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  • Journal article
    Beaghton PJ, Burt A, 2022,

    Gene drives and population persistence vs elimination: The impact of spatial structure and inbreeding at low density

    , Theoretical Population Biology, Vol: 145, ISSN: 0040-5809

    Synthetic gene drive constructs are being developed to control disease vectors, invasive species, and other pest species. In a well-mixed random mating population a sufficiently strong gene drive is expected to eliminate a target population, but it is not clear whether the same is true when spatial processes play a role. In species with an appropriate biology it is possible that drive-induced reductions in density might lead to increased inbreeding, reducing the efficacy of drive, eventually leading to suppression rather than elimination, regardless of how strong the drive is. To investigate this question we analyse a series of explicitly solvable stochastic models considering a range of scenarios for the relative timing of mating, reproduction, and dispersal and analyse the impact of two different types of gene drive, a Driving Y chromosome and a homing construct targeting an essential gene. We find in all cases a sufficiently strong Driving Y will go to fixation and the population will be eliminated, except in the one life history scenario (reproduction and mating in patches followed by dispersal) where low density leads to increased inbreeding, in which case the population persists indefinitely, tending to either a stable equilibrium or a limit cycle. These dynamics arise because Driving Y males have reduced mating success, particularly at low densities, due to having fewer sisters to mate with. Increased inbreeding at low densities can also prevent a homing construct from eliminating a population. For both types of drive, if there is strong inbreeding depression, then the population cannot be rescued by inbreeding and it is eliminated. These results highlight the potentially critical role that low-density-induced inbreeding and inbreeding depression (and, by extension, other sources of Allee effects) can have on the eventual impact of a gene drive on a target population.

  • Journal article
    Ghani L, Kim S, Wang H, Lee HS, Mortensen JS, Katsube S, Du Y, Sadaf A, Ahmed W, Byrne B, Guan L, Loland CJ, Kobilka BK, Im W, Chae PSet al., 2022,

    Foldable detergents for membrane protein study: importance of setergent core flexibility in protein stabilization.

    , Chemistry: A European Journal, ISSN: 0947-6539

    Membrane proteins are of biological and pharmaceutical significance. However, their structural study is extremely challenging mainly due to the fact that only a small number of chemical tools are suitable for stabilizing membrane proteins in solution. Detergents are widely used in membrane protein study, but conventional detergents are generally poor at stabilizing challenging membrane proteins such as G protein-coupled receptors and protein complexes. In the current study, we prepared tandem triazine-based maltosides (TZMs) with two amphiphilic triazine units connected by different diamine linkers, hydrazine (TZM-Hs) and 1,2-ethylenediamine (TZM-Es). These TZMs were consistently superior to a gold standard detergent (DDM) in terms of stabilizing a few membrane proteins. In addition, the TZM-Es containing a long linker showed more general protein stabilization efficacy with multiple membrane proteins than the TZM-Hs containing a short linker. This result indicates that introduction of the flexible1,2-ethylenediamine linker between two rigid triazine rings enables the TZM-Es to fold into favourable conformations in order to promote membrane protein stability. The novel concept of detergent foldability introduced in the current study has potential in rational detergent design and membrane protein applications.

  • Journal article
    Ledesma Amaro R, Ouldridge T, O'Hare D, Team I, Baldwin Get al., 2022,

    Synthetic biology and bioelectrochemical tools for electrogenetic system engineering

    , Science Advances, Vol: 8, ISSN: 2375-2548

    Synthetic biology research and its industrial applications rely on deterministic spatiotemporal control of gene expression. Recently, electrochemical control of gene expression has been demonstrated in electrogenetic systems (redox-responsive promoters used alongside redox inducers and electrodes), allowing for the direct integration of electronics with biological processes. However, use of electrogenetic systems is limited by poor activity, tunability and standardisation. In this work we developed a strong, unidirectional, redox-responsive promoter before deriving a mutant promoter library with a spectrum of strengths. We constructed genetic circuits with these parts and demonstrated their activation by multiple classes of redox molecules. Finally, we demonstrated electrochemical activation of gene expression in aerobic conditions using a novel, modular bioelectrochemical device. These genetic and electrochemical tools facilitate the design and improve the performance of electrogenetic systems. Furthermore, the genetic design strategies used can be applied to other redox-responsive promoters to further expand the available tools for electrogenetics.

