• Gerontobiology of the Hair Follicle

      Tobin, Desmond J. (2010)
      The word ¿gerontology¿ is familiar to most of us as a term that captures the study of the social, psychological, and biological aspects of aging. However, its derivative ¿gerontobiology¿ as applied to the hair follicle is more concerned with the latter aspect ¿ the biology of aging in the hair follicle mini-organ. As with any complex multicellular tissue system, the hair follicle is prone to broadly similar underlying processes that determine the functional longevity of organs and tissues. No matter how complex the tissue system is, it will contain cells that eventually lose functionality, reproductive potential and will ultimately die. The hair follicle is somewhat unusual among mammalian tissues in that it is a veritable histologic mélange of multiple cell types (e.g., epithelial, mesenchymal and neuro-ectodermal) that function contemporaneously in all stages of their life histories e.g., stem cells, transit-amplifying cells, and terminally differentiating cells. Some of these interactive cell systems appear to be nonessential for overall hair follicle survival (e.g., melanocytes). However, strikingly graying hair follicles may grow even more vigorously than their pigmented predecessors. Moreover, the hair follicle is unique in the adult mammal in that it follows a tightly regulated script of multiple lifelong cycles of cellular birth, proliferation, differentiation, and death. Powerful evolutionary selection ensures that the hair follicle is, in the main, hardwired against significant aging-related loss of function, even after 12 or more decades of life ¿ although some would argue with this view, if only on purely cosmetic grounds. Processes underlying aging in general, e.g., oxidative damage, telomere shortening, age-relating deficiencies related to nuclear/mitochondrial DNA damage and repair as well as age-related reductions in the cells¿ energy supply, will all impact on whether some follicular cell subpopulations will enter cellular senescence. This chapter will focus on how gerontobiology of the hair follicle may impact on certain aspects of hair fiber phenotype.
    • Gestational stress induces post-partum depression-like behaviour and alters maternal care in rats

      Smith, Jeremy W.; Seckl, J.R.; Evans, A. Tudor; Costall, Brenda; Smythe, James W. (2004)
      Gestational stress (GS) produces profound behavioural impairments in the offspring and may permanently programme hypothalamic¿pituitary¿adrenal (HPA) axis function. We investigated whether or not GS produced changes in the maternal behaviour of rat dams, and measured depression-like behaviour in the dam, which might contribute to effects in the progeny. We used the Porsolt test, which measures immobility in a forced-swim task, and models depression in rodents, while monitoring maternal care (arched-back nursing, licking/grooming, nesting/grouping pups). Pregnant rats underwent daily restraint stress (1 h/day, days 10¿20 of gestation), or were left undisturbed (control). On post-parturition days 3 and 4, dams were placed into a swim tank, and time spent immobile was measured. GS significantly elevated immobility scores by approximately 25% above control values on the second test day. Maternal behaviours, in particular arched-back nursing and nesting/grouping pups, were reduced in GS dams over post-natal days 1¿10. Adult offspring showed increased immobility in the Porsolt test, and also hypersecreted ACTH and CORT in response to an acute stress challenge. These data show that GS can alter maternal behaviour in mothers, and this might contribute to alterations in the offspring. GS may be an important factor in maternal post-natal depression, which may in turn detrimentally effect the offspring because depressed mothers do not sufficiently care for their offspring.
    • Gesture politics and the art of ambiguity: the Iron Age statue from Hirschlanden

      Armit, Ian; Grant, P. (2008)
      The discovery of the extraordinary Hirschlanden figure was reported in this journal in 1964. Since then the statue has featured in numerous discussions of Iron Age art and society, to the extent that it has become one of the iconic images of the European Iron Age. It has become almost taken for granted that the Hirschlanden figure is an `intensely masculine¿ warrior statue representing the heroised dead. However, certain aspects of the figure suggest a rather deeper, more ambiguous symbolism. The authors use their up-to-date critique to raise questions about the eclectic character of Iron Age spirituality.
    • Gesturing Beyond Bones: Proposing a Decolonised Zooarchaeology

