Biology subjects

Obaid, A.

Publications and source records attributed to Obaid, A..

3 recordsLinked to original sources

bioRxiv2021

The impact of mutations on the structural and functional properties of SARS-CoV-2 proteins: A comprehensive bioinformatics analysis

An in-depth analysis of first wave SARS-CoV-2 genome is required to identify various mutations that significantly affect viral fitness. In the present study, we have performed comprehensive in-silico mutational analysis of 3C-like protease (3CLpro), RNA dependent RNA polymerase (RdRp), and spike (S) proteins with the aim of gaining important insights into first wave virus mutations and their functional and structural impact on SARS-CoV-2 proteins. Our integrated analysis gathered 3465 SARS-CoV-2 sequences and identified 92 mutations in S, 37 in RdRp, and 11 in 3CLpro regions. The impact of those mutations was also investigated using various in silico approaches. Among these 32 mutations in S, 15 in RdRp, and 3 in 3CLpro proteins are found to be deleterious in nature and could alter the structural and functional behavior of the encoded proteins. D614G mutation in spike and P323L in RdRp are the globally dominant variants with a high frequency. Most of them have also been found in the binding moiety of the viral proteins which determine their critical involvement in the host-pathogen interactions and drug targets. The findings of the current study may facilitate better understanding of COVID-19 diagnostics, vaccines, and therapeutics.

bioinformatics↗

bioRxiv2020

Ultra-sensitive measurement of brain penetration mechanics and blood vessel rupture with microscale probes

Microscale electrodes, on the order of 10-100 m, are rapidly becoming critical tools for neuroscience and brain-machine interfaces (BMIs) for their high channel counts and spatial resolution, yet the mechanical details of how probes at this scale insert into brain tissue are largely unknown. Here, we performed quantitative measurements of the force and compression mechanics together with real-time microscopy for in vivo insertion of a systematic series of microelectrode probes as a function of diameter (7.5-100 m and rectangular Neuropixels) and tip geometry (flat, angled, and electrochemically sharpened). Results elucidated the role of tip geometry, surface forces, and mechanical scaling with diameter. Surprisingly, the insertion force post-pia penetration was constant with distance and did not depend on tip shape. Real-time microscopy revealed that at small enough lengthscales (<25 m), blood vessel rupture and bleeding during implantation could be entirely avoided. This appears to occur via vessel displacement, avoiding capture on the probe surface which led to elongation and tearing for larger probes. We propose a new, three-zone model to account for the probe size dependence of bleeding, and provide mechanistic guidance for probe design. Significance StatementMicroscale neural probes are central to next-generation brain-machine interfaces, yet how they physically penetrate living brain remains poorly quantified. Using a high-sensitivity force sensor integrated with real-time microscopy, we measured in vivo force-displacement and visualized vascular responses for microwires (7.5-100 m) and Neuropixels. We find that once the brains protective pia membrane is breached, insertion force remains essentially constant with depth, while pia puncture force and pre-penetration compression scale linearly with probe diameter. Real-time imaging reveals a sub-25 m regime in which blood vessels are displaced rather than ruptured. These results motivate a three-zone model of vessel capture versus displacement and provide actionable mechanical design rules for low-trauma, high-density neural interfaces.

neuroscience↗

bioRxiv2019

CHIME: CMOS-hosted in-vivo microelectrodes for massively scalable neuronal recordings

Mammalian brains consist of 10s of millions to 100s of billions of neurons operating at millisecond time scales, of which current recording techniques only capture a tiny fraction. Recording techniques capable of sampling neural activity at such temporal resolution have been difficult to scale: The most intensively studied mammalian neuronal networks, such as the neocortex, show layered architecture, where the optimal recording technology samples densely over large areas. However, the need for application-specific designs as well as the mismatch between the threedimensional architecture of the brain and largely two-dimensional microfabrication techniques profoundly limits both neurophysiological research and neural prosthetics.\n\nHere, we propose a novel strategy for scalable neuronal recording by combining bundles of glass-ensheathed microwires with large-scale amplifier arrays derived from commercial CMOS of in-vitro MEA systems or high-speed infrared cameras. High signal-to-noise ratio (<20 V RMS noise floor, SNR up to 25) is achieved due to the high conductivity of core metals in glass-ensheathed microwires allowing for ultrathin metal cores (down to <1 m) and negligible stray capacitance. Multi-step electrochemical modification of the tip enables ultra-low access impedance with minimal geometric area and largely independent of core diameter. We show that microwire size can be reduced to virtually eliminate damage to the blood-brain-barrier upon insertion and demonstrate that microwire arrays can stably record single unit activity.\n\nCombining microwire bundles and CMOS arrays allows for a highly scalable neuronal recording approach, linking the progress of electrical neuronal recording to the rapid scaling of silicon microfabrication. The modular design of the system allows for custom arrangement of recording sites. Our approach of employing bundles of minimally invasive, highly insulated and functionalized microwires to lift a 2-dimensional CMOS architecture into the 3rd dimension can be translated to other CMOS arrays such as electrical stimulation devices.

neuroscience↗