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  • Journal article
    Duarte A, Pym A, Garrood WT, Troczka BJ, Zimmer CT, Davies TGE, Nauen R, O'Reilly AO, Bass Cet al., 2022,

    P450 gene duplication and divergence led to the evolution of dual novel functions and insecticide cross-resistance in the brown planthopper Nilaparvata lugens

    , PLOS GENETICS, Vol: 18, ISSN: 1553-7404
  • Conference paper
    Mountain K, MacIntyre D, Chan D, Hyde A, Lee Y, Brown R, David A, Dell A, Ten F, Haslam S, Liu Y, Lewis H, Norman J, Stock S, Teoh TG, Terzidou V, Kundu S, Bennett P, Sykes Let al., 2022,

    Blood group antigens influence host-microbe interactions and risk of early preterm birth

    , Publisher: WILEY, Pages: 55-56, ISSN: 1470-0328
  • Journal article
    Banks-Leite C, Betts MG, Ewers RM, Orme CDL, Pigot ALet al., 2022,

    The macroecology of landscape ecology

    , Trends in Ecology and Evolution, Vol: 37, ISSN: 0169-5347

    One of landscape ecology's main goals is to unveil how biodiversity is impacted by habitat transformation. However, the discipline suffers from significant context dependency in observed spatial and temporal trends, hindering progress towards understanding the mechanisms driving species declines and preventing the development of accurate estimates of future biodiversity change. Here, we discuss recent evidence that populations' and species' responses to habitat change at the landscape scale are modulated by factors and processes occurring at macroecological scales, such as historical disturbance rates, distance to geographic range edges, and climatic suitability. We suggest that placing landscape ecology studies in a macroecological lens will help to explain seemingly inconsistent results and will ultimately create better predictive models to help mitigate the biodiversity crisis.

  • Journal article
    Oliver Huidobro M, Tica J, Wachter GKA, Isalan Met al., 2022,

    Synthetic spatial patterning in bacteria: advances based on novel diffusible signals

    , Microbial Biotechnology, Vol: 15, Pages: 1685-1694

    Engineering multicellular patterning may help in the understanding of some fundamental laws of pattern formation and thus may contribute to the field of developmental biology. Furthermore, advanced spatial control over gene expression may revolutionize fields such as medicine, through organoid or tissue engineering. To date, foundational advances in spatial synthetic biology have often been made in prokaryotes, using artificial gene circuits. In this review, engineered patterns are classified into four levels of increasing complexity, ranging from spatial systems with no diffusible signals to systems with complex multi-diffusor interactions. This classification highlights how the field was held back by a lack of diffusible components. Consequently, we provide a summary of both previously characterized and some new potential candidate small-molecule signals that can regulate gene expression in Escherichia coli. These diffusive signals will help synthetic biologists to successfully engineer increasingly intricate, robust and tuneable spatial structures.

  • Journal article
    Giannos P, Triantafyllidis KK, Giannos G, Kechagias Ket al., 2022,

    SPP1 in infliximab resistant ulcerative colitis and associated colorectal cancer: an analysis of differentially expressed genes

    , European Journal of Gastroenterology and Hepatology, Vol: 34, Pages: 598-606, ISSN: 0954-691X

    Objective:Infliximab, a tumour necrosis factor-α (TNFα) antagonist, has advanced the management of ulcerative colitis. Although efficacious, considerable percentage of patients are resistant to treatment. Accumulative inflammatory burden in long-term ulcerative colitis patients refractory to therapy increases the risk of developing colorectal cancer (CRC). Our study investigated anti-TNFα-naïve patients with active ulcerative colitis to identify gene biomarkers whose dysregulated expression correlated with resistance to infliximab (IFX) treatment and poor prognosis in CRC.Methods:Differentially expressed genes (DEGs) from two studies (GSE73661 and GSE14580) with colonic mucosal samples were retrieved. Noninflammatory bowel disease controls were compared with those with active ulcerative colitis that either responded or were resistant to IFX before treatment. DEGs from ulcerative colitis samples resistant to IFX were used to construct a protein–protein interaction network, and clustering gene modules were identified. Module DEGs that overlapped with ulcerative colitis samples responsive to IFX were analysed, based on topological closeness and radiality. Hub genes were obtained, and their correlation with CRC progression was evaluated. Their expression in CRC tissues and their tumour microenvironment immune status was estimated.Results:Three clusters composed of 582 DEGs from ulcerative colitis samples resistant to IFX were retrieved. Comparative analysis identified 305 overlapping DEGs with ulcerative colitis samples responsive to IFX. Topological analysis revealed a hub gene – SPP1 – whose overexpression in CRC tissues and patients correlated with increased infiltration of immune signatures and poor prognosis.Conclusion:SPP1 may serve as potential gene biomarker and predictor of resistance to IFX therapy in ulcerative colitis and CRC development.

