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  • Journal article
    Dunne EM, Thompson SED, Butler RJ, Rosindell J, Close RAet al., 2023,

    Mechanistic neutral models show that sampling biases drive the apparent explosion of early tetrapod diversity

    , Nature Ecology and Evolution, Vol: 7, Pages: 1480-1489, ISSN: 2397-334X

    Estimates of deep-time biodiversity typically rely on statistical methods to mitigate the impacts of sampling biases in the fossil record. However, these methods are limited by the spatial and temporal scale of the underlying data. Here we use a spatially explicit mechanistic model, based on neutral theory, to test hypotheses of early tetrapod diversity change during the late Carboniferous and early Permian, critical intervals for the diversification of vertebrate life on land. Our simulations suggest that apparent increases in early tetrapod diversity were not driven by local endemism following the ‘Carboniferous rainforest collapse’. Instead, changes in face-value diversity can be explained by variation in sampling intensity through time. Our results further demonstrate the importance of accounting for sampling biases in analyses of the fossil record and highlight the vast potential of mechanistic models, including neutral models, for testing hypotheses in palaeobiology.

  • Conference paper
    Bubeck D, 2023,

    Controlling the membrane attack complex

    , Publisher: ELSEVIER GMBH, Pages: 1-1, ISSN: 0171-2985
  • Conference paper
    Mountain K, MacIntyre D, Chan D, Hyde A, Pasint-Magyar J, Lee Y, Brown R, David A, Dell A, Ten F, Haslam S, Liu Y, Lewis H, Norman J, Stock S, Teoh T, Terzidou V, Kundu S, Bennett P, Sykes Let al., 2023,

    ABO blood group antigens and preterm birth risk

    , 12th International Workshop Reunion Island Reproductive Immunology, Immunological tolerance and Immunology of preeclampsia, Publisher: ELSEVIER IRELAND LTD, Pages: 37-37, ISSN: 0165-0378
  • Conference paper
    Gimeno-Molina B, Bayar E, Mountain K, Love R, Lee Y, Muller I, Dell A, Haslam S, Grassi P, Wu G, MacIntyre D, Bennett P, Kropf P, Sykes Let al., 2023,

    The role of cervical neutrophils in cervicovaginal inflammation in women at high-risk of delivering preterm

    , 12th International Workshop Reunion Island Reproductive Immunology, Immunological tolerance and Immunology of preeclampsia, Publisher: ELSEVIER IRELAND LTD, Pages: 31-31, ISSN: 0165-0378
  • Other
    Rowell J, Lau C-I, Yánez DC, Zhang E, Crompton Tet al., 2023,

    Hedgehog signalling in allograft vasculopathy: a new therapeutic target?

    Allograft vasculopathy (AV) leads to chronic rejection of organ transplants, but its causes are obscure. New research from the Jane-Wit laboratory showed that Sonic Hedgehog (SHH) signalling from damaged graft endothelium drives vasculopathy by promoting proinflammatory cytokine production and NLRP3-inflammasome activation in alloreactive CD4+PTCH1hiPD-1hiT memory cells, offering new diagnostic and therapeutic strategies.

  • Journal article
    Huang X, Torre I, Chiappi M, Yin Z, Vydyanath A, Cao S, Raschdorf O, Beeby M, Quigley B, de Tombe PP, Liu J, Morris EP, Luther PKet al., 2023,

    Cryo-electron tomography of intact cardiac muscle reveals myosin binding protein-C linking myosin and actin filaments

    , JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY, Vol: 44, Pages: 165-178, ISSN: 0142-4319
  • Journal article
    Moratto E, Rothery S, Bozkurt TO, Sena Get al., 2023,

    Enhanced germination and electrotactic behaviour of Phytophthora palmivora zoospores in weak electric fields

    , Physical Biology, Vol: 20, Pages: 1-10, ISSN: 1478-3967

    Soil-dwelling microorganisms use a variety of chemical and physical signals to navigate their environment. Plant roots produce endogenous electric fields which result in characteristic current profiles. Such electrical signatures are hypothesised to be used by pathogens and symbionts to track and colonise plant roots.
The oomycete pathogen Phytophthora palmivora generates motile zoospores which swim towards the positive pole when exposed to an external electric field in vitro.
Here, we provide a quantitative characterization of their electrotactic behaviour in 3D. We found that a weak electric field (0.7 - 1.0 V/cm) is sufficient to induce an accumulation of zoospore at the positive pole, without affecting their encystment rate. We also show that the same external electric field increases the zoospore germination rate and orients the germ tube's growth. We conclude that several early stages of the P. palmivora infection cycle are affected by external electric fields.
Taken together, our results are compatible with the hypothesis that pathogens use plant endogenous electric fields for host targeting.

