Reversible Blockade of Complex I or Inhibition of PKCβ Reduces Activation and Mitochondria Translocation of p66\u3csup\u3eShc\u3c/sup\u3e to Preserve Cardiac Function after Ischemia

Aim Excess mitochondrial reactive oxygen species (mROS) play a vital role in cardiac ischemia reperfusion (IR) injury. P66Shc, a splice variant of the ShcA adaptor protein family, enhances mROS production by oxidizing reduced cytochrome c to yield H2O2. Ablation of p66Shc protects against IR injury, but it is unknown if and when p66Shc is activated during cardiac ischemia and/or reperfusion and if attenuating complex I electron transfer or deactivating PKCβ alters p66Shc activation during IR is associated with cardioprotection. Methods Isolated guinea pig hearts were perfused and subjected to increasing periods of ischemia and reperfusion with or without amobarbital, a complex I blocker, or hispidin, a PKCβ inhibitor. Phosphorylation of p66Shc at serine 36 and levels of p66Shc in mitochondria and cytosol were measured. Cardiac functional variables and redox states were monitored online before, during and after ischemia. Infarct size was assessed in some hearts after 120 min reperfusion. Results Phosphorylation of p66Shc and its translocation into mitochondria increased during reperfusion after 20 and 30 min ischemia, but not during ischemia only, or during 5 or 10 min ischemia followed by 20 min reperfusion. Correspondingly, cytosolic p66Shc levels decreased during these ischemia and reperfusion periods. Amobarbital or hispidin reduced phosphorylation of p66Shc and its mitochondrial translocation induced by 30 min ischemia and 20 min reperfusion. Decreased phosphorylation of p66Shc by amobarbital or hispidin led to better functional recovery and less infarction during reperfusion. Conclusion Our results show that IR activates p66Shc and that reversible blockade of electron transfer from complex I, or inhibition of PKCβ activation, decreases p66Shc activation and translocation and reduces IR damage. These observations support a novel potential therapeutic intervention against cardiac IR injury

A Note on Venture Capital Networks: Promise and Performance

Since 1984 Informal Venture Networks (VCNs) have been formed and are currently operating in several states and Canada. However, little has been written in regard to the performance of these networks. This article presents the results of preliminary research concerning their performance. Our research reveals several factors that are presently limiting the VCNs’ success and will continue to do so until diey are changed. The limited success of the VCNs to date is primarily the result of a lack of funding. Because of small operating budgets, most VCNs have only minimal amounts available for marketing and promotion. Until the VCNs are adequately funded, their high promise will not be matched by performance

A Pilot Study to Measure Upper Extremity H-reflexes Following Neuromuscular Electrical Stimulation Therapy after Stroke

Upper extremity (UE) hemiparesis persists after stroke, limiting hand function. Neuromuscular electrical stimulation (NMES) is an effective intervention to improve UE recovery, although the underlying mechanisms are not fully understood. Our objective was to establish a reliable protocol to measure UE agonist–antagonist forearm monosynaptic reflexes in a pilot study to determine if NMES improves wrist function after stroke. We established the between-day reliability of the H-reflex in the extensor carpi radialis longus (ECRL) and flexor carpi radialis (FCR) musculature for individuals with prior stroke (n = 18). The same-day generation of ECRL/FCR H-reflex recruitment curves was well tolerated, regardless of age or UE spasticity. The between-day reliability of the ECRL H-reflex was enhanced above FCR, similar to healthy subjects [20], with the Hmax the most reliable parameter quantified in both muscles. H-reflex and functional measures following NMES show the potential for NMES-induced increases in ECRL Hmax, but confirmation requires a larger clinical study. Our initial results support the safe, easy, and efficacious use of in-home NMES, and establish a potential method to measure UE monosynaptic reflexes after stroke

Laser-Induced Plasma Analysis for Surrogate Nuclear Debris

This work identifies analytical lines in laser-induced plasma for chemical analyses of major elements found in surrogate nuclear debris. These lines are evaluated for interferences and signal strength to insure they would be useful to measure relative concentrations. Compact, portable instruments are employed and can be included as part of a mobile nuclear forensics laboratory for field screening of nuclear debris and contamination. The average plasma temperature is measured using the well-established Boltzmann plot technique, and plasma\u27s average electron density is determined using empirical formulae based on Stark broadening of the H-alpha line. These measurements suggest existence of partial local thermal equilibrium

