Dynamic impacts of the inhibition of the molecular chaperone hsp90 on the T-cell proteome have implications for anti-cancer therapy.

The molecular chaperone Hsp90-dependent proteome represents a complex protein network of critical biological and medical relevance. Known to associate with proteins with a broad variety of functions termed clients, Hsp90 maintains key essential and oncogenic signalling pathways. Consequently, Hsp90 inhibitors are being tested as anti-cancer drugs. Using an integrated systematic approach to analyse the effects of Hsp90 inhibition in T-cells, we quantified differential changes in the Hsp90-dependent proteome, Hsp90 interactome, and a selection of the transcriptome. Kinetic behaviours in the Hsp90-dependent proteome were assessed using a novel pulse-chase strategy (Fierro-Monti et al., accompanying article), detecting effects on both protein stability and synthesis. Global and specific dynamic impacts, including proteostatic responses, are due to direct inhibition of Hsp90 as well as indirect effects. As a result, a decrease was detected in most proteins that changed their levels, including known Hsp90 clients. Most likely, consequences of the role of Hsp90 in gene expression determined a global reduction in net de novo protein synthesis. This decrease appeared to be greater in magnitude than a concomitantly observed global increase in protein decay rates. Several novel putative Hsp90 clients were validated, and interestingly, protein families with critical functions, particularly the Hsp90 family and cofactors themselves as well as protein kinases, displayed strongly increased decay rates due to Hsp90 inhibitor treatment. Remarkably, an upsurge in survival pathways, involving molecular chaperones and several oncoproteins, and decreased levels of some tumour suppressors, have implications for anti-cancer therapy with Hsp90 inhibitors. The diversity of global effects may represent a paradigm of mechanisms that are operating to shield cells from proteotoxic stress, by promoting pro-survival and anti-proliferative functions. Data are available via ProteomeXchange with identifier PXD000537.

Inclusion of soil erosion impacts in life cycle assessment on a global scale: application to energy crops in Spain

Purpose: Despite the fundamental role of ecosystem goods and services in sustaining human activities, there is no harmonized and internationally agreed method for including them in life cycle assessment (LCA). The main goal of this study was to develop a globally applicable and spatially resolved method for assessing land-use impacts on the erosion regulation ecosystem service.Methods: Soil erosion depends much on location. Thus, unlike conventional LCA, the endpoint method was regionalized at the grid-cell level (5 arc-minutes, approximately 10×10 km2) to reflect the spatial conditions of the site. Spatially explicit characterization factors were not further aggregated at broader spatial scales. Results and discussion: Life cycle inventory data of topsoil and topsoil organic carbon (SOC) losses were interpreted at the endpoint level in terms of the ultimate damage to soil resources and ecosystem quality. Human health damages were excluded from the assessment. The method was tested on a case study of five three-year agricultural rotations, two of them with energy crops, grown in several locations in Spain. A large variation in soil and SOC losses was recorded in the inventory step, depending on climatic and edaphic conditions. The importance of using a spatially explicit model and characterization factors is shown in the case study.Conclusions and outlook: The regionalized assessment takes into account the differences in soil erosion-related environmental impacts caused by the great variability of soils. Taking this regionalized framework as the starting point, further research should focus on testing the applicability of the method trough the complete life cycle of a product and on determining an appropriate spatial scale at which to aggregate characterization factors, in order to deal with data gaps on location of processes, especially in the background system. Additional research should also focus on improving reliability of the method by quantifying and, insofar as it is possible, reducing uncertainty.

