Meta-analysis of heat- and chemically upregulated chaperone genes in plant and human cells.

Molecular chaperones are central to cellular protein homeostasis. In mammals, protein misfolding diseases and aging cause inflammation and progressive tissue loss, in correlation with the accumulation of toxic protein aggregates and the defective expression of chaperone genes. Bacteria and non-diseased, non-aged eukaryotic cells effectively respond to heat shock by inducing the accumulation of heat-shock proteins (HSPs), many of which molecular chaperones involved in protein homeostasis, in reducing stress damages and promoting cellular recovery and thermotolerance. We performed a meta-analysis of published microarray data and compared expression profiles of HSP genes from mammalian and plant cells in response to heat or isothermal treatments with drugs. The differences and overlaps between HSP and chaperone genes were analyzed, and expression patterns were clustered and organized in a network. HSPs and chaperones only partly overlapped. Heat-shock induced a subset of chaperones primarily targeted to the cytoplasm and organelles but not to the endoplasmic reticulum, which organized into a network with a central core of Hsp90s, Hsp70s, and sHSPs. Heat was best mimicked by isothermal treatments with Hsp90 inhibitors, whereas less toxic drugs, some of which non-steroidal anti-inflammatory drugs, weakly expressed different subsets of Hsp chaperones. This type of analysis may uncover new HSP-inducing drugs to improve protein homeostasis in misfolding and aging diseases.

The membrane-associated transient receptor potential vanilloid channel is the central heat shock receptor controlling the cellular heat shock response in epithelial cells.

The heat shock response (HSR) is a highly conserved molecular response to various types of stresses, including heat shock, during which heat-shock proteins (Hsps) are produced to prevent and repair damages in labile proteins and membranes. In cells, protein unfolding in the cytoplasm is thought to directly enable the activation of the heat shock factor 1 (HSF-1), however, recent work supports the activation of the HSR via an increase in the fluidity of specific membrane domains, leading to activation of heat-shock genes. Our findings support the existence of a plasma membrane-dependent mechanism of HSF-1 activation in animal cells, which is initiated by a membrane-associated transient receptor potential vanilloid receptor (TRPV). We found in various non-cancerous and cancerous mammalian epithelial cells that the TRPV1 agonists, capsaicin and resiniferatoxin (RTX), upregulated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70 and Hsp90 respectively, while the TRPV1 antagonists, capsazepine and AMG-9810, attenuated the accumulation of Hsp70, Hsp90 and Hsp27 and Hsp70, Hsp90, respectively. Capsaicin was also shown to activate HSF-1. These findings suggest that heat-sensing and signaling in mammalian cells is dependent on TRPV channels in the plasma membrane. Thus, TRPV channels may be important drug targets to inhibit or restore the cellular stress response in diseases with defective cellular proteins, such as cancer, inflammation and aging.

Exposure to superfluous information reduces cooperation and increases antisocial punishment in reputation-based interactions

Human cooperation is often based on reputation gained from previous interactions with third parties. Such reputation can be built on generous or punitive actions, and both, one's own reputation and the reputation of others have been shown to influence decision making in experimental games that control for confounding variables. Here we test how reputation-based cooperation and punishment react to disruption of the cognitive processing in different kinds of helping games with observers. Saying a few superfluous words before each interaction was used to possibly interfere with working memory. In a first set of experiments, where reputation could only be based on generosity, the disruption reduced the frequency of cooperation and lowered mean final payoffs. In a second set of experiments where reputation could only be based on punishment, the disruption increased the frequency of antisocial punishment (i.e. of punishing those who helped) and reduced the frequency of punishing defectors. Our findings suggest that working memory can easily be constraining in reputation-based interactions within experimental games, even if these games are based on a few simple rules with a visual display that provides all the information the subjects need to play the strategies predicted from current theory. Our findings also highlight a weakness of experimental games, namely that they can be very sensitive to environmental variation and that quantitative conclusions about antisocial punishment or other behavioral strategies can easily be misleading.

