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In the southwestern United States, climate change and climate–fire dynamics are affecting the distribution of natural and managed ecosystems. Forest obligate species on sky islands can experience a restriction in range with the increase of destructive forest fires. Using presence/absence data collected by hair tubes, we identified key habitat features that determine the western gray squirrel (Sciurus griseus) distribution on the sky island of the San Bernardino Mountains (California, USA) and determined post-fire differential use of burn severity in a landscape modified by fire. Gray squirrel presence was related to habitat features important for this species’ ecology and behavior, especially those associated with mature forests. The species was detected in areas with a high percentage of conifers that provide both an important food resource and good branches and cavities for nest sites. Gray squirrels occurred in all burn severities but occurred more in low and high severity sites than unburned sites. These results suggest that the gray squirrel can persist after a wildfire and can take advantage of the post-fire habitat structure if a mosaic of burn severities is maintained in the forest.

Leber congenital amaurosis type 10 is a severe retinal dystrophy caused by mutations in the CEP290 gene1,2. We developed EDIT-101, a candidate genome-editing therapeutic, to remove the aberrant splice donor created by the IVS26 mutation in the CEP290 gene and restore normal CEP290 expression. Key to this therapeutic, we identified a pair of Staphylococcus aureus Cas9 guide RNAs that were highly active and specific to the human CEP290 target sequence. In vitro experiments in human cells and retinal explants demonstrated the molecular mechanism of action and nuclease specificity. Subretinal delivery of EDIT-101 in humanized CEP290 mice showed rapid and sustained CEP290 gene editing. A comparable surrogate non-human primate (NHP) vector also achieved productive editing of the NHP CEP290 gene at levels that met the target therapeutic threshold, and demonstrated the ability of CRISPR/Cas9 to edit somatic primate cells in vivo. These results support further development of EDIT-101 for LCA10 and additional CRISPR-based medicines for other inherited retinal disorders. In human cells, a humanized mouse model and non-human primates, CRISPR/Cas9 corrects the splicing defect in a gene associated with congenital blindness.

Purpose Glucocorticoid receptor (GR) overexpression is associated with poor prognosis ER-negative breast cancer. GR antagonism with mifepristone increases chemotherapy-induced breast cancer cell death, therefore we conducted a phase I clinical trial of mifepristone and nab-paclitaxel in advanced breast cancer. Methods A novel randomized phase I design was used to assess the effect of mifepristone on nab-paclitaxel pharmacokinetics and toxicity. Patients were randomized to placebo or mifepristone for the first cycle; mifepristone was given to all for subsequent cycles. Results Nine patients were enrolled. All were found to have a twofold or greater increase in serum cortisol after mifepristone administration, reflecting effective GR inhibition. Neutropenia occurred at both nab-paclitaxel dose levels studied (100 and 80 mg/m2), and was easily managed with dose reduction and/or growth factor administration. Pharmacokinetic data suggest an interaction between nab-paclitaxel and mifepristone in some patients. Two patients had complete responses (CR), three partial responses (PR), one stable disease (SD), and three progressive disease (PD). Immunohistochemical staining for GR found six of nine tumors were GR-positive. All six GR-positive tumors were triple-negative at the time of recurrence. Of these six patients, two had CRs, two PRs, one SD, and one PD. Conclusions GR appears to be a promising target in TNBC, and GR inhibition plus chemotherapy produces manageable toxicity. While neutropenia was observed in some, a nab-paclitaxel dose of 100 mg/m2 plus mifepristone 300 mg was found to be tolerable, and a randomized phase II trial of nab-paclitaxel with/without mifepristone is planned in GR-positive advanced TNBC. Electronic supplementary material The online version of this article (doi:10.1186/s40064-016-2457-1) contains supplementary material, which is available to authorized users.

