Comprehensive Characterization of the Transmitted/Founder env Genes From a Single MSM Cohort in China

Background: The men having sex with men (MSM) population has become one of the major risk groups for HIV-1 infection in China. However, the epidemiological patterns, function of the env genes, and autologous and heterologous neutralization activity in the same MSM population have not been systematically characterized. Methods: The env gene sequences were obtained by the single genome amplification. The time to the most recent common ancestor was estimated for each genotype using the Bayesian Markov Chain Monte Carlo approach. Coreceptor usage was determined in NP-2 cells. Neutralization was analyzed using Env pseudoviruses in TZM-bl cells. Results: We have obtained 547 full-length env gene sequences by single genome amplification from 30 acute/early HIV-1–infected individuals in the Beijing MSM cohort. Three genotypes (subtype B, CRF01_AE, and CRF07_BC) were identified and 20% of the individuals were infected with multiple transmitted/founder (T/F) viruses. The tight clusters of the MSM sequences regardless of geographic origins indicated nearly exclusive transmission within the MSM population and limited number of introductions. The time to the most recent common ancestor for each genotype was 10–15 years after each was first introduced in China. Disparate preferences for coreceptor usages among 3 genotypes might lead to the changes in percentage of different genotypes in the MSM population over time. The genotype-matched and genotype-mismatched neutralization activity varied among the 3 genotypes. Conclusions: The identification of unique characteristics for transmission, coreceptor usage, neutralization profile, and epidemic patterns of HIV-1 is critical for the better understanding of transmission mechanisms, development of preventive strategies, and evaluation of vaccine efficacy in the MSM population in China

Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection

New Fe-based superconductors: properties relevant for applications

Less than two years after the discovery of high temperature superconductivity in oxypnictide LaFeAs(O,F) several families of superconductors based on Fe layers (1111, 122, 11, 111) are available. They share several characteristics with cuprate superconductors that compromise easy applications, such as the layered structure, the small coherence length, and unconventional pairing, On the other hand the Fe-based superconductors have metallic parent compounds, and their electronic anisotropy is generally smaller and does not strongly depend on the level of doping, the supposed order parameter symmetry is s wave, thus in principle not so detrimental to current transmission across grain boundaries. From the application point of view, the main efforts are still devoted to investigate the superconducting properties, to distinguish intrinsic from extrinsic behaviours and to compare the different families in order to identify which one is the fittest for the quest for better and more practical superconductors. The 1111 family shows the highest Tc, huge but also the most anisotropic upper critical field and in-field, fan-shaped resistive transitions reminiscent of those of cuprates, while the 122 family is much less anisotropic with sharper resistive transitions as in low temperature superconductors, but with about half the Tc of the 1111 compounds. An overview of the main superconducting properties relevant to applications will be presented. Upper critical field, electronic anisotropy parameter, intragranular and intergranular critical current density will be discussed and compared, where possible, across the Fe-based superconductor families

Science Models as Value-Added Services for Scholarly Information Systems

The paper introduces scholarly Information Retrieval (IR) as a further dimension that should be considered in the science modeling debate. The IR use case is seen as a validation model of the adequacy of science models in representing and predicting structure and dynamics in science. Particular conceptualizations of scholarly activity and structures in science are used as value-added search services to improve retrieval quality: a co-word model depicting the cognitive structure of a field (used for query expansion), the Bradford law of information concentration, and a model of co-authorship networks (both used for re-ranking search results). An evaluation of the retrieval quality when science model driven services are used turned out that the models proposed actually provide beneficial effects to retrieval quality. From an IR perspective, the models studied are therefore verified as expressive conceptualizations of central phenomena in science. Thus, it could be shown that the IR perspective can significantly contribute to a better understanding of scholarly structures and activities.Comment: 26 pages, to appear in Scientometric

