Politics, ecology, and the new anthropology of energy: exploring the emerging frontiers of hydraulic fracking

This article reviews recent literature relevant to the ongoing shale gas boom and introduces the Journal of Political Ecology's Special Section on hydraulic fracking. We highlight the need for ethnographic studies of the tumultuous social and physical transformations resulting from, and produced by, an unfolding frontier of energy production that unsettles social, economic, and ecological landscapes. We examine how intercommunity connections are vital to recognizing the shared structural conditions produced by the oil and gas industry's expansion, through examining the roles played by the oil field services industry, the sequestration of information and agnotology (the deliberate production of ignorance), divide and conquer tactics, and shared experiences of risk and embodied effects. Summarizing the contributions of the five articles included in the Special Section, we offer recommendations for further inquiry. We examine how social science studies of hydraulic fracking are producing new and innovative methodologies for developing participatory academic and community research projects. Key words: digital media, embodiment, energy, hydraulic fracturing, oil field services industry, shale ga

Ascl1 phospho-status regulates neuronal differentiation in a Xenopus developmental model of neuroblastoma.

Neuroblastoma (NB), although rare, accounts for 15% of all paediatric cancer mortality. Unusual among cancers, NBs lack a consistent set of gene mutations and, excluding large-scale chromosomal rearrangements, the genome seems to be largely intact. Indeed, many interesting features of NB suggest that it has little in common with adult solid tumours but instead has characteristics of a developmental disorder. NB arises overwhelmingly in infants under 2 years of age during a specific window of development and, histologically, NB bears striking similarity to undifferentiated neuroblasts of the sympathetic nervous system, its likely cells of origin. Hence, NB could be considered a disease of development arising when neuroblasts of the sympathetic nervous system fail to undergo proper differentiation, but instead are maintained precociously as progenitors with the potential for acquiring further mutations eventually resulting in tumour formation. To explore this possibility, we require a robust and flexible developmental model to investigate the differentiation of NB's presumptive cell of origin. Here, we use Xenopus frog embryos to characterise the differentiation of anteroventral noradrenergic (AVNA) cells, cells derived from the neural crest. We find that these cells share many characteristics with their mammalian developmental counterparts, and also with NB cells. We find that the transcriptional regulator Ascl1 is expressed transiently in normal AVNA cell differentiation but its expression is aberrantly maintained in NB cells, where it is largely phosphorylated on multiple sites. We show that Ascl1's ability to induce differentiation of AVNA cells is inhibited by its multi-site phosphorylation at serine-proline motifs, whereas overexpression of cyclin-dependent kinases (CDKs) and MYCN inhibit wild-type Ascl1-driven AVNA differentiation, but not differentiation driven by a phospho-mutant form of Ascl1. This suggests that the maintenance of ASCL1 in its multiply phosphorylated state might prevent terminal differentiation in NB, which could offer new approaches for differentiation therapy in NB.This work was supported by a grant from the UK Neuroblastoma Society (A.P., L.A.W. and T.D.P.). C.J.T. and L.A.W. are supported by the intramural research program of the National Cancer Institute, National Institutes of Health. L.A.W. is an NIH-OxCam Scholar. L.J.A.H. is supported by a UK Medical Research Council Doctoral Training Award.This is the final version of the article. It first appeared from The Company of Biologists via http://dx.doi.org/10.1242/dmm.01863

Ageing well with diabetes: A workshop to co‐design research recommendations for improving the diabetes care of older people

Aims:To identify key research questions where answers could improve care for older people living with diabetes (PLWD), and provide detailed recommendations for researchers and research funders on how best to address them.Methods:A series of online research workshops were conducted, bringing together a range of PLWD and an acknowledged group of academic and clinical experts in their diabetes care to identify areas for future research. Throughout the pre-workshop phase, during each workshop, and in manuscript preparation and editing, PLWD played an active and dynamic role in discussions as part of both an iterative and narrative process.Results:The following key questions in this field were identified, and research recommendations for each were developed:How can we improve our understanding of the characteristics of older people living with diabetes (PLWD) and their outcomes, and can this deliver better person-centred care?How are services to care for older PLWD currently delivered, both for their diabetes and other conditions? How can we optimise and streamline the process and ensure everyone gets the best care, tailored to their individual needs?What tools might be used to evaluate the level of understanding of diabetes in the older population amongst non-specialist Healthcare Professionals (HCPs)?How can virtual experts or centres most effectively provide access to specialist multi-disciplinary team (MDT) expertise for older PLWD and the HCPs caring for them?Is a combination of exercise and a nutrition-dense, high protein diet effective in the prevention of the adverse effects of type 2 diabetes and deterioration in frailty, and how might this be delivered in a way which is acceptable to people with type 2 diabetes?How might we best use continuous glucose monitoring (CGM) in older people and, for those who require support, how should the data be shared?How can older PLWD be better empowered to manage their diabetes in their own home, particularly when living with additional long-term conditions?What are the benefits of models of peer support for older PLWD, both when living independently and when in care?Conclusions:This paper outlines recommendations supported by PLWD through which new research could improve their diabetes care and calls on the research community and funders to address them in future research programmes and strategies

