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Description

Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the

Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within the complex. Mimicking this method of substrate channelling outside the cellular environment requires precise control over the spatial parameters of the individual components within the assembled complex. DNA nanostructures can be used to organize functional molecules with nanoscale precision and can also provide nanomechanical control. Until now, protein–DNA assemblies have been used to organize cascades of enzymatic reactions by controlling the relative distance and orientation of enzymatic components or by facilitating the interface between enzymes/cofactors and electrode surfaces. Here, we show that a DNA nanostructure can be used to create a multi-enzyme complex in which an artificial swinging arm facilitates hydride transfer between two coupled dehydrogenases. By exploiting the programmability of DNA nanostructures, key parameters including position, stoichiometry and inter-enzyme distance can be manipulated for optimal activity.

ContributorsFu, Jinglin (Author) / Yang, Yuhe (Author) / Johnson-Buck, Alexander (Author) / Liu, Minghui (Author) / Liu, Yan (Author) / Walter, Nils G. (Author) / Woodbury, Neal (Author) / Yan, Hao (Author) / Biodesign Institute (Contributor)
Created2014-07-01
Description

A structurally and compositionally well-defined and spectrally tunable artificial light-harvesting system has been constructed in which multiple organic dyes attached to a three-arm-DNA nanostructure serve as an antenna conjugated to a photosynthetic reaction center isolated from Rhodobacter sphaeroides 2.4.1. The light energy absorbed by the dye molecules is transferred to

A structurally and compositionally well-defined and spectrally tunable artificial light-harvesting system has been constructed in which multiple organic dyes attached to a three-arm-DNA nanostructure serve as an antenna conjugated to a photosynthetic reaction center isolated from Rhodobacter sphaeroides 2.4.1. The light energy absorbed by the dye molecules is transferred to the reaction center, where charge separation takes place. The average number of DNA three-arm junctions per reaction center was tuned from 0.75 to 2.35. This DNA-templated multichromophore system serves as a modular light-harvesting antenna that is capable of being optimized for its spectral properties, energy transfer efficiency, and photostability, allowing one to adjust both the size and spectrum of the resulting structures. This may serve as a useful test bed for developing nanostructured photonic systems.

ContributorsDutta, Palash (Author) / Levenberg, Symon (Author) / Loskutov, Andrey (Author) / Jun, Daniel (Author) / Saer, Rafael (Author) / Beatty, J. Thomas (Author) / Lin, Su (Author) / Liu, Yan (Author) / Woodbury, Neal (Author) / Yan, Hao (Author) / Department of Chemistry and Biochemistry (Contributor)
Created2014-11-26
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Description

Background: Blindness has evolved repeatedly in cave-dwelling organisms, and many hypotheses have been proposed to explain this observation, including both accumulation of neutral loss-of-function mutations and adaptation to darkness. Investigating the loss of sight in cave dwellers presents an opportunity to understand the operation of fundamental evolutionary processes, including drift, selection,

Background: Blindness has evolved repeatedly in cave-dwelling organisms, and many hypotheses have been proposed to explain this observation, including both accumulation of neutral loss-of-function mutations and adaptation to darkness. Investigating the loss of sight in cave dwellers presents an opportunity to understand the operation of fundamental evolutionary processes, including drift, selection, mutation, and migration.

Results: Here we model the evolution of blindness in caves. This model captures the interaction of three forces: (1) selection favoring alleles causing blindness, (2) immigration of sightedness alleles from a surface population, and (3) mutations creating blindness alleles. We investigated the dynamics of this model and determined selection-strength thresholds that result in blindness evolving in caves despite immigration of sightedness alleles from the surface. We estimate that the selection coefficient for blindness would need to be at least 0.005 (and maybe as high as 0.5) for blindness to evolve in the model cave-organism, Astyanax mexicanus.

Conclusions: Our results indicate that strong selection is required for the evolution of blindness in cave-dwelling organisms, which is consistent with recent work suggesting a high metabolic cost of eye development.

