Understanding Behavioral Responses of Wildlife to Traffic to Improve Mitigation Planning

Creating and maintaining sustainable transportation systems depends in part on understanding and mitigating ecological impacts. Wildlife crossing structures (WCS) are often used to mitigate impacts on wildlife populations. WCS and existing structures may provide passage for multiple species, depending on their sensitivity to traffic disturbance and perception of the roadway. In a previous project, the research team found that traffic conditions and traffic noise could reduce WCS effectiveness in facilitating passage of diverse and sensitive species. In the current project, they expanded the geographic scope to 26 sites throughout California, including detailed measurements of vehicle noise and lighting impacts on wildlife use of structures. They investigated individual animal behavior as the animals approached structures as a possible mechanism for reducing species diversity due to traffic disturbance. In order to inform future WCS planning, placement and construction, the team studied traffic noise and light impacts on wildlife in the vicinity of the proposed Liberty Canyon wildlife over-crossing (over US 101), the first and largest of its kind in California. They improved a preliminary statistical model of the effects of traffic on WCS use of existing structures. The authors recommend strategies for transportation agencies to use in developing and modifying WCS to improve wildlife passage.View the NCST Project Webpag

Is screening for lead poisoning justified?

Evidence is insufficient to recommend for or against universal screening of young children for lead poisoning in high- prevalence communities (strength of recommendation [SOR]: C). In low-prevalence communities, evidence is insufficient to recommend for or against a targeted screening approach, employing locale-specific demographic risk factors and personal risk questionnaires to inform screening decisions (SOR: C). Although evidence does not suggest that treatment of individuals with elevated blood lead levels improves individual outcomes, public health strategies aimed at decreasing lead in the environment appear to have resulted in a significant decline in the number of children with elevated blood lead levels in recent decades. One could thus argue that screening may identify communities with high rates of lead poisoning, where environmental strategies could be targeted. Because the epidemiology of lead poisoning continues to change, local and state health authorities must continuously update information on which to base decisions about screening

Mapping the interaction of B cell Leukemia 3 (BCL-3) and nuclear factor κB (NF-κB) p50 identifies a BCL-3-mimetic anti-inflammatory peptide

The NF-κB transcriptional response is tightly regulated by a number of processes including the phosphorylation, ubiquitination, and subsequent proteasomal degradation of NF-κB subunits. The IκB family protein BCL-3 stabilizes a NF-κB p50 homodimer·DNA complex through inhibition of p50 ubiquitination. This complex inhibits the binding of the transcriptionally active NF-κB subunits p65 and c-Rel on the promoters of NF-κB target genes and functions to suppress inflammatory gene expression. We have previously shown that the direct interaction between p50 and BCL-3 is required for BCL-3-mediated inhibition of pro-inflammatory gene expression. In this study we have used immobilized peptide array technology to define regions of BCl-3 that mediate interaction with p50 homodimers. Our data show that BCL-3 makes extensive contacts with p50 homodimers and in particular with ankyrin repeats (ANK) 1, 6, and 7, and the N-terminal region of Bcl-3. Using these data we have designed a BCL-3 mimetic peptide based on a region of the ANK1 of BCL-3 that interacts with p50 and shares low sequence similarity with other IκB proteins. When fused to a cargo carrying peptide sequence this BCL-3-derived peptide, but not a mutated peptide, inhibited Toll-like receptor-induced cytokine expression in vitro. The BCL-3 mimetic peptide was also effective in preventing inflammation in vivo in the carrageenan-induced paw edema mouse model. This study demonstrates that therapeutic strategies aimed at mimicking the functional activity of BCL-3 may be effective in the treatment of inflammatory disease

Silencing HoxA1 by Intraductal Injection of siRNA Lipidoid Nanoparticles Prevents Mammary Tumor Progression in Mice

