Structural and functional analysis of parameters governing tankyrase-1 interaction with telomeric repeat-binding factor 1 and GDP-mannose 4,6-dehydratase.

Human tankyrase-1 (TNKS) is a member of the poly(ADPribose) polymerase (PARP) superfamily of proteins that posttranslationally modify themselves and target proteins with ADP-ribose (termed PARylation). The TNKS ankyrin repeat domain mediates interactions with a growing number of structurally and functionally diverse binding partners, linking TNKS activity to multiple critical cell processes, including Wnt signaling, Golgi trafficking, and telomere maintenance. However, some binding partners can engage TNKS without being modified, suggesting that separate parameters influence TNKS interaction and PARylation. Here, we present an analysis of the sequence and structural features governing TNKS interactions with two model binding partners: The PARylated partner telomeric repeat-binding factor 1 (TRF1) and the non-PARylated partner GDP-mannose 4,6-dehydratase (GMD). Using a combination of TNKS-binding assays, PARP activity assays, and analytical ultracentrifugation sedimentation analysis, we found that both the specific sequence of a given TNKS-binding peptide motif and the quaternary structure of individual binding partners play important roles in TNKS interactions. We demonstrate that GMD forms stable 1:1 complexes with the TNKS ankyrin repeat domain; yet, consistent with results from previous studies, we were unable to detect GMD modification. We also report in vitro evidence that TNKS primarily directs PAR modification to glutamate/aspartate residues. Our results suggest that TNKS-binding partners possess unique sequence and structural features that control binding and PARylation. Ultimately, our findings highlight the binding partner:ankyrin repeat domain interface as a viable target for inhibition of TNKS activity

Structural and functional analysis of parameters governing tankyrase-1 interaction with telomeric repeat-binding factor 1 and GDP-mannose 4,6-dehydratase.

Human tankyrase-1 (TNKS) is a member of the poly(ADPribose) polymerase (PARP) superfamily of proteins that posttranslationally modify themselves and target proteins with ADP-ribose (termed PARylation). The TNKS ankyrin repeat domain mediates interactions with a growing number of structurally and functionally diverse binding partners, linking TNKS activity to multiple critical cell processes, including Wnt signaling, Golgi trafficking, and telomere maintenance. However, some binding partners can engage TNKS without being modified, suggesting that separate parameters influence TNKS interaction and PARylation. Here, we present an analysis of the sequence and structural features governing TNKS interactions with two model binding partners: The PARylated partner telomeric repeat-binding factor 1 (TRF1) and the non-PARylated partner GDP-mannose 4,6-dehydratase (GMD). Using a combination of TNKS-binding assays, PARP activity assays, and analytical ultracentrifugation sedimentation analysis, we found that both the specific sequence of a given TNKS-binding peptide motif and the quaternary structure of individual binding partners play important roles in TNKS interactions. We demonstrate that GMD forms stable 1:1 complexes with the TNKS ankyrin repeat domain; yet, consistent with results from previous studies, we were unable to detect GMD modification. We also report in vitro evidence that TNKS primarily directs PAR modification to glutamate/aspartate residues. Our results suggest that TNKS-binding partners possess unique sequence and structural features that control binding and PARylation. Ultimately, our findings highlight the binding partner:ankyrin repeat domain interface as a viable target for inhibition of TNKS activity

Non-Target Hazard Assessment of Using DRC-1339 Avicide to Manage Blackbirds in Sunflower

Terrestrial hazard assessments were conducted for the spring blackbird baiting program to protect sunflower crops. Risk Assessment methodology proposed by the Ecological Committee on FIFRA Risk Assessment Methods (ECOFRAM) and the method currently used by the U.S. Environmental Protection Agency (LD50s/ft2) were compared for their predictive strengths and for the ease of adapting the assessment to site specific conditions. While the ECOFRAM and LD50s/ft2 methods identified the same groups of organisms as being at risk, the flexibility of the ECOFRAM methodology allowed more latitude in adapting the assessment to unique behaviors of individual species. These risk assessment approaches indicate that blackbird baiting with DRC-1339 presents acute hazards to select nontarget birds like western meadowlarks and mourning doves but few hazards to most mammals or small granivorous birds like sparrows and finches. However, field experiments indicate that the mitigation measures currently employed in the baiting program, minimize the nontarget hazards

Chapter 11 An International Perspective on the Regulation of Rodenticides

In the late 1940s, anticoagulant active ingredients were introduced into the global rodenticide market. They were rapidly favored over existing rodenticides, such as red squill, zinc phosphide, strychnine and inorganic compounds, because they were comparatively inexpensive and did not appear to have any unpalatable taste, odor or cause any immediate post-ingestive reaction that could lead to bait shyness in rodents (Wardrop and Keeling 2008). The number of products registered in the United States (US) under Section 3 of the Federal Fungicide, Insecticide and Rodenticide Act (FIFRA), which was passed in 1947 and was the first US law to require product registration, illustrates the rapid dominance of anticoagulants in the US rodenticide market (Fig. 11.1). It is striking that the number of anticoagulant-based rodenticide products (ARs) registered under FIFRA was more than two times greater than the other categories of rodenticide active ingredients 40 years after the enactment of FIFRA. The greatest number of rodenticide products registered in a single year under Section 3 of FIFRA (750) was in 1985, and ARs accounted for 547 (73%) o

