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| Open AccessAzoles activate type I and type II programmed cell death pathways in crop pathogenic fungi
Antifungal azoles inhibit ergosterol biosynthesis, but how that leads to fungistatic or fungicidal activities in many pathogenic fungi is poorly understood. Here, Schuster, Kilaru & Steinberg show that azole lethality in the plant pathogens Zymoseptoria tritici and Magnaporthe oryzae is due to a combination of reactive oxygen species-induced apoptosis and macroautophagy.
- Martin Schuster
- , Sreedhar Kilaru
- & Gero Steinberg
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Article
| Open AccessThe real-time infection hospitalisation and fatality risk across the COVID-19 pandemic in England
The severity of SARS-CoV-2 infection varied over the course of the pandemic due to factors such as changes in variant characteristics and population immunity from previous infection or vaccination. Here, the authors estimate infection hospitalisation and infection fatality rates in England over time from the start of the pandemic until March 2023.
- Thomas Ward
- , Martyn Fyles
- & Christopher E. Overton
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Article
| Open AccessTwo noncompeting human neutralizing antibodies targeting MPXV B6 show protective effects against orthopoxvirus infections
There are limited therapeutics available for treatment of mpox. In this study, the authors identify two non-competing human neutralizing monoclonal antibodies with protective effects against orthopoxvirus infection in a mouse model and structurally resolve the targeted epitope within the MPXV B6 protein.
- Runchu Zhao
- , Lili Wu
- & Qihui Wang
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Article
| Open AccessNanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles
The precise cellular localization of the SARS-CoV-2 RNA and replication partners has been elusive. Here, the authors use super-resolution fluorescence microscopy and specific labeling to reveal the nanoscale structure of viral replication organelles.
- Leonid Andronov
- , Mengting Han
- & W. E. Moerner
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Article
| Open AccessUniversal paramyxovirus vaccine design by stabilizing regions involved in structural transformation of the fusion protein
There is a lack of vaccines for prevention of human respirovirus 3 (RV3) infection. Bakkers et al. report the design of a stabilized RV3 preF protein vaccine candidate that induces strong neutralizing antibodies and protective responses in small animal models.
- Johannes P. M. Langedijk
- , Freek Cox
- & Mark J. G. Bakkers
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Article
| Open AccessComplete telomere-to-telomere genomes uncover virulence evolution conferred by chromosome fusion in oomycete plant pathogens
Frequent chromosome fusion and fission in oomycetes drive changes in chromosome number. Here, Zhang et al show that these dynamics facilitate the adaptive evolution of genes related to pathogenicity.
- Zhichao Zhang
- , Xiaoyi Zhang
- & Yuanchao Wang
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Perspective
| Open AccessThe link between ancient microbial fluoride resistance mechanisms and bioengineering organofluorine degradation or synthesis
Microbial degradation and biosynthesis of fluorinated compounds is a field of increasing importance, but is hampered by the significant toxicity of fluoride. Here authors discuss emerging ideas on microbial defluorination/fluorination and fluoride resistance mechanisms, providing guidance on how this knowledge can guide future bioengineering approaches.
- Randy B. Stockbridge
- & Lawrence P. Wackett
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Article
| Open AccessCryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses
In this study the authors present the Thogoto virus polymerase cryo-EM structures and reveal unique RNA synthesis mechanisms among orthomyxoviruses. RNA synthesis by Thogoto virus polymerase is shown to be weakly dependent on the host factors ANP32A/B/E in human cells in contrast to influenza viruses.
- Lu Xue
- , Tiancai Chang
- & Xiaoli Xiong
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Article
| Open AccessStructural insights into the DNA topoisomerase II of the African swine fever virus
African swine fever virus is the sole mammalian-infecting virus encoding a type II topoisomerases (pP1192R). The authors present pP1192R structures in different states, illustrating the enzymatic mechanisms of viral type II topoisomerases.
- Jingyuan Cong
- , Yuhui Xin
- & Yutao Chen
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Article
| Open AccessPlasmodium falciparum infection in humans and mosquitoes influence natural Anopheline biting behavior and transmission
Mosquito biting preferences and their impact on malaria transmission are not well understood. Here, the authors report findings from a longitudinal cohort study in Western Kenya which show that males aged 5-15 years tend to be bitten the most, and infectious mosquitoes appear to be more likely to bite infected individuals.