  • Journal article
    Ellis D, Avraam GP, Hoermann A, Wyer CASP, Ong YX, Christophides GP, Windbichler Net al., 2022,

    Testing non-autonomous antimalarial gene drive effectors using self-eliminating drivers in the African mosquito vector Anopheles gambiae

    , PLOS GENETICS, Vol: 18, ISSN: 1553-7404
  • Journal article
    Miracca G, Anuncibay Soto B, Tossell K, Yustos R, Vyssotski A, Franks N, Wisden Wet al., 2022,

    NMDA receptors in the lateral preoptic hypothalamus are essential for sustaining NREM and REM sleep

    , The Journal of Neuroscience, Vol: 42, Pages: 5389-5409, ISSN: 0270-6474

    The lateral preoptic (LPO) hypothalamus is a center for NREM and REM sleep induction and NREM sleep homeostasis. Although LPO is needed for NREM sleep, we found that calcium signals were, surprisingly, highest in REM sleep. Furthermore, and equally surprising, NMDA26 receptors in LPO were the main drivers of excitation. Deleting the NMDA receptor GluN1 subunit from LPO abolished calcium signals in all cells and produced insomnia. Mice of both sexes had highly fragmented NREM sleep-wake patterns and could not generate conventionally classified REM sleep. The sleep phenotype produced by deleting NMDA receptors depended on where in the hypothalamus the receptors were deleted. Deleting receptors from the anterior hypothalamic area did not influence sleep-wake states. The sleep fragmentation originated from NMDA receptors on GABA neurons in LPO. Sleep fragmentation could be transiently overcome with sleeping medication (zolpidem) or sedatives (dexmedetomidine). By contrast, fragmentation persisted under high sleeppressure produced by sleep deprivation - mice had a high propensity to sleep but woke up. By analyzing changes in delta power, sleep homeostasis (also referred to as “sleep drive”) remained intact after NMDA receptor ablation. We suggest NMDA glutamate receptor activation stabilizes firing of sleep-on neurons, and that mechanisms of sleep maintenance differ from that of the sleep drive itself.

  • Journal article
    Sanchez Garrido J, Ruano-Gallego D, Choudhary JS, Frankel Get al., 2022,

    The type III secretion system effector network hypothesis

    , Trends in Microbiology, Vol: 30, Pages: 524-533, ISSN: 0966-842X

    Type III secretion system (T3SS) effectors are key virulence factors that underpin the infection strategy of many clinically important Gram-negative pathogens, including Salmonella enterica, Shigella spp, enteropathogenic and enterohaemorrhagic Escherichia coli and their murine equivalent, Citrobacter rodentium. The cellular processes or proteins targeted by the effectors can be common to multiple pathogens or pathogen-specific. The main approach to understanding T3SS-mediated pathogenesis has been to determine the contribution of one effector at a time, with the aim to piece together individual functions and unveil infection mechanisms. However, in contrast to this prevailing approach, simultaneous deletion of multiple effectors revealed that they function as an interconnected network in vivo, uncoveringeffector co-dependency and context-dependent effector essentiality. This paradigm shift in T3SS biology is at the heart of this opinion.

  • Journal article
    Prokopidis K, Giannos P, Katsikas Triantafyllidis K, Kechagias KS, Mesinovic J, Witard OC, Scott Det al., 2022,

    Effect of vitamin D monotherapy on indices of sarcopenia in community‐dwelling older adults: a systematic review and meta‐analysis

    , Journal of Cachexia, Sarcopenia and Muscle, Vol: 13, Pages: 1642-1652, ISSN: 2190-5991

