Lack of spatial segregation in the representation of pheromones and kairomones in the mouse medial amygdala

The nervous system is organized to detect, internally represent and process sensory information to generate appropriate behaviors. Despite the crucial importance of odors that elicit instinctive behaviors, such as pheromones and kairomones, their neural representation remains little characterized in the mammalian brain. Here we used expression of the immediate early gene product c-Fos as a marker of neuronal activity to find that a wide range of pheromones and kairomones produces activation in the medial nucleus of the amygdala, a brain area anatomically connected with the olfactory sensory organs. We see that activity in this nucleus depends on vomeronasal organ input, and that distinct vomeronasal stimuli activate a dispersed ensemble of cells, without any apparent spatial segregation. This activity pattern does not reflect the chemical category of the stimuli, their valence or the induced behaviors. These findings will help build a complete understanding of how odor information is processed in the brain to generate instinctive behaviors.9FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP09/00473-

Caracterização molecular e funcional da degradação de lisina pela via da sacaropina em eucariotos superiores

Orientador: Paulo ArrudaTese (doutorado) - Universidade Estadual de Campinas, Instituto de BiologiaDoutorad

Contagem de reads sequenciamento Illumina - Expansão biblioteca Bison sgRNA library

Tabela contendo contagem de reads para cada sgRNA da biblioteca Bison sgRNA (Addgene 169942) após expansão do DNA plasmidial e produção de partículas lentivirais. Na tabela, CP corresponde a contagem de reads da biblioteca de DNA plasmidial, enquanto que CL corresponde a contagem de reads da biblioteca lentiviral

Transcription factor 4 and its association with psychiatric disorders.

The human transcription factor 4 gene (TCF4) encodes a helix-loop-helix transcription factor widely expressed throughout the body and during neural development. Mutations in TCF4 cause a devastating autism spectrum disorder known as Pitt-Hopkins syndrome, characterized by a range of aberrant phenotypes including severe intellectual disability, absence of speech, delayed cognitive and motor development, and dysmorphic features. Moreover, polymorphisms in TCF4 have been associated with schizophrenia and other psychiatric and neurological conditions. Details about how TCF4 genetic variants are linked to these diseases and the role of TCF4 during neural development are only now beginning to emerge. Here, we provide a comprehensive review of the functions of TCF4 and its protein products at both the cellular and organismic levels, as well as a description of pathophysiological mechanisms associated with this gene

Transcription factor 4 and its association with psychiatric disorders.

The human transcription factor 4 gene (TCF4) encodes a helix-loop-helix transcription factor widely expressed throughout the body and during neural development. Mutations in TCF4 cause a devastating autism spectrum disorder known as Pitt-Hopkins syndrome, characterized by a range of aberrant phenotypes including severe intellectual disability, absence of speech, delayed cognitive and motor development, and dysmorphic features. Moreover, polymorphisms in TCF4 have been associated with schizophrenia and other psychiatric and neurological conditions. Details about how TCF4 genetic variants are linked to these diseases and the role of TCF4 during neural development are only now beginning to emerge. Here, we provide a comprehensive review of the functions of TCF4 and its protein products at both the cellular and organismic levels, as well as a description of pathophysiological mechanisms associated with this gene

Questioning a witness

This thesis is dealing with the subject of a witness in criminal proceedings. It contains an examination of the term of witness, its rights and duties and specificities of a questioning of a witness who is a victim of crimes and a person under the age of 18 years. The thesis is then dealing with possibilities of protection of a witness. There is a presentation of measures ensuring a witness at a questioning and of limits of forcing a witness to testify. The thesis is also dismantling a questioning of a witness in different stages of criminal proceedings, different methods of questioning including videoconferences and briefly also psychological aspects of questioning a witness

Disease-associated mutations in topoisomerase IIβ result in defective NK cells.

BackgroundHoffman syndrome is a syndromic, inborn error of immunity due to autosomal-dominant mutations in TOP2B, an essential gene required to alleviate topological stress during DNA replication and gene transcription. Although mutations identified in patients lead to a block in B-cell development and the absence of circulating B cells, an effect on natural killer (NK) cells was not previously examined.ObjectiveWe sought to determine whether disease-associated mutations in TOP2B impact NK-cell development and function.MethodsUsing a knockin murine model and patient-derived induced pluripotent stem cells (iPSCs), we investigated NK-cell development in mouse bone marrow and spleen, and performed immunophenotyping by flow cytometry, gene expression, and functional assessment of cytotoxic activity in murine NK cells, and human IPSC-derived NK cells.ResultsMature NK cells were reduced in the periphery of TOP2B knockin mice consistent with patient reports, with reduced cytotoxicity toward target cell lines. IPSCs were successfully derived from patients with Hoffman syndrome, but under optimal conditions showed reduced cytotoxicity compared with iPSC-derived NK cells from healthy controls.ConclusionsHoffman syndrome-associated mutations in TOP2B impact NK-cell development and function in murine and human models