Schnyder, A.; Krähenbühl, S.; Török, M.; Drewe, J.; Huwyler, J. Targeting of skeletal muscle in vitro using biotinylated immunoliposomes. Biochem. J. 2004, 377, 61–67. [ Google Scholar] [ CrossRef] Newton, A. C. Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. Biochem. J. 370, 361–371 (2003). Recent studies have expanded the repertoire of biological functions that are linked to the RSK family of protein kinases, ranging from the regulation of transcription, translation and protein stability to the control of cell survival, cell motility, cell growth and proliferation. Wang, Y.; Newman, M.R.; Benoit, D.S.W. Development of controlled drug delivery systems for bone fracture-targeted therapeutic delivery: A review. Eur. J. Pharm. Biopharm. 2018, 127, 223–236. [ Google Scholar] [ CrossRef] [ PubMed]

All other MSK programs that I know of are reactive in nature. When an individual is feeling pain or has had an obvious injury like a sprain, strain, slip/fall, etc. than the program starts to resolve the symptoms they are experiencing. This is usually focused on pain; however, can also include limitations in range of motion (mobility) and a reduction in strength. Those are the direct symptoms of an MSK and there are many more indirect symptoms that include depression, anxiety, fear, and of course a loss of productivity (presenteeism and absenteeism). That is why we use what we affectionately refer to as the “blood test” of mobility health with our patented Computer-Aided MSK Assessment (CAMA) system. This system is marker-less (meaning there are no sensors to attach to your body) and takes less than ten minutes to produce a mountain of OBJECTIVE data on your employee’s mobility health by looking at every joint in every motion they perform and analyzing their dynamic posture (as opposed to static posture when not moving) throughout. The system analyzes the range of motion health of each joint based on what the American Academy of Orthopedic Surgeons (AAOS) has determined as ideal based on age, weight, height, and gender. Range of motion limitations are the first indicator of an issue that will produce pain. Our brains are wired to protect our joints from further insult to tissues and injury and the first defense mechanism is to limit your ability to move or use that joint. These limitations might be slight and have been something that came on slowly and worsened over a long period of time making us unaware of the limitation.Ghadakzadeh, S.; Mekhail, M.; Aoude, A.; Hamdy, R.; Tabrizian, M. Small Players Ruling the Hard Game: siRNA in Bone Regeneration. J. Bone Miner. Res. 2016, 31, 475–487. [ Google Scholar] [ CrossRef] [ PubMed][ Green Version] Our dataset of 64 FSKs yielded important information about the demographics, professional careers, socioeconomic status, relationships, and even physical appearance of women who have committed serial murder in the United States. All but one FSK in our sample were born in the USA, for example. For those whose ethnicity was documented, almost all (about 90%) were White. Religious affiliation was seldom mentioned in cases, but in all instances when it was, the killer was noted as Christian. Congruent with the data from our study, “Jolly” Jane Toppan was White, had a pleasant appearance, had at least some postsecondary education and training, and was a nurse and caretaker. We might further surmise, but cannot verify, that her Boston Irish heritage included Christianity, as most Irish immigrants to Boston in the 1800s were Roman Catholic. 69 Like the typical FSK from our dataset, she likely began killing in her 20s or 30s, but seems to have gotten away with it for about 15 years – longer than our reported mean, but still within about one standard deviation of it. Like many other FSKs, which I discuss in Chapter 4, Toppan had strong indications of severe mental illness. Arthur, J. S. et al. Mitogen- and stress-activated protein kinase 1 mediates cAMP response element-binding protein phosphorylation and activation by neurotrophins. J. Neurosci. 24, 4324–4332 (2004). Blenis, J., Chung, J., Erikson, E., Alcorta, D. A. & Erikson, R. L. Distinct mechanisms for the activation of the RSK kinases/MAP2 kinase/pp90rsk and pp70–S6 kinase signaling systems are indicated by inhibition of protein synthesis. Cell Growth Differ. 2, 279–285 (1991).

FSKs have held a wide variety of jobs, including sex worker, drug dealer, psychic, food server, farmer, and Sunday school (religious) teacher. However, an alarming number of serial killers (39%) have worked in health-related positions (e.g., nurses and nurse’s aides). In addition, more than one out of five has held another direct caregiver role (e.g., stay-at-home mother, stay-at-home wife, babysitter). That means that most (more than 60%) of FSKs were in charge of others’ well-being, particularly of those who are vulnerable. Newman, M.R.; Benoit, D.S. Local and targeted drug delivery for bone regeneration. Curr. Opin. Biotechnol. 2016, 40, 125–132. [ Google Scholar] [ CrossRef][ Green Version]Richards, S. A., Dreisbach, V. C., Murphy, L. O. & Blenis, J. Characterization of regulatory events associated with membrane targeting of p90 ribosomal S6 kinase 1. Mol. Cell. Biol. 21, 7470–7480 (2001). Xing, J., Ginty, D. D. & Greenberg, M. E. Coupling of the RAS–MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase. Science 273, 959–963 (1996). Etchison, D., Milburn, S. C., Edery, I., Sonenberg, N. & Hershey, J. W. Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000-dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex. J. Biol. Chem. 257, 14806–14810 (1982).

Jensen, C. J. et al. 90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase-1. J. Biol. Chem. 274, 27168–27176 (1999). Provided evidence for the phosphorylation of RSK2 by PDK1, thus extending the findings which implicated PDK1 in the activation of AKT/PKB, PKC and S6K, and suggesting that PDK1 controls several crucial growth factor-activated signal-transduction pathways. Years later, a relative stated that, despite being a good student and doing well in school, Wuornos started acting out around age ten or eleven. She shoplifted and set a fire that burned her face. 84 When school officials recommended counseling for Wuornos, her grandmother declined to grant permission. When Wuornos got pregnant at age 14, she was sent to live at a home for unwed mothers. Staff reported her as hostile and unable to get along with others. She gave birth to a baby boy, whom she gave up for adoption.Zaru, R., Ronkina, N., Gaestel, M., Arthur, J. S. & Watts, C. The MAPK-activated kinase Rsk controls an acute Toll-like receptor signaling response in dendritic cells and is activated through two distinct pathways. Nature Immunol. 8, 1227–1235 (2007). Demonstrated that Toll-like receptor-dependent activation of RSK is activated not only by ERK but also by p38 through the intermediates MK2 and MK3. Carrière, A. et al. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediated raptor phosphorylation. Curr. Biol. 21 Aug 2008 (doi: 10.1016/j.cub.2008.07.078). Jativa, S.D.; Thapar, N.; Broyles, D.; Dikici, E.; Daftarian, P.; Jiménez, J.J.; Daunert, S.; Deo, S.K. Enhanced Delivery of Plasmid DNA to Skeletal Muscle Cells using a DLC8-Binding Peptide and ASSLNIA-Modified PAMAM Dendrimer. Mol. Pharm. 2019, 16, 2376–2384. [ Google Scholar] [ CrossRef] [ PubMed]