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

The surveys of F.P. MacCabe and his records of Aboriginal placenames at the Junction of the Murray and Darling Rivers

Surveyor Francis Peter MacCabe mapped sections of the Murrumbidgee, Murray and Darling Rivers between 1848 and 1850. In the process he recorded and mapped hundreds of Aboriginal placenames. His surveys traversed the country of three distinct language families, making his careful recordings of particular linguistic value. This paper provides an overview of his life and work and provides an analysis of some of his records from the Murray-Darling Junction area

A visit to Australia and New Zealand /

Also available online http://nla.gov.au/nla.aus-vn2240253; FERG copy from Ferguson First World War, 1914-1919 pamphlet collection. A daily account of a visit to Australia and New Zealand by Field-Marshal Lord Birdwood and his wife shortly after the end of the First World War

A Comparison of Cataloguing and Classification Education (CCE) in Library and Information Science in South Africa, Brazil and the USA (SOBUSA): An Overview

This article reports on initial findings of a three-country (South Africa, Brazil and United States) study on cataloguing and classification education. Copies of the questionnaire were distributed to the heads of library schools and to cataloguing and classification instructors in South Africa, the United States, and Brazil. The substance of the two questionnaires was the same in all three countries, but changes were made primarily to clarify terminology and national conventions for ethics review. The questionnaires included multiple choice questions and open-ended questions, producing both quantitative and qualitative data. Findings were confirmed through interviews and course syllabi. The results of the study found more similarities than differences in CCE among the countries. The authors speculate that these differences among the three countries may be due to the influence of different European traditions on the development of LIS education in each country. Other differences include the use and availability of technology and the L-word/I-word controversy. The findings of the initial data analysis reported here reveal numerous areas that merit further scrutiny. Further results are derived from analysis of correlations in the data and qualitative analysis of the questionnaires’ many open-ended questions.Keywords: Cataloguing and Classification Education, CCE, Knowledge Organisation, Information Organisation, LIS Education, Brazil, South Africa, US

De novo designed protein inhibitors of amyloid aggregation and seeding.

Neurodegenerative diseases are characterized by the pathologic accumulation of aggregated proteins. Known as amyloid, these fibrillar aggregates include proteins such as tau and amyloid-β (Aβ) in Alzheimer's disease (AD) and alpha-synuclein (αSyn) in Parkinson's disease (PD). The development and spread of amyloid fibrils within the brain correlates with disease onset and progression, and inhibiting amyloid formation is a possible route toward therapeutic development. Recent advances have enabled the determination of amyloid fibril structures to atomic-level resolution, improving the possibility of structure-based inhibitor design. In this work, we use these amyloid structures to design inhibitors that bind to the ends of fibrils, "capping" them so as to prevent further growth. Using de novo protein design, we develop a library of miniprotein inhibitors of 35 to 48 residues that target the amyloid structures of tau, Aβ, and αSyn. Biophysical characterization of top in silico designed inhibitors shows they form stable folds, have no sequence similarity to naturally occurring proteins, and specifically prevent the aggregation of their targeted amyloid-prone proteins in vitro. The inhibitors also prevent the seeded aggregation and toxicity of fibrils in cells. In vivo evaluation reveals their ability to reduce aggregation and rescue motor deficits in Caenorhabditis elegans models of PD and AD

Small molecules disaggregate alpha-synuclein and prevent seeding from patient brain-derived fibrils.

The amyloid aggregation of alpha-synuclein within the brain is associated with the pathogenesis of Parkinson's disease (PD) and other related synucleinopathies, including multiple system atrophy (MSA). Alpha-synuclein aggregates are a major therapeutic target for treatment of these diseases. We identify two small molecules capable of disassembling preformed alpha-synuclein fibrils. The compounds, termed CNS-11 and CNS-11g, disaggregate recombinant alpha-synuclein fibrils in vitro, prevent the intracellular seeded aggregation of alpha-synuclein fibrils, and mitigate alpha-synuclein fibril cytotoxicity in neuronal cells. Furthermore, we demonstrate that both compounds disassemble fibrils extracted from MSA patient brains and prevent their intracellular seeding. They also reduce in vivo alpha-synuclein aggregates in C. elegans. Both compounds also penetrate brain tissue in mice. A molecular dynamics-based computational model suggests the compounds may exert their disaggregating effects on the N terminus of the fibril core. These compounds appear to be promising therapeutic leads for targeting alpha-synuclein for the treatment of synucleinopathies

Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils.

The self-assembly of the Nucleocapsid protein (NCAP) of SARS-CoV-2 is crucial for its function. Computational analysis of the amino acid sequence of NCAP reveals low-complexity domains (LCDs) akin to LCDs in other proteins known to self-assemble as phase separation droplets and amyloid fibrils. Previous reports have described NCAP's propensity to phase-separate. Here we show that the central LCD of NCAP is capable of both, phase separation and amyloid formation. Within this central LCD we identified three adhesive segments and determined the atomic structure of the fibrils formed by each. Those structures guided the design of G12, a peptide that interferes with the self-assembly of NCAP and demonstrates antiviral activity in SARS-CoV-2 infected cells. Our work, therefore, demonstrates the amyloid form of the central LCD of NCAP and suggests that amyloidogenic segments of NCAP could be targeted for drug development