Autophagy is impaired in cardiac ischemia-reperfusion injury

Accumulating evidence attests to a prosurvival role for autophagy under stress, by facilitating removal of damaged proteins and organelles and recycling basic building blocks, which can be utilized for energy generation and targeted macromolecular synthesis to shore up cellular defenses. These observations are difficult to reconcile with the dichotomous prosurvival and death-inducing roles ascribed to macroautophagy in cardiac ischemia and reperfusion injury, respectively. A careful reexamination of ‘flux’ through the macroautophagy pathway reveals that autophagosome clearance is markedly impaired with reperfusion (reoxygenation) in cardiomyocytes following an ischemic (hypoxic) insult, resulting from reactive oxygen species (ROS)-mediated decline in LAMP2 and increase in BECN1 abundance. This results in impaired autophagy that is ‘ineffective’ in protecting against cell death with ischemia-reperfusion injury. Restoration of autophagosome clearance and by inference, ‘adequate’ autophagy, attenuates reoxygenation-induced cell death

Combining ability studies in restorer lines of sunflower (Helianthus annuus L.)

The restorer lines are used to get fertile hybrids in hybrid seed production system of sunflower. Improve-ment of R-lines for fertility and oil content of sunflower is required to get desirable hybrids upon crossing. In the pre-sent study, 6 restorer lines were crossed in full diallele and both direct and reciprocal crosses along with parents were evaluated for their combining ability. The analysis of variance revealed higher magnitude of SCA variance than GCA variance for all the characters studied except for days to 50 per cent flowering. Among six parents, GMU -520 and R-GM-41 were best general combiner for plant height, head diameter, test weight and leaf size in the desired direction. However, GMU-520 has advantage of yield per plant and oil content. From 15 direct crosses R-GM-41 x R -GM-49 exhibited significant specific combining ability for viz., days to 50 per cent flowering (-1.08), plant height (13.69), head diameter (4.79), leaf size (0.74), yield per plant (17.14), volume weight (2.54), test weight (1.75) and oil content (0.34) followed by RCR-630 x GMU-520, R-GM-41 x EC-602060, R-GM-49 x GMU-520 and EC-602060 x GMU-520 each exhibiting good specific combining ability for majority of characters. Among reciprocal crosses R-GM -41 x RCR-8 exhibited a high reciprocal effects for head diameter (4.57), yield per plant (15.16), test weight (2.02) and leaf size (0.75)

Experiment Simulation Configurations Used in DUNE CDR

The LBNF/DUNE CDR describes the proposed physics program and experimental design at the conceptual design phase. Volume 2, entitled The Physics Program for DUNE at LBNF, outlines the scientific objectives and describes the physics studies that the DUNE collaboration will perform to address these objectives. The long-baseline physics sensitivity calculations presented in the DUNE CDR rely upon simulation of the neutrino beam line, simulation of neutrino interactions in the far detector, and a parameterized analysis of detector performance and systematic uncertainty. The purpose of this posting is to provide the results of these simulations to the community to facilitate phenomenological studies of long-baseline oscillation at LBNF/DUNE. Additionally, this posting includes GDML of the DUNE single-phase far detector for use in simulations. DUNE welcomes those interested in performing this work as members of the collaboration, but also recognizes the benefit of making these configurations readily available to the wider community.Comment: 9 pages, 4 figures, configurations in ancillary file

Large Non-perturbative Effects of Small \Delta m^2_{21}/\Delta m^2_{31} and \sin \theta_{13} on Neutrino Oscillation and CP Violation in Matter

In the framework of three generations, we consider the CP violation in neutrino oscillation with matter effects. At first, we show that the non-perturbative effects of two small parameters, \Delta m_{21}^2/\Delta m_{31}^2 and \sin \theta_{13}, become more than 50% in certain ranges of energy and baseline length. This means that the non-perturbative effects should be considered in detailed analysis in the long baseline experiments. Next, we propose a method to include these effects in approximate formulas for oscillation probabilities. Assuming the two natural conditions, \theta_{23}=45^\circ and the fact that the matter density is symmetric, a set of approximate formulas, which involve the non-perturbative effects, has been derived in all channels.Comment: 25 pages, 4 figures, version to appear in JHE

Very Long Baseline Neutrino Oscillation Experiment for Precise Measurements of Mixing Parameters and CP Violating Effects

We analyze the prospects of a feasible, Brookhaven National Laboratory based, very long baseline (BVLB) neutrino oscillation experiment consisting of a conventional horn produced low energy wide band beam and a detector of 500 kT fiducial mass with modest requirements on event recognition and resolution. Such an experiment is intended primarily to determine CP violating effects in the neutrino sector for 3-generation mixing. We analyze the sensitivity of such an experiment. We conclude that this experiment will allow determination of the CP phase $\delta_{CP}$ and the currently unknown mixing parameter $\theta_{13}$, if $\sin ^2 2 \theta_{13} \geq 0.01$, a value $\sim 15$ times lower than the present experimental upper limit. In addition to $\theta_{13}$ and $\delta_{CP}$, the experiment has great potential for precise measurements of most other parameters in the neutrino mixing matrix including $\Delta m^2_{32}$, $\sin^2 2\theta_{23}$, $\Delta m^2_{21}\times \sin 2 \theta_{12}$, and the mass ordering of neutrinos through the observation of the matter effect in the $\nu_\mu \to \nu_e$ appearance channel.Comment: 12 pages, 10 figure

Regulation of the transcription factor EB-PGC1α axis by beclin-1 controls mitochondrial quality and cardiomyocyte death under stress

In cardiac ischemia-reperfusion injury, reactive oxygen species (ROS) generation and upregulation of the hypoxia-inducible protein BNIP3 result in mitochondrial permeabilization, but impairment in autophagic removal of damaged mitochondria provokes programmed cardiomyocyte death. BNIP3 expression and ROS generation result in upregulation of beclin-1, a protein associated with transcriptional suppression of autophagy-lysosome proteins and reduced activation of transcription factor EB (TFEB), a master regulator of the autophagy-lysosome machinery. Partial beclin-1 knockdown transcriptionally stimulates lysosome biogenesis and autophagy via mTOR inhibition and activation of TFEB, enhancing removal of depolarized mitochondria. TFEB activation concomitantly stimulates mitochondrial biogenesis via PGC1α induction to restore normally polarized mitochondria and attenuate BNIP3- and hypoxia-reoxygenation-induced cell death. Conversely, overexpression of beclin-1 activates mTOR to inhibit TFEB, resulting in declines in lysosome numbers and suppression of PGC1α transcription. Importantly, knockdown of endogenous TFEB or PGC1α results in a complete or partial loss, respectively, of the cytoprotective effects of partial beclin-1 knockdown, indicating a critical role for both mitochondrial autophagy and biogenesis in ensuring cellular viability. These studies uncover a transcriptional feedback loop for beclin-1-mediated regulation of TFEB activation and implicate a central role for TFEB in coordinating mitochondrial autophagy with biogenesis to restore normally polarized mitochondria and prevent ischemia-reperfusion-induced cardiomyocyte death

Secondary Beam Monitors for the NuMI Facility at FNAL

The Neutrinos at the Main Injector (NuMI) facility is a conventional neutrino beam which produces muon neutrinos by focusing a beam of mesons into a long evacuated decay volume. We have built four arrays of ionization chambers to monitor the position and intensity of the hadron and muon beams associated with neutrino production at locations downstream of the decay volume. This article describes the chambers' construction, calibration, and commissioning in the beam.Comment: Accepted for publication in Nucl. Instr. Meth.