Neurology at Escola Paulista de Medicina (1933-1995). From Fausto Guerner to José Geraldo Camargo Lima

Escola Paulista de Medicina (EPM) was founded in 1933 and the first Professor of Neurology was Fausto Guerner, who could not effectively assume the teaching activities due to his premature death in 1938. Professor Guerner had had his neurological training at Paris. Professor Longo was his successor. Longo was one of the founders of Arquivos de Neuro-Psiquiatria the foremost journal of neurosciences in Latin American. Longo died in 1967 and Professor Paulo Pupo succeeded him. Pupo introduced electroencephalography in Brazil. After his death in 1970, Professor Dante Giorgi succeeded him until 1974. Professor José Geraldo Camargo Lima took over the position after Giorgi’s death. He created the Neurological Emergency unit, initiated the Post-Graduation in Neurology and divided the Discipline in specialized units. During the 1980’s and until his retirement in 1995, EPM had become one of most important centers of Brazil training neurologists and researchers in neurological sciences.A Escola Paulista de Medicina foi fundada em 1933 e o primeiro Professor de Neurologia foi Fausto Guerner, que morreu prematuramente em 1938, antes do início das aulas. O Professor Paulino Longo foi o seu sucessor. Longo, juntamente com outros, fundou os Arquivos de Neuro-Psiquiatria e a Academia Brasileira de Neurologia. Professor Paulo Pupo, seu sucessor, introduziu a eletroencefalografia no Brasil. O Professor José Geraldo Camargo Lima tornou-se chefe da Neurologia em 1974. Criou o Pronto-Socorro de Neurologia, iniciou a Pós-Graduação e dividiu a disciplina em setores especializadas. A partir dos anos 1980, a Neurologia da EPM tornou-se um dos centros acadêmicos mais importantes do Brasil.Universidade Federal de São Paulo (UNIFESP) Disciplina de NeurologiaUNIFESP, Disciplina de NeurologiaSciEL

HIPK2 and extrachromosomal histone H2B are separately recruited by Aurora-B for cytokinesis

Cytokinesis, the final phase of cell division, is necessary to form two distinct daughter cells with correct distribution of genomic and cytoplasmic materials. Its failure provokes genetically unstable states, such as tetraploidization and polyploidization, which can contribute to tumorigenesis. Aurora-B kinase controls multiple cytokinetic events, from chromosome condensation to abscission when the midbody is severed. We have previously shown that HIPK2, a kinase involved in DNA damage response and development, localizes at the midbody and contributes to abscission by phosphorylating extrachromosomal histone H2B at Ser14. Of relevance, HIPK2-defective cells do not phosphorylate H2B and do not successfully complete cytokinesis leading to accumulation of binucleated cells, chromosomal instability, and increased tumorigenicity. However, how HIPK2 and H2B are recruited to the midbody during cytokinesis is still unknown. Here, we show that regardless of their direct (H2B) and indirect (HIPK2) binding of chromosomal DNA, both H2B and HIPK2 localize at the midbody independently of nucleic acids. Instead, by using mitotic kinase-specific inhibitors in a spatio-temporal regulated manner, we found that Aurora-B kinase activity is required to recruit both HIPK2 and H2B to the midbody. Molecular characterization showed that Aurora-B directly binds and phosphorylates H2B at Ser32 while indirectly recruits HIPK2 through the central spindle components MgcRacGAP and PRC1. Thus, among different cytokinetic functions, Aurora-B separately recruits HIPK2 and H2B to the midbody and these activities contribute to faithful cytokinesis

The low-virulent African swine fever virus (ASFV/NH/P68) induces enhanced expression and production of relevant regulatory cytokines (IFNα, TNFα and IL12p40) on porcine macrophages in comparison to the highly virulent ASFV/L60

The impact of infection by the low-virulent ASFV/NH/P68 (NHV) and the highly virulent ASFV/L60 (L60) isolates on porcine macrophages was assessed through the quantification of IFNα, TNFα, IL12p40, TGFβ and ASFV genes by real-time PCR at 2, 4 and 6 h post-infection. Increased IFNα, TNFα and IL12p40 expression was found in infection with NHV, in which expression of TGFβ was lower than in infection with L60. Principal component analysis showed a positive interaction of cytokines involved in cellular immune mechanisms, namely IFNα and IL12p40 in the NHV infection. Quantification by ELISA confirmed higher production of IFNα, TNFα and IL12p40 in the NHV-infected macrophages. Overall, our studies reinforce and clarify the effect of the NHV infection by targeting cellular and cellular-based immune responses relevant for pig survival against ASFV infection

Expression of APOBEC3G/3F and G-to-A Hypermutation Levels in HIV-1-Infected Children with Different Profiles of Disease Progression

OBJECTIVE: Increasing evidence has accumulated showing the role of APOBEC3G (A3G) and 3F (A3F) in the control of HIV-1 replication and disease progression in humans. However, very few studies have been conducted in HIV-infected children. Here, we analyzed the levels of A3G and A3F expression and induced G-to-A hypermutation in a group of children with distinct profiles of disease progression. METHODOLOGY/PRINCIPAL FINDINGS: Perinatally HIV-infected children were classified as progressors or long-term non-progressors according to criteria based on HIV viral load and CD4 T-cell counts over time. A group of uninfected control children were also enrolled in the study. PBMC proviral DNA was assessed for G-to-A hypermutation, whereas A3G and A3F mRNA were isolated and quantified through TaqMan® real-time PCR. No correlation was observed between disease progression and A3G/A3F expression or hypermutation levels. Although all children analyzed showed higher expression levels of A3G compared to A3F (an average fold of 5 times), a surprisingly high A3F-related hypermutation rate was evidenced in the cohort, irrespective of the child's disease progression profile. CONCLUSION: Our results contribute to the current controversy as to whether HIV disease progression is related to A3G/A3F enzymatic activity. To our knowledge, this is the first study analyzing A3G/F expression in HIV-infected children, and it may pave the way to a better understanding of the host factors governing HIV disease in the pediatric setting