Chronic hindlimb ischemia impairs functional vasodilation and vascular reactivity in mouse feed arteries

Vasodilation of lower leg arterioles is impaired in animal models of chronic peripheral ischemia. In addition to arterioles, feed arteries are a critical component of the vascular resistance network, accounting for as much as 50% of the pressure drop across the arterial circulation. Despite the critical importance of feed arteries in blood flow control, the impact of ischemia on feed artery vascular reactivity is unknown. At 14 days following unilateral resection of the femoral–saphenous artery–vein pair, functional vasodilation of the profunda femoris artery was severely impaired, 11 ± 9 versus 152 ± 22%. Although endothelial and smooth muscle-dependent vasodilation were both impaired in ischemic arteries compared to control arteries (Ach: 40 ± 14 versus 81 ± 11%, SNP: 43 ± 12 versus and 85 ± 11%), the responses to acetylcholine and sodium nitroprusside were similar, implicating impaired smooth muscle-dependent vasodilation. Conversely, vasoconstriction responses to norepinephrine were not different between ischemic and control arteries, −68 ± 3 versus −66 ± 3%, indicating that smooth muscle cells were functional following the ischemic insult. Finally, maximal dilation responses to acetylcholine, ex vivo, were significantly impaired in the ischemic artery compared to control, 71 ± 9 versus 97 ± 2%, despite a similar generation of myogenic tone to the same intravascular pressure (80 mmHg). These data indicate that ischemia impairs feed artery vasodilation by impairing the responsiveness of the vascular wall to vasodilating stimuli. Future studies to examine the mechanistic basis for the impact of ischemia on vascular reactivity or treatment strategies to improve vascular reactivity following ischemia could provide the foundation for an alternative therapeutic paradigm for peripheral arterial occlusive disease

Direct CP violation and the ΔI=1/2 rule in K→ππ decay from the standard model

We present a lattice QCD calculation of the ΔI=1/2, K→ππ decay amplitude A0 and ϵ′, the measure of direct CP violation in K→ππ decay, improving our 2015 calculation [1] of these quantities. Both calculations were performed with physical kinematics on a 323×64 lattice with an inverse lattice spacing of a-1=1.3784(68)  GeV. However, the current calculation includes nearly 4 times the statistics and numerous technical improvements allowing us to more reliably isolate the ππ ground state and more accurately relate the lattice operators to those defined in the standard model. We find Re(A0)=2.99(0.32)(0.59)×10-7  GeV and Im(A0)=-6.98(0.62)(1.44)×10-11  GeV, where the errors are statistical and systematic, respectively. The former agrees well with the experimental result Re(A0)=3.3201(18)×10-7  GeV. These results for A0 can be combined with our earlier lattice calculation of A2 [2] to obtain Re(ϵ′/ϵ)=21.7(2.6)(6.2)(5.0)×10-4, where the third error represents omitted isospin breaking effects, and Re(A0)/Re(A2)=19.9(2.3)(4.4). The first agrees well with the experimental result of Re(ϵ′/ϵ)=16.6(2.3)×10-4. A comparison of the second with the observed ratio Re(A0)/Re(A2)=22.45(6), demonstrates the standard model origin of this “ΔI=1/2 rule” enhancement.We present a lattice QCD calculation of the $\Delta I=1/2$, $K\to\pi\pi$ decay amplitude $A_0$ and $\varepsilon'$, the measure of direct CP-violation in $K\to\pi\pi$ decay, improving our 2015 calculation of these quantities. Both calculations were performed with physical kinematics on a $32^3\times 64$ lattice with an inverse lattice spacing of $a^{-1}=1.3784(68)$ GeV. However, the current calculation includes nearly four times the statistics and numerous technical improvements allowing us to more reliably isolate the $\pi\pi$ ground-state and more accurately relate the lattice operators to those defined in the Standard Model. We find ${\rm Re}(A_0)=2.99(0.32)(0.59)\times 10^{-7}$ GeV and ${\rm Im}(A_0)=-6.98(0.62)(1.44)\times 10^{-11}$ GeV, where the errors are statistical and systematic, respectively. The former agrees well with the experimental result ${\rm Re}(A_0)=3.3201(18)\times 10^{-7}$ GeV. These results for $A_0$ can be combined with our earlier lattice calculation of $A_2$ to obtain ${\rm Re}(\varepsilon'/\varepsilon)=21.7(2.6)(6.2)(5.0) \times 10^{-4}$, where the third error represents omitted isospin breaking effects, and Re$(A_0)$/Re$(A_2) = 19.9(2.3)(4.4)$. The first agrees well with the experimental result of ${\rm Re}(\varepsilon'/\varepsilon)=16.6(2.3)\times 10^{-4}$. A comparison of the second with the observed ratio Re$(A_0)/$Re$(A_2) = 22.45(6)$, demonstrates the Standard Model origin of this "$\Delta I = 1/2$ rule" enhancement

Lattice determination of I=0 and 2 ππ scattering phase shifts with a physical pion mass

