Mammals of the Pleistocene

A thesis presented to the Graduate Faculty of the College of Arts and Sciences, Department of English and Rhetoric, of Georgia College & State University in partial fulfillment of the requirements for the Master of Fine Arts in Creative Writing degre

Enhancing the Structure of the WRF-Hydro Hydrologic Model for Semiarid Environments

In August 2016, the National Weather Service Office of Water Prediction (NWS/OWP) of the National Oceanic and Atmospheric Administration (NOAA) implemented the operational National Water Model (NWM) to simulate and forecast streamflow, soil moisture, and other model states throughout the contiguous United States. Based on the architecture of the WRF-Hydro hydrologic model, the NWM does not currently resolve channel infiltration, an important component of the water balance of the semiarid western United States. Here, we demonstrate the benefit of implementing a conceptual channel infiltration function (from the KINEROS2 semidistributed hydrologic model) into the WRF-Hydro model architecture, configured as NWM v1.1. After calibration, the updated WRF-Hydro model exhibits reduced streamflow errors for the Walnut Gulch Experimental Watershed (WGEW) and the Babocomari River in southeast Arizona. Model calibration was performed using NLDAS-2 atmospheric forcing, available from the NOAA National Centers for Environmental Prediction (NCEP), paired with precipitation forcing from NLDAS-2, NCEP Stage IV, or local gauge precipitation. Including channel infiltration within WRF-Hydro results in a physically realistic hydrologic response in the WGEW, when the model is forced with high-resolution, gauge-based precipitation in lieu of a national product. The value of accounting for channel loss is also demonstrated in the Babocomari basin, where the drainage area is greater and the cumulative effect of channel infiltration is more important. Accounting for channel infiltration loss thus improves the streamflow behavior simulated by the calibrated model and reduces evapotranspiration bias when gauge precipitation is used as forcing. However, calibration also results in increased high soil moisture bias, which is likely due to underlying limitations of the NWM structure and calibration methodology.University Corporation for Atmospheric Science (UCAR) COMET Cooperative Project; NOAA Joint Technology Transfer Initiative (JTTI) Federal Grant [NA17OAR4590183]6 month embargo; published online 22 April 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Titin visualization in real time reveals an unexpected level of mobility within and between sarcomeres

Contrary to prior models in which titin serves as a stable scaffold in sarcomeres, sarcomeric and soluble titin exchange dynamically in myofibers when calcium levels are low

Mouse intact cardiac myocyte mechanics: cross-bridge and titin-based stress in unactivated cells

A carbon fiber–based cell attachment and force measurement system was used to measure the diastolic stress–sarcomere length (SL) relation of mouse intact cardiomyocytes, before and after the addition of actomyosin inhibitors (2,3-butanedione monoxime [BDM] or blebbistatin). Stress was measured during the diastolic interval of twitching myocytes that were stretched at 100% base length/second. Diastolic stress increased close to linear from 0 at SL 1.85 µm to 4.2 mN/mm2 at SL 2.1 µm. The actomyosin inhibitors BDM and blebbistatin significantly lowered diastolic stress by ∼1.5 mN/mm2 (at SL 2.1 µm, ∼30% of total), suggesting that during diastole actomyosin interaction is not fully switched off. To test this further, calcium sensitivity of skinned myocytes was studied under conditions that simulate diastole: 37°C, presence of Dextran T500 to compress the myofilament lattice to the physiological level, and [Ca2+] from below to above 100 nM. Mean active stress was significantly increased at [Ca2+] > 55 nM (pCa 7.25) and was ∼0.7 mN/mm2 at 100 nM [Ca2+] (pCa 7.0) and ∼1.3 mN/mm2 at 175 nM Ca2+ (pCa 6.75). Inhibiting active stress in intact cells attached to carbon fibers at their resting SL and stretching the cells while first measuring restoring stress (pushing outward) and then passive stress (pulling inward) made it possible to determine the passive cell’s mechanical slack SL as ∼1.95 µm and the restoring stiffness and passive stiffness of the cells around the slack SL each as ∼17 mN/mm2/µm/SL. Comparison between the results of intact and skinned cells shows that titin is the main contributor to restoring stress and passive stress of intact cells, but that under physiological conditions, calcium sensitivity is sufficiently high for actomyosin interaction to contribute to diastolic stress. These findings are relevant for understanding diastolic function and for future studies of diastolic heart failure