Heart sparing radiotherapy techniques in breast cancer: A focus on deep inspiration breath hold

Adjuvant radiation therapy is a critical component of breast cancer management. However, when breast cancer patients receive incidental radiation to the heart, there is an increased risk of cardiac disease and mortality. This is most common for patients with left-sided breast cancers and those receiving nodal irradiation as part of treatment. The overall risk of cardiac toxicity increases 4-16% with each Gray increase in mean heart radiation dose, with data suggesting that no lower limit exists which would eliminate cardiac risk entirely. Radiation techniques have improved over time, leading to lower cardiac radiation exposure than in the past. This decline is expected to reduce the incidence of radiation-induced heart dysfunction in patients. Deep inspiration breath hold (DIBH) is one such technique that was developed to reduce the risk of cardiac death and coronary events. DIBH is a non-invasive approach that capitalizes on the natural physiology of the respiratory cycle to increase the distance between the heart and the therapeutic target throughout the course of radiation therapy. DIBH has been shown to decrease the mean incidental radiation doses to the heart and left anterior descending coronary artery by approximately 20-70%. In this review, we summarize different techniques for DIBH and discuss recent data on this technique

Complete transfer of populations from a single state to a pre-selected superposition of states using Piecewise Adiabatic Passage

We develop a method for executing robust and selective transfer of populations between a single level and pre-selected superpositions of energy eigenstates. Viewed in the frequency domain, our method amounts to executing a series of simultaneous adiabatic passages into each component of the target superposition state. Viewed in {the} time domain, the method works by accumulating the wavefunction of the target wave packet as it revisits the Franck Condon region, in what amounts to an extension of the Piecewise Adiabatic Passage technique [ Shapiro et.al., Phys. Rev. Lett. 99, 033002 (2007)] to the multi-state regime. The viability of the method is verified by performing numerical tests for the Na_2 molecule.Comment: 8 pages, 4 figure

Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

Background: Immunity, latent herpesvirus reactivation, physiological stress and circadian rhythms were assessed during six month spaceflight onboard ISS. Blood and saliva samples were collected early, mid and late in-flight and returned for immediate analysis. Mid-point study data (10 of 17 planned subjects) will be presented. Results: Some shifts in leukocyte distribution occurred during flight, including alterations in CD8+ T cell maturation. General T cell function was consistently reduced early in-flight. Levels CD8+/IFNg+ producing T cells were depressed early in-flight, and immediately upon landing. Persistent mitogen-dependant reductions were observed in IFNg, IL-17a, IL-10, TNFa and IL-6 production. Monocyte production of IL-10 was reduced, whereas IL-8 levels were increased. Levels of mRNA for the TNFa, IL-6 and IFNg were transiently elevated early in-flight, and the dynamics of TNF and IL-6 gene expression were somewhat antagonistic to their corresponding receptors during flight. The number of virus-specific CD8+ T-cells was measured using MHC tetramers, while their function was measured using intracellular cytokine analysis following peptide stimulation. Both the number and function of EBV-specific cells decreased during flight as compared to preflight levels. The number of CMV-specific T-cells generally increased as the mission progressed while their function was variable. Viral (EBV) load in blood was elevated postflight. Anti-EBV VCA antibodies were significantly elevated by R+0; anti-EA antibodies were not significantly elevated at landing; and anti-CMV antibodies were somewhat elevated during flight. Higher levels of salivary EBV DNA were found during flight. VZV DNA reactivation occurred in ~50 % of astronauts during flight, continuing for up to 30 days post-flight. CMV was shed in 35 % the in-flight and 30% of postflight urine samples of the crewmembers. There was generally a higher level of cortisol as measured in urine and saliva in the astronauts during flight, but plasma cortisol was relatively unchanged during flight. Circadian rhythm of salivary cortisol was altered during flight. Conclusion. Some alterations in immunity do not resolve during six month spaceflight, consequentially resulting in persistent herpesvirus reactivation. Ongoing immune dysregulation may represent specific clinical risks for exploration-class space missions