Global gene expression analysis of canine osteosarcoma stem cells reveals a novel role for COX-2 in tumour initiation

Osteosarcoma is the most common primary bone tumour of both children and dogs. It is an aggressive tumour in both species with a rapid clinical course leading ultimately to metastasis. In dogs and children distant metastasis occurs in >80% of individuals treated by surgery alone. Both canine and human osteosarcoma has been shown to contain a sub-population of cancer stem cells (CSCs), which may drive tumour growth, recurrence and metastasis, suggesting that naturally occurring canine osteosarcoma could act as a preclinical model for the human disease. Here we report the successful isolation of CSCs from primary canine osteosarcoma, as well as established cell lines. We show that these cells can form tumourspheres, and demonstrate relative resistance to chemotherapy. We demonstrate similar results for the human osteosarcma cell lines, U2OS and SAOS2. Utilizing the Affymetrix canine microarray, we are able to definitively show that there are significant differences in global gene expression profiles of isolated osteosarcoma stem cells and the daughter adherent cells. We identified 13,221 significant differences (p = 0.05), and significantly, COX-2 was expressed 141-fold more in CSC spheres than daughter adherent cells. To study the role of COX-2 expression in CSCs we utilized the COX-2 inhibitors meloxicam and mavacoxib. We found that COX-2 inhibition had no effect on CSC growth, or resistance to chemotherapy. However inhibition of COX-2 in daughter cells prevented sphere formation, indicating a potential significant role for COX-2 in tumour initiation

Gene Expression and Biological Pathways in Tissue of Men with Prostate Cancer in a Randomized Clinical Trial of Lycopene and Fish Oil Supplementation

Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial.Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n = 29) or fish oil (n = 27) supplementation or placebo (n = 28). Gene expression in morphologically normal prostate tissue was studied at baseline and at 3 months via cDNA microarray analysis. Differential gene expression and pathway analyses were performed to identify genes and pathways modulated by these micronutrients.Global gene expression analysis revealed no significant individual genes that were associated with high intake of fish or tomato at baseline or after 3 months of supplementation with lycopene or fish oil. However, exploratory pathway analyses of rank-ordered genes (based on p-values not corrected for multiple comparisons) revealed the modulation of androgen and estrogen metabolism in men who routinely consumed more fish (p = 0.029) and tomato (p = 0.008) compared to men who ate less. In addition, modulation of arachidonic acid metabolism (p = 0.01) was observed after 3 months of fish oil supplementation compared with the placebo group; and modulation of nuclear factor (erythroid derived-2) factor 2 or Nrf2-mediated oxidative stress response for either supplement versus placebo (fish oil: p = 0.01, lycopene: p = 0.001).We did not detect significant individual genes associated with dietary intake and supplementation of lycopene and fish oil. However, exploratory analyses revealed candidate in vivo pathways that may be modulated by these micronutrients.ClinicalTrials.gov NCT00402285

Economic Efficiency of Compost Production: The Case of Israel

This paper presents a comprehensive economic analysis of recycling organic wastes through composting. A mathematical programming model is developed to examine the optimal level of compost production from sources of organic municipal solid waste, livestock manure and wastewater-treatment sludge. The model incorporates the spatial nature of the problem by referring to the locations of the sources for raw organic matter, of the composting plants and agricultural regions. Agricultural demand for compost is derived using estimated production functions for 42 crops, price elasticity of the vegetative agricultural outputs, and farmers' stated willingness to utilize compost. The model accounts for the costs of waste collection, compost production, transportation and landfilling; all include both direct costs and externalities. The optimal allocation of raw materials and outputs is achieved when the financial contribution of the composting system is maximized relative to the alternative of disposing of these organic wastes in landfills. We apply the model to the case of Israel. Today, despite the relatively high levels of organic material in municipal solid waste, the scarcity of landfill sites, and the low level of organic content in agricultural soils, only 37% of Israel's composting potential is realized. Subject to compliance with new environmental regulations, our analysis points to the possibility of an 89% composting rate, in which all livestock manure and sludge are composted, but only 75% of the organic municipal solid waste is utilized in this manner. This finding supports the strict enforcement of these environmental regulations, and indicates the need for a composting encouraging policy. However, regulations aimed at increasing the rate of municipal solid waste recycling should leave enough freedom for municipalities to select their waste disposal strategies. It is also concluded that, given the high costs of separating municipal waste at the 2 source, the government can increase composting rates by initializing and stimulating the formation of regional cooperation to ensure steady long run consumption of raw organic materials. Moreover, the government can increase agricultural demand for compost by both setting clear standards for high quality compost, and spreading the scientific information on the advantages of composting via the governmental agricultural instruction system. The presented methodology is applicable to other cases, as is the scientific-based data, which include the external costs and the compost production functions. This information is relevant for regions facing the same challenges, particularly where the soil's organic content is less than 2%; e.g., Portugal, Spain, Italy and Greece

