Data from: Livestock grazing regulates ecosystem multifunctionality in semi‐arid grassland

1. Ecological theories and experimental evidence indicate that human activity induced losses in biodiversity can have substantial impacts on multiple ecosystem functions. It remains unclear, however, how grazing affects grassland biodiversity and ecosystem multifunctionallity (EMF). 2. Here, we assessed the grazing effects on different dimensions of biodiversity (i.e. plants and soil microbes) and EMF based on a 11-year field experiment in a semi-arid grassland. 3. We found that soil organic C, available nitrogen, and plant functional diversity all decreased even at low grazing intensity while aboveground primary production and bacterial abundance decreased only at high levels of grazing intensity. Grazing pressure effects on EMF can be well predicted by changes in plant functional diversity. 4. Structural equation models reveal that EMF was dominated by grazing pressure and was not directly affected by plant or microbial composition. 5. Synthesis. Our results showed that ecosystem functions differ in their sensitivity to grazing intensity, limiting the effectiveness of a target grazing level to achieve multiple goals in the Eurasian steppe. These findings suggest that grazing-induced alterations in interactions among plants, microbes and environmental factors critically affect the grazing threshold and deserve some major attention in decision-making for grazing

Supplement 1. Sample database and web application.

<h2>File List</h2><blockquote> <p><a href="mycodb.zip">mycodb.zip</a> -- complete MycoDB web application, including database </p> </blockquote><h2>Description</h2><blockquote> <p>The single zip file contains all of the source code and the database necessary to run the MycoDB application. This is a classic ASP application, written in vbscript, with a MS Access database (/fpdb/mycodb.mdb). The database contains some sample data. Anyone with experience setting up classic ASP websites should be able to help get the application up and running. The users table in the database has a sample user login.</p> </blockquote

Preclinical comparison of the blood-brain barrier permeability of osimertinib with other EGFR TKIs

Purpose: Osimertinib is a potent and selective EGFR tyrosine kinase inhibitor (EGFR-TKI) of both sensitizing and T790M resistance mutations. To treat metastatic brain disease, blood–brain barrier (BBB) permeability is considered desirable for increasing clinical efficacy. Experimental Design: We examined the level of brain penetration for 16 irreversible and reversible EGFR-TKIs using multiple in vitro and in vivo BBB preclinical models. Results: In vitro osimertinib was the weakest substrate for human BBB efflux transporters (efflux ratio 3.2). In vivo rat free brain to free plasma ratios (Kpuu) show osimertinib has the most BBB penetrance (0.21), compared with the other TKIs (Kpuu ≤ 0.12). PET imaging in Cynomolgus macaques demonstrated osimertinib was the only TKI among those tested to achieve significant brain penetrance (Cmax %ID 1.5, brain/blood Kp 2.6). Desorption electrospray ionization mass spectroscopy images of brains from mouse PC9 macrometastases models showed osimertinib readily distributes across both healthy brain and tumor tissue. Comparison of osimertinib with the poorly BBB penetrant afatinib in a mouse PC9 model of subclinical brain metastases showed only osimertinib has a significant effect on rate of brain tumor growth. Conclusions: These preclinical studies indicate that osimertinib can achieve significant exposure in the brain compared with the other EGFR-TKIs tested and supports the ongoing clinical evaluation of osimertinib for the treatment of EGFR-mutant brain metastasis. This work also demonstrates the link between low in vitro transporter efflux ratios and increased brain penetrance in vivo supporting the use of in vitro transporter assays as an early screen in drug discovery

Genome-wide studies of verbal declarative memory in nondemented older people: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

BACKGROUND: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. ME