Long-term impacts of forest harvesting related soil disturbance on log product yields and economic potential in a New Zealand forest

Abstract

Safety and Mobility Impacts of Winter Weather --Phase 3, SPR RB01-012, 2014

Highway agencies spend millions of dollars to ensure safe and efficient winter travel. However, the effectiveness of winter-weather maintenance practices on safety and mobility are somewhat difficult to quantify. Safety and Mobility Impacts of Winter Weather - Phase 1 investigated opportunities for improving traffic safety on state-maintained roads in Iowa during winter-weather conditions. In Phase 2, three Iowa Department of Transportation (DOT) high-priority sites were evaluated and realistic maintenance and operations mitigation strategies were also identified. In this project, site prioritization techniques for identifying roadway segments with the potential for safety improvements related to winter-weather crashes, were developed through traditional naïve statistical methods by using raw crash data for seven winter seasons and previously developed metrics. Additionally, crash frequency models were developed using integrated crash data for four winter seasons, with the objective of identifying factors that affect crash frequency during winter seasons and screening roadway segments using the empirical Bayes technique. Based on these prioritization techniques, 11 sites were identified and analyzed in conjunction with input from Iowa DOT district maintenance managers and snowplow operators and the Iowa DOT Road Weather Information System (RWIS) coordinator.

Allocation of above-ground growth in Pinus sylvestris - impacts of tree size and competition

Abstract

The value of intraoperative ultrasound in oblique corpectomy for cervical spondylotic myelopathy and ossified posterior longitudinal ligament.

Intraoperative ultrasound (IOUS) has been described to be useful during central corpectomy for compressive cervical myelopathy. This study aimed at documenting the utility of IOUS in oblique cervical corpectomy (OCC). Prospective data from 24 patients undergoing OCC for cervical spondylotic myelopathy and ossified posterior longitudinal ligament (OPLL) were collected. Patients had a preoperative cervical spine magnetic resonance (MR) image, IOUS and a postoperative cervical CT scan. Retrospective data from 16 historical controls that underwent OCC without IOUS were analysed to compare the incidence of residual compression between the two groups. IOUS identified the vertebral artery in all cases, detected residual cord compression in six (27%) and missed compression in two cases (9%). In another two cases with OPLL, IOUS was sub-optimal due to shadowing. IOUS measurement of the corpectomy width correlated well with these measurements on the postoperative CT. The extent of cord expansion noted on IOUS after decompression showed no correlation with immediate or 6-month postoperative neurological recovery. No significant difference in residual compression was noted in the retrospective and prospective groups of the study. Craniocaudal spinal cord motion was noted after the completion of the corpectomy. IOUS is an inexpensive and simple real-time imaging modality that may be used during OCC for cervical spondylotic myelopathy. It is helpful in identifying the vertebral artery and determining the trajectory of approach, however, it has limited utility in patients with OPLL due to artifacts from residual ossification.

Generation and nonlinear evolution of shore-oblique/transverse sand bars

The coupling between topography, waves and currents in the surf zone may selforganize to produce the formation of shore-transverse or shore-oblique sand bars on an otherwise alongshore uniform beach. In the absence of shore-parallel bars, this has been shown by previous studies of linear stability analysis, but is now extended to the finite-amplitude regime. To this end, a nonlinear model coupling wave transformation and breaking, a shallow-water equations solver, sediment transport and bed updating is developed. The sediment flux consists of a stirring factor multiplied by the depthaveraged current plus a downslope correction. It is found that the cross-shore profile of the ratio of stirring factor to water depth together with the wave incidence angle primarily determine the shape and the type of bars, either transverse or oblique to the shore. In the latter case, they can open an acute angle against the current (upcurrent oriented) or with the current (down-current oriented). At the initial stages of development, both the intensity of the instability which is responsible for the formation of the bars and the damping due to downslope transport grow at a similar rate with bar amplitude, the former being somewhat stronger. As bars keep on growing, their finite-amplitude shape either enhances downslope transport or weakens the instability mechanism so that an equilibrium between both opposing tendencies occurs, leading to a final saturated amplitude. The overall shape of the saturated bars in plan view is similar to that of the small-amplitude ones. However, the final spacings may be up to a factor of 2 larger and final celerities can also be about a factor of 2 smaller or larger. In the case of alongshore migrating bars, the asymmetry of the longshore sections, the lee being steeper than the stoss, is well reproduced. Complex dynamics with merging and splitting of individual bars sometimes occur. Finally, in the case of shore-normal incidence the rip currents in the troughs between the bars are jet-like while the onshore return flow is wider and weaker as is observed in nature.