Economic Efficiency of Compost Production: The Case of Israel

This paper presents a comprehensive economic analysis of recycling organic wastes through composting. A mathematical programming model is developed to examine the optimal level of compost production from sources of organic municipal solid waste, livestock manure and wastewater-treatment sludge. The model incorporates the spatial nature of the problem by referring to the locations of the sources for raw organic matter, of the composting plants and agricultural regions. Agricultural demand for compost is derived using estimated production functions for 42 crops, price elasticity of the vegetative agricultural outputs, and farmers' stated willingness to utilize compost. The model accounts for the costs of waste collection, compost production, transportation and landfilling; all include both direct costs and externalities. The optimal allocation of raw materials and outputs is achieved when the financial contribution of the composting system is maximized relative to the alternative of disposing of these organic wastes in landfills. We apply the model to the case of Israel. Today, despite the relatively high levels of organic material in municipal solid waste, the scarcity of landfill sites, and the low level of organic content in agricultural soils, only 37% of Israel's composting potential is realized. Subject to compliance with new environmental regulations, our analysis points to the possibility of an 89% composting rate, in which all livestock manure and sludge are composted, but only 75% of the organic municipal solid waste is utilized in this manner. This finding supports the strict enforcement of these environmental regulations, and indicates the need for a composting encouraging policy. However, regulations aimed at increasing the rate of municipal solid waste recycling should leave enough freedom for municipalities to select their waste disposal strategies. It is also concluded that, given the high costs of separating municipal waste at the 2 source, the government can increase composting rates by initializing and stimulating the formation of regional cooperation to ensure steady long run consumption of raw organic materials. Moreover, the government can increase agricultural demand for compost by both setting clear standards for high quality compost, and spreading the scientific information on the advantages of composting via the governmental agricultural instruction system. The presented methodology is applicable to other cases, as is the scientific-based data, which include the external costs and the compost production functions. This information is relevant for regions facing the same challenges, particularly where the soil's organic content is less than 2%; e.g., Portugal, Spain, Italy and Greece.Compost, Economics, Livestock-Manure, Mathematical-Programming, Municipal-Solid-Waste, Waste-Water-Treatment-Sludge,

Figure 3 in The northward extension of reptiles in the Palearctic, with the Jordan Valley (Israel) as a model: snakes outrace lizards (Reptilia: Squamata)

Figure 3. The geographical distribution of all records of snakes in the study area, solid circles. Some key localities for orientation are shown in Figure 1.Published as part of Shacham, Boaz, Federman, Roy, Lahav-Ginott, Shimrit & Werner, Yehudah L., 2015, The northward extension of reptiles in the Palearctic, with the Jordan Valley (Israel) as a model: snakes outrace lizards (Reptilia: Squamata), pp. 1017-1033 in Journal of Natural History 50 on page 1023, DOI: 10.1080/00222933.2015.1083057, http://zenodo.org/record/399011

Figure 1 in The northward extension of reptiles in the Palearctic, with the Jordan Valley (Israel) as a model: snakes outrace lizards (Reptilia: Squamata)

Figure 1. The geographical distribution of all records of lizards in the study area, solid circles. Also indicated are the approximate locations of some key localities for orientation, open squares.Published as part of Shacham, Boaz, Federman, Roy, Lahav-Ginott, Shimrit & Werner, Yehudah L., 2015, The northward extension of reptiles in the Palearctic, with the Jordan Valley (Israel) as a model: snakes outrace lizards (Reptilia: Squamata), pp. 1017-1033 in Journal of Natural History 50 on page 1021, DOI: 10.1080/00222933.2015.1083057, http://zenodo.org/record/399011

Health literacy, cognitive function, proper use, and adherence to inhaled asthma controller medications among older adults with asthma.

BACKGROUND: We sought to investigate the degree to which cognitive skills explain associations between health literacy and asthma-related medication use among older adults with asthma. METHODS: Patients aged ≥ 60 years receiving care at eight outpatient clinics (primary care, geriatrics, pulmonology, allergy, and immunology) in New York, New York, and Chicago, Illinois, were recruited to participate in structured, in-person interviews as part of the Asthma Beliefs and Literacy in the Elderly (ABLE) study (n = 425). Behaviors related to medication use were investigated, including adherence to prescribed regimens, metered-dose inhaler (MDI) technique, and dry powder inhaler (DPI) technique. Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Cognitive function was assessed in terms of fluid (working memory, processing speed, executive function) and crystallized (verbal) ability. RESULTS: The mean age of participants was 68 years; 40% were Hispanic and 30% non-Hispanic black. More than one-third (38%) were adherent to their controller medication, 53% demonstrated proper DPI technique, and 38% demonstrated correct MDI technique. In multivariable analyses, limited literacy was associated with poorer adherence to controller medication (OR, 2.3; 95% CI, 1.29-4.08) and incorrect DPI (OR, 3.51; 95% CI, 1.81-6.83) and MDI (OR, 1.64; 95% CI, 1.01-2.65) techniques. Fluid and crystallized abilities were independently associated with medication behaviors. However, when fluid abilities were added to the model, literacy associations were reduced. CONCLUSIONS: Among older patients with asthma, interventions to promote proper medication use should simplify tasks and patient roles to overcome cognitive load and suboptimal performance in self-care

Trends in Ecological Research during the Last Three Decades – A Systematic Review

<div><p>It is thought that the science of ecology has experienced conceptual shifts in recent decades, chiefly from viewing nature as static and balanced to a conception of constantly changing, unpredictable, complex ecosystems. Here, we ask if these changes are reflected in actual ecological research over the last 30 years. We surveyed 750 articles from the entire pool of ecological literature and 750 articles from eight leading journals. Each article was characterized according to its type, ecological domain, and applicability, and major topics. We found that, in contrast to its common image, ecology is still mostly a study of single species (70% of the studies); while ecosystem and community studies together comprise only a quarter of ecological research. Ecological science is somewhat conservative in its topics of research (about a third of all topics changed significantly through time), as well as in its basic methodologies and approaches. However, the growing proportion of problem-solving studies (from 9% in the 1980s to 20% in the 2000 s) may represent a major transition in ecological science in the long run.</p></div

Change in the frequency over time for the topics for which temporal change was significant at the Bonferroni-adjusted level (p<0.001) in at least one of the datasets.

<p>White bars denote ‘all journals’ and gray bars denote ‘core journals’. *** Temporal trend was significant (a logistic model, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059813#pone-0059813-t002" target="_blank">Table 2</a>), p<0.001. ** p<0.01. * p<0.05.</p