Now showing items 1434-1453 of 15044

    • Ca2+/CaM Modulates the Functional Effects of cMyBP-C on the Thin Filament

      Harris, Samantha P.; Yang, Yuanzhang; Harris, Samantha P.; Granzier, Hendrikus L.; Colson, Brett (The University of Arizona., 2017)
      Background. Cardiac myosin binding protein-C (cMyBP-C) is an essential regulator of heart muscle function that is necessary for both normal contraction and for increased contractility in response to inotropic stimuli(1-7). Effects of cMyBP-C on contraction are due to dynamic interactions of cMyBP-C with both actin and myosin, but the mechanism(s) by which cMyBP-C binding to these ligands is modulated are only partly understood. Recently, calmodulin (CaM) was shown to bind to cMyBP-C in the regulatory M-domain(8, 9) near a conserved actin binding site(10). Here we investigated whether CaM competes with actin for binding to cMyBP-C and thus whether CaM affects cMyBP-C function. Methods. Recombinant N’-terminal domains of cMyBP-C were used in pull-down assays, co-sedimentation binding assays, and actin activated myosin ATPase assays to determine effects of CaM binding on cMyBP-C. Results. In accordance with previous reports, we found that CaM binds to N’-terminal domains of cMyBP-C in the presence of Ca2+ (Ca2+/CaM) with a binding affinity comparable to cMyBP-C binding to actin (3-10 μM). We further show that Ca2+/CaM reduces cMyBP-C apparent binding affinity for actin, consistent with the competition between Ca2+/CaM and actin for binding to cMyBP-C. Ca2+/CaM also reversed the inhibitory effects of cMyBP-C N’-terminal domains on actin activated myosin ATPase rates, consistent with reduced cMyBP-C interactions with actin. However, apo-CaM (calcium-free calmodulin) did not influence the ability of cMyBP-C to activate actomyosin ATPase rates at low Ca2+. Phosphorylation of cMyBP-C by PKA significantly increased its binding to both Ca2+/CaM and apo-CaM. Phosphorylated cMyBP-C was also a less potent regulator of cross-bridge cycling in ATPase assays. Conclusions. These data demonstrate that Ca2+/CaM competes with actin for binding to cMyBP-C and selectively reverses the inhibitory effects of cMyBP-C on actomyosin interactions. However, apo-CaM does not compete with cMyBP-C binding to actin and does not affect the ability of cMyBP-C to activate the thin filament at low Ca2+. Ca2+/CaM may serve as additional regulatory mechanism in addition to phosphorylation of cMyBP-C to regulate its function. These data suggest that Ca2+/CaM is a novel modulator of cMyBP-C function that can dynamically tune cMyBP-C effects on contraction potentially as [Ca2+]i rises and falls during the time course of a single heart beat.
    • Cadmium content in sphalerites, copper ores, soils and plants in southern Arizona

      Kresan, Peter Lawrence, 1948- (The University of Arizona., 1975)
    • Cadmium distribution in the rat after subacute exposure to cadmium in drinking water

      Brancato, David Joseph, 1950- (The University of Arizona., 1974)
    • Caesalpinia pulcherrima, Calliandra californica, and Justicia specigera: Chemical and environmental regulation of their growth and development

      Bailey, Douglas A.; Davison, Elizabeth L., 1947- (The University of Arizona., 1989)
      Investigations of three low-water requiring landscape species produced the following results: (1) Although Calliandra californica flowered under photoperiods from 12 to 16 hours, plants produced more elongation under 16 hour days. Plants grew taller and developed greener foliage under irradiances of 600 μmol·m⁻²·s⁻¹. Branching was not stimulated by foliar sprays of BA, PBA, or BA + GA₄₊₇. (2) Caesalpinia pulcherrima increased biomass under 16 hour days, but were stunted and chlorotic under irradiances of 1950 μmol·m⁻²·s⁻¹. Internodal lengths were restricted with drenches of 3.75 mg · pot-1 uniconazole, and plants sprayed with 500 mg·liter⁻¹ PBA developed more axillary branching without negative elongating effects. (3) Justicia specigera gained more height under 12 hour days, and produced greener foliage, more elongation, and faster flowering under irradiances of 600 μmol·m⁻²·s⁻¹. Plants showed restricted internodal elongation and fewer flowers when drenched with 5.0 mg·pot⁻¹ uniconazole, and developed more axillary branching with no detrimental elongation effects when sprayed with 100 mg·liter⁻¹ BA + GA₄₊₇.
    • Caffeine consumption and symptom severity among midlife Filipina Americans

