Simulated responses of soil carbon to climate change in CMIP6 Earth system models: the role of false priming

This is the final version. Available from Copernicus Publications / European Geosciences Union via the DOI in this record. The CMIP data analysed during this study are available online: CMIP6 (https://esgf-node.llnl.gov/search/cmip6/, last access: 8 April 2022) and CMIP5 (https://esgf-node.llnl.gov/search/cmip5/, last access: 12 April 2022).Code is available on GitHub (https://github.com/rebeccamayvarney/CMIP6_dCs, last access: 28 July 2023).Reliable estimates of soil carbon change are required to determine the carbon budgets consistent with the Paris Agreement climate targets. This study evaluates projections of soil carbon during the 21st century in Coupled Model Intercomparison Project Phase 6 (CMIP6) Earth system models (ESMs) under a range of atmospheric composition scenarios. In general, we find a reduced spread of changes in global soil carbon (ΔCs) in CMIP6 compared to the previous CMIP5 model generation. However, similar reductions were not seen in the derived contributions to ΔCs due to both increases in plant net primary productivity (NPP, named ΔCs,NPP) and reductions in the effective soil carbon turnover time (τs, named ΔCs,τ). Instead, we find a strong relationship across the CMIP6 models between these NPP and τs components of ΔCs, with more positive values of ΔCs,NPP being correlated with more negative values of ΔCs,τ. We show that the concept of “false priming” is likely to be contributing to this emergent relationship, which leads to a decrease in the effective soil carbon turnover time as a direct result of NPP increase and occurs when the rate of increase in NPP is relatively fast compared to the slower timescales of a multi-pool soil carbon model. This finding suggests that the structure of soil carbon models within ESMs in CMIP6 has likely contributed towards the reduction in the overall model spread in future soil carbon projections since CMIP5.European Union’s Horizon 2020European Union’s Horizon 202

Inequalities, harm reduction and non-combustible nicotine products:A meta-ethnography of qualitative evidence

BACKGROUND: We sought to review qualitative evidence on how smokers in different socioeconomic groups engage with non-combustible nicotine products (NCNP), including electronic cigarettes and nicotine replacement therapies, in order to provide insight into how these products might impact on smoking inequalities. METHODS: We searched ten electronic databases in February 2017 using terms relating to NCNP and socioeconomic status. We included qualitative studies that were published since 1980 and were available in English. We used guidelines adapted from the Critical Appraisal Skills Programme for appraising qualitative research. RESULTS: The review only identified studies exploring the attitudes of socioeconomically disadvantaged smokers towards NCNP for harm reduction or cessation purposes (i.e. we did not identify any relevant studies of more advantaged socioeconomic groups). Using a lines-of-argument meta-ethnographic approach, we identified a predominantly pessimistic attitude to NCNP for harm reduction or cessation of smoking due to: wider circumstances of socioeconomic disadvantage; lack of a perceived advantage of alternative products over smoking; and a perceived lack of information about relative harms of NCNP compared to smoking. Optimistic findings, although fewer, suggested the potential of NCNP being taken up among smokers experiencing socioeconomic disadvantage. CONCLUSIONS: Overall, our review highlights the importance of considering the social, cultural and economic circumstances that influence experiences of smoking and of alternative product use

Identification of the Plasmodium berghei resistance locus 9 linked to survival on chromosome 9

Background: One of the main causes of mortality from severe malaria in Plasmodium falciparum infections is cerebral malaria (CM). An important host genetic component determines the susceptibility of an individual to develop CM or to clear the infection and become semi-immune. As such, the identification of genetic loci associated with susceptibility or resistance may serve to modulate disease severity. Methodology The Plasmodium berghei mouse model for experimental cerebral malaria (ECM) reproduces several disease symptoms seen in human CM, and two different phenotypes, a susceptible (FVB/NJ) and a resistant mouse strain (DBA/2J), were examined. Results: FVB/NJ mice died from infection within ten days, whereas DBA/2J mice showed a gender bias: males survived on average nineteen days and females either died early with signs of ECM or survived for up to three weeks. A comparison of brain pathology between FVB/NJ and DBA/2J showed no major differences with regard to brain haemorrhages or the number of parasites and CD3+ cells in the microvasculature. However, significant differences were found in the peripheral blood of infected mice: For example resistant DBA/2J mice had significantly higher numbers of circulating basophils than did FVB/NJ mice on day seven. Analysis of the F2 offspring from a cross of DBA/2J and FVB/NJ mice mapped the genetic locus of the underlying survival trait to chromosome 9 with a Lod score of 4.9. This locus overlaps with two previously identified resistance loci (char1 and pymr) from a blood stage malaria model. Conclusions: Survival best distinguishes malaria infections between FVB/NJ and DBA/2J mice. The importance of char1 and pymr on chromosome 9 in malaria resistance to P. berghei was confirmed. In addition there was an association of basophil numbers with survival

Systematic characterization of deubiquitylating enzymes for roles in maintaining genome integrity.

DNA double-strand breaks (DSBs) are perhaps the most toxic of all DNA lesions, with defects in the DNA-damage response to DSBs being associated with various human diseases. Although it is known that DSB repair pathways are tightly regulated by ubiquitylation, we do not yet have a comprehensive understanding of how deubiquitylating enzymes (DUBs) function in DSB responses. Here, by carrying out a multidimensional screening strategy for human DUBs, we identify several with hitherto unknown links to DSB repair, the G2/M DNA-damage checkpoint and genome-integrity maintenance. Phylogenetic analyses reveal functional clustering within certain DUB subgroups, suggesting evolutionally conserved functions and/or related modes of action. Furthermore, we establish that the DUB UCHL5 regulates DSB resection and repair by homologous recombination through protecting its interactor, NFRKB, from degradation. Collectively, our findings extend the list of DUBs promoting the maintenance of genome integrity, and highlight their potential as therapeutic targets for cancer.This is the author's accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ncb302

Allotment gardening and health: a comparative survey among allotment gardeners and their neighbors without an allotment

<p>Abstract</p> <p>Background</p> <p>The potential contribution of allotment gardens to a healthy and active life-style is increasingly recognized, especially for elderly populations. However, few studies have empirically examined beneficial effects of allotment gardening. In the present study the health, well-being and physical activity of older and younger allotment gardeners was compared to that of controls without an allotment.</p> <p>Methods</p> <p>A survey was conducted among 121 members of 12 allotment sites in the Netherlands and a control group of 63 respondents without an allotment garden living next to the home addresses of allotment gardeners. The survey included five self-reported health measures (perceived general health, acute health complaints, physical constraints, chronic illnesses, and consultations with GP), four self-reported well-being measures (stress, life satisfaction, loneliness, and social contacts with friends) and one measure assessing self-reported levels of physical activity in summer. Respondents were divided into a younger and older group at the median of 62 years which equals the average retirement age in the Netherlands.</p> <p>Results</p> <p>After adjusting for income, education level, gender, stressful life events, physical activity in winter, and access to a garden at home as covariates, both younger and older allotment gardeners reported higher levels of physical activity during the summer than neighbors in corresponding age categories. The impacts of allotment gardening on health and well-being were moderated by age. Allotment gardeners of 62 years and older scored significantly or marginally better on all measures of health and well-being than neighbors in the same age category. Health and well-being of younger allotment gardeners did not differ from younger neighbors. The greater health and well-being benefits of allotment gardening for older gardeners may be related to the finding that older allotment gardeners were more oriented towards gardening and being active, and less towards passive relaxation.</p> <p>Conclusions</p> <p>These findings are consistent with the notion that having an allotment garden may promote an active life-style and contribute to healthy aging. However, the findings may be limited by self selection and additional research is needed to confirm and extend the current findings.</p

Positional Cloning of “Lisch-like”, a Candidate Modifier of Susceptibility to Type 2 Diabetes in Mice

