Biology subjects

Last, A.

Publications and source records attributed to Last, A..

4 recordsLinked to original sources

bioRxiv2024

Extensive monolayer formation depends on a subpopulation of transplanted human iPSC-derived RPE cells

Loss of the retinal pigment epithelium (RPE) in the eye leads to photoreceptor dysfunction and death causing eventually vision loss. Cell replacement strategies using RPE cells derived in vitro from pluripotent stem cells (PSCs) are currently evaluated as a potential therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function, however, monolayer formation following transplantation of RPE cell suspensions has not been systematically assessed. Using the sodium iodate mouse model of acute RPE depletion, significant increase in monolayer formation capacity of passage (P) 1 vs. P2 human iPSC-derived RPE cells was observed three weeks after transplantation. Transplant-derived monolayers showed characteristic apicobasal polarity, RPE marker expression, phagocytosis function, and preservation of the host outer nuclear layer. The cell surface marker panel CD54+/PSA-NCAM- was identified to enrich for an RPE subpopulation with high potential for monolayer formation following transplantation. Results underline the importance of defining and isolating competent cell subpopulations for successful RPE transplantation.

neuroscience↗

bioRxiv2023

Novel hypervariable erythrocyte surface expressed recombinant proteins show promise as serological markers of exposure to Plasmodium falciparum infection.

Malaria caused by Plasmodium spp. leads to significant morbidity and mortality, particularly in Sub-Saharan African countries with Plasmodium falciparum being the predominant infectious species. The pathogenesis of P. falciparum depends on multiple host and parasitic factors, one of which is the evasion of host immune response due to antigenic variability during the blood stage of infection. The understudied infected erythrocyte expressed protein families STEVOR and RIFIN characterize with antigenic hypervariability and are associated with clinical outcome of the infection and protective acquired immunity based on their topology and localization. We have used two molecular tag methods for successful expression of members of STEVOR and RIFIN protein families as recombinant proteins in E. coli expression system. We have further established the antigenicity of those recombinants and have used Ugandan cohort samples with various P. falciparum infectious status and have compared the seropositivity rate to those recombinants in different age groups against already established short- and long-term markers of infection. We have demonstrated age-dependent immunity acquisition against the tested recombinants, and we have suggested the potential use of STEVOR and RIFIN recombinants as novel markers of P. falciparum infection in serosurveillance. Due to the hypervariability of those protein members we propose that further, more extensive research using a library of expressed variants is needed to strengthen the conclusions made in this study.

immunology↗

bioRxiv2019

Responses of the putative trachoma vector, Musca sorbens, to volatile semiochemicals from human faeces

BackgroundThe putative vector of trachoma, Musca sorbens, prefers to lay its eggs on human faeces on the ground. This study sought to determine whether M. sorbens females were attracted to volatile odours from human faeces in preference to odours from the faeces of other animals, and to determine whether specific volatile semiochemicals mediate selection of the faeces.\n\nMethodology/Principal findingsTraps baited with the faeces of humans and local domestic animals were used to catch flies at two trachoma-endemic locations in The Gambia and one in Ethiopia. At all locations, traps baited with faeces caught more female M. sorbens than control traps baited with soil, and human faeces was the most successful bait compared with soil (mean rate ratios 44.40, 61.40, 10.50 [P<0.001]; 8.17 for child faeces [P=0.004]). Odours from human faeces and some domestic animals were sampled by air entrainment. Extracts of the volatiles from human faeces were tested by coupled gas chromatography-electroantennography with laboratory-reared female M. sorbens. Twelve compounds were electrophysiologically active and tentatively identified by coupled mass spectrometry-gas chromatography, these included cresol, indole, 2-methylpropanoic acid, butanoic acid, pentanoic acid and hexanoic acid.\n\nConclusions/SignificanceIt is possible that some of these volatiles govern the strong attraction of M. sorbens flies to human faeces. If so, a synthetic blend of these chemicals, at the correct ratios, may prove to be a highly attractive lure. This could be used in odour-baited traps for monitoring or control of this species in trachoma-endemic regions.\n\nAuthor summaryMusca sorbens, also known as the Bazaar Fly, visits peoples faces to feed on ocular and nasal discharge. While feeding, M. sorbens can transmit Chlamydia trachomatis, the bacterium that causes the infectious eye disease trachoma. Around 1.9 million people worldwide are visually impaired or blind from this disease. Although it is believed that M. sorbens transmits trachoma, very few studies have looked at ways to control this fly. A large-scale trial has shown that control of fly populations with insecticide reduces active trachoma disease prevalence. Odour-baited traps for the suppression of disease vector populations are an attractive option as there is no widespread spraying of insecticide, however, highly attractive baits are critical to their success. Here we demonstrate that the preference of these flies for breeding in human faeces is probably mediated by odour cues, and we isolate chemicals in the odour of human faeces that cause a response in the antennae of M. sorbens. These compounds may play a role in the specific attractiveness of human faeces to these flies, perhaps by being present in greater amounts or at favourable ratios. These may be developed into a chemical lure for odour-baited trapping to suppress M. sorbens populations.

ecology↗

bioRxiv2019

Perceptions, attitudes and practices towards scabies in communities on the Bijagos Islands, Guinea-Bissau

IntroductionScabies is highly endemic among impoverished populations and has been recently included in the WHOs list of neglected tropical diseases (NTDs). Community support and behavioural changes are essential for the success of control interventions. This study aimed to explore beliefs, prevention attitudes and health care-seeking behaviours towards scabies in the Bijagos Archipelago of Guinea-Bissau. MethodsData were collected through two methods. Community key informants (community members, community health workers, healthcare workers and traditional healers) were interviewed using snowball sampling. A questionnaire covering perceptions, attitudes and practices was administered to community members using random cluster sampling. Thematic analysis of qualitative data was applied to identify themes. Descriptive statistics were used for quantitative data analysis. ResultsThere was a satisfactory awareness about scabies, but perceptions about disease causation and transmission were imprecise. Misconceptions about personal hygiene as the primary measure for scabies prevention were recurrent. Some participants recognised the importance of early treatment to interrupt transmission. Treatment of close contacts was not considered important. Costs were the main determining factor for treatment choice between traditional healer and the local health centre. Late presentation and delayed treatment were common and associated with poverty and stigmatisation. Scabies impaired quality of life by affecting social interactions, health, fitness to work and school attendance. ConclusionsThere is a need to improve education, recognition, management and affordable access to treatment. Community education, healthcare workers training and skin NTDs integrated control programmes should address the challenges highlighted in this study. Authors SummaryScabies is a common skin infection in low income settings. We conducted a study in Guinea-Bissau to explore the knowledge, attitudes and practices about scabies. We conducted interviews with healthcare workers, traditional healers and community members and additionally used an oral-administered questionnaire with a larger sample of community residents. Most individuals had knowledge of scabies and were aware that person to person transmission occurred. However personal and environmental hygiene were both incorrectly identified as particularly important in the transmission of scabies. Cost played a major role in determining where individuals sought care and both poverty and disease associated stigma resulted in delays seeking care. There is a need to improve community and health care worker education about scabies and improve affordable access to treatment.

epidemiology↗