• Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions.

      Rasoanaivo, P.; Wright, Colin W.; Willcox, M.L.; Gilbert, B. (2011)
      Background In traditional medicine whole plants or mixtures of plants are used rather than isolated compounds. There is evidence that crude plant extracts often have greater in vitro or/and in vivo antiplasmodial activity than isolated constituents at an equivalent dose. The aim of this paper is to review positive interactions between components of whole plant extracts, which may explain this. Methods Narrative review. Results There is evidence for several different types of positive interactions between different components of medicinal plants used in the treatment of malaria. Pharmacodynamic synergy has been demonstrated between the Cinchona alkaloids and between various plant extracts traditionally combined. Pharmacokinetic interactions occur, for example between constituents of Artemisia annua tea so that its artemisinin is more rapidly absorbed than the pure drug. Some plant extracts may have an immunomodulatory effect as well as a direct antiplasmodial effect. Several extracts contain multidrug resistance inhibitors, although none of these has been tested clinically in malaria. Some plant constituents are added mainly to attenuate the side-effects of others, for example ginger to prevent nausea. Conclusions More clinical research is needed on all types of interaction between plant constituents. This could include clinical trials of combinations of pure compounds (such as artemisinin + curcumin + piperine) and of combinations of herbal remedies (such as Artemisia annua leaves + Curcuma longa root + Piper nigum seeds). The former may enhance the activity of existing pharmaceutical preparations, and the latter may improve the effectiveness of existing herbal remedies for use in remote areas where modern drugs are unavailable.
    • The whole tooth and nothing but the tooth: or why temporal resolution of bone collagen may be unreliable

      Beaumont, Julia (Wiley, 2020-06)
      The carbon (δ13C) and nitrogen (δ15N) isotope ratios of human bone collagen have been used extensively over the last 40 years to investigate the diet of past populations. It has become apparent that bone collagen can give an unreliable temporal dietary signature especially in juveniles. With higher temporal resolution sampling of collagen from tooth dentine, it is possible to identify short‐term changes in diet previously invisible in bone. This paper discusses the inherent problems of using bone collagen for dietary studies and suggests better sample choices which can make our interpretations more robust, using breastfeeding and weaning as an example.
    • Whole-cell Currents Recording from Ion Channels in Human Lymphocytes Treated with Anti-inflammatory Drugs in Nanoparticles Forms

      Shang, Lijun; Najafzadeh, Mojgan; Anderson, Diana (2014)
      channels that are critical for their development and function. Many ion channels contribute to T cell-mediated autoimmune and/or inflammatory responses, so they are attractive targets for pharmacological immune modulations. In this study, we conduct patch clamp experiments to exam the whole cell currents from lymphocytes after nanoparticles exposure with the aim to test if nanoparticles exposure brings any electrophysiological changes for lymphocytes, and to compare the electrophysiological responses of lymphocytes to drugs in nanoparticles forms. Our result suggests a potential inhibition of effects of IBU N on lymphocytes. Such cytotoxicity of nanoparticles in Lymphocytes may be mainly associated with the early membrane damage. These results are also mirrored by the DNA damages occurred on lymphocytes after exposure of nanoparticles. Further detailed investigation is needed to explain the changes of Lymphocytes in response to NPs in real time and dose differences. This would provide useful information in the evaluation of toxicology of nanoparticles and in understanding the underlying mechanism of their effects on ion channels in health and diseases.
    • Whole-genome analysis of quorum-sensing Burkholderia sp. strain A9

      Chan, K.; Chen, J.W.; Tee, K.K.; Chang, Chien-Yi; Yin, W.; Chan, X. (2015-03)
      Burkholderia spp. rely on N-acyl homoserine lactone as quorum-sensing signal molecules which coordinate their phenotype at the population level. In this work, we present the whole genome of Burkholderia sp. strain A9, which enables the discovery of its N-acyl homoserine lactone synthase gene.
    • Whole-genome sequence and fosfomycin resistance of Bacillus sp. strain G3(2015) isolated from seawater off the coast of Malaysia