    BackgroundVitamin D supplementation is proposed as a potentially effective nutritional intervention to mitigate the risk of sarcopenia. The aim of this systematic review and meta-analysis was to investigate the impact of vitamin D supplementation monotherapy on indices of sarcopenia in community-dwelling older adults.MethodsA comprehensive search of the literature was conducted in PubMed, Web of Science, Scopus, and Cochrane Library. Eligible randomized controlled trials (RCTs) compared the effect of vitamin D supplementation (as monotherapy) with placebo on indices of sarcopenia in older (>50 years) adults. Using the random effects inverse-variance model, we calculated the mean difference (MD) in handgrip strength (HGS), short physical performance battery (SPPB), timed up and go (TUG), and appendicular lean mass (ALM) between groups. We also calculated the standardized mean difference (SMD) in general muscle strength and general physical performance (composite plot of all muscle strength and physical performance outcomes, respectively) between groups.ResultsTen RCTs were included in the meta-analysis. A significant decrease in SPPB scores was observed with vitamin D supplementation compared with placebo (MD: −0.23; 95% CI −0.40 to −0.06; I2 = 0%; P = 0.007). Vitamin D supplementation conferred no effect on HGS (MD: −0.07 kg; 95% CI −0.70 to 0.55; I2 = 51%, P = 0.82), TUG (MD: 0.07 s; 95% CI −0.08 to 0.22; I2 = 0%, P = 0.35), ALM (MD: 0.06 kg/m2; 95% CI: −0.32 to 0.44; I2 = 73%, P = 0.77), general muscle strength (SMD: −0.01; 95% CI −0.17 to 0.15; I2 = 42%, P = 0.90), or general physical performance (SMD: −0.02; 95% CI −0.23 to 0.18; I2 = 71%, P = 0.83).ConclusionsVitamin D supplementation did not improve any sarcopenia indices in community-dwelling older adults and may compromise some aspects of physical performance. Future studies are warranted to investigate the impact of vitamin D supplementati

  • Journal article
    Knoppová J, Sobotka R, Yu J, Bečková M, Pilný J, Trinugroho JP, Csefalvay L, Bína D, Nixon PJ, Komenda Jet al., 2022,

    Assembly of D1/D2 complexes of photosystem II: binding of pigments and a network of auxiliary proteins

    , Plant Physiology, Vol: 189, Pages: 790-804, ISSN: 0032-0889

    Photosystem II (PSII) is the multi-subunit light-driven oxidoreductase that drives photosynthetic electron transport using electrons extracted from water. To investigate the initial steps of PSII assembly, we used strains of the cyanobacterium Synechocystis sp. PCC 6803 arrested at early stages of PSII biogenesis and expressing affinity-tagged PSII subunits to isolate PSII reaction center assembly (RCII) complexes and their precursor D1 and D2 modules (D1mod and D2mod). RCII preparations isolated using either a His-tagged D2 or a FLAG-tagged PsbI subunit contained the previously described RCIIa and RCII* complexes that differ with respect to the presence of the Ycf39 assembly factor and high-light-inducible proteins (Hlips) and a larger complex consisting of RCIIa bound to monomeric PSI. All RCII complexes contained the PSII subunits D1, D2, PsbI, PsbE, and PsbF and the assembly factors rubredoxin A (RubA) and Ycf48, but we also detected PsbN, Slr1470, and the Slr0575 proteins, which all have plant homologs. The RCII preparations also contained prohibitins/stomatins (Phbs) of unknown function and FtsH protease subunits. RCII complexes were active in light-induced primary charge separation and bound chlorophylls, pheophytins, beta-carotenes, and heme. The isolated D1mod consisted of D1/PsbI/Ycf48 with some Ycf39 and Phb3, while D2mod contained D2/cytochrome b559 with co-purifying PsbY, Phb1, Phb3, FtsH2/FtsH3, CyanoP, and Slr1470. As stably bound chlorophyll was detected in D1mod but not D2mod, formation of RCII appears to be important for stable binding of most of the chlorophylls and both pheophytins. We suggest that chlorophyll can be delivered to RCII from either monomeric PSI or Ycf39/Hlip complexes.

