Re-evaluation of the phylogenetic position of the genus Dexiotrichides (Protozoa, Ciliophora, Scuticociliatida) inferred from stomatogenetic and molecular information for Dexiotrichides pangi

The divisional process and systematic position of the marine scuticociliate Dexiotrichides pangi are studied. Based on both stomatogenetic data and 18S rDNA gene sequences, the phylogeny and morphogenetic characteristics of this taxon, and of other related genera, are analyzed and discussed. Both the divisionary events and the molecular biological data indicate that this speciesgenus, together with certain other genera in the Dexiotricha-complex, occupies an intermediate position between the tetrahymenids and the “typical” scuticociliate, which suggests that the Dexiotricha-like taxa should be excluded from the “true” scuticociliates. As a further contribution, the process of stomatogenesis in D. pangi can be summarized as follows: (1) The oral primordia in the opisthe are formed only by the proliferation of basal bodies in the scutica field, which subsequently develop into three membranelles, while the new paroral membrane seems to be generated by the sub-anterior portion of somatic kinety 1 (the 1st postoral intercalary kinety). The latter character exhibits a mode similar to Tetrahymena. (2) In the proter the parental membranelles are retained and remain unchanged throughout the entire division process; only the old paroral membrane is disassembled and differentiated into the anlage, which then gives rise to the new paroral membrane and the scutica of the proter. The 18S rRNA gene sequence reported here is the first one for a ciliate in the Dexiotricha-complex.     

The structure of H5N1 avian influenza neuraminidase suggests new opportunities for drug design

The worldwide spread of H5N1 avian influenza has raised concerns that this virus might acquire the ability to pass readily among humans and cause a pandemic. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu) and zanamivir (Relenza), both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Neuraminidases from influenza type A viruses form two genetically distinct groups: group-1 contains the N1 neuraminidase of the H5N1 avian virus and group-2 contains the N2 and N9 enzymes used for the structure-based design of current drugs. Here we show by X-ray crystallography that these two groups are structurally distinct. Group-1 neuraminidases contain a cavity adjacent to their active sites that closes on ligand binding. Our analysis suggests that it may be possible to exploit the size and location of the group-1 cavity to develop new anti-influenza drugs.     

The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast

The autosomal recessive disorder Shwachman-Diamond syndrome, characterized by bone marrow failure and leukemia predisposition, is caused by deficiency of the highly conserved Shwachman-Bodian-Diamond syndrome (SBDS) protein. Here, we identify the function of the yeast SBDS ortholog Sdo1, showing that it is critical for the release and recycling of the nucleolar shuttling factor Tif6 from pre-60S ribosomes, a key step in 60S maturation and translational activation of ribosomes. Using genome-wide synthetic genetic array mapping, we identified multiple TIF6 gain-of-function alleles that suppressed the pre-60S nuclear export defects and cytoplasmic mislocalization of Tif6 observed in sdo1Delta cells. Sdo1 appears to function within a pathway containing elongation factor-like 1, and together they control translational activation of ribosomes. Thus, our data link defective late 60S ribosomal subunit maturation to an inherited bone marrow failure syndrome associated with leukemia predisposition.     

梳冬夜蛾和白边切夜蛾卵抗寒性研究

对梳冬夜蛾和白边切夜蛾卵的过冷却点、结冰点和不同低温强度及持续时间等指标的冷冻处理测定结果:梳冬夜蛾卵过冷却点为-18.76±4.09℃,结冰点为-17.7±5.02℃;白边切夜蛾卵的相应指标分别为-8.13±3.17℃和-7.15±3.09℃。两种蛾卵在一定的低温条件下,处理时间愈长,卵孵化率愈低;随着低温强度加大,卵孵化率明显降低。     

Induction of recombination between diverged sequences in a mammalian genome by a double-strand break

To investigate whether mammalian cells can carry out recombinational double-strand break (DSB) repair between highly diverged sequences, mouse fibroblasts were transfected with DNA substrates that contained a “recipient” thymidine kinase (tk) gene disrupted by the recognition site for endonuclease I-SceI. Substrates also contained a linked “donor” tk gene sequence. Following DSB induction by I-SceI, selection for tk-expressing clones allowed recovery of repair events occurring by nonhomologous end-joining or recombination with the donor sequence. Although recombinational repair was most efficient when donor and recipient shared near-perfect homology, we recovered recombination events between recipient and donor sequences displaying 20 % nucleotide mismatch. Recombination between such imperfectly matched (“homeologous”) sequences occurred at a frequency of 1.7 × 10^?7 events per cell and constituted 3 % of the DSB repair events recovered with the pair of homeologous sequences. Additional experiments were done with a substrate containing a donor sequence comprised of a region sharing high homology with the recipient and an adjacent region homeologous to the recipient. Recombinational DSB repair tracts initiating within high homology propagated into homeology in 11 of 112 repair events. These collective results contrasted with our earlier work in which spontaneous recombination (not intentionally induced by a DSB) between homeologous sequences occurred at an undetectable frequency of less than 10^?9 events per cell, and in which events initiating within high homology propagated into adjoining homeology in one of 81 events examined. Our current work suggests that homology requirements for recombination are effectively relaxed in proximity to a DSB in a mammalian genome.     

Hypothesis and experiment in the early development of Kekulé's Benzene theory

This article attempts a contextual study of the origin and early development of August Kekulé's theory of aromatic compounds. The terminus a quo is essentially August Hofmann's coining of the modern chemical denotation of ‘aromatic’ in 1855; the terminus ad quem is the first full codification of Kekulé's theory in the sixth fascicle of his Lehrbuch der organischen Chemie, published in the summer of 1866. Kekulé's theory is viewed in context with the earlier and concurrent experimental work of such chemists as Hermann Kolbe, Friedrich Beilstein, Rudolph Fittig, and Hugo Müller. The reception of the theory is briefly examined. Attention is paid to the role of Kekulé's molecular models and of his celebrated dream anecdote of the snake that seizes its own tail. The episode is used as a case study for the continuity of scientific progress, and to illustrate the close reciprocal interactions of hypothesis and experiment in the evolution of a scientific theory.     

Loss-of-function mutations in TGFB2 cause a syndromic presentation of thoracic aortic aneurysm

Loeys-Dietz syndrome (LDS) associates with a tissue signature for high transforming growth factor (TGF)-β signaling but is often caused by heterozygous mutations in genes encoding positive effectors of TGF-β signaling, including either subunit of the TGF-β receptor or SMAD3, thereby engendering controversy regarding the mechanism of disease. Here, we report heterozygous mutations or deletions in the gene encoding the TGF-β2 ligand for a phenotype within the LDS spectrum and show upregulation of TGF-β signaling in aortic tissue from affected individuals. Furthermore, haploinsufficient Tgfb2(+/-) mice have aortic root aneurysm and biochemical evidence of increased canonical and noncanonical TGF-β signaling. Mice that harbor both a mutant Marfan syndrome (MFS) allele (Fbn1(C1039G/+)) and Tgfb2 haploinsufficiency show increased TGF-β signaling and phenotypic worsening in association with normalization of TGF-β2 expression and high expression of TGF-β1. Taken together, these data support the hypothesis that compensatory autocrine and/or paracrine events contribute to the pathogenesis of TGF-β-mediated vasculopathies.