Stretch‐Induced Increase in Cardiac Contractility Is Independent of Myocyte Ca\u3csup\u3e2+\u3c/sup\u3e While Block of Stretch Channels by Streptomycin Improves Contractility After Ischemic Stunning

Stretching the cardiac left ventricle (LV) enhances contractility but its effect on myoplasmic [Ca2+] is controversial. We measured LV pressure (LVP) and [Ca2+] as a function of intra-LV stretch in guinea pig intact hearts before and after 15 min global stunning ± perfusion with streptomycin (STM), a stretch activated channel blocker. LV wall [Ca2+] was measured by indo-1 fluorescence and LVP by a saline-filled latex balloon inflated in 50 μL steps to stretch the LV. We implemented a mathematical model to interpret crossbridge dynamics and myofilament Ca2+ responsiveness from the instantaneous relationship between [Ca2+] and LVP ± stretching. We found that: (1) stretch enhanced LVP but not [Ca2+] before and after stunning in either control (CON) and STM groups, (2) after stunning [Ca2+] increased in both groups although higher in STM versus CON (56% vs. 39%), (3) STM-enhanced LVP after stunning compared to CON (98% vs. 76% of prestunning values), and (4) stretch-induced effects on LVP were independent of [Ca2+] before or after stunning in both groups. Mathematical modeling suggested: (1) cooperativity in cross-bridge kinetics and myofilament Ca2+ handling is reduced after stunning in the unstretched heart, (2) stunning results in depressed myofilament Ca2+ sensitivity in the presence of attached cross-bridges regardless of stretch, and (3) the initial mechanism responsible for increased contractility during stretch may be enhanced formation of cross-bridges. Thus stretch-induced enhancement of contractility is not due to increased [Ca2+], whereas enhanced contractility after stunning in STM versus CON hearts results from improved Ca2+ handling and/or enhanced actinomyosin cross-bridge cycling

Targeted grazing for the restoration of sub-alpine shrub-encroached grasslands

The decline of agro-pastoral activities has led to a widespread tree and shrub-encroachment of former semi-natural meso-eutrophic grasslands in many European mountain regions. Temporary night camp areas (TNCA) and mineral mix supplements for targeted cattle were arranged over shrub-encroached areas to restore grassland vegetation within the Val Troncea Natural Park (Italy). From 2011 to 2015, their effects on vegetation structure and pastoral value of forage were assessed along permanent transects. Four years after treatments, both practices were effective in reducing the shrub cover and increasing the cover and average height of the herbaceous layer, but changes were more remarkable within TNCA. Moreover, the arrangement of TNCA decreased the cover of nanophanerophytes and increased the cover of graminoids and high quality species, as well as the overall forage pastoral value. In conclusion, TNCA were the most effective pastoral practice to contrast shrub-encroachment and increase herbage mass and forage quality of sub-alpine grasslands

Probing 5f-state configurations in URu2Si2 with U L3-edge resonant x-ray emission spectroscopy

Resonant x-ray emission spectroscopy (RXES) was employed at the U L3 absorption edge and the La1 emission line to explore the 5f occupancy, nf, and the degree of 5f orbital delocalization in the hidden order compound URu2Si2. By comparing to suitable reference materials such as UF4, UCd11, and alpha-U, we conclude that the 5f orbital in URu2Si2 is at least partially delocalized with nf = 2.87 +/- 0.08, and does not change with temperature down to 10 K within the estimated error. These results place further constraints on theoretical explanations of the hidden order, especially those requiring a localized f2 ground state.Comment: 11 pages,7 figure

Pastoral practices to reverse shrub encroachment of sub-alpine grasslands: dung beetles (Coleoptera, Scrabaeoidea) respond more quickly than vegetation