      Fitzpatrick, Alexandra L. (2022-02-08)
      This is paper represents a long process of self-reflection and critique of prior work I have presented on decolonising zooarchaeology. Engaging with current discourse on the misuse and appropriation of decolonial theory, I instead propose a framework which promotes movement towards decolonisation without co-opting the terminology. Through this, I also propose some alterations and considerations to my original proposal from 2019.
    • Getting the measure of brochs: using survey records old and new to investigate Shetland's Iron Age archaeology

      Sou, Li Z.; Bond, Julie M.; Dockrill, Stephen J.; Hepher, J.; Rawlinson, A.; Sparrow, Thomas; Turner, V.; Wilson, L.; Wilson, Andrew S. (Springer Nature, 2022-04)
      Brochs are monumental Iron Age (c.400–200 BC) drystone towers or roundhouses. They are only found in Scotland, particularly the Atlantic north and west. Whilst the structural layout of brochs has long been debated, few measured surveys have been conducted. Three significant broch sites form the tentative World Heritage site of “Mousa, Old Scatness and Jarlshof: the Zenith of Iron Age Shetland” (UNESCO in Mousa, Old Scatness and Jarlshof: the zenith of Iron Age Shetland, UNESCO (2019) Mousa, Old Scatness and Jarlshof: the zenith of Iron Age Shetland. http://whc.unesco.org/en/tentativelists/5677. Accessed 9 Aug 2019). All three sites have undergone new surveys as part of a collaborative doctoral partnership research project. This chapter presents a diachronic perspective using digital documentation techniques to detect stone displacement and weathering at the site of Old Scatness using historic imagery, including photographs from the Old Scatness excavations (1995–2006) and regular condition monitoring undertaken by Shetland Amenity Trust to undertake retrospective digital structure-from-motion (SfM) photogrammetry. Whilst point clouds and 3D meshes were successfully generated from low-resolution digital images, analogue film transparencies without metadata could not produce accurate geospatial data without manually trying to extant reference data. It was possible to detect displacements in stonework over time by comparing two meshes together and measuring the distances between vertex point pairs. The reliability and accuracy of these results were dependent on how well pairs of meshes could be aligned.
    • ‘Gifts for the gods’: lake-dwellers' macabre remedies against floods in the Central European Bronze Age

      Menotti, Francesco; Jennings, Benjamin R.; Gollnisch-Moos, H. (2014-06)
      The lake-dwellings of the Circum-Alpine region have long been a rich source of detailed information about daily life in Bronze Age Europe, but their location made them vulnerable to changes in climate and lake level. At several Late Bronze Age examples, skulls of children were found at the edge of the lake settlement, close to the encircling palisade. Several of the children had suffered violent deaths, through blows to the head from axes or blunt instruments. They do not appear to have been human sacrifices, but the skulls may nonetheless have been offerings to the gods by communities faced with the threat of environmental change.
    • The Glenn A. Fry Award Lecture 2013: Blurred vision, spectacle correction, and falls in older adults

      Elliott, David B. (2014)
      This article reviews the literature on how blurred vision contributes to falls, gait, and postural control and discusses how these are influenced by spectacle correction. Falls are common and represent a very serious health risk for older people. They are not random events as studies have shown that falls are linked to a range of intrinsic and extrinsic risk factors. Vision provides a significant input to postural control in addition to providing information about the size and position of hazards and obstacles in the travel pathway and allows us to safely negotiate steps and stairs. Many studies have shown that reduced vision is a significant risk factor for falls. However, randomized controlled trials of optometric interventions and cataract surgery have not shown the expected reduction in falls rate, which may be due to magnification changes (and thus vestibuloocular reflex gain) in those participants who have large changes in refractive correction. Epidemiological studies have also shown that progressive addition lens and bifocal wearers are twice as likely to fall as non-multifocal wearers, laboratorybased studies have shown safer adaptive gait with single-vision glasses than progressive addition lenses or bifocals, and a randomized controlled trial has shown that an additional pair of distance vision single-vision glasses for outdoor use can reduce falls rate. Clinical recommendations to help optometrists prevent their frail, older patients from falling are suggested.
    • Glioblastoma Multiforme Therapy and Mechanisms of Resistance

