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Biology subjects

Carmichael, S.

Publications and source records attributed to Carmichael, S..

5 recordsLinked to original sources

Differential Capture Modalities of Insect Traps Produce Contrasting Biodiversity Patterns

Describing insect community and population trends is essential to their conservation. To assess insect populations and communities and identify potential drivers of change in insect populations, we often need to measure in a variety of ways and in a variety of ecosystems. Insect sampling is not standardized: data is frequently collected via different types of insect traps with different targets and modes of capture to sample the insect community. However, different traps may identify contrasting ecological signals, depending on their structure, deployment, and their effective range, and further, these differences may interact with the habitats they are deployed in. Here, we aim to assess the consistency of biodiversity patterns produced from different trapping methods deployed in array across several habitats. We investigated three trapping methods: an ant bait trap, a malaise trap, and a fermentation trap. We deployed these traps in a suburban forested area and at a restored forest. We computed richness and relative abundance of insects captured in each trap and assessed community compositional differences between traps and habitats. We found that each trap type produced differential patterns of richness, abundance, and composition from each other, and these patterns also varied between sites for most trap types. The contrasting patterns observed among traps is likely due to differing effective capture ranges of each trap; traps with smaller effective capture ranges were more sensitive to local habitat conditions than traps with broader effective capture ranges.

ecology↗

Development of a robotic cluster for automated and scalable cell therapy manufacturing

The production of commercial autologous cell therapies such as chimeric antigen receptor T cells requires complex manual manufacturing processes. Skilled labor costs and challenges in manufacturing scale-out have contributed to high prices for these products. Here, we present a robotic system that uses industry-standard cell therapy manufacturing equipment to automate the steps involved in cell therapy manufacturing. The robotic cluster consists of a robotic arm and customized modules, allowing the robot to manipulate a variety of standard cell therapy instruments and materials such as incubators, bioreactors, and reagent bags. This system enables existing manual manufacturing processes to be rapidly adapted to robotic manufacturing, without having to adopt a completely new technology platform. Proof-of-concept for the robotic clusters expansion module was demonstrated by activating and expanding human CD8+ T cells. The robotic cultures showed comparable cell yields, viability, and identity to those manually performed. Such modular robotic solutions may support scale-up and scale-out of cell therapies that are developed using classical manual methods in academic laboratories and biotechnology companies.

bioengineering↗

Spatial point pattern analysis identifies mechanisms shaping the skin parasite landscape in Leishmania donovani infection

Increasing evidence suggests that infectiousness of hosts carrying parasites of the Leishmania donovani complex, the causative agents of visceral leishmaniasis, is linked to parasite repositories in the host skin. However, a detailed understanding of the dispersal and dispersion of these obligatory-intracellular parasites and their host phagocytes in the skin is lacking. Using endogenously fluorescent parasites as a proxy, we apply image analysis combined with spatial point pattern models borrowed from ecology to characterize dispersion of parasitized myeloid cells (including ManR+ and CD11c+ cells) and predict dispersal mechanisms in a previously described immunodeficient model of L. donovani infection. Our results suggest that after initial seeding of infection in the skin, heavily parasite-infected myeloid cells are found in patches that resemble innate granulomas. Spread of parasites from these initial patches subsequently occurs through infection of recruited myeloid cells, ultimately leading to self-propagating networks of patch clusters. This combination of imaging and ecological pattern analysis to identify mechanisms driving the skin parasite landscape offers new perspectives on myeloid cell behavior following parasitism by L. donovani and may also be applicable to elucidating the behavior of other intracellular tissue-resident pathogens and their host cells.

microbiology↗

The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity

SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and in vitro replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics.

microbiology↗

Variable bites and dynamic populations; new insights in Leishmania transmission

Leishmaniasis is a neglected tropical disease which kills an estimated 50000 people each year, with its deadly impact confined mainly to lower to middle income countries. Leishmania parasites are transmitted to human hosts by sand fly vectors during blood feeding. Recent experimental work shows that transmission is modulated by the patchy landscape of infection in the hosts skin, and the parasite population dynamics within the vector. Here we assimilate these new findings into a simple probabilistic model for disease transmission which replicates recent experimental results, and assesses their relative importance. The results of subsequent simulations, describing random parasite uptake and dynamics across multiple blood meals, show that skin heterogeneity is important for transmission by short-lived flies, but that for longer-lived flies with multiple bites the population dynamics within the vector dominate transmission probability. Our results indicate that efforts to reduce fly lifespan beneath a threshold of around two weeks may be especially helpful in reducing disease transmission.

systems biology↗