Ancient DNA Provides New Insights into the Evolutionary History of New Zealand's Extinct Giant Eagle

Prior to human settlement 700 years ago New Zealand had no terrestrial mammals—apart from three species of bats—instead, approximately 250 avian species dominated the ecosystem. At the top of the food chain was the extinct Haast's eagle, Harpagornis moorei. H. moorei (10–15 kg; 2–3 m wingspan) was 30%–40% heavier than the largest extant eagle (the harpy eagle, Harpia harpyja), and hunted moa up to 15 times its weight. In a dramatic example of morphological plasticity and rapid size increase, we show that the H. moorei was very closely related to one of the world's smallest extant eagles, which is one-tenth its mass. This spectacular evolutionary change illustrates the potential speed of size alteration within lineages of vertebrates, especially in island ecosystems

What do we need to know to enhance the environmental sustainability of agricultural production?: a prioritisation of knowledge needs for the UK food system

Increasing concerns about global environmental change and food security have focused attention on the need for environmentally sustainable agriculture. This is agriculture that makes efficient use of natural resources and does not degrade the environmental systems that underpin it, or deplete natural capital stocks. We convened a group of 29 ‘practitioners’ and 17 environmental scientists with direct involvement or expertise in the environmental sustainability of agriculture. The practitioners included representatives from UK industry, non-government organizations and government agencies. We collaboratively developed a long list of 264 knowledge needs to help enhance the environmental sustainability of agriculture within the UK or for the UK market. We refined and selected the most important knowledge needs through a three-stage process of voting, discussion and scoring. Scientists and practitioners identified similar priorities. We present the 26 highest priority knowledge needs. Many of them demand integration of knowledge from different disciplines to inform policy and practice. The top five are about sustainability of livestock feed, trade-offs between ecosystem services at farm or landscape scale, phosphorus recycling and metrics to measure sustainability. The outcomes will be used to guide on-going knowledge exchange work, future science policy and funding

Pathogenic mutation in the ALS/FTD gene, CCNF, causes elevated Lys48-linked ubiquitylation and defective autophagy

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders that have common molecular and pathogenic characteristics, such as aberrant accumulation and ubiquitylation of TDP-43; however, the mechanisms that drive this process remain poorly understood. We have recently identified CCNF mutations in familial and sporadic ALS and FTD patients. CCNF encodes cyclin F, a component of an E3 ubiquitin–protein ligase (SCF) complex that is responsible for ubiquitylating proteins for degradation by the ubiquitin–proteasome system. In this study, we examined the ALS/FTD-causing p.Ser621Gly (p.S621G) mutation in cyclin F and its effect upon downstream Lys48-specific ubiquitylation in transfected Neuro-2A and SH-SY5Y cells. Expression of mutant cyclin F caused increased Lys48-specific ubiquitylation of proteins in neuronal cells compared to cyclin F. Proteomic analysis of immunoprecipitated Lys48-ubiquitylated proteins from mutant cyclin F-expressing cells identified proteins that clustered within the autophagy pathway, including sequestosome-1 (p62/SQSTM1), heat shock proteins, and chaperonin complex components. Examination of autophagy markers p62, LC3, and lysosome-associated membrane protein 2 (Lamp2) in cells expressing mutant cyclin F revealed defects in the autophagy pathway specifically resulting in impairment in autophagosomal–lysosome fusion. This finding highlights a potential mechanism by which cyclin F interacts with p62, the receptor responsible for transporting ubiquitylated substrates for autophagic degradation. These findings demonstrate that ALS/FTD-causing mutant cyclin F disrupts Lys48-specific ubiquitylation, leading to accumulation of substrates and defects in the autophagic machinery. This study also demonstrates that a single missense mutation in cyclin F causes hyper-ubiquitylation of proteins that can indirectly impair the autophagy degradation pathway, which is implicated in ALS pathogenesis

Genetic and immunopathological analysis of CHCHD10 in Australian amyotrophic lateral sclerosis and frontotemporal dementia and transgenic TDP-43 mice

Objective: Since the first report of CHCHD10 gene mutations in amyotrophiclateral sclerosis (ALS)/frontotemporaldementia (FTD) patients, genetic variation in CHCHD10 has been inconsistently linked to disease. A pathological assessment of the CHCHD10 protein in patient neuronal tissue also remains to be reported. We sought to characterise the genetic and pathological contribution of CHCHD10 to ALS/FTD in Australia. Methods: Whole-exome and whole-genome sequencing data from 81 familial and 635 sporadic ALS, and 108 sporadic FTD cases, were assessed for genetic variation in CHCHD10. CHCHD10 protein expression was characterised by immunohistochemistry, immunofluorescence and western blotting in control, ALS and/or FTD postmortem tissues and further in a transgenic mouse model of TAR DNA-binding protein 43 (TDP-43) pathology. Results: No causal, novel or disease-associated variants in CHCHD10 were identified in Australian ALS and/or FTD patients. In human brain and spinal cord tissues, CHCHD10 was specifically expressed in neurons. A significant decrease in CHCHD10 protein level was observed in ALS patient spinal cord and FTD patient frontal cortex. In a TDP-43 mouse model with a regulatable nuclear localisation signal (rNLS TDP-43 mouse), CHCHD10 protein levels were unaltered at disease onset and early in disease, but were significantly decreased in cortex in mid-stage disease. Conclusions: Genetic variation in CHCHD10 is not a common cause of ALS/FTD in Australia. However, we showed that in humans, CHCHD10 may play a neuron-specific role and a loss of CHCHD10 function may be linked to ALS and/or FTD. Our data from the rNLS TDP-43 transgenic mice suggest that a decrease in CHCHD10 levels is a late event in aberrant TDP-43-induced ALS/FTD pathogenesis

Future novel threats and opportunities facing UK biodiversity identified by horizon scanning.

1. Horizon scanning is an essential tool for environmental scientists if they are to contribute to the evidence base for Government, its agencies and other decision makers to devise and implement environmental policies. The implication of not foreseeing issues that are foreseeable is illustrated by the contentious responses to genetically modified herbicide-tolerant crops in the UK, and by challenges surrounding biofuels, foot and mouth disease, avian influenza and climate change. 2. A total of 35 representatives from organizations involved in environmental policy, academia, scientific journalism and horizon scanning were asked to use wide consultation to identify the future novel or step changes in threats to, and opportunities for, biodiversity that might arise in the UK up to 2050, but that had not been important in the recent past. At least 452 people were consulted. 3. Cases for 195 submitted issues were distributed to all participants for comments and additions. All issues were scored (probability, hazard, novelty and overall score) prior to a 2-day workshop. Shortlisting to 41 issues and then the final 25 issues, together with refinement of these issues, took place at the workshop during another two rounds of discussion and scoring. 4. We provide summaries of the 25 shortlisted issues and outline the research needs. 5. We suggest that horizon scanning incorporating wide consultation with providers and users of environmental science is used by environmental policy makers and researchers. This can be used to identify gaps in knowledge and policy, and to identify future key issues for biodiversity, including those arising from outside the domains of ecology and biodiversity. 6. Synthesis and applications. Horizon scanning can be used by environmental policy makers and researchers to identify gaps in knowledge and policy. Drawing on the experience, expertise and research of policy advisors, academics and journalists, this exercise helps set the agenda for policy, practice and research