Biology subjects

Shiau, J.

Publications and source records attributed to Shiau, J..

5 recordsLinked to original sources

bioRxiv2026

Impact of thermal variation on the transcriptome of Plasmodium falciparum infected Anopheles stephensi

Temperature is a key determinant of malaria transmission, influencing both parasite development and mosquito physiology, yet the underlying mechanisms remain poorly understood. Here, we examined how temperature and time modulate gene expression in Anopheles stephensi infected with Plasmodium falciparum. Using RNA-sequencing over 1-19 days post-blood meal and three temperature regimes (20, 24, and 28{degrees}C with diurnal fluctuations of 9{degrees}C), we characterize transcriptome responses to infection with P. falciparum at the site of infection in the midgut, and systemically, in the carcasses. Oocyst prevalence and density declined over the thermal gradient, albeit with distinct, non-linear temporal dynamics in parasite development rates. Although infection contributed minimally to global variation in gene expression relative to temperature and time, infection-associated genes in the midgut showed coordinated transcriptional responses enriched in canonical Plasmodium associated extracellular, proteolytic, immune, and metabolic functions; notably, decline in oocyst infections in the midguts over the thermal gradient was reflected in reduced expression of immune genes known to regulate P. falciparum. Network analysis demonstrated that these genes participate in a significantly interconnected protein-protein interaction network, within which a small number of high betweenness centrality proteins act as bottlenecks linking immune, metabolic, reproductive and behavioral processes. Our results suggest responses to infection may be mediated through coordinated physiological networks rather than large-scale transcriptional changes. Our findings also indicate that differences in thermal conditions may be an important factor when comparing mechanisms of vector- parasite interactions between Plasmodium species. Together, our results highlight the importance of integrating thermal context into mechanistic studies of vector-parasite interactions.

ecology↗

bioRxiv2024

Protamine Protects Against Vancomycin Induced Kidney Injury

IntroductionVancomycin causes kidney injury by accumulating in the proximal tubule, likely mediated by megalin uptake. Protamine is a putative megalin inhibitor that shares binding sites with heparin and is approved for heparin overdose in patients. MethodsWe employed a well characterized Sprague Dawley rat model to assess kidney injury and function in animals that received vancomycin, protamine alone, or vancomycin plus protamine over 5 days. Urinary KIM-1 was used as the primary measure for kidney injury while iohexol clearance was calculated to assess kidney function. Animals had samples drawn pre-treatment to serve as their own controls. Additionally, since protamine is not a known nephrotoxin, the protamine group also served as a control. Cellular inhibition studies were performed to assess the ability of protamine to inhibit OAT1, OAT3, and OCT2. ResultsRats that received vancomycin had significantly increased urinary KIM-1 on day 2 (24.9 ng/24h, 95% CI 1.87 to 48.0) compared to the protamine alone group. By day 4, animals that received protamine with vancomycin had urinary KIM-1 amounts that were elevated compared to protamine alone (KIM-1 29.0 ng/24h, 95% CI 5.0 to 53.0). No statistically significant differences were identified for iohexol clearance changes between drug groups or when comparing clearance change from baseline (P>0.05). No substantial inhibition of OAT1, OAT3, or OCT2 was observed with protamine. IC50 values for protamine were 1e-4 M for OAT1 and OAT3 and 4.3e-5 M for OCT2. ConclusionProtamine, when added to vancomycin therapy, delays vancomycin induced kidney injury as defined by urinary KIM-1 in the rat model by one to three days. Protamine putatively acts through blockade of megalin and does not appear to have significant inhibition on OAT1, OAT3, or OCT2. Since protamine is an approved FDA medication, it has clinical potential as a therapeutic to reduce vancomycin related kidney injury; however, greater utility may be found by pursuing compounds with fewer adverse event liabilities.

pharmacology and toxicology↗

bioRxiv2022

Direct type I Interferon signaling in hepatocytes control malaria

Malaria is a devastating disease impacting over half of the worlds population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has remained unresolved, preventing the manipulation of such responses to combat malaria. Utilizing transcriptomics, infection studies, and a novel transgenic Plasmodium strain that exports and traffics Cre recombinase, we show that direct type I IFN signaling in Plasmodium-infected hepatocytes is necessary and sufficient to control malaria. We also show that the majority of infected hepatocytes naturally eliminate Plasmodium infection, revealing the potential existence of anti-malarial cell-autonomous immune responses in such hepatocytes. These discoveries challenge the existing paradigms in Plasmodium immunobiology and are expected to inspire new anti-malarial drugs and vaccine strategies.

