Chelsea Massaro

A Potential Anticancer Therapy: Developing Selective, Irreversible Inhibitors of the JAK3 Kinase Domain

The Janus kinase (JAK) family of four non-receptor protein tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) plays a critical role in the transduction of cell surface signals to the nucleus and mediates inflammation, apoptosis, and hematopoiesis. Dysregulation of the JAK pathway through gene overexpression or a mutation is associated with various cancers and autoimmune diseases. This research focuses on developing selective, irreversible inhibitors of the JAK3 kinase domain as a potential anticancer therapy through modifications of FDA-approved multi-kinase nintedanib. Incorporation of a reactive acrylamide group on the phenyl moiety of nintedanib is predicted to result in a selective, irreversible inhibitor which reacts with Cys909 in the kinase domain of JAK3.

Scott McLean

Comparison of Kinematics, Kinetics and Muscle Activity of Walking on Motorized and Non-Motorized Treadmills and Overground in Older Adults

Previously, we demonstrated that walking on a non-motorized treadmill (NMT) elicited a 40% greater EMG activity from plantar flexor (calf) muscles compared to walking overground (OG) and on a motorized treadmill (MT) at similar speeds (SCOPE 2021, 2023). Recently we found that in addition to enhanced plantar flexor activity when walking, use of a NMT produced no observed kinematic changes in ankle movement. Observed kinetic changes suggested that despite greater plantar flexor muscle activity the peak forces were reduced by ~5% which may accommodate a more comfortable gait. Given the age-related shift of gait control from the ankle to the hip (Schloemer et al., 2017), these data suggest that use of a NMT may provide a viable means to elicit enhanced neuromuscular activity with minimal changes to the gait pattern. Therefore, use of NMT may provide a means of intervention to slow or minimize age-related declines in gait associated with an increased risk of falls, disability, cognitive deficiencies, and mortality (Hedrick et al., 2021). Our previous work used young adults to demonstrate the effect of NMT use on gait. The current project will examine NMT use in older adults using methodology developed in our 2023 SCOPE project.

Tatiana Zhuravleva

An Examination of Attentional Focus Instructions (Internal, External, and Holistic) on Behavioral and Physiological Outcome Measures During a Rowing Task

Attentional focus involves directing attention to movement characteristics or action preparation activities (Magill, 2007). Attentional focus can be categorized as either internal (IF) or external (EF). IF involves directing attention to the body’s movements (e.g., focusing on extending the knees), while EF directs attention toward the movement’s effect in the environment (e.g., focusing on an orange cone).Recently, a new attentional focus has been proposed, known as a holistic focus (HF). HF involves directing attention to the general feeling of the movement (e.g., focusing on being explosive) (Becker et al., 2019). It has been suggested that HF might yield performance benefits similar to those of EF. Therefore, further examination of the effect of HF on continuous tasks is required to fully understand the benefits of attentional focus. We chose the rowing task because it is a continuous task that has been investigated in previous studies (Neumann et al., 2020; Neumann et al., 2022).

Fay Guarraci

The Long-Term Effects of Periadolescent Vaporized Nicotine Exposure on Pubertal Onset, Reproductive Behavior and Sexual Motivation in Rats

We examine the long-term effects of periadolescent vaporized nicotine exposure on pubertal onset and the subsequent development of reproductive behavior and sexual motivation in female and male rats. We know that nicotine disrupts reproduction functioning in female and male rats, as well as in women and men. Teen smoking increases risk of drug addictions later in life. Furthermore, injections of nicotine alter the reward circuits of the brain and increase drug self-administration in rats. Therefore, we want to know if protracted peripubertal exposure to vaporized nicotine will disrupt pubertal onset, as well as alter sensitivity to the rewarding effects of sex. Methods: rats will receive single or multiple, daily e-cigarette vape sessions, using Juul 5% Virginia Tobacco Pods in a whole-body exposure chamber or air on consecutive days. The duration of exposure will start just before puberty and last some time into early adulthood. Puberty will be monitored daily until puberty starts. After the last vape session, the rats will be tested for reproductive behavior and sexual motivation using the partner preference paradigm, whereby subjects are given the opportunity to interact with either a sexual partner or a same-sex social partner. Immediately after this test, serum will be collected to measure the nicotine metabolite cotinine to assess level of nicotine exposure in the subjects.