  • Journal article
    Perez-Carrasco R, Franco-Onate M-J, Walter J-C, Dorignac J, Geniet F, Palmeri J, Parmeggiani A, Walliser N-O, Nord ALet al., 2022,

    Relaxation time asymmetry in stator dynamics of the bacterial flagellar motor

    , SCIENCE ADVANCES, Vol: 8, ISSN: 2375-2548
  • Journal article
    McFadden IR, Fritz SA, Zimmermann NE, Pellissier L, Kissling WD, Tobias JA, Schleuning M, Graham CHet al., 2022,

    Global plant-frugivore trait matching is shaped by climate and biogeographic history

    , ECOLOGY LETTERS, Vol: 25, Pages: 686-696, ISSN: 1461-023X
  • Journal article
    Stewart PS, Voskamp A, Santini L, Biber MF, Devenish AJM, Hof C, Willis SG, Tobias JAet al., 2022,

    Global impacts of climate change on avian functional diversity

    , ECOLOGY LETTERS, Vol: 25, Pages: 673-685, ISSN: 1461-023X
  • Journal article
    Tobias JA, Sheard C, Pigot AL, Devenish AJM, Yang J, Sayol F, Neate-Clegg MHC, Alioravainen N, Weeks TL, Barber RA, Walkden PA, MacGregor HEA, Jones SEI, Vincent C, Phillips AG, Marples NM, Montano-Centellas FA, Leandro-Silva V, Claramunt S, Darski B, Freeman BG, Bregman TP, Cooney CR, Hughes EC, Capp EJR, Varley ZK, Friedman NR, Korntheuer H, Corrales-Vargas A, Trisos CH, Weeks BC, Hanz DM, Topfer T, Bravo GA, Remes V, Nowak L, Carneiro LS, Moncada R AJ, Matysiokova B, Baldassarre DT, Martinez-Salinas A, Wolfe JD, Chapman PM, Daly BG, Sorensen MC, Neu A, Ford MA, Mayhew RJ, Fabio Silveira L, Kelly DJ, Annorbah NND, Pollock HS, Grabowska-Zhang AM, McEntee JP, Carlos T Gonzalez J, Meneses CG, Munoz MC, Powell LL, Jamie GA, Matthews TJ, Johnson O, Brito GRR, Zyskowski K, Crates R, Harvey MG, Jurado Zevallos M, Hosner PA, Bradfer-Lawrence T, Maley JM, Stiles FG, Lima HS, Provost KL, Chibesa M, Mashao M, Howard JT, Mlamba E, Chua MAH, Li B, Gomez MI, Garcia NC, Packert M, Fuchs J, Ali JR, Derryberry EP, Carlson ML, Urriza RC, Brzeski KE, Prawiradilaga DM, Rayner MJ, Miller ET, Bowie RCK, Lafontaine R-M, Scofield RP, Lou Y, Somarathna L, Lepage D, Illif M, Neuschulz EL, Templin M, Dehling DM, Cooper JC, Pauwels OSG, Analuddin K, Fjeldsa J, Seddon N, Sweet PR, DeClerck FAJ, Naka LN, Brawn JD, Aleixo A, Bohning-Gaese K, Rahbek C, Fritz SA, Thomas GH, Schleuning Met al., 2022,

    AVONET: morphological, ecological and geographical data for all birds

    , ECOLOGY LETTERS, Vol: 25, Pages: 581-597, ISSN: 1461-023X
  • Journal article
    Zhang P, Zhao X, Wang Y, Du K, Wang Z, Yu J, Chang G, Matthews S, Wang H, Liu Bet al., 2022,

    Bacteriophage protein Gp46 is a cross-species inhibitor of nucleoid-associated HU proteins

  • Journal article
    Spanu P, 2022,

    Pietro Spanu

    , New Phytologist, Vol: 233, Pages: 2337-2339, ISSN: 0028-646X
  • Journal article
    Freeman BG, Weeks T, Schluter D, Tobias JAet al., 2022,

    The latitudinal gradient in rates of evolution for bird beaks, a species interaction trait

