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Background In Alibori and Donga, two departments of high malaria incidence of Northern Benin, pirimiphos-methyl, mixture deltamethrin + clothianidin, as well as clothianidin were used at large scale for IRS. The present study aimed to assess the residual efficacy of these products. Methods Immatures of Anopheles gambiae sensu lato ( s.l .) collected in the communes of Kandi and Gogounou (Department of Alibori), Djougou and Copargo (Department of Donga) were reared until adulthood. Females aged 2–5 days were used for susceptibility tube tests following the WHO protocol. The tests were conducted with deltamethrin (0.05%), bendiocarb (0.1%), pirimiphos-methyl (0.25%) and clothianidin (2% weight per volume). For cone tests performed on cement and mud walls, the An. gambiae Kisumu susceptible strain was used. After the quality control of the IRS performed 1-week post-campaign, the evaluation of the residual activity of the different tested insecticides/mixture of insecticides was conducted on a monthly basis. Results Over the three study years, deltamethrin resistance was observed in all the communes. With bendiocarb, resistance or possible resistance was observed. In 2019 and 2020, full susceptibility to pirimiphos-methyl was observed, while possible resistance to the same product was detected in 2021 in Djougou, Gogounou and Kandi. With clothianidin, full susceptibility was observed 4–6 days post-exposure. The residual activity lasted 4–5 months for pirimiphos-methyl, and 8–10 months for clothianidin and the mixture deltamethrin + clothianidin. A slightly better efficacy of the different tested products was observed on cement walls compared to the mud walls. Conclusion Overall, An. gambiae s.l. was fully susceptible to clothianidin, while resistance/possible resistance was observed the other tested insecticides. In addition, clothianidin-based insecticides showed a better residual activity compared to pirimiphos-methyl, showing thus their ability to provide an improved and prolonged control of pyrethroid resistant vectors.

Background Malaria is a public health problem in the Brazilian Amazon region. In integrated vector management for malaria (anopheline) control, indoor residual spraying (IRS) represents one of the main tools in the basic strategy applied in the Amazonian states. It is essential to understand the residual efficacy of insecticides on different surfaces to determine spray cycles, ensure their rational use, and prevent wastage. This study aimed to evaluate the residual efficacy of six insecticide formulations used in the National Malaria Control Programme on four different types of walls in a field simulation at a “test house”. Methods The tests were performed as a field-simulating evaluation at a “test house” built in the municipality of Macapá. Six insecticide formulations comprising four pyrethroids, a carbamate, and an organophosphate were used, and evaluated when applied on different wall surfaces: painted wood, unpainted wood, plastered cement, and unplastered cement. The insecticides were applied to the interior walls of the “test house” by a trained technician. Results In the bioassays performed with pyrethroids, deltamethrin water-dispersible granules (WG) performed particularly well, presenting residual bioefficacy of 8 months on both wood surfaces after the IRS, whereas alpha-cypermethrin suspension concentrate (SC) and etofenprox wettable powder (WP) demonstrated residual bioefficacy of 4 months on at least one of the wood surfaces; however, the pyrethroid lambda-cyhalothrin WP showed a low residual bioefficacy (< 3 months) on all tested surfaces, demonstrating its inefficiency for areas with a long transmission cycle of malaria. For the carbamate-bendiocarb WP, residual bioefficacy for 3 months was achieved only on wood surfaces. In general, the organophosphate pirimifos-methyl capsule suspension (CS) demonstrated the best result, with a mortality rate < 80% over a period of 6 months on all surfaces tested. Conclusion Insecticide efficiency varies among different types of surface; therefore, a “test house” is a valuable evaluation tool. This work highlights the usefulness of associating the residual efficacy of insecticides on the surfaces commonly found in houses in endemic areas, together with knowledge about the transmission cycle duration of the transmission cycle and the insecticide susceptibility of the vector. This association helps in the decision-making for the malaria control intervention regarding.

Background Residual efficacy of indoor residual spray may vary with different spray quality and wall surfaces types. This study evaluated the impact of spray quality and wall surface types on residual efficacy of propoxur against wild Anopheles gambiae sensu lato (s.l.) in southwest Ethiopia. Methods Thirty houses of different mud wall surfaces (10 smooth, 10 rough, 10 painted) were selected and randomly allocated into routine and standard spray. The routine spray was conducted by district health office as usual, while the standard spray was done by strictly following guidelines. Three control houses were selected from unsprayed nearby semi-urban. Wild An. gambiae s.l. were used for wall bioassay tests. Two-way mixed model analysis of variance was used to analyse the data. The mean variation between wall and spray types was compared by post hoc analysis of IBM SPSS version 20. Results On standard spray, knockdown rate was 95.3% on painted, 82% on smooth and 72.5% on rough surface at week 17 of post-spray, whereas on routine spray it was 82.7% on painted, 48.7% on smooth and 60% on rough surface. On standard spray, mortality rate of An. gambiae s.l. was 99.3% on painted surface, 90% on smooth and 80% on rough surface. On routine spray, it was 89.3% on painted, 61.3% on smooth and 65% on rough surface at week 17 of post-spray. The painted wall surface showed the highest knockdown rate (86.4–100%) on standard and (73.8–91.5%) routine spray; mortality rate was more than 80% on both spray types during the 17 weeks of follow-up regardless of spray types. The lower mortality rate and residual effect was observed on routine smooth and rough wall surfaces. The residual efficacy of propoxur was > 80% at week 17 on standard spray regardless of the wall types and it was < 80% on routine spray except painted wall surface. Conclusion The painted wall surface and standard spray showed better residual efficacy. Therefore, it is recommended to consider the wall surface available in the community to estimate the residual lifespan of the insecticide, and strictly to follow the spray guideline to improve the effectiveness of indoor residual spray.

