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Writing in 2022 we are at a global crisis point, as our use of the planet’s finite resources outstrips supply. Our current lifestyles continue to perpetuate this problem by encouraging excessive and wasteful models of consumption. One of the most detrimental industries for this is the clothing industry. Our fashion cycle is now programmed to be ‘ultra-fast’, encouraging excessive consumption of garments causing myriad environmental issues. This article argues that there are developing models of both manufacture and consumption, which can satiate this need for ‘fast’ fashion whilst being part of the wider sustainable fashion conversation. Rather than understanding the short-term life cycle of clothing as inherently unsustainable, this can be reframed as matching a garment’s use phase to the longevity of the material it is made from. This article uses a material culture approach to explore original 1960s paper garments, alongside a critical analysis of the sustainability of their manufacture and disposal from a green chemical perspective. Using the combined knowledge and experience of its authors, from historians and sustainable fashion designers to green chemists and biochemical engineers, this article demonstrates how such garments could inspire new models of sustainable fashion production and consumption. We argue that the current paradigm of slow fashion as the only antidote to fast fashion must be challenged. Instead, the fashion and textile sector must consider a range of solutions to the environmental burden of fast fashion that are human-centred and sympathetic to all consumer demographics and needs.

Phenanthriplatin forms DNA mono-adducts and induces ribosome biogenesis stress. Using a semi-rational strategy, Ru(ii) complexes were created that act as biological mimics of phenanthriplatin with improved properties.

Table S4

Supplementary Data

Melanoma incidence is increasing worldwide, and metastatic melanoma is almost completely resistant to every known therapy. New approaches to treating melanoma are urgently needed, and a greater understanding of the biology of melanoma invasion and metastasis will aid in their creation. A high proportion of invasive melanomas have a constitutively active Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) signaling cascade; however, the downstream effectors of ERK signaling that contribute to melanoma invasion and metastasis are unknown. ERK signaling drives the production of the interstitial collagenase matrix metalloproteinase-1 (MMP-1), which is expressed specifically by invasive melanomas. Using short hairpin RNAs (shRNA) to knock down MMP-1 expression in a human melanoma cell line, we investigated the role of MMP-1 in melanoma metastasis in a xenograft model. Knockdown of MMP-1 had no effect on primary tumor growth, but reduction of MMP-1 expression significantly decreased the ability of the melanoma to metastasize from the orthotopic site in the dermis to the lung. Mechanistically, tumor cells expressing MMP-1 shRNAs had diminished collagenase activity, which is required for tumor cell invasion. Additionally, attenuation of MMP-1 expression reduced angiogenesis. These results show, for the first time, that targeted inhibition of MMP-1, a single effector of the Raf/MEK/ERK signaling cascade, prevents the progression of melanoma from a primary to metastatic tumor and, as such, may represent a useful therapeutic tool in controlling this disease. [Cancer Res 2007;67(22):10849–58]

Supplementary Table 1 from RNA Interference Inhibition of Matrix Metalloproteinase-1 Prevents Melanoma Metastasis by Reducing Tumor Collagenase Activity and Angiogenesis

Supplementary Figure 1 from RNA Interference Inhibition of Matrix Metalloproteinase-1 Prevents Melanoma Metastasis by Reducing Tumor Collagenase Activity and Angiogenesis

Made available in DSpace on 2022-04-28T19:52:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-18 Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale. Department of Biology University of Toronto Mississauga ON Centre for Urban Environments University of Toronto Mississauga ON Department of Biology University of North Carolina, Chapel Hill Department of Biology University of Louisiana LA Department of Biology Queen's University ON Department of Biology Concordia University QC Department of Biological Sciences DePaul University Department of Biology DePauw University IN Department of Urban Design and Planning, University of Washington, Seattle, WA, USA Colegio de Ciencias Biológicas y Ambientales Universidad San Francisco de Quito USFQ Department of Genetics University of Georgia Department of Ecology and Genetics Evolutionary Biology Centre Uppsala University Field Science Center for Northern Biosphere Hokkaido University Natural History Museum Zoology University of New England NSW Programa de Pós-Graduação em Geografia da UFMT campus de Rondonópolis Department of Botany and Biodiversity Research Centre University of British Columbia Graduate Program in Genome Sciences and Technology Genome Sciences Centre University of British Columbia Department of Microbiology and Immunology University of British Columbia Red de Biología Evolutiva Instituto de Ecología A. C. School of the Environment Yale University CT Departamento de Ciencias Ecológicas Universidad de Chile, Facultad de Ciencias Instituto de Ecología y Biodiversidad Universidad de Chile Department of Biology Mount Allison University Red de Ecoetología Instituto de Ecología A. C. Department of Biology University of Ottawa ON Department of Zoology University of Cambridge Department of Biology, Washington University in St. Louis, St. Louis, MO, USA Department of Biology University of Miami FL Centro de Investigación en Recursos Naturales y Sustentabilidad (CIRENYS) Universidad Bernardo O'Higgins Department of Biology, University of La Verne, La Verne, CA, USA Département des sciences du bois et de la forêt Université Laval QC Evolution & Ecology Research Centre School of Biological Earth and Environmental Sciences UNSW Sydney NSW Department of Biology Ghent University Department of Biology Monmouth University West Long Branch Centre for Ecology Evolution and Environmental Changes Faculdade de Ciências Universidade de Lisboa Lisboa Department of Biology KU Leuven School of Agriculture and Environment Wildlife and Ecology group Massey University, Palmerston North Department of Biological Sciences University of Cape Town Institute of Landscape Ecology University of Münster Gosnell School of Life Sciences, Rochester Institute of Technology, Rochester, NY, USA Department of Biological Sciences University of Alberta AB Louis Calder Center and Department of Biological Sciences, Fordham University, Armonk, NY, USA Departamento de Ecología Tropical, Universidad Autónoma de Yucatán, Mérida, Yucatán, México School of Life Sciences University of Sussex Department of Ecology Environment and Plant Sciences Stockholm University iBIOTROP Instituto de Biodiversidad Tropical Universidad San Francisco de Quito Department of Biology, San Francisco State University, San Francisco, CA, USA Unidad de Recursos Naturales, Centro de Investigación Científica de Yucatán AC, Mérida, Yucatán, México School of Ecological and Environmental Sciences East China Normal University Shanghai Engineering Research Center of Sustainable Plant Innovation Centre for Ecosystem Science School of Biological Earth and Environmental Sciences UNSW Sydney NSW Department of Ecology and Evolutionary Biology University of Michigan MI Department of Biosciences Rice University TX IFEVA Universidad de Buenos Aires Facultad de Agronomía, CONICET Biology Department Saint Mary's University NS Department of Biological Sciences, Universidad de los Andes Department of Biology and Biochemistry University of Houston TX Université de Rennes Department of Zoology and Biodiversity Research Centre University of British Columbia Department of Environmental Studies Dordt University Sioux Center IA Department of Biology Minneapolis Community and Technical College MN Department of Natural Sciences Ecology and Environment Research Centre Manchester Metropolitan University Instituto de Investigaciones en Ecosistemas y Sustentabilidad UNAM Department of Botany School of Biology Aristotle University of Thessaloniki Faculty of Biological and Environmental Science Organismal & Evolutionary Biology Research Programme University of Helsinki Institute of Biodiversity Animal Health and Comparative Medicine University of Glasgow Department of Biology Hendrix College Department of Ecological Science Vrije Universiteit Amsterdam Departamento de Ciencias Biológicas y Agropecuarias Universidad Técnica Particular de Loja Departamento de Biologia Universidade Federal de Santa Maria (UFSM) Department of Plant Sciences School of Biology College of Science University of Tehran NTNU University Museum Norwegian University of Science and Technology Red de Estudios Moleculares Avanzados Instituto de Ecología A. C. School of Biological Sciences, University of Reading, Whiteknights Park, Reading, Berkshire, UK Department of Biology Northern Arizona University AZ Department of Biological Sciences MacEwan University AB Max Planck Institute for Plant Breeding Research Departamento de Ecología Evolutiva Instituto de Ecología Universidad Nacional Autónoma de México Max Planck Institute of Molecular Plant Physiology Potsdam-Golm BIO5 Institute University of Arizona AZ Alaska Center for Conservation Science University of Alaska Anchorage Tropical Diversity, Royal Botanical Garden of Edinburgh Département de biologie Université de Moncton Department of Biological Sciences University of Manitoba MB Departments of Microbiology & Statistics University of Manitoba MB Department of Biology University of New Brunswick Department of Biology Kalamazoo College MI BioProtection Research Centre Lincoln University Departamento de Ciencias Facultad de Artes Liberales Universidad Adolfo Ibáñez Department of Ecology Evolution Behaviour University of Minnesota MN Department of Biological Sciences Brock University Department of Environmental Toxicology, University of California, Davis, CA, USA ICB - University of Talca School of Molecular and Life Science Curtin University College of Science Health Engineering and Education Murdoch University, Murdoch School of Life and Environmental Sciences University of Sydney NSW School of Biological Sciences, Monash University, Melbourne, VIC, Australia Department of Biological Sciences Wayne State University MI Department of Biology Western Oregon University, OR School of Natural Resources and the Environment University of Arizona AZ Departamento de Ecología Humana, Cinvestav Mérida Departamento de Ciencias Biológicas y Departamento de Ecología y Biodiversidad Facultad de Ciencias de la Vida, Universidad Andrés Bello Institute of Ecology and Biodiversity (IEB) Department of Biology Lund University Department of Biology Norwegian University of Science and Technology Escuela Superiro de Desarrollo Sustentable Universidad Autónoma de Guerrero -CONACYT Clarkson Secondary School Peel District School Board ON Homelands Sr. Public School Peel District School Board ON Department of Biological Sciences University of Illinois at Chicago Dufferin-Peel Catholic District School Board, St. James Catholic Global Learning Centre Department of Biosciences University of Calgary AB Ecological Processes Branch U.S. Army ERDC-CERL Department of Biology, Oberlin College, Oberlin, OH, USA Escuela Nacional de Estudios Superiores Unidad Morelia UNAM Institute of Evolution and Ecology University of Tübingen Tübingen Department of Evolutionary Biology and Environmental Studies University of Zurich, Winterthurerstrasse Urban Wildlife Institute Department of Conservation and Science, Lincoln Park Zoo Departamento de Ecología Universidad Católica de la Santísima Concepción Department of Biological Sciences University of Denver CO Department of Biological Sciences Mississippi State University MS Department of Biology Center for Computational & Integrative Biology Rutgers University-Camden Kunming Institute of Botany Chinese Academy of Sciences Department of Chemistry & Biochemistry Laurentian University ON Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering College of Life Sciences Beijing Normal University School of BioSciences, University of Melbourne, Melbourne, VIC, Australia Posgrado en Ciencias Biológicas Universidad Nacional Autónoma de México Department of Biological Sciences, Auburn University, Auburn, AL, USA Department of Entomology and Nematology, University of California, Davis, CA, USA Department of Biology University of New Mexico NM Department of Biology University of Wisconsin - Eau Claire Agriculture Institute Iranian Research Organization for Science and Technology (IROST) Department of Biology Colby College ME Instituto de Biología Universidad de Antioquia Department of Biology University of Massachusetts Boston MA Agricultural Biology Colorado State University CO Departamento de Biología Vegetal y Ecología Facultad de Biología Universidad de Sevilla, Av. Reina Mercedes s/n Facultad de Estudios Interdisciplinarios Centro GEMA- Genómica Universidad Mayor Evolutionary Ecology Group Naturalis Biodiversity Center Department of Biology and Chemistry Nipissing University ON, North Bay Center for Ecological Research Kyoto University Bonanza Creek Long Term Ecological Research Program University of Alaska Fairbanks Department of Botany and Molecular Evolution Senckenberg Research Institute and Natural History Museum Frankfurt Departamento de Biodiversidade Instituto de Biociências Univ Estadual Paulista - UNESP Nelson Institute for Environmental Studies University of Wisconsin-Madison WI Department of Biology, California State University, Northridge, Los Angeles, CA, USA Department of Ecology Swedish University of Agricultural Sciences Facultad de Ciencias y Biotecnologia Universidad CES Department of Biology Hofstra University Faculty of Biosciences and Aquaculture Nord University, Bodø Division of Biological Sciences, University of California San Diego, San Diego, CA, USA Department of Biology University of Richmond VA Estación de Biodiversidad Tiputini Colegio de Ciencias Biológicas y Ambientales Universidad San Francisco de Quito USFQ Department of Biological Sciences Institute of Environment Florida International University FL Agronomy Department University of Almería Department of Biological Sciences and Center for Urban Ecology and Sustainability Butler University IN Department of Biological Sciences Louisiana State University LA Faculty of Biological Sciences, Goethe University Frankfurt Institute of Biology Leiden Leiden University Department of Biological and Environmental Science University of Jyväskylä Jyväskylä Department of Biology University of Louisville KY Organization for Programs on Environmental Science University of Tokyo CNRS AgroParisTech Ecologie Systématique et Evolution, Université Paris-Saclay Department of Biology, Providence College, Providence, RI, USA General Zoology Institute for Biology Martin Luther University Halle-Wittenberg International Arctic Research Center University of Alaska Fairbanks Science, Technology and Society Department, Rochester Institute of Technology, Rochester, NY, USA SLU Swedish Species Information Centre Swedish University of Agricultural Sciences Department of Biology Westfield State University MA Centre of New Technologies University of Warsaw Department of Biology, Stanford University, Stanford, CA, USA Plant Biology Department Michigan State University MI Biology Department Davidson College College of Horticulture and Forestry Sciences/ Hubei Engineering Technology Research Center for Forestry Information Huazhong Agricultural University School of Life Sciences Technical University of Munich School of Life Sciences Lanzhou University Institute of Ecology and Evolution University of Bern Department of Evolution Ecology and Behaviour University of Liverpool Departamento de Biodiversidade Instituto de Biociências Univ Estadual Paulista - UNESP

Background Nanopore sequencing technology has revolutionized the field of genome biology with its ability to generate extra-long reads that can resolve regions of the genome that were previously inaccessible to short-read sequencing platforms. Over 50% of the zebrafish genome consists of difficult to map, highly repetitive, low complexity elements that pose inherent problems for short-read sequencers and assemblers. Results We used long-read nanopore sequencing to generate a de novo assembly of the zebrafish genome and compared our assembly to the current reference genome, GRCz11. The new assembly identified 1697 novel insertions and deletions over one kilobase in length and placed 106 previously unlocalized scaffolds. We also discovered additional sites of retrotransposon integration previously unreported in GRCz11 and observed the expression of these transposable elements in adult zebrafish under physiologic conditions, implying they have active mobility in the zebrafish genome and contribute to the ever-changing genomic landscape. Conclusions We used nanopore sequencing to improve upon and resolve the issues plaguing the current zebrafish reference assembly, GRCz11. Zebrafish is a prominent model of human disease, and our corrected assembly will be useful for studies relying on interspecies comparisons and precise linkage of genetic events to disease phenotypes.

Graphic abstract Sunscreen safety and efficacy is generally evaluated based upon the properties of the individual chemicals in a formulation. However, the photostability of sunscreens has been shown to be highly dependent on the mixture of chemicals present. To better understand how sunscreen formulation influences stability, and to establish a foundation for probing the influence of zinc oxide additives, we formulated five different small-molecule based ultraviolet-filter (UV-filter) mixtures with a Sun Protection Factor (SPF) of 15. These mixtures contained active ingredients approved in either the United States or European Union and were designed to represent formulations of actual products on the market. We evaluated the photostability and toxicity of these mixtures in the absence and presence of zinc oxide after UV exposure for two hours. Changes in UV absorbance were minimal for all five small-molecule-based mixtures without zinc oxide. The presence of either micro- or nano-sized zinc oxide caused significant small-molecule photodegradation and the degraded mixtures exhibited higher levels of toxicity in embryonic zebrafish assays. This study suggests that caution must be taken when formulating sunscreens containing both zinc oxide and small-molecule UV-filters to avoid unintended consequences during use. Supplementary Information The online version contains supplementary material available at 10.1007/s43630-021-00101-2.

The β-diketone scaffold is a commonly used synthetic intermediate, and is a functional group found in natural products such as curcuminoids. This core structure can also act as a chelating ligand for a variety of metals. In order to assess the potential of this scaffold for medicinal inorganic chemistry, seven different κ(2)-O,O’-chelating ligands were used to construct Ru(II) complexes with polypyridyl co-ligands, and their biological activity was evaluated. The complexes demonstrated promising structure-dependent cytotoxicity. Three complexes maintained high activity in a tumor spheroid model, and all complexes demonstrated low in vivo toxicity in a zebrafish model. From this series, the best compound exhibited a ~ 30-fold window between cytotoxicity in a 3-D tumor spheroid model and potential in vivo toxicity. These results suggest that κ(2)-O,O’-ligands can be incorporated into Ru(II)-polypyridyl complexes to create favorable candidates for future drug development.

Over 34 000 patients are diagnosed yearly with multiple myeloma (MM), which remains a fatal malignancy. Expression of the phosphatase PRL-3 is associated with poor prognosis in MM patients, and Vandsemb et al. have demonstrated that PRL-3 contributes to enhanced MM cell fitness through activation of a glycolysis-associated feedback loop. PRL-3 resulted in increased expression of signal transducer and activator of transcription 1 (STAT1) and 2 (STAT2) and increased glycolysis. Increased glucose metabolism in turn activated STAT1/2 and interferon 1-related genes. This discovery advances the MM field by providing a new potential treatment avenue. Comment on: https://doi.org/10.1111/febs.16058.

The AATCC TM22-2014 spray test (similarly BS EN ISO 4920:2012) is widely used to determine the water repellency of textiles. Given the ongoing move towards non-fluorinated chemistries to provide water repellent finishes on textiles, modifications to the spray test are suggested to discriminate between those which initially demonstrate similar repellency and aid in assessment of performance within laboratory textile testing. An extended shower duration of 60 minutes or 120 minutes is recommended, with additional calculations to objectively quantify surface wetting. This increased test period demonstrated differences in performance between repellent finishes with a 1.37 g mass difference between fluorinated and non-fluorinated chemistries after 120 minutes. Further quantification of repellent performance, as set out in this study, would determine the performance of non-fluorinated durable water repellent (DWR) chemistries and suitability for end use.

Introduction Tumor necrosis factor inhibitors (TNFi) are commonly used as first-line therapy (biologic disease-modifying antirheumatic drug [bDMARD] and targeted synthetic DMARD [tsDMARD]: defined as targeted therapy) for patients with moderate-to-severe rheumatoid arthritis (RA), usually combined with conventional synthetic DMARDs (csDMARDs) but sometimes as monotherapy. If treatment fails, patients cycle to another TNFi (cycling) or switch to a targeted therapy with a different mode of action (MOA; switching). The study aimed to examine prescribing patterns and reasons for current RA treatment practice in Europe (EU5: France, Germany, Italy, Spain, UK) and Japan. Methods Data were collected from the Adelphi Disease Specific Programme™ (DSP; Q1–Q2 2017). Rheumatologists seeing ≥ 10 (EU5) and ≥ 5 (Japan) patients with RA a month completed Patient Record Forms. Patients ≥ 18 years old, with RA diagnosis and complete RA-targeted therapy history were included. Patients were grouped based on first-line targeted therapy class, and on whether first-line targeted therapy was monotherapy (targeted therapy alone) or combination therapy (targeted therapy and csDMARD). Those patients receiving TNFi at first-line and with ≥ 1 targeted therapy were classified as TNFi cyclers or MOA switchers. Univariate analysis compared factors across groups. Patient demographics and characteristics compared across groups; physician reasoning for targeted therapy change; and time to discontinuation of targeted therapy. Results In EU5 and Japan, respectively, 1741 and 147 patients were included; at first-line, 80.8% and 64.6% received TNFi and 76.0% and 77.6% received combination therapy. Overall in EU5, more combination therapy than monotherapy patients reached maximum csDMARD dose before first-line targeted therapy (P

Introduction Some patients with rheumatoid arthritis (RA) using tumor necrosis factor inhibitors (TNFi) experience inefficacy or lack of tolerability and hence switch to another TNFi (cycling) or to a therapy with another mode of action (switching). This study examined patient characteristics, prescribing patterns and treatment practice for RA in the United States. Methods Data were from the Adelphi Disease Specific Programme (Q2–Q3 2016). Rheumatologists completed a survey and patient record forms for adult patients with RA who had received ≥ 1 targeted therapy. Patients were grouped by class of first-used targeted therapy, and monotherapy vs. combination therapy. TNFi patients who received ≥ 1 targeted therapy were classified as cyclers or switchers. Univariate analyses compared patient characteristics and physician factors across the analysis groups. Results Overall, 631 patients received ≥ 1 targeted therapy; 535 were prescribed a TNFi as first targeted therapy, 53 a nonTNFi biologic disease-modifying antirheumatic drug (bDMARD), and 43 tofacitinib. Of 577 patients with known conventional synthetic (cs) DMARD status, 18.7% were prescribed monotherapy and 81.3% combination therapy. Combination therapy patients received significantly more concomitant medications prior to initiation of first targeted therapy than monotherapy patients (P

Global ecosystem functions, services, and commodities are increasingly threatened by biological invasions. As a result, there is an urgent need to manage invasive species through global collaborative research. We propose an ‘applied empirical framework’ (AEF) to aggressively confront the current global biological invasion crisis. The AEF builds on existing models for invasion science that advocate 1) standardized research designs to reveal key aspects of biological invasion, and 2) collaborative research to facilitate the sharing of resources and information. The AEF further emphasizes the need for 3) the production of research ‘tools’ (e.g., data, methodologies, technical instruments) designed for direct uptake by agencies that manage biological invasion, and 4) a taxonomically targeted approach in which task forces conduct rapid, in-depth research on top-priority invasive species across their entire geographic range. We review collaborative science and the distinctive roles played by different collaborator types. We then provide an example of the AEF in action through the BioSAFE initiative (Biosurveillance of Alien Forest Enemies), a highly collaborative project aimed at developing genomic research tools to facilitate biosurveillance and intervention for forest invasive species. We illustrate the BioSAFE approach through our research on two polyphagous insect species: the wood-borer Anoplophora glabripennis, Motschusky (Coleoptera: Cerambycidae; Asian longhorned beetle) and the defoliator Lymantria dispar, Linnaeus spp. (Lepidoptera: Lymantriidae; gypsy moth). These examples illustrate how the AEF can focus and accelerate our response to the global biological invasion crisis by applying the resource capabilities of collaborative research groups to generate management tools for top-priority invasive species.

Acute Lymphoblastic Leukemia (ALL) patients that are positive for minimal residual disease (MRD) after therapy or have leukemic infiltration into the central nervous system (CNS) are considered high risk and receive intensive chemotherapy regimens. Current methods to diagnose MRD and CNS infiltration rely on detecting leukemic cells in patient samples using pathology, flow cytometry, or next-generation sequencing. However, leukemic blasts may persist in the patient but not be physically present in bone marrow biopsy or biofluid sample, leading to inaccurate or delayed patient diagnosis. We have developed a nanopore sequencing workflow to detect B-ALL-associated cell-free DNA (cfDNA) in blood and cerebrospinal fluid (CSF) samples. Quantitation of B-cell specific VDJ recombination events in cfDNA samples defined B-ALL clonal heterogeneity. This workflow allowed us to track the response of individual B-ALL clones throughout treatment. Detection of cfDNA also predicted the clinical diagnosis of MRD and CNS disease. Importantly, we identified patients diagnosed as CNS negative who had low B-cell derived cell-free DNA levels in their CSF sample that correlated with B-cell clones present in the bone marrow. These data suggest that cfDNA assays may be useful in detecting the presence of ALL in the patient even when blasts are not in the biofluid sample. Nanopore analysis of cell-free DNA is a simple, rapid, and inexpensive assay that can serve as a valuable complement to traditional clinical diagnostic approaches for ALL.Abstract Figure

John Mercer (1791–1866) was a pioneering textile and colour chemist with a legacy of achievements. His invention of mercerising that bears his name, treating cellulosics with sodium hydroxide to bring about advantageous changes in fibre and fabric properties, will stand for all time as one of the most important textile chemical treatments ever developed. However, Mercer's contributions to the textiles and coloration industries went far beyond mercerisation. A self‐taught chemical experimentalist par excellence, his keen observations and interest in calico printing led to many novel developments, such as his work on Chrome Yellow and other ‘mineral colours’. Mercer developed new methods for fixing Prussian Blue on calico and wool, developed new mordants for dyeing, improved the extraction of carminic acid from cochineal, and improved the oiling process in Turkey Red dyeing. He saved lives with his research into early antimicrobials, preventing the spread of cholera in textile villages in Lancashire. Mercer was an unsung hero of early photography, and developed light‐sensitive imaging materials and made some of the earliest recorded monochromatic colour photographs. His forward‐looking views on technical education, that workers in the industry should be fully instructed in the nature of the various substances used in their arts, later came to fruition in the establishment of the textile departments in Manchester, Leeds and Glasgow. To this day, Mercer remains the only textile chemist who has ever been elected as a Fellow of the Royal Society since 1852. He is thus quite rightly considered as the Father of Textile Chemistry.

Structure-activity relationships (SAR) in the aurone pharmacophore identified heterocyclic variants of the (Z)-2-benzylidene-6-hydroxybenzofuran-3(2H)-one scaffold that possessed low nanomolar in vitro potency in cell proliferation assays using various cancer cell lines, in vivo potency in prostate cancer PC-3 xenograft and zebrafish models, selectivity for the colchicine-binding site on tubulin, and absence of appreciable toxicity. Among the leading, biologically active analogs were (Z)-2-((2-((1-ethyl-5-methoxy-1H-indol-3-yl)methylene)-3-oxo-2,3-dihydrobenzofuran-6-yl)oxy)acetonitrile (5a) and (Z)-6-((2,6-dichlorobenzyl)oxy)-2-(pyridin-4-ylmethylene)benzofuran-3(2H)-one (5b) that inhibited in vitro PC-3 prostate cancer cell proliferation with IC50 values below 100 nM. A xenograft study in nude mice using 10 mg/kg of 5a had no effect on mice weight, and aurone 5a did not inhibit, as desired, the human ether-à-go-go-related (hERG) potassium channel. Cell cycle arrest data, comparisons of the inhibition of cancer cell proliferation by aurones and known antineoplastic agents, and in vitro inhibition of tubulin polymerization indicated that aurone 5a disrupted tubulin dynamics. Based on molecular docking and confirmed by liquid chromatography-electrospray ionization-tandem mass spectrometry studies, aurone 5a targets the colchicine-binding site on tubulin. In addition to solid tumors, aurones 5a and 5b strongly inhibited in vitro a panel of human leukemia cancer cell lines and the in vivo myc-induced T cell acute lymphoblastic leukemia (T-ALL) in a zebrafish model.

Objective: There are limited data on therapy selection and switching in psoriatic arthritis (PsA). This 18 country, real-world study assessed use and switching of immunomodulatory therapy (biologic/apremilast), the extent of treatment failure and its association with reduced physical functioning, health-related quality of life (HRQoL), and work productivity and activity impairment (WPAI). Methods: PsA patients under routine care and their treating physicians provided demographics, current therapy, reasons for switching, duration of first therapy, HRQoL, HAQ-DI, and WPAI. Current immunomodulatory therapy was determined as “failing” if, after ≥ 3 months, physician-rated disease severity had worsened, remained severe, was “unstable/deteriorating,” or they were dissatisfied with disease control and/or did not consider treatment a “success.” Results: Included were 3714 PsA patients; 1455 (40.6%) had never received immunomodulatory therapy; 1796 (50.1%) had ever received 1 immunomodulatory therapy and 331 (9.2%) ≥ 1. Lack of efficacy with first immunomodulatory therapy was the most common reason for switching; patients whose physicians indicated “primary lack of efficacy” as the reason, switched after a mean of 9.4 months. Patients currently failing immunomodulator therapies (n = 246) had poorer HRQoL compared with treatment success (n = 1472) measured by EQ-5D-3L (0.60 vs 0.77%; P

We are currently experiencing a global environmental crisis. Our waste culture is leading to huge irreversible damage to our planet and ecosystems. This is particularly evident in both the textile and food sectors, with a system-wide restructuring as to how we consume and source materials becoming ever more urgent. By considering our waste as resource, we can access a vast source of raw materials that is now being recognised as such. Viable materials in the form of waste have the potential for conversion into textiles. However, this proposed solution to our contemporary crisis is not new technology. Throughout the 20th century, science and industry have researched and developed materials from food waste to meet global demand for textiles in times of need, with a major development during the world wars being the invention of regenerated protein fibres (RPFs). For various reasons, this research was abandoned, but much of the development work remains valid. This research critically analyses work that has previously been done in the sector to better our understanding of the historical hindrances to the progression of this technology. By applying modern thinking and scientific advances to historical challenges, there is the potential to overcome previous barriers to utilising food waste as a resource. One of the key influences in the discontinuation of RPFs was the rise of petrochemical textiles. Our current understanding of the detriment caused by petrochemicals warrants a further review of historical emergent technologies. This paper uses Ardil fibre as a case study, and shows that there is a clear disparity between the location of historic research and where the research would now be helpful. Ardil was a British-made product, using peanuts sourced from the British Empire as the source of protein. Techniques used in the processing of Ardil could be better utilised by countries and climates currently producing large amounts of peanut byproducts and waste. Through this research, another historical concern that thwarted Ardil’s acceptance as a mainstream fibre was discovered to be its poor tensile strength. However, contemporary garment life cycles are far shorter than historical ones, with built-in obsolescence now being considered as a solution to fast fashion cycles by matching the longevity of the fibre to the expected use phase of the garment, but ensuring suitable disposal methods, such as composting. This research highlights the need for cross-disciplinary collaboration between sectors, with a specific focus on the wealth of valuable information available within historical archives for modern sustainability goals.

Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3) is an oncogenic dual-specificity phosphatase that drives tumor metastasis, promotes cancer cell survival, and is correlated with poor patient prognosis in a variety of solid tumors and leukemias. The mechanisms that drive PRL-3’s oncogenic functions are not well understood, in part due to a lack of research tools available to study this protein. The development of such tools has proven difficult, as the PRL family is ~80% homologous and the PRL catalytic binding pocket is shallow and hydrophobic. Currently available small molecules do not exhibit binding specificity for PRL-3 over PRL family members, and the only research antibody specific for PRL-3 can only recognize denatured protein. To address the lack of tools available to study PRL-3, we have developed alpaca-derived single domain antibodies, or nanobodies, targeting PRL-3. Nanobodies have emerged as a valuable research tool and show promise as cancer therapeutics as they are ~15kD and lack light chains, allowing them to reach cavities within active sites that conventional antibodies cannot normally reach. Nanobodies also maintain high specificity and affinity for their antigens. We identified seven unique nanobodies that bind to PRL-3 with no activity towards PRL-1 and PRL-2, making our nanobodies one of the first tools to selectively target PRL-3 in its native state. We used biolayer interferometry and found the nanobody binding affinity for PRL-3 to be within a KD of 30 - 300 nM, similar to that of antibodies currently on the market. We identified PRL-3:nanobody interactions with hydrogen-deuterium exchange mass spectrometry (HDX-MS) and showed binding outside the active site. These data were confirmed by analyzing the effects of nanobodies on PRL-3 phosphatase activity and substrate binding. Our anti-PRL-3 nanobodies specifically pulled down PRL-3 over PRL-1/-2 in immunoprecipitation experiments. Finally, we used these nanobodies to analyze PRL-3 localization in fixed immunofluorescence experiments in human cancer cells. We found that a C-terminal tag on PRL-3, such as FLAG or GFP, enhanced PRL-3 localization to the membrane, compared to untagged protein, which may have confounded previous PRL-3 functional studies. We are currently utilizing these nanobodies in two ways to understand PRL-3’s role in cancer. First, we will use the nanobody to stabilize PRL-3 for X-ray crystallography to develop higher resolution structures that could contribute to substrate identification and drug design. Secondly, we will examine PRL-3 function and trafficking during various cancer processes, such as proliferation, invasion, and stress, to determine how PRL-3 localization contributes to cancer progression. Citation Format: Caroline Noel Smith, Kyle Kihn, Zachary A. Williamson, K. Martin Chow, Louis B. Hersh, Konstantin Korotkov, Daniel Deredge, Jessica S. Blackburn. Development and validation of nanobodies specific to the oncogenic phosphatase protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 672.

Indigo (C.I. Vat Blue 1) is a water-insoluble pigment exhibiting no affinity for fibres, and must be chemically reduced in basic solution to form the water-soluble, alkaline leucoindigo (C.I. Reduced Vat Blue 1), in order exhibit substantivity for fibres. Typical vat dyeing processes are time and resource intensive, and hazardous by-products are formed, primarily through the use of reducing agents. We describe a method for synthesizing indigo in a flow reactor that allows for application of dye precursors to fibres moments before the reaction completes. The soluble precursors soak into the cotton fabric just prior to the precipitation of the insoluble indigo, effectively providing in-situ coloration, without the need for a traditional redox dyebath. The reaction may be coupled with a propellant, an adaptation that allows for a “sprayable” form of indigo. In-situ coloration with Tyrian purple (6,6′-dibromoindigo; C.I. Natural Violet 1) was also demonstrated using the flow chemistry method. The research provides compelling proof-of-concept, but we acknowledge that the process is in its infancy and needs further development to get it to a stage where it can compete commercially with current technology.

Movement disorders presenting in childhood include tics, dystonia, chorea, tremor, stereotypy, myoclonus, and parkinsonism, each of which can be part of various clinical syndromes with distinct etiologies. Some of these conditions are benign and require only reassurance; others are bothersome and require treatment, or may be clues that herald underlying pathology. Answers lie in the inherent characteristics of the movements themselves, together with the clinical context provided in the history obtained by the examiner. The aim of this review is to present an overview of the categories of involuntary movements, along with examples of common acquired and genetic causes, and an approach to history-taking, examination, and treatment.

Humanity is currently facing a crisis of excess, with a growing population and the trend towards disposable goods, and the world’s resources are under tremendous pressure. This is especially evident in the textiles industry, with increasing consumer numbers and the trend of ‘fast fashion’ causing demand to be at an all-time high, with non-renewable feedstocks depleting and production of natural fibres also under strain. Considering the future of textile production, it can be beneficial to investigate our past for inspiration towards more sustainable approaches. Much of the research into regenerated protein fibres was performed out of necessity during wartime, and while this demonstrates the potential for food waste to be exploited as a resource, the manufacturing methods used at the time now present issues for a circular economy due to the high amounts of toxic waste produced. Using a range of historical and modern literature sources, including journal articles, patents and conference papers, this review presents the historical precedent and research performed into azlons, regenerated fibres produced from waste protein-rich materials. Historical evidence shows that the success of these azlon fibres was short-lived, partly due to negative associations with deprivation and hardship, alongside the emergence of alternative man-made fibres, which were devoid of these connotations with never-before-seen physical properties. The social and political climate leading to the creation, and ultimate demise, of azlons is explored along with the influence of evolving technologies and the marketing of these textile products to consumers. Although the creation of products from waste is not a new concept, the literature has identified that the synergy between the challenges faced in a time of resource scarcity and the current trend of problematic excess reveals an exciting opportunity to learn from our past to create a greener future. Lessons that could help with the current crisis within the textile industry are extracted and presented within the concept of a circular textiles economy. Our findings show that there is notable potential for one regenerated protein fibre, made from casein extracted from milk waste, to be manufactured within a localised, circular economy in conjunction with the principles of green chemistry and sustainable textiles technology.

Phosphatase of Regenerating Liver-3 (PRL-3) is associated with cancer progression and metastasis in various solid tumors and leukemias. The mechanisms that drive PRL-3’s oncogenic functions are not well understood, in part due to a lack of research tools available to study this protein. In particular, small molecules do not exhibit binding specificity for PRL-3 over highly homologous family members PRL-1 and PRL-2, and antibodies directed against PRL-3 are limited by assay type. We have begun to address these issues by developing alpaca-derived single domain antibodies, or nanobodies, targeting PRL-3 with a KD of 30-300 nM and no activity towards PRL-1 and PRL-2. Hydrogen deuterium exchange mass spectrometry (HDX-MS) and co-immunoprecipitation with a known PRL-3 substrate showed the nanobodies bind PRL-3 outside of the active site, meaning they can be used to study PRL-3 interaction with binding partners. The nanobodies were also specific to PRL-3 over other PRLs in immunoprecipitation and immunofluorescence experiments in human cancer cells that overexpressed the PRL family. We found that N-terminal tags on PRL-3, such as GFP and FLAG, changed PRL-3 localization compared to untagged protein, indicating that the nanobodies may provide new insights into PRL-3 trafficking and function. The anti-PRL-3 nanobodies represent an important expansion of the research tools available to study PRL-3 function and can be used to define the role of PRL-3 in cancer progression.

Four structurally distinct classes of polypyridyl ruthenium complexes containing avobenzone exhibited low micromolar and submicromolar potencies in cancer cells, and were up to 273-fold more active than the parent ligand. Visible light irradiation enhanced the cytotoxicity of some complexes, making them promising candidates for combined chemo-photodynamic therapy.

Supplemental digital content is available in the text., Background/Objective Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity. Methods Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment. Results Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study–Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels. Conclusions Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways.

Background/ObjectiveThe incidence of pain and/or fatigue in people with psoriatic arthritis (PsA) is associated with reduced health-related quality of life (HRQoL) and the ability to work, despite modern advanced therapeutic approaches. This real-world, international study examined these relationships in patients with PsA treated with tumour necrosis factor inhibitors (TNFi).MethodsData from 13 countries were analysed. Patients with PsA and their physicians completed questionnaires capturing demographics, current therapy, current disease status, HRQoL and work status via Medical Outcomes Study 36-Item Short-Form version 2 (SF-36v2), 3-level 5-dimension EuroQoL questionnaire, Health Assessment Questionnaire Disability Index, and Work Productivity and Activity Impairment (WPAI) questionnaire.Results640 patients with PsA were included who had been receiving TNFi for ≥3 months and had completed SF-36v2 bodily pain and vitality domains. Of these, 33.1%, 29.2% and 37.7% of patients reported no, moderate and severe pain, respectively, and 31.9%, 22.5% and 45.6% of patients reported low, moderate and severe fatigue, respectively. Scores across HRQoL variables and WPAI were significantly different across pain and fatigue cohorts (all pConclusionsDespite treatment with biologic agents such as TNFi, data from this global study demonstrated that substantial pain and/or fatigue persist in patients with PsA and that these are significantly associated with reduced HRQoL, physical function and work productivity. These findings suggest that there is an unmet need for additional PsA therapies.

Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, there are currently no viable options to target PRL-3 in vivo. Here, we screened 1,443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad PRL inhibitors, Salirasib and Candesartan blocked PRL-3-induced migration in human embryonic kidney (HEK) cells with no negative impact on cell viability. Both drugs prevented migration of PRL-3 expressing human colorectal cancer cells to a similar degree as the research-grade PRL inhibitor, Thienopyridone, and are selective towards PRLs over other phosphatases. In silico modeling revealed that Salirasib binds a putative allosteric site near the WPD loop of PRL-3, while Candesartan binds a potentially novel targetable site adjacent to the CX5R motif. Inhibitor binding at either of these sites is predicted to trap PRL-3 in a closed conformation, preventing substrate binding and inhibiting function.

Patient derived xenograft models are critical in defining how different cancers respond to drug treatment in an in vivo system. Mouse models are the standard in the field, but zebrafish have emerged as an alternative model with several advantages, including the ability for high-throughput and low-cost drug screening. Zebrafish also allow for in vivo drug screening with large replicate numbers that were previously only obtainable with in vitro systems. The ability to rapidly perform large scale drug screens may open up the possibility for personalized medicine with rapid translation of results back to clinic. Zebrafish xenograft models could also be used to rapidly screen for actionable mutations based on tumor response to targeted therapies or to identify new anti-cancer compounds from large libraries. The current major limitation in the field has been quantifying and automating the process so that drug screens can be done on a larger scale and be less labor-intensive. We have developed a workflow for xenografting primary patient samples into zebrafish larvae and performing large scale drug screens using a fluorescence microscope equipped imaging unit and automated sampler unit. This method allows for standardization and quantification of engrafted tumor area and response to drug treatment across large numbers of zebrafish larvae. Overall, this method is advantageous over traditional cell culture drug screening as it allows for growth of tumor cells in an in vivo environment throughout drug treatment, and is more practical and cost-effective than mice for large scale in vivo drug screens.

Decision aids (DAs) are evidence-based tools that support shared decision-making (SDM) implementation in practice; this study aimed to identify existing osteoporosis DAs and assess their quality and efficacy; and to gain feedback from a patient advisory group on findings and implications for further research. We searched multiple bibliographic databases to identify research studies from 2000 to 2019 and undertook an environmental scan (search conducted February 2019, repeated in March 2020). A pair of reviewers, working independently selected studies for inclusion, extracted data, evaluated each trial's risk of bias, and conducted DA quality assessment using the International Patient Decision Aid Standards (IPDAS). Public contributors (patients and caregivers with experience of osteoporosis and fragility fractures) participated in discussion groups to review a sample of DAs, express preferences for a new DA, and discuss plans for development of a new DA. We identified 6 studies, with high or unclear risk of bias. Across included studies, use of an osteoporosis DA was reported to result in reduced decisional conflict compared with baseline, increased SDM, and increased accuracy of patients' perceived fracture risk compared with controls. Eleven DAs were identified, of which none met the full set of IPDAS criteria for certification for minimization of bias. Public contributors expressed preferences for encounter DAs that are individualized to patients' own needs and risk. Using a systematic review and environmental scan, we identified 11 decision aids to inform patient decisions about osteoporosis treatment and 6 studies evaluating their effectiveness. Use of decision aids increased accuracy of risk perception and shared decision-making but the decision aids themselves fail to comprehensively meet international quality standards and patient needs, underpinning the need for new DA development.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer. There are no immunotherapies and few molecularly targeted therapeutics available for treatment of this malignancy. The identification and characterization of genes and pathways that drive T-ALL progression are critical for the development of new therapies for T-ALL. Here, we determined that the protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) plays a critical role in T-ALL initiation and progression by promoting leukemia cell migration. PRL-3 is highly expressed in patient T-ALL samples at both the mRNA and protein levels compared to normal lymphocytes. Knock-down of PRL-3 expression using short-hairpin RNA (shRNA) in human T-ALL cell lines significantly impeded T-ALL cell migration capacity in vitro and reduced their ability to engraft and proliferate in vivo in xenograft mouse models. Additionally, PRL-3 overexpression in a Myc-induced zebrafish T-ALL model significantly accelerated disease onset and shortened the time needed for cells to enter blood circulation. Reverse-phase protein array (RPPA) and gene set enrichment analysis (GSEA) revealed that the SRC signaling pathway is affected by PRL-3. Immunoblot analyses validated that manipulation of PRL-3 expression in T-ALL cells affected the SRC signaling pathway, which is directly involved in cell migration, although Src was not a direct substrate of PRL-3. More importantly, T-ALL cell growth and migration were inhibited by small molecule inhibition of PRL-3, suggesting that PRL-3 has potential as a therapeutic target in T-ALL. Taken together, our study identifies PRL-3 as an oncogenic driver in T-ALL both in vitro and in vivo and provides a strong rationale for targeted therapies that interfere with PRL-3 function.

BackgroundSymptoms and comorbidities of ankylosing spondylitis (AS) considerably reduce health-related quality of life (HRQoL) and ability to work. This real-world study assessed rates of tumour necrosis factor inhibitor (TNFi) use and switching, treatment failure, and associations between failing TNFi and HRQoL, work productivity and activity impairment (WPAI).MethodsAS patients and their treating physicians completed questionnaires capturing patient demographics, clinical status, TNFi treatment history, reasons for switching TNFi, HRQoL and WPAI. Current TNFi was determined as “failing” if, after ≥3 months, physician-rated disease severity had worsened, remained severe, was “unstable/deteriorating”, physicians were dissatisfied with disease control and/or did not consider treatment a “success”.ResultsThe analysis included 2866 AS patients from 18 countries. Of 2795 patients with complete treatment data, 916 (32.8%) patients had never received TNFi therapy, 1623 (58.1%) patients were receiving their 1st TNFi and 200 (7.2%) patients had ever received ≥2 TNFi (treatment switch). Primary or secondary lack of efficacy were the commonest reasons for switching, and the mean delay in switching after primary lack of efficacy was 11.1 months. 232 (15.4%) patients on TNFi were currently “failing” who, compared to those with treatment success, reported poorer HRQoL: 5-dimension EuroQoL (EQ-5D-3 L): 0.63 vs. 0.78; Medical Outcomes Study Short-Form Health Survey version 2 (SF-36v2) mental component summary (MCS): 41.8 vs. 46.3; physical component summary (PCS): 40.2 vs. 45.1; impaired work productivity: 46.4% vs. 25.0%; and activity: 44.5% vs. 29.6%; allP ConclusionsAmong AS patients, switching TNFi is uncommon and delayed by nearly 1 year despite primary lack of efficacy. Patients currently failing TNFi experience worse physical function, HRQoL and work productivity.

Additional file 1: Table S1. Patient characteristics, Description of data: Detailed patient characteristics, including disease severity and disease scores, are provided.