  • Journal article
    Förderer A, Kourelis J, 2023,

    NLR immune receptors: structure and function in plant disease resistance

    , Biochemical Society Transactions, Vol: 51, Pages: 1473-1483, ISSN: 0300-5127

    Nucleotide-binding and leucine-rich repeat receptors (NLRs) are a diverse family of intracellular immune receptors that play crucial roles in recognizing and responding to pathogen invasion in plants. This review discusses the overall model of NLR activation and provides an in-depth analysis of the different NLR domains, including N-terminal executioner domains, the nucleotide-binding oligomerization domain (NOD) module, and the leucine-rich repeat (LRR) domain. Understanding the structure-function relationship of these domains is essential for developing effective strategies to improve plant disease resistance and agricultural productivity.

  • Journal article
    Gonzalez A, Vihervaara P, Balvanera P, Bates AE, Bayraktarov E, Bellingham PJ, Bruder A, Campbell J, Catchen MD, Cavender-Bares J, Chase J, Coops N, Costello MJ, Dornelas M, Dubois G, Duffy EJ, Eggermont H, Fernandez N, Ferrier S, Geller GN, Gill M, Gravel D, Guerra CA, Guralnick R, Harfoot M, Hirsch T, Hoban S, Hughes AC, Hunter ME, Isbell F, Jetz W, Juergens N, Kissling WD, Krug CB, Le Bras Y, Leung B, Londono-Murcia MC, Lord J-M, Loreau M, Luers A, Ma K, Macdonald AJ, Mcgeoch M, Millette KL, Molnar Z, Mori AS, Muller-Karger FE, Muraoka H, Navarro L, Newbold T, Niamir A, Obura D, O'Connor M, Paganini M, Pereira H, Poisot T, Pollock LJ, Purvis A, Radulovici A, Rocchini D, Schaepman M, Schaepman-Strub G, Schmeller DS, Schmiedel U, Schneider FD, Shakya MM, Skidmore A, Skowno AL, Takeuchi Y, Tuanmu M-N, Turak E, Turner W, Urban MC, Urbina-Cardona N, Valbuena R, van Havre B, Wright Eet al., 2023,

    A global biodiversity observing system to unite monitoring and guide action

    , NATURE ECOLOGY & EVOLUTION, ISSN: 2397-334X
  • Journal article
    Yip AYG, King OG, Omelchenko O, Kurkimat S, Horrocks V, Mostyn P, Danckert N, Ghani R, Satta G, Jauneikaite E, Davies FJ, Clarke TB, Mullish BH, Marchesi JR, McDonald JAKet al., 2023,

    Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites

    , Nature Communications, Vol: 14, Pages: 1-20, ISSN: 2041-1723

    The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.

  • Journal article
    Allen ME, Hindley J, O'Toole N, Cooke H, Contini C, Law R, Ces O, Elani Yet al., 2023,

    Biomimetic Behaviours in Hydrogel Artificial Cells through Embedded Organelles

    , Proceedings of the National Academy of Sciences of USA, Vol: 120, ISSN: 0027-8424

    Artificial cells are biomimetic structures formed from molecular building blocks that replicate biological processes, behaviors, and architectures. Of these building blocks, hydrogels have emerged as ideal, yet underutilized candidates to provide a gel-like chassis in which to incorporate both biological and nonbiological componentry which enables the replication of cellular functionality. Here, we demonstrate a microfluidic strategy to assemble biocompatible cell-sized hydrogel-based artificial cells with a variety of different embedded functional subcompartments, which act as engineered synthetic organelles. The organelles enable the recreation of increasingly biomimetic behaviors, including stimulus-induced motility, content release through activation of membrane-associated proteins, and enzymatic communication with surrounding bioinspired compartments. In this way, we showcase a foundational strategy for the bottom–up construction of hydrogel-based artificial cell microsystems which replicate fundamental cellular behaviors, paving the way for the construction of next-generation biotechnological devices.

