Selective ion changes during spontaneous mitochondrial transients in intact astrocytes.

The bioenergetic status of cells is tightly regulated by the activity of cytosolic enzymes and mitochondrial ATP production. To adapt their metabolism to cellular energy needs, mitochondria have been shown to exhibit changes in their ionic composition as the result of changes in cytosolic ion concentrations. Individual mitochondria also exhibit spontaneous changes in their electrical potential without altering those of neighboring mitochondria. We recently reported that individual mitochondria of intact astrocytes exhibit spontaneous transient increases in their Na(+) concentration. Here, we investigated whether the concentration of other ionic species were involved during mitochondrial transients. By combining fluorescence imaging methods, we performed a multiparameter study of spontaneous mitochondrial transients in intact resting astrocytes. We show that mitochondria exhibit coincident changes in their Na(+) concentration, electrical potential, matrix pH and mitochondrial reactive oxygen species production during a mitochondrial transient without involving detectable changes in their Ca(2+) concentration. Using widefield and total internal reflection fluorescence imaging, we found evidence for localized transient decreases in the free Mg(2+) concentration accompanying mitochondrial Na(+) spikes that could indicate an associated local and transient enrichment in the ATP concentration. Therefore, we propose a sequential model for mitochondrial transients involving a localized ATP microdomain that triggers a Na(+)-mediated mitochondrial depolarization, transiently enhancing the activity of the mitochondrial respiratory chain. Our work provides a model describing ionic changes that could support a bidirectional cytosol-to-mitochondria ionic communication.

Missouri River Flood Coordination Task Force Report, September 25, 2011

The Missouri River floods of 2011 will go down in history as the longest duration flooding event this state has seen to date. The combination of above normal snowfall in the upper Missouri River basin followed by the equivalent of nearly one year’s worth of rainfall in May created an above normal runoff situation which filled the Missouri River and the six main reservoirs within the basin. Compounding this problem was colder than normal temperatures which kept much of the snow pack in the upper basin on the ground longer into the spring, setting the stage for this historic event.

Coordination between zinc and phosphate homeostasis involves the transcription factor PHR1, the phosphate exporter PHO1, and its homologue PHO1;H3 in Arabidopsis.

Interactions between zinc (Zn) and phosphate (Pi) nutrition in plants have long been recognized, but little information is available on their molecular bases and biological significance. This work aimed at examining the effects of Zn deficiency on Pi accumulation in Arabidopsis thaliana and uncovering genes involved in the Zn-Pi synergy. Wild-type plants as well as mutants affected in Pi signalling and transport genes, namely the transcription factor PHR1, the E2-conjugase PHO2, and the Pi exporter PHO1, were examined. Zn deficiency caused an increase in shoot Pi content in the wild type as well as in the pho2 mutant, but not in the phr1 or pho1 mutants. This indicated that PHR1 and PHO1 participate in the coregulation of Zn and Pi homeostasis. Zn deprivation had a very limited effect on transcript levels of Pi-starvation-responsive genes such as AT4, IPS1, and microRNA399, or on of members of the high-affinity Pi transporter family PHT1. Interestingly, one of the PHO1 homologues, PHO1;H3, was upregulated in response to Zn deficiency. The expression pattern of PHO1 and PHO1;H3 were similar, both being expressed in cells of the root vascular cylinder and both localized to the Golgi when expressed transiently in tobacco cells. When grown in Zn-free medium, pho1;h3 mutant plants displayed higher Pi contents in the shoots than wild-type plants. This was, however, not observed in a pho1 pho1;h3 double mutant, suggesting that PHO1;H3 restricts root-to-shoot Pi transfer requiring PHO1 function for Pi homeostasis in response to Zn deficiency.

2014 Transportation Coordination in Iowa

The 2012 Iowa Code section 324A.4, subsection 2, states the Iowa Department of Transportation (DOT) “shall biennially prepare a report to be submitted to the general assembly and the governor prior to December 15 of even-numbered years. The report shall recommend methods to increase transportation coordination and improve the efficiency of federal, state, and local government programs used to finance public transit services and may address other topics as appropriate.” Iowa has long been a leader in transportation coordination, from designated public transit agencies covering all 99 counties with little duplication, to requiring any agency receiving public dollars for the provision of transportation to first coordinate with the local public transit agency before providing the transportation on their own, to the creation of the Iowa Transportation Coordination Council. Coordination allows Iowa to provide much needed transportation services to the citizens of Iowa with the most efficient use of public funds. Coordination has been an important topic in Iowa for many years, but during these times of economic constraint and restraint and Iowa’s changing demographics, coordination of transportation services becomes even more critical.

