxb8a, indicating that the haematopoietic defect results from perturbations in specific hox genes. Furthermore, the haematopoietic defect in kgg mutants is not rescued by scl overexpression, suggesting that cdx4 and hox genes act to make the posterior mesoderm competent for blood development. Overexpression of cdx4 during zebrafish development or in mouse embryonic stem cells induces blood formation and alters hox gene expression. Taken together, these findings demonstrate that cdx4 regulates hox genes and is necessary for the specification of haematopoietic cell fate during vertebrate embryogenesis.     

BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis

Glycolysis and apoptosis are considered major but independent pathways that are critical for cell survival. The activity of BAD, a pro-apoptotic BCL-2 family member, is regulated by phosphorylation in response to growth/survival factors. Here we undertook a proteomic analysis to assess whether BAD might also participate in mitochondrial physiology. In liver mitochondria, BAD resides in a functional holoenzyme complex together with protein kinase A and protein phosphatase 1 (PP1) catalytic units, Wiskott-Aldrich family member WAVE-1 as an A kinase anchoring protein, and glucokinase (hexokinase IV). BAD is required to assemble the complex in that Bad-deficient hepatocytes lack this complex, resulting in diminished mitochondria-based glucokinase activity and blunted mitochondrial respiration in response to glucose. Glucose deprivation results in dephosphorylation of BAD, and BAD-dependent cell death. Moreover, the phosphorylation status of BAD helps regulate glucokinase activity. Mice deficient for BAD or bearing a non-phosphorylatable BAD(3SA) mutant display abnormal glucose homeostasis including profound defects in glucose tolerance. This combination of proteomics, genetics and physiology indicates an unanticipated role for BAD in integrating pathways of glucose metabolism and apoptosis.     

Extreme deuterium enrichment in stratospheric hydrogen and the global atmospheric budget of H2

Molecular hydrogen (H2) is the second most abundant trace gas in the atmosphere after methane (CH4). In the troposphere, the D/H ratio of H2 is enriched by 120 per thousand relative to the world's oceans. This cannot be explained by the sources of H2 for which the D/H ratio has been measured to date (for example, fossil fuels and biomass burning). But the isotopic composition of H2 from its single largest source--the photochemical oxidation of methane--has yet to be determined. Here we show that the D/H ratio of stratospheric H2 develops enrichments greater than 440 per thousand, the most extreme D/H enrichment observed in a terrestrial material. We estimate the D/H ratio of H2 produced from CH4 in the stratosphere, where production is isolated from the influences of non-photochemical sources and sinks, showing that the chain of reactions producing H2 from CH4 concentrates D in the product H2. This enrichment, which we estimate is similar on a global average in the troposphere, contributes substantially to the D/H ratio of tropospheric H2.     

Utah plant types—historical perspective 1840 to 1981—annotated list, and bibliography

