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Biology subjects

Allan, K.

Publications and source records attributed to Allan, K..

3 recordsLinked to original sources

Alcama expressed in blood retina barrier and Muller glia is involved in zebrafish retina regeneration

Activated leukocyte cell adhesion molecule A (Alcama) plays a role in axonal guidance, cell differentiation, and retinal lamination in a developing retina and was identified as a marker for activated Muller glial cells in adult zebrafish. However, its spatiotemporal localization and its involvement in retina regeneration remains unclear. Here we induced focal photoreceptor damage in zebrafish using laser photocoagulation and examined the expression and localization of Alcama at different time points post lesion. Immunohistochemistry in wild type fish and Tg(kdrl-EGFP) fish showed Alcama localized to the blood retina barrier with increased expression in Muller glial end feet and radial processes in a regenerating retina. To confirm its role in retina regeneration, alcama expression was transiently knocked down using morpholinos in adult fish. Scanning laser ophthalmoscopy, Zpr1 immunostaining and EdU staining showed delayed retina regeneration in alcama knockdown fish, indicating a possible role for Alcama in zebrafish retina regeneration.

cell biology↗

Humans Modulate Walking Speed in Response to the Perceived Energy-Time Costs of Others

Humans tend to walk at speeds that minimize energy expenditure and time duration. While most walking experiments examine individuals in relative isolation, everyday locomotion frequently occurs in social contexts. We investigated whether walking speed is modulated in response to a social interaction during a cooperative task. Participants completed 96 randomized walking trials where they approached and retrieved boxes varying in distance (2.5-10 m) and mass (0-6.8 kg). Boxes either rested on the ground or were handed off by an experimenter, signaling prosocial effort benefitting the participant. Approach speed was measured with inertial measurement units placed at the feet and fit to a saturating exponential function of walking distance using a nonlinear mixed-effects regression model. Based on the energy-time optimization framework, we hypothesized that participants would approach more quickly when larger boxes were held at farther distances, to reduce energy and time costs of the experimenter, despite exerting more effort themselves. Participants walked 8.5% faster (1.29 m s-1 versus 1.19 m s-1; p = 3.85 x 10-6) when the largest box was held out by the experimenter versus left on the ground. However, the manner in which the box was held had no influence on approach speeds (p = 0.31). Exploratory analyses identified modest trends between experiment responses and individual characteristics, but none reached statistical significance. The findings suggest that locomotor decisions reflect not only an individuals own energy and time costs but also the perceived costs borne by others. This study demonstrates that social context can meaningfully influence walking behavior. Summary StatementHumans walk more quickly in response to the perceived energy and time others spend helping them, even at the cost of exerting more energy themselves.

biophysics↗

In silico and functional characterisation of an ultra-rare CFTR mutation identifies novel lasso motif interactions regulating channel gating

Characterisation of I37R - a novel mutation in the lasso motif of ABC-transporter CFTR, a chloride channel - was conducted by theratyping using CFTR potentiators which increase channel gating activity and correctors which repair protein trafficking defects. I37R-CFTR function was characterised using intestinal current measurements (ICM) in rectal biopsies, forskolin-induced swelling (FIS) in intestinal organoids and short circuit current measurements (Isc) in organoid-derived monolayers from an individual with I37R/F508del CFTR genotype. We demonstrated that the I37R-CFTR mutation results in a residual function defect amenable to treatment with potentiators and type III, but not to type I, correctors. Molecular dynamics of I37R-CFTR using an extended model of the phosphorylated, ATP-bound human CFTR identified an altered lasso motif conformation which results in an unfavourable strengthening of the interactions between the lasso motif, the regulatory (R) domain and the transmembrane domain two (TMD2). In conclusion, structural and functional characterisation of the I37R-CFTR mutation increases understanding of CFTR channel regulation and provides a potential pathway to access CFTR modulator treatments for individuals with CF caused by ultra-rare CFTR mutations.

molecular biology↗