During the course of fungal infection, pathogen recognition by the innate immune system is critical to initiate efficient protective immune responses. The primary event that triggers immune responses is the binding of Pattern Recognition Receptors (PRRs), which are expressed at the surface of host immune cells, to Pathogen-Associated Molecular Patterns (PAMPs) located predominantly in the fungal cell wall. Most fungi have mannosylated PAMPs in their cell walls and these are recognized by a range of C-type lectin receptors (CTLs). However, the precise spatial distribution of the ligands that induce immune responses within the cell walls of fungi are not well defined. We used recombinant IgG Fc-CTLs fusions of three murine mannan detecting CTLs, including dectin-2, the mannose receptor (MR) carbohydrate recognition domains (CRDs) 4-7 (CRD4-7), and human DC-SIGN (hDC-SIGN) and of the β-1,3 glucan-binding lectin dectin-1 to map PRR ligands in the fungal cell wall of fungi grown in vitro in rich and minimal media. We show that epitopes of mannan-specific CTL receptors can be clustered or diffuse, superficial or buried in the inner cell wall. We demonstrate that PRR ligands do not correlate well with phylogenetic relationships between fungi, and that Fc-lectin binding discriminated between mannosides expressed on different cell morphologies of the same fungus. We also demonstrate CTL epitope differentiation during different phases of the growth cycle of Candida albicans and that MR and DC-SIGN labelled outer chain N-mannans whilst dectin-2 labelled core N-mannans displayed deeper in the cell wall. These immune receptor maps of fungal walls of in vitro grown cells therefore reveal remarkable spatial, temporal and chemical diversity, indicating that the triggering of immune recognition events originates from multiple physical origins at the fungal cell surface.

The cell wall peptidoglycan of Gram-positive bacteria functions as a surface organelle for the transport and assembly of proteins that interact with the environment, in particular, the tissues of an infected host. Signal peptide-bearing precursor proteins are secreted across the plasma membrane of Gram-positive bacteria. Some precursors carry C-terminal sorting signals with unique sequence motifs that are cleaved by sortase enzymes and linked to the cell wall peptidoglycan of vegetative forms or spores. The sorting signals of pilin precursors are cleaved by pilus-specific sortases, which generate covalent bonds between proteins leading to the assembly of fimbrial structures. Other precursors harbour surface (S)-layer homology domains (SLH), which fold into a three-pronged spindle structure and bind secondary cell wall polysaccharides, thereby associating with the surface of specific Gram-positive microbes. Type VII secretion is a non-canonical secretion pathway for WXG100 family proteins in mycobacteria. Gram-positive bacteria also secrete WXG100 proteins and carry unique genes that either contribute to discrete steps in secretion or represent distinctive substrates for protein transport reactions.

Surface layers (S-layers) are highly ordered coats of proteins localized on the cell surface of many bacterial species. In these structures, one or more proteins form elementary units that self-assemble into a crystalline monolayer tiling the entire cell surface. Here, the cell envelope of the radiation-resistant bacterium Deinococcus radiodurans was studied by cryo-electron microscopy, finding the crystalline regularity of the S-layer extended into the layers below (outer membrane, periplasm, and inner membrane). The cell envelope appears to be highly packed and resulting from a three-dimensional crystalline distribution of protein complexes organized in close continuity yet allowing a certain degree of free space. The presented results suggest how S-layers, at least in some species, are mesoscale assemblies behaving as structural and functional scaffolds essential for the entire cell envelope.