- Christine F. Markwalter
- , Zena Lapp
- & Wendy Prudhomme O’Meara
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Article
| Open AccessBinding of Akkermansia muciniphila to mucin is O-glycan specific
Intestinal mucus consists of densely O-glycosylated mucins, serving as a nutrient source for bacteria. Elzinga et al. show that mucin-degrading Akkermansia muciniphila selectively binds to O-glycan structures found on human colonic mucins.
- Janneke Elzinga
- , Yoshiki Narimatsu
- & Hanne L. P. Tytgat
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Article
| Open AccessThe evolution of antibiotic resistance islands occurs within the framework of plasmid lineages
In their study, Wang and Dagan show that 84% of antibiotic resistance genes in multidrug resistance plasmids in Escherichia, Salmonella, and Klebsiella reside within resistance islands that evolve within the framework of plasmid lineages.
- Yiqing Wang
- & Tal Dagan
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Article
| Open AccessStochasticity, determinism, and contingency shape genome evolution of endosymbiotic bacteria
Endosymbionts often have small genomes that maintain minimal functions required to serve their hosts. This study examines cases of new endosymbiont acquisition and finds genome degeneration involves both stochastic and deterministic processes that shape gene content and organismal function.
- Bret M. Boyd
- , Ian James
- & Colin Dale
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Article
| Open AccessThe low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells
This study shows that Crimean-Congo hemorrhagic fever virus (CCHFV) recruits apoE, an exchangeable apolipoprotein that mediates LDL/LDL-R interaction, to promote virion entry via the LDLR. Molecules that down-regulate LDL-R inhibit CCHFV infection.
- Maureen Ritter
- , Lola Canus
- & Solène Denolly
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Article
| Open AccessPhysiochemical interaction between osmotic stress and a bacterial exometabolite promotes plant disease
A single exometabolite produced by an opportunistic bacterial pathogen of the root microbiome enhances host susceptibility to salt stress and promotes plant disease in complex soil systems.
- Felix Getzke
- , Lei Wang
- & Stéphane Hacquard
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Article
| Open AccessGut microbiome remodeling and metabolomic profile improves in response to protein pacing with intermittent fasting versus continuous caloric restriction
Here, in a follow-up of a clinical study, the authors show that protein pacing and intermittent fasting improves gut symptomatology and microbial diversity, as well as reduces visceral fat compared to a heart-healthy, calorie-restricted diet matched for overall energy intake and expenditure in free-living humans.
- Alex E. Mohr
- , Karen L. Sweazea
- & Paul J. Arciero
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Article
| Open AccessCrykey: Rapid identification of SARS-CoV-2 cryptic mutations in wastewater
Wastewater surveillance has the potential to be used for early detection of new SARS-CoV-2 lineages. Here, the authors present Crykey, a computational method for detecting cryptic SARS-CoV-2 mutations in wastewater that co-occur on the same sequencing read, potentially representing new lineages.
- Yunxi Liu
- , Nicolae Sapoval
- & Lauren B. Stadler
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Article
| Open AccessExposure to environmental pollutants selects for xenobiotic-degrading functions in the human gut microbiome
In this study, the authors employ metagenomics to explore the impact of environmental pollution on the human gut microbiome using samples from a cohort living in a very polluted area in Southern Italy, showing that pollutants degradation genes are more abundant in subjects with higher blood levels of those specific xenobiotics.
- Francesca De Filippis
- , Vincenzo Valentino
- & Danilo Ercolini
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Article
| Open AccessEnhanced surface colonisation and competition during bacterial adaptation to a fungus
Bacterial-fungal interactions can stimulate the production of specialised microbial metabolites. Here, Richter et al. use co-culture experimental evolution to show that the presence of a fungus selects for increased surfactin production in the bacterium Bacillus subtilis, which inhibits fungal growth and facilitates the competitive success of the bacterium.
- Anne Richter
- , Felix Blei
- & Ákos T. Kovács
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Article
| Open AccessSafety outcomes following COVID-19 vaccination and infection in 5.1 million children in England
COVID-19 vaccines reduce the risk of severe disease in young people, but the absolute risk is low, and side effects have been reported. Here, the authors use data on 5–17 year olds in England to assess the overall risk-benefit profile of the vaccines.