With advances in screening, the incidence of detection of premalignant breast lesions has increased in recent decades; however, treatment options remain limited to surveillance or surgical removal by lumpectomy or mastectomy. We hypothesized that disease progression could be blocked by RNA interference (RNAi) therapy and set out to develop a targeted therapeutic delivery strategy. Using computational gene network modeling, we identified HoxA1 as a putative driver of early mammary cancer progression in transgenic C3(1)-SV40TAg mice. Silencing this gene in cultured mouse or human mammary tumor spheroids resulted in increased acinar lumen formation, reduced tumor cell proliferation, and restoration of normal epithelial polarization. When the HoxA1 gene was silenced in vivo via intraductal delivery of nanoparticle-formulated small interfering RNA (siRNA) through the nipple of transgenic mice with early-stage disease, mammary epithelial cell proliferation rates were suppressed, loss of estrogen and progesterone receptor expression was prevented, and tumor incidence was reduced by 75%. This approach that leverages new advances in systems biology and nanotechnology offers a novel noninvasive strategy to block breast cancer progression through targeted silencing of critical genes directly within the mammary epithelium.Engineering and Applied Science

Summary of research projects supported by the Health Services Research Fund (HSRF) and the Health Care and Promotion Fund (HCPF)

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Destruction, Reconstruction, and Remembrance: Exploring \u27Memory\u27 and \u27Environment\u27 through Pennsylvania World War I Memorials in France

After examining the substantial efforts at land reclamation and environmental mitigation accompanying the State of Pennsylvania’s construction of memorials after World War I in France, I discovered a strong relationship between post-war memorialization and environmental mitigation in the areas in which the environmental consequences of WWI continue to affect humans and wildlife. My research illuminates how cultural impulses to build memorials that acknowledged the vast losses, acts of valor, and victories heavily influenced mitigation of France’s ecologically damaged Western Front. Many of France’s former battlefields, particularly in the devastated area known as the Red Zone, weren’t accessible to visitors before memorial-related mitigation efforts began in the 1920s. Even today, the Red Zone in France and Belgium, defined by millions of unfilled craters and unexploded ordnance, remains in place due to the cost and dangers involved with clean-up. Yet, when mitigation does occur in these devastated areas, it is still done with the intention to create memorial structures or spaces. Despite this, large expanses of agricultural land were never re-ploughed, many villages were never rebuilt, the prohibition against living in the Red Zone is still in effect, and WWI’s environmental consequences still persist in harmful ways, particularly affecting agriculture and tourism, the Western Front’s most lucrative industries. I approach environmental mitigation of warzones holistically in a way that treats people, land, and places of cultural significance as interconnected and context-dependent, a perspective that is under-studied in the existing scholarship on memorials and mitigation. My research has allowed me to analyze the crucial problem of war’s lasting effects on the environment through a novel perspective rooted in historical and cultural ecology. Concentrating on the construction of memorials as the focal points of returning damaged land to productive use has enabled me to conceptualize war’s environmental legacy through spaces of memorialization and the repair work done there

Mapping Amis Mill in Rogersville, Tennessee in the 1780s Using Geophysical Methods and Remote Sensing

Geophysics and remote sensing were used at the Amis Mill and Homesite to determine the location of structures during the 1780s. Areas of interest were surveyed using shallow geophysical and remote sensing techniques including the orchard, horse pasture, original kitchen on the east side of the house, the west side of the house, plowed field, store site, and cemetery. After analyzing the results of the geophysical surveys and remote sensing, 22 sites were chosen to test inside and outside potential features. A large rectangular feature, possibly a tavern with a cellar, was discovered. Four other features were identified, three of which could be possible cabins of the enslaved. The first 0.37m of a midden was excavated at the probable store site, the historic road was identified with LiDAR, and 27 potential graves were located

Precise targeted integration by a chimaeric transposase zinc-finger fusion protein

Transposons of the Tc1/mariner family have been used to integrate foreign DNA stably into the genome of a large variety of different cell types and organisms. Integration is at TA dinucleotides located essentially at random throughout the genome, potentially leading to insertional mutagenesis, inappropriate activation of nearby genes, or poor expression of the transgene. Here, we show that fusion of the zinc-finger DNA-binding domain of Zif268 to the C-terminus of ISY100 transposase leads to highly specific integration into TA dinucleotides positioned 6-17 bp to one side of a Zif268 binding site. We show that the specificity of targeting can be changed using Zif268 variants that bind to sequences from the HIV-1 promoter, and demonstrate a bacterial genetic screen that can be used to select for increased levels of targeted transposition. A TA dinucleotide flanked by two Zif268 binding sites was efficiently targeted by our transposase-Zif268 fusion, suggesting the possibility of designer ‘Z-transposases’ that could deliver transgenic cargoes to chosen genomic locations