      Berg, Judith A.; Zitzmann, Lori Jean (The University of Arizona., 2000)
      Caffeine has diverse effects on human physiology. Certain symptoms associated with caffeine consumption are similar to those reported by some women during midlife. Lifestyle factors such as caffeine consumption must be viewed within the context of culture and ethnicity. The Neuman Systems Model provided the theoretical framework for this secondary data analysis. A descriptive cross-sectional survey design was used to examine questions related to study variables. A cluster of symptoms (fatigue, palpitations, insomnia, GI distress) were described through the lens of both perimenopausal transition and caffeine consumption for a sample of 160 midlife Filipina Americans. No significant relationship was found between specific symptoms and symptom clusters and either caffeine consumption or perimenopausal status. Midlife Filipina Americans consume caffeine in low amounts and report mi nimal to mild symptom severity most often. Knowledge gained from this study may be applied to other groups to maintain congruency with ethnicity of clients.
    • Calcium Homeostasis Modulator (CALHM1/2) in Pulmonary Arterial Hypertension

      Yuan, Jason X.-J.; Garcia, Joe G.N.; Rodriguez, Marisela; Vanderpool, Rebecca; Carew, Jennifer S. (The University of Arizona., 2020)
      Calcium Homeostasis Modulator in Pulmonary Arterial Hypertension byMarisela Rodriguez Master of Science (M.S.) in Clinical Translational Sciences University of Arizona, Tucson 2020 Professor Jason Yuan, Co-Chair Professor Joe G.N. Garcia, Co-Chair Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that predominantly affects women. The increased pulmonary arterial pressure (PAP) in patients with PAH is mainly generated by increased pulmonary vascular resistance (PVR) (18, 70, 103). Sustained pulmonary vasoconstriction, excessive pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular wall stiffness are the major causes for the elevated PVR and PAP in patients with PAH. Concentric pulmonary vascular remodeling is among one of the major causes for the elevated pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP), also one the major causes for increasing afterload of right ventricle (RV) and inducing right heart failure leading to death if untreated (103). Excessive pulmonary artery smooth muscle cell (PASMC) proliferation and inhibited PASMC apoptosis have been implicated in the development and progression of pulmonary vascular wall thickening in patients with PAH and animals with severe experimental pulmonary hypertension (PH). An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in PASMCs is not only a trigger for PASMC contraction and pulmonary vasoconstriction, but also an important stimulus for PASMC proliferation, migration, and pulmonary vascular remodeling (16, 83, 85). [Ca2+]cyt in PASMCs is increased by Ca2+ influx through Ca2+-permeable cation channels in the plasma membrane (PM) and Ca2+ release or mobilization from the intracellular Ca2+ stores, mainly the sarcoplasmic (SR) or endoplasmic (ER) reticulum. There are at least three classes of Ca2+-permeable cation channels identified in human and animal PASMCs that are responsible for Ca2+ influx associated with excitation-concentration coupling (EC-coupling) and Ca2+-mediated PASMC proliferation and migration: (i) voltage-dependent Ca2+ channels (VDCC), (ii) receptor-operated Ca2+ channels (ROCC), and (iii) store-operated Ca2+ channels (SOCC) (50, 57). VDCC are opened or activated by membrane depolarization due to, for example, decreased activity or downregulated K+ channels (57) while ROCC is opened or activated by ligand-mediated binding to membrane receptors including G protein-coupled receptors (GPCR) and tyrosine kinase receptors (TKR). Activation of GPCR or TKR upon binding to respective ligands increases production of diacylglycerol (DAG) and inosital 1,4,5-triphosphate (IP3), two important intracellular second messengers. DAG then activates ROCC and introduces receptor-operated Ca2+ entry (ROCE), while IP3 activates IP3 receptors, also referred to as Ca2+ release channels, in the SR/ER membrane and induces Ca2+ release from the intracellular stores to the cytosol contributing to increasing [Ca2+]cyt. Depletion or significant reduction of Ca2+ levels in the ER/SR due to Ca2+ mobilization or release leads to Ca2+ influx through SOCC, commonly referred to as store-operated Ca2+ entry (SOCE). Active depletion of intracellularly stored Ca2+ in the SR/ER then also results in the dimerization and translocation