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Miller, P. J.

Publications and source records attributed to Miller, P. J..

2 recordsLinked to original sources

Unsupervised classification of graded animal vocalisations using fuzzy clustering

We present here an unsupervised procedure for the classification of graded animal vocalisations based on Mel frequency cepstral coefficients and fuzzy clustering. Cepstral coefficients compress information about the distribution of energy across the frequency spectrum into a reduced number of variables and are well-defined for signals of various acoustic characteristics (tonal, pulsed, or broadband). In addition, the Mel scale mimics the logarithmic perception of pitch by mammalian ears and is therefore well-suited to defined meaningful perceptual categories for mammals. Fuzzy clustering is a soft classification approach. It does not assign samples to a single category, but rather describes their position relative to overlapping categories. This method is capable of identifying stereotyped vocalisations - vocalisations located in a single category - and graded vocalisations - vocalisation which lie between categories - in a quantitative way. We evaluated the performance of this procedure on a set of long-finned pilot whale (Globicephala melas) calls. We compared our results with a call catalogue previously defined through audio-visual inspection of the calls by human experts. Our unsupervised classification achieved slightly lower precision than the catalogue approach: we described between two and ten fuzzy clusters compared to 11 call types in the catalogue. The fuzzy clustering did not replicate the manual classification. One-to-one correspondence between fuzzy clusters and catalogue call types were rare, however the same sets of call types were consistently grouped together within fuzzy clusters. There were also discrepancies between both classification approaches, with some catalogue call types being consistently spread over several fuzzy clusters. Compared to manual classification, the fuzzy clustering approach proved to be much less time-consuming (days vs. months) and provided additional quantitative information about the graded nature of the vocalisations. We discuss the scope of our unsupervised classifier and the need to investigate the functions of call gradation in future research. Author summaryThere is no consensus on how to describe the vocal repertoire of a species, an essential initial step to analyse how animals rely on different types of vocalisations according to social, ecological, and behavioural contexts. This task is even more challenging for species with graded vocal repertoires: their vocalisations do not fall into distinct categories but form a continuum which makes it difficult to draw strict boundaries between sound types. We present here a method to overcome this challenge using an unsupervised classification algorithm based on Mel frequency cepstral coefficients and fuzzy clustering. It is specifically designed to deal with the graded nature of animal vocalisations, as it can describe overlapping categories in a quantitative way. We tested our classification procedure on a particularly challenging set of long-finned pilot whale (Globicephala melas) calls. Indeed, this species can produce sounds of various acoustic natures (tonal, broadband, and pulsed) and their large vocal repertoire is a mix of stereotyped and highly graded sound types. We compared our results with an existing call catalogue established by human operators. We obtained promising results and recommend similar classification procedures in future studies to take a quantitative approach when studying the gradation of animals vocal repertoires.

animal behavior and cognition↗

Spontaneous selection of Cryptosporidium drug resistance in a calf model of infection

The intestinal protozoan Cryptosporidium is a leading cause of diarrheal disease and mortality in young children. There is currently no fully effective treatment for cryptosporidiosis, which has stimulated interest in anticryptosporidial development over the last [~]10 years with numerous lead compounds identified including several tRNA synthetase inhibitors. In this study, we report the results of a dairy calf efficacy trial of the methionyl-tRNA (CpMetRS) synthetase inhibitor 2093 and the spontaneous emergence of drug resistance. Dairy calves experimentally infected with Cryptosporidium parvum initially improved with 2093 treatment, but parasite shedding resumed in two of three calves on treatment day five. Parasites shed by each recrudescent calf had different amino acid altering CpMetRS mutations, coding either an aspartate 243 to glutamate (D243E) or a threonine 246 to isoleucine (T246I) mutation. Transgenic parasites engineered to have either the D243E or T246I CpMetRS mutation using CRISPR/Cas9 grew normally but were highly 2093 resistant; the D243E and T246I mutant expressing parasites respectively had 2093 EC50S of 613- or 128-fold that of transgenic parasites with wild-type CpMetRS. In studies using recombinant enzymes, the D243E and T246I mutations shifted the 2093 IC50 by >170-fold. Structural modeling of CpMetRS based on an inhibitor-bound Trypanosoma brucei MetRS crystal structure suggested that the resistance mutations reposition nearby hydrophobic residues, interfering with compound binding while minimally impacting substrate binding. This is the first report of naturally emerging Cryptosporidium drug resistance, highlighting the need to address the potential for anticryptosporidial resistance and establish strategies to limit its occurrence. ImportanceCryptosporidium is a leading protozoan cause of diarrhea in young children with no reliable treatment. We report results of a dairy calf drug efficacy trial and the spontaneous emergence of drug resistance. Cryptosporidium parvum infected calves initially improved with drug treatment, but infection relapsed in two animals. Parasites shed by each recrudescent calf had mutations in the gene encoding the drug target that altered its amino acid sequence. Recapitulation of the drug target mutations by CRISPR/Cas9 genome editing resulted in highly drug-resistant parasites, and recombinant mutant enzymes were resistant to inhibition. This is the first report of naturally emerging Cryptosporidium drug resistance. There is a currently a great opportunity to impact public health with new drugs to treat cryptosporidiosis, and this report highlights the need to address the potential for anticryptosporidial resistance and establish strategies to limit its occurrence in order to realize their full potential. One-sentence summaryDrug-target point mutations mediating anticryptosporidial resistance spontaneously arose in the dairy calf C. parvum infection model.

microbiology↗