Dephosphorylation of the Proneural Transcription Factor ASCL1 Re-Engages a Latent Post-Mitotic Differentiation Program in Neuroblastoma.

Pediatric cancers often resemble trapped developmental intermediate states that fail to engage the normal differentiation program, typified by high-risk neuroblastoma arising from the developing sympathetic nervous system. Neuroblastoma cells resemble arrested neuroblasts trapped by a stable but aberrant epigenetic program controlled by sustained expression of a core transcriptional circuit of developmental regulators in conjunction with elevated MYCN or MYC (MYC). The transcription factor ASCL1 is a key master regulator in neuroblastoma and has oncogenic and tumor-suppressive activities in several other tumor types. Using functional mutational approaches, we find that preventing CDK-dependent phosphorylation of ASCL1 in neuroblastoma cells drives coordinated suppression of the MYC-driven core circuit supporting neuroblast identity and proliferation, while simultaneously activating an enduring gene program driving mitotic exit and neuronal differentiation. IMPLICATIONS: These findings indicate that targeting phosphorylation of ASCL1 may offer a new approach to development of differentiation therapies in neuroblastoma. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/18/12/1759/F1.large.jpg.Work was supported by Cancer Research UK Programme Grant RG91505 (AP), Wellcome Trust Investigator Award 212253/Z/18/Z (AP), MRC Research Grant MR/L021129/1 (F.A, A.P); Neuroblastoma UK (D.M, T.P, A.P), CRUK Cambridge Centre Paediatric Programme (L.P), The Terry Fox Foundation (FA), MBRU College of Medicine Internal grant award MBRU-CM-RG2019-14 (FA), MBRU-ALMAHMEED Collaborative Research Award ALM1909 (FA) and core support from the Wellcome Trust and the MRC Cambridge Stem Cell Institute (F.A, D.M, J.D., A.P.) and Cancer Research UK Cambridge Insititute (I.C, J.C)

Forty years of Landscape research

Papers of four decades published in Landscape Research are reviewed in order to chronicle the journal’s development and to assess the academic performance of the journal relative to its own aims. Landscape Research intends to reach a wide audience, to have a broad thematic coverage and to publish different types of papers with various methodological orientations. Cutting across these first aims are the interdisciplinary ambition of the journal, and its overall focus on landscape. These aims are evaluated based upon categorisation of article content, authorship and methodology, using data derived through interpretative inquiry and quantitative analyses. The results tell the story of how Landscape Research has developed from a newsletter of the Landscape Research Group, mainly aimed at practitioners, into an interdisciplinary, international journal with academic researchers as its primary community of interest. The final section discusses the current profile of the journal and identifies issues for its future direction and development

Twenty questions about design behavior for sustainability, report of the International Expert Panel on behavioral science for design

How behavioral scientists, engineers, and architects can work together to advance how we all understand and practice design—in order to enhance sustainability in the built environment, and beyond.https://www.nature.com/documents/design_behavior_for_sustainability.pdfPublished versio

Cyclic strain induces dualmode endothelial-mesenchymal transformation of the cardiac valve