  • Journal article
    Davis D, Worboys J, Vowell K, Hare R, Amborse A, Bertuzzi M, Conner M, Patel F, Zammit W, Gali-Moya J, Hazime K, Jones K, Rey C, Jonjic S, Lenac T, Tannahill G, De Matos G, Waight Jet al., 2023,

    TIGIT can inhibit T cell activation via ligation-induced nanoclusters, independent of CD226 co-stimulation

    , Nature Communications, Vol: 14, ISSN: 2041-1723

    TIGIT is an inhibitory receptor expressed on lymphocytes and can inhibit T cells by preventing CD226 co-stimulation through interactions in cis or through competition of shared ligands. Whether TIGIT directly delivers cell-intrinsic inhibitory signals in T cells remains unclear. Here we show, by analysing lymphocytes from matched human tumour and peripheral blood samples, that TIGIT and CD226 co-expression is rare on tumour-infiltrating lymphocytes. Using super-resolution microscopy and other techniques, we demonstrate that ligation with CD155 causes TIGIT to reorganise into dense nanoclusters, which coalesce with T cell receptor (TCR)-rich clusters at immune synapses. Functionally, this reduces cytokine secretion in a manner dependent on TIGIT’s intracellular ITT-like signalling motif. Thus, we provide evidence that TIGIT directly inhibits lymphocyte activation, acting independently of CD226, requiring intracellular signalling that is proximal to the TCR. Within the subset of tumours where TIGIT-expressing cells do not commonly co-express CD226, this will likely be the dominant mechanism of action.

  • Journal article
    Abouelhadid S, Atkins ER, Kay EJ, Passmore IJ, North SJ, Lehri B, Hitchen P, Bakke E, Rahman M, Bossé JT, Li Y, Terra VS, Langford PR, Dell A, Wren BW, Cuccui Jet al., 2023,

    Development of a novel glycoengineering platform for the rapid production of conjugate vaccines

    , Microbial Cell Factories, Vol: 22, Pages: 1-13, ISSN: 1475-2859

    Conjugate vaccines produced either by chemical or biologically conjugation have been demonstrated to be safe and efficacious in protection against several deadly bacterial diseases. However, conjugate vaccine assembly and production have several shortcomings which hinders their wider availability. Here, we developed a tool, Mobile-element Assisted Glycoconjugation by Insertion on Chromosome, MAGIC, a novel biotechnological platform that overcomes the limitations of the current conjugate vaccine design method(s). As a model, we focused our design on a leading bioconjugation method using N-oligosaccharyltransferase (OTase), PglB. The installation of MAGIC led to at least twofold increase in glycoconjugate yield via MAGIC when compared to conventional N-OTase based bioconjugation method(s). Then, we improved MAGIC to (a) allow rapid installation of glycoengineering component(s), (b) omit the usage of antibiotics, (c) reduce the dependence on protein induction agents. Furthermore, we show the modularity of the MAGIC platform in performing glycoengineering in bacterial species that are less genetically tractable than the commonly used Escherichia coli. The MAGIC system promises a rapid, robust and versatile method to develop vaccines against serious bacterial pathogens. We anticipate the utility of the MAGIC platform could enhance vaccines production due to its compatibility with virtually any bioconjugation method, thus expanding vaccine biopreparedness toolbox.

  • Journal article
    Liang G, Stark J, Waring B, 2023,

    Mineral reactivity determines root effects on soil organic carbon

    , Nature Communications, Vol: 14, Pages: 1-10, ISSN: 2041-1723

    Modern conceptual models of soil organic carbon (SOC) cycling focus heavily on the microbe-mineral interactions that regulate C stabilization. However, the formation of ‘stable’ (i.e. slowly cycling) soil organic matter, which consists mainly of microbial residues associated with mineral surfaces, is inextricably linked to C loss through microbial respiration. Therefore, what is the net impact of microbial metabolism on the total quantity of C held in the soil? To address this question, we constructed artificial root-soil systems to identify controls on C cycling across the plant-microbe-mineral continuum, simultaneously quantifying the formation of mineral-associated C and SOC losses to respiration. Here we show that root exudates and minerals interacted to regulate these processes: while roots stimulated respiratory C losses and depleted mineral-associated C pools in low-activity clays, root exudates triggered formation of stable C in high-activity clays. Moreover, we observed a positive correlation between the formation of mineral-associated C and respiration. This suggests that the growth of slow-cycling C pools comes at the expense of C loss from the system.