      Chan, X.; Chen, J.; Adrian, T.; Hong, K.; Chang, Chien-Yi; Yin, W.; Chan, K. (2017-03)
      Bacillus sp. is a Gram-positive bacterium that is commonly found in seawater. In this study, the genome of marine Bacillus sp. strain G3(2015) was sequenced using MiSeq. The fosfomycin resistant gene fosB was identified upon bacterial genome annotation.
    • Whole-genome sequencing analysis of quorumsensing Aeromonas hydrophila strain M023 from freshwater

      Tan, W.; Yin, W.; Chang, Chien-Yi; Chan, K. (2015-02)
      Aeromonas hydrophila is a well-known waterborne pathogen that recently was found to infect humans. Here, we report the draft genome of a freshwater isolate from a Malaysian waterfall, A. hydrophila strain M023, which portrays N-acylhomoserine lactone-dependent quorum sensing.
    • Whole-genome sequencing for TB source investigations: principles of ethical precision public health.

      van Rie, A.; de Viedma, D.G.; Meehan, Conor J.; Comas, I.; Heupink, T.H.; De Vos, E.; de Onate, W.A.; Mathys, V.; Ceyssens, P-J.; Groenen, G.; et al. (2021-03)
      BACKGROUND: Whole-genome sequencing (WGS) of Mycobacterium tuberculosis allows rapid, accurate inferences about the sources, location and timing of transmission. However, in an era of heightened concern for personal privacy and science distrust, such inferences could result in unintended harm and undermine the public´s trust. METHODS: We held interdisciplinary stakeholder discussions and performed ethical analyses of real-world illustrative cases to identify principles that optimise benefit and mitigate harm of M. tuberculosis WGS-driven TB source investigations.RESULTS: The speed and precision with which real-time WGS can be used to associate M. tuberculosis strains with sensitive information has raised important concerns. While detailed understanding of transmission events could mitigate harm to vulnerable patients and communities when otherwise unfairly blamed for TB outbreaks, the precision of WGS can also identify transmission events resulting in social blame, fear, discrimination, individual or location stigma, and the use of defaming language by the public, politicians and scientists. Public health programmes should balance the need to safeguard privacy with public health goals, transparency and individual rights, including the right to know who infects whom or where.CONCLUSIONS: Ethical challenges raised by real-time WGS-driven TB source investigation requires public health authorities to move beyond their current legal mandate and embrace transparency, privacy and community engagement.
    • Whole-genome shotgun sequencing of mitochondria from ancient hair shafts

      Gilbert, M.T.P.; Tomsho, L.P.; Rendulic, S.; Packard, M.; Drautz, D.I.; Sher, A.; Tikhonov, A.; Dalen, L.; Kuznetsova, T.; Kosintsev, P.; et al. (2007-09-28)
      Although the application of sequencing-by-synthesis techniques to DNA extracted from bones has revolutionized the study of ancient DNA, it has been plagued by large fractions of contaminating environmental DNA. The genetic analyses of hair shafts could be a solution: We present 10 previously unexamined Siberian mammoth (Mammuthus primigenius) mitochondrial genomes, sequenced with up to 48-fold coverage. The observed levels of damage-derived sequencing errors were lower than those observed in previously published frozen bone samples, even though one of the specimens was >50,000 14C years old and another had been stored for 200 years at room temperature. The method therefore sets the stage for molecular-genetic analysis of museum collections.
    • Why do people drive when they can’t see clearly?

      Fylan, F.; Hughes, A.; Wood, J.M.; Elliott, David B. (2018-07)
      Purpose Refractive blur is associated with decreased hazard perception and impairments in driving performance, but little is known about why people who have spectacles to correct their distance vision drive with uncorrected vision. Methods We conducted six focus groups. Participants were 30 drivers (mean age 45) who reported having driven uncorrected at least twice in the past six months despite having spectacles to correct their distance vision. Focus groups were audio recorded, transcribed verbatim and analysed thematically. Results We identified three themes. 1. Responsibility: participants did not feel obliged to drive with optimal vision and believed that others have a responsibility to ensure drivers maintain clear vision. 2. Safe Enough: participants felt safe to drive uncorrected, did not believe they need to wear spectacles to see sufficiently clearly and that they would know if their uncorrected eyesight fails to meet minimum standards. 3. Situations: participants discussed how they would drive uncorrected for short and familiar journeys, when they feel alert, in daylight and in good weather. Conclusions Beliefs about the importance of driving with clear vision compete with the benefits of not wearing spectacles. Eyecare professionals should provide more direct advice to patients regarding the need to wear their visual correction for driving.
    • Why is the General Ophthalmic Services (GOS) Contract that underpins primary eye care in the UK contrary to the public health interest?

