Metrics details Recent reports suggest that cell-surface and intracellular immune receptors function synergistically to activate robust defence against pathogens Here we determined the numbers of cell-surface and intracellular immune receptors in 350 species the number of receptor genes that are predicted to encode cell-surface and intracellular immune receptors is strongly correlated We suggest this is consistent with mutual potentiation of immunity initiated by cell-surface and intracellular receptors being reflected in the concerted co-evolution of the size of their repertoires across plant species PTI and ETI function synergistically to provide robust immunity against pathogens As PRRs and NLRs are functionally inter-dependent we investigated whether the sizes of these two receptor gene families are correlated Phylogenetic tree of 350 plant species 79 monocot species and 208 eudicot species Heat maps represent the percentages (%) of LRR-RLKs LRR-RLK-XIIs + LRR-RLPs (magenta) and NB-ARCs (blue) in their corresponding annotated proteomes Grey boxes in heat maps indicate null values where no receptors were identified Scatter plot of %LRR-RLP + LRR-RLK-XII against %NB-ARC with dark-grey shade representing the 95% confidence interval and light-grey shade representing the 95% prediction interval aquatic species and trees are indicated as yellow inverted triangles Model organisms are also indicated as spheres of different colours Schematic illustration of the co-expansion and co-contraction of immune receptors in plant genomes we conclude that PRR gene families specifically involved in pathogen recognition co-expand or co-contract with NB-ARC gene families thomaeum has a similar number of predicted proteins as other Poales species such as Ananas comosus suggesting that the contraction of immune receptor families could be independent of the reduced genome size some plant lifestyles might also correlate with expansion of immune receptor gene families As %LRR-RLK-III and %LRR-RLK-XI do not show positive correlation with %NB-ARC while NB-ARC-encoding genes can form genomic clusters adjacent to LRR-RLK-XIIs the co-expansion/contraction of these immune receptors is likely to be caused by mechanisms other than genomic clustering partial or complete submersion of aquatic species results in reduced exposure to airborne pathogenic spores removing an interface for interaction with pathogens Lifespan may also drive changes in the immune receptor repertoire We found that trees generally show higher %PRR and %NB-ARC than other species While annual plants are subject to shorter periods of pathogen pressure before reproduction this long-term pathogen pressure could drive the expansion of immune receptor gene families inbreeding species may require an increased number of immune receptors compared with their outbreeding ancestors an outcome that can also result from polyploidy As the concerted expansion and contraction of immune receptors in plant genomes is not due to genomic clustering further study is needed to understand the mechanism(s) underpinning these observations As functionally inter-dependent genes often co-expand/contract together it is likely that the functional relationship between cell-surface and intracellular immune receptors is conserved across plant species NB-ARCs were identified using the set of proteins with a minimal length of 150 AA Proteins were then searched for the presence of NB-ARC (PF00931.23) domains (hmmer option -E 1e-10 for NB-ARC) Candidates were split into LysM-RLKs and LysM-RLPs by searching for presence/absence of a kinase domain (PF00069.26 The latter contained 238 out of the 350 genomes analysed Statistical analyses were performed with OriginPro (version 2022; https://www.originlab.com/) and R (version 3.4.4) Further information on research design is available in the Nature Research Reporting Summary linked to this article All the analyses were done as described in Methods with publicly available tools (hmmer, tmhmm, diamond, FastTree, FAMSA, gotree and R). Scripts are available on github.com/MWSchmid/Ngou-et-al.-2022 Thirty years of resistance: zig-zag through the plant immune system Mutual potentiation of plant immunity by cell-surface and intracellular receptors Pattern-recognition receptors are required for NLR-mediated plant immunity The EDS1-PAD4-ADR1 node mediates Arabidopsis pattern-triggered immunity Activation of TIR signalling boosts pattern-triggered immunity and exploitation of plant pattern recognition receptors for broad-spectrum disease resistance Expansion of the receptor-like kinase/Pelle gene family and receptor-like proteins in Arabidopsis Origin and diversity of plant receptor-like kinases Evolutionary history and stress regulation of plant receptor-like kinase/pelle genes Arabidopsis transmembrane receptor-like kinases (RLKs): a bridge between extracellular signal and intracellular regulatory machinery The sequenced genomes of nonflowering land plants reveal the innovative evolutionary history of peptide signaling Intracellular innate immune surveillance devices in plants and animals Long-term evolution of nucleotide-binding site-leucine-rich repeat genes: understanding gained from and beyond the legume family Convergent loss of an EDS1/PAD4 signaling pathway in several plant lineages reveals coevolved components of plant immunity and drought response New insights on leucine-rich repeats receptor-like kinase orthologous relationships in angiosperms RGAugury: a pipeline for genome-wide prediction of resistance gene analogs (RGAs) in plants Quinone perception in plants via leucine-rich-repeat receptor-like kinases Hydrogen peroxide sensor HPCA1 is an LRR receptor kinase in Arabidopsis is required for cellooligomer-induced responses in Arabidopsis thaliana Loss-of-function of Arabidopsis receptor-like kinase BIR1 activates cell death and defense responses mediated by BAK1 and SOBIR1 a tool for generating plant phylogenies and an analysis of phylogenetic community structure An angiosperm NLR Atlas reveals that NLR gene reduction is associated with ecological specialization and signal transduction component deletion Single-molecule sequencing of the desiccation-tolerant grass Oropetium thomaeum Overview of tomato (Solanum lycopersicum) candidate pathogen recognition genes reveals important Solanum R locus dynamics Resistance gene analogs in the Brassicaceae: identification Oak genome reveals facets of long lifespan The role of hybridization in the evolution and emergence of new fungal plant pathogens Emergence of the Ug99 lineage of the wheat stem rust pathogen through somatic hybridisation Sexual reproduction as an adaptation to resist parasites (a review) Fast and sensitive protein alignment using DIAMOND FAMSA: fast and accurate multiple sequence alignment of huge protein families Current methods for automated filtering of multiple sequence alignments frequently worsen single-gene phylogenetic inference FastTree 2—approximately maximum-likelihood trees for large alignments Gotree/Goalign: toolkit and Go API to facilitate the development of phylogenetic workflows Multi-omics approach highlights differences between RLP classes in Arabidopsis thaliana Phylogenomic analysis of the receptor-like proteins of rice and Arabidopsis Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation Controlling the false discovery rate: a practical and powerful approach to multiple testing Ngou, B. P. M., Heal, R., Wyler, M., Schmid, M. W. & Jones, J. D. Genome-wide identification of cell-surface and intracellular immune receptors in 350 plant species. Zenodo https://doi.org/10.5281/zenodo.7017981 (2022) Download references was supported by the Norwich Research Park Biosciences Doctoral Training Partnership from the Biotechnology and Biological Sciences Research Council (BBSRC) (grant agreement BB/M011216/1) These authors contributed equally: Bruno Pok Man Ngou RIKEN Center for Sustainable Resource Science conceived and conceptualized the study; B.P.M.N. designed and performed the bioinformatic analyses; B.P.M.N. performed the statistical analyses; B.P.M.N The authors declare no competing interests reviewer(s) for their contribution to the peer review of this work Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations ETI is activated by estradiol-induced expression of AvrRps4 in Arabidopsis thaliana for 4 hours Number of genes (n) from each LRR-RLK subgroup: I with heatmaps representing the assembled genome size number (no.) of annotated proteins and number (no.) of primary transcripts Brown branches indicates monocots and teal branches represent eudicots Protein sequences from all 350 proteomes were first filtered for the primary gene models Primary-transcript proteomes were then filtered and NB-ARC LysM-RLP and LRR-RLK proteins were identified LRR-RLK genes were further classified into 20 subgroups according to their alignment to the Arabidopsis thaliana subgroups Details of the pipeline are described in the methods section the black line represents the linear trend with dark grey shade represents the 95% confidence interval and light grey shade represents the 95% prediction interval Bottom left boxes include scatter plot between the corresponding % receptor-gene families in 300 angiosperms Grey dots represent basal angiosperms (n = 13) brown dots represent monocots (n = 79) and green dots represent eudiots (n = 208) The Pearson correlation coefficient (Pearson’s r) is indicated below each scatter plot The diagonal boxes include the distribution of % receptor-gene families in 300 angiosperms Phylogenetic tree of the species used in the analysis Pearson correlation between %LRR-RLK_XII+LRR-RLP and %NB-ARC in b Phylogenetic tree of the Asterids clade used in the analysis Carnivorous plants are marked with orange stars; parasitic plants are marked with yellow triangles and aquatic plants are marked with blue circles Pearson correlation between %LRR-RLK_XII+LRR-RLP and %NB-ARC in the Asterids clade Number of species (n) in each category: non-parasitic species Table summarizing the statistical analysis of genomic clustering between PRRs (LRR-RLKs and LRR-RLPs) and NB-ARCs in Solanum tuberosum (a) The 90-percentile distance (bp) between PRR gene family members and the next closest NB-ARC genes were calculated This is then compared to a distribution (n = 1000) of 90-percentile distances between randomly-sampled genes and the next closest NB-ARC genes One-sided test was performed to test the differences between tested distance (PRRs) and sampled distance (randomly-sampled) P-values are calculated based on the comparison to 1000 cases of randomly-sampled genes Significant values are indicated in bold (p-value < 0.05 is considered as significant) Distribution (n = 1000) of 90-percentile distances (bp) between randomly-sampled genes and the next closest NB-ARC genes in Solanum tuberosum (b) Red lines indicate the 90-percentile distance between the corresponding PRR gene family members and the next closest NB-ARC genes Percentage of receptor genes in each species Download citation DOI: https://doi.org/10.1038/s41477-022-01260-5 Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science Metrics details but that mediated by intracellular receptors has rarely been investigated in the absence of surface-receptor-mediated immunity interactions between these two immune pathways are poorly understood by activating intracellular receptors without inducing surface-receptor-mediated immunity we analyse interactions between these two distinct immune systems in Arabidopsis Pathogen recognition by surface receptors activates multiple protein kinases and NADPH oxidases and we find that intracellular receptors primarily potentiate the activation of these proteins by increasing their abundance through several mechanisms the hypersensitive response that depends on intracellular receptors is strongly enhanced by the activation of surface receptors Activation of either immune system alone is insufficient to provide effective resistance against the bacterial pathogen Pseudomonas syringae immune pathways activated by cell-surface and intracellular receptors in plants mutually potentiate to activate strong defences against pathogens These findings reshape our understanding of plant immunity and have broad implications for crop improvement Prices may be subject to local taxes which are calculated during checkout Regulation of pattern recognition receptor signalling in plants and genomic diversity of plant NLR proteins: an evolved resource for rational engineering of plant immunity Reconstitution and structure of a plant NLR resistosome conferring immunity Structure of the activated ROQ1 resistosome directly recognizing the pathogen effector XopQ Direct pathogen-induced assembly of an NLR immune receptor complex to form a holoenzyme A comparative overview of the intracellular guardians of plants and animals: NLRs in innate immunity and beyond A coevolved EDS1-SAG101-NRG1 module mediates cell death signaling by TIR-domain immune receptors Estradiol-inducible AvrRps4 expression reveals distinct properties of TIR-NLR-mediated effector-triggered immunity Callose-mediated resistance to pathogenic intruders in plant defense-related papillae Direct regulation of the NADPH oxidase RBOHD by the PRR-associated kinase BIK1 during plant immunity The FLS2-associated kinase BIK1 directly phosphorylates the NADPH oxidase RbohD to control plant immunity MAPK cascades in plant disease resistance signaling Defended to the nines: 25 years of resistance gene cloning identifies nine mechanisms for R protein function Translatome analysis of an NB-LRR immune response identifies important contributors to plant immunity in Arabidopsis High-resolution expression profiling of selected gene sets during plant immune activation Ding, P. et al. Chromatin accessibility landscapes activated by cell surface and intracellular immune receptors. Preprint at https://doi.org/10.1101/2020.06.17.157040 (2020) Ligand-induced monoubiquitination of BIK1 regulates plant immunity Regulation of reactive oxygen species during plant immunity through phosphorylation and ubiquitination of RBOHD Translational gene regulation in plants: a green new deal The Arabidopsis leucine-rich repeat receptor-like kinases BAK1/SERK3 and BKK1/SERK4 are required for innate immunity to hemibiotrophic and biotrophic pathogens Yuan, M. et al. Pattern-recognition receptors are required for NLR-mediated plant immunity. Nature, https://doi.org/10.1038/s41586-021-03316-6 (2021) Active photosynthetic inhibition mediated by MPK3/MPK6 is critical to effector-triggered immunity Arabidopsis gp91phox homologues AtrbohD and AtrbohF are required for accumulation of reactive oxygen intermediates in the plant defense response Quantitative phosphoproteomic analysis reveals common regulatory mechanisms between effector- and PAMP-triggered immunity in plants A chemical genetic approach demonstrates that MPK3/MPK6 activation and NADPH oxidase-mediated oxidative burst are two independent signaling events in plant immunity Regulation of sugar transporter activity for antibacterial defense in Arabidopsis Decreased abundance of type III secretion system-inducing signals in Arabidopsis mkp1 enhances resistance against Pseudomonas syringae Putting knowledge of plant disease resistance genes to work Luo, M. et al. A five-transgene cassette confers broad-spectrum resistance to a fungal rust pathogen in wheat. Nat. Biotechnol. https://doi.org/10.1038/s41587-020-00770-x (2021) Transgressive segregation reveals mechanisms of Arabidopsis immunity to Brassica-infecting races of white rust (Albugo candida) The NLRP3 inflammasome: an overview of mechanisms of activation and regulation Peptidoglycan recognition by the innate immune system Phosphorylation-dependent differential regulation of plant growth and innate immunity by the regulatory receptor-like kinase BAK1 A downy mildew effector evades recognition by polymorphism of expression and subcellular localization Large-scale structure-function analysis of the Arabidopsis RPM1 disease resistance protein Dual regulation of gene expression mediated by extended MAPK activation and salicylic acid contributes to robust innate immunity in Arabidopsis thaliana Recognition of the protein kinase AVRPPHB SUSCEPTIBLE1 by the disease resistance protein RESISTANCE TO PSEUDOMONAS SYRINGAE5 is dependent on S-acylation and an exposed loop in AVRPPHB SUSCEPTIBLE1 Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method Near-optimal probabilistic RNA-seq quantification Guo, W. et al. 3D RNA-seq - a powerful and flexible tool for rapid and accurate differential expression and alternative splicing analysis of RNA-seq data for biologists. RNA Biol. https://doi.org/10.1080/15476286.2020.1858253 (2020) Pescadillo plays an essential role in plant cell growth and survival by modulating ribosome biogenesis Proteomic analysis of SUMO1-SUMOylome changes during defense elicitation in Arabidopsis requires in planta processing and the KRVY domain to function Recombineering and stable integration of the Pseudomonas syringae pv syringae 61 hrp/hrc cluster into the genome of the soil bacterium Pseudomonas fluorescens Pf0-1 Download references He for critical reading of the manuscript; and the Gatsby Foundation for funding to the J.D.G.J B.P.M.N was supported by the Norwich Research Park Biosciences Doctoral Training Partnership from the Biotechnology and Biological Sciences Research Council (BBSRC) (grant agreement BB/M011216/1); H.-K.A was supported by European Research Council Advanced Grant ‘ImmunitybyPairDesign’ (grant agreement: 669926); and P.D acknowledges support from the European Union’s Horizon 2020 Research and Innovation Program under Marie Skłodowska-Curie Actions (grant agreement 656243) and a Future Leader Fellowship from BBSRC (grant agreement BB/R012172/1) Present address: Institute of Biology Leiden conceived and conceptualized the study; B.P.M.N HR assay and electrolyte leakage assay; B.P.M.N performed the extraction of plasma membrane proteins with assistance from H.-K.A.; H.-K.A designed and performed the cycloheximide and MG132 experiment; H.-K.A Peer review information Nature thanks Thorsten Nürnberger and the other All experiments were repeated at least three times with similar results Source data Tabular summary of total ROS production in different phases after different PAMP or DAMP treatments with co-activation of PTI and ETIAvrRps4 Source data CERK1 and MPK4 after activation of ETI for 4 h and 8 h in several effector-inducible lines AvrRps4 and AvrRpp4 lines were infiltrated with 50 μM dexamethasone (for Dex:AvrRpm1) or 50 μM oestradiol 4 h and 8 h after infiltration for protein extraction Molecular weight markers (in kDa) are indicated on the left Ponceau staining (PS) was used as loading control Source data Source data Source data Ponceau staining was used as loading control Source data Source data Source data nlp20 or chitin does not lead to macroscopic HR Co-activation of PTI (triggered by these PAMPs or DAMP) with ETIAvrRps4 leads to macroscopic HR The numbers indicate the number of leaves that display HR of the total number of leaves infiltrated Five-week-old inducible AvrRpm1 (Dex:AvrRpm1) AvrRps4 (Est:AvrRps4) and AvrRpp4 (Est:AvrRpp4) Arabidopsis leaves were infiltrated with either dexamethasone (for Dex:AvrRpm1 only) or oestradiol The combination of PTI and ETI leads to stronger macroscopic HR in inducible AvrRpm1 Source data MPK phosphorylation during ETI triggered by multiple effectors Est:AvrPphB and Est:AvrRpp4 lines were soaked in dexamethasone or oestradiol solution Untreated seedlings were used as a negative control; seedlings treated with 100 nM flg22 for 15 min (red RBOHD phosphorylation during ETI triggered by multiple effectors Est:AvrPphB and Est:AvrRpp4 were soaked in mock (black) dexamethasone or oestradiol solution (dark yellow) for 6 h Microsomal fractions from seedlings were isolated for immunoblotting with RBOHD(pS39) antibody Ponceau staining was used as the loading control MPK6SR#58 (mpk3 mpk6 PMPK6:MPK6YG) is a conditional mpk3 mpk6 double mutant MPK6YG has a larger ATP-binding pocket than wild-type MPK6 and is sensitive to the inhibitor 1-naphthyl-PP1 (NA-PP1 Pre-treatment with NA-PP1 inhibits MPK6YG and temporarily generates a mpk3 mpk6 double mutant Both Col-0 and MPK6SR#58 leaves were pre-infiltrated with either 1% DMSO (mock) or 10 μM NA-PP1 these leaves were infiltrated with either Pf0-1:empty vector (triggers PTI) or Pf0-1:AvrRps4 (triggers PTI + ETIAvrRps4) Pf0-1:AvrRps4 infiltration leads to macroscopic HR in both Col-0 and MPKS6R#58 NA-PP1 pre-treatment attenuates HR caused by Pf0-1:AvrRps4 only in the MPK6SR#58 line Col-0 and rbohd rbohf leaves were infiltrated with either Pf0-1:empty vector (triggers PTI) or Pf0-1:AvrRps4 (triggers PTI + ETIAvrRps4) at a varying OD600 Pf0-1:AvrRps4 infiltration leads to less macroscopic HR in rbohd rbohf leaves Activation of an NLR (ETI without PTI) increases the accumulation of PTI signalling components Co-activation of both PTI and ETI increases this accumulation and enhances the activation of multiple PTI signalling components Molecular weight in kDa (kilodalton) is indicated on the left This file contains Supplementary Tables 1-3 Differentially expressed gene list during ETI List of differentially expressed (DE) genes identified in the comparison between Est:AvrRps4 treated with estradiol for 0h (seti_e2_0h) and 4h (seti_e2_4h) Positive log2FC values (red) indicates upregulation and negative log2FC values (blue) indicates downregulation P-values for differentially expressed (DE) genes were generated with Fisher Z-transformation after Student’s t-test DE genes with “Benjamini and Hochberg’s (BH) method” false discovery rate (FDR) two-sided adjusted P-value (adj.pval) < 0.05 (green) is categorized as significant Summary of all statistical analysis are listed The specification of samples and the number of samples used for each dataset and the statistical tests and the P-values are summarized The methods used for adjustment of P-values are also shown The source data of all the statistical analysis can be found in the Source File Download citation DOI: https://doi.org/10.1038/s41586-021-03315-7 Plants are continuously evolving new immune receptors to ever-changing pathogens Researchers at the RIKEN Center for Sustainable Resource Science (CSRS) have traced the origin and evolutionary trajectory of plant immune receptors Their discovery will make it easier to identify immune receptor genes from genomic information and could help in the development of pathogen-resistant crops This study was published in the scientific journal Nature Communications on February 1 plants have immune responses that help them defend against pathogens such as viruses and this is accomplished by pattern recognition receptors located on the surface of plant cells The ability of these receptors to detect molecular patterns associated with pathogens depends on two types of proteins both of which can contain leucine-rich repeats—sections in which the amino acid leucine appears multiple times the international research team led by Ken Shirasu and Yasuhiro Kadota at RIKEN CSRS examined the numbers and patterns of receptors They analyzed over 170,000 genes encoding RLKs and about 40,000 genes encoding RLPs which they obtained from publicly available data taken from 350 plant species They discovered that RLKs and RLPs with leucine-rich repeats were the most abundant receptor types among all the plant species making up nearly half of RLKs and 70% of RLPs are known to contain a special island region that is crucial for recognizing parts of pathogens Investigation by the RIKEN CSRS team revealed that amongRLPsthat contain the leucine-rich repeats this special region was almost always located in the same place; between the 4th and 5th leucine-rich repeat These RLPs were found to be associated with immune responses They also discovered that the island region was located at the same position in some RLKs nearly all of which belong to a functional group that regulates growth and development Comparative analysis showed that the sequence of the four repeats below the island region was very similar between the two types of protein detectors suggesting that they have a common evolutionary ancestry these four sets of leucine repeats contained sections needed for bonding to the same co-receptor This means that immunity-related RLPs and growth-related RLKs inherited the ability to bind BAK1 from a common ancestor we found that exchanging the four regions of leucine-rich repeats among these receptors did not disrupt their functionality,” says Bruno Pok Man Ngou Creating a hybrid receptor by combining a growth-related RLK with an immunity-related RLP resulted in a hybrid receptor that recognized pathogens and induced both immune and growth-related responses This means that scientists should be able to engineer receptors with new functions by swapping those modules This study addressed the origins of plant immunity at a molecular level showing that simultaneously analyzing information from multiple plant genomes can allow straightforward and precise prediction of genes involved in plant immunity and growth “We are currently isolating immune receptors from various plants using this information aiming for practical applications such as developing disease-resistant crops in the future,” says Shirasu Masataka Sasabe RIKEN International Affairs Division Tel: +81-(0)48-462-1225 Email: masataka.sasabe [at] riken.jp Both immunity-related LRR-RLPs and growth-related LRR-RLKs have evolved from a common ancestor to inherit the last four LRRs and the ability to bind the co-receptor BAK1 The chimeric receptor that incorporates the cytoplasmic kinase domain of a growth-related LRR-RLK into an immunity-related LRR-RLP activates both immune and growth responses upon sensing a pathogen-derived molecule Top Forbes contributors publish independent expert analyses and insights Christine Ro is a journalist covering science and development ShareSaveCommentA nurse prepares a dose of vaccine against malaria at a district hospital in Soa More (Photo by Kepseu/Xinhua via Getty Images) Prossy Muyingo is worried. Uganda announced an Ebola outbreak on Jan and they help to plug the gap where nurses and doctors are in short supply president and secretary of state abruptly cut off most aid While people had been preparing for some sort of foreign aid review by the new administration the rug-pulled-out part was that aid was immediately stopped while the review was pending The State Department’s new spokesperson said that the 90-day cutoff of foreign aid was necessary because they didn’t trust aid workers to provide information otherwise — even though continuation of funding typically depends on regular reporting such as antiretroviral drugs to keep HIV in check The aid freeze means that they will likely have to pay out of pocket — as well as going without the reminders and health information that are a key part of a CHW’s work What will happen to them?” Muyingo wonders She estimates that perhaps 2% of her patients will be able to afford the medicines they need And she knows just how expensive these medicines are as one of her children lives with sickle cell disease Community health workers are already feeling the effects of the uncertainty, service cutoffs and loss of work, says Madeleine Ballard, the CEO of