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Biology subjects

Bollavaram, K.

Publications and source records attributed to Bollavaram, K..

3 recordsLinked to original sources

A Biosynthetic Thumb Prosthesis

In cases of severe damage to the extremities, the function and structure of compromised biological tissues must be replaced. If biological reconstruction using autologous tissue is not feasible, amputation and replacement with a synthetic prosthesis is often the next best option. Currently, the synthetic materials available for prostheses are limited, especially in their ability to restore skin sensation. Here we show a biosynthetic prosthesis that combines the versatility of titanium with the rich sensory capabilities of biological skin, to both increase movement and restore sensation to an amputated thumb. The prosthesis recreates opposition pinch by linking motion of the prosthetic joint to that of the residual biological joint. The device is enclosed in neurotized skin from the patients own body, providing natural sensation. We validated the biosynthetic thumbs ability to reproduce opposition pinch on the benchtop and in a cadaver, and showed in vivo viability of the skin interface in an animal model. These results provide a framework for functional reconstruction of amputated digits using a combination of synthetic materials and biological tissues. One Sentence SummaryA prosthetic thumb made up of a titanium mechanism and living skin can restore opposition pinch and touch sensation following thumb amputation.

bioengineering↗

Multiple Sites on SARS-CoV-2 Spike Protein are Susceptible to Proteolysis by Cathepsins B, K, L, S, and V

SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Proteases are central to the infection process of SARS-CoV-2. Cleavage of the spike protein on the viruss capsid causes the conformational change that leads to membrane fusion and viral entry into the target cell. Since inhibition of one protease, even the dominant protease like TMPRSS2, may not be sufficient to block SARS-CoV-2 entry into cells, other proteases that may play an activating role and hydrolyze the spike protein must be identified. We identified amino acid sequences in all regions of spike protein, including the S1/S2 region critical for activation and viral entry, that are susceptible to cleavage by furin and cathepsins B, K, L, S, and V using PACMANS, a computational platform that identifies and ranks preferred sites of proteolytic cleavage on substrates, and verified with molecular docking analysis and immunoblotting to determine if binding of these proteases can occur on the spike protein that were identified as possible cleavage sites. Together, this study highlights cathepsins B, K, L, S, and V for consideration in SARS-CoV-2 infection and presents methodologies by which other proteases can be screened to determine a role in viral entry. This highlights additional proteases to be considered in COVID-19 studies, particularly regarding exacerbated damage in inflammatory preconditions where these proteases are generally upregulated.

bioengineering↗

Age-dependent characterization of the carotid and cerebral artery morphologies in a transgenic mouse model of sickle cell anemia using ultrasound and microcomputed tomography

Children with sickle cell anemia have elevated stroke risks as well as other arterial complications, but morphological changes to large arteries are not well defined, and the focus has been on the microcirculation where deoxygenation promotes sickling of red blood cells. The goal of this study was to define morphological changes in carotid and cerebral arteries in the Townes transgenic sickle cell mouse model, and to specifically determine anatomical measurement differences in mice homozygous for {beta}-globin S mutation (SS) compared to heterozygous (AS) littermate controls. We used a combination of live imaging with ultrasound and microcomputed tomography (micro-CT) imaging of corrosion casted vessels to quantify arterial dimensions and changes in mice 4, 12, and 24 weeks of age with or without sickle cell anemia. 12 week SS mice had significantly larger common carotid artery diameters than AS mice, and significantly larger diameters in the extracranial and intracranial portions of the internal carotid artery (ICA), determined by ultrasound and micro-CT, respectively. There were also side specific differences between the left and right vessels. There was significant narrowing along ICA length in 12-and 24-week SS mice, decreasing by as much as 70%, such that there was no difference in size between the anterior and middle cerebral arteries, where the ICA terminates, by genotype. Significant narrowing along the length was also measured in the anterior cerebral arteries of 12-and 24-week SS mice, but not AS. Collectively, these findings indicate that sickle cell anemia causes increased arterial dimensions in 12-and 24-week aged mice. We also provide these measurements for the common carotid, internal carotid, anterior cerebral, and middle cerebral arteries for left and right sides, for AS and SS genotypes as a reference for other investigators using in silico modeling of arterial complications caused by aging with sickle cell anemia.

pathology↗