      Shickle, D.; Davey, Christopher J.; Slade, S.V. (2015)
      The model for delivery of primary eye care in Europe varies from country to country with differing reliance on ophthalmologists, optometrists and dispensing opticians. Comparative analysis of models has tended to focus on interprofessional working arrangements, training and regulatory issues, rather than on whether a particular model is effective for delivering public health goals for that country. National Health Service (NHS) primary eye care services in the UK are predominantly provided under a General Ophthalmic Services (GOS) Contract between the NHS and practice owners (Contractors). Over two-thirds of sight tests conducted in England, Wales and Northern Ireland and all in Scotland are performed under a GOS Contract, however many people entitled to a GOS sight test do not take up their entitlement. The fee paid for sight tests conducted under a GOS Contract in England, Wales and Northern Ireland does not cover the full cost of conducting the examination. The shortfall must be made up through profits of sale of optical appliances but this business model can be a deterrent to establishing practices within socioeconomically deprived communities, and can also be a barrier to uptake of sight tests, even though many people are entitled to a NHS optical voucher towards the cost of spectacles or contact lenses. This paper critiques the GOS Contracts within the UK. We argue that aspects of the way the GOS Contract is implemented are contrary to the public health interest and that different approaches are needed to address eye health inequalities and to reduce preventable sight loss.
    • Will-o'-the-Wisp: an ancient mystery with extremophile origins?

      Edwards, Howell G.M. (2014)
      This paper draws a comparison between the 700-year-old historically reported will-o'-the-wisp phenomenon and the more recent discovery of extremophilic colonization of hostile environments; both have been observed as present in isolated, stressed environmental regions and originating from biological phenomena. However, whereas extremophilic activity can be understood in terms of a survival strategy based upon the synthesis of specific suites of protective biochemicals which are designed to control biogeologically the stressed habitats and to provide protection against the extreme environments, the analytical techniques that have proved so successful for the illumination of these survival strategies of extremophiles and which are now being miniaturized for in-field studies and for extraterrestrial exploration have not been applied to a clarification or evaluation of the phenomenon of will-o'-the-wisp. The reason is simply that the will-o'-the-wispsightings have now disappeared completely. Tantalizingly, all of the most reasonable physico-chemical and biological explanations for the will-o'-the-wisp phenomenon proved to be unsatisfactory in some respect and it is clear that, just as in the case of extremophilic colonization, will-o'-the-wisp would benefit from a modern rigorous analytical study which would produce the data from which the potentially novel biological behaviour could be characterized and which would help a better understanding to be made of our natural world.
    • Wise Up to Cancer Bradford: Improving cancer prevention and earlier diagnosis for South Asian women in Bradford

      Almas, Nisa; Haith-Cooper, Melanie; Nejadhamzeegilani, Z.; Payne, D.; Rattray, Marcus (University of Bradford, 2019-09)
    • Wnt Signaling as a Therapeutic Target in Cancer and Metastasis