the Community Health Impact Coalition both witnessing suffering and themselves experiencing suffering,” Ballard says “I think it’s always the most devastating when those who care for others are not themselves cared for.” there’s no clear line between emergency aid (which is allowed yet still ambiguous) and longer-term support that also saves lives For instance, Olivia Ngou is the executive director of Impact Santé Afrique which works from Cameroon to increase local political advocacy and community engagement around malaria She hasn’t heard that malaria aid has been included in the lifesaving assistance exception Delays are critical to ongoing malaria treatment and testing conducted by community health workers in remote areas But it also affects months-long preparation for the rainy season “The preparation for that has stopped,” Ngou reports we are going to lose a lot of children.” Even more urgent is the 48-hour window to get tested and treated following a mosquito bite The system for requesting waivers to the near-blanket freeze has also been confusing Some organizations report a lack of clarity about where to even submit the requests (The State Department did not immediately respond to a request for comment.) the idea that contraception is unacceptable aid makes no sense to people who have seen loved ones die of AIDS Muyingo has also seen the benefits of neutral science-backed information on contraception: “Family planning has helped many students to finish their studies,” among other things Some people don’t use condoms simply because they can’t afford them the Heritage Foundation’s view that “education and abstinence could end the AIDS epidemic” has failed in the U.S One phrase that’s being repeated over and over is “safer, stronger, and more prosperous.” This is the State Department’s mantra for justifiable aid. “Our test is simple,” the department’s spokesperson tweeted Scientists have also overcome the challenges of developing vaccines for parasitic diseases and vaccination against malaria is now routine in several African countries after starting in Cameroon But vaccination programs have now halted due to the aid shutoff sometimes before children have finished the full four-dose course of the malaria vaccine Malaria No More estimates that a 90-day U.S aid freeze could stop delivery of 15.6 million doses of medicine trainings for 64,700 health workers and 9 million insecticide-treated mosquito nets accounting for the contributions of all U.S is that every day that the 90-day aid freeze continues over 1,000 additional people will die of malaria Much of U.S. aid on malaria comes through the U.S. President’s Initiative on Malaria, a nonpartisan program working in Africa and Southeast Asia. PMI has saved the lives of over 11 million people Ngou says that it especially targets those at highest risk and in highest need: pregnant women and children under the age of 5 African countries have been stepping up to fight malaria, Ngou points out. In 2024, ministers of health from 11 African nations signed the Yaoundé Declaration committing to putting more domestic resources to malaria control And countries highly affected by malaria continue to build up health facilities and other infrastructure that U.S While she and fellow advocates have been urging local leaders to release emergency funds to make up for aid gaps “unfortunately the economic context right now is very challenging.” there is talk of health and peace-building aid countering terrorism or Chinese influence Some of the arguments have been pragmatic to the point of coldhearted In an era when the State Department is proudly pointing to money being cut from aid this detached approach may ultimately be effective But bending over backward to justify certain aid projects as aligning with the new administration’s agenda risks undermining the core ethical imperative of aid community health worker Muyingo agrees that her country will need more self-reliant health services She believes that this will happen within the next decade; for now the Ugandan government and other donors can’t fill the enormous gap left by the U.S She would like the American government to remember that diseases have no borders Metrics details Cell-surface receptors play pivotal roles in many biological processes How cell-surface receptors evolve to become specialised in different biological processes remains elusive To shed light on the immune-specificity of cell-surface receptors we analyzed more than 200,000 genes encoding cell-surface receptors from 350 genomes and traced the evolutionary origin of immune-specific leucine-rich repeat receptor-like proteins (LRR-RLPs) in plants we discovered that the motifs crucial for co-receptor interaction in LRR-RLPs are closely related to those of the LRR-receptor-like kinase (RLK) subgroup Xb which perceives phytohormones and primarily governs growth and development Functional characterisation further reveals that LRR-RLPs initiate immune responses through their juxtamembrane and transmembrane regions while LRR-RLK-Xb members regulate development through their cytosolic kinase domains Our data suggest that the cell-surface receptors involved in immunity and development share a common origin and cytosolic regions have either diversified or stabilised to recognise diverse ligands and activate differential downstream responses Our work reveals a mechanism by which plants evolve to perceive diverse signals to activate the appropriate responses in a rapidly changing environment the origins of PRR families involved in PAMP perception in plants remain largely unclear Given the striking resemblance in their domain architecture it is reasonable to infer that immunity- and development-related cell-surface receptors share a common origin the evolutionary trajectory that led to their divergence and specialisation in distinct biological processes remains poorly understood The bottom panel represents the presence or absence of different receptor classes in algal and plant lineages ‘-’ represents ectodomains with no transmembrane or kinase domain ‘RLP’ represents ectodomains with a transmembrane domain but no kinase domain ‘RLK’ represents ectodomains with both transmembrane and kinase domains The number of species available from each algal and plant lineage is indicated by the numbers within respective boxes A grey box indicates the absence of receptors and a green box indicates their presence in each lineage The origin of a receptor is indicated with a circle (○) Expansion rates of receptor classes are indicated by boxplots The percentages (%) of cell-surface receptors from each genome were calculated as (number of identified genes/number of searched genes × 100) the percentages from each species within a lineage (e.g. Rhodophtya or green algae) were grouped and the median percentage was calculated Median value was used instead of mean to avoid outliers within the lineages The expansion rate within a species is calculated by ((% cell surface receptors in that species)-(median))/(median) The cyan boxplot represents the expansion rate from Glaucophyta and Rhodophyta to green algae (LRR The yellow boxplot represents the expansion rate from green algae to Embryophytes (LRR n = 0) and the orange boxplot represents the differences between early land plants to Tracheophytes (LRR Light blue area represents expansion and light pink area represents contraction of the gene family X-axis values represent expansion rate (×) Values larger than 0 indicate expansion; values equal to 0 indicate no expansion reinforcing the idea that cell surface immune receptors underwent extensive expansions as the plant lineage diversified and evolved to adapt to a wide range of environments The origin of a protein family is indicated with a circle (○) followed by another circle indicating the origin of the orthologs of PTI-signalling component Expansion rates of PTI-signalling component families are indicated by boxplots The percentages (%) of signalling components from each genome were calculated as (number of identified genes/number of searched genes × 100) the percentages from each species within a lineage (e.g The expansion rate within a species is calculated by ((%signalling components in that species)-(median))/(median) The cyan boxplot represents the expansion rate from Glaucophyta and Rhodophyta to green algae (SERKs The yellow boxplot represents the expansion rate from green algae to Embryophytes (SERKs n = 0) and the orange boxplot represents the differences between early land plants to Tracheophytes (SERKs This observation implies a functional necessity for the specific placement of IDs in LRR-RLPs d The concentric ring pie chart presents the percentage of LRR-containing cell-surface receptors (PRRs) from 350 species The inner ring represents all LRR-containing cell-surface receptors (113,794); the middle ring represents LRR-containing PRRs with ID (20,556); the outer ring represents LRR-containing PRRs with an ID preceding the last 4 LRR (ID + 4LRR) at the C terminus (16,885) e The presence or absence of receptor classes in various algal and plant lineages and a green box indicates the presence of a given receptor class in each lineage The origin of LRR-RLP and LRR-RLK-Xb with ID + 4LRR is indicated with a circle (○) f Sequence similarity tree of the C3 region (last 4 LRRs) from all LRR-containing cell-surface receptors of 350 species The inner ring and middle ring indicate the lineage and subclass/order of the corresponding protein (species) from the branch Outer ring represents the LRR-RLP or LRR-RLK classification The light grey area indicates clustering of LRR-RLK-Xb and LRR-RLP with ID + 4LRR The pruned sequence similarity tree on the right g corresponds to the light grey area in the left tree with clades labelled in dark grey areas accordingly Characterized LRR-RLK-Xb and LRR-RLP members are labelled The BRI/BRL-clade and the PSKR/PSY1R-clades are also labelled Considering the similarity in structural motifs between LRR-RLPs and LRR-RLK-Xbs it is likely that these two receptor classes share a common origin e Alignment of amino acids in the last LRR motifs from NbRXEG1 Amino acid residues involved in the interaction between NbRXEG1 and BAK1 are highlighted in green The QxxT motif positions are highlighted in yellow Amino acids with similar properties to AtRLP23 are highlighted in grey The last LRR motif of AtRLP23 is exchanged with either AtPSY1R AtBRI1 have also been mutated to threonine (T) l Immuno-precipitation to test interactions between AtRLP23 chimeras Nb leaves expressing the indicated constructs were treated with either mock or 1 μM nlp20 for 5 min h–k Functionality testing of AtRLP23 chimeras Nb leaves expressing the indicated constructs were treated with 1 μM nlp20 and samples were collected at indicated time points Phosphorylation of NbSIPK and NbWIPK was detected with p-P42/44 antibody k Nb leaf discs expressing the indicated constructs were collected and treated with either mock or 1 μM nlp20 and ROS production was measured for indicated time points the experiments were repeated at least twice with similar results the residues around and within the TQxxx motif are both crucial for SERK interactions We concluded that the C3 region in LRR-RLPs and some LRR-RLK-Xbs (such as PSY1R and PSKR1) interact with SERKs in a similar manner while some LRR-RLK-Xbs (PSKR2 and BRI1) have evolved to interacts with SERKs in a slightly different manner our results strongly support the functional conservation of C3 regions in LRR-RLK-Xbs and LRR-RLPs specifically their ability to interact with SERKs tracing back the origin of IDs is challenging due to their considerable diversity We therefore propose that the IDs of LRR-RLK-Xbs and LRR-RLPs likely originated from a common ancestor with the IDs of LRR-RLPs expanding and diversifying after the divergence of LRR-RLK-Xb and LRR-RLPs We propose that these RLPs may either recognise endogenous molecules to activate growth and development or participate in the recognition of pathogen-mimicking molecules to trigger immune signalling Number of cell-surface receptors (n) in each LRR-RLK subgroup: I Number of cell-surface receptors (n) in each LRR-RLP subgroup: LRR-RLP (RLP) a The top panel depicts the presence of cell-surface receptors and downstream signalling components (downstream) in Glaucophyta and Rhodophyta Nodes are labelled in colours as indicated on the left The absence of a node indicates the absence of a gene family from the lineage Nodes with dotted outlines indicate the presence of a gene family but the absence of immunity-related orthologs Nodes with thick outlines indicate the expansion of gene families Repeated expansion is indicated with thicker outlines The middle panel (top) displays the percentages (%) of cell-surface receptors and signalling components in the genome of each species within the lineage Middle panel (bottom) represents the distribution of signalling components in the genome of each species within a lineage Bars are labelled in colours as indicated on top left The bottom panel shows examples of plant species and the classification of the plant lineages Left panel: expansion of PRR family gene repertoires throughout the plant lineage which leads to recognition of a larger range of PAMPs/MAMPs and helper NLRs are absent from many algal species A more complex immune network involving these signalling components apparently developed in vascular plants Right panel: An ancient PRR with LRRID + 4LRR with unknown function evolved into LRR-RLK-Xbs and LRR-RLPs which are involved in development- and immune-signalling eJM-TM-cJM region of LRR-RLPs evolved to allow interactions with SOBIR1 to induce immunity (negatively charged eJM and