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Mack, J.

Publications and source records attributed to Mack, J..

3 recordsLinked to original sources

Sundoli: A necro(w)bot with multi-stiffness joints built using geared mechanical metastructures

In this communication, we design and analyse Sundoli, a necrobot (a bionically engineered robot using decreased animal parts). It is manufactured using a crow endoskeleton, supported and rearticulated by a geared mechanical metastructure to enable controllable passive deformation. The metastructures and bone braces are designed to affix the femur bone to the tibiotarsus, whilst still permitting kinematic movement between the tibiotarsus and the tarsometatarsus of the crow skeleton. The rearticulated hips function as a fulcrum between the upper and lower body parts, whilst concurrently enabling sagittal rotation of the crow skeleton about the hips. Static compression tests, finite element analyses, and in-situ tests conducted using Sundoli shows that the deformation behaviours of metastructures with and without supports are acutely sensitive to the angle of the tarsometatarsus relative to both the ground and the loading direction, highlighting the importance of designing the metastructure holistically and with consideration to the entire skeletal structure. At different loads and angles, the metastructures exhibit variable stiffnesses over their full deformational ranges, demonstrating their effectiveness in protecting the brittle biological bones. Using a metastructure as a mechanism for passive joint rearticulation enables Sundoli an ability to support a payload 8.7 times its body weight without lateral support (an 870% payload ratio) and 14 times its body weight with lateral support (a 1400% payload ratio). This payload capacity is achievable through the full range of its upper body movement in the sagittal plane throughout the full range of its upper body movement in the sagittal plane.

bioengineering↗

Exercise Mitigates Flow Recirculation and Activates Mechanosensitive Transcriptome to Uncover Endothelial SCD1-Catalyzed Anti-Inflammatory Metabolites

Exercise modulates vascular plasticity in multiple organ systems; however, the metabolomic transducers underlying exercise and vascular protection in the disturbed flow-prone vasculature remain under-investigated. We simulated exercise-augmented pulsatile shear stress (PSS) to mitigate flow recirculation in the lesser curvature of the aortic arch. When human aortic endothelial cells (HAECs) were subjected to PSS ({tau}ave = 50 dyne{middle dot}cm-2, {partial}{tau}/{partial}t = 71 dyne{middle dot}cm-2{middle dot}s-1, 1 Hz), untargeted metabolomic analysis revealed that Stearoyl-CoA Desaturase (SCD1) in the endoplasmic reticulum (ER) catalyzed the fatty acid metabolite, oleic acid (OA), to mitigate inflammatory mediators. Following 24 hours of exercise, wild-type C57BL/6J mice developed elevated SCD1-catalyzed lipid metabolites in the plasma, including OA and palmitoleic acid (PA). Exercise over a 2-week period increased endothelial SCD1 in the ER. Exercise further modulated the time-averaged wall shear stress (TAWSS or{tau} ave) and oscillatory shear index (OSIave), upregulated Scd1 and attenuated VCAM1 expression in the disturbed flow-prone aortic arch in Ldlr-/- mice on high-fat diet but not in Ldlr-/-Scd1EC-/- mice. Scd1 overexpression via recombinant adenovirus also mitigated ER stress. Single cell transcriptomic analysis of the mouse aorta revealed interconnection of Scd1 with mechanosensitive genes, namely Irs2, Acox1 and Adipor2 that modulate lipid metabolism pathways. Taken together, exercise modulates PSS ({tau}ave and OSIave) to activate SCD1 as a metabolomic transducer to ameliorate inflammation in the disturbed flow-prone vasculature.

physiology↗

A 2.08 A resolution structure of HLB5, a novel cellulase from the anaerobic gut bacterium Parabacteroides johnsonii DSM 18315.

Cellulases play a significant role in the degradation of complex carbohydrates. In the human gut anaerobic bacteria are essential to the well-being of the host by producing these essential enzymes that convert plant polymers into simple sugars that can then be further metabolized by the host. Here we report the 2.08 [A] resolution structure of HLB5, a chemically verified cellulase that was identified previously from an anaerobic gut bacterium and that has no structural cellulase homologues in PDB nor possesses any conserved region typical for enzymes that degrade carbohydrates. We anticipate that the information presented here will facilitate the identification of additional cellulases for which no homologues have been identified until to date and in enhancing our understanding how these novel cellulases bind and hydrolyze their substrates.

systems biology↗