  • Journal article
    Macleod K, Greer SF, Bramham LE, Pimenta RJG, Nellist CF, Hackenburg D, Teakle GR, Barker GC, Walsh JAet al., 2023,

    A review of sources of resistance to turnip yellows virus (TuYV) in <i>Brassica</i> species

    , ANNALS OF APPLIED BIOLOGY, ISSN: 0003-4746
  • Journal article
    Hutchison CDM, Baxter JM, Fitzpatrick A, Dorlhiac G, Fadini A, Perrett S, Maghlaoui K, Lefevre SB, Cordon-Preciado V, Ferreira JL, Chukhutsina VU, Garratt D, Barnard J, Galinis G, Glencross F, Morgan RM, Stockton S, Taylor B, Yuan L, Romei MG, Lin C-Y, Marangos JP, Schmidt M, Chatrchyan V, Buckup T, Morozov D, Park J, Park S, Eom I, Kim M, Jang D, Choi H, Hyun H, Park G, Nango E, Tanaka R, Owada S, Tono K, DePonte DP, Carbajo S, Seaberg M, Aquila A, Boutet S, Barty A, Iwata S, Boxer SG, Groenhof G, van Thor JJet al., 2023,

    Optical control of ultrafast structural dynamics in a fluorescent protein

    , NATURE CHEMISTRY, ISSN: 1755-4330
  • Journal article
    Rosindell J, 2023,

    Indicators to monitor the status of the Tree of Life

    , Conservation Biology, ISSN: 0888-8892
  • Journal article
    Grockowiak E, Korn C, Rak J, Lysenko V, Hallou A, Panvini FM, Williams M, Fielding C, Fang Z, Khatib-Massalha E, Garcia-Garcia A, Li J, Khorshed RA, Gonzalez-Anton S, Baxter EJ, Kusumbe A, Wilkins BS, Green A, Simons BD, Harrison CN, Green AR, Lo Celso C, Theocharides APA, Mendez-Ferrer Set al., 2023,

    Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms

    , NATURE CANCER
  • Journal article
    Pilkington C, Contini C, Barritt J, Simpson P, Seddon J, Elani Yet al., 2023,

    A microfluidic platform for the controlled synthesis of architecturally complex liquid crystalline nanoparticles

    , Scientific Reports, Vol: 13, Pages: 1-14, ISSN: 2045-2322

    Soft-matter nanoparticles are of great interest for their applications in biotechnology, therapeutic delivery, and in vivo imaging. Underpinningthis is their biocompatibility, potential for selective targeting, attractive pharmacokinetic properties, and amenability to downstreamfunctionalisation. Morphological diversity inherent to soft-matter particles can give rise to enhanced functionality. However, this diversityremains untapped in clinical and industrial settings, and only the simplest of particle architectures (spherical lipid vesicles and lipid/polymernanoparticles (LNPs)) have been exploited. To address this, we have designed a scalable microfluidic hydrodynamic focusing (MHF)technology for the controllable, rapid, and continuous production of lyotropic liquid crystalline (LLC) nanoparticles (both cubosomes andhexosomes), colloidal dispersions of higher-order lipid assemblies with intricate internal structures of 3-D and 2-D symmetry. These particleshave been proposed as the next generation of soft-matter nano-carriers, with unique fusogenic and physical properties. Crucially, unlikealternative approaches, our microfluidic method gives control over LLC size, a feature we go on to exploit in a fusogenic study with modelcell membranes, where a dependency on particle diameter is evident. We believe our platform has the potential to serve as a tool for futurestudies involving non-lamellar soft nanoparticles, and anticipate it allowing for the rapid prototyping of LLC particles of diverse functionality,paving the way toward their eventual uptake at an industrial level.

