The karyotypic chaos exhibited by human epithelial cancers complicates efforts to identify mutations critical for malignant transformation. Here we integrate complementary genomic approaches to ...identify human oncogenes. We show that activation of the ERK and phosphatidylinositol 3-kinase (PI3K) signaling pathways cooperate to transform human cells. Using a library of activated kinases, we identify several kinases that replace PI3K signaling and render cells tumorigenic. Whole genome structural analyses reveal that one of these kinases, IKBKE (IKKɛ), is amplified and overexpressed in breast cancer cell lines and patient-derived tumors. Suppression of IKKɛ expression in breast cancer cell lines that harbor IKBKE amplifications induces cell death. IKKɛ activates the nuclear factor-kappaB (NF-κB) pathway in both cell lines and breast cancers. These observations suggest a mechanism for NF-κB activation in breast cancer, implicate the NF-κB pathway as a downstream mediator of PI3K, and provide a framework for integrated genomic approaches in oncogene discovery.
Boron isotopes in marine carbonates are increasingly used to reconstruct seawater pH and atmospheric pCO2 through Earth’s history. While isotope ratio measurements from individual laboratories are ...often of high quality, it is important that records generated in different laboratories can equally be compared. Within this Boron Isotope Intercomparison Project (BIIP), we characterised the boron isotopic composition (commonly expressed in δ11B) of two marine carbonates: Geological Survey of Japan carbonate reference materials JCp‐1 (coral Porites) and JCt‐1 (giant clam Tridacna gigas). Our study has three foci: (a) to assess the extent to which oxidative pre‐treatment, aimed at removing organic material from carbonate, can influence the resulting δ11B; (b) to determine to what degree the chosen analytical approach may affect the resultant δ11B; and (c) to provide well‐constrained consensus δ11B values for JCp‐1 and JCt‐1. The resultant robust mean and associated robust standard deviation (s*) for un‐oxidised JCp‐1 is 24.36 ± 0.45‰ (2s*), compared with 24.25 ± 0.22‰ (2s*) for the same oxidised material. For un‐oxidised JCt‐1, respective compositions are 16.39 ± 0.60‰ (2s*; un‐oxidised) and 16.24 ± 0.38‰ (2s*; oxidised). The consistency between laboratories is generally better if carbonate powders were oxidatively cleaned prior to purification and measurement.
Key Points
The boron isotopic composition (δ11B) of two biogenic carbonate reference materials was measured in ten laboratories.
Unprecedentedly good interlaboratory consistency for both carbonate materials.
Gentle oxidative pre‐treatment of biogenic carbonates led to better overall consistency between laboratories.
Because depression and anxiety are typically studied in isolation, our purpose was to examine the relative importance of these overlapping emotional factors in predicting incident cardiovascular ...disease (CVD).
We examined depression and anxiety screens, and their individual items, as predictors of incident hard CVD events, myocardial infarction, and stroke for 8 years in a diverse sample of 2041 older primary care patients initially free of CVD. At baseline, participants completed self-report depression and anxiety screens. Data regarding CVD events were obtained from an electronic medical record system and the Centers for Medicare and Medicaid Services analytic files.
During follow-up, 683 (33%) experienced a CVD event. Cox proportional hazards models-adjusted for demographic and CVD risk factors-revealed that a positive anxiety screen, but not a positive depression screen, was associated with an increased risk of a hard CVD event in separate models (Years 0-3: anxiety hazard ratio HR = 1.54, 95% confidence interval CI = 1.21-1.96, p < .001; Years 3+: anxiety HR = 0.99, CI = 0.81-1.21), p = .93; depression HR = 1.10, CI = 0.88-1.36, p = .41), as well as when entered into the same model (Years 0-3: anxiety HR = 1.53, CI = 1.20-1.95, p < .001; Years 3+: anxiety HR = 0.99, CI = 0.80-1.21, p = .99; depression HR = 1.03, CI = 0.82-1.29, p = .82). Analyses examining individual items and secondary outcomes showed that the anxiety-CVD association was largely driven by the feeling anxious item and the myocardial infarction outcome.
