The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Data from: Resolving Cypriniformes relationships using an anchored enrichment approach

Background: Cypriniformes (minnows, carps, loaches, and suckers) is the largest group of freshwater fishes in the world (~4300 described species). Despite much attention, previous attempts to elucidate relationships using molecular and morphological characters have been incongruent. In this study we present the first phylogenomic analysis using anchored hybrid enrichment for 172 taxa to represent the order (plus three out-group taxa), which is the largest dataset for the order to date (219 loci, 315,288 bp, average locus length of 1011 bp). Results: Concatenation analysis establishes a robust tree with 97 % of nodes at 100 % bootstrap support. Species tree analysis was highly congruent with the concatenation analysis with only two major differences: monophyly of Cobitoidei and placement of Danionidae. Conclusions: Most major clades obtained in prior molecular studies were validated as monophyletic, and we provide robust resolution for the relationships among these clades for the first time. These relationships can be used as a framework for addressing a variety of evolutionary questions (e.g. phylogeography, polyploidization, diversification, trait evolution, comparative genomics) for which Cypriniformes is ideally suited

A scandal of invisibility: making everyone count by counting everyone (Series 1st of 4)

Most people in Africa and Asia are born and die without leaving a trace in any legal record or official statistic. Absence of reliable data for births, deaths, and causes of death are at the root of this scandal of invisibility, which renders most of th

Civil registration systems and vital statistics: successes and missed opportunities (Series 2nd of 4)

Vital statistics generated through civil registration systems are the major source of continuous monitoring of births and deaths over time. The usefulness of vital statistics depends on their quality. In the second paper in this Series we propose a comprehensive and practical framework for assessment of the quality of vital statistics. With use of routine reports to the UN and cause-of-death data reported to WHO, we review the present situation and past trends of vital statistics in the world and note little improvement in worldwide availability of general vital statistics or cause-of-death statistics. Only a few developing countries have been able to improve their civil registration and vital statistics systems in the past 50 years. International efforts to improve comparability of vital statistics seem to be effective, and there is reasonable progress in collection and publication of data. However, worldwide efforts to improve data have been limited to sporadic and short-term measures. We conclude that countries and developmental partners have not recognised that civil registration systems are a priority

Interim measures for meeting needs for health sector data: births, deaths, and causes of death

Most developing countries do not have fully effective civil registration systems to provide necessary information about population health. Interim approaches-both innovative strategies for collection of data, and methods of assessment or estimation of these data-to fill the resulting information gaps have been developed and refined over the past four decades. To respond to the needs for data for births, deaths, and causes of death, data collection systems such as population censuses, sample vital registration systems, demographic surveillance sites, and internationally-coordinated sample survey programmes in combination with enhanced methods of assessment and analysis have been successfully implemented to complement civil registration systems. Methods of assessment and analysis of incomplete information or indirect indicators have also been improved, as have approaches to ascertainment of cause of death by verbal autopsy, disease modelling, and other strategies. Our knowledge of demography and descriptive epidemiology of populations in developing countries has been greatly increased by the widespread use of these interim approaches; although gaps remain, particularly for adult mortality. However, these approaches should not be regarded as substitutes for complete civil registration but rather as complements, essential parts of any fully comprehensive health information system. International organisations, national governments, and academia all have responsibilities in ensuring that data continue to be collected and that methods continue to be improved

In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer.

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours

In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours

The way forward.

Good public-health decisionmaking is dependent on reliable and timely statistics on births and deaths (including the medical causes of death). All high-income countries, without exception, have national civil registration systems that record these events and generate regular, frequent, and timely vital statistics. By contrast, these statistics are not available in many low-income and lower-middle-income countries, even though it is in such settings that premature mortality is most severe and the need for robust evidence to back decisionmaking most critical. Civil registration also has a range of benefits for individuals in terms of legal status, and the protection of economic, social, and human rights. However, over the past 30 years, the global health and development community has failed to provide the needed technical and financial support to countries to develop civil registration systems. There is no single blueprint for establishing and maintaining such systems and ensuring the availability of sound vital statistics. Each country faces a different set of challenges, and strategies must be tailored accordingly. There are steps that can be taken, however, and we propose an approach that couples the application of methods to generate better vital statistics in the short term with capacity-building for comprehensive civil registration systems in the long run