  • Journal article
    Zhao Z, Vercellino I, Knoppová J, Sobotka R, Murray JW, Nixon PJ, Sazanov LA, Komenda Jet al., 2023,

    The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis

    , Nature Communications, Vol: 14, Pages: 1-11, ISSN: 2041-1723

    Robust oxygenic photosynthesis requires a suite of accessory factors to ensure efficient assembly and repair of the oxygen-evolving photosystem two (PSII) complex. The highly conserved Ycf48 assembly factor binds to the newly synthesized D1 reaction center polypeptide and promotes the initial steps of PSII assembly, but its binding site is unclear. Here we have used cryo-electron microscopy to determine the structure of a cyanobacterial PSII D1/D2 reaction center assembly complex with Ycf48 attached. Ycf48, a 7-bladed beta propeller, binds to the amino-acid residues of D1 that ultimately ligate the water-oxidising Mn4CaO5 cluster, thereby preventing the premature binding of Mn2+ and Ca2+ ions and protecting the site from damage. Interactions with D2 help explain how Ycf48 promotes assembly of the D1/D2 complex. Overall, our work provides valuable insights into the early stages of PSII assembly and the structural changes that create the binding site for the Mn4CaO5 cluster.

  • Journal article
    Fantuzzi A, Haniewicz P, Farci D, Loi MC, Park K, Büchelf C, Bochtler M, Rutherford A, Piano Det al., 2023,

    Bicarbonate activation of the monomeric photosystem II-PsbS/Psb27 complex

    , Plant Physiology, Vol: 192, Pages: 2656-2671, ISSN: 0032-0889

    In thylakoid membranes, Photosystem II (PSII) monomers from the stromal lamellae contain the subunits PsbS and Psb27 (PSIIm-S/27), while PSII monomers from granal regions (PSIIm) lack these subunits. Here, we have isolated and characterised these two types of Photosystem II complexes in tobacco (Nicotiana tabacum). PSIIm-S/27 showed enhanced fluorescence, the near-absence of oxygen evolution, as well as limited and slow electron transfer from QA to QB compared to the near-normal activities in the granal PSIIm. However, when bicarbonate was added to PSIIm-S/27, water splitting and QA to QB electron transfer rates were comparable to those in granal PSIIm. The findings suggest that the binding of PsbS and/or Psb27 inhibits forward electron transfer and lowers the binding affinity for bicarbonate. This can be rationalized in terms of the recently discovered photoprotection role played by bicarbonate binding via the redox tuning of the QA/QA•– couple, which controls the charge recombination route, and this limits chlorophyll triplet mediated 1O2 formation. These findings suggest that PSIIm-S/27 is an intermediate in the assembly of PSII in which PsbS and/or Psb27 restrict PSII activity while in transit using a bicarbonate-mediated switch and protective mechanism.

  • Journal article
    Tan G, Spillane KM, Maher J, 2023,

    The Role and Regulation of the NKG2D/NKG2D Ligand System in Cancer

    , Biology, Vol: 12

    The family of human NKG2D ligands (NKG2DL) consists of eight stress-induced molecules. Over 80% of human cancers express these ligands on the surface of tumour cells and/or associated stromal elements. In mice, NKG2D deficiency increases susceptibility to some types of cancer, implicating this system in immune surveillance for malignancy. However, NKG2DL can also be shed, released via exosomes and trapped intracellularly, leading to immunosuppressive effects. Moreover, NKG2D can enhance chronic inflammatory processes which themselves can increase cancer risk and progression. Indeed, tumours commonly deploy a range of countermeasures that can neutralise or even corrupt this surveillance system, tipping the balance away from immune control towards tumour progression. Consequently, the prognostic impact of NKG2DL expression in human cancer is variable. In this review, we consider the underlying biology and regulation of the NKG2D/NKG2DL system and its expression and role in a range of cancer types. We also consider the opportunities for pharmacological modulation of NKG2DL expression while cautioning that such interventions need to be carefully calibrated according to the biology of the specific cancer type.

