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Biology subjects

Mohammad, H.

Publications and source records attributed to Mohammad, H..

4 recordsLinked to original sources

A Computational Study of the Role of Counterions and Solvent Dielectric in Determining the Conductance of B-DNA

DNA naturally exists in a solvent environment, comprised of water and salt molecules such as sodium, potassium, magnesium, etc. Along with the sequence, the solvent conditions become a vital factor determining DNA structure and thus its conductance. Over the last two decades, researchers have measured DNA conductivity both in hydrated and almost dry (dehydrated) conditions. However, due to experimental limitations (the precise control of the environment), it is very difficult to analyze the conductance results in terms of individual contributions of the environment. Therefore, modeling studies can help us to gain a valuable understanding of various factors playing a role in charge transport phenomena. DNA naturally has negative charges located at the phosphate groups in the backbone, which provides both the connections between the base pairs and the structural support for the double helix. Positively charged ions such as the Sodiumion (Na+), one of the most commonly used counterions, balance the negative charges at the backbone. This modeling study investigates the role of counterions both with and without the solvent (water) environment on charge transport through double-stranded DNA. Our computational experiments show that in dry DNA, the presence of counterions affects electron transmission at the lowest unoccupied molecular orbital energies. However, in solution, the counterions have a negligible role in transmission. Using the polarizable continuum model calculations, we demonstrate that the transmission is significantly higher at both the highest occupied and lowest unoccupied molecular orbital energies in a water environment as opposed to in a dry one. Moreover, calculations also show that the energy levels of neighboring bases are more closely aligned to ease electron flow in the solution.

biophysics↗

Local and global dichotomic dysfunction in resting and evoked functional connectivity precedes tauopathy

Functional network activity alterations are one of the earliest hallmarks of Alzheimers disease (AD), detected prior to amyloidosis and tauopathy. Better understanding the neuronal underpinnings of such network alterations could offer mechanistic insight into AD progression. Here, we examined a mouse model (early-tauopathy 3xTgAD mice) recapitulating this early AD stage. We found resting functional connectivity loss within ventral networks, including the entorhinal cortex, aligning with the spatial distribution of tauopathy reported in humans. Unexpectedly, in contrast to decreased connectivity at rest, 3xTgAD mice show enhanced fMRI signal within several projection areas following optogenetic activation of the entorhinal cortex. We corroborate this finding by demonstrating neuronal facilitation within ventral networks and synaptic hyperexcitability in projection targets. 3xTgAD mice thus reveal a dichotomic hypo-connected resting/hyper-responsive active phenotype. The strong homotopy between the areas affected supports the translatability of this pathophysiological model to tau-related deficits in humans.

neuroscience↗

Dopamine D1 receptor signalling in dyskinetic Parkinsonian rats revealed by fiber photometry using FRET-based biosensors

Like many G protein-coupled receptors (GPCRs), the signalling pathways regulated by the dopamine D1 receptor (D1R) are dynamic, cell-type specific, and can change in response to disease or drug exposures. In striatal neurons, the D1R activates cAMP/protein kinase A (PKA) signalling. However, in Parkinsons disease (PD), alterations in this pathway lead to activation of extracellular regulated kinases (ERK1/2), contributing to L-DOPA-induced dyskinesia (LID). In order to detect D1R activation in vivo and to study the progressive dysregulation of D1R signalling in PD and LID, we developed ratiometric fiber-photometry with Forster resonance energy transfer (FRET) biosensors and optically detected PKA and ERK1/2 signalling in freely moving rats. We show that in Parkinsonian animals, D1R signalling through PKA and ERK1/2 is sensitized, but that following chronic treatment with L-DOPA, these pathways become partially desensitized while concurrently D1R activation leads to greater induction of dyskinesia.

neuroscience↗

Annihilation of Methicillin-resistant Staphylococcus aureus via Photobleaching of Staphyloxanthin

Given that the dearth of new antibiotic development loads an existential burden on successful infectious disease therapy1, health organizations are calling for alternative approaches to combat methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we report a drug-free photonic approach to eliminate MRSA through photobleaching of staphyloxanthin, an indispensable membrane-bound antioxidant of S. aureus2-5. The photobleaching process, uncovered through a transient absorption imaging study and quantitated by absorption spectroscopy and mass spectrometry, decomposes staphyloxanthin and sensitizes MRSA to reactive oxygen species attack. Consequently, staphyloxanthin bleaching by low-level blue light eradicates MRSA synergistically with external or internal reactive oxygen species. The effectiveness of this synergistic therapy is validated in MRSA culture, MRSA-infected macrophage cells, S. aureus biofilms, and a mouse wound infection model. Collectively, these findings highlight broad applications of staphyloxanthin photobleaching for treatment of MRSA infections.

microbiology↗