The bacterium Staphylococcus aureus is an important cause of skin infections and is also associated with the occurrence and severity of eczema. Langerhans cells (LCs), a specific subset of skin immune cells, participate in the immune response to S. aureus , but it is yet unclear how LCs recognize S. aureus . Therefore, we investigated the molecular mechanism underlying the interaction between LCs and S. aureus . We identified that wall teichoic acid, an abundant polymer on the S. aureus surface, is recognized by langerin, a receptor unique to LCs. This interaction allows LCs to discriminate S. aureus from other related staphylococcal species and initiates a proinflammatory response similar to that observed in patients with eczema. Our data therefore provide important new insights into the relationship between S. aureus , LCs, and eczema. Staphylococcus aureus is a major cause of skin and soft tissue infections and aggravator of the inflammatory skin disease atopic dermatitis (AD [eczema]). Epicutaneous exposure to S. aureus induces Th17 responses through skin Langerhans cells (LCs), which paradoxically contribute to host defense but also to AD pathogenesis. The molecular mechanisms underlying the interaction between S. aureus and LCs are poorly understood. Here we demonstrate that human LCs directly interact with S. aureus through the pattern recognition receptor langerin (CD207). Human, but not mouse, langerin interacts with S. aureus through the conserved β- N- acetylglucosamine (GlcNAc) modifications on wall teichoic acid (WTA), thereby discriminating S. aureus from other staphylococcal species. Importantly, the specific S. aureus WTA glycoprofile strongly influences the level of proinflammatory cytokines that are produced by in vitro -generated LCs. Finally, in a murine epicutaneous infection model, S. aureus strongly upregulated transcripts of Cxcl1 , Il6 , and Il17 , which required the presence of both human langerin and WTA β-GlcNAc. Our findings provide molecular insight into the unique proinflammatory capacities of S. aureus in relation to skin inflammation. IMPORTANCE The bacterium Staphylococcus aureus is an important cause of skin infections and is also associated with the occurrence and severity of eczema. Langerhans cells (LCs), a specific subset of skin immune cells, participate in the immune response to S. aureus , but it is yet unclear how LCs recognize S. aureus . Therefore, we investigated the molecular mechanism underlying the interaction between LCs and S. aureus . We identified that wall teichoic acid, an abundant polymer on the S. aureus surface, is recognized by langerin, a receptor unique to LCs. This interaction allows LCs to discriminate S. aureus from other related staphylococcal species and initiates a proinflammatory response similar to that observed in patients with eczema. Our data therefore provide important new insights into the relationship between S. aureus , LCs, and eczema.

The present study explores the effectiveness of powder mixed electrical discharge machining (PM-EDM) by utilizing the unique properties of multi-walled carbon nanotubes (MWCNTs) on machining of hard-grade medical alloy (β-type titanium). To investigate the capabilities of the PM-EDM in terms of machinability, biocompatibility, tribological characteristics and surface integrity, the experiments were conducted according to the L18 orthogonal array. The analysis of variance (ANOVA) technique was employed for identifying the significant process parameters affecting metal removal rate (MRR). The ANOVA results revealed that the dielectric medium was the most significant factor that majorly affects the MRR (63.25 mm 3 /mm) and it was followed by the peak current ( I p ), pulse on ( p on ), pulse off ( p off ) and electrode material. A 15A peak current at pulse-on/pulse-off time of 100/20 μs by using MWCNTs in the dielectric medium with a tungsten/copper tool electrode is the optimum parametric set. The biocompatibility of machined surfaces was scrutinized by cytotoxicity test which confirmed that the machining with MWCNTs elevated the biological responses of reformed surface and contributed to achieve the cell viability of 94%. The pin-on-disc wear results revealed that MWCNTs machined surface had the least value of wear rate and acted as a low frictional surface. Also, the recast layer produced after MWCNTs machining adhered strongly to the base material and exhibited twofold adhesion strength as compared to the water machined substrate. The formation of oxides and carbides in the presence of MWCNTs entities contributed to the tribological behaviour and biocompatibility of alloy. Thus, the excellent assets of MWCNTs elevate the potential of EDMing by diminishing the bottlenecks like the creation of surface defects in conventional EDM (deionized water medium) at high discharge energies.

Background As highly-conserved types of lipid flippases among fungi, P4-ATPases play a significant role in various cellular processes. Cdc50 acts as the regulatory subunit of flippases, forming heterodimers with Drs2 to translocate aminophospholipids. Cdc50 homologs have been reported to be implicated in protein trafficking, drug susceptibility, and virulence in Saccharomyces cerevisiae , Candida albicans and Cryptococcus neoformans . It is likely that Cdc50 has an extensive influence on fungal cellular processes. The present study aimed to determine the function of Cdc50 in Candida glabrata by constructing a Δcdc50 null mutant and its complemented strain. Results In Candida glabrata , the loss of Cdc50 led to difficulty in yeast budding, probably caused by actin depolarization. The Δcdc50 mutant also showed hypersensitivity to azoles, caspofungin, and cell wall stressors. Further experiments indicated hyperactivation of the cell wall integrity pathway in the Δcdc50 mutant, which elevated the major cell wall contents. An increase in exposure of β-(1,3)-glucan and chitin on the cell surface was also observed through flow cytometry. Interestingly, we observed a decrease in the phagocytosis rate when the Δcdc50 mutant was co-incubated with THP-1 macrophages. The Δ cdc50 mutant also exhibited weakened virulence in nematode survival tests. Conclusion The results suggested that the lipid flippase subunit Cdc50 is implicated in yeast budding and cell wall integrity in C. glabrata , and thus have a broad influence on drug susceptibility and virulence. This work highlights the importance of lipid flippase, and offers potential targets for new drug research.