Photodynamic therapy induces selective extravasation of macromolecules: Insights using intravital microscopy.

Photodynamic therapy (PDT) with Visudyne acts by direct cellular phototoxicity and/or by an indirect vascular-mediated effect. Here, we demonstrate that the vessel integrity interruption by PDT can promote the extravasation of a macromolecular agent in normal tissue. To obtain extravasation in normal tissue PDT conditions were one order of magnitude more intensive than the ones in tissue containing neovessels reported in the literature. Fluorescein isothiocyanate dextran (FITC-D, 2000 kDa), a macromolecular agent, was intravenously injected 10 min before (LK0 group, n=14) or 2h (LK2 group, n=16) after Visudyne-mediated PDT in nude mice bearing a dorsal skin fold chamber. Control animals had no PDT (CTRL group, n=8). The extravasation of FITC-D from blood vessels in striated muscle tissue was observed in both groups in real-time for up to 2500 s after injection. We also monitored PDT-induced leukocyte rolling in vivo and assessed, by histology, the corresponding inflammatory reaction score in the dorsal skin fold chambers. In all animals, at the applied PDT conditions, FITC-D extravasation was significantly enhanced in the PDT-treated areas as compared to the surrounding non-treated areas (p<0.0001). There was no FITC-D leakage in the control animals. Animals from the LK0 group had significantly less FITC-D extravasation than those from the LK2 group (p=0.0002). In the LK0 group FITC-D leakage correlated significantly with the inflammation (p<0.001). At the selected conditions, Visudyne-mediated PDT promotes vascular leakage and FITC-D extravasation into the interstitial space of normal tissue. The intensity of vascular leakage depends on the time interval between PDT and FITC-D injection. This concept could be used to locally modulate the delivery of macromolecules in vivo.

Selective resonance suppression 1H-[13C] NMR spectroscopy with asymmetric adiabatic RF pulses.

Despite obvious improvements in spectral resolution at high magnetic field, the detection of 13C labeling by 1H-[13C] NMR spectroscopy remains hampered by spectral overlap, such as in the spectral region of 1H resonances bound to C3 of glutamate (Glu) and glutamine (Gln), and C6 of N-acetylaspartate (NAA). The aim of this study was to develop, implement, and apply a novel 1H-[13C] NMR spectroscopic editing scheme, dubbed "selective Resonance suppression by Adiabatic Carbon Editing and Decoupling single-voxel STimulated Echo Acquisition Mode" (RACED-STEAM). The sequence is based on the application of two asymmetric narrow-transition-band adiabatic RF inversion pulses at the resonance frequency of the 13C coupled to the protons that need to be suppressed during the mixing time (TM) period, alternating the inversion band downfield and upfield from the 13C resonance on odd and even scans, respectively, thus suppressing the detection of 1H resonances bound to 13C within the transition band of the inversion pulse. The results demonstrate the efficient suppression of 1H resonances bound to C3 of Glu and Gln, and C4 of Glu, which allows the 1H resonances bound to C6 of NAA and C4 of Gln to be revealed. The measured time course of the resolved labeling into NAA C6 with the new scheme was consistent with the slow turnover of NAA.

Evolution of Coordination in Social Networks: A Numerical Study

Coordination games are important to explain efficient and desirable social behavior. Here we study these games by extensive numerical simulation on networked social structures using an evolutionary approach. We show that local network effects may promote selection of efficient equilibria in both pure and general coordination games and may explain social polarization. These results are put into perspective with respect to known theoretical results. The main insight we obtain is that clustering, and especially community structure in social networks has a positive role in promoting socially efficient outcomes.

The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis.