In recent decades, pastoral abandonment has produced profound ecological changes in the Alps. In particular, the reduction in grazing has led to extensive shrub encroachment of semi-natural grasslands, which may represent a threat to open habitat biodiversity. To reverse shrub encroachment, we assessed short-term effects of two different pastoral practices on vegetation and dung beetles (Coleoptera, Scarabaeoidea). Strategic placement of mineral mix supplements (MMS) and arrangement of temporary night camp areas (TNCA) for cattle were carried out during summer 2011 in the Val Troncea Natural Park, north-western Italian Alps. In 2012, one year after treatment, a reduction in shrub cover and an increase in bare ground cover around MMS sites was detected. A more intense effect was detected within TNCA through increases in forage pastoral value, and in the cover and height of the herbaceous layer. Immediately after treatment, changes in dung beetle diversity (total abundance, species richness, Shannon diversity, taxonomic and functional diversity) showed a limited disturbance effect caused by high cattle density. In contrast, dung beetle diversity significantly increased one year later both at MMS and TNCA sites, with a stronger effect within TNCA. Multivariate Regression Trees and associated Indicator Value analyses showed that some ecologically relevant dung beetle species preferred areas deprived of shrub vegetation. Our main conclusions are: i) TNCA are more effective than MMS in terms of changes to vegetation and dung beetles, ii) dung beetles respond more quickly than vegetation to pastoral practices, and iii) the main driver of the rapid response by dung beetles is the removal of shrubs. The resulting increase in dung beetle abundance and diversity, which are largely responsible for grassland ecosystem functioning, may have a positive effect on meso-eutrophic grassland restoration. Shrub encroachment in the Alps may therefore be reversed, and restoration of grassland enhanced, by using appropriate pastoral practices

Ischemia reperfusion dysfunction changes model-estimated kinetics of myofilament interaction due to inotropic drugs in isolated hearts

BACKGROUND: The phase-space relationship between simultaneously measured myoplasmic [Ca(2+)] and isovolumetric left ventricular pressure (LVP) in guinea pig intact hearts is altered by ischemic and inotropic interventions. Our objective was to mathematically model this phase-space relationship between [Ca(2+)] and LVP with a focus on the changes in cross-bridge kinetics and myofilament Ca(2+ )sensitivity responsible for alterations in Ca(2+)-contraction coupling due to inotropic drugs in the presence and absence of ischemia reperfusion (IR) injury. METHODS: We used a four state computational model to predict LVP using experimentally measured, averaged myoplasmic [Ca(2+)] transients from unpaced, isolated guinea pig hearts as the model input. Values of model parameters were estimated by minimizing the error between experimentally measured LVP and model-predicted LVP. RESULTS: We found that IR injury resulted in reduced myofilament Ca(2+ )sensitivity, and decreased cross-bridge association and dissociation rates. Dopamine (8 μM) reduced myofilament Ca(2+ )sensitivity before, but enhanced it after ischemia while improving cross-bridge kinetics before and after IR injury. Dobutamine (4 μM) reduced myofilament Ca(2+ )sensitivity while improving cross-bridge kinetics before and after ischemia. Digoxin (1 μM) increased myofilament Ca(2+ )sensitivity and cross-bridge kinetics after but not before ischemia. Levosimendan (1 μM) enhanced myofilament Ca(2+ )affinity and cross-bridge kinetics only after ischemia. CONCLUSION: Estimated model parameters reveal mechanistic changes in Ca(2+)-contraction coupling due to IR injury, specifically the inefficient utilization of Ca(2+ )for contractile function with diastolic contracture (increase in resting diastolic LVP). The model parameters also reveal drug-induced improvements in Ca(2+)-contraction coupling before and after IR injury

International sport federations in the world city network

In this article, we analyze the transnational urban geographies produced by international sport federations (ISFs) through their global, regional, and national headquarter locations. Data on the global urban presence of 35 major ISFs are examined through connectivity analysis and principal component analysis. The connectivity analysis reveals the relative dominance of cities in Europe and Pacific Asia, whereby Seoul, Tokyo, Kuala Lumpur, Cairo, and Lausanne stand out. The principal component analysis reveals the main subnetworks produced through ISF location decisions, which includes inter alia a "winter sports subnetwork" centered on Ankara, Belgrade, Helsinki, and Stockholm; an "Olympic subnetwork" centered on Lausanne; and a decentered subnetwork with truly "global sports."