A Robust AFPTAS for Online Bin Packing with Polynomial Migration

In this paper we develop general LP and ILP techniques to find an approximate solution with improved objective value close to an existing solution. The task of improving an approximate solution is closely related to a classical theorem of Cook et al. in the sensitivity analysis for LPs and ILPs. This result is often applied in designing robust algorithms for online problems. We apply our new techniques to the online bin packing problem, where it is allowed to reassign a certain number of items, measured by the migration factor. The migration factor is defined by the total size of reassigned items divided by the size of the arriving item. We obtain a robust asymptotic fully polynomial time approximation scheme (AFPTAS) for the online bin packing problem with migration factor bounded by a polynomial in $\frac{1}{\epsilon}$. This answers an open question stated by Epstein and Levin in the affirmative. As a byproduct we prove an approximate variant of the sensitivity theorem by Cook at el. for linear programs

Longevity of Rodenticide Bait Pellets in a Tropical Environment Following a Rat Eradication Program

Invasive rodents (primarily Rattus spp.) are responsible for loss of biodiversity in island ecosystems worldwide. Large-scale rodenticide applications are typically used to eradicate rats and restore ecological communities. In tropical ecosystems, environmental conditions rapidly degrade baits and competition for baits by non-target animals can result in eradication failure. Our objective was to evaluate persistence of rodenticide baits during a rat eradication program on Palmyra Atoll; a remote tropical atoll with intense competition for resources by land crabs. Following aerial application, bait condition was monitored in four terrestrial environments and in the canopy foliage of coconut palms. Ten circular PVC hoops were fixed in place in each of Palmyra\u27s four primary terrestrial habitats and five rodenticide pellets were placed in each hoop. Five coconut palms were selected in three distinct regions of the atoll. One rodenticide pellet was placed on each of five palm fronds in each coconut palm. Fresh baits were placed in all monitoring locations after each broadcast bait application. Bait condition and survival was monitored for 7 days after the first bait application and 6 days after second application. Bait survival curves differed between applications at most monitoring sites, suggesting a decrease in overall rat activity as a result of rodenticide treatment. One terrestrial site showed near 100%bait survival after both applications, likely due to low localized rat and crab densities. Median days to pellet disappearance were one and two days for the first and second application, respectively. Differences in survival curves were not detected in canopy sites between bait applications. Median days to pellet disappearance in canopy sites were 2 and 4 days for the first and second application, respectively. Frequent rainfall likely contributed to rapid degradation of bait pellets in coconut palm fronds

Assessing spatial variation and overall density of aerially broadcast toxic bait during a rat eradication on Palmyra Atoll

Baits containing brodifacoum rodenticide were aerially applied to eradicate invasive black rats from Palmyra Atoll, an important biodiversity center. Bait application must be sufficient to be effective, while minimizing environmental hazards by not exceeding designated label rates, prompting our bait density assessments for two aerial drops. With few physical or human resources on this remote, uninhabited atoll, assessments were particularly challenging, requiring observations within 30 min of aerial application to avoid bait loss to rats, crabs, or elements. We estimated bait density using quadrat sampling within 13 terrestrial sampling areas. We also sampled 10 tidal flat areas to assess inadvertent bait scatter into marine aquatic environments. Of particular value for challenging sampling circumstances, our quadrats had to be lightweight and durable, which we addressed by using widely available PVC hoops (“Hula Hoops”), the size of which was ideal for sampling purposes. At 77.5 and 78.7 kg/ha, overall bait densities were very near to the target densities of 80 and 75 kg/ha, respectively. However, considerable variability in bait densities existed among sampled areas, 8.6–178.2 and 31.4–129.5 kg/ha for the respective drops. Environmental, human, and equipment factors likely accounted for this variability. Tidal flat sampling revealed variable bait scatter into aquatic environments, from 0–46.3 kg/ha across the two drops. No differences were found in average bait densities among 1-, 4-, and 7-m distances from high tide lines. Our methods might broadly assist bait density (and other) surveys under challenging circumstances

Assessing spatial variation and overall density of aerially broadcast toxic bait during a rat eradication on Palmyra Atoll

Baits containing brodifacoum rodenticide were aerially applied to eradicate invasive black rats from Palmyra Atoll, an important biodiversity center. Bait application must be sufficient to be effective, while minimizing environmental hazards by not exceeding designated label rates, prompting our bait density assessments for two aerial drops. With few physical or human resources on this remote, uninhabited atoll, assessments were particularly challenging, requiring observations within 30 min of aerial application to avoid bait loss to rats, crabs, or elements. We estimated bait density using quadrat sampling within 13 terrestrial sampling areas. We also sampled 10 tidal flat areas to assess inadvertent bait scatter into marine aquatic environments. Of particular value for challenging sampling circumstances, our quadrats had to be lightweight and durable, which we addressed by using widely available PVC hoops (“Hula Hoops”), the size of which was ideal for sampling purposes. At 77.5 and 78.7 kg/ha, overall bait densities were very near to the target densities of 80 and 75 kg/ha, respectively. However, considerable variability in bait densities existed among sampled areas, 8.6–178.2 and 31.4–129.5 kg/ha for the respective drops. Environmental, human, and equipment factors likely accounted for this variability. Tidal flat sampling revealed variable bait scatter into aquatic environments, from 0–46.3 kg/ha across the two drops. No differences were found in average bait densities among 1-, 4-, and 7-m distances from high tide lines. Our methods might broadly assist bait density (and other) surveys under challenging circumstances

Stereo-consistent screen-space ambient occlusion

Screen-space ambient occlusion (SSAO) shows high efficiency and is widely used in real-time 3D applications. However, using SSAO algorithms in stereo rendering can lead to inconsistencies due to the differences in the screen-space information captured by the left and right eye. This will affect the perception of the scene and may be a source of viewer discomfort. In this paper, we show that the raw obscurance estimation part and subsequent filtering are both sources of inconsistencies. We developed a screen-space method involving both views in conjunction, leading to a stereo-aware raw obscurance estimation method and a stereo-aware bilateral filter. The results show that our method reduces stereo inconsistencies to a level comparable to geometry-based AO solutions, while maintaining the performance benefits of a screen-space approach