  • Journal article
    Wang H, Wang R, Harrison SP, Prentice ICet al., 2022,

    Leaf morphological traits as adaptations to multiple climate gradients

    , Journal of Ecology, Vol: 110, Pages: 1344-1355, ISSN: 0022-0477

    1. Leaf morphological traits vary systematically along climatic gradients. However, recent studies in plant functional ecology have mainly analysed quantitative traits, while numerical models of species distributions and vegetation function have focused on traits associated with resource acquisition; both ignore the wider functional significance of leaf morphology.2. A data set comprising 22 leaf morphological traits for 662 woody species from 92 sites, representing all biomes present in China, was subjected to multivariate analysis in order to identify leading dimensions of trait covariation (correspondence analysis), quantify climatic and phylogenetic contributions (canonical correspondence analysis with variation partitioning), and characterize co-occurring trait syndromes (k-means clustering) and their climatic preferences. 3. Three axes accounted for > 20% of trait variation in both evergreen and deciduous species. Moisture index, precipitation seasonality and growing-season temperature accounted for 8–10% of trait variation; family 15–32%. Microphyll or larger, mid- to dark green leaves with drip-tips in wetter climates contrasted with nanophyll or smaller glaucous leaves without drip-tips in drier climates. Thick, entire leaves in less seasonal climates contrasted with thin, marginal dissected, aromatic, and involute/revolute leaves in more seasonal climates. Thick, involute, hairy leaves in colder climates contrasted with thin leaves with marked surface structures (surface patterning) in warmer climates. Distinctive trait clusters were linked to the driest and most seasonal climates, for example the clustering of picophyll, fleshy and succulent leaves in the driest climates and leptophyll, linear, dissected, revolute or involute, and aromatic leaves in regions with highly seasonal rainfall. Several trait clusters co-occurred in wetter climates, including clusters characterised by microphyll, moderately thick, patent, and entire leaves or notop

  • Journal article
    Kotta-Loizou I, Coutts RHA, Ictv Report Consortium, 2022,

    ICTV virus taxonomy profile: polymycoviridae 2022.

    , Journal of General Virology, Vol: 103, Pages: 1-2, ISSN: 0022-1317

    Members of the family Polymycoviridae are small viruses with multi-segmented and non-conventionally encapsidated double-stranded (ds) RNA genomes. Typically, polymycoviruses have four genomic segments, although some have up to eight. The genus Polymycovirus includes several species whose members infect fungi (ascomycetes and basidiomycetes), and oomycetes, altering host morphology, sporulation, growth and virulence. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Polymycoviridae, which is available at

  • Journal article
    Higginson EE, Nkeze J, Permala-Booth J, Kasumba IN, Lagos R, Hormazabal JC, Byrne A, Frankel G, Levine MM, Tennant SMet al., 2022,

    Detection of Salmonella Typhi in Bile by Quantitative Real-Time PCR

    , MICROBIOLOGY SPECTRUM, Vol: 10, ISSN: 2165-0497
  • Journal article
    Deere NJ, Bicknell JE, Mitchell SL, Afendy A, Baking EL, Bernard H, Chung AYC, Ewers RM, Heroin H, Joseph N, Lewis OT, Luke SH, Milne S, Fikri AH, Parrett JM, Payne M, Rossiter SJ, Vairappan CS, Vian CV, Wilkinson CL, Williamson J, Wong ABH, Slade EM, Davies ZG, Struebig MJet al., 2022,

    Riparian buffers can help mitigate biodiversity declines in oil palm agriculture

  • Journal article
    Lockwood DC, Amin H, Costa TRD, Schroeder GNet al., 2022,

    The Legionella pneumophila Dot/Icm type IV secretion system and its effectors

    , Microbiology, Vol: 168, ISSN: 1350-0872

    To prevail in the interaction with eukaryotic hosts, many bacterial pathogens use protein secretion systems to release virulence factors at the host–pathogen interface and/or deliver them directly into host cells. An outstanding example of the complexity and sophistication of secretion systems and the diversity of their protein substrates, effectors, is the Defective in organelle trafficking/Intracellular multiplication (Dot/Icm) Type IVB secretion system (T4BSS) of Legionella pneumophila and related species. Legionella species are facultative intracellular pathogens of environmental protozoa and opportunistic human respiratory pathogens. The Dot/Icm T4BSS translocates an exceptionally large number of effectors, more than 300 per L. pneumophila strain, and is essential for evasion of phagolysosomal degradation and exploitation of protozoa and human macrophages as replicative niches. Recent technological advancements in the imaging of large protein complexes have provided new insight into the architecture of the T4BSS and allowed us to propose models for the transport mechanism. At the same time, significant progress has been made in assigning functions to about a third of L. pneumophila effectors, discovering unprecedented new enzymatic activities and concepts of host subversion. In this review, we describe the current knowledge of the workings of the Dot/Icm T4BSS machinery and provide an overview of the activities and functions of the to-date characterized effectors in the interaction of L. pneumophila with host cells.

