Estimating changes in temperature extremes from millennial scale climate simulations using generalized extreme value (GEV) distributions

Changes in extreme weather may produce some of the largest societal impacts of anthropogenic climate change. However, it is intrinsically difficult to estimate changes in extreme events from the short observational record. In this work we use millennial runs from the CCSM3 in equilibrated pre-industrial and possible future conditions to examine both how extremes change in this model and how well these changes can be estimated as a function of run length. We estimate changes to distributions of future temperature extremes (annual minima and annual maxima) in the contiguous United States by fitting generalized extreme value (GEV) distributions. Using 1000-year pre-industrial and future time series, we show that the magnitude of warm extremes largely shifts in accordance with mean shifts in summertime temperatures. In contrast, cold extremes warm more than mean shifts in wintertime temperatures, but changes in GEV location parameters are largely explainable by mean shifts combined with reduced wintertime temperature variability. In addition, changes in the spread and shape of the GEV distributions of cold extremes at inland locations can lead to discernible changes in tail behavior. We then examine uncertainties that result from using shorter model runs. In principle, the GEV distribution provides theoretical justification to predict infrequent events using time series shorter than the recurrence frequency of those events. To investigate how well this approach works in practice, we estimate 20-, 50-, and 100-year extreme events using segments of varying lengths. We find that even using GEV distributions, time series that are of comparable or shorter length than the return period of interest can lead to very poor estimates. These results suggest caution when attempting to use short observational time series or model runs to infer infrequent extremes.Comment: 33 pages, 22 figures, 1 tabl

Genome Phylogenies Indicate a Meaningful a-Proteobacterial Phylogeny and Support a Grouping of the Mitochondria with the Rickettsiales

Placement of the mitochondrial branch on the tree of life has been problematic. Sparse sampling, the uncertainty of how lateral gene transfer might overwrite phylogenetic signals, and the uncertainty of phylogenetic inference have all contributed to the issue. Here we address this issue using a supertree approach and completed genomic sequences. We first determine that a sensible a-proteobacterial phylogenetic tree exists and that it can confidently be inferred using orthologous genes. We show that congruence across these orthologous gene trees is significantly better than might be expected by random chance. There is some evidence of horizontal gene transfer within the a-proteobacteria, but it appears to be restricted to a minority of genes (;23%) most of whom (;74%) can be categorized as operational. This means that placement of the mitochondrion should not be excessively hampered by interspecies gene transfer. We then show that there is a consistently strong signal for placement of the mitochondrion on this tree and that this placement is relatively insensitive to methodological approach or data set. A concatenated alignment was created consisting of 15 mitochondrion-encoded proteins that are unlikely to have undergone any lateral gene transfer in the timeline under consideration. This alignment infers that the sister group of the mitochondria, for the taxa that have been sampled, is the order Rickettsiales

Generalizability of achievement goal profiles across five cultural groups : more similarities than differences

Previous results have shown possible cultural differences in students’ achievement goals endorsement and in their relations with various predictors and outcomes. In this person-centered study, we sought to identify achievement goal profiles and to assess the extent to which these configurations and their associations with predictors and outcomes generalize across cultures. We used a new statistical approach to assess latent profile similarities across adolescents from five cultural backgrounds (N = 2643, including Non-Indigenous Australians, Indigenous Australians, Indigenous American, Middle Easterners, and Asians). Our results supported the cross-cultural generalizability of the profiles, their predictors, and their outcomes. Five similar profiles were identified in each cultural group, but their relative frequency differed across cultures. The results revealed advantages of exploring multidimensional goal profiles

Safeguarding sandalwood: A review of current and emerging tools to support sustainable and legal forestry

Societal Impact Statement: Sandalwood and other high value tree species are under significant threat from illegal harvest. Illegal logging is an increasing problem contributing to deforestation, biodiversity loss, human rights abuses and funding transnational crime. Successful prosecution of illegal logging is hindered by a lack of methods to provide evidence of the origin of timber. New analytical techniques have been developed to trace timber back to its source. These methods, together with the establishment of sustainable sources of forest resources, can help protect vulnerable species by providing evidence to prosecute illegal harvest and ensure that commercially available forest products come from sustainable sources. Summary: Sandalwood is highly valued for its fragrant oil and has a long history of cultural and economic importance in many regions of the world. Historical overharvest and poor management have depleted natural populations of sandalwood, which are slow to regenerate. The increasing establishment of plantation sandalwood creates an alternative resource for the sandalwood industry while potentially relieving harvesting pressure on natural stands. Due to the high demand for sandalwood, remaining wild populations are still under threat from illegal logging and methods to identify the source of harvested sandalwood are needed. Laws and regulations aimed at preventing illegal harvest and possession of sandalwood have been put in place but cannot be enforced without the forensic tools to independently verify claimed origin or product quality. The high value of sandalwood combined with the difficulties in enforcing illegal logging laws makes these species particularly vulnerable to poaching. There is an immediate need to develop tools that can identify illegally sourced and adulterated sandalwood products. This paper reviews the current and developing scientific tools that can help identify and control illegal activity in sandalwood supply chains and provides recommendations for future research. Topics include isotope and DNA analysis for tracing illegally harvested sandalwood, chemical profiling for quality control of sandalwood oils, network and policy development to establish a framework for future regulation of the sandalwood trade

Autophagic flux blockage by accumulation of weakly basic tenovins leads to elimination of B-Raf mutant tumour cells that survive vemurafenib

This work was supported by five grants to Sonia Laín: Vetenskapsrådet (VR) 521-2014-3341, Cancerfonden (Swedish Cancer Society) 150393, CAN 2014/702, Association for International Cancer Research (AICR) 130086, Barncancerfonden (Swedish Childhood Cancer Foundation) TJ-2014-0038, Barncancerfonden (Swedish Childhood Cancer Foundation) PR-2014-0038; two grants to Ravi Bhatia: Leukemia and Lymphoma Society (LLS) 6137-14 and NIH R01 CA95684; one grant to David P Lane: Vetenskapsrådet (VR) 538-2013-8807; one grant to Marcus J G W Ladds: Karolinska Institute KID Doctoral Student Funding; one grant to Gergana Popova: Karolinska Institutet KID Doctoral Student Funding; two grants to Nicholas J Westwood: Cancer Research UK C21383 and Cancer Research UK A6950; two grants to Gerald McInerney: Vetenskapsrådet (VR) 621-2014-4718 and Cancerfonden (Swedish Cancer Society) 150393, CAN 2015/751; and four grants to Emmet McCormack: Kreftforeningen 182735, Kreftforeningen 732200, Halse Vest 911884, Halse Vest 911789.Tenovin-6 is the most studied member of a family of small molecules with antitumour activity in vivo. Previously, it has been determined that part of the effects of tenovin-6 associate with its ability to inhibit SirT1 and activate p53. However, tenovin-6 has also been shown to modulate autophagic flux. Here we show that blockage of autophagic flux occurs in a variety of cell lines in response to certain tenovins, that autophagy blockage occurs regardless of the effect of tenovins on SirT1 or p53, and that this blockage is dependent on the aliphatic tertiary amine side chain of these molecules. Additionally, we evaluate the contribution of this tertiary amine to the elimination of proliferating melanoma cells in culture. We also demonstrate that the presence of the tertiary amine is sufficient to lead to death of tumour cells arrested in G1 phase following vemurafenib treatment. We conclude that blockage of autophagic flux by tenovins is necessary to eliminate melanoma cells that survive B-Raf inhibition and achieve total tumour cell kill and that autophagy blockage can be achieved at a lower concentration than by chloroquine. This observation is of great relevance as relapse and resistance are frequently observed in cancer patients treated with B-Raf inhibitors.Publisher PDFPeer reviewe

Implementation of the StandingTall programme to prevent falls in older people:a process evaluation protocol

INTRODUCTION: One in three people aged 65 years and over fall each year. The health, economic and personal impact of falls will grow substantially in the coming years due to population ageing. Developing and implementing cost-effective strategies to prevent falls and mobility problems among older people is therefore an urgent public health challenge. StandingTall is a low-cost, unsupervised, home-based balance exercise programme delivered through a computer or tablet. StandingTall has a simple user-interface that incorporates physical and behavioural elements designed to promote compliance. A large randomised controlled trial in 503 community-dwelling older people has shown that StandingTall is safe, has high adherence rates and is effective in improving balance and reducing falls. The current project targets a major need for older people and will address the final steps needed to scale this innovative technology for widespread use by older people across Australia and internationally. METHODS AND ANALYSIS: This project will endeavour to recruit 300 participants across three sites in Australia and 100 participants in the UK. The aim of the study is to evaluate the implementation of StandingTall into the community and health service settings in Australia and the UK. The nested process evaluation will use both quantitative and qualitative methods to explore uptake and acceptability of the StandingTall programme and associated resources. The primary outcome is participant adherence to the StandingTall programme over 6 months. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the South East Sydney Local Health District Human Research Ethics Committee (HREC reference 18/288) in Australia and the North West- Greater Manchester South Research Ethics Committee (IRAS ID: 268954) in the UK. Dissemination will be via publications, conferences, newsletter articles, social media, talks to clinicians and consumers and meetings with health departments/managers. TRIAL REGISTRATION NUMBER: ACTRN12619001329156

A stable genetic polymorphism underpinning microbial syntrophy

Syntrophies are metabolic cooperations, whereby two organisms co-metabolize a substrate in an interdependent manner. Many of the observed natural syntrophic interactions are mandatory in the absence of strong electron acceptors, such that one species in the syntrophy has to assume the role of electron sink for the other. While this presents an ecological setting for syntrophy to be beneficial, the potential genetic drivers of syntrophy remain unknown to date. Here, we show that the syntrophic sulfate-reducing species Desulfovibrio vulgaris displays a stable genetic polymorphism, where only a specific genotype is able to engage in syntrophy with the hydrogenotrophic methanogen Methanococcus maripaludis. This 'syntrophic' genotype is characterized by two genetic alterations, one of which is an in-frame deletion in the gene encoding for the ion-translocating subunit cooK of the membrane-bound COO hydrogenase. We show that this genotype presents a specific physiology, in which reshaping of energy conservation in the lactate oxidation pathway enables it to produce sufficient intermediate hydrogen for sustained M. maripaludis growth and thus, syntrophy. To our knowledge, these findings provide for the first time a genetic basis for syntrophy in nature and bring us closer to the rational engineering of syntrophy in synthetic microbial communities