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Signal transduction and exercise
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Brendan Egan, Adam P. Sharples
In summary, the working model for exercise-induced signal transduction and its role in adaptation to exercise begins when a myriad of perturbations to homeostasis occurs, broadly within our bodies and specifically within our muscles, including important changes in energy turnover and muscle tension. All these perturbations act as ‘signals’ (Step 1) to be sensed by molecular ‘sensors’ (Step 2) or sensor proteins that are then computed and conveyed by ‘signal transduction’ pathways and/or networks (Step 3). Such signalling works by protein-protein binding, phosphorylation and other modifications, and signalling proteins move, for example, in between the cytosol and nucleus. Finally, the exercise-induced downstream signalling proteins regulate ‘effectors’ (Step 4), which are effector proteins and processes that include transcription factors, regulators of protein synthesis and protein breakdown and can be thought of as regulators of gene ‘transcription’ (Step 5) and protein ‘translation’ (Step 6) that over time determine adaptations to exercise in skeletal muscle, described in later chapters.
The Future Is Not What It Used to Be
Published in Tom Lawry, Hacking Healthcare, 2022
Biohacking refers to applying IT hacks to biological systems – most prominently, the human body. These opportunities range from simple diagnostics to deep neural implants. For example, biochips hold the possibility of detecting or predicting diseases from cancer to smallpox before the patient even develops symptoms. Such chips would be made from an array of intelligent molecular sensors that can analyze biological elements and chemicals.
Gold Nanomaterials at Work in Biomedicine *
Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Xuan Yang, Miaoxin Yang, Pang Bo, Madeline Vara, Younan Xia
To better control the FRET process, a nanosensor for the detection of DNA strands with single-base mismatch was developed based on a hybrid material that was comprised of ssDNAs, Au nanoparticles, and fluorophors [476]. Through a distance-dependent process, the photoluminescence from the hybrid material could be increased by a factor of several thousand after the binding of complementary ssDNAs. Based on this nanosensor, the ability to detect single-base mismatches could be increased by 8-fold compared to other types of molecular sensors [476]. In another study, Dulkeith and coworkers found that the photoluminescence from dye molecules could be efficiently quenched when they were attached to the surface of Au nanoparticles with different sizes via a thioether linker [477]. The quenching was caused not only by an increase in the nonradiative rate but also by a drastic decrease in the radiative rate of the dye. They further investigated the quantum yield of Cy5 molecules attached to the surface of Au nanoparticles via an ssDNA spacer to control the distance between the Cy5 molecules and the Au surface [478]. The distance-dependent quantum efficiency was almost exclusively governed by the radiative rate.
3D bioprinting for organ and organoid models and disease modeling
Published in Expert Opinion on Drug Discovery, 2023
Amanda C. Juraski, Sonali Sharma, Sydney Sparanese, Victor A. da Silva, Julie Wong, Zachary Laksman, Ryan Flannigan, Leili Rohani, Stephanie M. Willerth
Recent advancements in capturing laser-focused phenotypes of engineered cardiac tissues (e.g. 3D bioprinted constructs) are categorized into three specific areas: 1) high-speed, high-resolution 3D imaging platforms and real-time functional assay, 2) imaging-friendly design of engineered tissues, such as sheet-like geometries, 3) advancements in 3D imaging modalities, and improvements in deep learning image analysis tools, 4) noninvasive, live-cell molecular probes such as fluorescence gene-reporter systems, protein tags, and molecular sensors, and finally, 5) incorporation of flexible embedded biosensors into 3D printed cardiac tissues enabling noninvasive, real-time measurements of tissue-generated contractile forces [93]. These recent crucial techniques could help capture phenotypes of 3D-printed cardiac tissues more accurately and precisely, facilitating the identification of drug candidates that could be used to treat cardiovascular diseases.
Advances in luminescence-based technologies for drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Bolormaa Baljinnyam, Michael Ronzetti, Anton Simeonov
The split luciferase approach combined with bioluminescence resonance energy transfer (BRET, for more details about BRET see next section) has also been used to develop unique molecular ‘sensors’ with marked advantages to their fluorescent counterparts. In one such approach, a construct fusing LgBiT to two SmBiT with differing affinities to LgBiT was used to create a bioluminescent Zn2+ sensor that shows vast improvement over existing fluorescent-based sensors [46]. Michielsen et al. attached a red Cy3 fluorophore to the higher affinity SmBiT (SB2) resulting in a high BRET efficiency in the absence of Zn2+. Only after binding of Zn2+ is the interaction of SB2 to LB interrupted, allowing the lower-affinity SB1 to complement with LgBiT and change the emission from red to blue wavelengths.
Local immune response as novel disease mechanism underlying abdominal pain in patients with irritable bowel syndrome
Published in Acta Clinica Belgica, 2022
J. Aguilera-Lizarraga, M. Florens, H. Hussein, G. Boeckxstaens
Visceral pain is initiated by the activation of spinal sensory afferents that innervate the gastrointestinal tract (colonic nociceptors). These afferents express a plethora of molecular nociceptors, i.e. pro-nociceptive ion channels and receptors, including acid-sensing ion channels (ASIC), protease activated receptors, G protein-coupled receptors, transient receptor potential (TRP) channels, ionotrophic receptors, purinergic receptors, and voltage-gated ion channels (CaV, NaV) [49]. These molecular sensors can detect noxious stimuli among which are reactive chemicals, damaging temperatures (either heat or cold), mechanical injury, and ATP and immune mediators (including histamine and cytokines). The latter are released from a wide range of immune cells such as mast cells, macrophages, and neutrophils wherewith the peripheral nerve terminals are located in close proximity. Upon detection of the noxious stimuli, molecular sensors are activated, upregulated and/or sensitized, and action potentials are generated at colonic nociceptive nerve terminals. Based on the location of their soma, colonic nociceptors can be subdivided into splanchnic nerves, whose cell bodies are located within the thoracolumbar dorsal root ganglia (DRG) (T10-L1), and pelvic afferents, with cell bodies within the lumbosacral DRG (L5-S2) [49]. When activated, visceral afferents signal to the dorsal horn of the spinal cord. Prolonged stimulations of primary afferent endings, in turn, can result in chronic facilitation of nociceptive transmission from the gut.