Genetic and Epigenetic Inheritance at Telomeres.

Transgenerational inheritance can occur at telomeres in distinct contexts. Deficiency for telomerase or telomere-binding proteins in germ cells can result in shortened or lengthened chromosome termini that are transmitted to progeny. In human families, altered telomere lengths can result in stem cell dysfunction or tumor development. Genetic inheritance of altered telomeres as well as mutations that alter telomeres can result in progressive telomere length changes over multiple generations. Telomeres of yeast can modulate the epigenetic state of subtelomeric genes in a manner that is mitotically heritable, and the effects of telomeres on subtelomeric gene expression may be relevant to senescence or other human adult-onset disorders. Recently, two novel epigenetic states were shown to occur at C. elegans telomeres, where very low or high levels of telomeric protein foci can be inherited for multiple generations through a process that is regulated by histone methylation.Together, these observations illustrate that information relevant to telomere biology can be inherited via genetic and epigenetic mechanisms, although the broad impact of epigenetic inheritance to human biology remains unclear.

Trends in Water Use, Energy Consumption, and Carbon Emissions from Irrigation: Role of Shifting Technologies and Energy Sources.

Novel low-pressure irrigation technologies have been widely adopted by farmers, allowing both reduced water and energy use. However, little is known about how the transition from legacy technologies affected water and energy use at the aquifer scale. Here, we examine the widespread adoption of low-energy precision application (LEPA) and related technologies across the Kansas High Plains Aquifer. We combine direct energy consumption and carbon emission estimates with life cycle assessment to calculate the energy and greenhouse gas (GHG) footprints of irrigation. We integrate detailed water use, irrigation type, and pump energy source data with aquifer water level and groundwater chemistry information to produce annual estimates of energy use and carbon emissions from 1994 to 2016. The rapid adoption of LEPA technologies did not slow pumping, but it reduced energy use by 19.2% and GHG emissions by 15.2%. Nevertheless, water level declines have offset energy efficiency gains because of LEPA adoption. Deeper water tables quadrupled the proportion of GHG emissions resulting from direct carbon emissions, offsetting the decarbonization of the regional electrical grid. We show that low-pressure irrigation technology adoption, absent policies that incentivize or mandate reduced water use, ultimately increases the energy and carbon footprints of irrigated agriculture.

Immune signatures associated with improved progression-free and overall survival for myeloma patients treated with AHSCT.

Multiple therapeutic options exist for multiple myeloma (MM), including autologous hematopoietic stem cell transplantation (AHSCT). Measurement of minimal residual disease (MRD) and immune reconstitution is rapidly becoming an integral part of the care of MM patients. We investigated comprehensive immune profiling (IP) associated with progression-free survival (PFS) and overall survival (OS). From August 2007 to January 2014, 101 consecutive MM patients underwent peripheral blood IP and marrow MRD testing before and approximately 100 days after AHSCT. Higher pre-AHSCT CD19+ B-cell counts correlated with improved 2-year PFS (83% [highest quartile] vs 53% [lowest quartile]; P = .01) and OS (93% [highest quartile] vs 63% [lowest quartile]; P = .0003). This effect was seen primarily in patients with MRD-positive marrow tests. Higher γδ T-cell counts post-AHSCT correlated with improved 2-year PFS (65% [highest quartile] vs 45% [lowest quartile]; P = .02) and OS (89% [highest quartile] vs 65% [lowest quartile]; P = .01). Higher CD4+ central memory (CM) cell counts post-AHSCT were associated with improved 2-year OS (95% [upper quartile] vs 47% [lowest quartile]; P = .0003) but not PFS. The higher γδ T-cell and CD4+ CM-cell count associations were primarily observed in MRD-negative patients post-AHSCT and in patients not receiving maintenance therapy. This proof-of-concept study demonstrates that IP before and after AHSCT can be of complementary prognostic value for depth of response. Maintenance therapy seems to overcome negative IP. IP and MRD should be measured in clinical trials of maintenance therapy with novel agents post-AHSCT for MM to confirm their utility for prognosis and management.