of STIM1 (and/or STIM2) in the SR/ER membrane and forms STIM protein puncta close to the SR/ER-plasma membrane junctions. Then the multimer STIM1/2 proteins in the ER-PM recruit Orai proteins in the plasma membrane to form SOCC responsible for SOCE (16). It has been shown that transient receptor potential (TRP) channels are involved in forming ROCC in PASMCs and can be activated directly by DAG. In our previous publishing, we have determined that the proliferative phenotype of PASMCs employs SOCC leading to increased expression levels of STIM2, not STIM1, and also Orai2 and TRPC6 expressions from IPAH patients- altogether providing an underlying mechanism for enhanced SOCE. TRP channels are also reported to participate in the regulation of SOCE in many cell types (21). In addition to TRP channels, many other types of Ca2+-permeable cation channels may also participate in ROCE and SOCE. Calcium homeostasis modulators (CALHM) including CALHM1 and CALHM2, have been identified as a family of physiologically important plasma membrane ion channels that are permeable to both cations and anions. These channels are allosterically regulated by membrane voltage (or membrane potential) and extracellular Ca2+; CALHM1 and CALHM2 channels are closed at the resting membrane potential but can be opened by strong membrane depolarization. Reduction of extracellular [Ca2+] increases the probability for CALHM channels to open, which allow the channels to be activated at a negative potential. Ultimately, it is widely known that the increased [Ca2+]cyt due to upregulated and activated Ca2+-permeable cation channels contribute to pulmonary vasoconstriction and excessive proliferation of PASMCs (and other cell types, for example fibroblasts and myofibroblasts) in patients with PAH, eventually this leads to concentric pulmonary vascular remodeling (17). Therefore, a rise in intracellular [Ca2+] and activated Ca2+ in PASMC via upregulated and/or activated Ca2+-permeable cation channels play a major role. CALHM1 and CALHM2 have a significant impact on the pathogenesis that lead to the development and progression of PAH. As discussed earlier, sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling comprise of two major causes for the elevated PVR and PAP in patients with PAH and animals with experimental PH (50). Pulmonary vasoconstriction is certainly a major cause for increasing PVR and PAP at the early stage of disease development, while concentric pulmonary vascular remodeling and obliterative intima and plexiform lesions are made up of the late state pathological changes that contribute to maintaining high PVR and PAP (57). The transition from the contractile or differentiated phenotype to the synthetic or proliferative phenotype of PASMC is thus an important pathogenic process that promotes vascular remodeling (62) in which we aimed at investigating. In this study, I hypothesized that CALHM1 and/or CALHM2 are involved in PASMC phenotypical transition from the contractile or differentiated phenotype to the synthetic or proliferative phenotype, while CALHM1/2 are upregulated in PASMC from patients with PAH and animals with experimental PH.
    • Calcium intake, physical activity, and bone mineral status in children and youth aged ten to fifteen years

      Lohman, Timothy G.; Hall, Matthew Charles, 1960- (The University of Arizona., 1988)
      This study was conducted to determine if either calcium intake or physical activity is related to bone mineral status in children and youth aged 10 to 15 years. Subjects (n = 30) with high, medium, and low bone mineral status were selected based on radius bone mineral index measurements from a sample of 108 subjects measured 9 to 12 months previously. Calcium intake was estimated from two 24-hour recalls and a food frequency questionnaire. Assessment of activity level was conducted by questionnaire. Single photon absorptiometry was used to obtain bone mineral content (g/cm) and bone mineral index (g/cm²) measurements for the radius and ulna at the midshaft and distal sites. Calcium intake and activity level were found to be similar among the bone mineral index groups. Using regression analysis, however, calcium intake was shown to be significantly related to midshaft ulna bone mineral index and activity level (sports participation) was found to be significantly related to distal ulna bone mineral index.
    • Calcium metasomatism in the Josephine peridotite, southwest Oregon

      Harris, Raymond Charles, 1957- (The University of Arizona., 1989)
    • Calcium movement in a calcareous soil