  • Journal article
    Fattorini R, Egan PA, Rosindell J, Farrell IW, Stevenson PCet al., 2023,

    Grayanotoxin I variation across tissues and species of Rhododendron suggests pollinator-herbivore defence trade-offs

    , Phytochemistry: the international journal of plant chemistry, plant biochemistry and molecular biology, Vol: 212, Pages: 1-7, ISSN: 0031-9422

    Grayanotoxin I (GTX I) is a major toxin in leaves of Rhododendron species, where it provides a defence against insect and vertebrate herbivores. Surprisingly, it is also present in R. ponticum nectar, and this can hold important implications for plant-pollinator mutualisms. However, knowledge of GTX I distributions across the genus Rhododendron and in different plant materials is currently limited, despite the important ecological function of this toxin. Here we characterise GTX I expression in the leaves, petals, and nectar of seven Rhododendron species. Our results indicated interspecific variation in GTX I concentration across all species. GTX I concentrations were consistently higher in leaves compared to petals and nectar. Our findings provide preliminary evidence for phenotypic correlation between GTX I concentrations in defensive tissues (leaves and petals) and floral rewards (nectar), suggesting that Rhododendron species may commonly experience functional trade-offs between herbivore defence and pollinator attraction.

  • Journal article
    Shepherd S, Yuen ELH, Carella P, Bozkurt TOet al., 2023,

    The wheels of destruction: Plant NLR immune receptors are mobile and structurally dynamic disease resistance proteins

    , CURRENT OPINION IN PLANT BIOLOGY, Vol: 74, ISSN: 1369-5266
  • Journal article
    Xie Y, Zhao F, Freitag N, Borowski S, Wang Y, Harms C, Pang P-C, Desforges J, Wen T, Schwedhelm E, Singh M, Dechend R, Dell A, Haslam SM, Dveksler G, Garcia MG, Blois SMet al., 2023,

    Maternal-derived galectin-1 shapes the placenta niche through Sda terminal glycosylation: implication for preeclampsia

    , PNAS Nexus, Vol: 2, ISSN: 2752-6542

    Placental abnormalities cause impaired fetal growth and poor pregnancy outcome (e.g. preeclampsia [PE]) with long-lasting consequences for the mother and offspring. The molecular dialogue between the maternal niche and the developing placenta is critical for the function of this organ. Galectin-1 (gal-1), a highly expressed glycan-binding protein at the maternal–fetal interface, orchestrates the maternal adaptation to pregnancy and placenta development. Down-regulation or deficiency of gal-1 during pregnancy is associated with the development of PE; however, the maternal- and placental-derived gal-1 contributions to the disease onset are largely unknown. We demonstrate that lack of gal-1 imposes a risk for PE development in a niche-specific manner, and this is accompanied by a placental dysfunction highly influenced by the absence of maternal-derived gal-1. Notably, differential placental glycosylation through the Sda-capped N-glycans dominates the invasive trophoblast capacity triggered by maternal-derived gal-1. Our findings show that gal-1 derived from the maternal niche is essential for healthy placenta development and indicate that impairment of the gal-1 signaling pathway within the maternal niche could be a molecular cause for maternal cardiovascular maladaptation during pregnancy.

  • Journal article
    Canton APM, Tinano FR, Guasti L, Montenegro LR, Ryan F, Shears D, de Melo ME, Gomes LG, Piana MP, Brauner R, Espino-Aguilar R, Escribano-Muñoz A, Paganoni A, Read JE, Korbonits M, Seraphim CE, Costa SS, Krepischi AC, Jorge AAL, David A, Kaisinger LR, Ong KK, Perry JRB, Abreu AP, Kaiser UB, Argente J, Mendonca BB, Brito VN, Howard SR, Latronico ACet al., 2023,

    Rare variants in the MECP2 gene in girls with central precocious puberty: a translational cohort study

