Green Prosperity: How Clean-Energy Policies Can Fight Poverty and Raise Living Standards in the United States

This study, co-commissioned by Natural Resources Defense Council and Green For All, considers the employment and other policy effects of a $150 billion annual investment in clean-energy specifically in terms of its ability to raise living standards for lower-income workers and families. This report shows that investments in clean energy can benefit lower-income families first by expanding job opportunities, and also by lowering household utility bills through energy efficiency investments and transportation costs by making public transportation more accessible. >> Read more about the study and download state and regional fact sheets here

Session 3: Digital Merrill

1:15 p.m. — Session 3: Digital Merrill Shannon Davis, digital library services manager, WU: The James Merrill Digital Archive: Process and Product Annelise Duerden, PhD candidate in English, WU — “Admit It Arguably A priori Admittedly I have failed”: Re-vision in the Merrill Archive Heidi Lim, PhD candidate in English, WU — To Tag or Not to Tag: The Digital Markup Process as a Form of Reading Timothy Materer, professor emeritus, University of Missouri — The Poem as a Netscap

Promoter targeted siRNAs induce transcriptional gene silencing (TGS) in Simian Immunodeficiency Virus (SIV)

RNA interference is a phenomenon by which double-stranded RNA is processed into small interfering RNAs (siRNAs) that can cause gene silencing in plants, yeast, Drosophila (fruit fly) and human cells. Small interfering double stranded RNAs (siRNAs) can induce gene silencing via two pathways: post-transcriptional gene silencing (PTGS) and transcriptional gene silencing (TGS). PTGS involves siRNA triggering of sequence- specific degradation of mRNA takes place in the cell's cytoplasm. In contrast, siRNAs, which induce TGS have sequence complementary to regions within a gene's promoter and the action happens in the nucleus and is associated with de novo methylation of CpG sites and histone methylation within the promoter region. Suziki et al. utilised siRNAs to target regions within 5'-long-terminal repeat (5'LTR) promoter region of human immunodeficiency virus-1 (HIV-1) and subsequently induce silencing of HIV-1 in HeLa cells. Here I recapitulate the previous findings in HIV-1 by showing that certain promoter-targeted siRNAs can also induce silencing of simian immunodeficiency virus (SIV) replication by inducing CpG methylation and epigenetic changes. A similar silencing effect was observed by using shRNA and miRNA mimics based on the most effective siRNAs. The shRNAs and miRNA mimics after conversion gained a PTGS effect in addition of TGS effect. The dual effect appeared to enhance the silencing efficiency. Here I show that the co-localisation of Ago1 and Ago2 with a TGS inducing siRNA (si2A) in nucleus and at the rim of the nucleus respectively in SIV infected cells but not in non-infected cells. The P-body protein, GW182 complexed with si2A was found in both the nucleus and nuclear envelope and was consistent with the location Ago1/si2A and Ago2/si2A complexes. This indicated a role for this protein in TGS together with Ago proteins. Using SIV 5'-LTR luciferase reporter cells, complexes containing Ago1/Ago2/si2A were showed to work in combination and provide the optimal suppression

"I think it is right": a qualitative exploration of the acceptability and desired future use of oral swab and finger-prick HIV self-tests by lay users in KwaZulu-Natal, South Africa.

The uptake of HIV testing has increased in sub-Saharan Africa over the past three decades. However, the proportion of people aware of their HIV status remains lower than required to change the pandemic. HIV self-testing (HIVST) may meet this gap. Assessment of readiness for and the acceptability of HIVST by lay users in South Africa is limited. This paper presents results from a formative study designed to assess the perceived usability and acceptability of HIVST among lay users using several self-test prototypes. Fifty lay users were purposively selected from rural and peri-urban KwaZulu-Natal, South Africa. Acceptability of HIVST was assessed using a simple post-test quantitative assessment tool addressing confidence, ease-of-use, intended future use and willingness to pay. In-depth qualitative interviews explored what participants felt about the HIVST and why, their willingness to recommend and how much they would pay for a test. The key finding is that there is high acceptability regardless of self-test prototype. Acceptability is framed by two domains: usability and perceived need. Perceived usability was explored through perceived ease of use, which, regardless of actual correct usage, was reported by many of the respondents. Acceptability is influenced by perceived need, expressed by many who felt that the need for the self-test to protect privacy and autonomy. Ease of access and widespread availability of the test, not at a significant cost, were also important factors. Many participants would recommend self-test use to others and also indicated that they would choose to conduct the test again if it was free while some also indicated being willing to buy a test. The positive response and readiness amongst lay users for an HIVST in this context prototype suggests that there would be a ready and willing market for HIVST. For scalability and sustainability usability, including access and availability that are here independent indications of acceptability, should be considered. So too should the desire for future use, as an additional factor pointing to acceptability. The results show high acceptability in all of these areas domains and a general interest in HIVST amongst lay users in a community in KwaZulu-Natal

Moving towards a cure in genetics : what is needed to bring somatic gene therapy to the clinic?

Clinical trials using somatic gene editing (e.g., CRISPR-Cas9) have started in Europe and the United States and may provide safe and effective treatment and cure, not only for cancers but also for some monogenic conditions. In a workshop at the 2018 European Human Genetics Conference, the challenges of bringing somatic gene editing therapies to the clinic were discussed. The regulatory process needs to be considered early in the clinical development pathway to produce the data necessary to support the approval by the European Medicines Agency. The roles and responsibilities for geneticists may include counselling to explain the treatment possibilities and safety interpretation.Peer reviewe

Oceans across the solar system and the search for extraoceanic life: technologies for remote sensing and in situ exploration

Earth’s ocean comprises 99% of the habitable volume of our planet and contains the largest biomass and species diversity in the known universe. Perhaps unsurprisingly, recent advances in the search for life elsewhere in our solar system have increasingly pointed to potentially viable niches for life on other dynamic ocean worlds such as Titan, Europa, and Enceladus, among other moons of the outer gas giants. Indeed, the discovery of extraterrestrial life on these icy water bodies may motivate adopting an altogether new terminology and further non-anthropic perspective on the cosmos. Extraoceanic life, to coin a term, may well prove to be a designation more representative of the abundance and diversity of life in space. Exploration of such ocean worlds across the solar system will undoubtedly be enabled by technological developments in a range of sensing methodologies primarily developed for oceanography on Earth. As we have learned studying our home ocean, where less than 10% of the benthic surface has been optically imaged, the challenge is daunting, yet recent advances give hope. Here, we review some of the state-of-the-art techniques from oceanography and planetary science that may inform sensing of the biological and geophysical properties of ocean worlds, ranging from large-scale synoptic views afforded by active and passive remote sensing to in situ autonomous sampling and methods for detecting biosignatures

Integrins and ERp57 Coordinate to Regulate Cell Surface Calreticulin in Immunogenic Cell Death

Therapy-induced presentation of cell surface calreticulin (CRT) is a pro-phagocytic immunogen beneficial for invoking anti-tumor immunity. Here, we characterized the roles of ERp57 and α-integrins as CRT-interacting proteins that coordinately regulate CRT translocation from the ER to the surface during immunogenic cell death. Using T-lymphoblasts as a genetic cell model, we found that drug-induced surface CRT is dependent on ERp57, while drug-induced surface ERp57 is independent of CRT. Differential subcellular immunostaining assays revealed that ERp57−/− cells have minimal cytosolic CRT, indicating that ERp57 is indispensable for extra-ER accumulation of CRT. Stimulation of integrin activity, with either cell adhesion or molecular agonists, resulted in decreased drug-induced surface CRT and ERp57 levels. Similarly, surface CRT and ERp57 was reduced in cells expressing GFFKR, a conserved α-integrin cytosolic motif that binds CRT. Drug-induced surface ERp57 levels were consistently higher in CRT−/− cells, suggesting integrin inhibition of surface ERp57 is an indirect consequence of α-integrin binding to CRT within the CRT-ERp57 complex. Furthermore, β1−/− cells with reduced expression of multiple α-integrins, exhibit enhanced levels of drug-induced surface CRT and ERp57. Our findings highlight the coordinate involvement of plasma membrane integrins as inhibitors, and ERp57 originating from the ER as promoters, of CRT translocation from the ER to the cell surface

Enzymatic, urease-mediated mineralization of gellan gum hydrogel with calcium carbonate, magnesium-enriched calcium carbonate and magnesium carbonate for bone regeneration applications.

Mineralization of hydrogel biomaterials is considered desirable to improve their suitability as materials for bone regeneration. Calcium carbonate (CaCO3) has been successfully applied as a bone regeneration material, but hydrogel‐CaCO3 composites have received less attention. Magnesium (Mg) has been used as a component of calcium phosphate biomaterials to stimulate bone‐forming cell adhesion and proliferation and bone regeneration in vivo, but its effect as a component of carbonate‐based biomaterials remains uninvestigated. In the present study, gellan gum (GG) hydrogels were mineralized enzymatically with CaCO3, Mg‐enriched CaCO3 and magnesium carbonate to generate composite biomaterials for bone regeneration. Hydrogels loaded with the enzyme urease were mineralized by incubation in mineralization media containing urea and different ratios of calcium and magnesium ions. Increasing the magnesium concentration decreased mineral crystallinity. At low magnesium concentrations calcite was formed, while at higher concentrations magnesian calcite was formed. Hydromagnesite (Mg5(CO3)4(OH)2.4H2O) formed at high magnesium concentration in the absence of calcium. The amount of mineral formed and compressive strength decreased with increasing magnesium concentration in the mineralization medium. The calcium:magnesium elemental ratio in the mineral formed was higher than in the respective mineralization media. Mineralization of hydrogels with calcite or magnesian calcite promoted adhesion and growth of osteoblast‐like cells. Hydrogels mineralized with hydromagnesite displayed higher cytotoxicity. In conclusion, enzymatic mineralization of GG hydrogels with CaCO3 in the form of calcite successfully reinforced hydrogels and promoted osteoblast‐like cell adhesion and growth, but magnesium enrichment had no definitive positive effect

Direct evidence of nuclear Argonaute distribution during transcriptional silencing links the actin cytoskeleton to nuclear RNAi machinery in human cells

Mammalian RNAi machinery facilitating transcriptional gene silencing (TGS) is the RNA-induced transcriptional gene silencing-like (RITS-like) complex, comprising of Argonaute (Ago) and small interfering RNA (siRNA) components. We have previously demonstrated promoter-targeted siRNA induce TGS in human immunodeficiency virus type-1 (HIV-1) and simian immunodeficiency virus (SIV), which profoundly suppresses retrovirus replication via heterochromatin formation and histone methylation. Here, we examine subcellular co-localization of Ago proteins with promoter-targeted siRNAs during TGS of SIV and HIV-1 infection. Analysis of retrovirus-infected cells revealed Ago1 co-localized with siRNA in the nucleus, while Ago2 co-localized with siRNA in the inner nuclear envelope. Mismatched and scrambled siRNAs were observed in the cytoplasm, indicating sequence specificity. This is the first report directly visualizing nuclear compartment distribution of Ago-associated siRNA and further reveals a novel nuclear trafficking mechanism for RITS-like components involving the actin cytoskeleton. These results establish a model for elucidating mammalian TGS and suggest a fundamental mechanism underlying nuclear delivery of RITS-like components

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015:a systematic analysis for the Global Burden of Disease Study 2015

Published by Elsevier Ltd. This is an Open Access article under the CC BY license.Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden