• Higher risk of gastrointestinal parasite infection at lower elevation suggests possible constraints in the distributional niche of Alpine marmots

      Zanet, Stefania; Miglio, Giacomo; Ferrari, Caterina; Bassano, Bruno; Ferroglio, Ezio; von Hardenberg, Achaz; Università di Torino; Gran Paradiso National Park; University of Chester (Public Library of Science, 2017-08-01)
      Alpine marmots Marmota marmota occupy a narrow altitudinal niche within high elevation alpine environments. For animals living at such high elevations where resources are limited, parasitism represents a potential major cost in life history. Using occupancy models, we tested if marmots living at higher elevation have a reduced risk of being infected with gastrointestinal helminths, possibly compensating the lower availability of resources (shorter feeding season, longer snow cover and lower temperature) than marmots inhabiting lower elevations. Detection probability of eggs and oncospheres of two gastro-intestinal helminthic parasites, Ascaris laevis and Ctenotaenia marmotae, sampled in marmot feces, was used as a proxy of parasite abundance. As predicted, the models showed a negative relationship between elevation and parasite detectability (i.e. abundance) for both species, while there appeared to be a negative effect of solar radiance only for C. marmotae. Site-occupancy models are used here for the first time to model the constrains of gastrointestinal parasitism on a wild species and the relationship existing between endoparasites and environmental factors in a population of free-living animals. The results of this study suggest the future use of site-occupancy models as a viable tool to account for parasite imperfect detection in ecoparasitological studies, and give useful insights to further investigate the hypothesis of the contribution of parasite infection in constraining the altitudinal niche of Alpine marmots.
    • Nicotinamide alone accelerates the conversion of mouse embryonic stem cells into mature neuronal populations.

      Griffin, Sile M.; Pickard, Mark R.; Orme, Rowan P.; Hawkins, Clive P.; Williams, Adrian C.; Fricker, Rosemary; Keele University; University of Chester; University Hospital of North Staffordshire; University of Birmingham (Public Library of Science, 2017-08-17)
      Vitamin B3 has been shown to play an important role during embryogenesis. Specifically, there is growing evidence that nicotinamide, the biologically active form of vitamin B3, plays a critical role as a morphogen in the differentiation of stem cells to mature cell phenotypes, including those of the central nervous system (CNS). Detailed knowledge of the action of small molecules during neuronal differentiation is not only critical for uncovering mechanisms underlying lineage-specification, but also to establish more effective differentiation protocols to obtain clinically relevant cells for regenerative therapies for neurodegenerative conditions such as Huntington's disease (HD). Thus, this study aimed to investigate the potential of nicotinamide to promote the conversion of stem cells to mature CNS neurons. METHODS: Nicotinamide was applied to differentiating mouse embryonic stem cells (mESC; Sox1GFP knock-in 46C cell line) during their conversion towards a neural fate. Cells were assessed for changes in their proliferation, differentiation and maturation; using immunocytochemistry and morphometric analysis methods. RESULTS: Results presented indicate that 10 mM nicotinamide, when added at the initial stages of differentiation, promoted accelerated progression of ESCs to a neural lineage in adherent monolayer cultures. By 14 days in vitro (DIV), early exposure to nicotinamide was shown to increase the numbers of differentiated βIII-tubulin-positive neurons. Nicotinamide decreased the proportion of pluripotent stem cells, concomitantly increasing numbers of neural progenitors at 4 DIV. These progenitors then underwent rapid conversion to neurons, observed by a reduction in Sox 1 expression and decreased numbers of neural progenitors in the cultures at 14 DIV. Furthermore, GABAergic neurons generated in the presence of nicotinamide showed increased maturity and complexity of neurites at 14 DIV. Therefore, addition of nicotinamide alone caused an accelerated passage of pluripotent cells through lineage specification and further to non-dividing mature neurons. CONCLUSIONS: Our results show that, within an optimal dose range, nicotinamide is able to singly and selectively direct the conversion of embryonic stem cells to mature neurons, and therefore may be a critical factor for normal brain development, thus supporting previous evidence of the fundamental role of vitamins and their metabolites during early CNS development. In addition, nicotinamide may offer a simple effective supplement to enhance the conversion of stem cells to clinically relevant neurons.
    • Nicotinamide restricts neural precursor proliferation to enhance catecholaminergic neuronal subtype differentiation from mouse embryonic stem cells

      Borlongan, Cesar V.; Griffin, Síle M.; orcid: 0000-0002-6670-5084; email: silemgriffin@gmail.com; Pickard, Mark R.; Hawkins, Clive P.; Williams, Adrian C.; Fricker, Rosemary A.; orcid: 0000-0001-8768-510X (Public Library of Science, 2020-09-14)
      Emerging evidence indicates that a strong relationship exists between brain regenerative therapies and nutrition. Early life nutrition plays an important role during embryonic brain development, and there are clear consequences to an imbalance in nutritional factors on both the production and survival of mature neuronal populations and the infant’s risk of diseases in later life. Our research and that of others suggest that vitamins play a fundamental role in the formation of neurons and their survival. There is a growing body of evidence that nicotinamide, the water-soluble amide form of vitamin B3, is implicated in the conversion of pluripotent stem cells to clinically relevant cells for regenerative therapies. This study investigated the ability of nicotinamide to promote the development of mature catecholaminergic neuronal populations (associated with Parkinson’s disease) from mouse embryonic stem cells, as well as investigating the underlying mechanisms of nicotinamide’s action. Nicotinamide selectively enhanced the production of tyrosine hydroxylase-expressing neurons and serotonergic neurons from mouse embryonic stem cell cultures (Sox1GFP knock-in 46C cell line). A 5-Ethynyl-2´-deoxyuridine (EdU) assay ascertained that nicotinamide, when added in the initial phase, reduced cell proliferation. Nicotinamide drove tyrosine hydroxylase-expressing neuron differentiation as effectively as an established cocktail of signalling factors, reducing the proliferation of neural progenitors and accelerating neuronal maturation, neurite outgrowth and neurotransmitter expression. These novel findings show that nicotinamide enhanced and enriched catecholaminergic differentiation and inhibited cell proliferation by directing cell cycle arrest in mouse embryonic stem cell cultures, thus driving a critical neural proliferation-to-differentiation switch from neural progenitors to neurons. Further research into the role of vitamin metabolites in embryogenesis will significantly advance cell-based regenerative medicine, and help realize their role as crucial developmental signalling molecules in brain development.
    • Non-territorial GPS-tagged golden eagles Aquila chrysaetos at two Scottish wind farms: avoidance influenced by preferred habitat distribution, wind speed and blade motion status

      Fielding, Alan H; Anderson, David; Benn, Stuart; Dennis, Roy; Weston, Ewan; Whitfield, Philip; Natural Research Ltd; Forestry and Land Scotland; RSPB Scotland; Roy Dennis Wildlife Foundation; University of Chester (Public Library of Science, 2021-08-05)
      Wind farms can have two broad potential adverse effects on birds via antagonistic processes: displacement from the vicinity of turbines (avoidance), or death through collision with rotating turbine blades. These effects may not be mutually exclusive. Using detailed data from 99 turbines at two wind farms in central Scotland and thousands of GPS-telemetry data from dispersing golden eagles, we tested three hypotheses. Before-and-after-operation analyses supported the hypothesis of avoidance: displacement was reduced at turbine locations in more preferred habitat and with more preferred habitat nearby. After-operation analyses (i.e. from the period when turbines were operational) showed that at higher wind speeds and in highly preferred habitat eagles were less wary of turbines with motionless blades: rejecting our second hypothesis. Our third hypothesis was supported, since at higher wind speeds eagles flew closer to operational turbines; especially – once more – turbines in more preferred habitat. After operation, eagles effectively abandoned inner turbine locations, and flight line records close to rotor blades were rare. While our study indicated that whole-wind farm functional habitat loss through avoidance was the substantial adverse impact, we make recommendations on future wind farm design to minimise collision risk further. These largely entail developers avoiding outer turbine locations which are in and surrounded by swathes of preferred habitat. Our study illustrates the insights which detailed case studies of large raptors at wind farms can bring and emphasises that the balance between avoidance and collision can have several influences.
    • A Pilot Study to Evaluate Haemostatic Function, following Shock Wave Lithotripsy (SWL) for the Treatment of Solitary Kidney Stones

      Hughes, Stephen F.; Thomas-Wright, Samantha J.; Banwell, Joseph; Williams, Rachel; Moyes, Alyson J.; Mushtaq, Sohail; Abdulmajed, Mohamed; Shergill, Iqbal; University of Chester; BCUHB Wrexham Maelor Hospital (Public Library of Science, 2015-05-04)
      Purpose: The number of patients undergoing shock wave lithotripsy (SWL) in the UK for solitary unilateral kidney stones is increasing annually. The development of postoperative complications such as haematuria and sepsis following SWL is likely to increase. Comparing a range of biological markers with the aim of monitoring or predicting postoperative complications following SWL has not been extensively researched. The main purpose of this pilot-study was to test the hypothesis that SWL results in changes to haemostatic function. Subsequently, this pilot-study would form a sound basis to undertake future investigations involving larger cohorts. Methods: Twelve patients undergoing SWL for solitary unilateral kidney stones were recruited. From patients (8 male and 4 females) aged between 31–72 years (median—43 years), venous blood samples were collected pre-operatively (baseline), at 30, 120 and 240 minutes postoperatively. Specific haemostatic biomarkers [platelet counts, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, von Willebrand Factor (vWF), sE-selectin and plasma viscosity (PV)] were measured. Results: Platelet counts and fibrinogen concentration were significantly decreased following SWL (p = 0.027 and p = 0.014 respectively), while D-dimer and vWF levels significantly increased following SWL (p = 0.019 and p = 0.001 respectively). PT, APTT, sE-selectin and PV parameters were not significantly changed following SWL (p>0.05). Conclusions: Changes to specific biomarkers such as plasma fibrinogen and vWF suggest that these represent a more clinically relevant assessment of the extent of haemostatic involvement following SWL. Analysis of such markers, in the future, may potentially provide valuable data on “normal” response after lithotripsy, and could be expanded to identify or predict those patients at risk of coagulopathy following SWL. The validation and reliability will be assessed through the assessment of larger cohorts.