Biology subjects

Call, C.

Publications and source records attributed to Call, C..

3 recordsLinked to original sources

bioRxiv2026

Evolution of the highest fidelity DNA replication systems

DNA mutation on average is deleterious, and evolution generally acts to reduce mutation rates to the limit of natural selection. The limit of natural selection is set by multiple factors, of which effective population size is only one. We consider lethal mutagenesis as an upper bound to mutation rates for any organism, an argument that is congruent with a biophysical context, wherein random mutations are a form of entropy. In this analysis, coding genome size, body mass, generation time, and temperature potentially explain more than 90% of the variation in mutation rate per generation across the Tree of Life. The organisms with larger genomes, longer lifespans and relatively larger body sizes, known and unknown, represent the lineages which have likely evolved novel mechanisms to lower mutation rates, a desirable trait for reducing cancer incidence. Though these variables are largely shared by Petos Paradox, this selective pressure responsible for the evolution of lower mutation rates occurs through germline mutation rate evolution rather than the soma. SignificanceDNA replication varies and is influenced by natural selection. Mutations are usually harmful and contribute to human diseases like cancer, Understanding the evolutionary factors behind DNA replication fidelity may help identify and develop novel strategies to reduce human mutation rates.

molecular biology↗

bioRxiv2026

Cacna1b alternative splicing is linked to associative learning

Voltage-gated CaV2.2 channels are essential for neurotransmitter release throughout the nervous system including areas related to learning and memory like the hippocampus. Previous results have shown that CaV2.2 channels are involved in cognitive processes. However, a link between alternative splicing of the Cacna1b (gene that encodes for CaV2.2) pre-mRNA and cognitive processes has not been described. The Cacna1b pre-mRNA undergoes extensive cell-specific alternative splicing. In this body of work, we focus on the cassette exon 18a. Alternative splicing of exon 18a generates two splice variants, +18a-Cacna1b and {Delta}18a-Cacna1b. Exon 18a encodes a 21-amino acid sequence within the SYNaptic PRotein INTeraction (synprint) site. Splice variants containing exon 18a (+18a-CaV2.2) show reduced cumulative inactivation and increased Ca{superscript 2} current density compared to splice variants lacking exon 18a ({Delta}18a-CaV2.2), suggesting functional specialization. We previously showed that +18a-Cacna1b splice variants are enriched in cholecystokinin-expressing interneurons (CCK+INs). This neuronal type is strongly implicated in associative learning. Therefore, we tested whether alternative splicing of exon 18a contributes to associative learning. To test this hypothesis, we used genetically engineered mice that constitutively express either +18a-Cacna1b (+18a) or {Delta}18a-Cacna1b ({Delta}18a). We first validated that restricted splicing of exon 18a did not alter downstream alternative or constitutive spliced exons in the Cacna1b pre-mRNA, nor total CaV2.2 protein levels. We then performed a comprehensive behavioral analysis that included assessment of associate learning. We found that in the trace fear conditioning task, +18a mice exhibited less freezing during the trace interval in both the acquisition and memory phases compared to WT mice. Whereas {Delta}18a mice showed enhanced freezing during the same intervals relative to WT mice. These bidirectional phenotypes reveal that exon 18a shapes aversive associative learning. Furthermore, exon 18a splicing did not influence spatial working memory, spatial navigation under stress, nociceptive responses in basal and inflammatory conditions, overall locomotion or exploratory behavior. These results suggest that the behavioral impact of exon 18a splicing is highly selective. Together, our findings identify alternative splicing of exon 18a as a molecular contributor to associative learning.

neuroscience↗

bioRxiv2019

Capture and visualization of live Mycobacterium tuberculosis bacilli from tuberculosis bioaerosols

The tuberculosis (TB) pandemic demands urgent interventions such as those designed to interrupt Mycobacterium tuberculosis (Mtb) transmission, a challenge exacerbated by our poor understanding of the events enabling successful transfer of infectious bacilli between hosts. To address this problem, we developed the Respiratory Aerosol Sampling Chamber (RASC), a personal clean-room equipped with high-efficiency filtration and sampling technologies that allow biosafe capture and isolation of particulate matter - including Mtb bacilli - released by patients during natural breathing and (non-induced) cough. Here, we demonstrate the use of DMN-trehalose labelling to detect and quantify live Mtb bacilli among complex bioaerosol samples arrayed in a bespoke nanowell device following capture in the RASC. A pilot study identified Mtb in more than 85 % of known TB patients, improving significantly on previous work which has relied on animal infection and cough sampling to estimate transmission events. Moreover, intra-patient comparisons of bioaerosol and sputum samples indicated that Mtb aerosols likely derive from a compartment other than sputum. These results support the utility of the RASC platform for research aimed at interrupting Mtb transmission, including the non-invasive detection of Mtb-infected individuals who are predicted to contribute to bacillary spread despite the absence of clinical symptoms.

microbiology↗