- Emma Copland
- , Martina Patone
- & Julia Hippisley-Cox
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Article
| Open AccessLongitudinal viral shedding and antibody response characteristics of men with acute infection of monkeypox virus: a prospective cohort study
Here the authors measure viral load in samples from skin lesions, saliva, oropharynx, and rectum of 77 patients with acute monkeypox virus infection as well as from environmental fomite swabs and show a high seropositivity rate for antibodies against A29L and H3L.
- Yang Yang
- , Shiyu Niu
- & Yingxia Liu
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Article
| Open AccessDeciphering bat influenza H18N11 infection dynamics in male Jamaican fruit bats on a single-cell level
Here, Kessler et al use single-cell RNA sequencing of the intestine and mesentery from H18N11 influenza-infected bats to show that viral infection is predominant in leukocytes and causes activation of immune cells and antiviral gene signatures.
- Susanne Kessler
- , Bradly Burke
- & Kevin Ciminski
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Article
| Open AccessAcute and post-acute respiratory complications of SARS-CoV-2 infection: population-based cohort study in South Korea and Japan
Respiratory complications of SARS-CoV-2 infection have been described in the acute (within 30 days) and post-acute (after 30 days) phase. Here, the authors characterise the risk of acute and post-acute respiratory complications of SARS-CoV-2 using population-based data from South Korea and Japan.
- Yujin Choi
- , Hyeon Jin Kim
- & Dong Keon Yon
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Article
| Open AccessHuman neutralizing antibodies target a conserved lateral patch on H7N9 hemagglutinin head
Here the authors isolate two human antibodies, H7.HK1 and H7.HK2, that achieve broad and potent neutralization against H7N9 influenza by targeting a distinct lateral patch on the hemagglutinin head, thus making them favorable to complement other antibodies for combination therapy.
- Manxue Jia
- , Hanjun Zhao
- & Xueling Wu
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Article
| Open AccessProximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by PJA2
Type I IFN is vital for antiviral defense. Here, the authors use TurboID-based proximity labeling to comprehensively map the protein landscapes surrounding core IFN signaling members. Among factors uncovered, PJA2 emerged as a negative regulator of IFN signaling that ubiquitinates the Janus kinases.
- Samira Schiefer
- & Benjamin G. Hale
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Article
| Open AccessMetabolism of l-arabinose converges with virulence regulation to promote enteric pathogen fitness
Here, Cottam et al. identify an L-arabinose transporter in Enterohaemorrhagic Escherichia coli and show that metabolism of this dietary sugar upregulates the type 3 secretion system, thus enhancing its fitness within the host gut.
- Curtis Cottam
- , Rhys T. White
- & James P. R. Connolly
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Article
| Open AccessContractile injection systems facilitate sporogenic differentiation of Streptomyces davawensis through the action of a phage tapemeasure protein-related effector
Bacteria can use contractile injection systems, similar to viral tail structures, to deliver toxic proteins into other cells. Here, Nagakubo et al. identify a related system that modulates sporulation in multicellular Streptomyces bacteria.
- Toshiki Nagakubo
- , Tatsuya Nishiyama
- & Masanori Toyofuku
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Article
| Open AccessRelative dispersion ratios following fecal microbiota transplant elucidate principles governing microbial migration dynamics
Microbial migration profoundly impacts ecosystems. Here, the authors introduce a statistical approach to explore microbial dispersion following fecal microbiota transplant, uncovering dependencies between colonizing taxa, with insights into community dynamics.
- Yadid M. Algavi
- & Elhanan Borenstein
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Article
| Open AccessPhosphorus deficiency alleviates iron limitation in Synechocystis cyanobacteria through direct PhoB-mediated gene regulation
Iron and phosphorus exist at low concentrations in surface waters and may be co-limiting resources for phytoplankton growth. Here, the authors show that phosphorus deficiency increases the growth of iron-limited cyanobacteria through a PhoB-mediated regulatory network.
- Guo-Wei Qiu
- , Wen-Can Zheng
- & Bao-Sheng Qiu
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Article
| Open AccessEnvironment modulates protein heterogeneity through transcriptional and translational stop codon readthrough
This study unveils that stop codon readthrough is prevalent in E. coli, particularly under stress conditions. It highlights the influence of stop codon type and genetic context, with both transcriptional and translational origins.