  • Journal article
    Keenan TFC, Luo X, De Kauwe MG, Medlyn BE, Prentice IC, Stocker BD, Smith NG, Terrer C, Wang H, Zhang Y, Zhou Set al., 2022,

    A constraint on historic growth in global photosynthesis due to increasing CO2 (Retraction of Vol 600, Pg 253, 2021)

    , NATURE, Vol: 606, Pages: 420-420, ISSN: 0028-0836
  • Journal article
    Roberts L, Berkachy R, Wane M, Patel D, Schnoeller C, Lord G, Gounaris K, Ryffel B, Quesniaux V, Darby M, Horsnell W, Selkirk Met al., 2022,

    Differential regulation of allergic airway inflammation by acetylcholine

    , Frontiers in Immunology, Vol: 13, ISSN: 1664-3224

    Acetylcholine (ACh) from neuronal and non-neuronal sources plays important roles in the regulation of immune responses and is associated with the development of several disease pathologies. We have previously demonstrated that group 2 innate lymphoid cell (ILC2)-derived ACh is required for optimal type 2 responses to parasitic infection, and therefore sought to determine whether this also plays a role in allergic inflammation. RoraCre+ChatLoxP mice (in which ILC2s cannot synthesize ACh) were exposed to an allergenic extract of the fungus Alternaria alternata, and immune responses in the airways and lung tissues analysed. Airway neutrophilia and expression of the neutrophil chemoattractants CXCL1 and CXCL2 were enhanced 24 hours after exposure, suggesting that ILC2-derived ACh plays a role in limiting excessive pulmonary neutrophilic inflammation. The effect of non-selective depletion of ACh was examined by intranasal administration of a stable parasite-secreted acetylcholinesterase. Depletion of airway ACh in this manner resulted in more profound enhancement of neutrophilia and chemokine expression, suggesting multiple cellular sources for release of ACh. In contrast, depletion of ACh inhibited Alternaria-induced activation of ILC2s, suppressing expression of IL-5, IL-13 and subsequent eosinophilia. Depletion of ACh resulted in a reduction of macrophages with an alternatively activated M2 phenotype, and an increase in M1 macrophage marker expression. These data suggest that ACh regulates allergic airway inflammation in several ways, enhancing ILC2-driven eosinophilia, but suppressing neutrophilia through reduced chemokine expression.

  • Journal article
    Leong JX, Raffeiner M, Spinti D, Langin G, Franz-Wachtel M, Guzman AR, Kim J-G, Pandey P, Minina AE, Macek B, Hafren A, Bozkurt TO, Mudgett MB, Boernke F, Hofius D, Uestuen Set al., 2022,

    A bacterial effector counteracts host autophagy by promoting degradation of an autophagy component

    , EMBO JOURNAL, Vol: 41, ISSN: 0261-4189
  • Journal article
    Shen Y, Sweeney L, Liu M, Lopez-Saez JA, Perez-Diaz S, Luelmo-Lautenschlaeger R, Gil-Ramera E, Hoefer D, Jimenez-Moreno G, Schneider H, Prentice IC, Harrison SPet al., 2022,

    Reconstructing burnt area during the Holocene: an Iberian case study

    , Climate of the Past, Vol: 18, Pages: 1189-1201, ISSN: 1814-9324

    Charcoal accumulated in lake, bog or other anoxic sediments through time has been used to document the geographical patterns in changes in fire regimes. Such reconstructions are useful to explore the impact of climate and vegetation changes on fire during periods when human influence was less prevalent than today. However, charcoal records only provide semi-quantitative estimates of change in biomass burning. Here we derive quantitative estimates of burnt area from vegetation data in two stages. First, we relate the modern charcoal abundance to burnt area using a conversion factor derived from a generalised linear model of burnt area probability based on eight environmental predictors. Then, we establish the relationship between fossil pollen assemblages and burnt area using tolerance-weighted weighted averaging partial least-squares regression with a sampling frequency correction (fxTWA-PLS). We test this approach using the Iberian Peninsula as a case study because it is a fire-prone region with abundant pollen and charcoal records covering the Holocene. We derive the vegetation–burnt area relationship using the 31 records that have both modern and fossil charcoal and pollen data and then reconstruct palaeoburnt area for the 113 records with Holocene pollen records. The pollen data predict charcoal-derived burnt area relatively well (R2 = 0.44), and the changes in reconstructed burnt area are synchronous with known climate changes through the Holocene. This new method opens up the possibility of reconstructing changes in fire regimes quantitatively from pollen records, after regional calibration of the vegetation–burnt area relationship, in regions where pollen records are more abundant than charcoal records.