ContributorsCartwright, Reed (Author) / Schwartz, Rachel (Author) / Merry, Alexandra (Author) / Howell, Megan (Author) / Biodesign Institute (Contributor)
Created2017-02-07
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Description

The sensitivity of Earth’s wetlands to observed shifts in global precipitation and temperature patterns and their ability to produce large quantities of methane gas are key global change questions. We present a microwave satellite-based approach for mapping fractional surface water (FW) globally at 25-km resolution. The approach employs a land

The sensitivity of Earth’s wetlands to observed shifts in global precipitation and temperature patterns and their ability to produce large quantities of methane gas are key global change questions. We present a microwave satellite-based approach for mapping fractional surface water (FW) globally at 25-km resolution. The approach employs a land cover-supported, atmospherically-corrected dynamic mixture model applied to 20+ years (1992–2013) of combined, daily, passive/active microwave remote sensing data. The resulting product, known as Surface Water Microwave Product Series (SWAMPS), shows strong microwave sensitivity to sub-grid scale open water and inundated wetlands comprising open plant canopies. SWAMPS’ FW compares favorably (R2 = 91%–94%) with higher-resolution, global-scale maps of open water from MODIS and SRTM-MOD44W. Correspondence of SWAMPS with open water and wetland products from satellite SAR in Alaska and the Amazon deteriorates when exposed wetlands or inundated forests captured by the SAR products were added to the open water fraction reflecting SWAMPS’ inability to detect water underneath the soil surface or beneath closed forest canopies. Except for a brief period of drying during the first 4 years of observation, the inundation extent for the global domain excluding the coast was largely stable. Regionally, inundation in North America is advancing while inundation is on the retreat in Tropical Africa and North Eurasia. SWAMPS provides a consistent and long-term global record of daily FW dynamics, with documented accuracies suitable for hydrologic assessment and global change-related investigations.

ContributorsSchroeder, Ronny (Author) / McDonald, Kyle C. (Author) / Chapman, Bruce D. (Author) / Jensen, Katherine (Author) / Podest, Erika (Author) / Tessler, Zachary D. (Author) / Bohn, Theodore (Author) / Zimmermann, Reiner (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-12-09
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Description

A warming climate is altering land-atmosphere exchanges of carbon, with a potential for increased vegetation productivity as well as the mobilization of permafrost soil carbon stores. Here we investigate land-atmosphere carbon dioxide (CO2) cycling through analysis of net ecosystem productivity (NEP) and its component fluxes of gross primary productivity (GPP)

A warming climate is altering land-atmosphere exchanges of carbon, with a potential for increased vegetation productivity as well as the mobilization of permafrost soil carbon stores. Here we investigate land-atmosphere carbon dioxide (CO2) cycling through analysis of net ecosystem productivity (NEP) and its component fluxes of gross primary productivity (GPP) and ecosystem respiration (ER) and soil carbon residence time, simulated by a set of land surface models (LSMs) over a region spanning the drainage basin of Northern Eurasia. The retrospective simulations cover the period 1960–2009 at 0.5° resolution, which is a scale common among many global carbon and climate model simulations. Model performance benchmarks were drawn from comparisons against both observed CO2 fluxes derived from site-based eddy covariance measurements as well as regional-scale GPP estimates based on satellite remote-sensing data.

The site-based comparisons depict a tendency for overestimates in GPP and ER for several of the models, particularly at the two sites to the south. For several models the spatial pattern in GPP explains less than half the variance in the MODIS MOD17 GPP product. Across the models NEP increases by as little as 0.01 to as much as 0.79 g C m-2 yr-2, equivalent to 3 to 340 % of the respective model means, over the analysis period. For the multimodel average the increase is 135 % of the mean from the first to last 10 years of record (1960–1969 vs. 2000–2009), with a weakening CO2 sink over the latter decades. Vegetation net primary productivity increased by 8 to 30 % from the first to last 10 years, contributing to soil carbon storage gains. The range in regional mean NEP among the group is twice the multimodel mean, indicative of the uncertainty in CO2 sink strength.