Anxiety, especially feeling anxious, is a unique risk factor for CVD events in older adults, independent of conventional risk factors and depression. Anxiety deserves increased attention as a potential factor relevant to CVD risk stratification and a potential target of CVD primary prevention efforts.
Worldwide, native predators are killed to protect livestock, an action that can undermine wildlife conservation efforts and create conflicts among stakeholders. An ongoing example is occurring in the ...western United States, where wolves (Canis lupus) were eradicated by the 1930s but are again present in parts of their historic range. While livestock losses to wolves represent a small fraction of overall livestock mortality, the response to these depredations has resulted in widespread conflicts including significant efforts at lethal wolf control to reduce impacts on livestock producers, especially those with large-scale grazing operations on public lands. A variety of nonlethal methods have proven effective in reducing livestock losses to wolves in small-scale operations but in large-scale, open-range grazing operations, nonlethal management strategies are often presumed ineffective or infeasible. To demonstrate that nonlethal techniques can be effective at large scales, we report a 7-year case study where we strategically applied nonlethal predator deterrents and animal husbandry techniques on an adaptive basis (i.e., based on terrain, proximity to den or rendezvous sites, avoiding overexposure to techniques such as certain lights or sound devices that could result in wolves losing their fear of that device, etc.) to protect sheep (Ovis aries) and wolves on public grazing lands in Idaho. We collected data on sheep depredation mortalities in the protected demonstration study area and compared these data to an adjacent wolf-occupied area where sheep were grazed without the added nonlethal protection measures. Over the 7-year period, sheep depredation losses to wolves were 3.5 times higher in the Nonprotected Area (NPA) than in the Protected Area (PA). Furthermore, no wolves were lethally controlled within the PA and sheep depredation losses to wolves were just 0.02% of the total number of sheep present, the lowest loss rate among sheep-grazing areas in wolf range statewide, whereas wolves were lethally controlled in the NPA. Our demonstration project provides evidence that proactive use of a variety of nonlethal techniques applied conditionally can help reduce depredation on large open-range operations.
Endurance exercise at altitude can increase cardiac output and pulmonary vascular pressure to levels that may exceed the stress-tolerability of the alveolar-capillary unit. This study examined the ...effect of ultra-marathon trail racing at different altitudes (ranging from <1000 m to between 1500 - 2700 m) on alveolar-capillary recruitment and lung diffusion.
Cardiac and lung function were examined before and after an ultra-marathon in 67 runners (age:41 ± 9y, BMI:23 ± 2 kg/m2, 10 females), and following 12-24 h of recovery in a subset (n = 27). Cardiac biomarkers (cTnI & BNP) were assessed from whole blood, while lung fluid accumulation (comet tails), stroke volume (SV) and cardiac output (Q) were quantified via echocardiography. Lung diffusing capacity for carbon monoxide (DLco) and its components, alveolar membrane conductance (Dm) and capillary blood volume (Vc), were determined via a single-breath method at rest and during three stages of submaximal semi-recumbent cycling (20, 30, & 40 W).
Average race time was 25 ± 12 h. From pre- to post-race, there was an increase in cardiac biomarkers (cTnI: 0.04 ± .02 vs 0.13 ± .03 ng/ml; BNP: 20 ± 2 vs 112 ± 21 pg/ml, p < 0.01) and lung comet tails (2 ± 1 vs 7 ± 6, p < 0.01), a decrease in resting and exercise SV (76 ± 2 vs 69 ± 2 ml; 40 W: 93 ± 2 vs 88 ± 2 ml, p < 0.01), and an elevation in Q at rest (4.1 ± 0.1 vs 4.6 ± 0.2 l/min, p < 0.01; 40 W: 7.3 ± 0.2 vs 7.4 ± 0.3 l/min, p = 0.899). Resting DLco and Vc decreased after the race (p < 0.01), while Dm was unchanged (p = 0.465); however, during the three stages of exercise DLco, Vc and Dm were all reduced from pre- to post-race (40 W: 36.3 ± 0.9 vs 33.0 ± 0.8 mL/min/mmHg; 83 ± 3 vs 73 ± 2 mL; 186 ± 6 vs 170 ± 7 mL/min/mmHg, respectively, p < 0.01). When corrected for alveolar volume and Q, DLco decreased from pre- to post-race (p < 0.01), and changes in DLco were similar for all ultra-marathon events (p > 0.05).