GxxxG) LRR-RLK-Xbs utilize Xb kinase domains to induce distinct downstream responses The initial set of proteins included only the primary gene models from all 350 species (12,979,225 proteins in total) sequences were filtered for a minimal length of 250 AA in the case of LRR-RLKs (7,690,505 proteins) or 150 AA in the case of all others (10,224,242 proteins) Based on the presence of a kinase domain (KD) and/or a trans-membrane domain (TM) the proteins fell into three major groups: (1) RLKs with KD and TM and (3) ectodomain candidates without KD or TM To identify RLPs and ectodomain candidates (without KD or TM) we first removed all proteins with a kinase domain match (hmmer with the option -E1000) leaving 9,746,585 from the initial 10,224,242 proteins We next removed potential signalling peptides from the sequences with SignalP because they are sometimes identified as TM domains (trimmed 796,385 sequences) We then searched for TMs with tmhmm and kept proteins with no TM (7,917,087 To test whether RLPs contained potentially functional endodomain sequences we extracted endo- and ectodomain sequences As tmhmm sometimes reverts in- and outside locations we defined the stretch that was matched by the motif (e.g the ectodomain sequence was defined as the stretch that contained the most LRR repeats The endodomain was the remaining longest internal sequence stretch The lengths of these sequences were visualized We also searched for all available PFAM patterns in the endodomains of all RLPs as well as the proteins with kinase and TM domain with hmmsearch (with a strict e-value threshold of 1e-10 to ensure a minimum of partial matches) we only kept the hit with the best score and counted the number of hits per PFAM domain and species We only kept domains that were found in more than 1 or 1 out of 10,000 input sequences Within the endodomains of the proteins with kinase and TM domains 99.42% were best matched by a kinase pattern in all the RLPs we only found five kinase pattern matches among the 3'860 endodomains of WAK-RLPs (0.13%) endodomains of RLPs were rarely matched by any PFAM pattern: 1.27% of the Duf26-RLPs The WAK-RLPs were slightly different as 15.36% of their ectodomains matched to a PFAM pattern: most of them (13.94%) to a RING finger domain which might be involved in protein-protein interaction (PF13639.7) and RBOHs were identified by hmmer searches (option -E 10) for specific domains Ion transport protein domains (PFAM: PF00520.32) were used for CNGCs PHM7_cyt (PFAM: PF14703.7) and RSN1_TM (PFAM: PF13967.7) were used for OSCAs and FAD-binding domains (PFAM: PF08022.13) ferric reductase like transmembrane components (PFAM: PF01794.20) and ferric reductase NAD binding domains (PFAM: PF08030.13) were used for RBOHs and Solyc02g067660) proteins were found in exactly one cluster each we used the three matching clusters as EDS1 RPW8-NLRs (NRG1 and ADR1) were identified similarly using the NB-ARC (PFAM: PF00931.23) and RPW8 (PFAM: PF05659.12) domains we found all known NRG1 and ADR1 sequences in one single cluster This allowed us to extract and re-cluster these sequences with more stringent parameters (options --min-seq-id 0.3 -c 0.75) and Niben101Scf02118g00018.1) and ADR1 (AT1G33560 and Niben101Scf02422g02015) proteins in exactly one cluster each indicating that the two matching clusters could be considered as NRG1 and ADR1 proteins The following patterns were used for the families of interest: SOBIR1: RLK-Pelle_LRR-XI-2 The percentages (%) of cell-surface receptors and signalling components from each genome were calculated as (number of identified genes/number of searched genes × 100) The expansion rate within a species is calculated by ((% cell surface receptors or signalling components in that species)-(median))/(median) the expansion rate of LRR-RLP family in Marchantia polymorpha from green algae is calculated by ((%LRR-RLP in Marchantia polymorpha)-(median %LRR-RLP in green algae)/(median %LRR-RLP in green algae) Note that the reliability of the expansion rate is dependent on the number of species used to calculate the median which is also dependent on the available genomes in Glaucophyta We then pruned the sequences to include everything from the C3 domain to the C terminus we further searched sequences for kinase domains and removed sequences upstream of the start of the kinase domain C3 or eJM) were subsequently extracted from this alignment the sequence similarity trees of specific domains were constructed as described above (FAMSA In-depth analysis of the ectodomains from all Duf26 and WAK candidates was done using the ectodomain sequences extracted from the ectodomain-only proteins Ectodomain sequences from the ectodomain-only proteins were extracted based on the location of the hmm-pattern match Phylogenies were constructed as described above with FAMSA and gotree (rooted with a sequence from the most basal species according to the NCBI taxonomy) and AtBES1 were amplified by PCR with KoD one (Toyobo and the PCR products were cloned into the epiGreenB5 (3× HA) vector between the ClaI and BamHI restriction sites with In-Fusion HD Cloning Kit (Clontech USA) to generate p35S::BES1-HA or p35S::cell-surface receptor-HA (epiGreenB5-Cauliflower mosaic virus (CaMV) p35S:gene of interest-3 × HA) The constructs were then transformed into Agrobacterium tumefaciens strain AGL1 for transient expression in Nicotiana benthamiana All chimeric cell-surface receptors generated in this study contain the EFR signal peptide to ensure consistency between the constructs and expression levels tumefaciens strain AGL1 carrying the binary expression vectors described above were grown on LB agar plates amended with selection antibiotics and then resuspended in infiltration buffer (10 mM MgCl2 The concentration of AGL1 was then adjusted to OD600 = 0.5 and syringe-infiltrated into N Protein extraction for immunoprecipitation was performed as previously described93 benthamiana leaves were treated with elicitors and snap-frozen The tissues were then ground in liquid nitrogen and extracted in extraction buffer (50 mM Tris-HCl at pH 7.5 1% Protease Inhibitor Cocktail (P9599; Sigma-Aldrich) 100 μM phenylmethylsulphonyl fluoride and 2% IGEPAL CA-630 (v/v; Sigma-Aldrich) and 2 mM EDTA) at a concentration of 3 mL/g tissue powder Samples were then incubated at 4 °C for an hour and debris was removed by centrifugation at 13,000 rpm for 10 min at 4 °C protein concentrations were adjusted to 5 mg/mL then incubated with rotation for an hour at 4 °C with 50 μL anti-HA magnetic beads (Miltenyi Biotec) for immunoprecipitation Magnetic beads were then washed twice with extraction buffer and the HA-tagged protein was eluted with sodium dodecyl sulphate (SDS) sample buffer at 95 °C Protein extractions were performed as previously described94 benthamiana leaves were infiltrated with elicitors and snap-frozen at indicated time points The tissues were then lysed in liquid nitrogen and extracted in 1×NuPAGE™ LDS Sample Buffer (Invitrogen™) with 10 mM DTT at 70 °C for 10 min Total proteins were then separated by SDS-PAGE and blotted onto a nitrocellulose membrane (Trans-Blot Turbo Transfer System The membrane was then blocked in a solution of either 5% skimmed milk (for BES1 and cell-surface receptor detection) or 5% bovine serum albumin (BSA; for MAPK detection) in Tris-buffered saline 0.1% Tween 20 detergent (TBST) for an hour Phosphorylated MAPKs were detected using α-phospho-p44/42 MAPK rabbit monoclonal antibody (D13.14.4E USA) in a solution of 5% BSA in TBST overnight at 4 °C HA-tagged BES1 or cell surface receptors were detected using Anti-HA-Peroxidase rat IgG1 antibody (Roche) in a solution of 5% skimmed milk in TBST overnight at 4 °C this was followed by incubation with α-rabbit IgG-HRP-conjugated secondary antibodies (1:10,000 USA) in a solution of 5% BSA in TBST for an hour at room temperature HRP signal was then detected by Clarity Western ECL Substrate (Bio-Rad) with a LAS 4000 system (GE Healthcare Nitrocellulose membranes were stained with Coomassie Brilliant Blue (CBB) to ensure equal loading ROS burst assays were performed as described previously93 benthamiana leaf discs were collected with a 4-mm-diameter cork borer and placed in 96-well plates with 120 μl deionised water overnight in the dark (abaxial surface of the leaves facing down) benthamiana leaf discs were then treated with either mock (water) or 1 μM nlp20 in 20 mM luminol (Wako Japan) and 0.02 mg ml−1 horseradish peroxidase (Sigma-Aldrich) Luminescence was then measured over indicated periods of time with a Tristar2 multimode reader (Berthold Technologies Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article Evolutionary dynamics of the leucine-rich repeat receptor-like kinase (LRR-RLK) subfamily in angiosperms Concerted expansion and contraction of immune receptor gene repertoires in plant genomes NLR surveillance of essential SEC-9 SNARE proteins induces programmed cell death upon allorecognition in filamentous fungi Prokaryotic innate immunity through pattern recognition of conserved viral proteins Innate immunity in plants and animals: emerging parallels between the recognition of general elicitors and pathogen-associated molecular patterns Receptor-like kinases from Arabidopsis form a monophyletic gene family related to animal receptor kinases Flourishing in water: the early evolution and diversification of plant receptor-like kinases Phytocytokines function as immunological modulators of plant immunity Plant cell surface receptor-mediated signaling - a common theme amid diversity Out of water: the origin and early diversification of plant R-genes Structural evolution drives diversification of the large LRR-RLK gene family Molecular mechanisms of early plant pattern-triggered immune signaling Roles of receptor-like cytoplasmic kinase VII members in pattern-triggered immune signaling Signaling mechanisms in pattern-triggered immunity (PTI) The structural basis of ligand perception and signal activation by receptor kinases Receptor-like kinase SOBIR1/EVR interacts with receptor-like proteins in plant immunity against fungal infection EDS1 signalling: at the nexus of intracellular and surface receptor immunity Plant NLRs get by with a little help from their friends Receptor-like cytoplasmic kinases directly link diverse pattern recognition receptors to the activation of mitogen-activated protein kinase cascades in Arabidopsis Huang, W. R. H. et al. Receptor-like cytoplasmic kinases belonging to different subfamilies mediate immune responses downstream of the Cf-4 resistance protein in Nicotiana benthamiana. BioRxiv. https://doi.org/10.1101/2023.04.25.538242 (2023) Tyrosine phosphorylation of the lectin receptor-like kinase LORE regulates plant immunity The calcium-dependent protein kinase CPK28 buffers plant immunity and regulates BIK1 turnover Calcium-dependent protein kinase/NADPH oxidase activation circuit is required for rapid defense signal propagation Bifurcation of Arabidopsis NLR immune signaling via Ca2+-dependent protein kinases Differential innate immune signalling via Ca(2+) sensor protein kinases A Phytophthora capsici RXLR effector targets and inhibits the central immune kinases to suppress plant immunity The Arabidopsis E3 ubiquitin ligase PUB4 regulates BIK1 and is targeted by a bacterial type-III effector Receptor-like cytoplasmic kinases integrate signaling from multiple plant immune receptors and are targeted by a Pseudomonas syringae effector Perturbations of the ZED1 pseudokinase activate plant immunity Activation of a plant nucleotide binding-leucine rich repeat disease resistance protein by a modified self protein The Arabidopsis ZED1 pseudokinase is required for ZAR1-mediated immunity induced by the Pseudomonas syringae type III effector HopZ1a The decoy substrate of a pathogen effector and a pseudokinase specify pathogen-induced modified-self recognition and immunity in plants Leucine-rich repeat (LRR) domains containing intervening motifs in plants Plant Receptor-like proteins (RLPs): Structural features enabling versatile immune recognition Arabidopsis leucine-rich repeat receptor-like kinase NILR1 is required for induction of innate immunity to parasitic nematodes Signaling of cell fate determination by the TPD1 small protein and EMS1 receptor kinase Tyrosine-sulfated glycopeptide involved in cellular proliferation and expansion in Arabidopsis A LRR receptor kinase involved in perception of a peptide plant hormone A putative leucine-rich repeat receptor kinase involved in brassinosteroid signal transduction a receptor kinase pair mediating brassinosteroid signaling Allosteric receptor activation by the plant peptide hormone phytosulfokine An RLP23-SOBIR1-BAK1 complex mediates NLP-triggered immunity Structure reveals that BAK1 as a co-receptor recognizes the BRI1-bound brassinolide Structural basis of steroid hormone perception by the receptor kinase BRI1 Molecular mechanism for plant steroid receptor activation by somatic embryogenesis co-receptor kinases Plant receptor-like protein activation by a microbial glycoside hydrolase Structural insight into brassinosteroid perception by BRI1 Structural basis for flg22-induced activation of the Arabidopsis FLS2-BAK1 immune complex Kinase activity of SOBIR1 and BAK1 is required for immune signalling Peptide ligand-mediated trade-off between plant growth and stress response Arabidopsis thaliana resistance to fusarium oxysporum 2 implicates tyrosine-sulfated peptide signaling in susceptibility and resistance to root infection SOBIR1 requires the GxxxG dimerization motif in its transmembrane domain to form constitutive complexes with receptor-like proteins BES1 accumulates in the nucleus in response to