Endothelial-mesenchymal transformation (EMT) is a critical event for the embryonic morphogenesis of cardiac valves. Inducers of EMT during valvulogenesis include VEGF, TGF-β1, and wnt/β-catenin (where wnt refers to the wingless-type mammary tumor virus integration site family of proteins), that are regulated in a spatiotemporal manner. EMT has also been observed in diseased, strain-overloaded valve leaflets, suggesting a regulatory role for mechanical strain. Although the preponderance of studies have focused on the role of soluble mitogens, we asked if the valve tissue microenvironment contributed to EMT. To recapitulate these microenvironments in a controlled, in vitro environment, we engineered 2D valve endothelium from sheep valve endothelial cells, using microcontact printing to mimic the regions of isotropy and anisotropy of the leaflet, and applied cyclic mechanical strain in an attempt to induce EMT. We measured EMT in response to both low (10%) and high strain (20%), where low-strain EMT occurred via increased TGF-β1 signaling and high strain via increased wnt/β-catenin signaling, suggesting dual strain-dependent routes to distinguish EMT in healthy versus diseased valve tissue. The effect was also directionally dependent, where cyclic strain applied orthogonal to axis of the engineered valve endothelium alignment resulted in severe disruption of cell microarchitecture and greater EMT. Once transformed, these tissues exhibited increased contractility in the presence of endothelin-1 and larger basal mechanical tone in a unique assay developed to measure the contractile tone of the engineered valve tissues. This finding is important, because it implies that the functional properties of the valve are sensitive to EMT. Our results suggest that cyclic mechanical strain regulates EMT in a strain magnitude and directionally dependent manner. tight junctions | cytokines | activated myofibroblast C ardiac valves are sophisticated structures that function in a complex mechanical environment, opening and closing more than 3 billion times during the average human lifetime (1). Initially considered passive flaps of tissue, it is now acknowledged that valves contain a highly heterogeneous population of endothelial (VEC) and interstitial (VIC) cells. The VICs exist as synthetic, myofibroblast, or smooth muscle-like phenotypes (2, 3) and alter their tone in response to vasoactive mediators (4-7). The VECs line the surface of the valve leaflet and are unique in their ability to undergo endothelial-mesenchymal transformation (EMT), a process that is crucial for valvulogenesis (8, 9). Recent clinical evidence of EMT has been observed in pathologies such as ischemic cardiomyopathy and concomitant mitral regurgitation and is correlated with increased leaflet mechanical strains (10, 11). These pathological strains can be oriented obliquely to cell and tissue orientation (12, 13), suggesting the possible interaction between mechanical forces and tissue architecture in regulating EMT. Prior work has focused on the regulation of EMT via soluble factors. Modulation of VEGF and increases in wnt/β-catenin and TGF-β1 expression, among other factors, direct EMT during valvulogenesis (8, 14) and in the mature valve (15, 16). Additionally, mechanical forces are known to modulate valve remodeling and disease progression (17, 18). However, the influence of mechanical forces and its synergy with tissue architecture in influencing cardiac valve EMT is unknown. During embryonic development, valve morphogenesis has been correlated with an increase in fluid shear stresses, mechanical strains, and altered geometry of the developing heart (19-22). These observations potentially suggests interaction between mechanical forces and the factors that regulate EMT. Additionally, it is also unknown if EMT results in a functional change of the VEC to a contractile myofibroblast-like VIC. We hypothesized that cyclic strain may potentiate valve EMT in a manner dependent on cell orientation and the direction of applied strain. We developed an in vitro model that combines cyclic stretching of engineered valve endothelium reconstituted from primary sheep VECs for biochemical and expression studies. In addition, we present a functional assay for EMT using valve thin films (vTFs), a biohybrid construct of the engineered valve endothelium on an elastomer thin film that is deformed during tissue contraction. We report strain-dependent dual-mode EMT, with TGF-β1 signaling triggering EMT under low strain (10%) and wnt/β-catenin signaling under high strain (20%). We also report strain-dependent increased contractility of transformed VEC tissues when treated with endothelin-1, suggesting transformation of the normally noncontractile VEC to a contractile VIC-like cell

COVID-19 Risk Factors for Cancer Patients: A First Report with Comparator Data from COVID-19 Negative Cancer Patients