Phase shifts for s-wave ππ scattering in both the I=0 and I=2 channels are determined from a lattice QCD calculation performed on 741 gauge configurations obeying G-parity boundary conditions with a physical pion mass and lattice size of 323×64. These results support our recent 2021 study of direct CP violation in K→ππ decay, improving our earlier 2015 calculation. The phase shifts are determined for both stationary and moving ππ systems, at three (I=0) and four (I=2) different total momenta. We implement several ππ interpolating operators including a scalar bilinear “σ” operator and paired single-pion bilinear operators with the constituent pions carrying various relative momenta. Several techniques, including correlated fitting and a bootstrap determination of p-values have been used to refine the results and a comparison with the generalized eigenvalue problem method is given. A detailed systematic error analysis is performed which allows phase shift results to be presented at a fixed energy

A Novel Non-Lens βγ−Crystallin and Trefoil Factor Complex from Amphibian Skin and Its Functional Implications

In vertebrates, non-lens betagamma-crystallins are widely expressed in various tissues, but their functions are unknown. The molecular mechanisms of trefoil factors, initiators of mucosal healing and being greatly involved in tumorigenesis, have remained elusive.A naturally existing 72-kDa complex of non-lens betagamma-crystallin (alpha-subunit) and trefoil factor (beta-subunit), named betagamma-CAT, was identified from frog Bombina maxima skin secretions. Its alpha-subunit and beta-subunit (containing three trefoil factor domains), with a non-covalently linked form of alphabeta(2), show significant sequence homology to ep37 proteins, a group of non-lens betagamma-crystallins identified in newt Cynops pyrrhogaster and mammalian trefoil factors, respectively. betagamma-CAT showed potent hemolytic activity on mammalian erythrocytes. The specific antiserum against each subunit was able to neutralize its hemolytic activity, indicating that the two subunits are functionally associated. betagamma-CAT formed membrane pores with a functional diameter about 2.0 nm, leading to K(+) efflux and colloid-osmotic hemolysis. High molecular weight SDS-stable oligomers (>240-kDa) were detected by antibodies against the alpha-subunit with Western blotting. Furthermore, betagamma-CAT showed multiple cellular effects on human umbilical vein endothelial cells. Low dosages of betagamma-CAT (25-50 pM) were able to stimulate cell migration and wound healing. At high concentrations, it induced cell detachment (EC(50) 10 nM) and apoptosis. betagamma-CAT was rapidly endocytosed via intracellular vacuole formation. Under confocal microscope, some of the vacuoles were translocated to nucleus and partially fused with nuclear membrane. Bafilomycin A1 (a specific inhibitor of the vacuolar-type ATPase) and nocodazole (an agent of microtuble depolymerizing), while inhibited betagamma-CAT induced vacuole formation, significantly inhibited betagamma-CAT induced cell detachment, suggesting that betagamma-CAT endocytosis is important for its activities.These findings illustrate novel cellular functions of non-lens betagamma-cyrstallins and action mechanism via association with trefoil factors, serving as clues for investigating the possible occurrence of similar molecules and action mechanisms in mammals

Lattice QCD and Particle Physics

Contribution from the USQCD Collaboration to the Proceedings of the US Community Study on the Future of Particle Physics (Snowmass 2021).Comment: 27 pp. main text, 4 pp. appendices, 30 pp. reference

Lattice QCD and Particle Physics

Contribution from the USQCD Collaboration to the Proceedings of the US Community Study on the Future of Particle Physics (Snowmass 2021)

Variation in size at birth and post-natal growth in the insectivorous bat Pipistrellus subflavus (Chiroptera: Vespertilionidae)

We describe the size and developmental state at birth, examine factors which influence intra- and inter-year variation in post-natal growth, and derive age-predictive equations and logistic growth parameters for the eastern pipistrelle bat, Pipistrellus subflavus. Ambient and roost temperature and insect abundance were lowest, and precipitation highest, before and during the post-natal growth period in 1982, as compared to 1981. We found no sex differences in the size of pups at birth or in post-natal growth rates in a given year; however, body mass and length of forearm of neonates differed significantly between years, being smaller in 1982 than in 1981. During the first two weeks of post-natal growth in both years, the body mass and length of forearm of pups increased linearly at mean rates of 0.15 g.day−1 and 1.12 mm.day−1, respectively. Post-natal growth rates for length of forearm and body mass were the same during the early linear phase of growth, but the intercept for body mass was less and growth trajectories were more variable in 1982. Length of forearm was the least variable and thus most reliable character for estimating age of P. subflavus pups during the first 14 days of post-natal growth. When length of forearm was used in combination with mean changes in the length of the fourth metacarpal-phalangeal epiphyseal gap, we derived reliable age-estimation equations ranging from 1 to 45 days. Litter size averaged 1.96 and 1.93 at birth, but this was reduced to one by the time pups became volant. At birth, litter mass represented 44, and 54% of the post-partum mass of females in 1981 and 1982, respectively. This maternal effort during pregnancy is among the highest reported for bats. At weaning, the body mass of pups approached 80% of adult post-partum body mass, and the length of forearm exceeded 90% of adult female size. Our results suggest that size at birth and post-natal growth are influenced by ambient and roost temperature, rainfall, and the quantity of insects available to pregnant and lactating females. Thus, energetic constraints on both mothers and pups can lead to inter-year and inter-individual differences in maternal effort and post-natal growth of pups