Noninvasive Blood Flow and Oxygenation Measurements in Diseased Tissue

The research presented in this dissertation focused on the application of optical imaging techniques to establish blood flow and oxygen saturation as effective biomarkers for two disease cases, Autism Spectrum Disorder (ASD) and Huntington’s Disease (HD). The BTBR mouse model of ASD was utilized to validate measurements of cerebral blood flow and oxygenation as biomarkers for autism. The R6/2 mouse model of juvenile HD was utilized to validate measurements of skeletal muscle blood flow following tetanic muscle contractions induced by electrical nerve stimulation. Next, a noncontact, camera-based system to measure blood flow and oxygen saturation maps was implemented to improve upon the previous HD mouse results by providing spatial heterogeneity in a wild-type mouse model. Finally, translational research was performed to validate a research design conducting concurrent grip strength force and skeletal muscle blood flow and oxygenation measurements in a healthy human population that will be used to establish HD biomarkers in humans in future clinical applications

TOI 122b and TOI 237b: Two Small Warm Planets Orbiting Inactive M Dwarfs Found by TESS

peer reviewedWe report the discovery and validation of TOI 122b and TOI 237b, two warm planets transiting inactive M dwarfs observed by the Transiting Exoplanet Survey Satellite (TESS). Our analysis shows that TOI 122b has a radius of 2.72 ± 0.18 R[SUB]⊕[/SUB] and receives 8.8 ± 1.0 times Earth's bolometric insolation, and TOI 237b has a radius of 1.44±0.12 R⊕ and receives 3.7 ± 0.5 times Earth's insolation, straddling the 6.7 × Earth insolation that Mercury receives from the Sun. This makes these two of the cooler planets yet discovered by TESS, even on their 5.08 and 5.43 day orbits. Together, they span the small-planet radius valley, providing useful laboratories for exploring volatile evolution around M dwarfs. Their relatively nearby distances (62.23 ± 0.21 pc and 38.11 ± 0.23 pc, respectively) make them potentially feasible targets for future radial velocity follow-up and atmospheric characterization, although such observations may require substantial investments of time on large telescopes

The TESS Objects of Interest Catalog from the TESS Prime Mission

We present 2241 exoplanet candidates identified with data from the Transiting Exoplanet Survey Satellite (TESS) during its 2 yr Prime Mission. We list these candidates in the TESS Objects of Interest (TOI) Catalog, which includes both new planet candidates found by TESS and previously known planets recovered by TESS observations. We describe the process used to identify TOIs, investigate the characteristics of the new planet candidates, and discuss some notable TESS planet discoveries. The TOI catalog includes an unprecedented number of small planet candidates around nearby bright stars, which are well suited for detailed follow-up observations. The TESS data products for the Prime Mission (sectors 1-26), including the TOI catalog, light curves, full-frame images, and target pixel files, are publicly available at the Mikulski Archive for Space Telescopes

Comprehensive profiling of the STE20 kinase family defines features essential for selective substrate targeting and signaling output.

Specificity within protein kinase signaling cascades is determined by direct and indirect interactions between kinases and their substrates. While the impact of localization and recruitment on kinase-substrate targeting can be readily assessed, evaluating the relative importance of direct phosphorylation site interactions remains challenging. In this study, we examine the STE20 family of protein serine-threonine kinases to investigate basic mechanisms of substrate targeting. We used peptide arrays to define the phosphorylation site specificity for the majority of STE20 kinases and categorized them into four distinct groups. Using structure-guided mutagenesis, we identified key specificity-determining residues within the kinase catalytic cleft, including an unappreciated role for the kinase β3-αC loop region in controlling specificity. Exchanging key residues between the STE20 kinases p21-activated kinase 4 (PAK4) and Mammalian sterile 20 kinase 4 (MST4) largely interconverted their phosphorylation site preferences. In cells, a reprogrammed PAK4 mutant, engineered to recognize MST substrates, failed to phosphorylate PAK4 substrates or to mediate remodeling of the actin cytoskeleton. In contrast, this mutant could rescue signaling through the Hippo pathway in cells lacking multiple MST kinases. These observations formally demonstrate the importance of catalytic site specificity for directing protein kinase signal transduction pathways. Our findings further suggest that phosphorylation site specificity is both necessary and sufficient to mediate distinct signaling outputs of STE20 kinases and imply broad applicability to other kinase signaling systems

Single-molecule magnet engineering: building-block approaches

Tailoring the specific magnetic properties of any material relies on the topological control of the constituent metal ion building blocks. Although this general approach does not seem to be easily applied to traditional inorganic bulk magnets, coordination chemistry offers a unique tool to delicately tune, for instance, the properties of molecules that behave as ''magnets'', the so-called single-molecule magnets (SMMs). Although many interesting SMMs have been prepared by a more or less serendipitous approach, the assembly of predesigned, isolatable molecular entities into higher nuclearity complexes constitutes an elegant and fascinating strategy. This Feature article focuses on the use of building blocks or modules (both terms being used indiscriminately) to direct the structure, and therefore also the magnetic properties, of metal ion complexes exhibiting SMM behaviour