Numerical Renormalization Group Study of Pseudo-Fermion and Slave-Boson Spectral Functions in the Single Impurity Anderson Model

We use the numerical renormalization group to calculate the auxiliary spectral functions of the $U=\infty$ Anderson impurity model. The slave--boson and pseudo--fermion spectral functions diverge at the threshold with exponents $\alpha_{b}$ and $\alpha_{f}$ given in terms of the conduction electron phase shifts by the X--ray photoemission and the X--ray absorption exponents respectively. The exact exponents obtained here depend on the impurity occupation number, in contrast to the NCA results. Vertex corrections in the convolution formulae for physical Green's functions are singular at the threshold and may not be neglected in the Fermi liquid regime.Comment: 12 pages, RevTeX 3.0, 2 PS figures appende

Monitoring Subcellular Calcium by Designed Calcium Sensors and the Calcium Sensing Receptor Structure and Function

Calcium (Ca2+) regulates various biological and pathological functions via calcium dynamics and interacting with key calcium binding proteins such as the calcium sensing receptor (CaSR). In this dissertation, the first X-ray structure of the extracellular domain of CaSR was determined by engineering mammalian expression systems. The revealed Ca2+/Mg2+ and Trp derivative L-1,2,3,4-tetrahydronorharman-3-carboxylic acid (TNCA) binding sites and key determinants contribute to the functional cooperativity of CaSR in cells. Magnesium (Mg2+) acts as a heterotropic cooperative co-agonist with calcium to co-activate the function of CaSR, including calcium oscillations. TNCA potentiates CaSR co-activation and recovers a loss of function caused by mutation at the dimer interface calcium binding site. Several mutations of the main Ca2+/TNCA binding site at the hinge region eliminate CaSR activity. Mutations S272A and D216N at the hinge region lead to a loss of Ca2+ binding and complete loss of cooperative binding for Tb3+ using bacterially expressed protein and Trp-sensitized FRET assay. Efforts in the development of new CaSR therapeutics using structure-based drug design were also explored. Next, we aimed to monitor endoplasmic/sarcoplasmic reticulum (ER/SR) mediated subcellular Ca2+ dynamics using our designed calcium sensors CatchER+ and CatchER+-JP45. Using highly inclined laminated optical (HILO) microscopy, we report calcium dynamics in the ER/SR with differential calcium responses to 4-cmc for release and recovery indicating differential Ca2+ signaling from Ca2+ and protein expression subcellular microdomains. We find Ca2+ dynamic differences between the localized high Ca2+ release region of the junctional SR for E-C coupling with targeted CatchER+-JP45 to ryanodine receptor over the global Ca2+ ER/SR regulation of CatchER+ sensor. To understand ER Ca2+ dynamics in neurons, we utilized our sensor CatchER+ and high-resolution HILO imaging to show that 100 µM DHPG induced mGluR1/5 activation leads to IP3R Ca2+ release as well as Ca2+ uptake throughout the soma and dendrites. The differential release and uptake for the ER Ca2+ dynamics in response to DHPG indicates subcellular microdomains throughout the neurons as well. These sensors will significantly impact Ca2+ dynamics research and molecular basis of ER Ca2+ related diseases by exposing Ca2+ dynamics, function, mobility, and trafficking in the ER/SR

Elastocaloric effect with a broad temperature window and low energy loss in a nanograin Ti-44Ni-5Cu-1Al (at%) shape memory alloy

Superelastic Ti-Ni-based shape memory alloys are promising elastocaloric materials for solid-state refrigeration. In this paper, we studied the mechanical properties and elastocaloric effect of a severely cold rolled Ti-44Ni-5Cu-1Al (at.%) alloy composed of nanograins (∼5-16 nm). The alloy exhibits partial stress-induced martensitic transformation with a large quasilinear reversible strain of ∼3.4 % and a small energy dissipation of ∼1.6 MJ/m3 when a maximum stress of 1 GPa is applied. The temperature decrease induced by adiabatic removal of a stress of 1 GPa is of about −5 K, which is mainly due to the reverse transition occurring during unloading. The effective working temperature window of elastocaloric effect larger than 200 K. The coefficient of performance of this alloy reaches ∼13, which is higher than values reported so far for Ti-Ni alloys