- Maria Luisa Romero Romero
- , Jonas Poehls
- & Agnes Toth-Petroczy
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Article
| Open AccessDevelopment of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus
Highly pathogenic avian influenza viruses from H5 clade 2.3.4.4b are circulating widely in birds and have recently caused large outbreaks in mammals. Here, Furey et al. develop a clade 2.3.4.4b HA-expressing mRNA-LNP vaccine and show that it elicits strong protective immune responses in mice and ferrets.
- Colleen Furey
- , Gabrielle Scher
- & Scott E. Hensley
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Article
| Open AccessTranslation initiation factor eIF1.2 promotes Toxoplasma stage conversion by regulating levels of key differentiation factors
Wang et al. show that Toxoplasma gondii translation initiation factor eIF1.2 is critical for acute to chronic stage transition during infection, underscoring the importance of protein translation in controlling stage differentiation.
- Fengrong Wang
- , Michael J. Holmes
- & Vern B. Carruthers
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Article
| Open AccessCompound mortality impacts from extreme temperatures and the COVID-19 pandemic
Extreme weather and pandemics are classified as two of the most serious risks facing the UK in its National Risk Register. Here, the authors investigate the compound mortality impacts of extreme high and low temperatures and COVID-19 in England and Wales.
- Y. T. Eunice Lo
- , Dann M. Mitchell
- & Antonio Gasparrini
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Article
| Open AccessEnteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy
The digestive form of Chagas disease (American trypanosomiasis) involves damage to the nervous system of the gastrointestinal tract and problems with peristalsis. Here, Khan et al show that infection causes damage to the colon that can be reversed if it is successfully treated early in the process.
- Archie A. Khan
- , Harry C. Langston
- & Michael D. Lewis
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Article
| Open AccessThe patatin-like protein PlpD forms structurally dynamic homodimers in the Pseudomonas aeruginosa outer membrane
The Omp85 superfamily is a widely distributed class of outer membrane proteins found in Gram-negative bacteria, mitochondria and chloroplasts. Here the authors show that PlpD has a different structure and topology than other Omp85 proteins that have been studied.
- Sarah E. Hanson
- , Tyrone Dowdy
- & Harris D. Bernstein
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Article
| Open AccessFar-East Asian Toxoplasma isolates share ancestry with North and South/Central American recombinant lineages
The population genome structure of Asian Toxoplasma remains incompletely understood. This study analyzes intercontinental genomic admixture in 17 isolates from Japan and China, providing insights into the evolution of parasites and their impact on public health.
- Fumiaki Ihara
- , Hisako Kyan
- & Masahiro Yamamoto
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Article
| Open AccessPrediction of Klebsiella phage-host specificity at the strain level
Bacterial viruses (phages) are promising alternatives to treat antibiotic-resistant bacterial infections, but finding matching phages against bacteria of interest is challenging. Here, Boeckaerts et al. present a machine learning approach that predicts phage-bacteria pairs at the strain level for Klebsiella pathogens.
- Dimitri Boeckaerts
- , Michiel Stock
- & Yves Briers
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Article
| Open AccessPost-COVID conditions following COVID-19 vaccination: a retrospective matched cohort study of patients with SARS-CoV-2 infection
The impact of COVID-19 vaccination on post-COVID conditions is not well understood. Here, the authors use electronic health record data from a network of eight integrated healthcare systems in the United States to compare rates of post-COVID conditions in those with and without vaccination.
- Debbie E. Malden
- , In-Lu Amy Liu
- & Sara Y. Tartof
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Article
| Open AccessA potent Henipavirus cross-neutralizing antibody reveals a dynamic fusion-triggering pattern of the G-tetramer
There are no approved interventions for Hendra or Nipah viruses. Here, the authors isolate a G glycoprotein-specific antibody with cross-neutralizing and in vivo protective activities, and structurally resolve its binding pattern to the G protein.
- Pengfei Fan
- , Mengmeng Sun
- & Sandra Chiu
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Article
| Open AccessHuman CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains
Here the authors isolate monoclonal antibody HmAb64 from a healthy volunteer who received an experimental polyvalent DNA prime-protein boost HIV vaccine, and show that it’s specific for the CD4 binding site and neutralizes cross-subtype HIV isolates including several tier-2 viruses.
- Shixia Wang
- , Kun-Wei Chan
- & Shan Lu
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Article
| Open AccessProdrug-conjugated tumor-seeking commensals for targeted cancer therapy
The chemotherapeutic efficacy of prodrug is limited by its cancer-targeting ability. Here this group reports an engineered commensal Lactobacillus plantarum strain with anticancer prodrugs loading on the surface for nasopharyngeal carcinoma cell-targeting and growth inhibition.
- Haosheng Shen
- , Changyu Zhang
- & Matthew Wook Chang
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Article
| Open AccessThe sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species
Antifungal triazoles inhibit biosynthesis of ergosterol, a crucial component of the fungal plasma membrane. Here, Xie et al. show that Erg6, the enzyme that catalyzes a previous step in ergosterol biosynthesis, is essential for the viability of Aspergillus fumigatus, and its repression reduces the virulence of this fungal pathogen in an animal model of infection.
- Jinhong Xie
- , Jeffrey M. Rybak
- & Jarrod R. Fortwendel
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Article
| Open AccessFunctionality of chimeric TssA proteins in the type VI secretion system reveals sheath docking specificity within their N-terminal domains
The bacterium Pseudomonas aeruginosa has three type-VI secretion systems that exhibit differences in the size and domain organization of one of their components, protein TssA. Here, Fecht et al. provide insights into the functions of the different TssA domains and propose a model for the role played by TssA proteins in secretion-system assembly.
- Selina Fecht
- , Patricia Paracuellos
- & Alain Filloux
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Article
| Open AccessDevelopment of a long noncoding RNA-based machine learning model to predict COVID-19 in-hospital mortality
Identifying biomarkers associated with risk of severe COVID-19 disease could inform clinical management. Here, the authors identify a long noncoding RNA associated with severe disease using data from three European countries, and validate their finding in data from Canada.
- Yvan Devaux
- , Lu Zhang
- & Hüseyin Firat
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Article
| Open AccessProduction of deoxycholic acid by low-abundant microbial species is associated with impaired glucose metabolism
Secondary bile acids are microbially produced metabolites linked to metabolic diseases. A challenge in microbiota research is to understand how bacteria collaborate to produce such bioactive molecules. Here, the authors show that adding a single low-abundance bacterial species to a community can significantly affect the metabolic output and host physiology.
- Annika Wahlström
- , Ariel Brumbaugh
- & Fredrik Bäckhed
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Review Article
| Open AccessShaping of microbial phenotypes by trade-offs
Trade-offs play a key role in controlling bacterial growth and shaping microbial phenotypes, which further drives the emergence of ecologically relevant phenomena including co-existence, population heterogeneity and oligotrophic/copiotrophic lifestyles.
- Manlu Zhu
- & Xiongfeng Dai
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Article
| Open AccessNitrous oxide respiration in acidophilic methanotrophs
Aerobic methanotrophic bacteria are considered strict aerobes but are often highly abundant in hypoxic or anoxic environments. Here, the authors show that acidophilic methanotrophs can respire nitrous oxide and grow anaerobically on diverse non-methane substrates, including methanol, C-C substrates, and hydrogen.
- Samuel Imisi Awala
- , Joo-Han Gwak
- & Sung-Keun Rhee
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Article
| Open AccessSpatial disparities in the mortality burden of the covid-19 pandemic across 569 European regions (2020-2021)
Excess mortality can be used as an indicator of the impacts of the COVID-19 pandemic. Here, the authors estimate excess mortality in 569 European regions in 25 countries for 2020 and 2021 and describe how impacts changed over time.
- Florian Bonnet
- , Pavel Grigoriev
- & Carlo-Giovanni Camarda
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Article
| Open AccessEnhanced CD95 and interleukin 18 signalling accompany T cell receptor Vβ21.3+ activation in multi-inflammatory syndrome in children
Multi-Inflammatory Syndrome in Children (MIS-C) is a severe post-infectious presentation related to SARS-CoV-2 infection. Here authors used multi-omics approaches to characterise MIS-C cases and found increased CD95 and IL-18 signalling accompanying the expansion of TCR Vβ 21.3+ T cells.
- Zhenguang Zhang
- , Iain R. L. Kean
- & Nazima Pathan
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