    , The Lancet Diabetes & Endocrinology, Vol: 11, Pages: 545-554, ISSN: 2213-8587

    BackgroundIdentification of genetic causes of central precocious puberty have revealed epigenetic mechanisms as regulators of human pubertal timing. MECP2, an X-linked gene, encodes a chromatin-associated protein with a role in gene transcription. MECP2 loss-of-function mutations usually cause Rett syndrome, a severe neurodevelopmental disorder. Early pubertal development has been shown in several patients with Rett syndrome. The aim of this study was to explore whether MECP2 variants are associated with an idiopathic central precocious puberty phenotype.MethodsIn this translational cohort study, participants were recruited from seven tertiary centres from five countries (Brazil, Spain, France, the USA, and the UK). Patients with idiopathic central precocious puberty were investigated for rare potentially damaging variants in the MECP2 gene, to assess whether MECP2 might contribute to the cause of central precocious puberty. Inclusion criteria were the development of progressive pubertal signs (Tanner stage 2) before the age of 8 years in girls and 9 years in boys and basal or GnRH-stimulated LH pubertal concentrations. Exclusion criteria were the diagnosis of peripheral precocious puberty and the presence of any recognised cause of central precocious puberty (CNS lesions, known monogenic causes, genetic syndromes, or early exposure to sex steroids). All patients included were followed up at the outpatient clinics of participating academic centres. We used high-throughput sequencing in 133 patients and Sanger sequencing of MECP2 in an additional 271 patients. Hypothalamic expression of Mecp2 and colocalisation with GnRH neurons were determined in mice to show expression of Mecp2 in key nuclei related to pubertal timing regulation.FindingsBetween Jun 15, 2020, and Jun 15, 2022, 404 patients with idiopathic central precocious puberty (383 [95%] girls and 21 [5%] boys; 261 [65%] sporadic cases and 143 [35%] familial cases from 134 unrelated families) were enrolled and

  • Journal article
    Ruehr S, Keenan TF, Williams C, Zhou Y, Lu X, Bastos A, Canadell JG, Prentice IC, Sitch S, Terrer Cet al., 2023,

    Evidence and attribution of the enhanced land carbon sink

    , Nature Reviews Earth & Environment, Vol: 4, Pages: 518-534, ISSN: 2662-138X

    Climate change has been partially mitigated by an increasing net land carbon sink in the terrestrial biosphere; understanding the processes that drive the land carbon sink is thus essential for protecting, managing, and projecting this important ecosystem service. In this Review, we examine evidence for an enhanced land carbon sink and attribute the observed response to drivers and processes. The land carbon sink has doubled from 1.2 ± 0.5 PgC yr-1 in the 1960s to 3.1 ± 0.6 PgC yr-1 in the 2010s. This trend results largely from carbon dioxide (CO2) fertilization increasing photosynthesis (driving an increase in the annual land carbon sink of >2PgC globally since 1900), mainly in tropical forest regions, and elevated temperatures reducing cold-limitation, mainly at higher latitudes. Continued long term land carbon sequestration is possible through the end of this century under multiple emissions scenarios, especially if nature-based climate solutions and appropriate ecosystem management are deployed. A new generation of globally distributed field experiments are needed to improve understanding of future carbon sink potential by measuring belowground carbon release, the response to CO2 enrichment, and long-term shifts in carbon allocation and turnover .

  • Journal article
    Pearse WD, Stemkovski M, Lee BRR, Primack RB, Lee SDet al., 2023,

    Consistent, linear phenological shifts across a century of observations in South Korea

    , NEW PHYTOLOGIST, Vol: 239, Pages: 824-829, ISSN: 0028-646X
  • Journal article
    Beidler KV, Powers JS, Dupuy-Rada JM, Hulshof C, Medvigy D, Pizano C, Salgado-Negret B, Van Bloem SJ, Vargas GG, Waring BG, Kennedy PGet al., 2023,

    Seasonality regulates the structure and biogeochemical impact of ectomycorrhizal fungal communities across environmentally divergent neotropical dry forestsPalabras clave

    , JOURNAL OF ECOLOGY, Vol: 111, Pages: 1598-1613, ISSN: 0022-0477
  • Journal article
    Bellotto-Trigo FC, Uezu A, Hatfield JH, Morante-Filho JC, dos Anjos L, Develey PF, Clegg T, Orme DL, Banks-Leite Cet al., 2023,

    Intraspecific variation in sensitivity to habitat fragmentation is influenced by forest cover and distance to the range edge

    , BIOLOGICAL CONSERVATION, Vol: 284, ISSN: 0006-3207

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