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Biology subjects

Freeman, R.

Publications and source records attributed to Freeman, R..

26 records · Page 2Linked to original sources

Hyperconcentrated Mucus Unifies Submucosal Gland and Superficial Airway Dysfunction in Cystic Fibrosis

Cystic fibrosis (CF) is characterized by abnormal transepithelial ion transport. However, a description of CF lung disease pathophysiology unifying superficial epithelial and submucosal gland (SMG) dysfunctions has remained elusive. We hypothesized that biophysical abnormalities associated with CF mucus hyperconcentration provide a unifying mechanism. Studies of the anion secretion-inhibited pig airway CF model revealed elevated SMG mucus concentrations, osmotic pressures, and SMG mucus accumulation. Human airway studies revealed hyperconcentrated CF SMG mucus with raised osmotic pressures and cohesive forces predicted to limit SMG mucus secretion/release. Utilizing proline-rich protein 4 (PRR4) as a biomarker of SMG secretion, proteomics analyses of CF sputum revealed markedly lower PRR4 levels compared to healthy and bronchiectasis controls, consistent with a failure of CF SMGs to secrete mucus onto airway surfaces. Raised mucus osmotic/cohesive forces, reflecting mucus hyperconcentration, provide a unifying mechanism that describes disease-initiating mucus accumulation on airway surfaces and within SMGs of the CF lung.

pathology↗

A Programmable Toolkit to Dynamically Signal Cells using Peptide Strand Displacement

The native extracellular matrix communicates and interacts with cells by dynamically displaying signals to control their behavior. Mimicking this dynamic environment in vitro is essential in order to unravel how cell-matrix interactions guide cell fate. Here, we present a synthetic platform for the temporal display of cell adhesive signals using coiled-coil peptides. By designing an integrin-engaging coiled-coil pair to have a toehold (unpaired domain), we were able to use a peptide strand displacement reaction to remove the cell cue from the surface. This allowed us to test how the on-demand display of RGDS ligands at variable duration and periodicity of ligand exposure influence cell spreading degree and kinetics. Transient display of V{beta}3 selective ligands instructed fibroblast cells to reversibly spread and contract in response to changes in ligand exposure over multiple cycles, exhibiting a universal kinetic response. Also, cells that were triggered to spread and contract repeatedly exhibited greater enrichment of integrins in focal adhesions versus cells cultured on persistent RGDS-displaying surfaces. This dynamic platform will allow us to uncover the molecular code by which cells sense and respond to changes in their environment and will provide insights into ways to program cellular behavior.

bioengineering↗

Body mass and latitude predict the presence of multiple stressors in global vertebrate populations

Multiple stressors are recognised as a key threat to biodiversity, but our understanding of what might predispose species to multiple stressors remains limited. Here we analyse a global dataset of over 7000 marine, freshwater, and terrestrial vertebrate populations, alongside species-specific trait data, to identify factors which influence the number of stressors a species is subjected to at the population level. We find that body mass and latitude can both influence the number of stressors a population is subjected to across ecosystems, with large-bodied species tending to be more threatened, except terrestrial amphibians which show the opposite trend. Latitudinal forecasts predict higher stressor numbers between 20{degrees}N and 40{degrees}N, and towards the poles. Global stressor distributions suggest a link between human population centres and stressor frequency generally impacting larger-bodied species. Latitude and body mass hence provide key predictive tools to identify which vertebrate populations are likely to be highly threatened, despite the strength of these trends differing between ecological system and taxonomic class.

ecology↗

A global indicator of utilised wildlife populations: regional trends and the impact of management

The sustainable use of wildlife is a core aspiration of biodiversity conservation but is the subject of intense debate in the scientific literature as to how, and whether, species are best used and managed. While both positive and negative outcomes of sustainable use are known for specific taxa or local case studies, a global and regional picture of trends in wildlife populations in use is lacking. We use a global data set of over 11,000 time-series to derive indices of utilised and not utilised wildlife populations and assess global and regional changes, principally for mammals, birds and fishes. We also assess whether management makes a measurable difference to wildlife population trends, especially for the utilised species populations. Our results show that wildlife population trends globally are negative, but with utilised populations tending to decline more rapidly, especially in Africa and the Americas. Crucially, where utilised populations are managed, using a variety of mechanisms, there is a positive impact on the trend. It is therefore true that use of species can both be a driver of negative population trends, or a driver of species recovery, with numerous species and population specific case examples making up these broader trends. This work is relevant to the evidence base for the IPBES Sustainable Use Assessment, and to the development of indicators of sustainable use of species under the post-2020 Global Biodiversity Framework being developed under the Convention on Biological Diversity.

ecology↗

The Species Awareness Index (SAI): a Wikipedia-derived conservation culturomics metric for public biodiversity awareness

Threats to global biodiversity are well-known, but slowing currents rates of biodiversity loss remains an ongoing challenge. The Aichi Targets set out 20 goals on which the international community should act to alleviate biodiversity decline, one of which (Target 1) aimed to raise public awareness of the importance of biodiversity. Whilst conventional indicators for Target 1 are of low spatial and temporal coverage, conservation culturomics has demonstrated how biodiversity awareness can be quantified at the global scale. Following the Living Planet Index methodology, here we introduced the Species Awareness Index (SAI), an index of changing species awareness on Wikipedia. We calculated this index at the page level for 41,197 IUCN species across 10 Wikipedia languages, incorporating over 2 billion views. Bootstrapped indices for the page level SAI show that overall awareness of biodiversity is marginally increasing, although there are differences among taxonomic classes and languages. Among taxonomic classes, overall awareness of reptiles is increasing fastest, and amphibians slowest. Among languages, overall species awareness for the Japanese Wikipedias is increasing fastest, and the Chinese and German Wikipedias slowest. Although awareness of species on Wikipedia as a whole is increasing, and is significantly higher in traded species, over the period 2016-2020 change in interest appears not to be strongly related to the trade of species or animal pollinators. As a data source for public biodiversity awareness Wikipedia could be integrated into the Biodiversity Engagement Indicator, thereby incorporating a more direct link to biodiversity itself.

scientific communication and education↗

Multivalent Clustering of Adhesion Ligands in Nanofiber-Nanoparticle Composites

Because the positioning and clustering of biomolecules within the extracellular matrix dictates cell behaviors, the engineering of biomaterials incorporating bioactive epitopes with spatial organization tunable at the nanoscale is of primary importance. Here we used a highly modular composite approach combining peptide amphiphile (PA) nanofibers and silica nanoparticles, which are both easily functionalized with one or several bioactive signals. We show that the surface of silica nanoparticles allows the clustering of RGDS bioactive signals leading to improved adhesion and spreading of fibroblast cells on composite hydrogels at an epitope concentration much lower than in PA-only based matrices. Most importantly, by combining the two integrin-binding sequences RGDS and PHSRN on nanoparticle surfaces, we improved cell adhesion on the PA nanofiber/particle composite hydrogels, which is attributed to synergistic interactions known to be effective only for peptide intermolecular distance of ca. 5 nm. Such composites with soft and hard nanostructures offer a strategy for the design of advanced scaffolds to display multiple signals and control cell behavior.

bioengineering↗

Comparative physiology of five tropical montane songbirds reveals differential seasonal acclimatisation and cold adaption

The physiology of tropical birds is poorly understood, particularly in how it relates to local climate and changes between seasons. This is particularly true of tropical montane species, which may have sensitive thermal tolerances to local microclimates. We studied metabolic rates (using open flow respirometry), body mass and haemoglobin concentrations of five sedentary Mesoamerican songbirds between the summer and winter at two elevations (1550 m and 1950 m, respectively). We asked whether there were uniform seasonal shifts in physiological traits across species, and whether higher elevation species displayed evidence for cold tolerance. Seasonal shifts in metabolic rates differed between the three species for which data were collected. Basal metabolic rates in one species - black-headed nightingalethrushes Catharus mexicanus - were up-regulated in summer (~19% increase of winter metabolism), however two other species displayed no seasonal regulation. No species exhibited shifts in haemoglobin concentrations across season or across elevation, whereas body mass in two species was significantly higher in the summer. One species restricted to higher elevations - ruddy-capped nightingale-thrushes C. frantzii - displayed physiological traits indicative of cold-tolerance. Although only summer data were available for this species (C. frantzii), metabolic rates were constant across temperatures tested (5-34{degrees}C) and haemoglobin concentrations were significantly higher compared to the other four species. Our results suggest that seasonal acclimatisation in physiological traits is variable between species and appear unrelated to changes in local climate. As such, the distinct physiological traits observed in ruddy-capped nightingale-thrushes likely relate to historic isolation and conserved physiological traits rather than contemporary climatic adaption.

ecology↗

Bat Detective - Deep Learning Tools for Bat Acoustic Signal Detection

O_LIPassive acoustic sensing has emerged as a powerful tool for quantifying anthropogenic impacts on biodiversity, especially for echolocating bat species. To better assess bat population trends there is a critical need for accurate, reliable, and open source tools that allow the detection and classification of bat calls in large collections of audio recordings. The majority of existing tools are commercial or have focused on the species classification task, neglecting the important problem of first localizing echolocation calls in audio which is particularly problematic in noisy recordings.\nC_LIO_LIWe developed a convolutional neural network (CNN) based open-source pipeline for detecting ultrasonic, full-spectrum, search-phase calls produced by echolocating bats (BatDetect). Our deep learning algorithms (CNN FULL and CNN FAST) were trained on full-spectrum ultrasonic audio collected along road-transects across Romania and Bulgaria by citizen scientists as part of the iBats programme and labelled by users of www.batdetective.org. We compared the performance of our system to other algorithms and commercial systems on expert verified test datasets recorded from different sensors and countries. As an example application, we ran our detection pipeline on iBats monitoring data collected over five years from Jersey (UK), and compared results to a widely-used commercial system.\nC_LIO_LIHere, we show that both CNNFULL and CNNFAST deep learning algorithms have a higher detection performance (average precision, and recall) of search-phase echolocation calls with our test sets, when compared to other existing algorithms and commercial systems tested. Precision scores for commercial systems were reasonably good across all test datasets (>0.7), but this was at the expense of recall rates. In particular, our deep learning approaches were better at detecting calls in road-transect data, which contained more noisy recordings. Our comparison of CNNFULL and CNNFAST algorithms was favourable, although CNNFAST had a slightly poorer performance, displaying a trade-off between speed and accuracy. Our example monitoring application demonstrated that our open-source, fully automatic, BatDetect CNNFAST pipeline does as well or better compared to a commercial system with manual verification previously used to analyse monitoring data.\nC_LIO_LIWe show that it is possible to both accurately and automatically detect bat search-phase echolocation calls, particularly from noisy audio recordings. Our detection pipeline enables the automatic detection and monitoring of bat populations, and further facilitates their use as indicator species on a large scale, particularly when combined with automatic species identification. We release our system and datasets to encourage future progress and transparency.\nC_LI

ecology↗