ABSTRACT
Nausea is a common disease symptom, yet there is no consensus regarding its physiological markers. In contrast, the process of vomiting is well documented as sequential muscular contractions of the diaphragm and abdominal muscles and esophageal shortening. Nausea, like other self-reported perceptions, is difficult to distinguish in preclinical models, but based on human experience emesis is usually preceded by nausea. Here we focused on measuring gastrointestinal and cardiorespiratory changes prior to emesis to provide additional insights into markers for nausea. Felines were instrumented to chronically record heart rate, respiration, and electromyographic (EMG) activity from the stomach and duodenum before and after intragastric delivery of saline or copper sulfate (CuSO4, from 83 to 322 mg). CuSO4 is a prototypical emetic test agent that triggers vomiting primarily by action on GI vagal afferent fibers when administered intragastrically. CuSO4 infusion elicited a significant increase in heart rate, decrease in respiratory rate, and a disruption of gastric and intestinal EMG activity several minutes prior to emesis. The change in EMG activity was most consistent in the duodenum. Administration of the same volume of saline did not induce these effects. Increasing the dose of CuSO4 did not alter the physiologic changes induced by the treatment. It is postulated that the intestinal EMG activity was related to the retrograde movement of chyme from the intestine to the stomach demonstrated to occur prior to emesis by other investigators. These findings suggest that monitoring of intestinal EMG activity, perhaps in combination with heart rate, may provide the best indicator of the onset of nausea following treatments and in disease conditions, including GI disease, associated with emesis.
ABSTRACT
Genome size variation within plant taxa is due to presence/absence variation, which may affect low-copy sequences or genomic repeats of various frequency classes. However, identifying the sequences underpinning genome size variation is challenging because genome assemblies commonly contain collapsed representations of repetitive sequences and because genome skimming studies by design miss low-copy number sequences. Here, we take a novel approach based on k-mers, short sub-sequences of equal length k, generated from whole-genome sequencing data of diploid eyebrights (Euphrasia), a group of plants that have considerable genome size variation within a ploidy level. We compare k-mer inventories within and between closely related species, and quantify the contribution of different copy number classes to genome size differences. We further match high-copy number k-mers to specific repeat types as retrieved from the RepeatExplorer2 pipeline. We find genome size differences of up to 230Mbp, equivalent to more than 20% genome size variation. The largest contributions to these differences come from rDNA sequences, a 145-nt genomic satellite and a repeat associated with an Angela transposable element. We also find size differences in the low-copy number class (copy number ≤ 10×) of up to 27 Mbp, possibly indicating differences in gene space between our samples. We demonstrate that it is possible to pinpoint the sequences causing genome size variation within species without the use of a reference genome. Such sequences can serve as targets for future cytogenetic studies. We also show that studies of genome size variation should go beyond repeats if they aim to characterise the full range of genomic variants. To allow future work with other taxonomic groups, we share our k-mer analysis pipeline, which is straightforward to run, relying largely on standard GNU command line tools.