SAMHD1-Deficient CD14+ Cells from Individuals with Aicardi-Goutières Syndrome Are Highly Susceptible to HIV-1 Infection

Myeloid blood cells are largely resistant to infection with human immunodeficiency virus type 1 (HIV-1). Recently, it was reported that Vpx from HIV-2/SIVsm facilitates infection of these cells by counteracting the host restriction factor SAMHD1. Here, we independently confirmed that Vpx interacts with SAMHD1 and targets it for ubiquitin-mediated degradation. We found that Vpx-mediated SAMHD1 degradation rendered primary monocytes highly susceptible to HIV-1 infection; Vpx with a T17A mutation, defective for SAMHD1 binding and degradation, did not show this activity. Several single nucleotide polymorphisms in the SAMHD1 gene have been associated with Aicardi-Goutières syndrome (AGS), a very rare and severe autoimmune disease. Primary peripheral blood mononuclear cells (PBMC) from AGS patients homozygous for a nonsense mutation in SAMHD1 (R164X) lacked endogenous SAMHD1 expression and support HIV-1 replication in the absence of exogenous activation. Our results indicate that within PBMC from AGS patients, CD14+ cells were the subpopulation susceptible to HIV-1 infection, whereas cells from healthy donors did not support infection. The monocytic lineage of the infected SAMHD1 -/- cells, in conjunction with mostly undetectable levels of cytokines, chemokines and type I interferon measured prior to infection, indicate that aberrant cellular activation is not the cause for the observed phenotype. Taken together, we propose that SAMHD1 protects primary CD14+ monocytes from HIV-1 infection confirming SAMHD1 as a potent lentiviral restriction factor

Flow cytometry as a tool in the evaluation of blood leukocyte function in Chelonia mydas (Linnaeus, 1758) (Testudines, Cheloniidae)

Chelonia mydas is a sea turtle that feeds and nests on the Brazilian coast and a disease called fibropapillomatosis is a threat to this species. Because of this, it is extremely necessary to determine a methodology that would enable the analysis of blood leukocyte function in these sea turtles. In order to achieve this aim, blood samples were collected from C. mydas with or without fibropapillomas captured on the São Paulo north coast. Blood samples were placed in tubes containing sodium heparin and were transported under refrigeration to the laboratory in sterile RPMI 1640 cell culture medium. Leukocytes were separated by density gradient using Ficoll-PaqueTM Plus, Amershan Biociences®. The following stimuli were applied in the assessment of leukocyte function: Phorbol Miristate-Acetate (PMA) for oxidative burst activity evaluation and Zymosan A (Saccharomyces cerevisiae) Bio Particles®, Alexa Fluor® 594 conjugate for phagocytosis evaluation. Three cell populations were identified: heterophils, monocytes and lymphocytes. Monocytes were the cells responsible for phagocytosis and oxidative burst

Cannon de Hermeto Pascoal: aspectos musicais e religiosos em uma obra-prima para flauta Cannon by Hermeto Pascoal: musical and religious aspects in a flute masterpiece

Estudo de caso sobre Cannon de Hermeto Pascoal, obra para flauta, humming na flauta e sons pré-gravados, planejada como uma sessão espírita musical e gravada pelo compositor no disco Slaves Mass (PASCOAL, 1977). A partir do desenho artístico de uma pauta espiralada na capa interna do mesmo LP (PASCOAL e PEREIRA, 1977) e de uma transcrição baseada na faixa gravada, a partitura da obra foi detalhadamente reconstituída e editada (PASCOAL e BORÉM, 2010; incluída neste volume de Per Musi às p.80-82). A combinação das análises formal, escalar e proporcional da partitura e seu cruzamento com a análise espectral da gravação revelam grande unidade e uma íntima relação entre os conteúdos musicais e extra-musicais da obra, na qual elementos opostos dialogam: a improvisação e as camadas de superposição de sons pré-gravados, a sonoridade acústica e os sons manipulados, a performance individual e a coletiva, a estabilidade e a instabilidade modal, as linguagens popular (embolada, jazz modal, free jazz) e erudita (música concreta, atonalismo, cadenza, recitativo), os mundos terreno e espiritual. Apresenta também, em primeira mão, a abordagem analítica do "continuum separação-fusão paradoxal" da obra, a partir de ferramenta etnomusicológica criada e realizada por COSTA-LIMA NETO (2009). Inclui uma contextualização do papel da religião na música do "mago" multi-instrumentista, arranjador e compositor da música popular brasileira.<br>Case study on Cannon by Brazilian composer, arranger and multi-instrumentalist Hermeto Pascoal, a work for flute, flute humming and pre-recorded sounds, designed as a musical spiritism session and included in the LP Slaves Mass (PASCOAL, 1977). Departing from an artistic drawing of a music staff spiral included in the internal covers of the same LP (PASCOAL e PEREIRA, 1977) and a transcription based on the listening of the track in the same disc, the score of the work was reconstituted and edited in detail (PASCOAL e BORÉM, 2010; included in this issue of Per Musi, p.80-82). The combination of formal, scalar, proportional analyses with the spectral analysis reveal an intimate relation between the musical and extra-musical contents of the work, in which opposing elements dialog: improvisation and the layers of pre-recorded sounds, acoustical sounds and manipulated sonorities, individual and the collective performances, stable and unstable modalities, the popular (the Brazilian embolada, modal jazz, free jazz) and the classical (musique concrète, bimodalism, atonalism, cadenza, recitative) languages, the earth and the spiritual worlds. It presents an original analytical approach of the work based on the "paradoxal separation-fusion continuum", devised and realized by ethnomusicologist COSTA-LIMA NETO (2009). It also includes a context of the religion role in the music of the so-called "mago" (wizard) of the Brazilian popular music