      Morgan, Richard; Ankrah, R.; El-Tanani, S.; Patterson, Laurence H.; Loadman, Paul M.; Rudland, P.S.; El-Tanani, Mohamed (2017)
      Wnt signaling normally functions in cell determination and proliferation and is essential for embryonic development. It does this by regulating target genes through a tightly regulated but complex signaling cascade. Overexpression of these genes due to aberrant Wnt activity can lead to uncontrolled cell growth and survival, and ultimately oncogenesis. Wnt signaling is also involved in epithelial–mesenchymal transition that contributes to tumor progression and metastasis evidence that tumor growth can be suppressed irrespective of other neoplastic promoters when the Wnt pathway is blocked and this has led to interest in its use as a therapeutic target. Recent developments in our understanding of the Wnt signaling cascade have led to research into drugs that specifically target different levels in this pathway, and the identification of β-catenin as the primary cause of dysregulated Wnt signaling has led to a number of protein knockdown strategies. Moreover, increased knowledge of the 300–400 Wnt inducible genes has provided a large untapped source of new potential therapeutic targets. Existing drugs such as nonsteroidal anti-inflammatory drugs and vitamin A and D derivatives have also shown efficacy in disrupting the Wnt signaling pathway and, together with a new generation of derivatives, they may soon be in clinical trials. This chapter details the Wnt signaling pathway, its role in different cancers, and some potential therapeutic targets that may show promise as effective cancer treatments.
    • The WordPress Workshop: Blogging as a Method for Theory Development

      Fitzpatrick, Alexandra L. (2019-04)
      Blogs have proven to be a useful tool for academics as a tool for education and outreach in the Digital Age, with much written about their effectiveness in the classroom and as alternative means of publishing research. However, less consideration has been given to utilising the blog format for developing theory, particularly for graduate students and early career researchers. This paper will draw on both recent literature and personal experience to explore the potential of blogging as a means of introducing and developing unconventional and radical theory and research prior to more "formal" publication.
    • The World Wide reference collection: Zooarchaeological Twitter and the case for an international zooarchaeology database

      Fitzpatrick, Alexandra L. (2018-03)
      Social media platforms such as Twitter have allowed for a substantial increase in collaboration between academics, allowing access to information and advice from one side of the world to the other. This is especially true among both archaeologists and zooarchaeologists, who often turn to Twitter with faunal bones that they have been unable to identify so that another pair of zooarchaeological eyes can help. In many cases, Twitter has allowed access to reference collections that would have otherwise been inaccessible due to distance and monetary reasons. Based on numerous experiences in using the zooarchaeology community on Twitter to successfully identify archaeofaunal bones, this paper proposes that the next logical step for continuing collaboration among zooarchaeologists to is to develop an international digital database of faunal bone references, crowdsourced from reference collections of zooarchaeologists and institutions around the world. This database could bring zooarchaeology into the Open Access movement that will arguably define the future of archaeology in the digital world.
    • Wound healing protects against chemotherapy-induced alopecia in young rats via up-regulating interleukin-1β-mediated signaling

      Stojadinovic, O.; Wikramanayake, T.C.; Villasante Fricke, A.C.; Yin, N.C.; Liang, L.; Hinde, E.; Escandon, J.; Tomic-Canic, M.; Ansell, David M.; Paus, R.; et al. (2017-05-30)
      Wound healing is a complex process regulated by various cell types and a plethora of mediators. While interactions between wounded skin and the hair follicles (HFs) could induce HF neogenesis or promote wound healing, it remains unknown whether the wound healing-associated signaling milieu can be manipulated to protect against alopecia, such as chemotherapy-induced alopecia (CIA). Utilizing a well-established neonatal rat model of CIA, we show here that skin wounding protects from alopecia caused by several clinically relevant chemotherapeutic regimens, and that protection is dependent on the time of wounding and hair cycle stage. Gene expression profiling unveiled a significant increase in interleukin-1 beta (IL-1β) mediated signaling by skin wounding. Subsequently, we showed that IL-1β is sufficient and indispensable for mediating the CIA-protective effect. Administration of IL-1β alone to unwounded rats exhibited local CIA protection while IL-1β neutralization abrogated CIA protection by wounding. Mechanistically, IL-1β retarded postnatal HF morphogenesis, making HFs at the wound sites or IL-1β treated areas damage-resistant while the rats developed total alopecia elsewhere. We conclude that wound healing switches the cutaneous cytokine milieu to an IL-1β-dominated state thus retarding HF growth progression and rendering the HFs resistant to chemotherapy agents. In the future, manipulation of HF progression through interfering with the IL-1β signaling milieu may provide therapeutic benefits to a variety of conditions, from prevention of CIA to inhibition of hair growth and treatment of hirsutism.