Competing in an ultra-marathon leads to a transient increase in cardiac injury biomarkers, mild lung-fluid accumulation, and impairments in lung diffusion. Reductions in DLco are predominantly caused by a reduced Vc and possible pulmonary capillary de-recruitment at rest. However, impairments in alveolar-capillary recruitment and Dm both contribute to a fall in exertional DLco following an ultra-marathon. Perturbations in lung diffusion were evident across a range of event distances and varying environmental exposures.
Crassulacean acid metabolism (CAM) is a specialized mode of photosynthesis that features nocturnal CO2 uptake, facilitates increased water-use efficiency (WUE), and enables CAM plants to inhabit ...water-limited environments such as semi-arid deserts or seasonally dry forests. Human population growth and global climate change now present challenges for agricultural production systems to increase food, feed, forage, fiber, and fuel production. One approach to meet these challenges is to increase reliance on CAM crops, such as Agave and Opuntia, for biomass production on semi-arid, abandoned, marginal, or degraded agricultural lands. Major research efforts are now underway to assess the productivity of CAM crop species and to harness the WUE of CAM by engineering this pathway into existing food, feed, and bioenergy crops. An improved understanding of CAM has potential for high returns on research investment. To exploit the potential of CAM crops and CAM bioengineering, it will be necessary to elucidate the evolution, genomic features, and regulatory mechanisms of CAM. Field trials and predictive models will be required to assess the productivity of CAM crops, while new synthetic biology approaches need to be developed for CAM engineering. Infrastructure will be needed for CAM model systems, field trials, mutant collections, and data management.
Objective
Depression may be a predictor and consequence of obesity. However, available evidence for racial minorities has been inconsistent, and more prospective studies are needed. Thus, this ...study's objective was to examine whether depressive symptom severity is a predictor and/or consequence of total adiposity over a 9‐year period in a representative sample of late middle‐aged African‐Americans.
Methods
A total of 410 participants (aged 49–65 years; baseline) in the prospective cohort African American Health study were examined. Depressive symptom severity was assessed with the Center for Epidemiologic Studies‐Depression Scale (CES‐D). Total body fat percent (BF%) and body mass index (BMI; kg/m2) were assessed. Structural equation models were tested.
Results
All model fit statistics, other than χ2, indicated good fit (RMSEA ≤ 0.058, SRMR ≤ 0.052, CFI ≥ 0.95). Baseline CES‐D did not predict 9‐year changes in BF% (β = −0.01, P = 0.78) or BMI (β = −0.01, P = 0.77). Baseline BF% (β = 0.05, P = 0.39) and BMI (β = 0.08, P = 0.095) did not predict 9‐year change in CES‐D.
Conclusions
Depressive symptom severity was not a predictor or consequence of excess total adiposity in late middle‐aged African‐American adults. Including a depression module in obesity prevention and treatment programs specifically designed for late middle‐aged African‐Americans may not have a beneficial effect on obesity outcomes.
Because it is not known whether particular clusters of depressive symptoms are associated with a greater risk of adverse cardiac outcomes, we compared the utility of four clusters in predicting ...incident coronary artery disease (CAD) events during a 15-year period in a large cohort of primary care patients 60 years and older.
