Termination of asymmetric cell division and differentiation of stomata

Stomata consist of a pair of guard cells that mediate gas and water-vapour exchange between plants and the atmosphere. Stomatal precursor cells-meristemoids-possess a transient stem-cell-like property and undergo several rounds of asymmetric divisions before further differentiation. Here we report that the Arabidopsis thaliana basic helix-loop-helix (bHLH) protein MUTE is a key switch for meristemoid fate transition. In the absence of MUTE, meristemoids abort after excessive asymmetric divisions and fail to differentiate stomata. Constitutive overexpression of MUTE directs the entire epidermis to adopt guard cell identity. MUTE has two paralogues: FAMA, a regulator of guard cell morphogenesis, and SPEECHLESS (SPCH). We show that SPCH directs the first asymmetric division that initiates stomatal lineage. Together, SPCH, MUTE and FAMA bHLH proteins control stomatal development at three consecutive steps: initiation, meristemoid differentiation and guard cell morphogenesis. Our findings highlight the roles of closely related bHLHs in cell type differentiation in plants and animals.     

Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14

The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome.     

A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac

With the availability of complete genome sequence for Drosophila melanogaster, one of the next strategic goals for fly researchers is a complete gene knockout collection. The P-element transposon, the workhorse of D. melanogaster molecular genetics, has a pronounced nonrandom insertion spectrum. It has been estimated that 87% saturation of the approximately 13,500-gene complement of D. melanogaster might require generating and analyzing up to 150,000 insertions. We describe specific improvements to the lepidopteran transposon piggyBac and the P element that enabled us to tag and disrupt genes in D. melanogaster more efficiently. We generated over 29,000 inserts resulting in 53% gene saturation and a more diverse collection of phenotypically stronger insertional alleles. We found that piggyBac has distinct global and local gene-tagging behavior from that of P elements. Notably, piggyBac excisions from the germ line are nearly always precise, piggyBac does not share chromosomal hotspots associated with P and piggyBac is more effective at gene disruption because it lacks the P bias for insertion in 5' regulatory sequences.     

Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome

Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in fibrillin-1 (encoded by FBN1 in humans and Fbn1 in mice), a matrix component of extracellular microfibrils. A distinct subgroup of individuals with Marfan syndrome have distal airspace enlargement, historically described as emphysema, which frequently results in spontaneous lung rupture (pneumothorax; refs. 1-3). To investigate the pathogenesis of genetically imposed emphysema, we analyzed the lung phenotype of mice deficient in fibrillin-1, an accepted model of Marfan syndrome. Lung abnormalities are evident in the immediate postnatal period and manifest as a developmental impairment of distal alveolar septation. Aged mice deficient in fibrillin-1 develop destructive emphysema consistent with the view that early developmental perturbations can predispose to late-onset, seemingly acquired phenotypes. We show that mice deficient in fibrillin-1 have marked dysregulation of transforming growth factor-beta (TGF-beta) activation and signaling, resulting in apoptosis in the developing lung. Perinatal antagonism of TGF-beta attenuates apoptosis and rescues alveolar septation in vivo. These data indicate that matrix sequestration of cytokines is crucial to their regulated activation and signaling and that perturbation of this function can contribute to the pathogenesis of disease.     

Antiferromagnetic order as the competing ground state in electron-doped Nd1.85Ce0.15CuO4

Superconductivity in the high-transition-temperature (high-T(c)) copper oxides competes with other possible ground states. The physical explanation for superconductivity can be constrained by determining the nature of the closest competing ground state, and establishing if that state is universal among the high-T(c) materials. Antiferromagnetism has been theoretically predicted to be the competing ground state. A competing ground state is revealed when superconductivity is destroyed by the application of a magnetic field, and antiferromagnetism has been observed in hole-doped materials under the influence of modest fields. None of the previous experiments have revealed the quantum phase transition from the superconducting state to the antiferromagnetic state, because they failed to reach the upper critical field B(c2). Here we report the results of transport and neutron-scattering experiments on electron-doped Nd1.85Ce0.15CuO4 (refs 13, 14), where B(c2) can be reached. The applied field reveals a static, commensurate, anomalously conducting long-range ordered antiferromagnetic state, in which the induced moment scales approximately linearly with the field strength until it saturates at B(c2). This and previous experiments on the hole-doped materials therefore establishes antiferromagnetic order as a competing ground state in the high-T(c) copper oxide materials, irrespective of electron or hole doping.     

Seasonal trends and colonization patterns of macroinvertebrate assemblages in two streams with contrasting flow regimes

Patterns of colonization by macroinvertebrates were examined in two streams that differ in flow regime: a snowmelt system and a mesic groundwater system. Experiments were conducted during spring runoff, summer baseflow, and winter baseflow using artificial substrata. Colonization patterns reflected seasonal changes in benthic macroinvertebrate assemblages and life histories in each stream. The density and biomass of benthic organisms were approximately 3X greater in winter than in either spring or summer for both streams. Similarly, colonization was greater in winter than in spring or summer for both streams. In spring, colonization patterns were different between streams, with colonization being imperceptible in the snowmelt stream. Macroinvertebrate abundance fluctuated during the summer colonization experiment at both sites, resulting from a complex interplay among population emergence, recruitment, and/or movement. Assemblages in the snowmelt system primarily comprised mobile or ruderal taxa, such as Beatis tricaudatus and Chironomidae, whereas relatively sessile taxa, such as Glossoma nigrior , were predominant in the mesic groundwater system. Seasonal patterns of colonization differed among stream types primarily because of the profound interplay of flow regime and temperature on benthic community structure and organism life history.     

Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome

The genetic basis of most conditions characterized by congenital contractures is largely unknown. Here we show that mutations in the embryonic myosin heavy chain (MYH3) gene cause Freeman-Sheldon syndrome (FSS), one of the most severe multiple congenital contracture (that is, arthrogryposis) syndromes, and nearly one-third of all cases of Sheldon-Hall syndrome (SHS), the most common distal arthrogryposis. FSS and SHS mutations affect different myosin residues, demonstrating that MYH3 genotype is predictive of phenotype. A structure-function analysis shows that nearly all of the MYH3 mutations are predicted to interfere with myosin's catalytic activity. These results add to the growing body of evidence showing that congenital contractures are a shared outcome of prenatal defects in myofiber force production. Elucidation of the genetic basis of these syndromes redefines congenital contractures as unique defects of the sarcomere and provides insights about what has heretofore been a poorly understood group of disorders.