Biology subjects

Alghamdi, A.

Publications and source records attributed to Alghamdi, A..

7 recordsLinked to original sources

bioRxiv2025

Combined TIRF and 3D Super-Resolution Microscopy for Nanoscopic Spatiotemporal Characterization of Adhesion Molecules on Microvilli

The homing of hematopoietic stem/progenitor cells (HSPCs) and leukemic cells is a multistep process governed by complex spatiotemporal interactions between adhesion molecules under shear stress. While the molecular and biological mechanisms of this process have been extensively studied, the precise spatial and temporal organization of adhesion molecules that influences homing efficiency remains relatively poorly understood. In particular, the roles of the cell surface topography and its morphological changes during homing in shaping the spatial organization of adhesion molecules remain elusive. This is partly due to the lack of imaging techniques that simultaneously capture both nanoscopic cell surface morphology and the spatial distribution of the adhesion molecules. Here, we develop a microfluidics-based super-resolution (SR) imaging platform that enables the three-dimensional (3D) mapping of the cell surface morphology and the spatial distribution of the adhesion molecules during HSPC and leukemic cell rolling by integrating total internal reflection fluorescence microscopy (TIRFM) with single-molecule localization microscopy (SMLM). We reconstruct the cell surface morphology, which is critical to the homing, using TIRFM, and precisely overlay the spatial distribution of adhesion molecules, including CD44, PSGL-1, and actin cytoskeleton, determined by 3D-SMLM, on the topographic map. We show distinct nanoscopic localizations of adhesion molecules on the microvilli of HSPCs/leukemic cells and their reorganization under shear stress during cell rolling, at a spatial resolution of approximately 30 nm. The approach offers a powerful means to elucidate the complicated interplay between cell surface morphology and ligand-receptor interactions. TOC graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=106 SRC="FIGDIR/small/672391v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@19e513eorg.highwire.dtl.DTLVardef@e7dd0corg.highwire.dtl.DTLVardef@617295org.highwire.dtl.DTLVardef@1a9ae0a_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2024

Mangrove endophytes enhance yield and convey flooding and salt tolerance to Nipponbare rice

Global climate change increasingly challenges agriculture with flooding and salinity. Among strategies to enhance crop resilience to these stresses, we tested several endophytic bacterial strains from mangroves, which are permanently exposed to flooding and high salinity. We show several strains that can enhance flooding and salinity tolerance in Arabidopsis and rice plants. Two strains and their combination massively enhanced the growth and yield of Oryza sativa cv. Nipponbare under both soil and hydroponic growth conditions with and without salt treatment. The bacteria-induced transcriptome changes in O. sativa roots related to ABA-signaling with lignin and suberin deposition in root tissues explain the altered responses of colonized rice plants to hypoxic and saline stress conditions. While enhancing yield and grain quality, bacterially colonized rice plants also show much earlier flowering, thereby massively shortening the life cycle of rice plants and opening the possibility for an additional harvest per year. These results show that microbes can be a powerful tool for enhancing the yield and resilience of rice to hypoxic and saline stress conditions.

plant biology↗

bioRxiv2022

Landscape-scale exposure to multiazole-resistant Aspergillus fumigatus bioaerosols

We demonstrate country-wide exposures to aerosolized spores of a human fungal pathogen, Aspergillus fumigatus, that has acquired resistance to first line azole clinical antifungal drugs. Assisted by a network of citizen scientists across the United Kingdom, we show that 1 in 20 viable aerosolized spores of this mold are resistant to the agricultural fungicide tebuconazole and 1 in 140 spores are resistant to the four most used azoles for treating clinical aspergillosis infections. Season and proximity to industrial composters were associated with growth of A. fumigatus from air samples, but not with the presence of azole resistance, and hotspots were not stable between sampling periods suggesting a high degree of atmospheric mixing. Genomic analysis shows no distinction between those resistant genotypes found in the environment and in patients, indicating that ~40% (58/150 sequenced genomes) of azole-resistant A. fumigatus infections are acquired from environmental exposures. Due to the ubiquity of this measured exposure, it is crucial that we determine source(s) of azole-resistant A. fumigatus, who is at greatest risk of exposure and how to mitigate these exposures, in order to minimize treatment failure in patients with aspergillosis. One sentence summaryUK-wide citizen science surveillance finds a ubiquitous exposure to aerosolized spores of a human fungal pathogen that have evolved in the environment cross-resistance to essential clinical antifungal drugs

microbiology↗

bioRxiv2021

Age-Related Differences in Reward-Based Modulation of Sequential Reaching Performance