brassinosteroids to regulate gene expression and promote stem elongation Evolutionary gain and loss of a plant pattern-recognition receptor for HAMP recognition Pathogen-induced defense and innate immunity in macroalgae The receptor kinase FER is a RALF-regulated scaffold controlling plant immune signaling The leucine-rich repeat receptor kinase BIR2 is a negative regulator of BAK1 in plant immunity The Arabidopsis leucine-rich repeat receptor kinase BIR3 negatively regulates BAK1 receptor complex formation and stabilizes BAK1 Structural basis for BIR1-mediated negative regulation of plant immunity Regulation of cell death and innate immunity by two receptor-like kinases in Arabidopsis Regulation of plant immune signaling by calcium-dependent protein kinases Perception of brassinosteroids by the extracellular domain of the receptor kinase BRI1 Perception of a divergent family of phytocytokines by the Arabidopsis receptor kinase MIK2 The Arabidopsis MIK2 receptor elicits immunity by sensing a conserved signature from phytocytokines and microbes Database mining of plant peptide homologues A microbially derived tyrosine-sulfated peptide mimics a plant peptide hormone Plant-parasitic nematode secreted peptides hijack a plant secretory pathway SignalP 5.0 improves signal peptide predictions using deep neural networks Identification and characterization of the LRR repeats in plant LRR-RLKs Clustering huge protein sequence sets in linear time classification and function of the plant protein kinase superfamily LRRsearch: An asynchronous server-based application for the prediction of leucine-rich repeat motifs and an integrative database of NOD-like receptors FAMSA: Fast and accurate multiple sequence alignment of huge protein families ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R Fast unfolding of communities in large network The igraph software package for complex network research | CiNii Research Interactive Tree Of Life (iTOL) v5: an online tool for sequence similarity tree display and annotation Mechanisms of RALF peptide perception by a heterotypic receptor complex Chitin-induced dimerization activates a plant immune receptor Highly accurate protein structure prediction with AlphaFold a web-based 3D viewer for sharing 1D/2D/3D representations of biomolecular structures Timetree 5: an expanded resource for species divergence times Structural basis for differential recognition of brassinolide by its receptors Download references and Mizuki Yamamoto for providing technical support and Jonathan Jones for discussions and critical reading of the manuscript We also thank Markus Albert for sharing the information on chimeric receptors and BES1-HA experiments is an International Research Fellow of the Japan Society for the Promotion of Science (Postdoctoral Fellowships for Research in Japan (Standard) The research was financially supported by MEXT/JSPS KAKENHI Grant Numbers conceived and conceptualised the study; B.P.M.N. designed the bioinformatic analyses; M.W.S performed the bioinformatic analyses; B.P.M.N performed the vector construction with assistance from Y.K Download citation DOI: https://doi.org/10.1038/s41467-023-44408-3 Metrics details A Correction to this article was published on 04 October 2021 This article has been updated Malaria remains a serious public health problem in Cameroon Implementation of control interventions requires prior knowledge of the local epidemiological situation Here we report the results of epidemiological and entomological surveys carried out in Tibati an area where malaria transmission is seasonal 6 years after the introduction of long-lasting insecticidal bed nets Cross-sectional studies were carried out in July 2015 and 2017 in Tibati Thick blood smears and dried blood spots were collected from asymptomatic and symptomatic individuals in the community and at health centers and used for the molecular diagnosis of Plasmodium species Adult mosquitoes were collected by indoor residual spraying and identified morphologically and molecularly and positivity of PCR-positive samples was confirmed by Sanger sequencing Overall malaria prevalence in our study population was 55.0% (752/1367) and Plasmodium falciparum was the most prevalent parasite species (94.3%) ovale (0.8%); 92 (12.7%) infections were mixed infections Infection parameters varied according to clinical status (symptomatic/asymptomatic) and age of the sampled population and the collection sites Infection prevalence was higher in asymptomatic carriers (60.8%) but asexual and sexual parasite densities were lower Prevalence and intensity of infection decreased with age in both the symptomatic and asymptomatic groups Heterogeneity in infections was observed at the neighborhood level Among the 592 Anopheles mosquitoes collected A total of 26 (4.39%) mosquito specimens were infected by Plasmodium sp and the three Anopheles mosquitoes transmitted Plasmodium at equal efficiency coluzzii specimen infected by Plasmodium vivax which confirms circulation of this species in Cameroon The positivity of all 26 PCR-positive Plasmodium-infected mosquitoes was successively confirmed by sequencing analysis Our study presents the baseline malaria parasite burden in Tibati Our results highlight the high malaria endemicity in the area and hotspots of disease transmission are identified Parasitological indices suggest low bednet usage and that implementation of control interventions in the area is needed to reduce malaria burden We also report for the first time a mosquito vector with naturally acquired P vivax with human infections in both Duffy-positive and -negative individuals has been reported no study has yet looked at which local malaria vector species is involved in the transmission of P we aimed to characterize malaria parasites and vectors circulating in an area of seasonal transmission in the Adamawa region vivax detection as this species was recently reported in other parts of the country and we conducted entomological surveys to identify its putative vector which has not been investigated in earlier studies Our main goal was to examine the potential risk of transmission of P vivax and to determine which local malaria vector species could be implicated in its transmission in this region of Cameroon Map of Tibati showing collection sites Blood samples were collected from symptomatic malaria patients in three health facilities: the Missionary hospital of Ngaoubela (MDH) District Medical Center (DMC) and the Integrated Medical Center (IMC) Blood samples were collected from asymptomatic persons in the community in eight neighborhoods of Tibati: Malarba which were the same neighborhoods that mosquito collections were performed stored at room temperature in a desiccant container and brought to the Malaria Research Unit for further analysis Plasmodium-positive patients were treated with an ACT according to the recommendations of the Ministry of Health of Cameroon (National Malaria Control Program [NMCP]) All female Anopheles specimens were dissected individually and the carcasses and head-thoraces were stored separately in tubes containing a desiccant archived and kept at − 20 °C for further molecular analysis three 5-mm discs of a dried blood spot were cut out using a sterile paper punch and transferred to a 1.5-ml sample tube filled with 500 µl of sterile water The tubes were vortexed three times for at least 5 s each time and centrifuged at 2000 rpm for few seconds the paper discs were transferred into a 0.5-ml tube containing 120 µl sterile water and incubated at 95 °C in a heat block for 15 min (Gene Amp®; Applied Biosystems the tubes were centrifuged for few seconds and the extracted DNA was stored at − 20 °C for molecular diagnosis To optimize the DNA extraction and allow for a better separation of DNA from some nucleases we used the Qiagen DNeasy® Blood and Tissue Kit (Hilden Germany) to isolate DNA from the blood samples collected in 2017 in accordance with the manufacturer’s instructions and resuspended the isolated DNA in 60 µl elution buffer DNA from the head-thoraces was isolated using the Qiagen DNeasy® Blood and Tissue Kit according to the manufacturer’s instructions The amplified products were visualized by electrophoresis in a 2% agarose gel and stained with SYBR dye (Green Nucleic Acid stain; Biotium The expected amplicon size was 276 bp for P All PCR products were analyzed in a 2% agarose gel Reaction mixtures were performed with 1 μl of template DNA in a final volume of 10 μl with EvaGreen® (5× HOT Pol EvaGreen® RT PCR Mix Plus; Euromodex France) and amplified in a 7300 Real-time PCR system (Applied Biosystems) A dissociation curve was used to estimate the specific melting temperature for each reaction The final volume of the reaction mixture was 10 μl The PCR conditions consisted of an initial preincubation step at 95 °C for 10 min; followed a three-step amplification of 95 °C/10 s (ramp 4.4 °C/s) 50 °C/5 s (2.2 °C/s) and 72 °C/20 s (4.4 °C/s) Amplification was directly followed by a melting program of 95 °C/120 s (2.2 °C/s) 68 °C/120 s (2.2 °C/s) and 90 °C/1 s (ramp 0.2 °C/s with 15 readings/°C) and a stepwise temperature increase of 0.03 °C/s until 95 °C falciparum 3D7 clone was used as positive control for Plasmodium species differentiation The qPCR products of Plasmodium-positive mosquitoes were sequenced using the Big Dye Terminator v3.1 Sequencing Kit (Applied Biosystems) and run on an Applied Biosystems 3130xl Sequencer at the GenSeq technical facility of the Institut des Sciences de l’Evolution de Montpellier Sequences were verified using SeqScape software (Applied Biosystems) Data were stored in Microsoft Office Excel files (Microsoft Corp. USA) and transferred into GraphPad Prism 7 (GraphPad Software Inc. The Mann–Whitney test was used to compare mean parasite densities according to clinical status The Chi-square test was used to compare the prevalence of Plasmodium infections among population age groups and mosquito species The non-parametric Kruskal–Wallis test was used to assess differences in parasite densities between age groups The significance threshold was set at alpha = 0.05 The relative risk (RR) was computed to estimate the protection associated with LLIN use R software version 3.5.3 with maptools and ggplot2 packages was used to generate the map and figures respectively (R Foundation for Statistical Computing while melting temperatures of qPCR-positive controls were retrieved by using functional bases (without package) A total of 1367 participants were enrolled in this study, 418 through the health centers (symptomatics) and 949 at the community level (asymptomatics). The main characteristics of the participants are detailed in Table 1 Boxplot of parasite densities for each age group in symptomatic and asymptomatic individuals malaria diagnostic tools revealed 752 (55.01%) infections with Plasmodium The infection rate was 41.8% (175/418) in samples from symptomatic patients and 60.8% (577/949) in samples from asymptomatic individuals which is significantly different (X2 = 41.21; P < 0.0001) Plasmodium falciparum was the most prevalent Plasmodium species collected during both collection periods and represented 98.8 and 92.9% of human infections in 2015 and 2017 ovale each accounted for 0.6% of clinical infections in samples from asymptomatic persons a higher prevalence was recorded for P Mixed infections were only found in asymptomatic carriers and were mostly represented by P vivax infection was detected in any blood sample LLIN use based on self-report only conferred slight protection: malaria infection among LLIN users was only 7% less than that among non-users (non-significant difference; RR = 0.89 95% confidence interval [CI] 0.58–0.98); however the difference varied with collection site with up to 20% protection found in Malarba Distribution of Anopheles mosquitoes according to collection time Melting curve peak of the YK60 and NG239 samples identified as being infected by a Plasmodium sp The x-axis represents the melting temperature (Tm) and the y-axis represents the results of quantitative PCR on the Lightcycler real-time PCR system (dF/dT negative derivative of the fluorescence/derivative temperature) Each red and blue curve represents the Tm of each Plasmodium falciparum-positive control The green curve represents the Tm of the sample All Plasmodium-positive specimens were monoinfected A single sample was found by qPCR to be positive for An All Plasmodium-positive mosquitoes were processed for sequencing, and the sequence alignment of the P. vivax infection is presented in Fig. 5. vivax sample isolated from an infected Anopheles coluzzii sampled in 2015 with the reference DNA sequence Pv_ECPR (accession number AY423071.1) P4G2_F and P4G2_R represent the forward and reverse sequences Numbering corresponds to that of the Pv_ECPR sequence This study was performed to assess epidemiological and entomological parameters of malaria in Tibati a locality situated in the Adamawa region of Cameroon 9% of the negative blood smears by microscopic examination were found to be positive upon molecular analysis in our study and modifications to the habitat in Tibati (e.g home improvement) that occurred during the 2 years between the studies have probably contributed to the creation of breeding sites more suitable for An which is a widely used method for sampling endophilic mosquitoes could have favored the collection of endophilic resting Anopheles over other mosquito species The percentage of infected mosquitoes sampled in 2017 varied between neighborhoods with the highest infection rate recorded in Yoko (5.2%) which could be explained by a high malaria prevalence and the lower LLIN coverage (21.1%) in this neighborhood