Use of Incentive/Disincentive Contracting to Mitigate Work Zone Traffic Impacts, 2012

Incentive/disincentive clauses (I/D) are designed to award payments to contractors if they complete work ahead of schedule and to deduct payments if they exceed the completion time. A previously unanswered question is, “Did the costs of the actual work zone impacts that were avoided justify the incentives paid?” This report answers that question affirmatively based on an evaluation of 20 I/D projects in Missouri from 2008 to 2011. Road user costs (RUC) were used to quantify work zone impacts and included travel delays, vehicle operating costs, and crash costs. These were computed using work zone traffic conditions for partial-closure projects and detour volumes and routes for full-closure projects. Conditions during construction were compared to after construction. Crash costs were computed using Highway Safety Manual methodology. Safety Performance Functions produced annual crash frequencies that were translated into crash cost savings. In considering an average project, the percentage of RUC savings was around 13% of the total contract amount, or $444,389 of $3,464,620. The net RUC savings produced was around $7.2 million after subtracting the approximately $1.7 million paid in incentives. In other words, for every dollar paid in incentives, approximately 5.3 dollars of RUC savings resulted. I/D provisions were very successful in saving RUC for projects with full-closure, projects in urban areas, and emergency projects. Rural, non-emergency projects successfully saved RUC but not at the same level as other projects. The I/D contracts were also compared to all Missouri Department of Transportation contracts for the same time period. The results show that I/D projects had a higher on-time completion percentage and a higher number of bids per call than average projects. But I/D projects resulted in 4.52% higher deviation from programmed costs and possibly more changes made after the award. A survey of state transportation departments and contractors showed that both agreed to the same issues that affect the success of I/D contracts. Legal analysis suggests that liquidated damages is preferred to disincentives, since enforceability of disincentives may be an issue. Overall, in terms of work zone impact mitigation, I/D contracts are very effective at a relatively low cost.

Assessment of debris-flow susceptibility at medium-scale in the Barcelonnette Basin, France

Debris flows are among the most dangerous processes in mountainous areas due to their rapid rate of movement and long runout zone. Sudden and rather unexpected impacts produce not only damages to buildings and infrastructure but also threaten human lives. Medium- to regional-scale susceptibility analyses allow the identification of the most endangered areas and suggest where further detailed studies have to be carried out. Since data availability for larger regions is mostly the key limiting factor, empirical models with low data requirements are suitable for first overviews. In this study a susceptibility analysis was carried out for the Barcelonnette Basin, situated in the southern French Alps. By means of a methodology based on empirical rules for source identification and the empirical angle of reach concept for the 2-D runout computation, a worst-case scenario was first modelled. In a second step, scenarios for high, medium and low frequency events were developed. A comparison with the footprints of a few mapped events indicates reasonable results but suggests a high dependency on the quality of the digital elevation model. This fact emphasises the need for a careful interpretation of the results while remaining conscious of the inherent assumptions of the model used and quality of the input data.

Western Iowa Missouri River Flooding -- Geo-Infrastructure Damage Assessment, Repair and Mitigation Strategies, TR-638, 2013

The 2011 Missouri River flooding caused significant damage to many geo-infrastructure systems including levees, bridge abutments/foundations, paved and unpaved roadways, culverts, and embankment slopes in western Iowa. The flooding resulted in closures of several interchanges along Interstate 29 and of more than 100 miles of secondary roads in western Iowa, causing severe inconvenience to residents and losses to local businesses. The main goals of this research project were to assist county and city engineers by deploying and using advanced technologies to rapidly assess the damage to geo-infrastructure and develop effective repair and mitigation strategies and solutions for use during future flood events in Iowa. The research team visited selected sites in western Iowa to conduct field reconnaissance, in situ testing on bridge abutment backfills that were affected by floods, flooded and non-flooded secondary roadways, and culverts. In situ testing was conducted shortly after the flood waters receded, and several months after flooding to evaluate recovery and performance. Tests included falling weight deflectometer, dynamic cone penetrometer, three-dimensional (3D) laser scanning, ground penetrating radar, and hand auger soil sampling. Field results indicated significant differences in roadway support characteristics between flooded and non-flooded areas. Support characteristics in some flooded areas recovered over time, while others did not. Voids were detected in culvert and bridge abutment backfill materials shortly after flooding and several months after flooding. A catalog of field assessment techniques and 20 potential repair/mitigation solutions are provided in this report. A flow chart relating the damages observed, assessment techniques, and potential repair/mitigation solutions is provided. These options are discussed for paved/unpaved roads, culverts, and bridge abutments, and are applicable for both primary and secondary roadways.

