Prolonged amelioration of acute lung allograft rejection by overexpression of human interleukin-10 under control of a long acting ubiquitin C promoter in rats

BACKGROUND: The prolonged effect of electroporation-mediated human interleukin-10 (hIL-10) overexpression in skeletal muscle under the control of the constitutional polyubiquitin C promoter (pUb hIL-10) on rat lung allograft rejection was evaluated. METHODS: Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Either 2.5 mug pCIK hIL-10 (hIL-10/cytomegalovirus early promoter enhancer) alone (Group I/sacrifice Day 5 and II/sacrifice Day 10) or in combination with 2.5 mug pUb hIL-10 (hIL-10/UbC promoter; Group III/sacrifice Day 10) were injected into the tibialis anterior muscle of the recipient, followed by electroporation 24 hours before transplantation. Animals in Control Groups IV and V without gene transfer were euthanized on Day 5 and 10, respectively. All animals received a daily non-therapeutic dose of cyclosporine A (2.5 mg/kg). RESULTS: In Control Group IV, complete rejection (median A3B3) was noted on Day 5 with a Pao(2) of 43 +/- 9 mm Hg. In recipients of Control Group V, measurement of gas exchange on Day 10 and rejection grading was impossible because of complete destruction of the allograft. Group I animals on Day 5 (233 +/- 123 mm Hg; p = 0.02 vs Group IV) and Group II animals on Day 10 (150 +/- 139 mm Hg; p = 0.15 vs Group IV) demonstrated improved graft function. Graft function in Group III was further improved on Day 10 (299 +/- 123 mm Hg; p = 0.002 vs Group IV; p = 0.05 vs Group II; p = 0.36 vs Group I). Rejection was significantly reduced in Group III (median, A2B2) compared with Group II (median, A4B3; p < 0.05). CONCLUSIONS: Interleukin-10 overexpression under control of the constitutive ubiquitin C promoter ameliorates acute rejection and preserves lung graft function for a prolonged time.

TA-RE: An Exchange Language for Mining Software Repositories

Software repositories have been getting a lot of attention from researchers in recent years. In order to analyze software repositories, it is necessary to first extract raw data from the version control and problem tracking systems. This poses two challenges: (1) extraction requires a non-trivial effort, and (2) the results depend on the heuristics used during extraction. These challenges burden researchers that are new to the community and make it difficult to benchmark software repository mining since it is almost impossible to reproduce experiments done by another team. In this paper we present the TA-RE corpus. TA-RE collects extracted data from software repositories in order to build a collection of projects that will simplify extraction process. Additionally the collection can be used for benchmarking. As the first step we propose an exchange language capable of making sharing and reusing data as simple as possible.

Electrophysiological indices of response inhibition in a Go/NoGo task predict self-control in a social context.

Recent research demonstrates that response inhibition-a core executive function-may subserve self-regulation and self-control. However, it is unclear whether response inhibition also predicts self-control in the multifaceted, high-level phenomena of social decision-making. Here we examined whether electrophysiological indices of response inhibition would predict self-control in a social context. Electroencephalography was recorded as participants completed a widely used Go/NoGo task (the cued Continuous Performance Test). Participants then interacted with a partner in an economic exchange game that requires self-control. Results demonstrated that greater NoGo-Anteriorization and larger NoGo-P300 peak amplitudes-two established electrophysiological indices of response inhibition-both predicted more self-control in this social game. These findings support continued integration of executive function and self-regulation and help extend prior research into social decision-making processes.

Molecular control of cardiac sodium homeostasis in health and disease.

INTRODUCTION Cardiac myocytes utilize three high-capacity Na transport processes whose precise function can determine myocyte fate and the triggering of arrhythmias in pathological settings. We present recent results on the regulation of all three transporters that may be important for an understanding of cardiac function during ischemia/reperfusion episodes. METHODS AND RESULTS Refined ion selective electrode (ISE) techniques and giant patch methods were used to analyze the function of cardiac Na/K pumps, Na/Ca exchange (NCX1), and Na/H exchange (NHE1) in excised cardiac patches and intact myocytes. To consider results cohesively, simulations were developed that account for electroneutrality of the cytoplasm, ion homeostasis, water homeostasis (i.e., cell volume), and cytoplasmic pH. The Na/K pump determines the average life-time of Na ions (3-10 minutes) as well as K ions (>30 minutes) in the cytoplasm. The long time course of K homeostasis can determine the time course of myocyte volume changes after ion homeostasis is perturbed. In excised patches, cardiac Na/K pumps turn on slowly (-30 seconds) with millimolar ATP dependence, when activated for the first time. In steady state, however, pumps are fully active with <0.2 mM ATP and are nearly unaffected by high ADP (2 mM) and Pi (10 mM) concentrations as may occur in ischemia. NCX1s appear to operate with slippage that contributes to background Na influx and inward current in heart. Thus, myocyte Na levels may be regulated by the inactivation reactions of the exchanger which are both Na- and proton-dependent. NHE1 also undergo strong Na-dependent inactivation, whereby a brief rise of cytoplasmic Na can cause inactivation that persists for many minutes after cytoplasmic Na is removed. This mechanism is blocked by pertussis toxin, suggesting involvement of a Na-dependent G-protein. Given that maximal NCX1- and NHE1-mediated ion fluxes are much greater than maximal Na/K pump-mediated Na extrusion in myocytes, the Na-dependent inactivation mechanisms of NCX1 and NHE1 may be important determinants of cardiac Na homeostasis. CONCLUSIONS Na/K pumps appear to be optimized to continue operation when energy reserves are compromised. Both NCX1 and NHE1 activities are regulated by accumulation of cytoplasmic Na. These principles may importantly control cardiac cytoplasmic Na and promote myocyte survival during ischemia/reperfusion episodes by preventing Ca overload.

Outcomes after early administration of plasma exchange in pediatric central nervous system inflammatory demyelination.

The use of plasma exchange has been described in steroid-refractory central nervous system inflammatory demyelination in adults, but less has been published regarding its use in children and adolescents. We describe 12 children treated with plasma exchange for acute severe central nervous system inflammatory demyelination. The clinical attack leading to plasma exchange included symptomatic spinal cord lesions in 10 and symptomatic brainstem lesions in 2 children. Diagnosis was acute transverse myelitis in 6, relapsing-remitting multiple sclerosis in 5, and acute disseminated encephalomyelitis in 1 child. Adverse events related to plasma exchange necessitating intervention were observed in 3 children. Median Expanded Disability Status Scale score at plasma exchange start was 7.5 (range 4-9.5). At 3 months, 7 children were ambulatory without aid (Expanded Disability Status Scale score of ≤4). This retrospective study suggests that plasma exchange can be effective in ameliorating symptoms in severe pediatric central nervous system inflammatory demyelination, although lack of randomization or control group limits the ability to attribute this outcome entirely to plasma exchange.