none32siSimple SummaryThe COVID-19 pandemic has had a detrimental impact on cancer patients globally. Whilst there are several studies looking at the potential risk factors for COVID-19 disease and related death, most of these include non-cancerous patients as the COVID-19 negative comparator group, meaning it is difficult to draw hard conclusions as to the implications for cancer patients. In our study, we utilized data from over 2000 cancer patients from a large tertiary Cancer Centre in London. In summary, our study found that patients who are male, of Black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19. The use of cancer patients as the COVID-19 negative comparator group is a major advantage to the study as it means we can better understand the true impact of COVID-19 on cancer patients and identify which factors pose the biggest risk to their likelihood of infection with SARS-CoV2.Very few studies investigating COVID-19 in cancer patients have included cancer patients as controls. We aimed to identify factors associated with the risk of testing positive for SARS CoV2 infection in a cohort of cancer patients. We analyzed data from all cancer patients swabbed for COVID-19 between 1(st) March and 31(st) July 2020 at Guy's Cancer Centre. We conducted logistic regression analyses to identify which factors were associated with a positive COVID-19 test. Results: Of the 2152 patients tested for COVID-19, 190 (9%) tested positive. Male sex, black ethnicity, and hematological cancer type were positively associated with risk of COVID-19 (OR = 1.85, 95%CI:1.37-2.51; OR = 1.93, 95%CI:1.31-2.84; OR = 2.29, 95%CI:1.45-3.62, respectively) as compared to females, white ethnicity, or solid cancer type, respectively. Male, Asian ethnicity, and hematological cancer type were associated with an increased risk of severe COVID-19 (OR = 3.12, 95%CI:1.58-6.14; OR = 2.97, 95%CI:1.00-8.93; OR = 2.43, 95%CI:1.00-5.90, respectively). This study is one of the first to compare the risk of COVID-19 incidence and severity in cancer patients when including cancer patients as controls. Results from this study have echoed those of previous reports, that patients who are male, of black or Asian ethnicity, or with a hematological malignancy are at an increased risk of COVID-19.openRussell, Beth; Moss, Charlotte L; Palmer, Kieran; Sylva, Rushan; D'Souza, Andrea; Wylie, Harriet; Haire, Anna; Cahill, Fidelma; Steel, Renee; Hoyes, Angela; Wilson, Isabelle; Macneil, Alyson; Shifa, Belul; Monroy-Iglesias, Maria J; Papa, Sophie; Irshad, Sheeba; Ross, Paul; Spicer, James; Kordasti, Shahram; Crawley, Danielle; Zaki, Kamarul; Sita-Lumsden, Ailsa; Josephs, Debra; Enting, Deborah; Swampillai, Angela; Sawyer, Elinor; Fields, Paul; Wrench, David; Rigg, Anne; Sullivan, Richard; Van Hemelrijck, Mieke; Dolly, SaoirseRussell, Beth; Moss, Charlotte L; Palmer, Kieran; Sylva, Rushan; D'Souza, Andrea; Wylie, Harriet; Haire, Anna; Cahill, Fidelma; Steel, Renee; Hoyes, Angela; Wilson, Isabelle; Macneil, Alyson; Shifa, Belul; Monroy-Iglesias, Maria J; Papa, Sophie; Irshad, Sheeba; Ross, Paul; Spicer, James; Kordasti, Shahram; Crawley, Danielle; Zaki, Kamarul; Sita-Lumsden, Ailsa; Josephs, Debra; Enting, Deborah; Swampillai, Angela; Sawyer, Elinor; Fields, Paul; Wrench, David; Rigg, Anne; Sullivan, Richard; Van Hemelrijck, Mieke; Dolly, Saoirs

Applying Recovery Biomarkers to Calibrate Self-Report Measures of Energy and Protein in the Hispanic Community Health Study/Study of Latinos

We investigated measurement error in the self-reported diets of US Hispanics/Latinos, who are prone to obesity and related comorbidities, by background (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American) in 2010–2012. In 477 participants aged 18–74 years, doubly labeled water and urinary nitrogen were used as objective recovery biomarkers of energy and protein intakes. Self-report was captured from two 24-hour dietary recalls. All measures were repeated in a subsample of 98 individuals. We examined the bias of dietary recalls and their associations with participant characteristics using generalized estimating equations. Energy intake was underestimated by 25.3% (men, 21.8%; women, 27.3%), and protein intake was underestimated by 18.5% (men, 14.7%; women, 20.7%). Protein density was overestimated by 10.7% (men, 11.3%; women, 10.1%). Higher body mass index and Hispanic/Latino background were associated with underestimation of energy (P < 0.05). For protein intake, higher body mass index, older age, nonsmoking, Spanish speaking, and Hispanic/Latino background were associated with underestimation (P < 0.05). Systematic underreporting of energy and protein intakes and overreporting of protein density were found to vary significantly by Hispanic/Latino background. We developed calibration equations that correct for subject-specific error in reporting that can be used to reduce bias in diet-disease association studies