The Move to the Middle: The Enduring Threat of “Harmful” Speech to the End-to-End Principle

This Essay traces the evolution of thinking regarding the technical concept of the end-to-end principle and the legal concept of the regulation of the flow of packets across the Internet. We focus on the manner in which the state, in concert with private parties, has approached the tension between restricting the flow of certain packets and vindicating their citizens’ interests, both legal and otherwise, in free expression. We argue that the primary mode of legal regulation of the Internet has shifted from a focus on outlawing activities at the nodes—end-points in the network—to a growing emphasis on regulating closer to the middle of the network. This trend is, on its face, good for the law enforcement officer, but worrisome to the technologist and the democratic activist; the end-to-end principle, held dear by those who built the Internet for decades, is under threat. In the process, this shift also places corporations, often based in other jurisdictions, in the position of enforcing the rules of the regime in which they are doing business, but whose views on free expression and other civil liberties the corporations’ officers and directors do not necessarily share. We argue that the end-to-end principle, once translated loosely into political speak as “net neutrality,” is a forceful rhetorical concept—and, if done right, sound public policy—but that it no longer describes the Internet on the ground, if it ever did

Functions of long non-coding RNAs in human disease and their conservation in Drosophila development

Genomic analysis has found that the transcriptome in both humans and Drosophila melanogaster features large numbers of long non-coding RNA transcripts (lncRNAs). This recently discovered class of RNAs regulates gene expression in diverse ways and has been involved in a large variety of important biological functions. Importantly, an increasing number of lncRNAs have also been associated with a range of human diseases, including cancer. Comparative analyses of their functions among these organisms suggest that some of their modes of action appear to be conserved. This highlights the importance of model organisms such as Drosophila, which shares many gene regulatory networks with humans, in understanding lncRNA function and its possible impact in human health. This review discusses some known functions and mechanisms of action of lncRNAs and their implication in human diseases, together with their functional conservation and relevance in Drosophila development

Mucopolysaccharidosis I, II, and VI: Brief review and guidelines for treatment

Mucopolysaccharidoses (MPS) are rare genetic diseases caused by the deficiency of one of the lysosomal enzymes involved in the glycosaminoglycan (GAG) breakdown pathway. This metabolic block leads to the accumulation of GAG in various organs and tissues of the affected patients, resulting in a multisystemic clinical picture, sometimes including cognitive impairment. Until the beginning of the XXI century, treatment was mainly supportive. Bone marrow transplantation improved the natural course of the disease in some types of MPS, but the morbidity and mortality restricted its use to selected cases. The identification of the genes involved, the new molecular biology tools and the availability of animal models made it possible to develop specific enzyme replacement therapies (ERT) for these diseases. At present, a great number of Brazilian medical centers from all regions of the country have experience with ERT for MPS I, II, and VI, acquired not only through patient treatment but also in clinical trials. Taking the three types of MPS together, over 200 patients have been treated with ERT in our country. This document summarizes the experience of the professionals involved, along with the data available in the international literature, bringing together and harmonizing the information available on the management of these severe and progressive diseases, thus disclosing new prospects for Brazilian patients affected by these conditions