RIO-kinase 2 is essential for hematopoiesis.

Regulation of protein synthesis is a key factor in hematopoietic stem cell maintenance and differentiation. Rio-kinase 2 (RIOK2) is a ribosome biogenesis factor that has recently been described an important regulator of human blood cell development. Additionally, we have previously identified RIOK2 as a regulator of protein synthesis and a potential target for the treatment of acute myeloid leukemia (AML). However, its functional relevance in several organ systems, including normal hematopoiesis, is not well understood. Here, we investigate the consequences of RIOK2 loss on normal hematopoiesis using two different conditional knockout mouse models. Using competitive and non-competitive bone marrow transplantations, we demonstrate that RIOK2 is essential for the differentiation of hematopoietic stem and progenitor cells (HSPCs) as well as for the maintenance of fully differentiated blood cells in vivo as well as in vitro. Loss of RIOK2 leads to rapid death in full-body knockout mice as well as mice with RIOK2 loss specific to the hematopoietic system. Taken together, our results indicate that regulation of protein synthesis and ribosome biogenesis by RIOK2 is essential for the function of the hematopoietic system.

An alternative NURF complex sustains acute myeloid leukemia by regulating the accessibility of insulator regions.

Efficient treatment of acute myeloid leukemia (AML) patients remains a challenge despite recent therapeutic advances. Here, using a CRISPRi screen targeting chromatin factors, we identified the nucleosome-remodeling factor (NURF) subunit BPTF as an essential regulator of AML cell survival. We demonstrate that BPTF forms an alternative NURF chromatin remodeling complex with SMARCA5 and BAP18, which regulates the accessibility of a large set of insulator regions in leukemic cells. This ensures efficient CTCF binding and boundary formation between topologically associated domains that is essential for maintaining the leukemic transcriptional programs. We also demonstrate that the well-studied PHD2-BROMO chromatin reader domains of BPTF, while contributing to complex recruitment to chromatin, are dispensable for leukemic cell growth. Taken together, our results uncover how the alternative NURF complex contributes to leukemia and provide a rationale for its targeting in AML.

Estudio clínico de los accidentes cerebro-vasculares en 111 pacientes (Hospital General de Guatire-Guarenas 1986-1990) / Clinical study of the cerebrovascular diseases in 111 patients (Hospital General of Guatire-Guarena 1986-1990)

Se hizo una revisión retrospectiva de 111 casos de ACV en el período de 1986-1990, en el Hospital General de Guatire-Guarenas. Se revisaron los accidentes patológicos, factores de riesgo, características clínicas, estudios neuroradiólogos, tratamiento y evolución en todos los casos. Los resultados obtenidos revelaron la influencia de la edad, HTA, hábitos alcohólicos y tabaquicos como factores predisponentes, así como, la aparición de signos de focalización en la mayoría de los casos estudiados, el tratamiento de los pacientes incluyó múltiples drogas: Calciantagonistas, antiagregantes, anticonvulsivantes, antihipertensivos y otras de reciente aparición como la Nimodipina

Hemorragia intracraneal supra e infratentorial después de una craniectomía de fosa posterior: presentación de un caso / Intracranial hemorrhage supra and infratentorial after a craniotomy of posterior fossa: presentation of a case

La hemorragia intracraneal a distancia de la zona operatoria es una complicación infrecuente posterior a intervenciones neuroquirúrgicas. Se presenta un caso de un niño de 5 años de edad con una lesión tumoral media en el cerebelo, a quien se practicó una craniectomía sub-occipital bilateral,en posición lateral, posterior a la cual presentó una hemorragia supra e infratentorial masiva, falleciendo al tercer día del post-operatorio. Se discuten las probables hipótesis que explican esta complicación, y se revisa la bibliografía en relación al tema