Fact sheet: Characterizing spatial reference conditions in southwestern warm/dry mixed-conifer forests

Reference conditions describe attributes of ecosystem structure, composition, and function and are used to inform ecological restoration efforts. Reference condition information on tree spatial patterns that occurred prior to wide-spread fire exclusion is limited for warm/dry mixed-conifer forests of the western U.S. (Romme et al. 2009), particularly those in the Southwest (see Table 1). Spatial patterns of trees, and groups of trees, are important because they are known to influence understory biodiversity and productivity, fire behavior, distribution of surface fuels, wildlife habitat value, and regeneration (North et al. 2007, Sanchez Meador et al. 2009, Fry and Stephens 2010), yet this information is rarely quantified. The purpose of this fact sheet is to provide an overview of the existing research on spatial patterns in warm/dry mixed-conifer forests, and provide recommendations of future research

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

Design of finite and infinite proteinaceous nanomaterials

Over the early 21st century, structural biology has laid a robust foundation for our understanding of protein molecules. The atomic principles of their structure, how their sequence specifies such a structure, and conversely, how to enumerate an amino acid sequence to adopt a fold, are problems each closer to solved than not. Once the domain of material science and chemistry, materials of various shapes and sizes can now be made out of protein precursors. Designed protein building blocks have been synthesized that self-assemble into tetrahedral, octahedral, and icosahedral molecular cages, as well as infinitely ordered lattices such as two dimensional layers and three dimensional crystals. This thesis provides descriptions used to both create and apply protein nanomaterials towards the study of biochemical phenomenon. Particular interest is given to methods of searching for native like contacts and emulating their assembly into defined quaternary structures. By taking inspiration from nature and utilizing hypothesis driven symmetric materials engineering, I demonstrate the creation of proteins which form new materials in the laboratory and methods to engineer existing materials, including a high resolution imaging scaffold. These advances remove barriers to nanomaterials development and deepen the understanding of protein molecules

Characteristics of AA amyloidosis patients in San Francisco

BackgroundAA amyloidosis due to subcutaneous injection of drugs of abuse has been described in the USA, but all the existing literature is from more than 20 years ago. There is more recent literature from Europe. We have observed a high incidence of AA amyloidosis in the county hospital in San Francisco.DesignHere, we describe 24 patients who had kidney biopsy-proven AA amyloidosis from our hospital from 1998 to 2013. All the patients were thought to have AA amyloidosis from skin popping of illicit drugs after having exhausted the intravenous route. These patients with biopsy-proven AA amyloidosis were analysed further.ResultsAll patients were found to have hepatitis C infection, hypertension was not common, most had advanced kidney failure, and acidosis was common as was tubulointerstitial involvement on the kidney biopsy. Other organ involvement included hepatomegaly and splenomegaly in a number of patients; direct myocardial involvement was not seen, but pulmonary hypertension, history of deep vein thrombosis and pulmonary embolism were common. The prognosis of these patients was poor. The mortality rate approached 50% 1 year after biopsy, and most of the patient needed dialysis shortly after diagnosis. Cessation of drug use seemed beneficial but rarely achievable.ConclusionAA amyloidosis from skin popping is common in San Francisco. Most patients with renal involvement end up on dialysis, and mortality rates are exceedingly high

Cryo-EM structure determination of small therapeutic protein targets at 3 Å-resolution using a rigid imaging scaffold.

Cryoelectron microscopy (Cryo-EM) has enabled structural determination of proteins larger than about 50 kDa, including many intractable by any other method, but it has largely failed for smaller proteins. Here, we obtain structures of small proteins by binding them to a rigid molecular scaffold based on a designed protein cage, revealing atomic details at resolutions reaching 2.9 Å. We apply this system to the key cancer signaling protein KRAS (19 kDa in size), obtaining four structures of oncogenic mutational variants by cryo-EM. Importantly, a structure for the key G12C mutant bound to an inhibitor drug (AMG510) reveals significant conformational differences compared to prior data in the crystalline state. The findings highlight the promise of cryo-EM scaffolds for advancing the design of drug molecules against small therapeutic protein targets in cancer and other human diseases