Biologie oxydative et implications cliniques du peroxynitrite [Oxidative biology and clinical implications of peroxynitrite]

Peroxynitrite is a strong biological oxidant formed from the reaction between two free radicals, superoxide and nitric oxide. It inflicts serious damages to most biomolecules, including proteins, lipids and nucleic acids, either through direct oxidation or through the secondary generation of highly reactive free radicals. When such damage reaches a critical threshold, cells eventually die by necrosis or apoptosis. An excessive production of peroxynitrite is instrumental in the development of organ damage and dysfunction in conditions such as circulatory shock and ischemia-reperfusion. In such circumstances, various synthetic metalloporphyrins, able to degrade peroxynitrite, disclose important beneficial effects in animal models, and might therefore represent novel pharmacological agents in the future.

Indemnizaciones a las victimas del terrorismo

En este informe de legislación, el autor da razón del contenido básico de la Ley 32/1999, de 8 de octubre, de solidaridad con las víctimas del terrorismo, así como de los reglamentos que la desarrollan, aprobados por los Reales Decretos 1.912/1999 y 1.974/1999, de 17 y 23 de diciembre.

Indemnitzacions a les víctimes del terrorisme

En aquest informe de legislació, l'autor exposa el contingut bàsic de la Llei 32/1999, de 8 d¿octubre, de solidaritat amb les víctimes del terrorisme, així com els reglaments que la desenvolupen, aprovats pels Reials Decrets 1.912/1999 i 1.974/1999, de 17 i 23 de desembre.

Sin opción. Comentario a la STS, 1ª, 17.2.2006, por la que se niega el derecho de opción de las víctimas de exigir responsabilidad civil a los funcionarios públicos ante los órganos de la jurisdicción ordinaria

Actualmente, tras la reforma del art. 146.1 de la Ley 30/1992, de 26 de noviembre, de régimen jurídico de las Administraciones públicas y del procedimiento administrativo común (LRJPAC) llevada a cabo por la Ley 4/1999, de 13 de enero, nadie duda ya que las víctimas de daños causados por los funcionarios y demás agentes públicos en el ejercicio de sus funciones están obligadas a dirigir su reclamación indemnizatoria a la Administración a la que aquellos pertenezcan, sin poder demandarles ante los órganos de la jurisdicción civil en exigencia de su responsabilidad extracontractual. Según el art. 145 LRJPAC, la víctima deberá reclamar directamente a la Administración ­iniciando la tramitación del procedimiento administrativo específico previsto en los arts. 142 y 143 LRJPAC e interponiendo, eventualmente, recurso contencioso-administrativo contra la resolución desestimatoria que le ponga fin­, y ésta, una vez haya satisfecho la indemnización, ejercerá acción de repetición contra el funcionario o agente responsable cuando el mismo haya ocasionado el daño con dolo o culpa grave. Ya no existe, por tanto, el genérico derecho de opción anteriormente reconocido por el art. 43 de la Ley de régimen jurídico de la administración del Estado de 1957.