The ability of pollutants to affect human health is a major concern, justified by the wide demonstration that reproductive functions are altered by endocrine disrupting chemicals. The definition of endocrine disruption is today extended to broader endocrine regulations, and includes activation of metabolic sensors, such as the peroxisome proliferator-activated receptors (PPARs). Toxicology approaches have demonstrated that phthalate plasticizers can directly influence PPAR activity. What is now missing is a detailed molecular understanding of the fundamental basis of endocrine disrupting chemical interference with PPAR signaling. We thus performed structural and functional analyses that demonstrate how monoethyl-hexyl-phthalate (MEHP) directly activates PPARgamma and promotes adipogenesis, albeit to a lower extent than the full agonist rosiglitazone. Importantly, we demonstrate that MEHP induces a selective activation of different PPARgamma target genes. Chromatin immunoprecipitation and fluorescence microscopy in living cells reveal that this selective activity correlates with the recruitment of a specific subset of PPARgamma coregulators that includes Med1 and PGC-1alpha, but not p300 and SRC-1. These results highlight some key mechanisms in metabolic disruption but are also instrumental in the context of selective PPAR modulation, a promising field for new therapeutic development based on PPAR modulation.

Thrombin-sensitive photodynamic agents: a novel strategy for selective synovectomy in rheumatoid arthritis.

Protease-sensitive macromolecular prodrugs have attracted interest for bio-responsive drug delivery to sites with up-regulated proteolytic activities such as inflammatory or cancerous lesions. Here we report the development of a novel polymeric photosensitizer prodrug (T-PS) to target thrombin, a protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients, for minimally invasive photodynamic synovectomy. In T-PS, multiple photosensitizer units are tethered to a polymeric backbone via short, thrombin-cleavable peptide linkers. Photoactivity of the prodrug is efficiently impaired due to energy transfer between neighbouring photosensitizer units. T-PS activation by exogenous and endogenous thrombin induced an increase in fluorescence emission by a factor of 16 after in vitro digestion and a selective fluorescence enhancement in arthritic lesions in vivo, in a collagen-induced arthritis mouse model. In vitro studies on primary human synoviocytes showed a phototoxic effect only after enzymatic digestion of the prodrug and light irradiation, thus demonstrating the functionality of T-PS induced PDT. The developed photosensitizer prodrugs combine the passive targeting capacity of macromolecular drug delivery systems with site-selective photosensitizer release and activation. They illuminate lesions with pathologically enhanced proteolytic activity and induce cell death, subsequent to irradiation.

Selective ablation of photovoltaic materials with UV laser sources for monolithic interconnection of devices based on a-Si:H

Lasers are essential tools for cell isolation and monolithic interconnection in thin-film-silicon photovoltaic technologies. Laser ablation of transparent conductive oxides (TCOs), amorphous silicon structures and back contact removal are standard processes in industry for monolithic device interconnection. However, material ablation with minimum debris and small heat affected zone is one of the main difficulty is to achieve, to reduce costs and to improve device efficiency. In this paper we present recent results in laser ablation of photovoltaic materials using excimer and UV wavelengths of diode-pumped solid-state (DPSS) laser sources. We discuss results concerning UV ablation of different TCO and thin-film silicon (a-Si:H and nc-Si:H), focussing our study on ablation threshold measurements and process-quality assessment using advanced optical microscopy techniques. In that way we show the advantages of using UV wavelengths for minimizing the characteristic material thermal affection of laser irradiation in the ns regime at higher wavelengths. Additionally we include preliminary results of selective ablation of film on film structures irradiating from the film side (direct writing configuration) including the problem of selective ablation of ZnO films on a-Si:H layers. In that way we demonstrate the potential use of UV wavelengths of fully commercial laser sources as an alternative to standard backscribing process in device fabrication.

Pancréatite aiguë clinique après chimio-embolisation sélective d'un carcinome hépatocellulaire [Acute clinical pancreatitis following selective transcatheter arterial chemoembolization of hepatocellular carcinoma]

Acute pancreatitis can complicate non-selective transcatheter arterial embolization of hepatocellular carcinoma with an incidence ranging from 1,7% (acute clinical pancreatitis) to 40% (biological pancreatitis). This complication is thought to be related to embolization of extrahepatic arterial collaterals.We report herein a case of acute clinical pancreatitis developing within 24 hours after a second course of selective transcatheter arterial chemo-embolization into the proper hepatic artery. Neither anatomical arterial variation nor particular risk factor for acute pancreatitis could be identified. This complication is unusual after selective arterial embolization. Because it may clinically mimick a postembolization syndrome, dosage of serum pancreatic enzymes should be performed systematically in case of abdominal pain following chemoembolization.

Collective bargaining in U.S. higher education, 1960-1971 : a selective bibliography, 1972.

This document represents a substantial attempt to survey the literature of labor negotiations as it relates to the faculty in higher education.