    , Ecology Letters, Vol: 25, Pages: 635-646, ISSN: 1461-023X

    Where is evolution fastest? The biotic interactions hypothesis proposes that greater species richness creates more ecological opportunity, driving faster evolution at low latitudes, whereas the ‘empty niches’ hypothesis proposes that ecological opportunity is greater where diversity is low, spurring faster evolution at high latitudes. We tested these contrasting predictions by analysing rates of beak evolution for a global dataset of 1141 avian sister species. Rates of beak size evolution are similar across latitudes, with some evidence that beak shape evolves faster in the temperate zone, consistent with the empty niches hypothesis. The empty niches hypothesis is further supported by a meta-analysis showing that rates of trait evolution and recent speciation are generally faster in the temperate zone, whereas rates of molecular evolution are slightly faster in the tropics. Our results suggest that drivers of evolutionary diversification are either similar across latitudes or more potent in the temperate zone, thus calling into question multiple hypotheses that invoke faster tropical evolution to explain the latitudinal diversity gradient.

  • Journal article
    Weeks BC, Naeem S, Lasky JR, Tobias JAet al., 2022,

    Diversity and extinction risk are inversely related at a global scale

    , ECOLOGY LETTERS, Vol: 25, Pages: 697-707, ISSN: 1461-023X
  • Conference paper
    MacIntyre DA, Pruski P, Correia G, Lewis H, Capuccini K, Inglese P, Chan D, Brown R, Kindinger L, Lee YS, Smith A, Marchesi J, McDonald J, Cameron S, Alexander-Hardiman K, David A, Stock S, Norman J, Terzidou V, Teoh TG, Sykes L, Bennett PR, Takats Zet al., 2022,

    Rapid Assessment of Vaginal Microbiota Host Interactions During Pregnancy and Preterm Birth by Direct On-Swab Desorption Electrospray Ionization Mass Spectrometry

    , Publisher: SPRINGER HEIDELBERG, Pages: 53-53, ISSN: 1933-7191
  • Journal article
    Sol D, Garcia-Porta J, Gonzalez-Lagos C, Pigot AL, Trisos C, Tobias JAet al., 2022,

    A test of Darwin's naturalization conundrum in birds reveals enhanced invasion success in the presence of close relatives

    , ECOLOGY LETTERS, Vol: 25, Pages: 661-672, ISSN: 1461-023X
  • Journal article
    Tobias JA, 2022,

    A bird in the hand: global-scale morphological trait datasets open new frontiers of ecology, evolution and ecosystem science

    , Ecology Letters, Vol: 25, Pages: 573-580, ISSN: 1461-023X
  • Journal article
    Crouch NMA, Tobias JA, 2022,

    The causes and ecological context of rapid morphological evolution in birds

    , ECOLOGY LETTERS, Vol: 25, Pages: 611-623, ISSN: 1461-023X
  • Journal article
    Salvalaio M, Oliver N, Tiknaz D, Maximillian S, Kral N, Kim S-J, Sena Get al., 2022,

    Root electrotropism in Arabidopsis does not depend on auxin distribution but requires cytokinin biosynthesis

    , Plant Physiology, Vol: 188, Pages: 1604-1616, ISSN: 0032-0889

    Efficient foraging by plant roots relies on the ability to sense multiple physical and chemical cues in soil and to reorient growth accordingly (tropism). Root tropisms range from sensing gravity (gravitropism), light (phototropism), water (hydrotropism), touch (thigmotropism), and more. Electrotropism, also known as galvanotropism, is the phenomenon of aligning growth with external electric fields and currents. Although root electrotropism has been observed in a few species since the end of the 19th century, its molecular and physical mechanisms remain elusive, limiting its comparison with the more well-defined sensing pathways in plants. Here we provide a quantitative and molecular characterization of root electrotropism in the model system Arabidopsis (Arabidopsis thaliana), showing that it does not depend on an asymmetric distribution of the plant hormone auxin, but instead requires the biosynthesis of a second hormone, cytokinin. We also show that the dose-response kinetics of the early steps of root electrotropism follows a power law analogous to the one observed in some physiological reactions in animals. Future studies involving more extensive molecular and quantitative characterization of root electrotropism would represent a step towards a better understanding of signal integration in plants and would also serve as an independent outgroup for comparative analysis of electroreception in animals and fungi.