  • Journal article
    Giannos P, 2022,

    Gene expression profiles of the aging rat hippocampus imply altered immunoglobulin dynamics

    , Frontiers in Neuroscience, Vol: 16, Pages: 1-6, ISSN: 1662-453X

    Aging is a process that leads to the deterioration in physiological functioning of the brain. Prior research has proposed that hippocampal aging is accompanied by genetic alterations in neural, synaptic, and immune functions. Nevertheless, interactome-based interrogations of gene alterations in hippocampal aging, remain scarce. Our study integrated gene expression profiles of the hippocampus from young and aged rats and functionally classified network-mapped genes based on their interactome. Hippocampal differentially expressed genes (DEGs) between young (5–8 months) and aged (21–26 months) male rats (Rattus norvegicus) were retrieved from five publicly available datasets (GSE14505, GSE20219, GSE14723, GSE14724, and GSE14725; 38 young and 29 aged samples). Encoded hippocampal proteins of age-related DEGs and their interactome were predicted. Clustered network DEGs were identified and the highest-ranked was functionally annotated. A single cluster of 19 age-related hippocampal DEGs was revealed, which was linked with immune response (biological process, P = 1.71E-17), immunoglobulin G binding (molecular function, P = 1.92E-08), and intrinsic component of plasma membrane (cellular component, P = 1.25E-06). Our findings revealed dysregulated hippocampal immunoglobulin dynamics in the aging rat brain. Whether a consequence of neurovascular perturbations and dysregulated blood-brain barrier permeability, the role of hippocampal immunoregulation in the pathobiology of aging warrants further investigation.

  • Journal article
    Bikmetov D, Hall AMJ, Livenskyi A, Gollan B, Ovchinnikov S, Gilep K, Kim JY, Larrouy-Maumus G, Zgoda V, Borukhov S, Severinov K, Helaine S, Dubiley Set al., 2022,

    GNAT toxins evolve toward narrow tRNA target specificities

    , NUCLEIC ACIDS RESEARCH, Vol: 50, Pages: 5807-5817, ISSN: 0305-1048
  • Journal article
    Webberley TS, Masetti G, Bevan RJ, Kerry-Smith J, Jack AA, Michael DR, Thomas S, Glymenaki M, Li J, McDonald JAK, John D, Morgan JE, Marchesi JR, Good MA, Plummer SF, Hughes TRet al., 2022,

    The Impact of Probiotic Supplementation on Cognitive, Pathological and Metabolic Markers in a Transgenic Mouse Model of Alzheimer's Disease

  • Journal article
    Pirillo C, Birch F, Tissot FS, Anton SG, Haltalli M, Tini V, Kong I, Piot C, Partridge B, Pospori C, Keeshan K, Santamaria S, Hawkins E, Falini B, Marra A, Duarte D, Lee CF, Roberts E, Lo Celso Cet al., 2022,

    Metalloproteinase inhibition reduces AML growth, prevents stem cell loss, and improves chemotherapy effectiveness

    , BLOOD ADVANCES, Vol: 6, Pages: 3126-3141, ISSN: 2473-9529
  • Journal article
    Mazur-Michałek I, Ruciński M, Sowiński M, Pietras P, Leśniczak-Staszak M, Szaflarski W, Isalan M, Mielcarek MLet al., 2022,

    Identification of the transcriptional biomarkers panel linked to pathological remodelling of the eye tissues in various HD mouse models.

    , Cells, Vol: 11, ISSN: 2073-4409

    Ocular abnormalities are becoming associated with a spectrum of pathological events in various neurodegenerative diseases. Huntington’s disease (HD) is just such an example of a fatal neurological disorder, where mutated genes (CAG trinucleotide expansions in the Huntingtin gene) have widespread expression, leading to the production of mutant Huntingtin (mHTT) protein. It is well known that mutant HTT protein is prone to form toxic aggregates, which are a typical pathological feature, along with global transcriptome alterations. In this study, we employed well-established quantitative methods like Affymetrix arrays and quantitative PCR (qPCR) to identify a set of transcriptional biomarkers that will track HD progression in three well-established mouse models: R6/2, R6/1 and HdhQ150. Our array analysis revealed significantly deregulated networks that are related to visual processes and muscle contractions. Furthermore, our targeted quantitative analysis identified a panel of biomarkers with some being dysregulated even at the presymptomatic stage of the disease, e.g. Opn1mw, Opn1sw and Pfkfb2. Some of the deregulated genes identified in this study have been linked to other genetic ocular disorders like: GNAT2, a source of achromatopasia; and REEP6, linked to Retinitis pigmentosa. It may thus be a useful platform for preclinical evaluations of therapeutic interventions.