immunology↗

bioRxiv2019

Microclimate and larval habitat density predict adult Aedes albopictus abundance in urban areas

The Asian tiger mosquito, Aedes albopictus, transmits several arboviruses of public health importance, including chikungunya and Zika. Since its introduction to the United States in 1985, the species has invaded over forty states, including temperate areas not previously at risk of Aedes-transmitted arboviruses. Mathematical models incorporate climatic variables in predictions of site-specific Ae. albopictus abundances to identify human populations at risk of disease. However, these models rely on coarse resolutions of environmental data that may not accurately represent the climatic profile experienced by mosquitoes in the field, particularly in climatically-heterogeneous urban areas. In this study, we pair field surveys of larval and adult Ae. albopictus mosquitoes with site-specific microclimate data across a range of land use types to investigate the relationships between microclimate, density of larval habitat, and adult mosquito abundance and determine whether these relationships change across an urban gradient. We find no evidence for a difference in larval habitat density or adult abundance between rural, suburban, and urban land classes. Adult abundance increases with increasing larval habitat density, which itself is dependent on microclimate. Adult abundance is strongly explained by microclimate variables, demonstrating that theoretically derived, lab-parameterized relationships in ectotherm physiology apply to the field. Our results provide support for the continued use of temperature-dependent models to predict Ae. albopictus abundance in urban areas.

ecology↗

bioRxiv2018

Cryogenically preserved RBCs support gametocytogenesis of Plasmodium falciparum in vitro and gametogenesis in mosquitoes.

BackgroundThe malaria Eradication Research Agenda (malERA) has identified human-to-mosquito transmission of Plasmodium falciparum as a major target for eradication. The cornerstone for identifying and evaluating transmission in the laboratory is small membrane feeding assays (SMFAs) where mature gametocytes of P. falciparum generated in vitro are offered to mosquitoes as part of a blood-meal. However, propagation of \"infectious\" gametocytes requires 10-12 days with considerable physico-chemical demands imposed on host RBCs and thus, \"fresh\" RBCs that are [≤]1-week old post-collection are generally recommended. However, in addition to the costs, physico-chemical characteristics unique to RBC donors may confound reproducibility and interpretation of SMFAs. Cryogenic storage of RBCs (cryo-preserved RBCs herein) is approved by the European and US FDAs as an alternative to refrigeration (4{degrees}C) for preserving RBC quality and while cryo-preserved RBCs have been used for in vitro cultures of other Plasmodia and the asexual stages of P. falciparum, none of the studies required RBCs to support parasite development for >4 days.\n\nResultsUsing the standard laboratory strain, P. falciparum NF54, we first demonstrate that cryo-preserved RBCs preserved in the gaseous phase of liquid nitrogen and thawed after storage for 1, 4, 8 and 12 weeks, supported gametocytogenesis in vitro and subsequent gametogenesis in Anopheles stephensi mosquitoes. Using data from 11 SMFAs and RBCs from 4 separate donors with 3 donors re-tested following various periods of cryo-preservation, we show that overall levels of sporogony in the mosquito, as measured by oocyst prevalence and burdens in the midguts and sporozoites in salivary glands, were similar or better than using [≤]1-week old refrigerated RBCs. Additionally, the potential for cryo-preserved RBCs to serve as a universal substrate for SMFAs is shown for a Cambodian isolate of P. falciparum.\n\nConclusionsConsidering the suitability of cryo-preserved RBCs for P. falciparum SMFAs, we suggest guidelines for their use and how they can be integrated into an existing laboratory/insectary framework with the potential to significantly reduce running costs and provide greater reliability. Finally, we discuss scenarios where cryo-preserved RBCs may be especially useful in enhancing our understanding and/or providing novel insights into the patterns and process underlying human-to-mosquito transmission.

microbiology↗