Comprehensive translational control of tyrosine kinase expression by upstream open reading frames

Post-transcriptional control has emerged as a major regulatory event in gene expression and often occurs at the level of translation initiation. Although overexpression or constitutive activation of tyrosine kinases (TKs) through gene amplification, translocation or mutation are well-characterized oncogenic events, current knowledge about translational mechanisms of TK activation is scarce. Here, we report the presence of translational cis-regulatory upstream open reading frames (uORFs) in the majority of transcript leader sequences of human TK mRNAs. Genetic ablation of uORF initiation codons in TK transcripts resulted in enhanced translation of the associated downstream main protein-coding sequences (CDSs) in all cases studied. Similarly, experimental removal of uORF start codons in additional non-TK proto-oncogenes, and naturally occurring loss-of-uORF alleles of the c-met proto-oncogene (MET) and the kinase insert domain receptor (KDR), was associated with increased CDS translation. Based on genome-wide sequence analyses we identified polymorphisms in 15.9% of all human genes affecting uORF initiation codons, associated Kozak consensus sequences or uORF-related termination codons. Together, these data suggest a comprehensive role of uORF-mediated translational control and delineate how aberrant induction of proto-oncogenes through loss-of-function mutations at uORF initiation codons may be involved in the etiology of cancer. We provide a detailed map of uORFs across the human genome to stimulate future research on the pathogenic role of uORFs

Sistemas Deliberativos Em Perspectiva Meso: A Abordagem Dos Subsistemas Aplicada Aos Conselhos De Políticas Públicas Em Belo Horizonte

This article presents a critical dialogue with the literature about deliberative systems. It features an innovative proposal to investigate deliberative arenas in their connections with other parts of the political system and society. It adopts a method present in the field of Social Network Analysis (SNA) to conduct an empirical investigation of public policy councils of the city of Belo Horizonte. Our working hypothesis was that the main links among the councils would be informal mechanisms that promotes institutional interaction. The results show that government councillors are part of various councils simultaneously, so they play the role of links between the practices and institutions in which they work. It suggests the necessity to carry out future studies that would be able to show the connection of councils to the other parts of the broader deliberative system.22116719

The COVID-19 pandemic, emergency aid and social work in Brazil.

This essay reflects on the implementation of federal government emergency aid in Brazil in the context of the COVID-19 pandemic, highlighting elements from the work of Social Workers in the context of growing demand for the supply of material provisions. Economic and social conditions in Brazil have particularities that impact the operationalisation of this benefit, which is aimed at the poor, that add complexity and impose limits. When considering the structural limits set, this context imposes challenges on the work of Social Workers. The need to reconnect and enhance the struggle for social rights is emphasised through the different strategies of the working class

On the verge of Umdeutung in Minnesota: Van Vleck and the correspondence principle (Part One)

In October 1924, the Physical Review, a relatively minor journal at the time, published a remarkable two-part paper by John H. Van Vleck, working in virtual isolation at the University of Minnesota. Van Vleck combined advanced techniques of classical mechanics with Bohr's correspondence principle and Einstein's quantum theory of radiation to find quantum analogues of classical expressions for the emission, absorption, and dispersion of radiation. For modern readers Van Vleck's paper is much easier to follow than the famous paper by Kramers and Heisenberg on dispersion theory, which covers similar terrain and is widely credited to have led directly to Heisenberg's "Umdeutung" paper. This makes Van Vleck's paper extremely valuable for the reconstruction of the genesis of matrix mechanics. It also makes it tempting to ask why Van Vleck did not take the next step and develop matrix mechanics himself.Comment: 82 page