Roadway Lighting on Secondary Roads in Iowa, HR-251, 1984

There are approximately 800 installations of destination lighting at secondary road intersections in Iowa. Approximately 90% of these have only a single luminaire. The other installations have two luminaires. No warrants currently exist for justifying the use of this type of lighting. Previous research has examined the safety benefits from full lighting of rural intersections that generally serve substantially higher traffic volumes than secondary road intersections in Iowa. However, the safety benefit of destination lighting at intersections carrying relatively low volumes has not been the subject of previous research. The research reported here, sponsored by the Iowa Department of Transportation, was undertaken to identify locations where destination lighting could be expected to improve highway safety. If destination lighting were shown to reduce accident frequency, warrants for its use on secondary roads could be developed. An inventory of secondary road lighting installations in Iowa was assembled. From this inventory, two samples were constituted that would permit two separate comparisons of the accident experience with and without destination lighting. Before and after comparisons were made for the same locations if accident records were available for at least one full year both preceding and following the installation of destination lighting. Accident records for this purpose were available from a statewide computerized record system covering the period from 1977 through 1982. The accident experience at locations having destination lighting installed before 1978 was compared with a sample of comparable locations not having destination lighting. The sample of secondary road intersections used for the before and after comparison included 91 locations. The sample of continuously lighted locations included 102 intersections. Accident experience at these locations was compared with the experience at 102 intersections that were not lighted. The intersections included in these samples averaged only 0.31 accidents per year. The accident rate at secondary road intersections that had destination lighting did not differ significantly from the accident rate at intersections that were not lighted. This conclusion was derived from both comparisons, the before and after experience and the comparison of experience at intersections that were continuously lighted with that at unlighted locations. Furthermore, no significant differences were noted between lighted and unlighted locations in the proportion of accidents that occurred at night. The distribution of accidents by type also did not differ between unlighted intersections and those having destination lighting. It was not possible to formulate warrants for destination lighting since analyses directed toward identifying specific characteristics of an intersection that could be correlated with highway safety did not yield any useful relationships. However, it was noted that the average damages for night accidents that occurred at lighted intersections were lower than for accidents at unlighted intersections. Even in the absence of a more definitive demonstration of beneficial effects, destination lighting is perceived by officials in most of the counties having such installations as yielding desirable effects and is recognized as helpful to motorists in performing the guidance function in driving. Given this benefit and a relatively low cost (an average of $74 per year for one luminaire), and given that the subjective criteria that have been used in the past to justify the installation of destination lighting have led to a high degree of public acceptance and satisfaction, it is recommended that the same subjective criteria continue to be used in lieu of definitive warrants.

Stream Stabilization in Western Iowa, HR-352, 1994

Stream channel erosion in the deep loess soils region of western Iowa causes severe damage along hundreds of miles of streams in twenty-two counties. The goal of this project was to develop information, systems, and procedures for use in making resource allocation decisions related to the protection of transportation facilities and farmland from damages caused by stream channel erosion. Section one of this report provides an introduction. Section two presents an assessment of stream channel conditions from aerial and field reconnaissance conducted in 1993 and 1994 and a classification of the streams based on a six stage model of stream channel evolution. A Geographic Information System is discussed that has been developed to store and analyze data on the stream conditions and affected infrastructure and assist in the planning of stabilization measures. Section three presents an evaluation of two methods for predicting the extent of channel degradation. Section four presents an estimate of costs associated with damages from stream channel erosion since the time of channelization until 1992. Damage to highway bridges represent the highest costs associated with channel erosion, followed by railroad bridges and right-of-way; loss of agricultural land represents the third highest cost. An estimate of costs associated with future channel erosion on western Iowa streams is also presented in section four. Section four also presents a procedure to estimate the benefits and costs of implementing stream stabilization measures. The final section of this report, section five, presents information on the development of the organizational structure and administrative procedures which are being used to plan, coordinate, and implement stream stabilization projects and programs in western Iowa.

