Epigenetic Strategies to Boost Cancer Immunotherapies

The CNIO- Lilly Epigenetics Laboratory is supported by Eli Lilly and Company.Recently, immunotherapeutic approaches have shown impressive responses in a subset of cancer patients. However, the rate of success is low and a large percentage of treated patients do not experience clinical benefits. Therefore, additional strategies are needed to improve responses and select responsive patients. Emerging data suggest that epigenetic drugs can improve the responses to immunotherapy. Understanding the mechanisms of resistance to immunotherapy and the epigenetic events that take place during immune evasion is critical to providing a rational combined use of immunotherapies and epigenetic drugs. This review focuses in the epigenetic mechanisms involved in the responses to immunotherapy and how current drugs that target epigenetic regulators impact on them.S

Long Social Distancing

More than ten percent of Americans with recent work experience say they will continue social distancing after the COVID-19 pandemic ends, and another 45 percent will do so in limited ways. We uncover this Long Social Distancing phenomenon in our monthly Survey of Working Arrangements and Attitudes. It is more common among older persons, women, the less educated, those who earn less, and in occupations and industries that require many face-to-face encounters. People who intend to continue social distancing have lower labor force participation—unconditionally, and conditional on demographics and other controls. Regression models that relate outcomes to intentions imply that Long Social Distancing reduced participation by 2.5 percentage points in the first half of 2022. Separate self-assessed causal effects imply a reduction of 2.0 percentage points. The impact on the earnings-weighted participation rate is smaller at about 1.4 percentage points. This drag on participation reduces potential output by nearly one percent and shrinks the college wage premium. Economic reasoning and evidence suggest that Long Social Distancing and its effects will persist for many months or years

Why working from home will stick

COVID-19 drove a mass social experiment in working from home (WFH). We survey more than 30,000 Americans over multiple waves to investigate whether WFH will stick, and why. Our data say that 20 percent of full workdays will be supplied from home after the pandemic ends, compared with just 5 percent before. We develop evidence on five reasons for this large shift: better-than-expected WFH experiences, new investments in physical and human capital that enable WFH, greatly diminished stigma associated with WFH, lingering concerns about crowds and contagion risks, and a pandemic-driven surge in technological innovations that support WFH. We also use our survey data to project three consequences: First, employees will enjoy large benefits from greater remote work, especially those with higher earnings. Second, the shift to WFH will directly reduce spending in major city centers by at least 5-10 percent relative to the pre-pandemic situation. Third, our data on employer plans and the relative productivity of WFH imply a 5 percent productivity boost in the post-pandemic economy due to re-optimized working arrangements. Only one-fifth of this productivity gain will show up in conventional productivity measures, because they do not capture the time savings from less commuting

Internet access and its implications for productivity, inequality and resilience

About one-fifth of paid workdays will be supplied from home in the post-pandemic economy, and more than one-fourth on an earnings-weighted basis. In view of this projection, we consider some implications of home internet access quality, exploiting data from the new Survey of Working Arrangements and Attitudes. Moving to high-quality, fully reliable home internet service for all Americans ('universal access') would raise earnings-weighted labor productivity by an estimated 1.1% in the coming years. The implied output gains are $160 billion per year, or$4 trillion when capitalized at a 4% rate. Estimated flow output payoffs to universal access are nearly three times as large in economic disasters like the COVID-19 pandemic. Our survey data also say that subjective well-being was higher during the pandemic for people with better home internet service conditional on age, employment status, earnings, working arrangements, and other controls. In short, universal access would raise productivity, and it would promote greater economic and social resilience during future disasters that inhibit travel and in-person interactions

A role for jasmonates in the release of dormancy by cold stratification in wheat

Hydration at low temperatures, commonly referred to as cold stratification, is widely used for releasing dormancy and triggering germination in a wide range of species including wheat. However, the molecular mechanism that underlies its effect on germination has largely remained unknown. Our previous studies showed that methyl-jasmonate, a derivative of jasmonic acid (JA), promotes dormancy release in wheat. In this study, we found that cold-stimulated germination of dormant grains correlated with a transient increase in JA content and expression of JA biosynthesis genes in the dormant embryos after transfer to 20 (o)C. The induction of JA production was dependent on the extent of cold imbibition and precedes germination. Blocking JA biosynthesis with acetylsalicylic acid (ASA) inhibited the cold-stimulated germination in a dose-dependent manner. In addition, we have explored the relationship between JA and abscisic acid (ABA), a well-known dormancy promoter, in cold regulation of dormancy. We found an inverse relationship between JA and ABA content in dormant wheat embryos following stratification. ABA content decreased rapidly in response to stratification, and the decrease was reversed by addition of ASA. Our results indicate that the action of JA on cold-stratified grains is mediated by suppression of two key ABA biosynthesis genes, TaNCED1 and TaNCED2.This project was funded by a CSIRO Office of the Chief Executive PDF scheme

Arquitectura española moderna y contemporánea

[ES] En este trabajo se pretende analizar y contextualizar el grupo de viviendas de la calle Santa María Micaela de Valencia (1958), obra de Santiago Artal, para conocer cuál fue su aportación a la modernidad española. Para ello, se establece un análisis comparativo partiendo de la base de datos y libros de los registros DOCOMOMO Ibérico, una fundación orientada a inventariar, divulgar y proteger el patrimonio arquitectónico del Movimiento Moderno. Entre todos los ejemplos de arquitectura residencial inventariados en DOCOMOMO se selecciona para la comparación el grupo residencial Escorial de Barcelona (1952) y el grupo residencial Milans del Bosch (1962), también en Barcelona. Ambos conjuntos son claros ejemplos de cómo abrir la manzana, uno de los puntos a destacar en el grupo de Santiago Artal.Barrero Mateo, JA. (2019). Arquitectura española moderna y contemporánea. http://hdl.handle.net/10251/139184TFG

ALTERED MERISTEM PROGRAM 1 Is involved in Development of Seed Dormancy in Arabidopsis

Mutants in the rice PLASTOCHRON 3 and maize VIVIPAROUS 8 genes have been shown to have reduced dormancy and ABA levels. In this study we used several mutants in the orthologous gene ALTERED MERISTEM PROGRAM 1 (AMP1) to determine its role in seed dormancy in Arabidopsis. Here we report that there are accession-specific effects of mutations in AMP1. In one accession, amp1 mutants produce seeds with higher dormancy, while those in two other accessions produce seeds of lower dormancy. These accession-specific effects of mutating AMP1 were shown to extend to ABA levels. We assayed global gene transcription differences in seeds of wild-type and mutant from two accessions demonstrating opposing phenotypes. The transcript changes observed indicate that the amp1 mutation shifts the seed transcriptome from a dormant into an after-ripened state. Specific changes in gene expression in the mutants give insight into the direct and indirect effects that may be contributing to the opposing dormancy phenotypes observed, and reveal a role for AMP1 in the acquisition and/or maintenance of seed dormancy in Arabidopsis

The shift to remote work lessens wage-growth pressure

The recent shift to remote work raised the amenity value of employment. As compensation adjusts to share the amenity-value gains with employers, wage-growth pressures moderate. We find empirical support for this mechanism in the wage-setting behavior of U.S. employers, and we develop novel survey data to quantify its force. Our data imply a cumulative wage-growth moderation of 2.0 percentage points over two years. This moderation offsets more than half the real-wage catchup effect that Blanchard (2022) highlights in his analysis of near-term inflation pressures. The amenity-values gains associated with the recent rise of remote work also lower Labor's share of national income by 1.1 percentage points. In addition, the 'unexpected compression' of wages since early 2020 (Autor and Dube, 2022) is partly explained by the same amenity-value effect, which operates differentially across the earnings distribution