Participants were 2537 primary care patients 60 years or older who were screened for depression between 1991 and 1993 and had no existing CAD diagnosis. Depressive symptoms cluster scores (depressed affect, somatic symptoms, interpersonal distress, and positive affect) were computed from responses on the Center for Epidemiologic Studies Depression Scale administered at baseline. CAD events, defined as the occurrence of a nonfatal acute myocardial infarction or CAD death during the follow-up period, were identified using electronic medical record and National Death Index data.
There were 678 CAD events. In separate fully adjusted Cox proportional hazard models (controlling for demographics and cardiovascular risk factors), the depressed affect (hazard ratio HR = 1.11, 95% confidence interval CI = 1.04-1.20), somatic (HR = 1.17, 95% CI = 1.08-1.26), and positive affect (HR = 0.88, 95% CI = 0.82-0.95) clusters each predicted CAD events. When the depressive symptom clusters were entered simultaneously into the fully adjusted model, however, only the somatic cluster remained predictive of CAD events (HR = 1.13, 95% CI = 1.03-1.23).
Our findings suggest that the longitudinal relationship between overall depressive symptom severity and incident CAD events may be driven primarily by the somatic cluster.
1. Priority question exercises are becoming an increasingly common tool to frame future agendas in conservation and ecological science. They are an effective way to identify research foci that ...advance the field and that also have high policy and conservation relevance. 2. To date, there has been no coherent synthesis of key questions and priority research areas for palaeoecology, which combines biological, geochemical and molecular techniques in order to reconstruct past ecological and environmental systems on time-scales from decades to millions of years. 3. We adapted a well-established methodology to identify 50 priority research questions in palaeoecology. Using a set of criteria designed to identify realistic and achievable research goals, we selected questions from a pool submitted by the international palaeoecology research community and relevant policy practitioners. 4. The integration of online participation, both before and during the workshop, increased international engagement in question selection. 5. The questions selected are structured around six themes: human–environment interactions in the Anthropocene; biodiversity, conservation and novel ecosystems; biodiversity over long time-scales; ecosystem processes and biogeochemical cycling; comparing, combining and synthesizing information from multiple records; and new developments in palaeoecology. 6. Future opportunities in palaeoecology are related to improved incorporation of uncertainty into reconstructions, an enhanced understanding of ecological and evolutionary dynamics and processes and the continued application of long-term data for better-informed landscape management. 7. Synthesis. Palaeoecology is a vibrant and thriving discipline, and these 50 priority questions highlight its potential for addressing both pure (e.g. ecological and evolutionary, methodological) and applied (e.g. environmental and conservation) issues related to ecological science and global change.
Recent evidence suggests that depressive symptoms and hostility may act together, as interacting factors, to have an effect on the circulating levels of inflammatory markers relevant to coronary ...artery disease. Further research, however, is needed to clarify the nature of this interaction and to determine whether previous findings extend to older adults. In this report we examined the cross-sectional associations of depressive symptoms, hostility, and their interaction with circulating levels of two such inflammatory markers-interleukin-6 (IL-6) and C-reactive protein (CRP).
A total of 316 healthy, older adults underwent a blood draw for the assessment of serum IL-6 and CRP and completed the Beck Depression Inventory-II and the Cook-Medley Hostility Scale. Regression analyses were performed to examine depressive symptoms, hostility, and their interaction as predictors of serum IL-6 and CRP.
After adjustment for demographic factors, cardiovascular risk factors, and health behaviors, we detected depressive symptoms x hostility interactions for serum IL-6 (DeltaR(2) = .027, p < .01) and CRP (DeltaR(2) = .015, p < .05). Simple slope analyses revealed that hostility was positively related to serum IL-6 only among individuals with higher depressive symptoms. The pattern of results was similar for serum CRP, although none of the simple slopes was significant.
Our findings suggest that depressive symptoms may moderate the hostility-inflammation relationship such that hostility may augment inflammatory processes relevant to coronary artery disease only in the presence of depressive symptoms. Our results also extend previous findings from younger adults to older adults from the general community.
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