Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Parkinsonismo secundario a mielinolisis extrapontina: reporte de caso

Parkinsonism is a syndrome characterized by hypokinetic extrapiramidal motor manifestations, it can be divided into idiopathic or secondary accordingly. The most common cause is the idiopathic Parkinson’s diseases. The secondary causes are less common and they do not usually respond to dopaminergic substitutive therapy, among the causes is the osmotic demyelination syndrome characterized by pontine and extrapontine myelinolysis caused by abrupt changes in the osmolarity in the central nervous system; This condition can be developed in patients with hydro-electrolyte imbalances like hyponatremia with a rapid correction of sodium. 47-year-old male that presented acute parkinsonism secondary to osmotic demyelination syndrome, posterior to a rapid sodium correction; he was treated with levodopa. Secondary parkinsonism caused by osmotic damage triggered by hydro-electrolyte imbalance is an uncommon complication with a variable therapeutic response; with an ongoing acute or subacute presentation and bilateral clinical manifestations of a parkinsonian motor syndrome, an exhaustive approach must be done to study a secondary cause because the dopaminergic substitutive therapy response differs from idiopathic Parkinson diseases.El parkinsonismo es un síndrome caracterizado por manifestaciones motoras extrapiramidales hipokinéticas en el cual las causas pueden ser primarias o secundarias. La causa más común es la enfermedad idiopática de Parkinson, un proceso neurodegenerativo. Las causas secundarias son menos frecuentes y no suelen responder a la terapia sustitutiva dopaminérgica, entre ellas se encuentra el síndrome de desmielinizacion osmótica caracterizado por mielinolisis pontina y extrapontina provocada por cambios abruptos de osmolaridad en el sistema nervioso central; Este puede presentarse en pacientes con trastornos hidroelectrolíticos como la hiponatremia con reposición rápida de sodio. Reportamos el caso de un paciente masculino de 47 años que presentó parkinsonismo secundario a síndrome de desmielinizacion osmótica, posterior a corrección rápida de sodio; recibió manejo terapéutico con levodopa. El Parkinsonismo secundario, como consecuencia de una injuria osmótica por desbalance electrolítico, es una complicación poco frecuente la cual tiene una respuesta terapéutica variable. Ante una presentación aguda o subaguda y con manifestaciones clínicas bilaterales de un síndrome motor Parkinsoniano se debe hacer un abordaje exhaustivo en busca de una causa secundaria ya que la respuesta a la terapia sustitutiva dopaminérgica difiere en comparación a la enfermedad de Parkinson idiopática

Variante atípica aguda de esclerosis múltiple con lesiones pseudotumorales: reporte de caso

Multiple sclerosis that appears with a magnetic resonance image similar to a tumor in appearance has been considered a relatively rare condition: 1-2/1000 cases of multiple sclerosis or around 3 cases per million habitants per year. The demyelinating diseases of the central nervous system include a broad spectrum of different etiologies, with multiple sclerosis being the most frequent one. Multiple sclerosis is a chronic demyelinating disease, autoimmune and inflammatory that affects all the central nervous system. The diagnostic criteria require magnetic resonance imaging in which demyelinating areas can be appreciated. Occasionally atypical lesions of multiple sclerosis are identified, showing a size, morphology and pattern of unusual contrast enhancement. Pseudotumoral lesions represent one of these atypical forms of lesions in multiple sclerosis. The treatment of pseudotumoral forms of multiple sclerosis is not well defined. In cases reported in literature corticoid therapy is the one that is used the most. We present the case of a 24 year old female patient, without vascular risk who presented with rapidly progressive right hemiparesis accompanied by mutism. Image studies show multifocal white matter lesions predominantly in the fronto-parietal region, with pseudotumoral demyelinating features, compatible with demyelinating disease, confirmed by biopsy for which corticoid treatment was started with satisfactory outcome. The acute variants of multiple sclerosis must be taken into consideration in all cases of pseudotumoral lesions with symptoms pertinent to multiple sclerosis, in spite of it being a rare variant, it´s course is usually acute and fulminant, and so, a timely detection and management is essential.La aparición de esclerosis múltiple con imagen de resonancia magnética similar a un tumor en apariencia ha sido considerada una condición relativamente rara: 1-2/1000 casos de esclerosis múltiple o alrededor de 3 casos por millón de habitantes por año. Las enfermedades desmielinizantes del sistema nervioso central incluyen un vasto espectro de distintas etiologías siendo la más frecuente la esclerosis múltiple. La esclerosis múltiple es una enfermedad desmielinizante crónica, autoinmune e inflamatoria que afecta a todo el sistema nervioso central. Los criterios diagnósticos exigen imágenes por resonancia magnética en las que se aprecien áreas de desmielinización. Ocasionalmente lesiones atípicas de esclerosis múltiple son identificadas, mostrando un tamaño, morfología o patrón de captación de contraste inusual. Las lesiones pseudotumorales representan una de estas formas atípicas de lesiones de esclerosis múltiple. El tratamiento de las formas pseudotumorales de esclerosis múltiple no está bien definida. La terapia corticoesteroide es la más usada en casos reportados en la literatura. Presentamos el caso de una paciente de 24 años, sin riesgo vascular, quien presenta hemiparesia derecha rápidamente progresiva acompañado de mutismo. Los estudios de imagen muestran lesiones multifocales de substancia blanca de predominio fronto-parietal y de aspecto pseudotumoral desmielinizante, compatible con patología desmielinizante, confirmada por biopsia, por lo que se inicia tratamiento con corticoesteroides con resultado satisfactorio. Se deben tener en consideración las variantes agudas de esclerosis múltiple en todo caso de lesiones pseudotumorales con sintomatología pertinente a esclerosis múltiple, a pesar de ser una variante rara, su curso es usualmente agudo y fulminante, por lo que su detección y manejo oportuno es imprescindible

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field