Impacts of Internal Curing on Concrete Properties, TR-676, 2015

Conventional concrete is typically cured using external methods. External curing prevents drying of the surface, allows the mixture to stay warm and moist, and results in continued cement hydration (Taylor 2014). Internal curing is a relatively recent technique that has been developed to prolong cement hydration by providing internal water reservoirs in a concrete mixture that do not adversely affect the concrete mixture’s fresh or hardened physical properties. Internal curing grew out of the need for more durable structural concretes that were resistant to shrinkage cracking. Joint spacing for concrete overlays can be increased if slab warping is reduced or eliminated. One of the most promising potential benefits from using internal curing for concrete overlays, then, is the reduced number of joints due to increased joint spacing (Wei and Hansen 2008).

The environmental roots of non-communicable diseases (NCDs) and the epigenetic impacts of globalization

BACKGROUND: Non-communicable diseases (NCDs) are increasing worldwide. We hypothesize that environmental factors (including social adversity, diet, lack of physical activity and pollution) can become "embedded" in the biology of humans. We also hypothesize that the "embedding" partly occurs because of epigenetic changes, i.e., durable changes in gene expression patterns. Our concern is that once such factors have a foundation in human biology, they can affect human health (including NCDs) over a long period of time and across generations. OBJECTIVES: To analyze how worldwide changes in movements of goods, persons and lifestyles (globalization) may affect the "epigenetic landscape" of populations and through this have an impact on NCDs. We provide examples of such changes and effects by discussing the potential epigenetic impact of socio-economic status, migration, and diet, as well as the impact of environmental factors influencing trends in age at puberty. DISCUSSION: The study of durable changes in epigenetic patterns has the potential to influence policy and practice; for example, by enabling stratification of populations into those who could particularly benefit from early interventions to prevent NCDs, or by demonstrating mechanisms through which environmental factors influence disease risk, thus providing compelling evidence for policy makers, companies and the civil society at large. The current debate on the '25 × 25 strategy', a goal of 25% reduction in relative mortality from NCDs by 2025, makes the proposed approach even more timely. CONCLUSIONS: Epigenetic modifications related to globalization may crucially contribute to explain current and future patterns of NCDs, and thus deserve attention from environmental researchers, public health experts, policy makers, and concerned citizens.

Iowa's Renewable Energy and Infrastructure Impacts, TR-593, 2010

The federal government is aggressively promoting biofuels as an answer to global climate change and dependence on imported sources of energy. Iowa has quickly become a leader in the bioeconomy and wind energy production, but meeting the United States Department of Energy’s goal having 20% of U.S. transportation fuels come from biologically based sources by 2030 will require a dramatic increase in ethanol and biodiesel production and distribution. At the same time, much of Iowa’s rural transportation infrastructure is near or beyond its original design life. As Iowa’s rural roadway structures, pavements, and unpaved roadways become structurally deficient or functionally obsolete, public sector maintenance and rehabilitation costs rapidly increase. More importantly, costs to move all farm products will rapidly increase if infrastructure components are allowed to fail; longer hauls, slower turnaround times, and smaller loads result. When these results occur on a large scale, Iowa will start to lose its economic competitive edge in the rapidly developing bioeconomy. The primary objective of this study was to document the current physical and fiscal impacts of Iowa’s existing biofuels and wind power industries. A four-county cluster in north-central Iowa and a two-county cluster in southeast Iowa were identified through a local agency survey as having a large number of diverse facilities and were selected for the traffic and physical impact analysis. The research team investigated the large truck traffic patterns on Iowa’s secondary and local roads from 2002 to 2008 and associated those with the pavement condition and county maintenance expenditures. The impacts were quantified to the extent possible and visualized using geographic information system (GIS) tools. In addition, a traffic and fiscal assessment tool was developed to understand the impact of the development of the biofuels on Iowa’s secondary road system. Recommended changes in public policies relating to the local government and to the administration of those policies included standardizing the reporting and format of all county expenditures, conducting regular pavement evaluations on a county’s system, cooperating and communicating with cities (adjacent to a plant site), considering utilization of tax increment financing (TIF) districts as a short-term tool to produce revenues, and considering alternative ways to tax the industry.