  • Journal article
    Hordley LA, Powney GD, Brereton T, Gillings S, Petchey OL, Roy DB, Tobias JA, Williams J, Oliver THet al., 2022,

    Developing a national indicator of functional connectivity

    , Ecological Indicators, Vol: 136, ISSN: 1470-160X

    Habitat loss is a significant driver of biodiversity loss, causing fragmentation into small, isolated patches of suitable land cover. This reduces the permeability of landscapes to the movement of individuals and reduces the likelihood of metapopulation persistence. Quantifying functional connectivity, the ability of a focal species to move between resource patches, is therefore essential for conservation management. There is substantial evidence supporting a technique based on ‘population synchrony’- the degree of correlation in time-series of annual population growth rates between different long-term monitoring sites, to provide a measure of functional connectivity. However, synchronised population dynamics are not only driven by the movement of individuals between sites, but also shared environmental conditions which must be accounted for. Here, we use species survey data from over four decades to investigate average levels and temporal trends in population synchrony for 58 British bird and butterfly species. We first show that population synchrony is significantly associated with synchrony in some seasonal climatic variables. Once we accounted for spatiotemporal climatic patterns, we found that synchrony in butterflies declined over time by 71% between 1985 and 2000 but increased by 64% in recent years. Synchrony in birds showed some decline between 1999 and 2005, after which there appears to being recovery, however most species (74%) show no significant overall change in synchrony. Our proposed indicator provides a ‘species-eye-view’ of functional connectivity using widely available abundance data. Developing such indicators of functional connectivity, which can be updated annually, is crucial to improve the effectiveness of land management strategies for conservation under increasing environmental change.

  • Conference paper
    Kundu S, Lee Y, Sykes L, Chan D, Lewis H, Brown R, Kindinger L, Dell A, Feizi T, Haslam S, Liu Y, Marchesi J, MacIntyre D, Bennett Pet al., 2022,

    The Effect of Secretor Status and the Vaginal Microbiome on Birth Outcome

    , Publisher: SPRINGER HEIDELBERG, Pages: 197-197, ISSN: 1933-7191
  • Journal article
    Chen C, Riley W, Prentice IC, Keenan Tet al., 2022,

    CO2 fertilization of terrestrial photosynthesis inferred from site to global scales

    , Proceedings of the National Academy of Sciences of USA, Vol: 119, ISSN: 0027-8424

    Global photosynthesis is increasing with elevated atmospheric CO2 concentrations, a response known as the CO2 fertilization effect (CFE), but the key processes of CFE are not constrained and therefore remain uncertain. Here we quantify CFE by combining observations from a globally distributed network of eddy covariance measurements with a novel analyticalframework based on three well-established photosynthetic optimization theories. We report a strong enhancement of photosynthesis across the observational network (9.1 gC m–2 yr–2) and show that the CFE is responsible for 44% of the gross primary production (GPP) enhancementsince the 2000s, with additional contributions primarily from warming (28%). Soil moisture and specific humidity are the two largest contributors to GPP interannual variation through their influences on plant hydraulics. Applying our framework to satellite observations and meteorological reanalysis data, we diagnose a global CO2-induced GPP trend of 4.4 gC m–2 yr–2, which is at least one-third stronger than the median trends of 13 Dynamic Global Vegetation Models and 8 satellite-derived GPP products, mainly due to their differences in the magnitude of CFE in evergreen broadleaf forests. These results highlight the critical role that CFE has had on the global carbon cycle in recent decades.

  • Journal article
    Morfopoulos C, Muller J-F, Stavrakou T, Bauwens M, De Smedt I, Friedlingstein P, Prentice IC, Regnier Pet al., 2022,

    Vegetation responses to climate extremes recorded by remotely sensed atmospheric formaldehyde

    , Global Change Biology, Vol: 28, Pages: 1809-1822, ISSN: 1354-1013

    Accurate monitoring of vegetation stress is required for better modelling and forecasting of primary production, in a world where heatwaves and droughts are expected to become increasingly prevalent. Variability in formaldehyde (HCHO) concentrations in the troposphere is dominated by local emissions of short-lived biogenic (BVOC) and pyrogenic volatile organic compounds. BVOCs are emitted by plants in a rapid protective response to abiotic stress, mediated by the energetic status of leaves (the excess of reducing power when photosynthetic light and dark reactions are decoupled, as occurs when stomata close in response to water stress). Emissions also increase exponentially with leaf temperature. New analytical methods for the detection of spatiotemporally contiguous extremes in remote-sensing data are applied here to satellite-derived atmospheric HCHO columns. BVOC emissions are shown to play a central role in the formation of the largest positive HCHO anomalies. Although vegetation stress can be captured by various remotely sensed quantities, spaceborne HCHO emerges as the most consistent recorder of vegetation responses to the largest climate extremes, especially in forested regions.