The models simulate that inputs to the soil carbon pool exceeded losses, resulting in a net soil carbon gain amid a decrease in residence time. Our analysis points to improvements in model elements controlling vegetation productivity and soil respiration as being needed for reducing uncertainty in land-atmosphere CO2 exchange. These advances will require collection of new field data on vegetation and soil dynamics, the development of benchmarking data sets from measurements and remote-sensing observations, and investments in future model development and intercomparison studies.

ContributorsRawlins, M. A. (Author) / McGuire, A. D. (Author) / Kimball, J. S. (Author) / Dass, P. (Author) / Lawrence, D. (Author) / Burke, E. (Author) / Chen, X. (Author) / Delire, C. (Author) / Koven, C. (Author) / MacDougall, A. (Author) / Peng, S. (Author) / Rinke, A. (Author) / Saito, K. (Author) / Zhang, W. (Author) / Alkama, R. (Author) / Bohn, Theodore (Author) / Ciais, P. (Author) / Decharme, B. (Author) / Gouttevin, I. (Author) / Hajima, T. (Author) / Ji, D. (Author) / Krinner, G. (Author) / Lettenmaier, D. P. (Author) / Miller, P. (Author) / Moore, J. C. (Author) / Smith, B. (Author) / Sueyoshi, T. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-07-28
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Description

Soil temperature (Ts) change is a key indicator of the dynamics of permafrost. On seasonal and interannual timescales, the variability of Ts determines the active-layer depth, which regulates hydrological soil properties and biogeochemical processes. On the multi-decadal scale, increasing Ts not only drives permafrost thaw/retreat but can also trigger and

Soil temperature (Ts) change is a key indicator of the dynamics of permafrost. On seasonal and interannual timescales, the variability of Ts determines the active-layer depth, which regulates hydrological soil properties and biogeochemical processes. On the multi-decadal scale, increasing Ts not only drives permafrost thaw/retreat but can also trigger and accelerate the decomposition of soil organic carbon. The magnitude of permafrost carbon feedbacks is thus closely linked to the rate of change of soil thermal regimes. In this study, we used nine process-based ecosystem models with permafrost processes, all forced by different observation-based climate forcing during the period 1960–2000, to characterize the warming rate of Ts in permafrost regions. There is a large spread of Ts trends at 20 cm depth across the models, with trend values ranging from 0.010 ± 0.003 to 0.031 ± 0.005 °C yr-1. Most models show smaller increase in Ts with increasing depth. Air temperature (Tsub>a) and longwave downward radiation (LWDR) are the main drivers of Ts trends, but their relative contributions differ amongst the models. Different trends of LWDR used in the forcing of models can explain 61 % of their differences in Ts trends, while trends of Ta only explain 5 % of the differences in Ts trends. Uncertain climate forcing contributes a larger uncertainty in Ts trends (0.021 ± 0.008 °C yr-1, mean ± standard deviation) than the uncertainty of model structure (0.012 ± 0.001 °C yr-1), diagnosed from the range of response between different models, normalized to the same forcing. In addition, the loss rate of near-surface permafrost area, defined as total area where the maximum seasonal active-layer thickness (ALT) is less than 3 m loss rate, is found to be significantly correlated with the magnitude of the trends of Ts at 1 m depth across the models (R = −0.85, P = 0.003), but not with the initial total near-surface permafrost area (R = −0.30, P = 0.438). The sensitivity of the total boreal near-surface permafrost area to Ts at 1 m is estimated to be of −2.80 ± 0.67 million km2°C-1. Finally, by using two long-term LWDR data sets and relationships between trends of LWDR and Ts across models, we infer an observation-constrained total boreal near-surface permafrost area decrease comprising between 39 ± 14  ×  103 and 75 ± 14  ×  103km2yr-1 from 1960 to 2000. This corresponds to 9–18 % degradation of the current permafrost area.

