Biology subjects

Ahsan, A.

Publications and source records attributed to Ahsan, A..

3 recordsLinked to original sources

bioRxiv2023

Use of nanomaterials-modified carbon microfiber electrode material for superior electrochemical performance in lake sediment inoculated microbial fuel cells

High cathodic overpotential of the oxygen reduction reaction (ORR) in MFC carbon-based cathodes is one of the key barriers to the widespread adoption of the technology. Current Pt-based ORR catalysts are expensive. The use of novel and inexpensive catalysts as replacements for platinum is therefore desirable. In this study, nanomaterials were directly chemically synthesized on carbon microfiber electrodes to improve the performance of lake sediment inoculated MFCs. Nanomaterial of MnO2, MnO2/polyaniline (PANI), ZnO/NiO and ZnO/NiO/PANI attachments were directly chemically synthesized on the carbon material and used as cathode electrodes. The maximum power densities recorded for the different treatments were; MnO2 78.5 mW/m2, MnO2/PANI (Polyaniline) 141.6 mW/m2, ZnO/NiO 67.6 mW/m2, and ZnO/NiO/PANI 129.4 mW/m2. The current and poswer densities were more than six-fold higher in ZnO/NiO/PANI and MnO2/PANI nanoparticle modified cathodes compared to the control MFCs with no catalyst. Cyclic voltammetry (CV) and FTIR data and SEM images suggest that the nanoparticle attached carbon material is morphologically, chemically and electrochemically different from the controls with no nanomaterial attachment. The outcome of this study demonstrates that nanomaterials-incorporated carbon microfiber cathodes bring about significant enhancements to power densities and may potentially have applications in cost-effective MFCs.

bioengineering↗

bioRxiv2022

Neuronal membrane proteasomes homeostatically regulate neural circuit activity in vivo and are required for learning-induced behavioral plasticity

Protein degradation is critical for brain function through processes that remain poorly understood. Here we investigated the in vivo function of a recently reported neuronal membrane-associated proteasome (NMP) in the brain of Xenopus laevis tadpoles. We demonstrated that NMPs are present in the tadpole brain with biochemistry and electron microscopy, and showed that they actively degrade neuronal activity-induced nascent proteins. Using in vivo calcium imaging in the optic tectum, we showed that acute inhibition of NMP function rapidly increased spontaneous neuronal activity, resulting in hyper-synchronization among tectal neurons. At the circuit level, inhibiting NMPs abolished learning-dependent improvement in a visuomotor behavior paradigm in live animals. Our data provide the first in vivo characterization of NMP functions in the vertebrate nervous system and suggest that NMP-mediated degradation of activity-induced nascent proteins may serve as a homeostatic modulatory mechanism in neurons that is critical for regulating neuronal activity and experience-dependent circuit plasticity.

neuroscience↗

bioRxiv2020

Mutant EGFR is a preferred SMURF2 substrate of ubiquitination: role in enhanced receptor stability and TKI sensitivity

We previously reported that differential protein degradation of TKI-sensitive [L858R, del(E746-A750)] and resistant (T790M) epidermal growth factor receptor (EGFR) mutants upon erlotinib treatment correlates with drug sensitivity. However, the molecular mechanism remains unclear. We also reported SMAD ubiquitination regulatory factor 2 (SMURF2) ligase activity is important in stabilizing EGFR. Here, using in vitro and in vivo ubiquitination assays, mass spectrometry, and super-resolution microscopy, we show SMURF2-EGFR functional interaction is critical in receptor stability and TKI sensitivity. We found that L858R/T790M EGFR is a preferred substrate of SMURF2-UBCH5 (an E3-E2) complex-mediated K63-linked polyubiquitination, which preferentially stabilizes mutant receptor. We identified four lysine (K) residues (K721, 846, 1037 and 1164) as the sites of ubiquitination and replacement of K to acetylation-mimicking asparagine (Q) at K1037 position in L858R/T790M background converts the stable protein sensitive to erlotinib-induced degradation. Using STochastic Optical Reconstruction Microscopy (STORM) imaging, we show that SMURF2 presence allows longer membrane retention of activated EGFR upon EGF treatment, whereas, siRNA-mediated SMURF2 knockdown fastens receptor endocytosis and lysosome enrichment. In an erlotinib-sensitive PC9 cells, SMURF2 overexpression increased EGFR levels with improved erlotinib tolerance, whereas, SMURF2 knockdown decreased EGFR steady state levels in NCI-H1975 and PC9-AR cells to overcome erlotinib and AZD-9291 resistance respectively. Additionally, by genetically altering the SMURF2-UBCH5 complex formation destabilized EGFR. Together, we propose that SMURF2-mediated preferential polyubiquitination of L858R/T790M EGFR may be competing with acetylation-mediated receptor internalization to provide enhanced receptor stability and that disruption of the E3-E2 complex may be an attractive alternate to overcome TKI resistance.

cancer biology↗