  • Journal article
    Serafini N, Jarade A, Surace L, Goncalves P, Sismeiro O, Varet H, Legendre R, Coppee J-Y, Disson O, Durum SK, Frankel G, Di Santo JPet al., 2022,

    Trained ILC3 responses promote intestinal defense

    , SCIENCE, Vol: 375, Pages: 859-+, ISSN: 0036-8075
  • Journal article
    Hards K, Cheung C-Y, Waller N, Adolph C, Keighley L, Tee ZS, Harold LK, Menorca A, Bujaroski RS, Buckley BJ, Tyndall JDA, McNeil MB, Rhee KY, Opel-Reading HK, Krause K, Preiss L, Langer JD, Meier T, Hasenoehrl EJ, Berney M, Kelso MJ, Cook GMet al., 2022,

    An amiloride derivative is active against the F1Fo-ATP synthase and cytochrome bd oxidase of Mycobacterium tuberculosis.

    , Commun Biol, Vol: 5

    Increasing antimicrobial resistance compels the search for next-generation inhibitors with differing or multiple molecular targets. In this regard, energy conservation in Mycobacterium tuberculosis has been clinically validated as a promising new drug target for combatting drug-resistant strains of M. tuberculosis. Here, we show that HM2-16F, a 6-substituted derivative of the FDA-approved drug amiloride, is an anti-tubercular inhibitor with bactericidal properties comparable to the FDA-approved drug bedaquiline (BDQ; Sirturo®) and inhibits the growth of bedaquiline-resistant mutants. We show that HM2-16F weakly inhibits the F1Fo-ATP synthase, depletes ATP, and affects the entry of acetyl-CoA into the Krebs cycle. HM2-16F synergizes with the cytochrome bcc-aa3 oxidase inhibitor Q203 (Telacebec) and co-administration with Q203 sterilizes in vitro cultures in 14 days. Synergy with Q203 occurs via direct inhibition of the cytochrome bd oxidase by HM2-16F. This study shows that amiloride derivatives represent a promising discovery platform for targeting energy generation in drug-resistant tuberculosis.

  • Journal article
    Spanu PD, 2022,

    Slicing the cost of bread

    , NATURE PLANTS, Vol: 8, Pages: 200-201, ISSN: 2055-026X
  • Journal article
    Wayman JP, Sadler JP, Pugh TAM, Martin TE, Tobias JA, Matthews TJet al., 2022,

    Assessing taxonomic and functional change in British breeding bird assemblages over time

    , GLOBAL ECOLOGY AND BIOGEOGRAPHY, Vol: 31, Pages: 925-939, ISSN: 1466-822X
  • Journal article
    Fu Z, Ciais P, Prentice IC, Gentine P, Makowski D, Bastos A, Luo X, Green J, Stoy P, Yang H, Hajima Tet al., 2022,

    Atmospheric dryness reduces photosynthesis along a large range of soil water deficits

    , Nature Communications, Vol: 13, ISSN: 2041-1723

    Both low soil water content (SWC) and high atmospheric dryness (vapor pressure deficit, VPD) can negatively affect terrestrial gross primary production (GPP). The sensitivity of GPP to soil versus atmospheric dryness is difficult to disentangle, however, because of their covariation. Using global eddy-covariance observations, here we show that a decrease in SWC is not universally associated with GPP reduction. GPP increases in response to decreasing SWC when SWC is high and decreases only when SWC is below a threshold. By contrast, the sensitivity of GPP to an increase of VPD is always negative across the full SWC range. We further find canopy conductance decreases with increasing VPD (irrespective of SWC), and with decreasing SWC on drier soils. Maximum photosynthetic assimilation rate has negative sensitivity to VPD, and a positive sensitivity to decreasing SWC when SWC is high. Earth System Models underestimate the negative effect of VPD and the positive effect of SWC on GPP such that they should underestimate the GPP reduction due to increasing VPD in future climates.