ContributorsPeng, S. (Author) / Ciais, P. (Author) / Krinner, G. (Author) / Wang, T. (Author) / Gouttevin, I. (Author) / McGuire, A. D. (Author) / Lawrence, D. (Author) / Burke, E. (Author) / Chen, X. (Author) / Decharme, B. (Author) / Koven, C. (Author) / MacDougall, A. (Author) / Rinke, A. (Author) / Saito, K. (Author) / Zhang, W. (Author) / Alkama, R. (Author) / Bohn, Theodore (Author) / Delire, C. (Author) / Hajima, T. (Author) / Ji, D. (Author) / Lettenmaier, D. P. (Author) / Miller, P. A. (Author) / Moore, J. C. (Author) / Smith, B. (Author) / Sueyoshi, T. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-01-20
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Description

There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide microarrays can do this through antibody signatures (immunosignatures). Unfortunately, printed

There is an increasing awareness that health care must move from post-symptomatic treatment to presymptomatic intervention. An ideal system would allow regular inexpensive monitoring of health status using circulating antibodies to report on health fluctuations. Recently, we demonstrated that peptide microarrays can do this through antibody signatures (immunosignatures). Unfortunately, printed microarrays are not scalable. Here we demonstrate a platform based on fabricating microarrays (~10 M peptides per slide, 330,000 peptides per assay) on silicon wafers using equipment common to semiconductor manufacturing. The potential of these microarrays for comprehensive health monitoring is verified through the simultaneous detection and classification of six different infectious diseases and six different cancers. Besides diagnostics, these high-density peptide chips have numerous other applications both in health care and elsewhere.

ContributorsLegutki, Joseph Barten (Author) / Zhao, Zhan-Gong (Author) / Greving, Matt (Author) / Woodbury, Neal (Author) / Johnston, Stephen (Author) / Stafford, Phillip (Author) / Biodesign Institute (Contributor)
Created2014-09-03
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Description

A realistic simulation of snow cover and its thermal properties are important for accurate modelling of permafrost. We analyse simulated relationships between air and near-surface (20  cm) soil temperatures in the Northern Hemisphere permafrost region during winter, with a particular focus on snow insulation effects in nine land surface models,

A realistic simulation of snow cover and its thermal properties are important for accurate modelling of permafrost. We analyse simulated relationships between air and near-surface (20  cm) soil temperatures in the Northern Hemisphere permafrost region during winter, with a particular focus on snow insulation effects in nine land surface models, and compare them with observations from 268 Russian stations. There are large cross-model differences in the simulated differences between near-surface soil and air temperatures (ΔT; 3 to 14 °C), in the sensitivity of soil-to-air temperature (0.13 to 0.96 °C °C-1), and in the relationship between ΔT and snow depth. The observed relationship between ΔT and snow depth can be used as a metric to evaluate the effects of each model's representation of snow insulation, hence guide improvements to the model's conceptual structure and process parameterisations. Models with better performance apply multilayer snow schemes and consider complex snow processes. Some models show poor performance in representing snow insulation due to underestimation of snow depth and/or overestimation of snow conductivity. Generally, models identified as most acceptable with respect to snow insulation simulate reasonable areas of near-surface permafrost (13.19 to 15.77 million  km2). However, there is not a simple relationship between the sophistication of the snow insulation in the acceptable models and the simulated area of Northern Hemisphere near-surface permafrost, because several other factors, such as soil depth used in the models, the treatment of soil organic matter content, hydrology and vegetation cover, also affect the simulated permafrost distribution.