      Ramirez, Y.P.; Weatherbee, J.L.; Wheelhouse, Richard T.; Ross, A.H. (2013-11-25)
      Glioblastoma multiforme (GBM) is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12–14 month survival period post-diagnosis. Long-term survival for GBM patients remains uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. In this review we will describe the mechanisms of resistance, and how they may be overcome to improve the survival of GBM patients by implementing novel chemotherapy drugs, new drug combinations and new approaches relating to DNA damage, angiogenesis and autophagy.
    • Global shape aftereffects in composite radial frequency patterns

      Lawrence, S.J.D.; Keefe, B.D.; Vernon, R.J.W.; Wade, A.R.; McKeefry, Declan J.; Morland, A.B. (2016-05-16)
      Individual radial frequency (RF) patterns are generated by modulating a circle's radius as a sinusoidal function of polar angle and have been shown to tap into global shape processing mechanisms. Composite RF patterns can reproduce the complex outlines of natural shapes and examining these stimuli may allow us to interrogate global shape mechanisms that are recruited in biologically relevant tasks. We present evidence for a global shape aftereffect in a composite RF pattern stimulus comprising two RF components. Manipulations of the shape, location, size and spatial frequency of the stimuli revealed that this aftereffect could only be explained by the attenuation of intermediate-level global shape mechanisms. The tuning of the aftereffect to test stimulus size also revealed two mechanisms underlying the aftereffect; one that was tuned to size and one that was invariant. Finally, we show that these shape mechanisms may encode some RF information. However, the RF encoding we found was not capable of explaining the full extent of the aftereffect, indicating that encoding of other shape features such as curvature are also important in global shape processing.
    • Glucomannan-poly(N-vinyl pyrrolidinone) bicomponent hydrogels for wound healing

      Shahbuddin, M.; Bullock, A.J.; MacNeil, S.; Rimmer, Stephen (2014)
      Polysaccharides interact with cells in ways that can be conducive to wound healing. We have recently reported that konjac glucomannan (KGM) which is comprised of D-mannose and D-glucose linked by beta-1,4 glycosidic chains, stimulates fibroblast proliferation. The aim of this study was to produce a range of crosslinked KGMs and bicomponent KGM containing hydrogels and to examine their potential for wound healing. Two types of KGM hydrogel were synthesized, biodegradable from crosslinked KGM and non-biodegradable by forming semi-IPNs and graft-conetworks with a second synthetic component, poly(N-vinyl pyrrolidinone-co-poly(ethyleneglycol) diacrylate) (P(NVP-co-PEGDA)), which was produced by UV initiated radical polymerization. Crosslinked KGM was formed by bimolecular termination of macro-radicals formed by oxidation with Ce(IV). Semi-IPNs were formed by copolymerization of NVP and PEGDA in the presence of KGM and in the graft-conetworks the KGM was also crosslinked using the Ce(IV) procedure. The hydrogels had different swelling properties and differences could be observed in their chemical structure using C-13 solid state NMR, DSC and FTIR. Both forms were cytocompatible but only the graft-conetworks had the ability to stimulate fibroblast metabolic activity and to stimulate the migration of both fibroblasts and keratinocytes. In conclusion a form of KGM hydrogel has been produced that could benefit wound healing.
    • Glucose reduces endothelin inhibition of voltage-gated potassium channels in rat arterial smooth muscle cells