  • Journal article
    Edwards E, Livanos M, Krueger A, Dell A, Haslam SM, Mark Smales C, Bracewell DGet al., 2022,

    Strategies to control therapeutic antibody glycosylation during bioprocessing: synthesis and separation.

    , Biotechnology and Bioengineering, Vol: 119, ISSN: 0006-3592

    Glycosylation can be a critical quality attribute (CQA) in biologic manufacturing. In particular, it has implications on the half-life, immunogenicity and pharmacokinetics of therapeutic monoclonal antibodies (mAbs) and must be closely monitored throughout drug development and manufacturing. To address this, advances have been made primarily in upstream processing, including mammalian cell line engineering to yield more predictably glycosylated mAbs, and the addition of media supplements during fermentation to manipulate the metabolic pathways involved in glycosylation. A more robust approach would be a conjoined upstream-downstream processing strategy. This could include implementing novel downstream technologies, such as the use of Fc gamma-based affinity ligands for the separation of mAb glycovariants. This review highlights the importance of controlling therapeutic antibody glycosylation patterns, the challenges faced in terms of glycosylation during mAb biosimilar development, current efforts both upstream and downstream to control glycosylation and their limitations, and the need for research in the downstream space in order to establish holistic and consistent manufacturing processes for the production of antibody therapies. This article is protected by copyright. All rights reserved.

  • Journal article
    Merali N, Chouari T, Kayani K, Rayner C, Jimenez Zarco J, Giovannetti E, Krell J, Bagwan I, Relph K, Rockall T, Dhillon T, Pandha H, Annels N, Frampton Aet al., 2022,

    A comprehensive review of the current and future role of the microbiome in pancreatic ductal adenocarcinoma

    , Cancers, Vol: 14, Pages: 1-34, ISSN: 2072-6694

    Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second most common cause of cancer death in the USA by 2030, yet progress continues to lag behind that of other cancers, with only 9% of patients surviving beyond 5 years. Long-term survivorship of PDAC and improving survival has, until recently, escaped our understanding. One recent frontier in the cancer field is the microbiome. The microbiome collectively refers to the extensive community of bacteria and fungi that colonise us. It is estimated that there is one to ten prokaryotic cells for each human somatic cell, yet, the significance of this community in health and disease has, until recently, been overlooked. This review examines the role of the microbiome in PDAC and how it may alter survival outcomes. We evaluate the possibility of employing microbiomic signatures as biomarkers of PDAC. Ultimately this review analyses whether the microbiome may be amenable to targeting and consequently altering the natural history of PDAC.

  • Journal article
    Jeffers V, Child MA, 2022,

    No acetyl-CoA keeps Plasmodium at bay

    , CELL CHEMICAL BIOLOGY, Vol: 29, Pages: 174-176, ISSN: 2451-9448
  • Journal article
    Demmer J, Phillips B, Uhrig L, Filloux A, Allsopp L, Bublitz M, Meier Tet al., 2022,

    Structure of ATP synthase from ESKAPE pathogen Acinetobacter baumannii

    , Science Advances, Vol: 8, ISSN: 2375-2548

    The global spread of multi-drug resistant Acinetobacter baumannii infections urgently calls for the identification of novel drug targets. We solved the cryo- electron microscopy structure of the F1Fo-ATP synthase from A. baumannii in three distinct conformational states. The nucleotide-converting F1 sub-complex reveals a specific self-inhibition mechanism, which supports a uni-directional ratchet mechanism to avoid wasteful ATP consumption. In the membrane-embedded Fo complex, the structure shows unique structural adaptations along both the entry and exit pathways of the proton-conducting a-subunit. These features, absent in mitochondrial ATP synthases, represent attractive targets for the development of next generation therapeutics that can act directly at the culmination of bioenergetics in this clinically relevant pathogen.

  • Journal article
    Antonaru LA, Cardona T, Larkum AWD, Nurnberg DJet al., 2022,

    Global distribution of a chlorophyll f cyanobacterial marker (vol 14, pg 2275, 2020)

    , ISME JOURNAL, Vol: 16, Pages: 1680-1680, ISSN: 1751-7362

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