ContributorsWang, Wenli (Author) / Rinke, Annette (Author) / Moore, John C. (Author) / Ji, Duoying (Author) / Cui, Xuefeng (Author) / Peng, Shushi (Author) / Lawrence, David M. (Author) / McGuire, A. David (Author) / Burke, Eleanor J. (Author) / Chen, Xiaodong (Author) / Decharme, Bertrand (Author) / Koven, Charles (Author) / MacDougall, Andrew (Author) / Saito, Kazuyuki (Author) / Zhang, Wenxin (Author) / Alkama, Ramdane (Author) / Bohn, Theodore (Author) / Ciais, Philippe (Author) / Delire, Christine (Author) / Gouttevin, Isabelle (Author) / Hajima, Tomohiro (Author) / Krinner, Gerhard (Author) / Lettenmaier, Dennis P. (Author) / Miller, Paul A. (Author) / Smith, Benjamin (Author) / Sueyoshi, Tetsuo (Author) / Sherstiukov, Artem B. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-08-11
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Description

The most common evolutionary events at the molecular level are single-base substitutions, as well as insertions and deletions (indels) of short DNA segments. A large body of research has been devoted to develop probabilistic substitution models and to infer their parameters using likelihood and Bayesian approaches. In contrast, relatively little

The most common evolutionary events at the molecular level are single-base substitutions, as well as insertions and deletions (indels) of short DNA segments. A large body of research has been devoted to develop probabilistic substitution models and to infer their parameters using likelihood and Bayesian approaches. In contrast, relatively little has been done to model indel dynamics, probably due to the difficulty in writing explicit likelihood functions. Here, we contribute to the effort of modeling indel dynamics by presenting SpartaABC, an approximate Bayesian computation (ABC) approach to infer indel parameters from sequence data (either aligned or unaligned). SpartaABC circumvents the need to use an explicit likelihood function by extracting summary statistics from simulated sequences. First, summary statistics are extracted from the input sequence data. Second, SpartaABC samples indel parameters from a prior distribution and uses them to simulate sequences. Third, it computes summary statistics from the simulated sets of sequences. By computing a distance between the summary statistics extracted from the input and each simulation, SpartaABC can provide an approximation to the posterior distribution of indel parameters as well as point estimates. We study the performance of our methodology and show that it provides accurate estimates of indel parameters in simulations. We next demonstrate the utility of SpartaABC by studying the impact of alignment errors on the inference of positive selection. A C ++ program implementing SpartaABC is freely available in http://spartaabc.tau.ac.il.

ContributorsLevy Karin, Eli (Author) / Shkedy, Dafna (Author) / Ashkenazy, Haim (Author) / Cartwright, Reed (Author) / Pupko, Tal (Author) / Biodesign Institute (Contributor)
Created2017-05-01
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Description

Under models of isolation-by-distance, population structure is determined by the probability of identity-by-descent between pairs of genes according to the geographic distance between them. Well established analytical results indicate that the relationship between geographical and genetic distance depends mostly on the neighborhood size of the population which represents a standardized

Under models of isolation-by-distance, population structure is determined by the probability of identity-by-descent between pairs of genes according to the geographic distance between them. Well established analytical results indicate that the relationship between geographical and genetic distance depends mostly on the neighborhood size of the population which represents a standardized measure of gene flow. To test this prediction, we model local dispersal of haploid individuals on a two-dimensional landscape using seven dispersal kernels: Rayleigh, exponential, half-normal, triangular, gamma, Lomax and Pareto. When neighborhood size is held constant, the distributions produce similar patterns of isolation-by-distance, confirming predictions. Considering this, we propose that the triangular distribution is the appropriate null distribution for isolation-by-distance studies. Under the triangular distribution, dispersal is uniform over the neighborhood area which suggests that the common description of neighborhood size as a measure of an effective, local panmictic population is valid for popular families of dispersal distributions. We further show how to draw random variables from the triangular distribution efficiently and argue that it should be utilized in other studies in which computational efficiency is important.

ContributorsFurstenau, Tara (Author) / Cartwright, Reed (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-03-29