  • Journal article
    Aguirre-Gutierrez J, Berenguer E, Menor IO, Bauman D, Corral-Rivas JJ, Guadalupe Nava-Miranda M, Both S, Ndong JE, Ondo FE, Bengone NN, Mihinhou V, Dalling JW, Heineman K, Figueiredo A, Gonzalez-M R, Norden N, Hurtado-M AB, Gonzalez D, Salgado-Negret B, Reis SM, Moraes de Seixas MM, Farfan-Rios W, Shenkin A, Riutta T, Girardin CAJ, Moore S, Abernethy K, Asner GP, Bentley LP, Burslem DFRP, Cernusak LA, Enquist BJ, Ewers RM, Ferreira J, Jeffery KJ, Joly CA, Marimon-Junior BH, Martin RE, Morandi PS, Phillips OL, Bennett AC, Lewis SL, Quesada CA, Marimon BS, Kissling WD, Silman M, Teh YA, White LJT, Salinas N, Coomes DA, Barlow J, Adu-Bredu S, Malhi Yet al., 2022,

    Functional susceptibility of tropical forests to climate change

    , NATURE ECOLOGY & EVOLUTION, Vol: 6, Pages: 878-+, ISSN: 2397-334X
  • Journal article
    Thorburn D-MJ, Bal TMP, Deflem IS, Volckaert FAM, Eizaguirre C, Raeymaekers JAMet al., 2022,

    Context-dependent parasite infection affects trophic niche in populations of sympatric stickleback species

    , PARASITOLOGY, Vol: 149, Pages: 1164-1172, ISSN: 0031-1820
  • Journal article
    Lee HC, Hastings C, Oliveira NMM, Perez-Carrasco R, Page KM, Wolpert L, Stern CDet al., 2022,

    'Neighbourhood watch' model: embryonic epiblast cells assess positional information in relation to their neighbours

    , Development, Vol: 149, ISSN: 0950-1991

    In many developing and regenerating systems, tissue pattern is established through gradients of informative morphogens, but we know little about how cells interpret these. Using experimental manipulation of early chick embryos, including misexpression of an inducer (VG1 or ACTIVIN) and an inhibitor (BMP4), we test two alternative models for their ability to explain how the site of primitive streak formation is positioned relative to the rest of the embryo. In one model, cells read morphogen concentrations cell-autonomously. In the other, cells sense changes in morphogen status relative to their neighbourhood. We find that only the latter model can account for the experimental results, including some counter-intuitive predictions. This mechanism (which we name the 'neighbourhood watch' model) illuminates the classic 'French Flag Problem' and how positional information is interpreted by a sheet of cells in a large developing system.

  • Journal article
    Zhou L, Kong G, Palmisano I, Cencioni MT, Danzi M, De Virgiliis F, Chadwick JS, Crawford G, Yu Z, De Winter F, Lemmon V, Bixby J, Puttagunta R, Verhaagen J, Pospori C, Lo Celso C, Strid J, Botto M, Di Giovanni Set al., 2022,

    Reversible CD8 T cell-neuron cross-talk causes aging-dependent neuronal regenerative decline.

