bioRxiv Science⌕ Search

Biology subjects

Dyer, C.

Publications and source records attributed to Dyer, C..

3 recordsLinked to original sources

Monovision-induced motion illusions in presbyopic and non-presbyopic populations

Monovision is a common correction for presbyopia that focuses one eye at far distances and the other at near distances, resulting in an interocular difference in blur between the eyes. Because blur increases the speed of visual processing by a few milliseconds, these optical conditions can induce dramatic misperceptions of the distances and 3D directions of moving objects. To date, however, the illusion has been demonstrated in only non-presbyopic individuals. We analyze the prevalence of both the processing speed differences and the visibility of the resulting illusions in the presbyopic and general populations.17 presbyopes (54.4{+/-}5.9years) and 36 non-presbyopes (22.2{+/-}5.0years) participated. The proportions of these participant populations approximately match their proportions in the general population. Two strips of horizontally moving bars were presented on an autostereoscopic display with interocular blur and light-level differences. The task was to report which strip appeared closer in depth. Blur- and light-level differences caused illusions that are respectively known as the reverse and classic Pulfrich effects. Interocular delay and an illusion visibility index--the ratio of interocular delay and the detection threshold--were obtained from each participant for both blur and light-level differences between the eyes. Blur- and light-level differences cause highly significant changes in processing speed at the individual and group levels. (The two populations were statistically indistinguishable in their susceptibility to stimulus-induced processing speed differences.) The reverse and classic Pulfrich effects occurred in 94% and in 96%, respectively, of the general participant population. The visibility index showed that the processing speed discrepancy exceeded the detection threshold in a smaller number of participants--30% and 43%, respectively. Interocular differences in optical blur reliably cause interocular differences in processing speed across presbyopic and non-presbyopic populations, although they create visible (suprathreshold) illusions in only a subset of participants. However, this subset included individuals with processing delays that were many times larger than the detection threshold. These latter participants are likely to be afflicted by large, highly visible illusions in real-world conditions. Methods for reducing or eliminating these illusions are discussed.+

neuroscience↗

Muscle regeneration can be rescued in a telomerase deficient zebrafish model of ageing by MMP inhibition

Ageing progressively impairs skeletal muscle regeneration, contributing to reduced mobility and quality of life in the ageing population. Whilst the molecular changes underlying muscle ageing have been well characterised, their impact on muscle stem cell (muSC) behaviour during regeneration remains poorly understood. Here, we leverage the telomerase-deficient tert mutant zebrafish larvae as an in vivo model of accelerated ageing to perform real-time analysis of muSC dynamics following muscle injury. We demonstrate that the ageing-like inflammatory environment in tert mutant disrupts muSC migration, impairs activation and proliferation, and compromises regenerative capacity. We further show that sustained inflammation, mediated by persistent macrophage presence and elevated matrix metalloproteinase (MMP) activity directly limits muSC recruitment and migration efficiency. Pharmacological inhibition of MMP9/13 activity and genetic depletion of macrophages partially restore muSC migratory behaviour and regenerative outcomes. Notably, we demonstrate that muSC migration dynamics correlate with regenerative success, providing a functional readout for therapeutic screening. Our findings reveal zebrafish tert mutants offer a tractable system for dissecting ageassociated changes to cell behaviour and for identifying rejuvenation interventions.

cell biology↗

Intranasal gene therapy to prevent infection by SARS-CoV-2 variants

SARS-CoV-2 variants have emerged with enhanced pathogenicity and transmissibility, and escape from pre-existing immunity, suggesting first-generation vaccines and monoclonal antibodies may now be less effective. This manuscript demonstrates an approach for preventing clinical sequelae and the spread of SARS-CoV-2 variants. First, we affinity-matured an angiotensin-converting enzyme 2 (ACE2) decoy protein, achieving 1000-fold binding improvements that extend across a wide range of SARS-CoV-2 variants and distantly related, ACE2-dependent coronaviruses. Next, we demonstrated the expression of this decoy in proximal airway when delivered via intranasal administration of an AAV vector. This intervention significantly diminished clinical and pathologic consequences of SARS-CoV-2 challenge in a mouse model and achieved therapeutic levels of decoy expression at the surface of proximal airways when delivered intranasally to nonhuman primates. Importantly, this long-lasting, passive protection approach is applicable in vulnerable populations such as the elderly and immune-compromised that do not respond well to traditional vaccination. This approach could be useful in combating COVID-19 surges caused by SARS-CoV-2 variants and should be considered as a countermeasure to future pandemics caused by pre-emergent members, ACE2-dependent CoVs that are poised for zoonosis. Author summarySARS-CoV-2 variants have emerged with enhanced pathogenicity and transmissibility, and escape from pre-existing immunity, suggesting first-generation vaccines and monoclonal antibodies may now be less effective. This manuscript demonstrates an approach for preventing clinical sequelae and the spread of SARS-CoV-2 variants. First, we affinity-matured an angiotensin-converting enzyme 2 (ACE2) decoy protein, achieving 1000-fold binding improvements that extend across a wide range of SARS-CoV-2 variants and distantly related, ACE2-dependent coronaviruses. Next, we demonstrated the expression of this decoy in proximal airway when delivered via intranasal administration of an AAV vector. This intervention significantly diminished clinical and pathologic consequences of SARS-CoV-2 challenge in a mouse model and achieved therapeutic levels of decoy expression at the surface of proximal airways when delivered intranasally to nonhuman primates. Importantly, this long-lasting, passive protection approach is applicable in vulnerable populations such as the elderly and immune-compromised that do not respond well to traditional vaccination. This approach could be useful in combating COVID-19 surges caused by SARS-CoV-2 variants and should be considered as a countermeasure to future pandemics caused by pre-emergent members, ACE2-dependent CoVs that are poised for zoonosis.

genetics↗