In 404 Lepob/ob F2 progeny of a C57BL/6J (B6) x DBA/2J (DBA) intercross, we mapped a DBA-related quantitative trait locus (QTL) to distal Chr1 at 169.6 Mb, centered about D1Mit110, for diabetes-related phenotypes that included blood glucose, HbA1c, and pancreatic islet histology. The interval was refined to 1.8 Mb in a series of B6.DBA congenic/subcongenic lines also segregating for Lepob. The phenotypes of B6.DBA congenic mice include reduced β-cell replication rates accompanied by reduced β-cell mass, reduced insulin/glucose ratio in blood, reduced glucose tolerance, and persistent mild hypoinsulinemic hyperglycemia. Nucleotide sequence and expression analysis of 14 genes in this interval identified a predicted gene that we have designated “Lisch-like” (Ll) as the most likely candidate. The gene spans 62.7 kb on Chr1qH2.3, encoding a 10-exon, 646–amino acid polypeptide, homologous to Lsr on Chr7qB1 and to Ildr1 on Chr16qB3. The largest isoform of Ll is predicted to be a transmembrane molecule with an immunoglobulin-like extracellular domain and a serine/threonine-rich intracellular domain that contains a 14-3-3 binding domain. Morpholino knockdown of the zebrafish paralog of Ll resulted in a generalized delay in endodermal development in the gut region and dispersion of insulin-positive cells. Mice segregating for an ENU-induced null allele of Ll have phenotypes comparable to the B.D congenic lines. The human ortholog, C1orf32, is in the middle of a 30-Mb region of Chr1q23-25 that has been repeatedly associated with type 2 diabetes

The expansion field: The value of H_0

Any calibration of the present value of the Hubble constant requires recession velocities and distances of galaxies. While the conversion of observed velocities into true recession velocities has only a small effect on the result, the derivation of unbiased distances which rest on a solid zero point and cover a useful range of about 4-30 Mpc is crucial. A list of 279 such galaxy distances within v<2000 km/s is given which are derived from the tip of the red-giant branch (TRGB), from Cepheids, and from supernovae of type Ia (SNe Ia). Their random errors are not more than 0.15 mag as shown by intercomparison. They trace a linear expansion field within narrow margins from v=250 to at least 2000 km/s. Additional 62 distant SNe Ia confirm the linearity to at least 20,000 km/s. The dispersion about the Hubble line is dominated by random peculiar velocities, amounting locally to <100 km/s but increasing outwards. Due to the linearity of the expansion field the Hubble constant H_0 can be found at any distance >4.5 Mpc. RR Lyr star-calibrated TRGB distances of 78 galaxies above this limit give H_0=63.0+/-1.6 at an effective distance of 6 Mpc. They compensate the effect of peculiar motions by their large number. Support for this result comes from 28 independently calibrated Cepheids that give H_0=63.4+/-1.7 at 15 Mpc. This agrees also with the large-scale value of H_0=61.2+/-0.5 from the distant, Cepheid-calibrated SNe Ia. A mean value of H_0=62.3+/-1.3 is adopted. Because the value depends on two independent zero points of the distance scale its systematic error is estimated to be 6%. Typical errors of H_0 come from the use of a universal, yet unjustified P-L relation of Cepheids, the neglect of selection bias in magnitude-limited samples, or they are inherent to the adopted models.Comment: 44 pages, 4 figures, 6 tables, accepted for publication in the Astronony and Astrophysics Review 15

SRA Regulates Adipogenesis by Modulating p38/JNK Phosphorylation and Stimulating Insulin Receptor Gene Expression and Downstream Signaling

The Steroid Receptor RNA Activator (SRA) enhances adipogenesis and increases both glucose uptake and phosphorylation of Akt and FOXO1 in response to insulin. To assess the mechanism, we differentiated ST2 mesenchymal precursor cells that did or did not overexpress SRA into adipocytes using combinations of methylisobutylxanthine, dexamethasone and insulin. These studies showed that SRA overexpression promotes full adipogenesis in part by stimulation of insulin/insulin-like growth factor-1 (IGF-1) signaling. SRA overexpression inhibited phosphorylation of p38 mitogen activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) in the early differentiation of ST2 cells. Conversely, knockdown of endogenous SRA in 3T3-L1 cells increased phosphorylation of JNK. Knockdown of SRA in mature 3T3-L1 adipocytes reduced insulin receptor (IR) mRNA and protein levels, which led to decreased autophosphorylation of IRβ and decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt. This likely reflects a stimulatory role of SRA on IR transcription, as transfection studies showed that SRA increased expression of an IR promoter-luciferase reporter construct