PRMT5-mediated regulation of developmental myelination

Oligodendrocytes (OLs) are the myelin-forming cells of the central nervous system. They are derived from differentiation of oligodendrocyte progenitors through a process requiring cell cycle exit and histone modifications. Here we identify the histone arginine methyl-transferase PRMT5, a molecule catalyzing symmetric methylation of histone H4R3, as critical for developmental myelination. PRMT5 pharmacological inhibition, CRISPR/cas9 targeting, or genetic ablation decrease p53-dependent survival and impair differentiation without affecting proliferation. Conditional ablation of Prmt5 in progenitors results in hypomyelination, reduced survival and differentiation. Decreased histone H4R3 symmetric methylation is followed by increased nuclear acetylation of H4K5, and is rescued by pharmacological inhibition of histone acetyltransferases. Data obtained using purified histones further validate the results obtained in mice and in cultured oligodendrocyte progenitors. Together, these results identify PRMT5 as critical for oligodendrocyte differentiation and developmental myelination by modulating the cross-talk between histone arginine methylation and lysine acetylation

Pancreas and islet transplantation in patients with diabetes mellitus

Pancreas and kidney transplants have specific indications, benefits and risks. The procedure has become more common and more often as long-term success has improved and risks have decreased. Compared with a patient being on dialysis, simultaneous pancreas-kidney transplant offers a distinct advantage when it comes to mortality, quality of life and diabetic complications. Since there can be a living-donor kidney transplant,, a possibly similar patient and graft survival by 10 years follow-up, this procedure should be considered. Pancreas after kidney transplants, when successful, can improve microvascular complications compared with kidney transplant alone, but immediate mortality may be higher. Solitary pancreas transplantation can improve the quality of life in selected patients, but it may also increase the immediate risk of mortality due to the complexity of the surgery and the risks of immunosupression. The results of Islet transplantation differ from the higher metabolic performance achieved by whole pancreas allotransplantation and its applicability is limited to selected adult diabetic patients.O transplante simultâneo de pâncreas/rim tem indicações específicas, riscos e benefícios. O procedimento, cada vez mais realizado, traz vantagens se comparado ao paciente em diálise, em relação à qualidade de vida, anos de vida ganhos e evolução das complicações crônicas. Se o paciente tiver a opção de realizar o transplante de rim com doador vivo, que apresenta sobrevida semelhante do enxerto e do paciente aos dez anos, o procedimento deverá ser considerado. O transplante de pâncreas após rim, quando efetivo, pode melhorar a evolução das complicações cardiovasculares, mas em contrapartida provoca maior mortalidade nos primeiros meses após a cirurgia. O transplante isolado de pâncreas também ocasiona a maior mortalidade pós-operatória, resultado da complexidade do procedimento e da imunossupressão. O transplante de ilhotas tem sua indicação para um seleto grupo de diabéticos com instabilidade glicêmica.Universidade Federal de São Paulo (UNIFESP) Departamento de Medicina Departamento de CirurgiaPontifícia Universidade Católica do Rio Grande do Sul Hospital São Lucas Serviço de NefrologiaUniversidade de São Paulo Núcleo de Terapia Celular e MolecularSistema de Saúde Centro de Pesquisa Médica Notre-Dame IntermédicaUSP Faculdade de Medicina Departamento de Clínica MédicaUniversidade Federal do Rio Grande do Sul Departamento de Medicina InternaHospital Israelita Albert Einstein Serviço de Transplante de PâncreasUNIFESP, Depto. de Medicina Depto. de CirurgiaSciEL

Supplemental Table 7

IlluminaMiSeq_16S data_run1_seq

Supplemental Table 1 - supplement of Figure 3

Unique OTUs in NOD_vehicle compared to NOD_baseline-

Supplemental Table 4 - supplement of Figure 6S2

Shared Operational Taxonomic Units (OTUs) in mice displaying a decreased social behavior (NOD_vehicle and C57BL_6 transplanted with NOD microbiota

Supplemental Table 6 – supplement of Figure 7

Pathway analysis results (metabolomics

Supplemental Table 10 - supplement of Figure 6S2

bacterial qPCR primer

Supplemental Table 8

IlluminaMiSeq_16S data_run2_seqs.run