      Rainbow, R.D.; Hardy, Matthew E.; Standen, N.B.; Davies, N.W. (2006-09)
      Prolonged hyperglycaemia impairs vascular reactivity and inhibits voltage-activated K+ (Kv) channels. We examined acute effects of altering glucose concentration on the activity and inhibition by endothelin-1 (ET-1) of Kv currents of freshly isolated rat arterial myocytes. Peak Kv currents recorded in glucose-free solution were reversibly reduced within 200 s by increasing extracellular glucose to 4 mm. This inhibitory effect of glucose was abolished by protein kinase C inhibitor peptide (PKC-IP), and Kv currents were further reduced in 10 mm glucose. In current-clamped cells, membrane potentials were more negative in 4 than in 10 mm glucose. In 4 mmd-glucose, 10 nm ET-1 decreased peak Kv current amplitude at +60 mV from 23.5 ± 3.3 to 12.1 ± 3.1 pA pF−1 (n = 6, P < 0.001) and increased the rate of inactivation, decreasing the time constant around fourfold. Inhibition by ET-1 was prevented by PKC-IP. When d-glucose was increased to 10 mm, ET-1 no longer inhibited Kv current (n = 6). Glucose metabolism was required for prevention of ET-1 inhibition of Kv currents, since fructose mimicked the effects of d-glucose, while l-glucose, sucrose or mannitol were without effect. Endothelin receptors were still functional in 10 mmd-glucose, since pinacidil-activated ATP-dependent K+ (KATP) currents were reduced by 10 nm ET-1. This inhibition was nearly abolished by PKC-IP, indicating that endothelin receptors could still activate PKC in 10 mmd-glucose. These results indicate that changes in extracellular glucose concentration within the physiological range can reduce Kv current amplitude and can have major effects on Kv channel modulation by vasoconstrictors.
    • Glycosyl disulfides: importance, synthesis and application to chemical and biological systems

      Ribeiro Morais, Goreti; Falconer, Robert A. (2021-01)
      The disulfide bond plays an important role in the formation and stabilisation of higher order structures of peptides and proteins, while in recent years interest in this functional group has been extended to carbohydrate chemistry. Rarely found in nature, glycosyl disulfides have attracted significant attention as glycomimetics, with wide biological applications including lectin binding, as key components of dynamic libraries to study carbohydrate structures, the study of metabolic and enzymatic studies, and even as potential drug molecules. This interest has been accompanied and fuelled by the continuous development of new methods to construct the disulfide bond at the anomeric centre. Glycosyl disulfides have also been exploited as versatile intermediates in carbohydrate synthesis, particularly as glycosyl donors. This review focuses on the importance of the disulfide bond in glycobiology and in chemistry, evaluating the different methods available to synthesise glycosyl disulfides. Furthermore, we review the role of glycosyl disulfides as intermediates and/or glycosyl donors for the synthesis of neoglycoproteins and oligosaccharides, before finally considering examples of how this important class of carbohydrates have made an impact in biological and therapeutic contexts.
    • The Golgi apparatus is a functionally distinct Ca2+ store regulated by PKA and Epac branches of the β1-adrenergic signaling pathway.

      Yang, Z.; Kirton, H.M.; MacDougall, D.A.; Boyle, J.P.; Deuchars, J.; Frater, B.; Ponnambalam, S.; Hardy, Matthew E.; White, M.; Calaghan, S.C.; et al. (2015-10-13)
      Ca2+ release from the Golgi apparatus regulates key functions of the organelle, including vesicle trafficking. However, the signaling pathways that control this form of Ca2+ release are poorly understood and evidence of discrete Golgi Ca2+ release events is lacking. Here, we identified the Golgi apparatus as the source of prolonged Ca2+ release events that originate from the nuclear ‘poles’ of primary cardiac cells. Once initiated, Golgi Ca2+ release was unaffected by global depletion of sarcoplasmic reticulum Ca2+, and disruption of the Golgi apparatus abolished Golgi Ca2+ release without affecting sarcoplasmic reticulum function, suggesting functional and anatomical independence of Golgi and sarcoplasmic reticulum Ca2+ stores. Maximal activation of β1-adrenoceptors had only a small stimulating effect on Golgi Ca2+ release. However, inhibition of phosphodiesterase (PDE) 3 or 4, or downregulation of PDE 3 and 4 in heart failure markedly potentiated β1-adrenergic stimulation of Golgi Ca2+ release, consistent with compartmentalization of cAMP signaling within the Golgi apparatus microenvironment. β1-adrenergic stimulation of Golgi Ca2+ release involved activation of both Epac and PKA signaling pathways and CaMKII. Interventions that stimulated Golgi Ca2+ release induced trafficking of vascular growth factor receptor-1 (VEGFR-1) from the Golgi apparatus to the surface membrane. These data establish the Golgi apparatus as a juxtanuclear focal point for Ca2+ and β1-adrenergic signaling, which functions independently from the sarcoplasmic reticulum and the global Ca2+ transients that underlie the primary contractile function of the cell.
    • Governance for sustainability: Towards a 'thick' analysis of environmental decisionmaking.

