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Seasonality of biological and physical systems as indicators of climatic variation and change
Evidence-based responses to climate change by society require operational and sustained information including biophysical indicator systems that provide up-to-date measures of trends and patterns against historical baselines. Two key components linking anthropogenic climate change to impacts on socio-ecological systems are the periodic inter- and intra-annual variations in physical climate systems (seasonality) and in plant and animal life cycles (phenology). We describe a set of national indicators that reflect sub-seasonal to seasonal drivers and responses of terrestrial physical and biological systems to climate change and variability at the national scale. Proposed indicators and metrics include seasonality of surface climate conditions (e.g., frost and freeze dates and durations), seasonality of freeze/thaw in freshwater systems (e.g., timing of stream runoff and durations of lake/river ice), seasonality in ecosystem disturbances (e.g., wildfire season timing and duration), seasonality in vegetated land surfaces (e.g., green-up and brown-down of landscapes), and seasonality of organismal life-history stages (e.g., timings of bird migration). Recommended indicators have strong linkages to variable and changing climates, include abiotic and biotic responses and feedback mechanisms, and are sufficiently simple to facilitate communication to broad audiences and stakeholders interested in understanding and adapting to climate change.Public domain articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Small-molecule inhibition of APT1 affects Ras localization and signaling
Cycles of depalmitoylation and repalmitoylation critically control the steady-state localization and function of various peripheral membrane proteins, such as Ras proto-oncogene products. Interference with acylation using small molecules is a strategy to modulate cellular localization—and thereby unregulated signaling—caused by palmitoylated Ras proteins. We present the knowledge-based development and characterization of a potent inhibitor of acyl protein thioesterase 1 (APT1), a bona fide depalmitoylating enzyme that is, so far, poorly characterized in cells. The inhibitor, palmostatin B, perturbs the cellular acylation cycle at the level of depalmitoylation and thereby causes a loss of the precise steady-state localization of palmitoylated Ras. As a consequence, palmostatin B induces partial phenotypic reversion in oncogenic HRasG12V-transformed fibroblasts. We identify APT1 as one of the thioesterases in the acylation cycle and show that this protein is a cellular target of the inhibitor
Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women’s Health Initiative
BACKGROUND: Adiponectin, a protein secreted by the adipose tissue, is an endogenous insulin sensitizer with circulating levels that are decreased in obese and diabetic subjects. Recently, circulating levels of adiponectin have been correlated with breast cancer risk. Our previous work showed that polymorphisms of the adiponectin pathway are associated with breast cancer risk. METHODS: We conducted the first study of adiponectin pathways in African Americans and Hispanics in the Women’s Health Initiative (WHI) SNP Health Association Resource (SHARe) cohort of 3,642 self-identified Hispanic women and 8,515 self-identified African American women who provided consent for DNA analysis. Single nucleotide polymorphisms (SNPs) from three genes were included in this analysis: ADIPOQ, ADIPOR1 and ADIPOR2. The Genome-wide Human SNP Array 6.0 (909,622 SNPs) (www.affymetrix.com) was used. RESULTS: We found that rs1501299, a functional SNP of ADIPOQ that we previously reported was associated with breast cancer risk in a mostly Caucasian population, was also significantly associated with breast cancer incidence (HR for the GG/TG genotype: 1.23; 95% CI: 1.059–1.43) in African American women. We did not find any other SNPs in these genes to be associated with breast cancer incidence. CONCLUSIONS: This is the first study assessing the role of adiponectin pathway SNPs in breast cancer risk in African Americans and Hispanics. RS1501299 is significantly associated with breast cancer risk in African American women. Impact: As the rates of obesity and diabetes increase in African Americans and Hispanics, adiponectin and its functional SNPs may aid in breast cancer risk assessment