New taxa include: Cryptantha cinerea (Torr.) Cronq. var. arenicola Higgins & Welsh; Physaria chambersii Rollins var. sobolifera Welsh (Cruciferae); Phacelia demissa Gray var. minor N. D. Atwood (Hydrophyllaceae); Iris pariensis Welsh (Iridaceae); Astragalus preussii var. cutleri Barneby and Pediomelum aromaticum (Payson) Welsh var. tuhyi Welsh (Leguminosae); Abronia nana Wats. var. harrisii Welsh (Nyctaginaceae); Camissonia atwoodii Cronq. (Onagraceae); Habenaria zothecina Higgins & Welsh (Orchidaceae); Aqiiilegia formosa Fisch. in DC. var. fosteri Welsh (Ranunculaceae). New nomenclatural combinations include: Rhus aromatica Ait. var. simplicifolia (Greene) Cronq. (Anacardiaceae); Lomatium kingii (Wats.) Cronq., L. kingii var. alpinum (Wats.) Cronq. (Apiaceae); Cryptantha cinerea (Torr.) Cronq. var. laxa (Macbr.) Higgins; Mertensia lanceolata (Pursh) DC. var. nivalis (Wats.) Higgins (Boraginaceae); Opuntia erinacea Engelm. var. aurea (Baxter) Welsh (Cactaceae); Arenaria fendleri Gray var. aculeata (Wats.) Welsh, A. fendleri var. eastwoodiae (Rydb.) Welsh, Lychnis apetala L. var. kingii (Wats.) Welsh, Stellaria longipes Goldie var. monantha (Hulten) Welsh (Caryophyllaceae); Draba densifolia Nutt. ex T. & G. var. apiculata (C. L. Hitchc.) Welsh, D. oligosperma Hook. var. juniperina (Dorn) Welsh, Physaria acutifolia Rydb. var. stylosa (Rollins) Welsh, Thelypodiopsis sagittata (Nutt.) Schulz var. ovalifolia (Rydb.) Welsh (Cruciferae); Lotus plebeius (T. Brandg.) Barneby, Lupinus polyphyllus Lindl. in Edwards var. ammophilus (Greene) Barneby, L polyphyllus var. humicola (A. Nels.) Barneby, L. argenteus Pursh var. fulvomaculatus (Payson) Barneby, L. argenteus var. palmeri (Wats.) Barneby, Pediomelum aromaticum (Payson) Welsh, P. epipsilum (Barneby) Welsh, Psoralidium lanceolatum (Pursh) Rydb. var. stenophyllum (Rydb.) Welsh, and P. lanceolatum var. stenostachys (Rydb.) Welsh (Leguminosae); Mirabilis linearis (Pursh) Hiemerl var. decipiens (Standl.) Welsh (Nyctaginaceae); Camissonia boothii var. condensata (Munz) Cronq., C. boothii var. villosa (Wats.) Cronq., C. clavaeformis (Torr. & Frem.) Raven var. purpurascens (Wats.) Cronq., C. scapoidea (T. & G.) var. utahensis (Raven) Welsh, Oenothera caespitosa var. macroglottis (Rydb.) Cronq., Oe. caespitosa var. navajoensis (Wagner, Stockhouse, & Klein) Cronq., Oe. flava (A. Nels.) Garrett var. acutissima (W. L. Wagner) Welsh, and Oe. primiveris Gray var. bufonis (Jones) Cronq. (Onagraceae); Papaver radicatum Rottb. var. pygmaeum (Rydb.) Welsh (Papaveraceae); Dodecatheon pulchellum (Raf.) Merr. var. zionense (Eastw.) Welsh (Primulaceae); Aquilegia flavescens Wats. var. rubicunda (Tidestr.) Welsh, Delphinium andersonii Gray var. scaposum (Greene) Welsh, D. occidentalis (Wats.) Wats. var. barbeyi (Huth) Welsh, and Ranunculus andersonii Gray var. juniperinus (Jones) Welsh (Ranunculaceae); Purshia mexicana (D. Don) Welsh and P. mexicana var. stansburyi (Torr.) Welsh (Rosaceae); Galium mexicanum H.B.K. var. asperrimum (Gray) Higgins & Welsh (Rubiaceae); Castilleja parvula Rydb. var. revealii (N. Holmgren) N. D. Atwood and C. rhexifolia Rydb. var. sulphurea (Rydb.) N. D. Atwood (Scrophulariaceae).     

New variety of Stephanomeria tenuifolia (Compositae) from Utah

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Mid-infrared images of beta Pictoris and the possible role of planetesimal collisions in the central disk

When viewed in optical starlight scattered by dust, the nearly edge-on debris disk surrounding the A5V star beta Pictoris (distance 19.3 pc; ref. 1) extends farther than 1,450 au from the star. Its large-scale complexity has been well characterized, but the detailed structure of the disk's central approximately 200-au region has remained elusive. This region is of special interest, because planets may have formed there during the star's 10-20-million-year lifetime, perhaps resulting in both the observed tilt of 4.6 degrees relative to the large-scale main disk and the partial clearing of the innermost dust. A peculiarity of the central disk (also possibly related to the presence of planets) is the asymmetry in the brightness of the 'wings', in which the southwestern wing is brighter and more extended at 12 microm than the northeastern wing. Here we present thermal infrared images of the central disk that imply that the brightness asymmetry results from the presence of a bright clump composed of particles that may differ in size from dust elsewhere in the disk. We suggest that this clump results from the collisional grinding of resonantly trapped planetesimals or the cataclysmic break-up of a planetesimal.     

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus

Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.     

MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia.

Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias. We propose that they constitute a distinct disease, denoted here as MLL, and show that the differences in gene expression are robust enough to classify leukemias correctly as MLL, acute lymphoblastic leukemia or acute myelogenous leukemia. Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets.