Biology subjects

Ware, C.

Publications and source records attributed to Ware, C..

6 recordsLinked to original sources

bioRxiv2021

The E3 ubiquitin ligase RNF216/TRIAD3 is a central regulator of the hypothalamic-pituitary-gonadal axis

RNF216/TRIAD3 is an E3 ligase that ubiquitinates substrates in the nervous system. Recessive mutations in RNF216/TRIAD3 cause Gordon Holmes syndrome (GHS), where hypogonadotropic hypogonadism is a core phenotype. However, the functions of RNF216/TRIAD3 within the neuroendocrine system are not well-understood. Here, we used the CRISPR-Cas9 system to knock out Rnf216/Triad3 in GT1-7 cells, a GnRH immortalized cell line derived from mouse hypothalamus. Rnf216/Triad3 knockout cells had decreased steady state Gnrh and reduced calcium transient frequency. To address functions of RNF216/TRIAD3 in vivo, we generated a Rnf216/Triad3 constitutive knockout (KO) mouse. KO mice of both sexes showed reductions in GnRH and soma size. Furthermore, KO mice exhibited sex-specific phenotypes with males showing gonadal impairment and derangements in gonadotropin release compared to KO females, which only had irregular estrous cyclicity. Our work shows that dysfunction of RNF216/TRIAD3 affects the HPG axis in a sex-dependent manner, implicating sex-specific therapeutic interventions for GHS. HighlightsO_LIRnf216/Triad3 controls Gnrh and intrinsic hypothalamic cell activity C_LIO_LIRnf216/Triad3 knockout male mice have greater reproductive impairments than females C_LIO_LIRnf216/Triad3 controls the HPG axis at multiple levels C_LI

neuroscience↗

bioRxiv2020

Global trends in biodiversity and ecosystem services from 1900 to 2050

Despite the scientific consensus on the extinction crisis and its anthropogenic origin, the quantification of historical trends and of future scenarios of biodiversity and ecosystem services has been limited, due to the lack of inter-model comparisons and harmonized scenarios. Here, we present a multi-model analysis to assess the impacts of land-use and climate change from 1900 to 2050. During the 20th century provisioning services increased, but biodiversity and regulating services decreased. Similar trade-offs are projected for the coming decades, but they may be attenuated in a sustainability scenario. Future biodiversity loss from land-use change is projected to keep up with historical rates or reduce slightly, whereas losses due to climate change are projected to increase greatly. Renewed efforts are needed by governments to meet the 2050 vision of the Convention on Biological Diversity. One Sentence SummaryDevelopment pathways exist that allow for a reduction of the rates of biodiversity loss from land-use change and improvement in regulating services but climate change poses an increasing challenge.

ecology↗

bioRxiv2019

Reconciling global priorities for conserving biodiversity habitat

Degradation and loss of natural habitat is the major driver of the current global biodiversity crisis. Most habitat conservation efforts to date have targeted small areas of highly threatened habitat, but emerging debate suggests retaining large intact natural systems may be just as important. We reconcile these perspectives by integrating fine-resolution global data on habitat condition and species assemblage turnover, to identify Earths high-value biodiversity habitat. These are areas in better condition than most other locations once supporting a similar assemblage of species, and are found within both intact regions and human dominated landscapes. However, only 18.6 % of this high-value habitat is currently protected globally. Averting permanent biodiversity loss requires clear spatially explicit targets for retaining these unprotected high-value habitats.

ecology↗

bioRxiv2019

A global indicator of the capacity of terrestrial ecosystems to retain biological diversity under climate change: the Bioclimatic Ecosystem Resilience Index