      Adger, W.M.; Brown, K.; Fairbrass, Jenny M.; Jordan, A.; Paavola J.; Rosendo, S.; Seyfang G. (2003)
      Environmental decisions made by individuals, civil society and the state involve questions of economic efficiency, environmental effectiveness, equity and political legitimacy. These four criteria are constitutive of economic, social and environmental dimensions of sustainable development, which has become the dominant rhetorical device of environmental governance. We discuss the tendency for different strands of social science to focus on particular subsets of the four criteria and argue that such a practice promotes solutions that do not acknowledge the dynamics of scale and the heterogeneity of institutional and historical contexts. We propose a more interdisciplinary approach to understanding environmental decisions that seeks to identify legitimate and context-sensitive institutional solutions producing equitable, efficient and effective outcomes. We examine two examples that illustrate the indivisible and integrated nature of the four criteria in actual environmental decisions. The first example relates to international efforts to reduce greenhouse gas emissions and the second one to local resource management in the UK. We utilise the example to outline a new agenda for future research on environmental governance and decision-making.
    • Graphitic carbon nitride nanosheet@metal-organic framework core-shell nanoparticles for photo-chemo combination therapy

      Chen, R.; Zhang, J.; Wang, Y.; Chen, Xianfeng; Zapien, J.A.; Lee, C-S. (2015-08-05)
      Recently, nanoscale metal-organic frameworks (NMOFs) have started to be developed as a promising platform for bioimaging and drug delivery. On the other hand, combination therapies using multiple approaches are demonstrated to achieve much enhanced efficacy. Herein, we report, for the first time, core-shell nanoparticles consisting of a photodynamic therapeutic (PDT) agent and a MOF shell while simultaneously carrying a chemotherapeutic drug for effective combination therapy. In this work, core-shell nanoparticles of zeolitic-imadazolate framework-8 (ZIF-8) as shell embedded with graphitic carbon nitride (g-C3N4) nanosheets as core are fabricated by growing ZIF-8 in the presence of g-C3N4 nanosheets. Doxorubicin hydrochloride (DOX) is then loaded into the ZIF-8 shell of the core-shell nanoparticles. The combination of the chemotherapeutic effects of DOX and the PDT effect of g-C3N4 nanosheets can lead to considerably enhanced efficacy. Furthermore, the red fluorescence of DOX and the blue fluorescence of g-C3N4 nanosheets provide the additional function of dual-color imaging for monitoring the drug release process.
    • The Great Irish Famine: identifying starvation in the tissues of victims using stable isotope analysis of bone and incremental dentine collagen

      Beaumont, Julia; Montgomery, Janet (2016-08-10)
      The major components of human diet both past and present may be estimated by measuring the carbon and nitrogen isotope ratios (δ13C and δ15N) of the collagenous proteins in bone and tooth dentine. However, the results from these two tissues differ substantially: bone collagen records a multi-year average whilst primary dentine records and retains timebound isotope ratios deriving from the period of tooth development. Recent studies harnessing a sub-annual temporal sampling resolution have shed new light on the individual dietary histories of our ancestors by identifying unexpected radical short-term dietary changes, the duration of breastfeeding and migration where dietary change occurs, and by raising questions regarding factors other than diet that may impact on δ13C and δ15N values. Here we show that the dentine δ13C and δ15N profiles of workhouse inmates dating from the Great Irish Famine of the 19th century not only record the expected dietary change from C3 potatoes to C4 maize, but when used together they also document prolonged nutritional and other physiological stress resulting from insufficient sustenance. In the adults, the influence of the maize-based diet is seen in the δ13C difference between dentine (formed in childhood) and rib (representing an average from the last few years of life). The demonstrated effects of stress on the δ13C and δ15N values will have an impact on the interpretations of diet in past populations even in slow-turnover tissues such as compact bone. This technique also has applicability in the investigation of modern children subject to nutritional distress where hair and nails are unavailable or do not record an adequate period of time.
    • A great wave: the Storegga tsunami and the end of Doggerland?