      Hilal, Mostafa Hassan Mohamed, 1937- (The University of Arizona., 1963)

      Gottung, Beth Ellen. (The University of Arizona., 1983)
    • Calculating the correlation coefficient between selected ability and achievement tests using validity generalization

      Sabers, Darrell; Shiroma, Paul Shigeo, 1960- (The University of Arizona., 1989)
      The correlation coefficient between an ability test and achievement test is necessary in order to estimate the effects of the regression of IQ on achievement when calculating a discrepancy between them for the purpose of classifying a child as learning disabled. Weighted mean correlations and their respective variances were computed across studies for one of 11 ability-achievement test pairs using a meta-analysis procedure called Validity Generalization. The results indicated that there is no "global correlation coefficient" that will accurately represent the relationship between all ability and achievement tests. Furthermore, critical data necessary to adjust correlations and their respective variances for statistical artifacts were not reported in the literature. Thus, the results obtained from the subgroups could be due to capitalization on chance.
    • Calculation of C¹³ and N¹⁵ production in the sun

      Kruger, Steven Toby, 1939- (The University of Arizona., 1963)
    • Calculation of transmission line parameters for multiconductor lines in a multi-dielectric medium

      Cangellaris, Andreas C.; McFarland, Robert Bynum, 1964- (The University of Arizona., 1992)
      A method for computing the per-unit-length capacitance matrix and the inductance matrix for multiconductor transmission lines in a multi-dielectric medium is presented. The multi-dielectric medium consists of both planar and non-planar dielectric regions. The formulation is based on an integral equation method for the free charge distribution on conductor surfaces and the polarization charge distribution on the non-planar dielectric interfaces. The kernel of the integral equation is a space domain Green's function for a layered medium. The numerical solution is obtained by the method of moments.
    • Calculations of the anisotropic hyperfine coupling constants in organic radicals

      Babaqi, Abdulla Saleh (The University of Arizona., 1980)
    • Calculus of variations solutions to problems of vertical flight

      Mason, Joseph David, 1937- (The University of Arizona., 1963)
    • The calendar heap: A new implementation of the calendar queue

      Sanchez, Paul J.; Ramsey, Terry, 1946- (The University of Arizona., 1989)
      A new implementation of the calendar queue is described in this thesis. The calendar queue as previously implemented depended upon the use of multiple linked lists for the control of queue discipline. In the calendar heap implementation, the heap has been used to replace the previous functions of the linked list. Testing of the claim of O(1) execution time for the calendar queue was done. Comparisons of execution times of the calendar queue and the calendar heap have been made. Descriptions of the implementation as well as the complete C code for the calendar heap are included.
    • Calibration and the decision variable partition model

      Smith, Mariam (The University of Arizona., 1981)
    • Calibration of a distributed land surface model for a semi-arid basin using remotely sensed data.

      Yatheendradas, Soni.; Gupta, Hoshin; Sorooshian, Soroosh (The University of Arizona., 2003)
      A meso-scale medium-resolution land surface model using the NCEP's NOAH code has been setup over the San Pedro basin in Arizona. The model is driven using the 50-year hydrologically balanced land surface data set developed at the University of Washington (UW), precipitation data from the PERSIANN (Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks) system, and solar radiation influx from the University of Maryland's SRB (Surface Radiation Budget). The remotely sensed forcings are introduced in stages to explore the sensitivity on the simulation results to the remote sensing information. The model was calibrated, using the available remote sensing forcings, to ground observations of the turbulent heat fluxes and ground temperatures using multi-criteria calibration techniques. The simulation results for the distributed model using the default (uncalibrated) and the calibrated parameters are intercompared against each other and against the UW outputs. Results show the PERSIANN data substitution to be a major improving factor in the results in capturing the surface runoffs and the soil moisture diurnal variations because of its fmer sub-hourly temporal resolution as against the UW precipitation forcing which is basically at a daily temporal resolution. Separately, the default seasonal vegetation variation in the NOAH, i.e., constant greenness leaf area index (LAI) and variable greenness fraction (GF) was changed to the opposite case of constant GF and varying LAI using LAI data from the MODIS sensor. Visual inspection of the simulation results show the incompatibility between the NOAH and the MODIS LAI as per the MODIS LAI substitution method used in this study.