Biology subjects

Grant, J. E.

Publications and source records attributed to Grant, J. E..

3 recordsLinked to original sources

bioRxiv2026

Waltz, AlphaFold and ESMfold Predictions on a Human Prion Protein Tiled Peptide Library Highlight a C-Terminal Region with Strong Conformational Sensitivity

Short, linear sequence motifs within the human prion protein (PrP) may encode local aggregation tendencies that are not apparent from full-length sequence analysis. To map intrinsic amyloidogenic potential across PrP, we generated a complete one-residue-step library of overlapping 15-mer peptides from the 253-residue human PrP sequence and evaluated each peptide using WALTZ in both high-specificity and best-overall-performance modes, with full-length SNPeffect4/WALTZ output used for comparison. Peptide-level WALTZ analysis identified several candidate amyloidogenic regions, including an N-terminal signal-peptide segment spanning approximately residues 8-21/22 that was not detected in the publicly available full-length WALTZ/SNPeffect4 output. Predictions made using AlphaFold 3.0 also identified a short C-terminal area whose representative peptides formed either -helix or pair of {beta}-strands, indicating a region of potential higher susceptibility to conformational dynamics. This computational study supports the use of peptide tiling as a complementary screening strategy for identifying candidate short aggregation-prone motifs in PrP and other misfolding-associated proteins.

biochemistry↗

bioRxiv2021

Cortical dopamine reduces the impact of motivational biases governing automated behaviour

Motivations shape our behaviour: the promise of reward invigorates, while in the face of punishment, we hold back. Abnormalities of motivational processing are implicated in clinical disorders characterised by excessive habits and loss of top-down control, notably substance and behavioural addictions. Striatal and frontal dopamine have been hypothesised to play complementary roles in the respective generation and control of these motivational biases. However, while dopaminergic interventions have indeed been found to modulate motivational biases, these previous pharmacological studies used regionally non-selective pharmacological agents. Here, we tested the hypothesis that frontal dopamine controls the balance between Pavlovian, bias-driven automated responding and instrumentally learned action values. Specifically, we examined whether selective enhancement of cortical dopamine either (i) enables adaptive suppression of Pavlovian control when biases are maladaptive; or (ii) non-specifically modulates the degree of bias-driven automated responding. Healthy individuals (n=35) received the catechol-o-methyltransferase (COMT) inhibitor tolcapone in a randomized, double-blind, placebo-controlled cross-over design, and completed a motivational Go NoGo task known to elicit motivational biases. In support of hypothesis (ii), tolcapone globally decreased motivational bias. Specifically, tolcapone improved performance on trials where the bias was unhelpful, but impaired performance in bias-congruent conditions. These results indicate a non-selective role for cortical dopamine in the regulation of motivational processes underpinning top-down control over automated behaviour. The findings have direct relevance to understanding neurobiological mechanisms underpinning addiction and obsessive-compulsive disorders, as well as highlighting a potential trans-diagnostic novel mechanism to address such symptoms.

neuroscience↗

bioRxiv2017

Effect of 40Gy irradiation on the ultrastructure, biochemistry, morphology and cytology during spermatogenesis in the southern green stink bug Nezara viridula (Hemiptera: Pentatomidae)

A study on the Nezara viridula male gonad cells was undertaken to compare normal development and development of insect cells after irradiation of 4th instar nymphs with a dose of 40 Gray. Visually, morphologically, biochemically and cytologically the insects were not all uniformly affected by the radiation. In all aspects of development there was a range from severely affected to nearly normal. Irradiated insects appeared to move slowly and were unable to mate with non-irradiated females. The testes of the males varied from bright orange to grey in colour and all were smaller in size than non-irradiated testes. The ultrastructure of the developing sperm showed abnormalities the axonemes, the mitochrondrial derivatives, nebenkern and centrioles. Cytochemically, the main difference observed was the presence of granules heavily stained with acid phosphatase in between mitochrondrial derivatives. The chromosomes of these irradiated insects were highly fragmented. Although a few sperm in irradiated insects appeared normal no progeny were produced as insect did not mate. The sterile insect technique (SIT) requires a balance between the effective radiation dose to achieve partial or full sterility, while maintaining physical fitness. The observation that abnormalities varied from almost none to severe at 40Gy could help the development of SIT for control of N. viridula and other Pentatomidae.

developmental biology↗