International Targets for Poverty Reduction and Food Security: A Mildly Sceptical But Resolutely Pragmatic View With a Call for Greater Subsidiarity

Summaries International development targets adopted by UN Conferences provide political impetus, focus expenditure and help in monitoring progress. However, simple targets can misrepresent complex realities and distort policy. Monitoring targets can have a high opportunity cost. Political impetus can be lost if targets are over?ambitious. Food security illustrates the uses of targets and the risks involved. Simple hunger or nutrition targets have been attractive to policymakers but have been problematic conceptually, and routinely overambitious in practice. Greater subsidiarity may be the answer, with simple international targets being used as a platform for local action. Subsidiarity means more than developing national action plans to implement international targets: it is potentially more open, participatory subversive and deviant

Altruism can proliferate through group/kin selection despite high random gene flow

The ways in which natural selection can allow the proliferation of cooperative behavior have long been seen as a central problem in evolutionary biology. Most of the literature has focused on interactions between pairs of individuals and on linear public goods games. This emphasis led to the conclusion that even modest levels of migration would pose a serious problem to the spread of altruism in group structured populations. Here we challenge this conclusion, by analyzing evolution in a framework which allows for complex group interactions and random migration among groups. We conclude that contingent forms of strong altruism can spread when rare under realistic group sizes and levels of migration. Our analysis combines group-centric and gene-centric perspectives, allows for arbitrary strength of selection, and leads to extensions of Hamilton's rule for the spread of altruistic alleles, applicable under broad conditions.Comment: 5 pages, 2 figures. Supplementary material with 50 pages and 26 figure

First semi-empirical test of the white dwarf mass-radius relationship using a single white dwarf via astrometric microlensing

Funding: Support for this research was provided by NASA through grants from STScI. HST data used in this paper are available from the Mikulski Archive for Space Telescopes at STScI (https://archive.stsci.edu/hst/search.php) under proposal IDs 15705, 15961 and 16251. PM acknowledges studentship funding support from the United Kingdom Science and Technology Facilities Council (STFC) and the Cambridge Centre for Doctoral Training in Data Intensive Science (CDT-DIS). MBN acknowledges support from the UK Space Agency. This research is based on observations made with the NASA/ESA Hubble Space Telescope obtained from the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5–26555. This work presents results from the European Space Agency (ESA) space mission Gaia. Gaia data are being processed by the Gaia Data Processing and Analysis Consortium (DPAC). Funding for the DPAC is provided by national institutions, in particular the institutions participating in the Gaia Multi-Lateral Agreement (MLA). The Gaia mission website is https://www.cosmos.esa.int/gaia. The Gaia Archive website is http://archives.esac.esa.int/gaia.In November 2019 the nearby single, isolated DQ-type white dwarf LAWD 37 (LP 145-141) aligned closely with a distant background source and caused an astrometric microlensing event. Leveraging astrometry from Gaia and followup data from the Hubble Space Telescope we measure the astrometric deflection of the background source and obtain a gravitational mass for LAWD 37. The main challenge of this analysis is in extracting the lensing signal of the faint background source whilst it is buried in the wings of LAWD 37's point spread function. Removal of LAWD 37's point spread function induces a significant amount of correlated noise which we find can mimic the astrometric lensing signal. We find a deflection model including correlated noise caused by the removal of LAWD 37's point spread function best explains the data and yields a mass for LAWD 37 of 0.56 ± 0.08 M ⊙. This mass is in agreement with the theoretical mass-radius relationship and cooling tracks expected for CO core white dwarfs. Furthermore, the mass is consistent with no or trace amounts of hydrogen that is expected for objects with helium-rich atmospheres like LAWD 37. We conclude that further astrometric followup data on the source is likely to improve the inference on LAWD 37's mass at the ≈3 percent level and definitively rule out purely correlated noise explanations of the data. This work provides the first semi-empirical test of the white dwarf mass-radius relationship using a single, isolated white dwarf and supports current model atmospheres of DQ white dwarfs and white dwarf evolutionary theory.PreprintPostprintPeer reviewe

Mycorrhizas and biomass crops: opportunities for future sustainable development

Central to soil health and plant productivity in natural ecosystems are in situ soil microbial communities, of which mycorrhizal fungi are an integral component, regulating nutrient transfer between plants and the surrounding soil via extensive mycelial networks. Such networks are supported by plant-derived carbon and are likely to be enhanced under coppiced biomass plantations, a forestry practice that has been highlighted recently as a viable means of providing an alternative source of energy to fossil fuels, with potentially favourable consequences for carbon mitigation. Here, we explore ways in which biomass forestry, in conjunction with mycorrhizal fungi, can offer a more holistic approach to addressing several topical environmental issues, including ‘carbon-neutral’ energy, ecologically sustainable land management and CO2 sequestration

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Advanced molecular pathology for rare tumours: A national feasibility study and model for centralised medulloblastoma diagnostics

Aims: Application of advanced molecular pathology in rare tumours is hindered by low sample numbers, access to specialised expertise/technologies and tissue/assay QC and rapid reporting requirements. We assessed the feasibility of co-ordinated real-time centralised pathology review (CPR), encompassing molecular diagnostics and contemporary genomics (RNA-seq/DNA methylation-array). Methods: This nationwide trial in medulloblastoma (<80 UK diagnoses/year) introduced a national reference centre (NRC) and assessed its performance and reporting to World Health Organisation standards. Paired frozen/formalin-fixed, paraffin-embedded tumour material were co-submitted from 135 patients (16 referral centres). Results: Complete CPR diagnostics were successful for 88% (120/135). Inadequate sampling was the most common cause of failure; biomaterials were typically suitable for methylation-array (129/135, 94%), but frozen tissues commonly fell below RNA-seq QC requirements (53/135, 39%). Late reporting was most often due to delayed submission. CPR assigned or altered histological variant (vs local diagnosis) for 40/135 tumours (30%). Benchmarking/QC of specific biomarker assays impacted test results; fluorescent in-situ hybridisation most accurately identified high-risk MYC/MYCN amplification (20/135, 15%), while combined methods (CTNNB1/chr6 status, methylation-array subgrouping) best defined favourable-risk WNT tumours (14/135; 10%). Engagement of a specialist pathologist panel was essential for consensus assessment of histological variants and immunohistochemistry. Overall, CPR altered clinical risk-status for 29% of patients. Conclusion: National real-time CPR is feasible, delivering robust diagnostics to WHO criteria and assignment of clinical risk-status, significantly altering clinical management. Recommendations and experience from our study are applicable to advanced molecular diagnostics systems, both local and centralised, across rare tumour types, enabling their application in biomarker-driven routine diagnostics and clinical/research studies

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin