| 1. |
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| 2. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Thomas, HS, et al.
(author)
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- 2019
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swepub:Mat__t
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| 5. |
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| 6. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 7. |
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| 10. |
- Hyde, K. D., et al.
(author)
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Global consortium for the classification of fungi and fungus-like taxa
- 2023
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In: MYCOSPHERE. - : Mushroom Research Foundation. - 2077-7000 .- 2077-7019. ; 14:1, s. 1960-2012
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Journal article (peer-reviewed)abstract
- The Global Consortium for the Classification of Fungi and fungus-like taxa is an international initiative of more than 550 mycologists to develop an electronic structure for the classification of these organisms. The members of the Consortium originate from 55 countries/regions worldwide, from a wide range of disciplines, and include senior, mid-career and early-career mycologists and plant pathologists. The Consortium will publish a biannual update of the Outline of Fungi and fungus-like taxa, to act as an international scheme for other scientists. Notes on all newly published taxa at or above the level of species will be prepared and published online on the Outline of Fungi website (https://www.outlineoffungi.org/), and these will be finally published in the biannual edition of the Outline of Fungi and fungus-like taxa. Comments on recent important taxonomic opinions on controversial topics will be included in the biannual outline. For example, 'to promote a more stable taxonomy in Fusarium given the divergences over its generic delimitation', or 'are there too many genera in the Boletales?' and even more importantly, 'what should be done with the tremendously diverse 'dark fungal taxa?' There are undeniable differences in mycologists' perceptions and opinions regarding species classification as well as the establishment of new species. Given the pluralistic nature of fungal taxonomy and its implications for species concepts and the nature of species, this consortium aims to provide a platform to better refine and stabilise fungal classification, taking into consideration views from different parties. In the future, a confidential voting system will be set up to gauge the opinions of all mycologists in the Consortium on important topics. The results of such surveys will be presented to the International Commission on the Taxonomy of Fungi (ICTF) and the Nomenclature Committee for Fungi (NCF) with opinions and percentages of votes for and against. Criticisms based on scientific evidence with regards to nomenclature, classifications, and taxonomic concepts will be welcomed, and any recommendations on specific taxonomic issues will also be encouraged; however, we will encourage professionally and ethically responsible criticisms of others' work. This biannual ongoing project will provide an outlet for advances in various topics of fungal classification, nomenclature, and taxonomic concepts and lead to a community-agreed classification scheme for the fungi and fungus-like taxa. Interested parties should contact the lead author if they would like to be involved in future outlines.
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| 11. |
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| 12. |
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- 2019
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Journal article (peer-reviewed)
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| 13. |
- Senanayake, Indunil C., et al.
(author)
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Fungal diversity notes 1611–1716: taxonomic and phylogenetic contributions on fungal genera and species emphasis in south China
- 2023
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In: Fungal Diversity. - 1560-2745 .- 1878-9129. ; 122, s. 161-403
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Journal article (peer-reviewed)abstract
- This article is the 15th contribution in the Fungal Diversity Notes series, wherein 115 taxa from three phyla, nine classes, 28 orders, 48 families, and 64 genera are treated. Fungal taxa described and illustrated in the present study include a new family, five new genera, 61 new species, five new combinations, one synonym, one new variety and 31 records on new hosts or new geographical distributions. Ageratinicolaceae fam. nov. is introduced and accommodated in Pleosporales. The new genera introduced in this study are Ageratinicola, Kevinia, Pseudomultiseptospora (Parabambusicolaceae), Marasmiellomycena, and Vizzinia (Porotheleaceae). Newly described species are Abrothallus altoandinus, Ageratinicola kunmingensis, Allocryptovalsa aceris, Allophoma yuccae, Apiospora cannae, A. elliptica, A. pallidesporae, Boeremia wisteriae, Calycina papaeana, Clypeococcum lichenostigmoides, Coniochaeta riskali-shoyakubovii, Cryphonectria kunmingensis, Diaporthe angustiapiculata, D. campylandrae, D. longipapillata, Diatrypella guangdongense, Dothiorella franceschinii, Endocalyx phoenicis, Epicoccum terminosporum, Fulvifomes karaiensis, F. pannaensis, Ganoderma ghatensis, Hysterobrevium baoshanense, Inocybe avellaneorosea, I. lucida, Jahnula oblonga, Kevinia lignicola, Kirschsteiniothelia guangdongensis, Laboulbenia caprina, L. clavulata, L. cobiae, L. cosmodisci, L. nilotica, L. omalii, L. robusta, L. similis, L. stigmatophora, Laccaria rubriporus, Lasiodiplodia morindae, Lyophyllum agnijum, Marasmiellomycena pseudoomphaliiformis, Melomastia beihaiensis, Nemania guangdongensis, Nigrograna thailandica, Nigrospora ficuum, Oxydothis chinensis, O. yunnanensis, Petriella thailandica, Phaeoacremonium chinensis, Phialocephala chinensis, Phytophthora debattistii, Polyplosphaeria nigrospora, Pronectria loweniae, Seriascoma acutispora, Setoseptoria bambusae, Stictis anomianthi, Tarzetta tibetensis, Tarzetta urceolata, Tetraploa obpyriformis, Trichoglossum beninense, and Tricoderma pyrrosiae. We provide an emendation for Urnula ailaoshanensis Agaricus duplocingulatoides var. brevisporus introduced as a new variety based on morphology and phylogeny.
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| 14. |
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| 15. |
- Ahmed, A., et al.
(author)
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Highly efficient composite electrolyte for natural gas fed fuel cell
- 2016
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In: International journal of hydrogen energy. - : Elsevier. - 0360-3199 .- 1879-3487. ; 41:16, s. 6972-6979
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Journal article (peer-reviewed)abstract
- Solid oxide fuel cells (SOFCs) have the ability to operate with different variants of hydro carbon fuel such as biogas, natural gas, methane, ethane, syngas, methanol, ethanol, hydrogen and any other hydrogen rich gas. Utilization of these fuels in SOFC, especially the natural gas, would significantly reduce operating cost and would enhance the viability for commercialization of FC technology. In this paper, the performance of two indigenously manufactured nanocomposite electrolytes; barium and samarium doped ceria (BSDC-carbonate); and lanthanum and samarium doped ceria (co-precipitation method LSDC-carbonate) using natural gas as fuel is discussed. The nanocomposite electrolytes were synthesized using co-precipitation and wet chemical methods (here after referred to as nano electrolytes). The structure and morphology of the nano electrolytes were examined by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The fuel cell performance (OCV) was tested at temperature (300-600 °C). The ionic conductivity of the nano electrolytes were measured by two probe DC method. The detailed composition analysis of nano electrolytes was performed with the help of Raman Spectroscopy. Electrochemical study has shown an ionic conductivity of 0.16 Scm-1 at 600 °C for BSDC-carbonate in hydrogen atmosphere, which is higher than conventional electrolytes SDC and GDC under same conditions. In this article reasonably good ionic conductivity of BSDC-carbonate, at 600 °C, has also been achieved in air atmosphere which is comparatively greater than the conventional SDC and GDC electrolytes.
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| 16. |
- Duggal, N, et al.
(author)
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INVESTIGATING THE ROLE OF ACCELERATED IMMUNESENESCENCE IN THE PATHOGENESIS OF RHEUMATOID ARTHRITIS
- 2022
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1152-1152
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Conference paper (other academic/artistic)abstract
- Advancing age is recognised as a major risk factor for autoimmune inflammatory conditions, such as Rheumatoid Arthritis (RA). Despite strong associations with older age we understand little of the role ageing processes play in disease pathogenesis in RA. The immune system undergoes a dramatic remodelling with age, termed immunesenescence, which contributes towards increased risk of autoimmunity1. Previous research in patients with established RA has shown certain features of immunesenescence, such as thymic atrophy and telomere shortening in T cells, at a younger age2,3.ObjectivesIn this study we aimed to determine if immunesenescence is seen in the very earliest stages of RA and therefore might be a contributor to RA pathogenesis rather than a result of the disease.MethodsWe have assessed aspects of the aged immune phenotype by immunostaining and flow cytometry4 in adults with arthralgia (n=25), undifferentiated arthritis (UA; n=41), confirmed RA of less than 3 months (n=25) and more than 3 months duration (n=78) and compared these to age and sex matched healthy controls (n=38). Nanostring methodology was used to determine gene expression changes associated with the development of RA.ResultsWe observed increased features of T and B cell immunesenescence in DMARD-naïve recently diagnosed RA patients driven by reduced naïve T cells (p<0.01) and B cells (p<0.01), increased senescent (CD28-ve, CD57+ve, KLRG1+ve) T cells (p<0.01), an increased Th17/Treg ratio (p<0.01) and increased frequency of age-associated B cells (p<0.01). With the exception of naïve T cell frequency, which was reduced in UA patients (p<0.05), these changes were not seen in the very early stages of RA, namely patients with arthralgia and UA. These data suggest that immunesenescence only occurs once disease is established. Furthermore, using nanostring we have identified several biological ageing processes (DNA damage, autophagy) associated with this state of immunesenescence in RA.ConclusionAccelerated immune ageing is an early feature of RA and biological ageing processes represent novel targets to modulate disease progression.References[1]Duggal NA, Upton JA, Phillips AC, Sapey E, Lord JM (2013) An age-related numerical and functional deficit in CD19+CD24hiCD38hi B cells is associated with an increase in systemic autoimmunity. Aging Cell 12:873-881.[2]Goronzy, J.J. and Weyand CM (2001). Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol. 22(5):251-5.[3]Steer SE, Williams FMK, Kato B, Gardner JP, Norman PJ, Hall MA, Kimra M, Vaughan R, Aviv A, Spector T (2007) Reduced telomere length in rheumatoid arthritis in independent of disease activity and duration. Ann Rheum Dis 66:476-480.[4]Duggal NA, Pollock RD, Lazarus NR, Harridge S, Lord JM (2018). Major features of immunesenescence, including reduced thymic output, are ameliorated by high levels of physical activity in adulthood. Aging Cell 17:e12750Disclosure of InterestsNone declared
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| 17. |
- Sharma-Oates, A, et al.
(author)
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INCREASED BIOLOGICAL AGE IN MALE PARTICIPANTS OF SWEDISH AND UK RHEUMATOID ARTHRITIS COHORTS IS NOT LINKED TO DISEASE
- 2022
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1177-1177
-
Conference paper (other academic/artistic)abstract
- Immunesenescence in the adaptive immune system, subsequent to thymic involution, results in compromised immunity and increased susceptibility to autoimmune disease and chronic inflammation. There are reports in the literature that immunesenescence, including thymic atrophy and telomere shortening, is accelerated in patients with rheumatoid arthritis (RA)1. What is unclear is whether RA includes accelerated biological ageing overall in addition to immune ageing which may help to explain the increased risk of age-related diseases in RA2. Recent studies have identified a set of DNA methylated sites across the genome that are highly correlated with chronological age and mortality, termed epigenetic clocks3,4 or DNAm age (DNAma), and can be used to determine an individual’s biological age.ObjectivesThe aim of our study is to determine if the biological epigenetic clocks of RA patients are accelerated.MethodsWe evaluated the Horvath3 and Hannum4 epigenetic clocks of control and RA patients using published DNAm data sets, accessions GSE42861 (EIRA, Swedish cohort of 342 RA patients and 328 non-RA controls) and E-MTAB-6988 (77 RA discordant monozygotic twins).ResultsWe did not detect significant differences between DNAma of RA and non-RA twins. Similarly, there were no significant differences between the DNAma of RA patients and controls from the Swedish EIRA cohort. However, we detected a significant acceleration in DNAma of male discordant twins, both RA and non-RA, by 5.4 years (p=3.29e-5) and 2.8 years (p=0.04) using the Hannum and Horvath clocks, respectively. Male participants, both control and RA patients, from the EIRA cohort also exhibited an accelerated DNAma, by 1.5 years (p=7.55e-5) using the Hannum clock but using the Horvath clock a significant DNAma acceleration, by 1.4 years (p=0.002) was detected in male RA patients from the EIRA cohort.ConclusionOverall, we detected a significant biological age acceleration in male participants from both RA and control groups and only found a significant difference between DNAma of Non-RA controls and RA patients for one of the epigenetic clocks. Further analysis using additional cohort data and biological clock algorithms is needed to confirm our findings.References[1]Goronzy, J.J. and Weyand CM (2001). Thymic function and peripheral T-cell homeostasis in rheumatoid arthritis. Trends Immunol. 22(5):251-5.[2]Meune C, et al. (2009) Trends in cardiovascular mortality in patients with rheumatoid arthritis over 50 years: a systematic review and meta-analysis of cohort studies. Rheumatol 48:1309-1313.[3]Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14:R115.[4]Hannum G, et al (2013) Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates. Mol Cell 49:359-367.AcknowledgementsThe study was funded by FOREUMDisclosure of InterestsNone declared
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| 18. |
- Young, William J., et al.
(author)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Journal article (peer-reviewed)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 19. |
- Afzal, Muhammad, et al.
(author)
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Charge transfer, transportation, and simulation
- 2020
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In: Solid Oxide Fuel Cells. - : Wiley. ; , s. 319-246
-
Book chapter (peer-reviewed)abstract
- This chapter discusses charge transfer and transportation in energy materials and devices, especially focusing on single layer or electrolyte-free fuel cells (EFFCs). Here, charge means electrons and both positive and negative ions, e.g. H+ and O2-. We will study the factors that affect the charges resulting in conduction either externally for electrons or internally for both electrons and ions in EFFCs. Theoretical simulations are carried out by considering specific characteristics EFFC processes. Moreover, the enhancement in ionic conductivity is discussed leading to superionic conduction.
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| 20. |
- Ahmed, Anisuddin, et al.
(author)
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Measuring the effectiveness of an integrated intervention package to improve the level of infection prevention and control : a multi-centre study in Bangladesh
- 2024
-
In: Journal of Hospital Infection. - : Elsevier. - 0195-6701 .- 1532-2939. ; 145, s. 22-33
-
Journal article (peer-reviewed)abstract
- Background: Infection prevention and control (IPC) is a critical component of delivering safe, effective and high -quality healthcare services, and eliminating avoidable healthcare -associated infections (HAIs) in health facilities, predominantly in populationdense settings such as Bangladesh.Aim: Our study aimed to assess the effect of an integrated intervention package in improving the IPC level of the health facilities in Bangladesh.Methods: We conducted a pre -post intervention study in six district hospitals (DHs) and 13 Upazila Health Complexes (UHCs) in the six districts of Bangladesh. Baseline and endline assessments were conducted between March and December 2021 using the adapted World Health Organization Infection Prevention and Control Assessment Framework (WHO-IPCAF) tool. The IPCAF score, ranging from 0-800, was calculated by adding the scores of eight components, and the IPC promotion and practice level was categorized as Inadequate (0 -200), Basic (201-400), Intermediate (401-600) and Advanced (601-800). The integrated intervention package including IPC committee formation, healthcare provider training, logistics provision, necessary guidelines distribution, triage/flu corners establishment, and infrastructure development was implemented in all facilities.Results: The average IPCAF score across all the facilities showed a significant increase from 16% (95% CI: 11.5-20.65%) to 54% (95% CI: 51.4-57.1%). Overall, the IPCAF score increased by 34 percentage points (P<0.001) in DHs and 40 percentage points (P<0.001) in UHCs. Following the intervention, 12 (three DHs, nine UHCs) of 19 facilities progressed from inadequate to intermediate, and another three DHs upgraded from basic to intermediate in terms of IPC level.Conclusion: The integrated intervention package improved IPCAF score in all facilities.
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| 26. |
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| 27. |
- Azevedo, Flavio, et al.
(author)
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Social and moral psychology of COVID-19 across 69 countries
- 2023
-
In: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1
-
Journal article (peer-reviewed)abstract
- The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
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| 28. |
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| 29. |
- Chi, Celestine N., et al.
(author)
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Interactions outside the Boundaries of the Canonical Binding Groove of a PDZ Domain Influence Ligand Binding
- 2012
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In: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 51:44, s. 8971-8979
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Journal article (peer-reviewed)abstract
- The postsynaptic density protein-95/discs large/zonula occludens-1 (PDZ) domain is a protein-protein interaction module with a shallow binding groove where protein ligands bind. However, interactions that are not part of this canonical binding groove are likely to modulate peptide binding. We have investigated such interactions beyond the binding groove for PDZ3 from PSD-95 and a peptide derived from the C-terminus of the natural ligand CRIPT. We found via nuclear magnetic resonance experiments that up to eight residues of the peptide ligand interact with the PDZ domain, showing that the interaction surface extends far outside of the binding groove as defined by the crystal structure. PDZ3 contains an extra structural element, a C-terminal helix (α3), which is known to affect affinity. Deletion of this helix resulted in the loss of several intermolecular nuclear Overhauser enhancements from peptide residues outside of the binding pocket, suggesting that α3 forms part of the extra binding surface in wild-type PDZ3. Site-directed mutagenesis, isothermal titration calorimetry, and fluorescence intensity experiments confirmed the importance of both α3 and the N-terminal part of the peptide for the affinity. Our data suggest a general mechanism in which different binding surfaces outside of the PDZ binding groove could provide sites for specific interactions.
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| 30. |
- Combe, B, et al.
(author)
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2016 update of the EULAR recommendations for the management of early arthritis
- 2017
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In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:6, s. 948-959
-
Journal article (peer-reviewed)abstract
- Since the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis.MethodsIn accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of ‘management’ and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process.ResultsThe updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research.ConclusionsThese recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.
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| 31. |
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| 32. |
- De Souza, S, et al.
(author)
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PATIENT AND PUBLIC INVOLVEMENT IN CLINICAL TRIAL DESIGN
- 2020
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 1285-1286
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Conference paper (other academic/artistic)abstract
- Patient and public involvement (PPI) is gaining increasing recognition as important in ensuring research is relevant and acceptable to participants. Rheuma Tolerance for Cure (RTCure) is a 5 year international collaboration between academia and industry; focusing on earlier detection and prevention of rheumatoid arthritis (RA) through the use of immune-tolerising treatments.Objectives:To bring lived experience and insight into scientific discussions; and to evolve collaboration between lay representatives and academia/industry.Methods:9 Patient Research Partners (PRPs) from 5 European countries were recruited via the EULAR PARE Network and institutions within the RTCure Consortium (8 PRPs with RA and 1 ‘at risk’). They were asked to enter into a legal agreement with the Consortium. PRPs participated in teleconferences (TCs) and were invited to attend face-to-face (F2F) meetings at least annually. Requests for input/feedback were sent from researchers to PRPs via the project’s Patient Engagement Expert [SK].Results:PRP involvement has given researchers and industry partners a new perspective on patient priorities, and focused thought on the ethics of recruitment for and participation in clinical trials of people ‘at risk’ of developing RA. PRPs have helped define the target populations, given their thoughts on what types of treatments are acceptable to people ‘at risk’ and have aided the development of a survey (sent to EULAR PARE members) regarding the use of animal models in biomedical research. Positive informal feedback has been received from researchers and industry regarding the contribution of PRPs to the ongoing project (formal evaluation of PPI in RTCure will be carried out in 2020 and at the project end in 2022).Challenges:Legal agreements- Many PRPs refused to sign the Consortium’s complex PRP Agreement; feeling it unnecessary, incomprehensible and inequitable. After extensive consultation with various parties (including EULAR and the Innovative Medicines Initiative) no similar contract was found. Views for its requirement even varied between legal experts. After 2 years of intense discussion, a simple non-disclosure agreement was agreed upon. Ideally any contract, if required, should be approved prior to project onset.Meeting logistics- Other improvements identified were to locate the meeting venue and accommodation on the same site to minimise travel, and to make it easier for PRPs to take breaks when required. This also facilitates informal discussions and patient inclusivity. We now have agreed a policy to fund PRPs extra nights before and after meetings, and to bring a carer if needed.Enabling understanding– Future annual meetings will start with a F2F meeting between PRPs and Work Package Leads. Researchers will be encouraged to start presentations with a summary slide in lay language. Additionally, an RTCure Glossary is in development.Enabling participation– SK will provide monthly project updates and PRP TCs will be held in the evening (as some PRPs remain employed). PRPs will be invited to all project TCs and F2F meetings. Recruitment is underway to increase the number of ‘at risk’ PRPs as their viewpoint is vital to this study.Conclusion:Currently PPI in RTCure is an ongoing mutual learning process. Universal guidance regarding what types of contracts are needed for PPI would be useful. Communication, trust and fruitful discussions have evolved through F2F meetings (both formal and informal) between PRPs, academia and industry. It is important that all parties can be open with each other in order to make PPI more meaningful.Acknowledgments:This work has received support from the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking RTCure grant number 777357.Disclosure of Interests:Savia de Souza: None declared, Ruth Williams: None declared, Eva Johansson: None declared, Codruta Zabalan: None declared, Tom Esterine: None declared, Margôt Bakkers: None declared, Wolfgang Roth: None declared, Neil Mc Carthy: None declared, Meryll Blake: None declared, Susanne Karlfeldt: None declared, Martina Johannesson: None declared, Karim Raza Grant/research support from: KR has received research funding from AbbVie and Pfizer, Consultant of: KR has received honoraria and/or consultancy fees from AbbVie, Sanofi, Lilly, Bristol-Myers Squibb, UCB, Pfizer, Janssen and Roche Chugai, Speakers bureau: KR has received honoraria and/or consultancy fees from AbbVie, Sanofi, Lilly, Bristol-Myers Squibb, UCB, Pfizer, Janssen and Roche Chugai
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| 33. |
- DiSantostefano, Rachael L., et al.
(author)
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Can the General Public Be a Proxy for an "At-Risk" Group in a Patient Preference Study? : A Disease Prevention Example in Rheumatoid Arthritis
- 2024
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In: Medical decision making. - : Sage Publications. - 0272-989X .- 1552-681X. ; 44:2, s. 189-202
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Journal article (peer-reviewed)abstract
- BackgroundWhen selecting samples for patient preference studies, it may be difficult or impractical to recruit participants who are eligible for a particular treatment decision. However, a general public sample may not be an appropriate proxy.ObjectiveThis study compares preferences for rheumatoid arthritis (RA) preventive treatments between members of the general public and first-degree relatives (FDRs) of confirmed RA patients to assess whether a sample of the general public can be used as a proxy for FDRs.MethodsParticipants were asked to imagine they were experiencing arthralgia and had screening tests indicating a 60% chance of developing RA within 2 yrs. Using a discrete choice experiment, participants were offered a series of choices between no treatment and 2 unlabeled hypothetical treatments to reduce the risk of RA. To assess data quality, time to complete survey sections and comprehension questions were assessed. A random parameter logit model was used to obtain attribute-level estimates, which were used to calculate relative importance, maximum acceptable risk (MAR), and market shares of hypothetical preventive treatments.ResultsThe FDR sample (n = 298) spent more time completing the survey and performed better on comprehension questions compared with the general public sample (n = 982). The relative importance ranking was similar between the general public and FDR participant samples; however, other relative preference measures involving weights including MARs and market share differed between groups, with FDRs having numerically higher MARs.ConclusionIn the context of RA prevention, the general public (average risk) may be a reasonable proxy for a more at-risk sample (FDRs) for overall relative importance ranking but not weights. The rationale for a proxy sample should be clearly justified.HighlightsParticipants from the general public were compared to first-degree relatives on their preferences for rheumatoid arthritis (RA) preventive treatments using a discrete choice experiment.Preferences were similar between groups in terms of the most important and least important attributes of preventive treatments, with effectiveness being the most important attribute. However, relative weights differed.Attention to the survey and predicted market shares of hypothetical RA preventive treatments differed between the general public and first-degree relatives.The general public may be a reasonable proxy for an at-risk group for patient preferences ranks but not weights in the disease prevention context; however, care should be taken in sample selection for patient preference studies when choosing nonpatients.
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| 34. |
- Elbeltagi, Ahmed, et al.
(author)
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Data intelligence and hybrid metaheuristic algorithms-based estimation of reference evapotranspiration
- 2022
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In: Applied water science. - : Springer. - 2190-5487 .- 2190-5495. ; 12:7
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Journal article (peer-reviewed)abstract
- For developing countries, scarcity of climatic data is the biggest challenge, and model development with limited meteorological input is of critical importance. In this study, five data intelligent and hybrid metaheuristic machine learning algorithms, namely additive regression (AR), AR-bagging, AR-random subspace (AR-RSS), AR-M5P, and AR-REPTree, were applied to predict monthly mean daily reference evapotranspiration (ET0). For this purpose, climatic data of two meteorological stations located in the semi-arid region of Pakistan were used from the period 1987 to 2016. The climatic dataset includes maximum and minimum temperature (Tmax, Tmin), average relative humidity (RHavg), average wind speed (Ux), and sunshine hours (n). Sensitivity analysis through regression methods was applied to determine effective input climatic parameters for ET0 modeling. The results of performed regression analysis on all input parameters proved that Tmin, RHAvg, Ux, and n were identified as the most influential input parameters at the studied station. From the results, it was revealed that all the selected models predicted ET0 at both stations with greater precision. The AR-REPTree model was located furthest and the AR-M5P model was located nearest to the observed point based on the performing indices at both the selected meteorological stations. The study concluded that under the aforementioned methodological framework, the AR-M5P model can yield higher accuracy in predicting ET0 values, as compared to other selected algorithms.
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| 35. |
- Gianni, Stefano, et al.
(author)
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Sequence-specific Long Range networks in PSD-95/Discs Large/ZO-1 (PDZ) Domains Tune Their Binding Selectivity
- 2011
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:31, s. 27167-27175
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Journal article (peer-reviewed)abstract
- Protein-protein interactions mediated by modular protein domains are critical for cell scaffolding, differentiation, signaling, and ultimately, evolution. Given the vast number of ligands competing for binding to a limited number of domain families, it is often puzzling how specificity can be achieved. Selectivity may be modulated by intradomain allostery, whereby a remote residue is energetically connected to the functional binding site via side chain or backbone interactions. Whereas several energetic pathways, which could mediate intradomain allostery, have been predicted in modular protein domains, there is a paucity of experimental data to validate their existence and roles. Here, we have identified such functional energetic networks in one of the most common protein-protein interaction modules, the PDZ domain. We used double mutant cycles involving site-directed mutagenesis of both the PDZ domain and the peptide ligand, in conjunction with kinetics to capture the fine energetic details of the networks involved in peptide recognition. We performed the analysis on two homologous PDZ-ligand complexes and found that the energetically coupled residues differ for these two complexes. This result demonstrates that amino acid sequence rather than topology dictates the allosteric pathways. Furthermore, our data support a mechanism whereby the whole domain and not only the binding pocket is optimized for a specific ligand. Such cross-talk between binding sites and remote residues may be used to fine tune target selectivity.
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| 36. |
- Haq, S Raza, et al.
(author)
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Side-Chain Interactions Form Late and Cooperatively in the Binding Reaction between Disordered Peptides and PDZ Domains
- 2012
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In: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 134:1, s. 599-605
-
Journal article (peer-reviewed)abstract
- Intrinsically disordered proteins are very common and mediate numerous protein-protein and protein-DNA interactions. While it is clear that these interactions are instrumental for the life of the mammalian cell, there is a paucity of data regarding their molecular binding mechanisms. Here we have used short peptides as a model system for intrinsically disordered proteins. Linear free energy relationships based on rate and equilibrium constants for the binding of these peptides to ordered target proteins, PDZ domains, demonstrate that native side-chain interactions form mainly after the rate-limiting barrier for binding and in a cooperative fashion. This finding suggests that these disordered peptides first form a weak encounter complex with non-native interactions. The data do not support the recent notion that the affinities of intrinsically disordered proteins toward their targets are generally governed by their association rate constants. Instead, we observed the opposite for peptide-PDZ interactions, namely, that changes in K-d correlate with changes in k(off).
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| 37. |
- Haq, Syed Raza, et al.
(author)
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The plastic energy landscape of protein folding : a triangular folding mechanism with an equilibrium intermediate for a small protein domain
- 2010
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 285:23, s. 18051-18059
-
Journal article (peer-reviewed)abstract
- Protein domains usually fold without or with only transiently populated intermediates, possibly to avoid misfolding, which could result in amyloidogenic disease. Whether observed intermediates are productive and obligatory species on the folding reaction pathway or dispensable by-products is a matter of debate. Here, we solved the crystal structure of a small protein domain, SAP97 PDZ2 I342W C378A, and determined its folding pathway. The presence of a folding intermediate was demonstrated both by single and double-mixing kinetic experiments using urea-induced (un) folding as well as ligand-induced folding. This protein domain was found to fold via a triangular scheme, where the folding intermediate could be either on-or off-pathway, depending on the experimental conditions. Furthermore, we found that the intermediate was present at equilibrium, which is rarely seen in folding reactions of small protein domains. The folding mechanism observed here illustrates the roughness and plasticity of the protein folding energy landscape, where several routes may be employed to reach the native state. The results also reconcile the folding mechanisms of topological variants within the PDZ domain family.
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| 38. |
- Hussain, M., et al.
(author)
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Optimization of lithium adsorption from seawater via aluminum chloride as adsorbent using response surface methodology
- 2024
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In: Energy Sources, Part A. - : Informa UK Limited. - 1556-7036 .- 1556-7230. ; 46:1, s. 2907-2921
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Journal article (peer-reviewed)abstract
- Lithium extraction from natural resources is an accelerating field of research owing to its growing demand in the medical, nuclear, battery, and air conditioning industries. Lithium compounds are used in various industries, including ceramics, glass, lubricant gases, rocket propellant, and aluminum production. The extraction of lithium from seawater via adsorption using AlCl3.6 H2O as an adsorbent is investigated in this study. The effect of process parameters such as pH, temperature, contact time, the molar ratio ([Al3+]/[Li+]), and stirring rate on process efficiency is investigated and optimized. The response surface methodology (RSM) is used to investigate the effects of operating parameters and choose the optimal configuration. A standard synthetic solution containing 50 ppm lithium is prepared and experimented with facilitating comprehension of the procedure. The adsorption efficiency of a synthetic solution is 88% at optimized values, while that of seawater is 78.5%. Seawater has a lower efficiency because it contains ions such as Mg2+, Ca2+, K+, and Na+ that compete for active points/sites during adsorption with lithium ions (Li+).
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| 39. |
- Khan, M. Ajmal, et al.
(author)
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Effect of titania concentration on the grain boundary conductivity of calcium-doped ceria electrolyte
- 2014
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In: Ceramics International. - : Elsevier BV. - 0272-8842 .- 1873-3956. ; 40:7, s. 9775-9781
-
Journal article (peer-reviewed)abstract
- A solid-state technique was used to synthesize ceria-based (CDC-xT, in which x=0-1 mol%) solid electrolyte ceramics. The effects of doping the ceramic solid electrolyte (CDC) with titanium oxide were studied with regard to densification, crystal structure, morphology, electro-impedance spectroscopy and fuel cell performance. TiO2 doping afforded materials a 95% relative density at 940 degrees C, approximately 200 degrees C lower than the temperature required without titanium oxide. The addition of titanium oxide (TiO2) reduced the CDC sintering temperature and significantly improved the grain boundary conduction. The minimum grain boundary resistivity was obtained at 0.8 mol% TiO2. X-ray diffraction (XRD) results showed that the lattice parameters enhanced with increased titanium oxide concentrations up to 0.8 mol%, revealing the solubility limit for Caria's fluorite structure. The optimum doping level (0.8 mol%) is provided maximum conductivity. Conductivities were measured using EIS (Electrochemical Impedance Spectroscopy) with a two-probe method, and the activation energies were calculated using the Arrhenius plots. The maximum power density (660 mW/cm(2)) was achieved with CDC 0.8T electrolyte at 650 degrees C using LiCuZnNi oxide electrodes.
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| 40. |
- Martins, I, et al.
(author)
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Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death
- 2018
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In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:7, s. 716-
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Journal article (peer-reviewed)abstract
- Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment.
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| 41. |
- Mushtaq, N., et al.
(author)
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Perovskite SrFe1-xTixO3-δ (x < = 0.1) cathode for low temperature solid oxide fuel cell
- 2018
-
In: Ceramics International. - : Elsevier. - 0272-8842 .- 1873-3956. ; 44:9, s. 10266-10272
-
Journal article (peer-reviewed)abstract
- Stable and compatible cathode materials are a key factor for realizing the low-temperature (LT, ≤600 °C) operation and practical implementations of solid oxide fuel cells (SOFCs). In this study, perovskite oxides SrFe1-xTixO3-δ (x < = 0.1), with various ratios of Ti doping, are prepared by a sol-gel method for cathode material for LT-SOFCs. The structure, morphology and thermo-gravimetric characteristics of the resultant SFT powders are investigated. It is found that the Ti is successfully doped into SrFeO3-δ to form a single phase cubic perovskite structure and crystal structure of SFT shows better stability than SrFeO3-δ. The dc electrical conductivity and electrochemical properties of SFT are measured and analysed by four-probe and electrochemical impedance spectra (EIS) measurements, respectively. The obtained SFT exhibits a very low polarization resistance (Rp),.01 Ωcm2 at 600◦C. The SFT powders using as cathode in fuel cell devices, exhibit maximum power density of 551 mW cm−2 with open circuit voltage (OCV) of 1.15 V at 600◦C. The good performance of the SFT cathode indicates a high rate of oxygen diffusion through the material at cathode. By enabling operation at low temperatures, SFT cathodes may result in a practical implementation of SOFCs.
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| 42. |
- Naqvi, Salman Raza, et al.
(author)
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Catalytic Pyrolysis Of Botryococcus Braunii (microalgae) Over Layered and Delaminated Zeolites For Aromatic Hydrocarbon Production
- 2017
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In: PROCEEDINGS OF THE 9TH INTERNATIONAL CONFERENCE ON APPLIED ENERGY. - : ELSEVIER SCIENCE BV. ; , s. 381-385
-
Conference paper (peer-reviewed)abstract
- Botryococcus braunii (B. Braunii) is considered as due to its high capability of large aromatic contents, prominent green microalgae as a renewable energy resource. The aim and novelty of this work is to exploit the pyrolysis characteristics of microalgae with layered and delaminated zeolites using Py-GC/MS. No catalyst and catalytic pyrolysis was compared to evaluate product components formed. Further, the catalytic pyrolysis of botryococcus braunii was carried out in the presence of two zeolites with different pore topology and acidity. The results from non-catalytic microalgae pyrolysis were compared to catalytic pyrolysis together with different catalysts to biomass ratios for aromatic hydrocarbons production. Py-GC/MS results showed the aromatic hydrocarbon production (area%) was significantly improved from zeolite catalytic pyrolysis than non-catalytic pyrolysis. The increase in catalyst to biomass ratio (3:1 and 5:1) resulted in higher aromatic hydrocarbon production. As the catalyst to biomass ratio increased, it is observed that aromatic hydrocarbon content increased as compared to low catalyst to biomass ratio. In addition, ITQ-2 zeolite generated higher aromatic hydrocarbons. This might be due to better pore structure and acidity of delaminated structure as compared to layered structure. This delaminated topology enhances the reactant diffusion and reduces the secondary cracking.
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| 43. |
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| 44. |
- Phukhamsakda, Chayanard, et al.
(author)
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The numbers of fungi: contributions from traditional taxonomic studies and challenges of metabarcoding
- 2022
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In: Fungal diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 114:1, s. 327-386
-
Journal article (peer-reviewed)abstract
- The global diversity of fungi has been estimated using several different approaches. There is somewhere between 2–11 million estimated species, but the number of formally described taxa is around 150,000, a tiny fraction of the total. In this paper, we examine 12 ascomycete genera as case studies to establish trends in fungal species descriptions, and introduce new species in each genus. To highlight the importance of traditional morpho-molecular methods in publishing new species, we introduce novel taxa in 12 genera that are considered to have low species discovery. We discuss whether the species are likely to be rare or due to a lack of extensive sampling and classification. The genera are Apiospora, Bambusicola, Beltrania, Capronia, Distoseptispora, Endocalyx, Neocatenulostroma, Neodeightonia, Paraconiothyrium, Peroneutypa, Phaeoacremonium and Vanakripa. We discuss host-specificity in selected genera and compare the number of species epithets in each genus with the number of ITS (barcode) sequences deposited in GenBank and UNITE. We furthermore discuss the relationship between the divergence times of these genera with those of their hosts. We hypothesize whether there might be more species in these genera and discuss hosts and habitats that should be investigated for novel species discovery.
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| 45. |
- Raza, Rizwan, et al.
(author)
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Ce-0.8(SmZr)(0.2)O-2-carbonate nanocomposite electrolyte for solid oxide fuel cell
- 2014
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In: International Journal of Energy Research. - : Hindawi Limited. - 0363-907X .- 1099-114X. ; 38:4, s. 524-529
-
Journal article (peer-reviewed)abstract
- A nanocomposite Zr/Sm-codoped ceria electrolyte coated with K2CO3/Na2CO3 was synthesized by a coprecipitation method. The electrochemical study of the two-phase nanocomposite electrolytes with carbonate coated on the doped ceria shows high oxygen ion mobility at low temperatures (300-600 degrees C). The interface between the two constituent phases was studied by electrochemical impedance spectroscopy. Ionic conductivities were also measured with electrochemical impedance spectroscopy. The morphology and structure of composite electrolyte were characterized using field-emission scanning electron microscopy and X-ray diffraction. The fuel cell power density is 700 mW cm(-2), and an open-circuit voltage of 1.00 V is achieved at low temperatures (400-550 degrees C). This codoped approach with a second phase provides a good indication regarding overcoming the challenges of solid oxide fuel cell technology.
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| 46. |
- Raza, Rizwan, et al.
(author)
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Composite electrolyte with proton conductivity for low-temperature solid oxide fuel cell
- 2015
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In: Applied Physics Letters. - : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 107:18
-
Journal article (peer-reviewed)abstract
- In the present work, cost-effective nanocomposite electrolyte (Ba-SDC) oxide is developed for efficient low-temperature solid oxide fuel cells (LTSOFCs). Analysis has shown that dual phase conduction of O-2 (oxygen ions) and H+ (protons) plays a significant role in the development of advanced LTSOFCs. Comparatively high proton ion conductivity (0.19 s/cm) for LTSOFCs was achieved at low temperature (460°C). In this article, the ionic conduction behaviour of LTSOFCs is explained by carrying out electrochemical impedance spectroscopy measurements. Further, the phase and structure analysis are investigated by X-ray diffraction and scanning electron microscopy techniques. Finally, we achieved an ionic transport number of the composite electrolyte for LTSOFCs as high as 0.95 and energy and power density of 90% and 550 mW/cm2, respectively, after sintering the composite electrolyte at 800°C for 4 h, which is promising. Our current effort toward the development of an efficient, green, low-temperature solid oxide fuel cell with the incorporation of high proton conductivity composite electrolyte may open frontiers in the fields of energy and fuel cell technology.
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| 47. |
- Raza, Rizwan, et al.
(author)
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Fuel cell technology for sustainable development in Pakistan - An over-view
- 2016
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In: Renewable & sustainable energy reviews. - : Elsevier. - 1364-0321 .- 1879-0690. ; 53, s. 450-461
-
Journal article (peer-reviewed)abstract
- Fuel cell technology holds the combination of benefits, which are barely offered by any other energy generating technology. Because the fuel used in this technology is found in abundance in nature and can also be renewed/sustained. Pakistan is blessed with renewable energy resources which are suitable for fuel cell technology. Therefore, fuel cell technology offers a great opportunity to meet the demand of energy and for the sustainable development of Pakistan. The energy research group at COMSATS Institute of Information Technology (CIIT), Lahore has made efforts to study the technical aspects of fuel cell technology and its commercial benefits. The research group is interested in finding ways and means of generating and storing the energy produced by using fuel cells. In this paper, the research activities on fuel cell technology in Pakistan have been reviewed and it is also discussed how this technology can resolve the current energy crises in Pakistan and can be the source of sustainable energy. It has been also reviewed that the country would greatly benefit from fuel cells and fuel cell hybrid system (environmental friendly technology), which could be the best solution for electricity production as well for automobile industry.
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| 48. |
- Reinert, Line S, et al.
(author)
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Brain immune cells undergo cGAS-STING-dependent apoptosis during herpes simplex virus type 1 infection.
- 2020
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In: The Journal of clinical investigation. - 1558-8238. ; 131:1
-
Journal article (peer-reviewed)abstract
- Protection of the brain from viral infections involves the type I interferon (IFN-I) system, defects in which renders humans susceptible to herpes simplex encephalitis (HSE). However, excessive cerebral IFN-I levels leads to pathologies, suggesting the need for tight regulation of responses. Based on data from mouse models, human HSE cases, and primary cell culture systems, we here show that microglia and other immune cells undergo apoptosis in the HSV-1-infected brain through a mechanism dependent on the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon genes (STING) pathway, but independent of IFN-I. HSV-1 infection of microglia induced cGAS-dependent apoptosis at high viral doses, while lower viral doses led to IFN-I responses. Importantly, inhibition of caspase activity prevented microglial cell death and augmented IFN-I responses. Accordingly, HSV-1-infected organotypic brain slices, or mice treated with caspase inhibitor, exhibited lower viral load and improved outcome of infection. Collectively, we identify an activation-induced apoptosis program in brain immune cells which down-modulates local immune responses.
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| 49. |
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| 50. |
- Secundino, Ismael, et al.
(author)
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Host and pathogen hyaluronan signal through human siglec-9 to suppress neutrophil activation.
- 2016
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In: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 1432-1440 .- 0946-2716. ; 94, s. 219-219
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Journal article (peer-reviewed)abstract
- Inhibitory CD33-related Siglec receptors regulate immune cell activation upon engaging ubiquitous sialic acids (Sias) on host cell surface glycans. Through molecular mimicry, Sia-expressing pathogen group B Streptococcus binds inhibitory human Siglec-9 (hSiglec-9) to blunt neutrophil activation and promote bacterial survival. We unexpectedly discovered that hSiglec-9 also specifically binds high molecular weight hyaluronan (HMW-HA), another ubiquitous host glycan, through a region of its terminal Ig-like V-set domain distinct from the Sia-binding site. HMW-HA recognition by hSiglec-9 limited neutrophil extracellular trap (NET) formation, oxidative burst, and apoptosis, defining HMW-HA as a regulator of neutrophil activation. However, the pathogen group A Streptococcus (GAS) expresses a HMW-HA capsule that engages hSiglec-9, blocking NET formation and oxidative burst, thereby promoting bacterial survival. Thus, a single inhibitory lectin receptor detects two distinct glycan "self-associated molecular patterns" to maintain neutrophil homeostasis, and two leading human bacterial pathogens have independently evolved molecular mimicry to exploit this immunoregulatory mechanism.
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