An important element of the Convention on Biological Diversitys Aichi Target 15 - i.e. to enhance \"ecosystem resilience ... through conservation and restoration\" - remains largely unaddressed by existing indicators. We here develop an indicator addressing just one of many possible dimensions of ecosystem resilience, by focusing on the capacity of ecosystems to retain biological diversity in the face of ongoing, and uncertain, climate change. The Bioclimatic Ecosystem Resilience Index (BERI) assesses the extent to which a given spatial configuration of natural habitat will promote or hinder climate-induced shifts in biological distributions. The approach uses existing global modelling of spatial turnover in species composition within three broad biological groups (plants, invertebrates and vertebrates) to scale projected changes in composition under a plausible range of climate scenarios. These projections serve as filters through which to analyse the configuration of habitat observed at a given point in time (e.g. for a particular year) - represented as a grid in which cells are scored in terms of habitat condition. BERI is then calculated, for each cell in this grid, as a function of the connectedness of that cell to areas of natural habitat in the surrounding landscape which are projected to support a similar composition of species under climate change to that currently associated with the focal cell. All analyses are performed at 30-arcsecond grid resolution (approximately 1km cells at the equator). Results can then be aggregated to report on status and trends for any desired set of reporting units - e.g. ecoregions, countries, or ecosystem types. We present example outputs for the Moist Tropical Forest Biome, based on a habitat-condition time series derived from the Global Forest Change dataset. We also describe how BERI is now being extended to cover all biomes (forest and non-forest) across the entire terrestrial surface of the planet.

ecology↗

bioRxiv2019

Complement-dependent synapse loss and microgliosis in a mouse model of multiple sclerosis

Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease of the CNS characterized by both grey and white matter injury. Microglial activation and a reduction in synaptic density are key features of grey matter pathology that can be modeled with experimental autoimmune encephalomyelitis (EAE). Complement deposition combined with microglial engulfment has been shown during normal development and in disease as a mechanism for pruning synapses. We tested whether there is excess complement production in the EAE hippocampus and whether complement-dependent synapse loss is a source of degeneration in EAE using C1qa and C3 knockout mice. We found that C1q and C3 protein levels were elevated in EAE mice. Genetic loss of C1qa provided a small degree of protection from EAE-induced decreases in synaptic density. However, C1qa knockout EAE mice had similar levels of microglial activation and identical clinical scores as WT EAE mice. C3 knockout mice were largely protected from EAE-induced synapse loss and microglial activation, results that correlated with a reduction in the EAE clinical score. Thus, pathologic expression and activation of the early complement pathway drives a portion of the synapse elimination observed in the EAE grey matter.

neuroscience↗

bioRxiv2018

Supporting global biodiversity assessment through high-resolution macroecological modelling: Methodological underpinnings of the BILBI framework

AimGlobal indicators of change in the state of terrestrial biodiversity are often derived by intersecting observed or projected changes in the distribution of habitat transformation, or of protected areas, with underlying patterns in the distribution of biodiversity. However the two main sources of data used to account for biodiversity patterns in such assessments - i.e. ecoregional boundaries, and vertebrate species ranges - are typically delineated at a much coarser resolution than the spatial grain of key ecological processes shaping both land-use and biological distributions at landscape scale. Species distribution modelling provides one widely used means of refining the resolution of mapped species distributions, but is limited to a subset of species which is biased both taxonomically and geographically, with some regions of the world lacking adequate data to generate reliable models even for better-known biological groups.\n\nInnovationMacroecological modelling of collective properties of biodiversity (e.g. alpha and beta diversity) as a correlative function of environmental predictors offers an alternative, yet highly complementary, approach to refining the spatial resolution with which patterns in the distribution of biodiversity can be mapped across our planet. Here we introduce a new capability - BILBI (the Biogeographic Infrastructure for Large-scaled Biodiversity Indicators) - which has implemented this approach by integrating advances in macroecological modelling, biodiversity informatics, remote sensing and high-performance computing to assess spatial-temporal change in biodiversity at ~1km grid resolution across the entire terrestrial surface of the planet. The initial implementation of this infrastructure focuses on modelling beta-diversity patterns using a novel extension of generalised dissimilarity modelling (GDM) designed to extract maximum value from sparsely and unevenly distributed occurrence records for over 400,000 species of plants, invertebrates and vertebrates.\n\nMain conclusionsModels generated by BILBI greatly refine the mapping of beta-diversity patterns relative to more traditional biodiversity surrogates such as ecoregions. This capability is already proving of considerable value in informing global biodiversity assessment through: 1) generation of indicators of past-to-present change in biodiversity based on observed changes in habitat condition and protected-area coverage; and 2) projection of potential future change in biodiversity as a consequence of alternative scenarios of global change in drivers and policy options.

ecology↗