    , Science, Vol: 376, Pages: 1-15, ISSN: 0036-8075

    INTRODUCTIONAxonal regeneration and neurological functional recovery are extremely limited in the elderly. Consequently, injuries to the nervous system are typically followed by severe and long-term disability. Our understanding of the molecular mechanisms underlying aging-dependent regenerative failure is poor, hindering progress in the development of effective therapies for neurological repair. To facilitate the design of repair strategies, there is a pressing need to identify critical molecular and cellular mechanisms that cause regenerative failure in aging.RATIONALEAging causes a broad spectrum of modifications in cell signaling, including changes in metabolism, immunity, and overall tissue homeostasis, which play key roles in nervous system physiology and response to insults. Thus, we hypothesized that injuries to the aged nervous system would be followed by unique molecular and cellular modifications that would contribute to aging-dependent regenerative decline. To this end, molecular and cellular signatures associated with aging and injury to the nervous system were systematically investigated by performing RNA sequencing from dorsal root ganglia (DRG) in a well-established model of sciatic nerve injury in young versus aged mice. Insight into these mechanisms could allow the discovery of previously unrecognized molecular targets to counteract aging-dependent regenerative decline.RESULTSInitial analysis of RNA sequencing data identified that aging was mainly associated with a marked increase in T cell activation and signaling in DRG after sciatic nerve injury in mice. Subsequent experiments demonstrated that aging was associated with increased inflammatory cytokines including lymphotoxins in DRG both preceding and following sciatic nerve injury. Specifically, we found that lymphotoxin β was required for the phosphorylation of NF-κB that drives the expression of the chemokine CXCL13 in DRG sensory neurons. CXCL13 attracted CD8+ T cells that expresse

  • Working paper
    Zhang D, Mullish BH, Wang J, Barker G, Chrysostomou D, Gao S, Chen L, McDonald JAK, Marchesi JR, Cheng Let al., 2022,

    Identifying transient and stable bacteria- metabolite interactions from longitudinal multi-omics data

    , Publisher: Research Square

    BackgroundUnderstanding the complex relationships between bacteria and metabolites in ecological systems are extremely important in studies of different microbiomes. Longitudinal multi-omics study is adopted to investigate interactions between bacteria and metabolites, by directly associating their longitudinal profiles. Since a bacteria/metabolite may involve in many different biological processes, the longitudinal profile is an average of different interactions. Therefore, direct association could only uncover the strongest interactions.ResultsHere we present a computational approach that can rebuild short- and long-term bacteria-metabolite interactions from longitudinal multi-omics datasets. For this task, we re-analyse data (both microbial sequencing and metabolomic analysis) from an in vitro model of Clostridioides difficile infection and faecal microbiota transplant, a disease state and mode of therapy in which perturbed microbiome-metabolome interactions (and their reversal) are well-established to be pertinent. By analysing such a dataset, we generated both a short-term and a long-term interaction network, which predicted many new interactions. Four new interactions were randomly selected to be validated. In batch culture experiments, we validated two of them: (1) Ruminococcus gnavus and Ruminococcus luti could generate 3-ketocholanic acid (2) Blautia obeum could consume succinate.ConclusionsThe deconvolution of the raw longitudinal signal into short- and long-term trends can help users to gain a deeper understanding of their data. This tool will be useful for high-throughput screening of microbe/metabolite/host interactions from a longitudinal multi-omics setting.

  • Journal article
    Mazur-Michałek I, Kowalska K, Zielonka D, Leśniczak-Staszak M, Pietras P, Szaflarski W, Isalan M, Mielcarek Met al., 2022,

    Structural abnormalities of the optic nerve and retina in Huntington’s disease pre-clinical and clinical settings

    , International Journal of Molecular Sciences, Vol: 23, ISSN: 1422-0067

    Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. HD-related pathological remodelling has been reported in HD mouse models and HD carriers. In this study, we studied structural abnormalities in the optic nerve by employing Spectral Domain Optical Coherence Tomography (SD-OCT) in pre-symptomatic HD carriers of Caucasian origin. Transmission Electron Microscopy (TEM) was used to investigate ultrastructural changes in the optic nerve of the well-established R6/2 mouse model at the symptomatic stage of the disease. We found that pre-symptomatic HD carriers displayed a significant reduction in the retinal nerve fibre layer (RNFL) thickness, including specific quadrants: superior, inferior and temporal, but not nasal. There were no other significant irregularities in the GCC layer, at the macula level and in the optic disc morphology. The ultrastructural analysis of the optic nerve in R6/2 mice revealed a significant thinning of the myelin sheaths, with a lamellar separation of the myelin, and a presence of myelonoid bodies. We also found a significant reduction in the thickness of myelin sheaths in peripheral nerves within the choroids area. Those ultrastructural abnormalities were also observed in HD photoreceptor cells that contained severely damaged membrane disks, with evident vacuolisation and swelling. Moreover, the outer segment of retinal layers showed a progressive disintegration. Our study explored structural changes of the optic nerve in pre- and clinical settings and opens new avenues for the potential development of biomarkers that would be of great interest in HD gene therapies.

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