A genome-wide comparison of recent chimpanzee and human segmental duplications

We present a global comparison of differences in content of segmental duplication between human and chimpanzee, and determine that 33% of human duplications (> 94% sequence identity) are not duplicated in chimpanzee, including some human disease-causing duplications. Combining experimental and computational approaches, we estimate a genomic duplication rate of 4-5 megabases per million years since divergence. These changes have resulted in gene expression differences between the species. In terms of numbers of base pairs affected, we determine that de novo duplication has contributed most significantly to differences between the species, followed by deletion of ancestral duplications. Post-speciation gene conversion accounts for less than 10% of recent segmental duplication. Chimpanzee-specific hyperexpansion (> 100 copies) of particular segments of DNA have resulted in marked quantitative differences and alterations in the genome landscape between chimpanzee and human. Almost all of the most extreme differences relate to changes in chromosome structure, including the emergence of African great ape subterminal heterochromatin. Nevertheless, base per base, large segmental duplication events have had a greater impact (2.7%) in altering the genomic landscape of these two species than single-base-pair substitution (1.2%).     

An aqueous extract of Liu Wei Di Huang Wan alters the labeling of blood constituents with Technetium-99m

The Liu Wei Di Huang Wan is a formula of a traditional Chinese medicine that is used to treat asthma patients and has been shown to have several important properties,such as antioxidant and free radical scavenging activities.The influence of an extract of Liu Wei Di Huang Wan on the labeling of blood constituents with technetium-99m was investigated.Anticoagulated blood(Wistar rats) was incubated with the extract,stannous chloride and technetium-99m,as sodium pertechnetate.Samples were centrifuged and aliquots of plasma and blood cells were separated and precipitated with trichloroacetic acid,to obtain soluble and insoluble fractions of the blood constituents.The percentage of radioactivity(%ATI) in all the fractions was determined.The analysis of the results shows that the extract at the highest concentration used(70 mg/mL) decreased significantly(P<0.05) the %ATI(from 96.48 ± 1.19 to 54.46 ± 7.38) on blood cells compartment,(from 81.11 ± 4.15 to 61.33 ± 4.74) on insoluble fractions of blood cells and(from 65.91 ± 2.44 to 13.15 ± 3.62) on insoluble fractions of plasma.In conclusion,the results suggest that the substances present on this extract can alter this labeling process,probably due to(i) redox properties(antioxidant and chelator activities) and/or(ii) specific actions in the binding sites where the 99mTc would be bound on the blood constituents.As a consequence,precaution is suggested on the interpretation of the nuclear medicine results from performed with blood constituents labeled with 99m Tc in patients that have undertaken LWDHW,although the current findings were obtained in experimental animal models.     

Molecular architecture of native HIV-1 gp120 trimers

The envelope glycoproteins (Env) of human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate virus binding to the cell surface receptor CD4 on target cells to initiate infection. Env is a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120), and forms trimers on the surface of the viral membrane. Using cryo-electron tomography combined with three-dimensional image classification and averaging, we report the three-dimensional structures of trimeric Env displayed on native HIV-1 in the unliganded state, in complex with the broadly neutralizing antibody b12 and in a ternary complex with CD4 and the 17b antibody. By fitting the known crystal structures of the monomeric gp120 core in the b12- and CD4/17b-bound conformations into the density maps derived by electron tomography, we derive molecular models for the native HIV-1 gp120 trimer in unliganded and CD4-bound states. We demonstrate that CD4 binding results in a major reorganization of the Env trimer, causing an outward rotation and displacement of each gp120 monomer. This appears to be coupled with a rearrangement of the gp41 region along the central axis of the trimer, leading to closer contact between the viral and target cell membranes. Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells.     

A new species and the phylogeny of the South American genus Gromphas Brullé, 1837 (Coleoptera: Scarabaeidae: Scarabaeinae: Phanaeini)

Gromphas jardim Cupello & Vaz-de-Mello sp. nov. is described from Bolivia and Central Brazil and is endemic to the biogeographic province of Rondônia. It resembles Gromphas amazonica and Gromphas inermis, but is distinguished primarily by the pattern of pronotal granulation and the form of the apical tubercle of male protibiae, which is modified in a tapered spur. Based on 31 morphological characters, a phylogenetic analysis returned a single most parsimonious tree where Gromphas is monophyletic and has the following internal topology: ((G. aeruginosa + G. lemoinei) (G. dichroa (G. inermis (G. amazonica + G. jardim)))).     

Following the signal sequence from ribosomal tunnel exit to signal recognition particle

Membrane and secretory proteins can be co-translationally inserted into or translocated across the membrane. This process is dependent on signal sequence recognition on the ribosome by the signal recognition particle (SRP), which results in targeting of the ribosome-nascent-chain complex to the protein-conducting channel at the membrane. Here we present an ensemble of structures at subnanometre resolution, revealing the signal sequence both at the ribosomal tunnel exit and in the bacterial and eukaryotic ribosome-SRP complexes. Molecular details of signal sequence interaction in both prokaryotic and eukaryotic complexes were obtained by fitting high-resolution molecular models. The signal sequence is presented at the ribosomal tunnel exit in an exposed position ready for accommodation in the hydrophobic groove of the rearranged SRP54 M domain. Upon ribosome binding, the SRP54 NG domain also undergoes a conformational rearrangement, priming it for the subsequent docking reaction with the NG domain of the SRP receptor. These findings provide the structural basis for improving our understanding of the early steps of co-translational protein sorting.     

Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.     

The inner-nuclear-envelope protein emerin regulates HIV-1 infectivity

Primate lentiviruses such as human immunodeficiency type 1 (HIV-1) have the capacity to infect non-dividing cells such as tissue macrophages. In the process, viral complementary DNA traverses the nuclear envelope to integrate within chromatin. Given the intimate association between chromatin and the nuclear envelope, we examined whether HIV-1 appropriates nuclear envelope components during infection. Here we show that emerin, an integral inner-nuclear-envelope protein, is necessary for HIV-1 infection. Infection of primary macrophages lacking emerin was abortive in that viral cDNA localized to the nucleus but integration into chromatin was inefficient, and conversion of viral cDNA to non-functional episomal cDNA increased. HIV-1 cDNA associated with emerin in vivo, and the interaction of viral cDNA with chromatin was dependent on emerin. Barrier-to-autointegration factor (BAF), the LEM (LAP, emerin, MAN) binding partner of emerin, was required for the association of viral cDNA with emerin and for the ability of emerin to support virus infection. Therefore emerin, which bridges the interface between the inner nuclear envelope and chromatin, may be necessary for chromatin engagement by viral cDNA before integration.     

Transiting extrasolar planetary candidates in the Galactic bulge

More than 200 extrasolar planets have been discovered around relatively nearby stars, primarily through the Doppler line shifts owing to reflex motions of their host stars, and more recently through transits of some planets across the faces of the host stars. The detection of planets with the shortest known periods, 1.2-2.5 days, has mainly resulted from transit surveys which have generally targeted stars more massive than 0.75 M(o), where M(o) is the mass of the Sun. Here we report the results from a planetary transit search performed in a rich stellar field towards the Galactic bulge. We discovered 16 candidates with orbital periods between 0.4 and 4.2 days, five of which orbit stars of masses in the range 0.44-0.75 M(o). In two cases, radial-velocity measurements support the planetary nature of the companions. Five candidates have orbital periods below 1.0 day, constituting a new class of ultra-short-period planets, which occur only around stars of less than 0.88 M(o). This indicates that those orbiting very close to more-luminous stars might be evaporatively destroyed or that jovian planets around stars of lower mass might migrate to smaller radii.