Mammalian target of rapamycin (mTOR) is an attractive target for cancer treatment. While rapamycin and its derivatives (e.g., everolimus) have been shown to inhibit mTOR signaling and cell proliferation in preclinical models of breast cancer, mTOR inhibition has demonstrated variable clinical efficacy with a trend toward better responses in estrogen receptor alpha positive (ERα+) compared to ERα negative (ERα-) tumors. Recently, serum- and glucocorticoid-regulated kinase 1 (SGK1) was identified as a substrate of mTOR kinase activity. Previous studies have alternatively suggested that either mTORC1 or mTORC2 is exclusively required for SGK1's Ser422 phosphorylation and activation in breast cancer cells. We investigated the effect of rapamycin on the growth of several ERα+ and ERα- breast cancer cell lines and examined differences in the phosphorylation of mTOR substrates (SGK1, p70S6K, and Akt) that might account for the differing sensitivity of these cell lines to rapamycin. We also examined which mTOR complex contributes to SGK1-Ser422 phosphorylation in ERα+ versus ERα- breast cell lines. We then assessed whether inhibiting SGK1 activity added to rapamycin-mediated cell growth inhibition by either using the SGK1 inhibitor GSK650394A or expressing an SGK1 shRNA. We observed sensitivity to rapamycin-mediated growth inhibition and inactivation of insulin-mediated SGK1-Ser422 phosphorylation in ERα+ MCF-7 and T47D cells, but not in ERα- MDA-MB-231 or MCF10A-Myc cells. In addition, either depleting SGK1 with shRNA or inhibiting SGK1 with GSK650394A preferentially sensitized MDA-MB-231 cells to rapamycin. Finally, we found that rapamycin-sensitive SGK1-Ser422 phosphorylation required ERα expression in MCF-7 derived cell lines. Therefore, targeting SGK1 activity may improve the efficacy of rapamycin and its analogs in the treatment of ERα- breast cancer.

Geological storage of CO2 in the offshore Gippsland Basin, Australia, is being investigated by the Cooperative Research Centre for Greenhouse Gas Technologies (CO2CRC) as a possible method for storing the very large volumes of CO2 emissions from the nearby Latrobe Valley area. A storage capacity of about 50 million tonnes of CO2 per annum for a 40-year injection period is required, which will necessitate several individual storage sites to be used both sequentially and simultaneously, but timed such that existing hydrocarbon assets will not be compromised. Detailed characterisation focussed on the Kingfish Field area as the first site to be potentially used, in the anticipation that this oil field will be depleted within the period 2015–2025. The potential injection targets are the interbedded sandstones of the Paleocene-Eocene upper Latrobe Group, regionally sealed by the Lakes Entrance Formation. The research identified several features to the offshore Gippsland Basin that make it particularly favourable for CO2 storage. These include: a complex stratigraphic architecture that provides baffles which slow vertical migration and increase residual gas trapping and dissolution; non-reactive reservoir units that have high injectivity; a thin, suitably reactive, lower permeability marginal reservoir just below the regional seal providing mineral trapping; several depleted oil fields that provide storage capacity coupled with a transient production-induced flow regime that enhances containment; and long migration pathways beneath a competent regional seal. This study has shown that the Gippsland Basin has sufficient capacity to store very large volumes of CO2. It may provide a solution to the problem of substantially reducing greenhouse gas emissions from future coal developments in the Latrobe Valley.

This study was carried out to identify the common moulds growing in selected commercial poultry feed sold in Owerri, Imo State, Nigeria. Forty-eight bulk samples derived froml92 bags of feeds were collected from broiler starter (BS), broiler finishers (BF), grower mash (GM) and layer mash (LM) across 4 different brands of ommercial poultry feeds, which included Livestock (LF), Top (TF) Guinea (GF) and Vital (VF) feeds. The feed samples were collected during the rainy season months of June, July and August. The common moulds isolated from these feeds were Aspergillus sp., Peicillium sp.,Mucor sp., Yeast sp., Rhizopus sp., Epicoecum sp., Gymnoaseus sp., Cladosporium sp., Mortierella sp. as well as Bacteria. Generally, more organisms were isolated in June than the other months with Mortierella sp. being the only one not isolated in that month. Vital feed with 8 different isolates had the highest diversity of fungal species while the others had between 4 and 5 species. Prevalence rates across the feed types, generally ranged from 18.76% in layer mash to 30.03% in broiler finisher. The four Aspergillus sp. isolated came from GM and BF. This study highlights the need for constant monitoring of moulds in commercial feedstuff produced in the humid tropical environments such as Imo state, Nigeria. There is also the need to routinely include fungal growth nhibitors in commercial feeds since moulds are capable of reducing the nutritional values of feedstuff as well as elaborating pathogenic toxins.