      Walker, James; Gaffney, Vincent L.; Fitch, Simon; Muru, Merle; Fraser, Andy; Bates, M.; Bates, R. (Cambridge University Press, 2020-12)
      Around 8150 BP, the Storegga tsunami struck North-west Europe. The size of this wave has led many to assume that it had a devastating impact upon contemporaneous Mesolithic communities, including the final inundation of Doggerland, the now submerged Mesolithic North Sea landscape. Here, the authors present the first evidence of the tsunami from the southern North Sea, and suggest that traditional notions of a catastrophically destructive event may need rethinking. In providing a more nuanced interpretation by incorporating the role of local topographic variation within the study of the Storegga event, we are better placed to understand the impact of such dramatic occurrences and their larger significance in settlement studies.
    • Greenbottle (Lucilia Sericata) larval secretions delivered from a prototype hydrogel wound dressing accelerate the closure of model wounds.

      Smith, Annie G.; Powis, Rachel A.; Pritchard, D.I.; Britland, Stephen T. (American Institute of Chemical Engineers (AIChE), 2008)
      The resurgence of larval biotherapy as a debridement tool in wound management has been accompanied by several clinical reports highlighting concomitant tissue regeneration. Studies employing in vitro cell motility assays have found that purified excretory/secretory (ES) products from Greenbottle larvae (blowfly, Lucilia sericata) are motogenic for human dermal fibroblasts when used as a supplement in culture media. The objective of the present study was to determine whether ES delivered using a prototype hydrogel wound dressing induced similar motogenic effects on fibroblastic (3T3) and epithelial cells (HaCaTs) comprising a scratched-monolayer wound model. Quantitative analysis by MTT assay failed to detect significant mitogenic effects of ES on either cell type. Quantitative image analysis revealed that ES exposure markedly accelerated wound closure through a motogenic effect on both fibroblasts and keratinocytes. Quantitative histochemical analysis detected significantly higher phosphotyrosine (pTyr) expression in ES-exposed cell cultures than in controls; moreover immunocytochemistry revealed conspicuously raised levels of pTyr expression in cells located at the wound margin. By attenuation with a panel of enzyme inhibitors these effects were attributed to the protease components of ES. The present results suggest that controlled delivery of ES as a follow-up to maggot debridement therapy may be an effective therapeutic option for stimulation of tissue regeneration in wound management.
    • Greener dye synthesis: continuous, solvent-free synthesis of commodity perylene diimides by twin-screw extrusion

      Cao, Q.; Crawford, Deborah E.; Shi, C.; James, S.L. (2020-03)
      A continuous, scalable, and solvent‐free method for the synthesis of various naphthalic imides and perylene diimides (PDIs) using twin‐screw extrusion (TSE) is reported. Using TSE, naphthalic imides were obtained quantitatively without the need for excess amine reactant or product purification. With good functional‐group tolerance, alkyl and benzyl amine derived PDIs (incl. commercial dyes) were obtained in 50–99 % yield. Use of K2CO3, enabled synthesis of more difficult aniline‐derived PDIs. Furthermore, an automated continuous TSE process for Pigments Black 31 and 32 is demonstrated, with a throughput rate of about 1500 g day−1, corresponding to a space time yield of about 30×103 kg m−3 day−1, which is 1–2 orders of magnitude greater than for solvent‐based batch methods. These methods provide substantial waste reductions and improved efficiency compared to conventional solvent‐based methods.
    • Greening Chemical Engineering laboratory at Bradford University

      Mujtaba, Iqbal M.; Patel, Rajnikant; Karodia, Nazira (2015)
      This paper highlights the work undertaken to assess the current state of the art of the Chemical Engineering Laboratory at the University of Bradford (UK) in terms of total energy and water usage and sound pollution and to propose an action plan to ‘greening’ the laboratory so that future students are trained in a laboratory where sustainability is the key feature of all learning activities. The project was funded by National Higher Education STEM (Science Technology Engineering and Mathematics) Programme. This review and assessment was carried out by two academic staff and one technical staff member with chemical engineering background.