Biology subjects

Swain, C.

Publications and source records attributed to Swain, C..

3 recordsLinked to original sources

bioRxiv2026

Network fixation expansion microscopy

Expansion microscopy (ExM) physically magnifies preserved biological specimens by using a specimen-permeating hydrogel to pull biomolecules, such as proteins, apart from each other. ExM protocols exhibit a tension between the need to initially fix proteins to each other during sample preservation, to retain proteins and their nanoscale organization, and the need to separate proteins from each other isotropically, to achieve physical magnification. We here propose to address this tension by fixing proteins directly to the hydrogel network itself, which then serves as a common substrate for both initial fixation and final separation. We equip proteins with chemical handles, then form a specimen-permeating hydrogel that binds the handles, in a ~15-minute chemical process conducted entirely at -20oC. This network fixation ExM (nfExM) procedure enables excellent epitope retention and nanoscale organization preservation, in cultured cells. nfExM may help support ultrastructural investigations of protein complexes and interactions.

molecular biology↗

bioRxiv2026

A novel rat model of body first subtype of Parkinsons disease

The recent growing evidence support the existence of two subtypes of Parkinsons disease (PD), a body first and brain first subtype owing to variability in the disease site of onset as well as disease progression. Animal models which could replicate the specific differences of these subtypes are important to explore the pathophysiology as well as to evaluate novel treatment options. Here, we describe an animal model of body first PD subtype developed using repeated low dose exposure of environmental neurotoxin Paraquat (P) and Lectin (L) to characterize its PD-like manifestations. We administered P+L (P+L, p.o.) daily to rats for 90 days. These animals underwent motor and non-motor behavioral tests at various time intervals. After 21 weeks, post-mortem histopathological analysis was performed to assess neurodegeneration. Onset of motor deficits initiated unilaterally from week 4 of P+L followed by gradual progression towards bilateral symptoms that were levodopa responsive. This model also replicates non motor features including cognitive deficits in tests like Novel Object Recognition Test and Y maze as well as sleep abnormalities. The histopathology showed nigrostriatal dopaminergic degeneration and proteinase K resistant S129 alpha-synucleinopathy both in the gut and the brain. The replication of both progressive motor and non-motor features in this rat model corroborates body first subtype of PD therefore making it an attractive option for testing neuroprotective experimental therapeutics and avenue to understand pathophysiological mechanisms.

neuroscience↗

bioRxiv2022

Using Extracellular Vesicles Released by GDNF-transfected Macrophages for Therapy of Parkinson's Disease

Extracellular vesicles (EVs) are cell-derived nanoparticles that facilitate transport of proteins, lipids and genetic material playing important roles in intracellular communication. They have a remarkable potential as non-toxic and non-immunogenic nanocarriers for drug delivery to unreachable organs and tissues, in particular, the central nervous system (CNS). Herein, we developed a novel platform based on macrophage derived EVs to treat Parkinsons disease (PD). Specifically, we evaluated the therapeutic potential of EVs secreted by autologous macrophages that were transfected ex vivo to express glial cell line-derived neurotrophic factor (GDNF). EV-GDNF were collected from conditioned media of GDNF-transfected macrophages and characterized for GDNF content, size, charge, and expression of EV-specific proteins. The data revealed that along with the encoded neurotrophic factor, EVs released by pre-transfected macrophages carry GDNF-encoding DNA. Four months-old transgenic Parkin Q311(X)A mice were treated with EV-GDNF via intranasal administration, and the effect of this therapeutic intervention on locomotor functions was assessed over a year. Significant improvements in mobility, increase in neuronal survival, and decrease in neuroinflammation were found in PD mice treated with EV-GDNF. No offsite toxicity caused by EV-GDNF administrations was detected. Overall, EV-based approach can provide a versatile and potent therapeutic intervention for PD.

bioengineering↗