Plasmodium vivax can then be considered to circulate in the study area and may also be underestimated vivax infections in humans are “hidden” since hypnozoites lie dormant in the liver for several months (or years) where they are undetected A limitation to this study is that mosquito samples were obtained at a single collection time and the results only provide a one-shot picture of malaria transmission in the study site Longitudinal surveys would be necessary to follow the dynamics of malaria transmission and will be crucial to perform parasitological and entomological surveys before and after the implementation of control interventions A second limitation is that sample sizes were small which is possibly the reason we did not detect P Regular monitoring of malaria infections will be necessary to assess the true circulation of P vivax in the area; we cannot exclude the possibility that the P vivax-positive mosquito got infected while feeding on a non-resident as Tibati is a cross-border city with a high circulation of people We have provided a picture of the epidemiological and entomological malaria situation in Tibati a small town in the Adamawa region of Cameroon Malaria prevalence varied from 42% in symptomatic patients to 61% in asymptomatic individuals and this finding highlights the high malaria endemicity in the area were responsible for the transmission of the disease with all three species contributing equally to Plasmodium transmission Parasitological indices suggest low bednet usage and that the implementation of control interventions in the area is needed to reduce the malaria burden We identified hotspots of disease transmission and these sites should be the target of malaria control efforts coluzzii mosquito prompts for regular monitoring as the spread of this species could introduce further complexity into malaria epidemiology and control measures in this area All data generated or analyzed during the current study are included in this published article A Correction to this paper has been published: https://doi.org/10.1186/s13071-021-04912-1 PCR‐restriction fragment length polymorphism World Health Organization. World malaria report. Geneva: World Health Organization; 2020. https://www.who.int/publications/i/item/9789240015791 Complexity of the malaria vectorial system in cameroon: contribution of secondary vectors to malaria transmission Anopheles species of the Mount Cameroon region: biting habits feeding behaviour and entomological inoculation rates Systematique et biologie des Anopheles vecteurs de Plasmodium en Afrique Données récentes Unravelling complexities in human malaria transmission dynamics in Africa through a comprehensive knowledge of vector populations Short report: first report of knockdown mutation in the malaria vector Anopheles gambiae from Cameroon Anopheles coluzzii larval habitat and insecticide resistance in the island area of Manoka Multiple insecticide resistance mechanisms in Anopheles gambiae s.l Multiple insecticide resistance in the malaria vector Anopheles funestus from Northern Cameroon is mediated by metabolic resistance alongside potential target site insensitivity mutations The distribution of insecticide resistance in Anopheles gambiae s.l Patterns of anopheline feeding/resting behaviour and Plasmodium infections in North Cameroon 2011–2014: implications for malaria control Status of insecticide resistance and its mechanisms in Anopheles gambiae and Anopheles coluzzii populations from forest settings in South Cameroon Molecular monitoring of Plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé Prevalence of Plasmodium falciparum parasites resistant to sulfadoxine/pyrimethamine in pregnant women in Yaoundé Cameroon: emergence of highly resistant pfdhfr/pfdhps alleles Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study Effects of drug policy changes on evolution of molecular markers of Plasmodium falciparum resistance to chloroquine and sulphadoxine-pyrimethamine in the south west region of Cameroon sulphadoxine-pyrimethamine and their combination for the treatment of uncomplicated Plasmodium falciparum malaria in children in Cameroon at the time of policy change to artemisinin-based combination therapy Genetic diversity of Plasmodium falciparum in Bolifamba on the slopes of Mount Cameroon: influence of MSP1 allelic variants on symptomatic malaria and anaemia Genetic diversity of Plasmodium falciparum and genetic profile in children affected by uncomplicated malaria in Cameroon Identification of the Plasmodium species in clinical samples from children residing in five epidemiological strata of malaria in Cameroon Comparison of the accuracy of four malaria diagnostic methods in a high transmission setting in coastal Cameroon Epidemiology of malaria in three geo-ecological zones along the chad-cameroon pipeline Rapport d’activité 2012 du programme de lutte contre le paludisme Molecular evidence of Plasmodium vivax mono and mixed malaria parasite infections in duffy-negative native Cameroonians Molecular typing reveals substantial Plasmodium vivax infection in asymptomatic adults in a rural area of Cameroon Molecular evidence of Plasmodium vivax infection in Duffy negative symptomatic individuals from Dschang An additional observation of Plasmodium vivax malaria infection in Duffy-negative individuals from Cameroon World Health Organization. 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northern savannah of Cameroon: a cross-sectional survey Habitat suitability and ecological niche profile of major malaria vectors in Cameroon Malaria vectors and transmission dynamics in coastal south-western Cameroon Bionomics and insecticides resistance profiling of malaria vectors at a selected site for experimental hut trials in central Cameroon Review of the evolution of insecticide resistance in main malaria vectors in Cameroon from 1990 to 2017 Investigation of the influence of a glutathione S-transferase metabolic resistance to pyrethroids/DDT on mating competitiveness in males of the African malaria vector Anopheles funestus Gene flow between chromosomal forms of the malaria vector Anopheles funestus in Cameroon Anopheles gambiae distribution and insecticide resistance in the cities of Douala and Yaoundé (Cameroon): influence of urban agriculture and pollution Distribution des espèces et de la fréquence du gène Kdr chez les populations d’Anopheles gambiae s.s et d’Anopheles coluzzii dans cinq sites agricoles de la Côte d’Ivoire Anthropogenic habitat disturbance and ecological divergence between incipient species of the malaria mosquito Anopheles gambiae Ecological niche partitioning between Anopheles gambiae molecular forms in Cameroon: the ecological side of speciation Water quality and Anopheles gambiae larval tolerance to pyrethroids in the cities of douala and yaoundé (Cameroon) Malaria in Mauritania: retrospective and prospective overview Small-scale land-use variability affects Anopheles spp distribution and concomitant Plasmodium infection in humans and mosquito vectors in southeastern Madagascar Malaria transmission and vector biology in manarintsoa Blood meal sources and entomological inoculation rates of anophelines along a highland altitudinal transect in south-central Ethiopia Moderate transmission but high prevalence of malaria in Madagascar Evidence for transmission of Plasmodium vivax among a duffy antigen negative population in western Kenya Download references We are grateful to all the residents of Tibati who agreed to participate in this study and gave permission to enter their houses for mosquito collection Our appreciation is also extended to Estelle Esssangui and Balotin Fongang for their support and cooperation during data analysis Our sincere thanks go to Rhoel Dinglasan for his contribution in reviewing the article This work was carried out as part of an AUF-IRD research project granted to SEN This research was supported by the French National Research Institute for Sustainable Development (IRD) through the JEAI-IMPALA project granted to SEN LBFD and EMSM were supported by a doctoral fellowship from the LabEx ParaFrap Lionel Brice Feufack-Donfack and Elangwe Milo Sarah-Matio contributed equally to this work Service de Paludisme du Centre Pasteur Cameroun Isabelle Morlais & Sandrine Eveline Nsango Institut de Recherche pour le Développement Christelle Maffo Ngou & Isabelle Morlais Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale Jean-Claude Toto & Parfait Awono-Ambene Centre for Research in Infectious Diseases Department of Microbiology and Infectious Diseases School of Veterinary Medicine and Sciences Faculté de Médecine et des Sciences Pharmaceutiques de l’Université de Douala (FMSP–UD) Carole Else Eboumbou Moukoko & Sandrine Eveline Nsango SEN and IM conceived and designed the study protocol MMS and SEN carried out the field and laboratory assays LA and PAA critically reviewed the manuscript All authors read and approved the final manuscript Our study was approved by the Cameroon National Ethics Committee (N°2015/04/579/CE/NERSH) and by the Delegate of Public Health from Adamaoua region (N°029/L/RA/DSP/SAGE/BPF/NGD/15;735/L/RA/DSP/SAGE/BPF/NGD/17) and the Health Director of the Evangelical Lutheran Church (N°004/EELC/OSEELC/SRH/15) All human volunteers were enrolled after providing written informed consent either by the participants and/or by their legal guardians Written informed consent were also provided by household owners prior to mosquito collection Free malaria treatments with ACT were given to all Plasmodium-infected patients as recommended by the Ministry of Health (NMCP) The authors declare that they have no competing interests Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations unless otherwise stated in a credit line to the data Download citation DOI: https://doi.org/10.1186/s13071-021-04745-y Metrics details The careHPV assay is a test for high-risk (HR) human papillomaviruses (HPV) detection designed to be affordable in resource-poor settings We evaluated the performance of careHPV screening among 1052 women living with HIV/AIDS included in the HARP (HPV in Africa Research Partnership) study in Burkina Faso (BF) and South Africa (SA) Cervical samples were tested for HR-HPV by the careHPV and the INNO-LiPA HPV genotyping Extra assays visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) and colposcopy Cervical biopsies were obtained for participants who were HR-HPV DNA positive by careHPV or who had abnormalities detected on cytology 45.1% of women had a positive careHPV test (46.5% in BF The careHPV positivity rate increased with the grade of cytological lesions Sensitivity and specificity of careHPV for the diagnosis of CIN2+ (n=60 both countries combined) were 93.3% (95% confidence interval (CI): 83.8–98.2) and 57.9% (95% CI: 54.5–61.2) careHPV had a similar clinical sensitivity but higher specificity than the INNO-LiPA assay for detection of CIN2+ Our results suggest that careHPV testing is a reliable tool for cervical cancer screening in HIV-1-infected women in sub-Saharan Africa there is a need for developing preventive measures in this highly exposed population of African women living with HIV/AIDS (WLHA) cervical cancer screening programs are lacking in most Sub-Saharan African countries and the diagnosis of cervical cancer is generally made at an advanced stage of the disease when treatment is unavailable or ineffective but evaluation among WLHA have only rarely been conducted it remained to be demonstrated that careHPV had a good performance among African WLHA we used the second round of screening in HARP 18 months after enrolment to evaluate the performance of careHPV for the detection of CIN2+ Participants were confirmed HIV-1− seropositive women aged 25–50 years recruited from the HIV outpatient clinic of the University Hospital of Ouagadougou and HIV treatment centres and surrounding primary health care clinics in Hillbrow Eligible women were invited for inclusion in the study if they were resident in the recruitment city did not had a total hysterectomy or history of cervical cancer treatment and were not pregnant or less than 8 weeks post partum Ethical approval was granted from Ministry of Health in Burkina Faso (no the Witwatersrand University in South Africa (no 110707) and the London School of Hygiene and Tropical Medicine (no All women provided a written informed consent at the screening visit and they were given a reflection period of at least 7 days before enrolment in the study A second written informed consent was obtained at the enrolment visit for enrolment and follow-up over scheduled visits at months (M) 6 endo- and ectocervical sampling was performed using the careHPV sample collection device consisting of a careBrush and a vial containing 1 ml of careHPV collection medium (Qiagen) the brush was stirred into the collection medium the cell collection was homogenised by vortexing and divided into four 0.25-ml aliquots One aliquot was maintained at 4 °C until careHPV analysis and the others were cryopreserved at −80 °C The careHPV test was performed using 50 μl of cervical sample in collection medium according to the manufacturer’s instruction The tests were performed at the respective sites by medical scientists specifically trained by a Qiagen’s scientist The positive or negative result of the careHPV assay was displayed by the careHPV test controller without additional specification of the luminescent signal intensity which is based on PCR amplification of HPV DNA using broad-spectrum SPF10 consensus primers followed by hybridisation of the amplicons with type-specific oligonucleotides probes immobilised on membrane strips including the 14 HR-HPV types targeted by the careHPV assay