The First Sequenced Carnivore Genome Shows Complex Host-Endogenous Retrovirus Relationships

Host-retrovirus interactions influence the genomic landscape and have contributed substantially to mammalian genome evolution. To gain further insights, we analyzed a female boxer (Canis familiaris) genome for complexity and integration pattern of canine endogenous retroviruses (CfERV). Intriguingly, the first such in-depth analysis of a carnivore species identified 407 CfERV proviruses that represent only 0.15% of the dog genome. In comparison, the same detection criteria identified about six times more HERV proviruses in the human genome that has been estimated to contain a total of 8% retroviral DNA including solitary LTRs. These observed differences in man and dog are likely due to different mechanisms to purge, restrict and protect their genomes against retroviruses. A novel group of gammaretrovirus-like CfERV with high similarity to HERV-Fc1 was found to have potential for active retrotransposition and possibly lateral transmissions between dog and human as a result of close interactions during at least 10.000 years. The CfERV integration landscape showed a non-uniform intra- and inter-chromosomal distribution. Like in other species, different densities of ERVs were observed. Some chromosomal regions were essentially devoid of CfERVs whereas other regions had large numbers of integrations in agreement with distinct selective pressures at different loci. Most CfERVs were integrated in antisense orientation within 100 kb from annotated protein-coding genes. This integration pattern provides evidence for selection against CfERVs in sense orientation relative to chromosomal genes. In conclusion, this ERV analysis of the first carnivorous species supports the notion that different mammals interact distinctively with endogenous retroviruses and suggests that retroviral lateral transmissions between dog and human may have occurred

Susceptibility of the human retrovirus XMRV to antiretroviral inhibitors

<p>Abstract</p> <p>Background</p> <p>XMRV (xenotropic murine leukemia virus-related virus) is the first known example of an exogenous gammaretrovirus that can infect humans. A limited number of reports suggest that XMRV is intrinsically resistant to many of the antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small subset of these inhibitors. In the present study, we used a novel marker transfer assay to directly compare the antiviral drug sensitivities of XMRV and HIV-1 under identical conditions in the same host cell type.</p> <p>Results</p> <p>We extend the findings of previous studies by showing that, in addition to AZT and tenofovir, XMRV and HIV-1 are equally sensitive to AZddA (3'-azido-2',3'-dideoxyadenosine), AZddG (3'-azido-2',3'-dideoxyguanosine) and adefovir. These results indicate that specific 3'-azido or acyclic nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT) also block XMRV infection with comparable efficacy <it>in vitro</it>. Our data confirm that XMRV is highly resistant to the non-nucleoside RT inhibitors nevirapine and efavirenz and to inhibitors of HIV-1 protease. In addition, we show that the integrase inhibitors raltegravir and elvitegravir are active against XMRV, with EC₅₀values in the nanomolar range.</p> <p>Conclusions</p> <p>Our analysis demonstrates that XMRV exhibits a distinct pattern of nucleoside analog susceptibility that correlates with the structure of the pseudosugar moiety and that XMRV is sensitive to a broader range of antiretroviral drugs than has previously been reported. We suggest that the divergent drug sensitivity profiles of XMRV and HIV-1 are partially explained by specific amino acid differences in their respective protease, RT and integrase sequences. Our data provide a basis for choosing specific antiretroviral drugs for clinical studies in XMRV-infected patients.</p

Relative effectiveness and adverse effects of cervical manipulation, mobilisation and the activator instrument in patients with sub-acute non-specific neck pain: results from a stopped randomised trial

<p>Abstract</p> <p>Background</p> <p>Neck pain of a mechanical nature is a common complaint seen by practitioners of manual medicine, who use a multitude of methods to treat the condition. It is not known, however, if any of these methods are superior in treatment effectiveness. This trial was stopped due to poor recruitment. The purposes of this report are (1) to describe the trial protocol, (2) to report on the data obtained from subjects who completed the study, (3) to discuss the problems we encountered in conducting this study.</p> <p>Methods</p> <p>A pragmatic randomised clinical trial was undertaken. Patients who met eligibility criteria were randomised into three groups. One group was treated using specific segmental high velocity low amplitude manipulation (diversified), another by specific segmental mobilisation, and a third group by the Activator instrument. All three groups were also treated for any myofascial distortions and given appropriate exercises and advice. Participants were treated six times over a three-week period or until they reported being pain free. The primary outcome measure for the study was Patient Global Impression of Change (PGIC); secondary outcome measures included the Short-Form Health Survey (SF-36v₂), the neck Bournemouth Questionnaire, and the numerical rating scale for pain intensity. Participants also kept a diary of any pain medication taken and noted any perceived adverse effects of treatment. Outcomes were measured at four points: end of treatment, and 3, 6, and 12 months thereafter.</p> <p>Results</p> <p>Between January 2007 and March 2008, 123 patients were assessed for eligibility, of these 47 were considered eligible, of which 16 were allocated to manipulation, 16 to the Activator instrument and 15 to the mobilisation group. Comparison between the groups on the PGIC adjusted for baseline covariants did not show a significant difference for any of the endpoints. Within group analyses for change from baseline to the 12-month follow up for secondary outcomes were significant for all groups on the Bournemouth Questionnaire and for pain, while the mobilisation group had a significant improvement on the PCS and MCS subscales of the SF-36_v2. Finally, there were no moderate, severe, or long-lasting adverse effects reported by any participant in any group.</p> <p>Conclusions</p> <p>Although the small sample size must be taken into consideration, it appears that all three methods of treating mechanical neck pain had a long-term benefit for subacute neck pain, without moderate or serious adverse events associated with any of the treatment methods. There were difficulties in recruiting subjects to this trial. This pragmatic trial should be repeated with a larger sample size.</p

Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation

A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilitated a rapid growth of their use and resulted in their ubiquity in complex organisms. The ease of motif acquisition simplifies access to basal housekeeping functions, facilitates the co-regulation of multiple biomolecules allowing them to respond in a coordinated manner to changes in the cell state, and supports the integration of multiple signals for combinatorial decision-making. Consequently, motifs are indispensable for temporal, spatial, conditional and basal regulation at the transcriptional, post-transcriptional and post-translational level. In this review, we highlight that many of the key regulatory pathways of the cell are recruited by motifs and that the ease of motif acquisition has resulted in large networks of co-regulated biomolecules. We discuss how co-operativity allows simple static motifs to perform the conditional regulation that underlies decision-making in higher eukaryotic biological systems. We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules

"as If It Was A Council-man Election": Participatory Dynamics And Party Disputes In The City Of São Paulo ["como Se Fosse Uma Eleição Para Vereador": Dinâmicas Participativas E Disputas Partidárias Na Cidade De São Paulo]

This article discloses and analyzes the mobilization of popular actors to elect their representatives in the fourth administration of the Conselho Municipal de Habitação (CMH - Municipal Housing Council) of Sao Paulo. We consider the relationship between social movement, parties, government, and also recover some facts that characterize the action of the representatives in this space, which is consolidating itself as a relevant political arena in the city's housing policy. One of the main findings of the research alludes to the importance of the connections and links between movement, governments and parties to understand the dynamic of participation and its results. 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São Paulo: FFLCH-USPMische, A., Cross-talk in movements: reconceiving the culturenetwork link (2003) Social movements and networks: relational approach to collective action, , DIANI, M.MCADAM, D. Oxford: Oxford University PressMische, A., (2008) Partisan publics, , New Jersey: Princeton University PressNeuhold, R.R., (2009) Os movimentos de moradia e sem-teto e as ocupações de móveis ociosos: a luta por políticas públicas habitacionais na área central dacidade de São Paulo, , Dissertação de mestrado. São Paulo: FFLCH-USPOliveira, N.C., (2010) Os movimentos dos sem-teto da Grande São Paulo (1995-2009). Dissertação de mestrado, , São Paulo: IFCH-UnicampSantos dos, A.L.T., (2010) A prática dos movimentos de moradia na produção do espaço da cidade de São Paulo: os limites da participação e a (im) possibilidade de emancipação, , Tese de doutorado. São Paulo: FAU-USPSilva, M.K., Trazendo os atores sociais de volta: pontos para uma agenda de pesquisa sobre ação coletiva, movimentos sociais e sociedade civil, , [Mimeo]Silva, M.K., Dos objetos às relações: esboço de uma proposta teórico-metodológica para a análise dos processos de participação social no Brasil (2007) Democracia, sociedade civil e participação, , DAGNINO, E.TATAGIBA, L. (orgs.). Chapecó: UniversitáriaSilva, M.K., De volta aos movimentos sociais? Reflexões a partir da literatura brasileira recente (2010) Ciências Sociais Unisinos, 46 (1), pp. 2-9(2006), 21 (1). , SOCIEDADE E ESTADO. Brasília: UnBTarrow, S., (1997) El poder in movimiento: los movimientos sociales, la acción colectiva y la política, , Madri: Alianza EditorialTatagiba, L., A institucionalização da participação: os conselhos municipais de políticas públicas na cidade de São Paulo (2004) A participação em São Paulo, , AVRITZER, L. (org). 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São Paulo: Instituto PólisTatagiba, L., Paterniani, S., A militância do movimento de moradia da cidade de São Paulo: um retrato a partir do 11o Encontro Estadual de Moradia Popular, , [No prelo]Tilly, C., (1978) From mobilization to revolution, , Nova York: Newberry Award RecordsWampler, B., Transformando o Estado e a sociedade civil por meio da expansão das comunidades - política, associativa e de políticas públicas (2010) A dinâmica da participação local no Brasil, , AVRITZER, L (org.). São Paulo, Corte