Blood-nervous Tissue Barriers In The Peripheral Nervous System

After years of investigation into blood-nervous tissue barriers controversies remain regarding the permeability of blood vessels to macromolecules in the enteric nervous system, the endoneurium of peripheral nerve, and the spaces between satellite cells and neurons in sensory and sympathetic ganglia.;The permeability of the above areas of the peripheral nervous system was investigated in rats using the following intravenously administered tracers: rhodamine-labelled bovine albumin; horseradish peroxidase; acriflavine and ethidium. The last two, which are fluorescent cationic dyes were shown to bind to serum proteins. In addition immunohistochemical staining for endogenous albumin was performed. One long-term study was done in which rhodamine-labelled bovine albumin was injected subcutaneously, once daily, for one week. With all these methods, it was possible to show that blood vessels in the brain were impermeable, whereas those in circumventricular organs were permeable, thus validating their application to regions in which the existence of permeable vessels was questionable.;Rhodamine-labelled bovine albumin was seen in all the extracellular spaces in sympathetic and sensory ganglia, even after short times in the circulation. The endoneurium of peripheral nerve contained this tracer only in rats in which it had been injected daily for one week. At no time did this fluorescent albumin enter the enteric ganglia. Positive immunohistochemical staining for endogenous albumin was present in the enteric nervous system, in the endoneurium of peripheral nerve, in the spaces between satellite cells and neurons in sensory ganglia, and around neurons in sympathetic ganglia. Horseradish peroxidase, which is present in the blood for about 5 minutes following intravenous injection, penetrated the enteric nervous system, and the extracellular spaces between satellite cells and neurons in sensory ganglia, but it did not enter the endoneurium of peripheral nerve. The fluorochromes acriflavine and ethidium entered enteric, sympathetic and sensory ganglia, but not the endoneurium of peripheral nerve.;In conclusion, the enteric nervous system, sympathetic and sensory ganglia are permeable to most circulating macromolecules. The endoneurium of peripheral nerve is permeable only to macromolecules that are present in the circulation for at least one week, so the transudation or diffusion in this tissue must occur more slowly than elsewhere. These permeabilities may explain how some pathogens enter the nervous system

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

Genomic reconstruction of the SARS-CoV-2 epidemic in England

AbstractThe evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.</jats:p