Biology subjects

Cliffe, R.

Publications and source records attributed to Cliffe, R..

3 recordsLinked to original sources

bioRxiv2024

Host specificity of gastrointestinal parasites in free-ranging sloths from Costa Rica

The diversity and host specificity of gastrointestinal parasites infecting free-ranging sloths is poorly known. We characterized gastrointestinal parasites of two sloth species from Costa Rica-- three-fingered sloth (Bradypus variegatus) and two-fingered sloth (Choloepus hoffmanni)--for the first time in both a primary forest and an urban habitat. We asked whether host-parasite interactions were predominantly structured by host identity, the habitats in which hosts occurred, or both. Protozoa and nematode eggs were present in both species, but cestode eggs were recorded only in C. hoffmanni. We found eight parasitic morphotypes, which matches the total number of parasite taxa described in sloths over the past 100 years, and these first reports of gastrointestinal parasites of sloths from primary forest radically expand our knowledge of the general diversity and host specificity of sloth parasites. We found no significant difference in overall parasite richness between sloth species or habitats, but the parasite richness of C. hoffmanni was 2-fold greater in the primary forest vs. urban habitat. As no parasite sharing was observed between sloth species, we found strong and significant differences in parasite composition between host species regardless of habitat. In B. variegatus, we observed eggs of four nematode taxa (Spirocercidae, Subuluroidea, Spirurida, Ascaridida) and cysts of Eimeriidae (Apicomplexa). By contrast, in C. hoffmanni, we observed cestodes (Anoplocephalidae), a different nematode from the family Spirocercidae and also cysts of Eimeriidae (Apicomplexa). Many rare taxa were recorded only in samples from the primary forest, and these did not match any sloth parasites that had been previously described in the literature, suggesting that at least some could be undescribed species. Together, these results highlight the need for further research in comparative wildlife parasitology, the characterization of host-parasite transmission networks, and the identification of any intermediate hosts that may be relevant to sloth health.

ecology↗

bioRxiv2019

ThX - A next-generation probe for the early detection of amyloid aggregates

Neurodegenerative diseases such as Alzheimers and Parkinsons are associated with protein misfolding and aggregation. Recent studies suggest that the small, rare and heterogeneous oligomeric species, formed early on in the aggregation process, may be a source of cytotoxicity. Thioflavin T (ThT) is currently the gold-standard fluorescent probe for the study of amyloid proteins and aggregation processes. However, the poor photophysical and binding properties of ThT impairs the study of oligomers. To overcome this challenge, we have designed Thioflavin X, (ThX), a next-generation fluorescent probe which displays superior properties; including a 5-fold increase in brightness and 7-fold increase in binding affinity to amyloidogenic proteins. As an extrinsic dye, this can be used to study unique structural amyloid features both in bulk and on a single-aggregate level. Furthermore, ThX can be used as a super-resolution imaging probe in single-molecule localisation microscopy. Finally, we demonstrate that ThX can be used to detect a distinct oligomeric species, not observed via traditional ThT imaging.

biophysics↗

bioRxiv2018

Filamentous aggregates are fragmented by the proteasome holoenzyme

Filamentous aggregates (fibrils) are regarded as the final stage in the assembly of amyloidogenic proteins and are formed in many neurodegenerative diseases. Accumulation of aggregates occurs as a result of an imbalance between their formation and removal. Although there have been numerous studies of the aggregation process in vitro, far fewer studies of aggregate disassembly and degradation are available. Here we use single-aggregate imaging to show that large fibrils assembled from full-length tau are substrates of the 26S proteasome holoenzyme, which fragments them into small aggregates. TEM further revealed that these small aggregate species had no distinct structure. The intact proteasome holoenzyme is required to effectively target fibrils. Interestingly, while degradation of monomeric tau was not inhibited by ATP{gamma}S, fibril fragmentation was predominantly dependent on the ATPase activity of the proteasome. The proteasome holoenzyme was also found to target fibrils assembled from -synuclein (S), suggesting that its fibril fragmenting function may be a general mechanism. The fragmented species produced by the proteasome showed significant toxicity to human cell lines compared to intact fibrils. Together, our results indicate that the proteasome holoenzyme possesses a novel fragmentation function that disassembles large fibrils into smaller and more cytotoxic species.

biophysics↗