Heterogeneity of genomic evolution and mutational profiles in multiple myeloma

Multiple myeloma is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Here we use whole-exome sequencing, copy-number profiling and cytogenetics to analyse 84 myeloma samples. Most cases have a complex subclonal structure and show clusters of subclonal variants, including subclonal driver mutations. Serial sampling reveals diverse patterns of clonal evolution, including linear evolution, differential clonal response and branching evolution. Diverse processes contribute to the mutational repertoire, including kataegis and somatic hypermutation, and their relative contribution changes over time. We find heterogeneity of mutational spectrum across samples, with few recurrent genes. We identify new candidate genes, including truncations of SP140, LTB, ROBO1 and clustered missense mutations in EGR1. The myeloma genome is heterogeneous across the cohort, and exhibits diversity in clonal admixture and in dynamics of evolution, which may impact prognostic stratification, therapeutic approaches and assessment of disease response to treatment

A decentralized approach to model national and global food and land use systems

The achievement of several sustainable development goals and the Paris Climate Agreement depends on rapid progress towards sustainable food and land systems in all countries. We have built a flexible, collaborative modeling framework to foster the development of national pathways by local research teams and their integration up to global scale. Local researchers independently customize national models to explore mid-century pathways of the food and land use system transformation in collaboration with stakeholders. An online platform connects the national models, iteratively balances global exports and imports, and aggregates results to the global level. Our results show that actions toward greater sustainability in countries could sum up to 1 Mha net forest gain per year, 950 Mha net gain in the land where natural processes predominate, and an increased CO2 sink of 3.7 GtCO2e yr−1 over the period 2020–2050 compared to current trends, while average food consumption per capita remains above the adequate food requirements in all countries. We show examples of how the global linkage impacts national results and how different assumptions in national pathways impact global results. This modeling setup acknowledges the broad heterogeneity of socio-ecological contexts and the fact that people who live in these different contexts should be empowered to design the future they want. But it also demonstrates to local decision-makers the interconnectedness of our food and land use system and the urgent need for more collaboration to converge local and global priorities

Sex Differences in the Age of Diagnosis for Cardiovascular Disease and Its Risk Factors Among US Adults: Trends From 2008 to 2017, the Medical Expenditure Panel Survey

Background Sex differences in the trends for control of cardiovascular disease (CVD) risk factors have been described, but temporal trends in the age at which CVD and its risk factors are diagnosed and sex-specific differences in these trends are unknown. Methods and Results We used the Medical Expenditure Panel Survey 2008 to 2017, a nationally representative sample of the US population. Individuals ≥18 years, with a diagnosis of hypercholesterolemia, hypertension, coronary heart disease, or stroke, and who reported the age when these conditions were diagnosed, were included. We included 100 709 participants (50.2% women), representing 91.9 million US adults with above conditions. For coronary heart disease and hypercholesterolemia, mean age at diagnosis was 1.06 and 0.92 years older for women, compared with men, respectively (both P<0.001). For stroke, mean age at diagnosis for women was 1.20 years younger than men (P<0.001). The mean age at diagnosis of CVD risk factors became younger over time, with steeper declines among women (annual decrease, hypercholesterolemia [women, 0.31 years; men 0.24 years] and hypertension [women, 0.23 years; men, 0.20 years]; P<0.001). Coronary heart disease was not statistically significant. For stroke, while age at diagnosis decreased by 0.19 years annually for women (P=0.03), it increased by 0.22 years for men (P=0.02). Conclusions The trend in decreasing age at diagnosis for CVD and its risk factors in the United States appears to be more pronounced among women. While earlier identification of CVD risk factors may provide opportunity to initiate preventive treatment, younger age at diagnosis of CVD highlights the need for the prevention of CVD earlier in life, and sex-specific interventions may be needed.Open access journalThis 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]

Effect of elevated CO2 on the dynamics of particle-attached and free-living bacterioplankton communities in an Arctic fjord

The increase in atmospheric carbon dioxide (CO2) results in acidification of the oceans, expected to lead to the fastest drop in ocean pH in the last 300 million years, if anthropogenic emissions are continued at present rate. Due to higher solubility of gases in cold waters and increased exposure to the atmosphere by decreasing ice cover, the Arctic Ocean will be among the areas most strongly affected by ocean acidification. Yet, the response of the plankton community of high latitudes to ocean acidification has not been studied so far. This work is part of the Arctic campaign of the European Project on Ocean Acidification (EPOCA) in 2010, employing 9 in situ mesocosms of about 45 000 l each to simulate ocean acidification in Kongsfjorden, Svalbard (78°56.2' N 11°53.6' E). In the present study, we investigated effects of elevated CO2 on the composition and richness of particle attached (PA; >3 μm) and free living (FL; 0.2 μm) bacterial communities by Automated Ribosomal Intergenic Spacer Analysis (ARISA) in 6 of the mesocosms and the surrounding fjord, ranging from 185 to 1050 initial μatm pCO2. ARISA was able to resolve about 20–30 bacterial band-classes per sample and allowed for a detailed investigation of the explicit richness. Both, the PA and the FL bacterioplankton community exhibited a strong temporal development, which was driven mainly by temperature and phytoplankton development. In response to the breakdown of a picophytoplankton bloom (phase 3 of the experiment), number of ARISA-band classes in the PA-community were reduced at low and medium CO2 (∼180–600 μatm) by about 25%, while it was more or less stable at high CO2 (∼ 650–800 μatm). We hypothesise that enhanced viral lysis and enhanced availability of organic substrates at high CO2 resulted in a more diverse PA-bacterial community in the post-bloom phase. Despite lower cell numbers and extracellular enzyme activities in the post-bloom phase, bacterial protein production was enhanced in high CO2-treatments, suggesting a positive effect of community richness on this function and on carbon cycling by bacteria