Wigner Crystallization in a Quasi-3D Electronic System

When a strong magnetic field is applied perpendicularly (along z) to a sheet confining electrons to two dimensions (x-y), highly correlated states emerge as a result of the interplay between electron-electron interactions, confinement and disorder. These so-called fractional quantum Hall (FQH) liquids form a series of states which ultimately give way to a periodic electron solid that crystallizes at high magnetic fields. This quantum phase of electrons has been identified previously as a disorder-pinned two-dimensional Wigner crystal with broken translational symmetry in the x-y plane. Here, we report our discovery of a new insulating quantum phase of electrons when a very high magnetic field, up to 45T, is applied in a geometry parallel (y-direction) to the two-dimensional electron sheet. Our data point towards this new quantum phase being an electron solid in a "quasi-3D" configuration induced by orbital coupling with the parallel field

Phase Separation and Magnetic Order in K-doped Iron Selenide Superconductor

Alkali-doped iron selenide is the latest member of high Tc superconductor family, and its peculiar characters have immediately attracted extensive attention. We prepared high-quality potassium-doped iron selenide (KxFe2-ySe2) thin films by molecular beam epitaxy and unambiguously demonstrated the existence of phase separation, which is currently under debate, in this material using scanning tunneling microscopy and spectroscopy. The stoichiometric superconducting phase KFe2Se2 contains no iron vacancies, while the insulating phase has a \surd5\times\surd5 vacancy order. The iron vacancies are shown always destructive to superconductivity in KFe2Se2. Our study on the subgap bound states induced by the iron vacancies further reveals a magnetically-related bipartite order in the superconducting phase. These findings not only solve the existing controversies in the atomic and electronic structures in KxFe2-ySe2, but also provide valuable information on understanding the superconductivity and its interplay with magnetism in iron-based superconductors

Dust-free quasars in the early Universe

The most distant quasars known, at redshifts z=6, generally have properties indistinguishable from those of lower-redshift quasars in the rest-frame ultraviolet/optical and X-ray bands. This puzzling result suggests that these distant quasars are evolved objects even though the Universe was only seven per cent of its current age at these redshifts. Recently one z=6 quasar was shown not to have any detectable emission from hot dust, but it was unclear whether that indicated different hot-dust properties at high redshift or if it is simply an outlier. Here we report the discovery of a second quasar without hot-dust emission in a sample of 21 z=6 quasars. Such apparently hot-dust-free quasars have no counterparts at low redshift. Moreover, we demonstrate that the hot-dust abundance in the 21 quasars builds up in tandem with the growth of the central black hole, whereas at low redshift it is almost independent of the black hole mass. Thus z=6 quasars are indeed at an early evolutionary stage, with rapid mass accretion and dust formation. The two hot-dust-free quasars are likely to be first-generation quasars born in dust-free environments and are too young to have formed a detectable amount of hot dust around them.Comment: To be published in Nature on the 18 March 2010

Observation of the Fractional Quantum Hall Effect in Graphene

When electrons are confined in two dimensions and subjected to strong magnetic fields, the Coulomb interactions between them become dominant and can lead to novel states of matter such as fractional quantum Hall liquids. In these liquids electrons linked to magnetic flux quanta form complex composite quasipartices, which are manifested in the quantization of the Hall conductivity as rational fractions of the conductance quantum. The recent experimental discovery of an anomalous integer quantum Hall effect in graphene has opened up a new avenue in the study of correlated 2D electronic systems, in which the interacting electron wavefunctions are those of massless chiral fermions. However, due to the prevailing disorder, graphene has thus far exhibited only weak signatures of correlated electron phenomena, despite concerted experimental efforts and intense theoretical interest. Here, we report the observation of the fractional quantum Hall effect in ultraclean suspended graphene, supporting the existence of strongly correlated electron states in the presence of a magnetic field. In addition, at low carrier density graphene becomes an insulator with an energy gap tunable by magnetic field. These newly discovered quantum states offer the opportunity to study a new state of matter of strongly correlated Dirac fermions in the presence of large magnetic fields

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.

BackgroundTo determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed.MethodsTen CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.ResultsAn average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q < 0.05, fold change >2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value <0.05, minimum inclusion level difference >0.1).ConclusionThe RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis