Emissions savings from equitable energy demand reduction

Energy demand reduction (EDR) will be required to reach climate targets in the Global North. To be compatible with just transitions principles, EDR needs to be equitable. Equitable EDR may involve targeting high energy users while ensuring the satisfaction of needs for all, which could require increasing consumption of low users. Emissions impacts of equitable EDR approaches have not yet been assessed. This Article finds that capping energy use of the top quintile of consumers across 27 European countries can achieve considerable greenhouse gas emissions reductions of 11.4% from domestic energy, 16.8% from transport and 9.7% from total energy consumption. Increasing consumption of low energy users in poverty reduces these savings by only 1.2, 0.9 and 1.4 percentage points, respectively. Additional high annual emissions cuts of 7.3–24.0% would be required for Europe to meet globally equitable 2050 emissions budgets. Equitable EDR could make an important contribution to increasing public acceptance of such transformative action

Proteomic evidence of biological aging in a child with a compound heterozygous ZMPSTE24 mutation

Background: Progeria-like syndromes offer a unique insight into ageing. Here we present the case of a boy affected with mandibuloacral dysplasia and compound heterozygous mutations in ZMPSTE24. Methods: Capillary electrophoresis-mass spectroscopy was used for proteome analysis to analyse peptides previously found to be differentially regulated in chronic kidney disease (273 peptides defining the CKD273 classifier), coronary artery disease (238 peptides defining the CAD238 classifier) and ageing (116 peptides defining the AGE116 classifier). Results: No evidence of renal disease was identified. Although the boy has no overt cardiovascular disease other than a raised carotid intima media thickness relative to his age, a proteomic classifier for the diagnosis of coronary artery disease was mildly raised. The biological age based on the proteomic AGE116 classifier was 24 years compared to the chronological ages of 5 and 10 years. In contrast, a control group of healthy children had a significantly lower (p<0.0001) calculated mean age of 13. Conclusion: Urinary proteomic analysis is effective in confirming advanced biological age and to identify early evidence of renal or cardiovascular damage. Our case highlights the value of proteomic approaches in ageing research and may represent a method for non-invasive monitoring of the effects of early ageing

Oxidation of Alpha-Ketoglutarate Is Required for Reductive Carboxylation in Cancer Cells with Mitochondrial Defects

SummaryMammalian cells generate citrate by decarboxylating pyruvate in the mitochondria to supply the tricarboxylic acid (TCA) cycle. In contrast, hypoxia and other impairments of mitochondrial function induce an alternative pathway that produces citrate by reductively carboxylating α-ketoglutarate (AKG) via NADPH-dependent isocitrate dehydrogenase (IDH). It is unknown how cells generate reducing equivalents necessary to supply reductive carboxylation in the setting of mitochondrial impairment. Here, we identified shared metabolic features in cells using reductive carboxylation. Paradoxically, reductive carboxylation was accompanied by concomitant AKG oxidation in the TCA cycle. Inhibiting AKG oxidation decreased reducing equivalent availability and suppressed reductive carboxylation. Interrupting transfer of reducing equivalents from NADH to NADPH by nicotinamide nucleotide transhydrogenase increased NADH abundance and decreased NADPH abundance while suppressing reductive carboxylation. The data demonstrate that reductive carboxylation requires bidirectional AKG metabolism along oxidative and reductive pathways, with the oxidative pathway producing reducing equivalents used to operate IDH in reverse

Energy demand for everyday mobility and domestic life: Exploring the justice implications

The consumption of energy services for everyday mobility and domestic life is a fundamental pre-condition for participating in many contemporary societies, but it can also impact upon current and future generations in ways that raise questions of equity and fairness. Whilst the field of ‘energy justice’ has become more established in recent years, much work remains to be done to further this area of study. In this lead article for a Special Issue on ‘Energy demand for mobility and domestic life: new insights from energy justice’, we begin by outlining the many interlocking issues of (in)justice raised by energy consumption for mobility and domestic services, identifying gaps in the current literature. We then describe the articles within the Special Issue, discussing these in relation to three themes: uneven access to energy and transport services; the unequal burdens of low-carbon policies; and reducing energy demand and the good society. We conclude by highlighting potential directions for future research; for example, conceptualising ‘excessive’ consumption as an issue of (in)justice, and identifying low-energy social practices and arrangements that simultaneously contribute to human well-being

Transport poverty and fuel poverty in the UK: From analogy to comparison

The notion of ’fuel poverty’, referring to affordable warmth, underpins established research and policy agendas in the UK and has been extremely influential worldwide. In this context, British researchers, official policymaking bodies and NGOs have put forward the notion of ’transport poverty’, building on an implicit analogy between (recognised) fuel poverty and (neglected) transport affordability issues. However, the conceptual similarities and differences between ’fuel’ and ’transport’ poverty remain largely unaddressed in the UK. This paper systematically compares and contrasts the two concepts, examining critically the assumption of a simple equivalence between them. We illustrate similarities and differences under four headings: (i) negative consequences of lack of warmth and lack of access; (ii) drivers of fuel and transport poverty; (iii) definition and measurement; (iv) policy interventions. Our review suggests that there are important conceptual and practical differences between transport and domestic energy consumption, with crucial consequences for how affordability problems amongst households are to be conceptualised and addressed. In a context where transport and energy exhibit two parallel policy worlds, the analysis in the paper and these conclusions reinforce how and why these differences matter. As we embark on an ever closer union between our domestic energy and transport energy systems the importance of these contradictions will become increasingly evident and problematic. This work contributes to the long-term debate about how best to manage these issues in a radical energy transition that properly pays attention to issues of equity and affordability

Enrichment of CpG island shore region hypermethylation in epigenetic breast field cancerization

While changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumour DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumour. Matched tumour, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select epithelial cells from normal tissue, and neoplastic cells from tumour for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array. We identified substantially more CpG loci that were differentially methylated between contralateral-normal and tumour (63,271 CpG loci q \u3c 0.01), than between ipsilateral-normal and tumour (38,346 CpG loci q \u3c 0.01). We identified differential methylation in ipsilateral-normal relative to contralateral-normal tissue (9,562 CpG loci p \u3c 0.01). In this comparison, hypomethylated loci were significantly enriched for breast cancer-relevant transcription factor binding sites including those for ESR1, FoxA1, and GATA3 and hypermethylated loci were significantly enriched for CpG island shore regions. In addition, progression of shore hypermethylation was observed in tumours compared to matched ipsilateral normal tissue, and these alterations tracked to several well-established tumour suppressor genes. Our results indicate an epigenetic field effect in surrounding histologically normal tissue. This work offers an opportunity to focus investigations of early DNA methylation alterations in breast carcinogenesis and potentially develop epigenetic biomarkers of disease risk

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

“Breaking up is hard to do”: the formation and resolution of sister chromatid intertwines

The absolute necessity to resolve every intertwine between the two strands of the DNA double helix provides a massive challenge to the cellular processes that duplicate and segregate chromosomes. Although the overwhelming majority of intertwines between the parental DNA strands are resolved during DNA replication, there are numerous chromosomal contexts where some intertwining is maintained into mitosis. These mitotic sister chromatid intertwines (SCIs) can be found as; short regions of unreplicated DNA, fully replicated and intertwined sister chromatids—commonly referred to as DNA catenation—and as sister chromatid linkages generated by homologous recombination-associated processes. Several overlapping mechanisms, including intra-chromosomal compaction, topoisomerase action and Holliday junction resolvases, ensure that all SCIs are removed before they can prevent normal chromosome segregation. Here, I discuss why some DNA intertwines persist into mitosis and review our current knowledge of the SCI resolution mechanisms that are employed in both prokaryotes and eukaryotes, including how deregulating SCI formation during DNA replication or disrupting the resolution processes may contribute to aneuploidy in cancer

Study design and participant characteristics of a randomized controlled trial of directly administered antiretroviral therapy in opioid treatment programs

<p>Abstract</p> <p>Background</p> <p>HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIV-infected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression.</p> <p>Methods/Design</p> <p>We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm³, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve.</p> <p>Conclusions</p> <p>This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00279110">NCT00279110</a></p

Vulnerability to fuel price increases in the UK: A household level analysis

In highly motorised countries, some sectors of the population own and use cars despite struggling to afford their running costs, and so may be particularly vulnerable to motor fuel prices increases, whether market-led or policy-driven. This paper proposes a novel, disaggregated approach to investigating vulnerability to such increases at the household level. We propose a set of indicators of ‘car-related economic stress’ (CRES), based on individual household level expenditure data for the UK, to identify which low-income households spend disproportionately on running motor vehicles, and to assess the depth of their economic stress. By subsequently linking the dataset to local fuel price data, we are able to model the disaggregated price elasticities of car fuel demand. This provides us with an indicator of each households’ adaptive capacity to fuel price increases. The findings show that ‘Low-Income, High Cost’ households (LIHC) account for 9% of UK households and have distinct socio-demographic characteristics. Interestingly, they are characterised by very low responses to fuel price increases, which may cause them to compromise on other important areas of their household expenditures. Simulations suggest that a 20% increase in fuel prices would substantially increase the depth, but not the incidence of CRES. Overall, the study sheds light on a sector of the population with high levels of vulnerability to fuel price increases, owing to high exposure, high sensitivity and low adaptive capacity. This raises challenges for social, environmental and resilience policy in the transport sector