Biology subjects

McGuire, C.

Publications and source records attributed to McGuire, C..

3 recordsLinked to original sources

bioRxiv2024

Palytoxin Evokes Reversible Spreading Depolarization in the Locust CNS

Spreading depolarization (SD) describes the near-complete depolarization of CNS neural cells as a consequence of chemical, electrical, and metabolic perturbations. It is well-established as the central mechanism underlying insect coma and various mammalian neurological dysfunctions. Despite significant progress in our understanding, the question remains: which cation channel, if any, generates SD in the CNS? Previously, we speculated that the sodium-potassium ATPase (NKA) might function as a large-conductance ion channel to initiate SD in insects, potentially mediated by a palytoxin (PLTX)-like endogenous activator. In the current study, we evaluate the effectiveness and properties of PLTX as an SD initiator in L. migratoria. Whereas bath-applied PLTX failed to ignite SD, direct injection into the neuropil triggered SD in 57% of the preparations. Notably, PLTX-induced SD onset was significantly more rapid compared to ouabain injection and azide controls, though their electrophysiological features remained similar. Furthermore, PLTX-induced SD was recoverable and resulted in a greater frequency of repetitive SD events compared to ouabain. Surprisingly, prior PLTX treatment disrupted the onset and recovery of subsequent SD evoked by other means. PLTX injection could attenuate the amplitude and hasten the onset time of azide-induced SD. Such an effect is associated with a complete inhibition at higher doses of subsequent anoxic SD induced through azide treatment or submersion. These results show that PLTX can trigger repetitive and reversible SD-like events in locusts and simultaneously interfere with anoxic SD occurrence. We suggest that the well-documented NKA pump conversion into an open non-selective cationic channel is a plausible mechanism of SD activation in the locust CNS, warranting additional investigations.

neuroscience↗

bioRxiv2020

Development of non-transgenic glyphosate tolerant wheat by TILLING

Glyphosate (N-phosphonomethyl-glycine) is the worlds most widely used broad spectrum, post-emergence herbicide. It inhibits the chloroplast-targeted enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.19), a component of the plant and microorganism-specific shikimate pathway and a key catalyst in the production of aromatic amino acids. Variants of EPSPS that are not inhibited by glyphosate due to particular amino acid alterations in the active site of the enzyme are known. Some of these variants have been identified in weed species that have developed resistance to glyphosate because of the strong selective pressure of continuous, heavy glyphosate use. We have used TILLING (Targeting Induced Local Lesions in Genomes), a non-transgenic, target-selected, reverse genetics mutation breeding technique, and conventional genetic crosses, to identify and combine, through two rounds of mutagenesis, wheat lines having both T102I and P106S (so-called TIPS enzyme) mutations in both the A and the D sub-genome homoeologous copies of the wheat EPSPS gene. The combined effects of the T102I and P106S mutations are known from previous work in multiple species to minimize the binding of the herbicide while maintaining the affinity of the catalytic site for its native substrates. These novel wheat lines exhibit substantial tolerance to commercially relevant levels of glyphosate.

plant biology↗

bioRxiv2018

Development of reduced gluten wheat enabled by determination of the genetic basis of the lys3a low hordein barley mutant

Celiac disease is the most common food-induced enteropathy in humans with a prevalence of approximately 1% world-wide [1]. It is induced by digestion-resistant, proline- and glutamine-rich seed storage proteins, collectively referred to as \"gluten,\" found in wheat. Related prolamins are present in barley and rye. Both celiac disease and a related condition called non-celiac gluten sensitivity (NCGS) are increasing in incidence [2] [3]. This has prompted efforts to identify methods of lowering gluten in wheat, one of the most important cereal crops. Here we used BSR-seq (Bulked Segregant RNA-seq) and map-based cloning to identify the genetic lesion underlying a recessive, low prolamin mutation (lys3a) in diploid barley. We confirmed the mutant identity by complementing the lys3a mutant with a transgenic copy of the wild type barley gene and then used TILLING (Targeting Induced Local Lesions in Genomes) [4] to identify induced SNPs (Single Nucleotide Polymorphisms) in the three homoeologs of the corresponding wheat gene. Combining inactivating mutations in the three sub-genomes of hexaploid bread wheat in a single wheat line lowered gliadin and low molecular weight glutenin accumulation by 50-60% and increased free and protein-bound lysine by 33%. This is the first report of the combination of mutations in homoeologs of a single gene that reduces gluten in wheat.

plant biology↗