Reward can increase the speed and accuracy of movements in both simple and sequential reaching tasks. Two mechanisms are thought to be responsible for this: an increase in maximum velocity, due to increased muscle stiffness, resulting in faster, but energetically inefficient, individual movements; or coarticulation - the blending of sub-movements into single, smoother, more energetically efficient movements. Older adults have shown reduced sensitivity to reward in decision paradigms, but there is little research relating reward and motor performance in older adults. Using a novel online sequential reaching task, we compared the effects of reward on motor performance between young (18-23 years) and older (65-79 years) participants. We found that movement time decreased across training in all groups, and reward invigorated this decrease in both age groups. This suggests that reward is a viable facilitator of motor performance to compensate for age-related motor decline and has the potential for use in the design of rehabilitation programmes for age-related motor deficits or disease.

neuroscience↗

bioRxiv2021

Citizen-science surveillance of triazole-resistant Aspergillus fumigatus in UK residential garden soils

Compost is an ecological niche for Aspergillus fumigatus due to its role as a decomposer of organic matter and its ability to survive the high temperatures associated with the composting process. Subsequently, composting facilities are associated with high levels of A. fumigatus spores that are aerosolised from compost and cause respiratory illness in workers. In the UK, gardening is an activity enjoyed by individuals of all ages and it is likely that they are being exposed to A. fumigatus spores when handling commercial compost or compost they have produced themselves. In this study, 246 citizen scientists collected 509 soil samples from locations in their garden in the UK, from which were cultured 5,174 A. fumigatus isolates. Of these isolates, 736 (14%) were resistant to tebuconazole: the third most-sprayed triazole fungicide in the UK, which confers cross-resistance to the medical triazoles used to treat A. fumigatus lung infections in humans. These isolates were found to contain the common resistance mechanisms in the A. fumigatus cyp51A gene TR34/L98H or TR46/Y121F/T289A, and less common resistance mechanisms TR34, TR53, TR46/Y121F/T289A/S363P/I364V/G448S and (TR46)2/Y121F/M172I/T289A/G448S. Regression analyses found that soil samples containing compost were significantly more likely to grow susceptible and tebuconazole-resistant A. fumigatus than those that did not, and that compost samples grew significantly higher numbers of A. fumigatus than other samples. ImportanceThese findings highlight compost as a potential health hazard to individuals with pre-disposing factors to A. fumigatus lung infections, and a potential health hazard to immunocompetent individuals who could be exposed to sufficiently high numbers of spores to develop infection. This raises the question of whether compost bags should carry additional health warnings regarding inhalation of A. fumigatus spores, whether individuals should be advised to wear facemasks whilst handling compost or whether commercial producers should be responsible for sterilising compost before shipping. The findings support increasing public awareness of the hazard posed by compost and investigating measures that can be taken to reduce the exposure risk.

microbiology↗

bioRxiv2020

Positively selected modifications in the pore of TbAQP2 allow pentamidine to enter Trypanosoma brucei

Mutations in the Trypanosoma brucei aquaporin AQP2 are associated with resistance to pentamidine and melarsoprol. We show that TbAQP2 but not TbAQP3 was positively selected for increased pore size from a common ancestor aquaporin. We demonstrate that TbAQP2s unique architecture permits pentamidine permeation through its central pore and show how specific mutations in highly conserved motifs affect drug permeation. Introduction of key TbAQP2 amino acids into TbAQP3 renders the latter permeable to pentamidine. Molecular dynamics demonstrates that permeation by dicationic pentamidine is energetically favourable in TbAQP2, driven by the membrane potential, although aquaporins are normally strictly impermeable for ionic species. We also identify the structural determinants that make pentamidine a permeant but exclude most other diamidine drugs. Our results have wide-ranging implications for optimising antitrypanosomal drugs and averting cross-resistance. Moreover, these new insights in aquaporin permeation may allow the pharmacological exploitation of other members of this ubiquitous gene family.

biochemistry↗

bioRxiv2017

The β3-integrin endothelial adhesome regulates microtubule dependent cell migration

Integrin {beta}3 is seen as a key anti-angiogenic target for cancer treatment due to its expression on neovasculature, but the role it plays in the process is complex; whether it is pro- or anti-angiogenic depends on the context in which it is expressed. To understand precisely {beta}3s role in regulating integrin adhesion complexes in endothelial cells, we characterised, by mass spectrometry, the {beta}3- dependent adhesome. We show that depletion of {beta}3-integrin in this cell type leads to changes in microtubule behaviour that control their migration. {beta}3- integrin regulates microtubule stability in endothelial cells through Rcc2/Anxa2 driven control of Rac1 activity. Our findings reveal that angiogenic processes, both in vitro and in vivo, are more sensitive to microtubule targeting agents when {beta}3-integrin levels are reduced.

cell biology↗