Beyond Academics: A Model for Simultaneously Advancing Campus-Based Supports for Learning Disabilities, STEM Students’ Skills for Self-Regulation, and Mentors’ Knowledge for Co-regulating and Guiding

Learning disabilities are highly prevalent on college campuses, yet students with learning disabilities graduate at lower rates than those without disabilities. Academic and psychosocial supports are essential for overcoming challenges and for improving postsecondary educational opportunities for students with learning disabilities. A holistic, multi-level model of campus-based supports was established to facilitate culture and practice changes at the institutional level, while concurrently bolstering mentors’ abilities to provide learning disability-knowledgeable support, and simultaneously creating opportunities for students’ personal and interpersonal development. Mixed methods were used to investigate implementation of coordinated personal, interpersonal, and institutional level supports for undergraduate science, technology, engineering, and math (STEM) students with learning disabilities. A one-group pre-test post-test strategy was used to examine undergraduate outcomes. Participants included 52 STEM undergraduates with learning disabilities, 57 STEM graduate student mentors, 34 STEM faculty mentors, and 34 university administrators and personnel as members of a university-wide council. Enrolled for 2 years, undergraduates were engaged in group meetings involving psychoeducation and reflective discussions, development of self-advocacy projects, and individual mentorship. Undergraduates reported improved self-efficacy (p = 0.001), campus connection (p < 0.001), professional development (p ≤ 0.002), and self-advocacy (p < 0.001) after two academic years. Graduate student mentors increased their understanding about learning disabilities and used their understanding to support both their mentees and other students they worked with. Council members identified and created opportunities for delivering learning disability-related trainings to faculty, mentors and advisors on campus, and for enhancing coordination of student services related to learning and related disorders. Disability-focused activities became integrated in broader campus activities regarding diversity. This research explicates a role that college campuses can play in fostering the wellbeing and the academic and career development of its students with developmental learning and related disorders. It offers an empirically tested campus-based model that is multilevel, holistic, and strengths-based for supporting positive outcomes of young people with learning disabilities in STEM. Moreover, findings advance the knowledge of supports and skills that are important for self-regulating and navigating complex and multi-faceted disability-related challenges within both the postsecondary educational environment and the young adults’ sociocultural context

Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules

Cardiac hypertrophy is enlargement of the heart in response to physiological or pathological stimuli, chiefly involving growth of myocytes in size rather than in number. Previous studies have shown that the expression pattern of a group of genes in hypertrophied heart induced by pressure overload resembles that at the embryonic stage of heart development, a phenomenon known as activation of the “fetal gene program”. Here, using a genome-wide approach we systematically defined genes and pathways regulated in short- and long-term cardiac hypertrophy conditions using mice with transverse aortic constriction (TAC), and compared them with those regulated at different stages of embryonic and postnatal development. In addition, exon-level analysis revealed widespread mRNA isoform changes during cardiac hypertrophy resulting from alternative usage of terminal or internal exons, some of which are also developmentally regulated and may be attributable to decreased expression of Fox-1 protein in cardiac hypertrophy. Genes with functions in certain pathways, such as cell adhesion and cell morphology, are more likely to be regulated by alternative splicing. Moreover, we found 3′UTRs of mRNAs were generally shortened through alternative cleavage and polyadenylation in hypertrophy, and microRNA target genes were generally de-repressed, suggesting coordinated mechanisms to increase mRNA stability and protein production during hypertrophy. Taken together, our results comprehensively delineated gene and mRNA isoform regulation events in cardiac hypertrophy and revealed their relations to those in development, and suggested that modulation of mRNA isoform expression plays an importance role in heart remodeling under pressure overload

Conformation-regulated mechanosensory control via titin domains in cardiac muscle

The giant filamentous protein titin is ideally positioned in the muscle sarcomere to sense mechanical stimuli and transform them into biochemical signals, such as those triggering cardiac hypertrophy. In this review, we ponder the evidence for signaling hotspots along the titin filament involved in mechanosensory control mechanisms. On the way, we distinguish between stress and strain as triggers of mechanical signaling events at the cardiac sarcomere. Whereas the Z-disk and M-band regions of titin may be prominently involved in sensing mechanical stress, signaling hotspots within the elastic I-band titin segment may respond primarily to mechanical strain. Common to both stress and strain sensor elements is their regulation by conformational changes in protein domains

Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions

British Heart Foundatio