Biology subjects

Ghahremani, M.

Publications and source records attributed to Ghahremani, M..

4 recordsLinked to original sources

bioRxiv2021

Characterization of Critical Determinants of ACE2-RBD Interaction

Despite sequence similarity to SARS-CoV-1, SARS-CoV-2 has demonstrated greater widespread virulence and unique challenges to researchers aiming to study its pathogenicity in humans. The interaction of the viral receptor binding domain (RBD) with its main host cell receptor, angiotensin-converting enzyme 2 (ACE2), has emerged as a critical focal point for the development of anti-viral therapeutics and vaccines. Utilizing our recently developed NanoBiT technology-based biosensor, we selectively identify and characterize the impact of mutating certain amino acid residues in the RBD of SARS-CoV-2 and in ACE2. Specifically, we examine the mutational effects on RBD-ACE2 binding ability, before and after the addition of competitive inhibitors, as well as neutralizing antibody activity. These critical determinants of virus-host interactions may provide more effective targets for ongoing vaccines, drug development, and potentially pave the way for determining the genetic variation underlying disease severity.

microbiology↗

bioRxiv2020

Phosphate and phosphite differentially impact the proteome and phosphoproteome of Arabidopsis suspension cell cultures

Phosphorus absorbed in the form of phosphate (H2PO4-) is an essential but limiting macronutrient for plant growth and agricultural productivity. A comprehensive understanding of how plants respond to phosphate starvation is essential to develop more phosphate-efficient crops. Here we employed label-free proteomics and phosphoproteomics to quantify protein-level responses to 48 h of phosphate versus phosphite (H2PO3-) resupply to phosphate-deprived Arabidopsis thaliana suspension cells. Phosphite is similarly sensed, taken up, and transported by plant cells as phosphate, but cannot be metabolized or used as a nutrient. Phosphite is thus a useful tool to delineate between non-specific processes related to phosphate sensing and transport, and specific responses to phosphorus nutrition. We found that responses to phosphate versus phosphite resupply occurred mainly at the level of protein phosphorylation, complemented by limited changes in protein abundance, primarily in protein translation, phosphate transport and scavenging, and central metabolism proteins. Altered phosphorylation of proteins involved in core processes such as translation, RNA splicing, and kinase signalling were especially important. We also found differential phosphorylation in response to phosphate and phosphite in 69 proteins, including splicing factors, translation factors, the PHT1;4 phosphate transporter and the HAT1 histone acetyltransferase--potential phospho-switches signalling changes in phosphorus nutrition. Our study illuminates several new aspects of the phosphate-starvation response and identifies important targets for further investigation and potential crop improvement.

plant biology↗

bioRxiv2019

Single unit activity in marmoset posterior parietal cortex in a gap saccade task

Abnormal saccadic eye movements can serve as biomarkers for patients with several neuropsychiatric disorders. To investigate cortical control mechanisms of saccadic responses, the common marmoset (Callithrix jacchus) is a promising non-human primate model. Their lissencephalic brain allows for accurate targeting of homologues of sulcal areas in the macaque brain. Here we recorded single unit activity in the posterior parietal cortex of two marmosets using chronic microelectrode arrays, while the monkeys performed a saccadic task with Gap trials (stimulus onset lagged fixation point offset by 200ms) interleaved with Step trials (fixation point disappeared when the peripheral stimulus appeared). Both marmosets showed a gap effect--shorter saccadic reaction times (SRTs) in Gap vs. Step trials. On average, stronger gap-period response across the entire neuronal population preceded shorter SRTs on trials with contralateral targets, although this correlation was stronger among the 15% gap neurons, which responded significantly during the gap. We also found 39% target neurons with significant visual target-related responses, which were stronger in Gap trials and correlated with the SRTs better than the remaining cells. Compared with slow saccades, fast saccades were preceded by both stronger gap-related and target-related response in all PPC neurons, regardless of whether such response reached significance. Our findings suggest that the PPC in the marmoset contains an area that is involved in the modulation of saccadic preparation and plays roles comparable to those of area LIP in macaque monkeys in eye movements.\n\nSIGNIFICANCE STATEMENTAbnormal saccadic eye movements can serve as biomarkers for different neuropsychiatric disorders. So far, processes of cerebral cortical control of saccades are not fully understood. Non-human primates are ideal models for studying such processes, and the marmoset is especially advantageous since their smooth cortex permits laminar analyses of cortical microcircuits. Using electrode arrays implanted in the posterior parietal cortex of marmosets, we found neurons responsive to key periods of a saccadic task in a manner that contribute to cortical modulation of saccadic preparation. Notably, this signal was correlated with subsequent saccadic reaction times and was present in the entire neuronal population. We suggest that the marmoset model will shed new light on the cortical mechanisms of saccadic control.

neuroscience↗

bioRxiv2019

Electrical microstimulation evokes saccades in posterior parietal cortex of common marmosets

The common marmoset (Callithrix jacchus) is a small-bodied New World primate, increasing in prominence as a model animal for neuroscience research. The lissencephalic cortex of this primate species provides substantial advantages for the application of electrophysiological techniques such as high-density and laminar recordings, which have the capacity to advance our understanding of local and laminar cortical circuits and their roles in cognitive and motor functions. This is particularly the case with respect to the oculomotor system, as critical cortical areas of this network such as the frontal eye fields (FEF) and lateral intraparietal area (LIP) lie deep within sulci in macaques. Studies of cytoarchitecture and connectivity have established putative homologies between cortical oculomotor fields in marmoset and macaque, but physiological investigations of these areas, particularly in awake marmosets, have yet to be carried out. Here, we addressed this gap by probing the function of posterior parietal cortex (PPC) of the common marmoset using electrical microstimulation. We implanted two animals with 32-channel Utah arrays at the location of the putative area LIP and applied microstimulation while they viewed a video display and made untrained eye movements. Similar to previous studies in macaques, stimulation evoked fixed-vector and goal-directed saccades, staircase saccades, and eye blinks. These data demonstrate that area LIP of the marmoset plays a role in the regulation of eye movements, provide additional evidence that this area is homologous with that of the macaque, and further establish the marmoset as valuable model for neurophysiological investigations of oculomotor and cognitive control.\n\nNew & NoteworthyThe macaque monkey has been the preeminent model for investigations of oculomotor control, but studies of cortical areas are limited as many of these areas are buried within sulci in this species. Here we applied electrical microstimulation to the putative area LIP of the lissencephalic cortex of awake marmosets. Similar to the macaque, microstimulation evoked contralateral saccades from this area, supporting the marmoset as a valuable model for studies of oculomotor control.

neuroscience↗