Construction and Maintenance Practices to Minimize the Potential Liability of Counties for Roads in Rural Subdivisions, HR-221, 1981

In an earlier research project, HR-204, the magnitude and nature of highway related tort claims against counties in Iowa were investigated. However, virtually all of the claims identified in that research resulted from incidents that occurred in areas with predominantly agricultural land use. With recent increases in the rural non-farm population, many traditionally urban problems are also appearing in built-up areas under county jurisdiction. This trend is expected to continue so that counties must anticipate a change in the nature of the tort claims they will encounter. Problems that heretofore have been unique to cities may become commonplace in areas for which counties are responsible. The research reported here has been directed toward an investigation of those problems in rural subdivisions that lead to claims growing out of the provision of highway services by counties. Lacking a sufficient database among counties for the types of tort claims of interest in this research, a survey was sent to 259 cities in Iowa in order to identify highway related problems leading to those claims. The survey covered claims during a five year period from 1975 to 1980. Over one-third of the claims reported were based on alleged street defects. Another 34 percent of the claims contained allegations of damages due to backup of sanitary sewers or defects in sidewalks. By expanding the sample from the 164 cities that responded to the survey, it was estimated that a total of $49,000,000 in claims had been submitted to all 259 cities. Over 34% of this amount resulted from alleged defects in the use of traffic signs, signals, and markings. Another 42% arose from claims of defects in streets and sidewalks. Payments in settlement of claims were about 13.4% of the amount asked for those claims closed during the period covered by the survey. About $9,000,000 in claims was pending on June 30, 1980 according to the information furnished. Officials from 23 cities were interviewed to provide information on measures to overcome the problems leading to tort claims. On the basis of this information, actions have been proposed that can be undertaken by counties to reduce the potential for highway-related claims resulting from their responsibilities in rural subdivisions and unincorporated communities. Suggested actions include the eight recommendations contained in the final report for the previous research under HR-204. In addition, six recommendations resulted from this research, as follows: 1. Counties should adopt county subdivision ordinances. 2. A reasonable policy concerning sidewalks should be adopted. 3. Counties should establish and implement a system for setting road maintenance priorities. 4. Counties should establish and implement a procedure for controlling construction or maintenance activities within the highway right of way. 5. Counties should establish and implement a system to record complaints that are received relating to highway maintenance and to assure timely correction of defective conditions leading to such complaints. 6. Counties should establish and implement a procedure to ensure timely advice of highway defects for which notice is not otherwise received.

In vivo gene transfer into the ocular ciliary muscle mediated by ultrasound and microbubbles.

This study aimed to assess application of ultrasound (US) combined with microbubbles (MB) to transfect the ciliary muscle of rat eyes. Reporter DNA plasmids encoding for Gaussia luciferase, β-galactosidase or the green fluorescent protein (GFP), alone or mixed with 50% Artison MB, were injected into the ciliary muscle, with or without US exposure (US set at 1 MHz, 2 W/cm(2), 50% duty cycle for 2 min). Luciferase activity was measured in ocular fluids at 7 and 30 days after sonoporation. At 1 week, the US+MB treatment showed a significant increase in luminescence compared with control eyes, injected with plasmid only, with or without MB (×2.6), and, reporter proteins were localized in the ciliary muscle by histochemical analysis. At 1 month, a significant decrease in luciferase activity was observed in all groups. A rise in lens and ciliary muscle temperature was measured during the procedure but did not result in any observable or microscopic damages at 1 and 8 days. The feasibility to transfer gene into the ciliary muscle by US and MB suggests that sonoporation may allow intraocular production of proteins for the treatment of inflammatory, angiogenic and/or degenerative retinal diseases.

Aging Watch, December 20, 2013, Vol. 13, no. 14

Aging Watch is provided in the spirit of information and education. The opinions expressed by the contributors do not necessarily reflect those of the Department or its programs. The Department shall not be liable for any damages that may result from errors or omissions in information distributed in this publication. Aging Watch will be published regularly during the legislative session and monthly in the interim by the Iowa Department on Aging. “Aging Watch.” The Department is providing this update to better inform you about policy affecting older Iowans. In addition to policy updates from the statehouse and the nation’s capitol, you’ll learn about Department programs and changes affecting the landscape. As you’ll learn reading this and future editions, big changes are coming for the Iowa Aging Network. Over the next year the Department will be reducing the number of local Area Agencies on Aging, as required by legislative action. Not surprisingly, this is a major change for everyone.