Testing was performed on an aliquot preserved at −80 °C A sample was considered HPV+ if at least one of the type-specific probes or one of the HPV control probes were detected An additional cervical brush was collected from the ecto- and endocervix and rolled on a glass slide which was fixed with ethanol for cytological reading using the Papanicolaou method (Pap test) Conventional cytology was used as liquid-based cytology was not available at that time in the African laboratories involved in the study All participants had visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) performed by trained nurses and colposcopy performed by trained colposcopists Systematic four-quadrant biopsy and directed biopsy from any suspicious lesions were performed for participants testing positive by careHPV or who had abnormalities detected on cytology (⩾ASC-US) The Bethesda system for reporting cervical cytology (Smith, 2002) was used for cytology results and the CIN classification for histology results Cytological and histological slides were independently examined at each site by two senior pathologists blinded to the other study results Pathologists were trained before the start of the study in order to harmonise slide interpretation between sites A quality assessment of over 10% of slides was organised at 6-month intervals by the reference pathology laboratory at Montpellier University Hospital for both sites in addition to existing internal and external quality assurance schemes adhered to by the National Health Laboratory Service (NHLS) in SA reviewed all histological slides from women with a local diagnosis of CIN2+ and ∼10% of slides from women with normal or CIN1 histological findings; the final classification of lesions was based on a consensus of the committee Women included in this analysis comprise all of the HARP participants who were not lost to follow-up at M18 visit including women who may have been treated for CIN2+ detected at baseline Proportions were compared between groups using χ2 or Fisher’s exact test positive and negative predictive values (NPV) were calculated with exact binomial 95% confidence intervals (CI) separately for each country first and then for both countries combined (sensitivity and specificity only) sensitivity and specificity analysis to detect CIN2+ was stratified by levels of CD4 T-cell counts (⩽200 cells per mm3 >350 cells per mm3) at entry in the study and at the time of screening (M18) and by age (<35 and ⩾35 years) and compared across strata using χ2 or Fisher’s exact tests as appropriate The comparative analysis of performance of all other methods and triage combinations for the detection of CIN2+ is not reported in this paper Agreement between the careHPV assay and the INNO-LiPA HPV genotyping Extra assay was assessed by percentage overall agreement and prevalence-adjusted bias-adjusted (PABA)-kappa coefficient All analyses were done using the Stata version 14 software (Stata Corp Study flowchart.BF=Burkina Faso; SA=South Africa The detection rates ranged from 40.0 (HPV56) to 86.4% (HPV58) Cytology results showed that the overall prevalence of high-grade squamous intraepithelial lesions (HSIL) was 10.5% (98/929) with a prevalence of 2.1% (9/426) in BF and of 17.7% (89/503) in SA. As shown in Table 2 the prevalence of HR-HPV detected by careHPV or the INNO-LiPA genotyping Extra assay increased with the lesion grade (P<0.0001) and the sensitivity and specificity values for the detection of HSIL were 88.8% (87/98) and 61.8% (514/831) for careHPV The sensitivity of careHPV for detecting HSIL was lower in SA than in BF (87.6% vs 100%) but specificity was higher (64.7% vs 56.3%) Negative predictive values for HSIL were 100% (95% CI: 98.4–100.0) and 96.1% (95% CI: 93.1–98.0) in BF and SA none of these studies had been conducted among WLHA the possible impact of HIV infection on the performance of careHPV for cervical screening deserved further investigation The high prevalence of HR-HPV in this highly exposed population which increases by level of immune suppression as not all HPV infections will progress to CIN2+ lesions which would make that HPV assay suitable for screening The overall sensitivity and specificity of 93.3 and 57.9% observed in the present study indicate that careHPV would perform equally well for cervical cancer screening of WLHA in sub-Saharan Africa Given the relative low specificity of HPV testing a triage test such as cytology might be required to determine which women should be referred to colposcopy The cost-effectiveness of this approach should be evaluated we can rule out issues of histological misclassification as final histological diagnosis of CIN2+ lesions was established by a consensus Expert Committee reviewing slides from both countries simultaneously our results indicate that the careHPV test would be a reliable tool for cervical cancer screening in WLHA Such a cost-affordable test should be considered for implementation in cervical cancer prevention programs in sub-Saharan Africa targeting women living with HIV/AIDS This paper was modified 12 months after initial publication to switch to Creative Commons licence terms Jeronimo JA (2015) Performance of cervical cancer techniques in HIV-infected women in Uganda Castle PE (2014) The concordance of HPV DNA detection by Hybrid Capture 2 and careHPV on clinician- and self-collected specimens Meijer CJ (2008) Overview of human papillomavirus-based and other novel options for cervical cancer screening in developed and developing countries Cancer Epidemiol Biomarkers Prev 21: 1434–1438 and cervical neoplasia and cancer in the era of highly active antiretroviral therapy Franceschi S (2012) Prevalence and determinants of human papillomavirus infection and cervical lesions in HIV-positive women in Kenya Segondy M (2006) Human papillomavirus genotype distribution and cervical squamous intraepithelial lesions among high-risk women with and without HIV-1 infection in Burkina Faso Bray F (2015) Cancer incidence and mortality worldwide: sources methods and major patterns in GLOBOCAN 2012 Smith JS (2013) Validation of cervical cancer screening methods in HIV positive women from Johannesburg South Africa Smith JS (2010) Association between cervical dysplasia and human papillomavirus in HIV seropositive women from Johannesburg South Africa Schiffman M (2012) Effectiveness of a simple rapid human papillomavirus DNA test in rural Nigeria Kiviat NB (2003) Increased risk of high-grade cervical squamous intraepithelial lesions and invasive cancer among African women with human immunodeficiency virus type 1 and 2 infections Jeronimo J (2014) CareHPV cervical cancer screening demonstration in a rural population of north India Eur J Obstet Gynecol Reprod Biol 176: 75–79 Qiao YL (2014) A parallel study of careHPV and Hybrid Capture2 human papillomavirus DNA testing for cervical cancer screening in rural China Longatto-Filho A (2013) Self-collection for high-risk HPV detection in Brazilian women using the careHPV™ test Segondy M (2015) Comparison of analytical and clinical performances of the Digene HC2 HPV DNA assay and the INNO-LiPA HPV genotyping assay for detecting high-risk HPV infection and cervical neoplasia among HIV-positive African women Segondy M (2013) Comparison of careHPV and hybrid capture 2 assays for detection of high-risk human Papillomavirus DNA in cervical samples from HIV-1-infected African women Lorincz AT (2008) A new HPV-DNA test for cervical-cancer screening in developing regions: a cross-sectional study of clinical accuracy in rural China Meijer CJ (2014) International HPV screening working group Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials Castle PE (2009) Human papillomavirus infection and cervical cytology in HIV-infected and HIV-uninfected Rwandan women Blumenthal PD (2013) Feasibility of community-based careHPV for cervical cancer prevention in rural Thailand Download references Other contributing members of the HARP study group included: E Cutler We wish to thank the members of the HARP International Scientific Advisory Group (ISAG): C Lacey (University of York Zimbabwe),Y Qiao (Chinese Academy of Medical Sciences and Peking Union Medical College China) and S de Sanjosé (Institut Catala d’Oncologia France) for her participation in the histological classification end point committee careHPV test kits and testing systems were obtained through a Qiagen Corporation donation programme The research leading to these results has received funding from the European Commission (EC) 7th Framework Programme under grant agreement No INSERM U1058 and University Hospital (CHU) London School of Hygiene and Tropical Medicine National Institute for Communicable Diseases Centre de Recherche Biomoléculaire Pietro Annigoni Centre de Recherche Internationale en Santé Sinead Delany-Moretlwe & Philippe Mayaud The authors declare no conflict of interest This work is published under the standard license to publish agreement After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ Download citation Journal of the Egyptian National Cancer Institute (2023) Gynecologic Oncology Research and Practice (2017) SINGAPORE — Even while she was under police investigation for peddling sham investments using part of her nearly S$300,000 loot to pay off her earlier victims after she admitted to 10 counts of cheating Another 21 counts were taken into consideration for sentencing purposes The court heard that Neo used the S$285,825 she fleeced from nine victims to repay debts she owed to unlicensed moneylenders and to repay some of the victims from her scams She has partially repaid S$32,300 — or around 11 per cent of the money she had cheated — to her victims marketed a sham investment in Janssen beauty products to some of her friends and acquaintances Deputy Public Prosecutor (DPP) Victoria Ting told the court that Neo claimed each box of these beauty products could be purchased in bulk at S$150 from the United States and sold for S$350 Neo promised her victims monthly payouts that were proportionate to their investments In one instance between October 2011 and February 2012 59-year-old Wong Ah Sen into investing in the products promising her that she would get a monthly dividend of S$1,000 for each tranche of S$1,500 invested who worked at a hair salon beside the beauty salon Neo was employed at had confided in her about her financial difficulties Neo said she would help Ms Wong invest the initial S$1,500 In order to raise the funds for the non-existent investment scheme Mr Khoo then threatened to lodge a police report when the payout was not given at the end of the month Despite being under police investigation in 2013 Neo tried to sell other beauty products-related investment scams involving deer placenta capsules and facial serums Neo told one of her clients Tan Chay Hua that the latter could stand to make a S$50 profit for every box of the products sold The court heard that Neo also misrepresented herself as the boss of a beauty salon and told an acquaintance that she hoped the two could invest in skincare products defence counsel Wilson Foo argued for a sentence of 30 months’ jail saying his client suffers from heart problems Neo’s “amateurish” scams were of “low levels of sophistication” which cannot be compared with that of someone in a financial position DPP Ting countered that the fact that Neo was not in a professional financial position was not a mitigating factor “(Neo’s) experience in the industry would have lent her scams greater credence and believability,” said the prosecutor That Neo perpetrated more scams even while under police investigation showed that she was “brazen (and had) a disregard for the law,” DPP Ting added urging the court to impose a jail sentence of at least three years (36 months) Neo’s 32-month jail sentence will be backdated to Sept 28 She could have been sentenced to 10 years’ imprisonment Todayonline.com and Today Online domains and apps are now part of 'Channelnewsasia.com' domain We know it's a hassle to switch browsers but we want your experience with TODAY to be fast Upgraded but still having issues? Contact us Massive MSC Turkiye to Dock in Kribi as New Container Terminal Opens Kribi Bitumen Plant Set to Start Construction in 2025 with Government Backing CEMAC Bond Market Hits CFA 8.45 Trillion in March 2025, Interest Rates Drop Cameroon’s Timber Output Projected to Rise in 2025 Despite Higher Export Taxes Central Africa Stock Exchange Sees 98% Drop in Trading Value in Q1 2025 Mboa Paris Trains 30 Young Cameroonians to Boost Tech and Entrepreneurship Cameroon Audit Targets Former Officials for Mismanagement in Agricultural Project Camwater Seeks Global Bids to Launch Bottled Water Lines in Five Cities Bafoussam Workshop Highlights Benefits of Cameroon-EU Trade Agreement Cameroon Could Reach 350,100 Tons of Cotton in 2025 (Beac) Paul Biya Appoints Johnny Razack as Chair of Cameroon’s National Investment Company Cameroon Refuses Work Visa Renewal for Casino and Super U Boss Over Toxic Workplace Claims Cameroon Joins Global Charter to Fight Illegal Fishing Cameroon Launches Construction of New Gas Filling Center in Kumba Cameroon Launches New CFA15bn Bond Issue After Recent Success Cameroon Eases Port Procedures to Keep CFA350bn in Chadian Transit Trade Douala Doubles Water Storage in Key Districts with New Reservoir Cameroon’s Supreme Court Reaffirms Exclusive Authority Over Public Finance Management "11 of the World’s 20 Fastest-Growing Economies in 2025 Are in Sub-Saharan Africa" (Amadou Sy, IMF) Douala Airport Customs Seizes $2.3mln Worth of Cocaine Bound for India Douala Port Shares CFA2bn in Rebates with Shippers and Shipping Lines in 2024 New Sosucam CEO Faces Tough Start as Worker Tensions Linger Rubber Output in Cameroon Could Reach 59,100 Tons in 2025 (BEAC) Cameroon Could Hit Highest Cocoa Output in Over Five Years Cameroon and Chad to Inaugurate CFA74bn Cross-Border Bridge on April 28 Cameroon Ranks Last in Global Fiber Optic Development Index Cameroon’s Finance Ministry Denies Budget Fraud After Audit Flags Irregularities Mbam Bridge Project in Cameroon Reassigned to CFHEC, Budget Increased Alucam Faces Financial Crisis: Audit Calls for CFA43bn Recapitalization to Avoid Shutdown CSPH Begins Construction of Ebolowa Gas Filling Center, Expected to Open in 2027 Cameroon Turns to BEAC Market for CFA25bn as Interest Rates Surge Every week the economy and investment news from Cameroon (Business in Cameroon) - The African Research Centre on Bananas and Plantains (CARBAP) is now an international institution since  May 30 a statement from the school board said last week in Njombe It was at the 7th Ordinary Session of the Njombe School Jean Daniel Ngou Ngoupayou and chaired by Valentin Pangou du Congo Minister of Scientific Research and Innovation Authorities see in the new status a valuable tool for advocacy with international partners and the strengthening of partnership with national agricultural research schemes in the region CARBAP wants to contribute to the development of sustainable agriculture that respects the environment diversify production and improve the income of farmers through the provision of new resistant varieties Cameroon Tribune said Thursday June 18 2013 In Central Africa over 8 million tons of plantain and 3 million tons of bananas are produced yearly for a consumer population of 250 million consumers Publication date 22 April 2014 | 08:15 ICT chairman of China Railway Major Bridge Engineering Group Co Ltd general manager of Cambodia Iron & Steel Mining Industry Group shake hands following a signing ceremony in Phnom Penhin 2012 The China Railway Group’s planned $7.5 billion Cambodian north-south railway line has been delayed due to funding shortages Originally slated to begin construction last year told the South China Morning Post that work on the 400-kilometre railway line was on hold due to funding problems The April 9 the Morning Post’s report did not say when construction would begin Part of a larger $9.6 billion agreement signed between China Railway and the Chinese-owned Cambodia Iron and Steel Mining Industry Group the railway is to connect a steel factory to be built in Preah Vihear province in the north to a new port in Koh Kong province on the gulf of Thailand in the south Construction has yet to begin on any part of what would be Cambodia’s largest-ever infrastructure project and little information has been made available from either of the companies involved or the government since the project was announced on December 31 From the iron-ore mining area of Preah Vihear the railway is to pass through the provinces of Kampong Thom Kampong Chhnang and Kampong Speu before reaching the proposed port in Koh Kong Chinese company Union Development Group holds 45,000 hectares of land concessions in Koh Kong It would be difficult for the railway to avoid passing through their holding which includes a golf course and luxury resort But they say they have not been told of any plans to lay tracks on their turf “I don’t think they will build the railway through our concession because until today no one has come to contact us,” the company’s representative Ngou Tieng Lung told the Phnom Penh Post in an interview last month Union Development has not been informed of any progress on the railway by the government The ministry of public works and transport could not be reached for comment yesterday told the Post in March that they too have not received word on the project “I think the company is still in the feasibility study phase because so far I have not received any news from them If they have any update on the project they have to inform us,” he said Pheakavanmony attributed the lack of information to delays in China Railway’s feasibility study brought on by political instability from last year’s national election ADDITIONAL REPORTING BY MAY KUNMAKARA AND DAVID BOYLE Secretaries General of ministries in Cameroon have said they will contribute to ongoing efforts for the implementation the National Malaria Multisectoral Plan in the country The administrators met at a working session in Yaounde on 18th July 2024 to discuss a common goal for malaria elimination in Cameroon by 2035 The meeting was a joint initiative of the Ministry of Public Health, the National Malaria Control Programme, and Impact Santé Afrique. Being the 11th country most affected by Malaria the implementation of the multisectoral plan is expected to reduce the Malaria burden in the country by 75% paving the way for its elimination by 2035 “ We must understand that Malaria is a real challenge for our country and this fight must be wholistic We will try to ensure that our directorate of norms and control is involved in this fight because this is an issue of habitat which is conditioned by key factors such as climate the fight will not be successful,” Paul Tchawa Secretary General of the Ministry of the Environment and Sustainable Development said The National Malaria Multisectoral Plan comes on the heels of the National Plan for the Fight Against Malaria This plan accounted for the reduction of Cameroon’s Malaria prevalence to 11% “ Seeing such personalities in such a meeting gives me hope that these ministries are going to be more committed to this fight against Malaria We want them to tell their Ministers that we need just one percent of their budget to kick out this disease President of the Parliamentary Caucus for Health Financing said Cameroon is the 11th country most affected by Malaria According to recent statistics from the Ministry of Public Health almost  three million cases and nearly 2000 deaths are recorded yearly in Cameroon Malaria also accounts for about 40% of the causes of hospitalization with children under 5 years of age accounting for 68% of deaths According to the National Malaria Control Programme Cameroon’s prevalence should be less than 1% The structure reports a reduction in mortality rates between 2019 and 2023 unfortunately threatened by a new anopheles mosquito “You should have noticed that we have lots of cases of Malaria in the urban areas because there are new anopheles mosquitoes which spread the disease quickly when the environment is favorable,” Olivia Ngou Executive Director of Impact Santé Afrique told CRTV WEB Proper sensitization on malaria prevention techniques in schools churches and other public places are among issues stakeholders are looking to effectively address Stakeholders hope the  multisectoral  Malaria plan will change the tides and significantly contribute to Malaria elimination in Cameroon “The multisectoral framework is  a real guide to multisectoral actions and resource mobilization developed and validated with the participation and consensus of all stakeholders,” Public Health Minister “Today we have a strategic document that guides every sector and permits them understand the activities that they can carry out and it will strongly contribute to the reduction of Malaria,” Olivia Ngou As efforts to implement the plan are  being intensified Manaouda calls on all actors to welcome the new plan and make it a permanent guide for the fight against the disease Cameroon is the first country in West and Central Africa to have set up a multisectoral plan to fight against Malaria Malaria stakeholders and other decision makers will put hands on deck to make the plan a reality in Cameroon They are looking forward to Cameroon’s elimination of Malaria like Cape Verte that just celebrated the elimination of this disease in their country Les champs obligatoires sont indiqués avec * mon e-mail et mon site dans le navigateur pour mon prochain commentaire Δdocument.getElementById( "ak_js_1" ).setAttribute( "value" Macau picked up its first medal at the Asian Games currently being held in Indonesia Wushu athlete Huang Junhua won a gold medal in the men’s Nanquan-Nangun category in the Asian Games 2018 During the competition held yesterday morning Huang scored 9.73 points in the Nangun category 0.03 higher than his earlier score of 9.70 points in the same category A silver medal went to Quoc Khanh Pham from Vietnam and a bronze medal was awarded to Yongmun Lee wushu athlete Harris Horatius failed to secure a medal in the category after he only scored 19.21 points he managed to improve his score to 9.71 points from an earlier 9.50 points A total of 28 gold medals were awarded yesterday more athletes set new records for Macau in swimming and Chou Kit set a new Macau record of 7 minutes and 51 seconds although they failed to advance in the competition You must be logged in to post a comment. Copyright © Macau Daily Times 2008-2022. All Rights Reserved A soldier of the Multinational Force of Central Africa searches a man in Bangui. Photo: Reuters Clashes between Muslims and Christians in Central African Republic’s capital killed three yesterday as angry residents threw grenades and torched homes, witnesses said. French and African troops deployed in the country have struggled to stop the tit-for-tat violence between Muslim Seleka rebels, who seized power in March, and Christian self-defence militia, clashes that killed more than 1,000 people in December. Residents of Bangui said that Seleka forces wearing civilian clothes threw grenades at Christian houses in a northern district of the city, setting them alight. Christian youths then launched reprisal attacks, burning nearby Muslim homes. “The Muslims came and set fire to the houses... Everyone was affected,” said Aristide Yenga, resident of the Ngou Simon neighbourhood in the north of the capital Bangui. “This morning they began shooting and when we heard that we left for the larger (displaced persons’) camps.” The body of a Seleka fighter, with his left hand severed off and missing, lay in the middle of a large avenue following the attacks, a Reuters witness said. A resident of the neighbourhood who asked not to be named said that two other Muslims had been killed there overnight. No peacekeepers were present, although a French helicopterflew overhead, the Reuters witness said. The incidents occurred in the city’s fifth district which houses both Muslims and Christians and near where heavy artillery battles took place the previous two nights. To view comments, please register for free or log in to your account. By EMN 1 (EMN): To mark the National Unity Day (Rashtriya Ekta Diwas) mini marathon race was organised by Police department on October 32 in Noklak Pritpal Kaur said National Unity Day is celebrated every year to mark the birth anniversary of Iron Man of India Sardar Vallabhbhai Patel who played a major role in the integration of India To acknowledge his efforts in uniting the nation India celebrate National Unity Day on his birth anniversary Kaur advised the students and youths to set aim in life He also encouraged them to contribute to the society in whatever way possible He further congratulated all the winners and participants of the mini marathon race and gave away the cash prize and certificates to them second and third prizes respectively while Monglon S and Mutchiu S got consolidation prizes second and third winners respectively while Thongkoi T and Tongzen H got consolation prizes SDO C Phuniang administrated the Rashtriya Ekta Diwas pledge and the programme was chaired by Additional Superintendent of Police Ngou Khiam The mini marathon race started at Government Middle School Junction (Penshe Sector) to GHSS Noklak (High School B Sector) where the prize distribution ceremony was held Participants in the unity run comprised of students The Republic of the Congo has been granted approximately US$ 59M to finance the construction works of the Dolisie-Kibangou road which is located in the department of Niari (in the southern region of the Central African country) This is financial facility was granted by the Development Bank of Central African States (BDEAC) subject to an agreement signed mid-August 2021 between Fortunato-Ofa Mbo Nchama The 93 km long Dolisie-Kibangou road is a part of the Brazzaville-Libreville road which is one of the eleven priority projects of the Regional Economic Program (PER) of the Central African Economic and Monetary Community (CEMAC) The scope of the Dolisie-Kibangou road project also includes the construction of bridges over the Niari and Louvakou rivers as well as the rehabilitation of 53 km of related rural roads the rehabilitation of socio-economic infrastructure the construction of 21 water boreholes along the river axis in Congo and the construction of a forest and wildlife control post in Mila Mila Also Read: Grand Zambi-Kribi Road construction in Cameroon about 84% complete In addition to the Dolisie-Kibangou road section the Brazzaville-Libreville road also includes the construction of the 49 km Ndendé-Doussala section in Gabon and the rehabilitation of the 132 km Ngongo-Kibangou section in Congo Considered as a strategic road project that will contribute to the integration and development of the Central African sub-region the Brazzaville-Libreville road is also listed among the priority achievements of the Gabonese government the latter approved two draft laws relating to borrowing authorizations for a total of US$ 162M for the financing of works related to the construction of the Ndendé-Doussala road section Welcome to Construction Review a portal that serves the building and construction industry through our blog social media presence and print publication Contact us Guest Posting Take down policy