213 research outputs found
Differential Binding of Co(II) and Zn(II) to Metallo-β-Lactamase Bla2 from \u3cem\u3eBacillus anthracis\u3c/em\u3e
In an effort to probe the structure, mechanism, and biochemical properties of metallo-β-lactamase Bla2 from Bacillus anthracis, the enzyme was overexpressed, purified, and characterized. Metal analyses demonstrated that recombinant Bla2 tightly binds 1 equiv of Zn(II). Steady-state kinetic studies showed that mono-Zn(II) Bla2 (1Zn-Bla2) is active, while di-Zn(II) Bla2 (ZnZn-Bla2) was unstable. Catalytically, 1Zn-Bla2 behaves like the related enzymes CcrA and L1. In contrast, di-Co(II) Bla2 (CoCo-Bla2) is substantially more active than the mono-Co(II) analogue. Rapid kinetics and UVâvis, 1H NMR, EPR, and EXAFS spectroscopic studies show that Co(II) binding to Bla2 is distributed, while EXAFS shows that Zn(II) binding is sequential. To our knowledge, this is the first documented example of a Zn enzyme that binds Co(II) and Zn(II) via distinct mechanisms, underscoring the need to demonstrate transferability when extrapolating results on Co(II)-substituted proteins to the native Zn(II)-containing forms
Structure and Metal Binding Properties of ZnuA, a Periplasmic Zinc Transporter from \u3cem\u3eEscherichia coli\u3c/em\u3e
ZnuA is the periplasmic Zn2+-binding protein associated with the high-affinity ATP-binding cassette ZnuABC transporter from Escherichia coli. Although several structures of ZnuA and its homologs have been determined, details regarding metal ion stoichiometry, affinity, and specificity as well as the mechanism of metal uptake and transfer remain unclear. The crystal structures of E. coli ZnuA (Eco-ZnuA) in the apo, Zn2+-bound, and Co2+-bound forms have been determined. ZnZnuA binds at least two metal ions. The first, observed previously in other structures, is coordinated tetrahedrally by Glu59, His60, His143, and His207. Replacement of Zn2+ with Co2+ results in almost identical coordination geometry at this site. The second metal binding site involves His224 and several yet to be identified residues from the His-rich loop that is unique to Zn2+ periplasmic metal binding receptors. Electron paramagnetic resonance and X-ray absorption spectroscopic data on CoZnuA provide additional insight into possible residues involved in this second site. The second site is also detected by metal analysis and circular dichroism (CD) titrations. Eco-ZnuA binds Zn2+ (estimated K d \u3c 20 nM), Co2+, Ni2+, Cu2+, Cu+, and Cd2+, but not Mn2+. Finally, conformational changes upon metal binding observed in the crystal structures together with fluorescence and CD data indicate that only Zn2+ substantially stabilizes ZnuA and might facilitate recognition of ZnuB and subsequent metal transfer
Studying stellar binary systems with the Laser Interferometer Space Antenna using Delayed Rejection Markov chain Monte Carlo methods
Bayesian analysis of LISA data sets based on Markov chain Monte Carlo methods
has been shown to be a challenging problem, in part due to the complicated
structure of the likelihood function consisting of several isolated local
maxima that dramatically reduces the efficiency of the sampling techniques.
Here we introduce a new fully Markovian algorithm, a Delayed Rejection
Metropolis-Hastings Markov chain Monte Carlo method, to efficiently explore
these kind of structures and we demonstrate its performance on selected LISA
data sets containing a known number of stellar-mass binary signals embedded in
Gaussian stationary noise.Comment: 12 pages, 4 figures, accepted in CQG (GWDAW-13 proceedings
Nutrient Enrichment Drives Gulf of Mexico Hypoxia
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95312/1/eost16763.pd
Ecological and genetic effects of introduced species on their native competitors
Species introductions to new habitats can cause a decline in the population
size of competing native species and consequently also in their genetic
diversity. We are interested in why these adverse effects are weak in some
cases whereas in others the native species declines to the point of extinction.
While the introduction rate and the growth rate of the introduced species in
the new environment clearly have a positive relationship with invasion success
and impact, the influence of competition is poorly understood. Here, we
investigate how the intensity of interspecific competition influences the
persistence time of a native species in the face of repeated and ongoing
introductions of the nonnative species. We analyze two stochastic models: a
model for the population dynamics of both species and a model that additionally
includes the population genetics of the native species at a locus involved in
its adaptation to a changing environment. Counterintuitively, both models
predict that the persistence time of the native species is lowest for an
intermediate intensity of competition. This phenomenon results from the
opposing effects of competition at different stages of the invasion process:
With increasing competition intensity more introduction events are needed until
a new species can establish, but increasing competition also speeds up the
exclusion of the native species by an established nonnative competitor. By
comparing the ecological and the eco-genetic model, we detect and quantify a
synergistic feedback between ecological and genetic effects.Comment: version accepted at Theoretical Population Biolog
Organic farming provides reliable environmental benefits but increases variability in crop yields: a global meta-analysis
To promote food security and sustainability, ecologically intensive farming systems should reliably produce adequate yields of high-quality food, enhance the environment, be profitable, and promote social wellbeing. Yet, while many studies address the mean effects of ecologically intensive farming systems on sustainability metrics, few have considered variability. This represents a knowledge gap because producers depend on reliable provisioning of yields, profits, and environmental services to enhance the sustainability of their production systems over time. Further, stable crop yields are necessary to ensure reliable access to nutritious foods. Here we address this by conducting a global meta-analysis to assess the average magnitude and variability of seven sustainability metrics in organic compared to conventional systems. Specifically, we explored the effects of these systems on (i) biotic abundance, (ii) biotic richness, (iii) soil organic carbon, (iv) soil carbon stocks, (v) crop yield, (vi) total production costs, and (vii) profitability. Organic farms promoted biotic abundance, biotic richness, soil carbon, and profitability, but conventional farms produced higher yields. Compared to conventional farms, organic farms had lower variability in abundance and richness but greater yield variability. Organic farms thus provided a âwin-winâ (high means and low variability) for environmental sustainability, while conventional farms provided a âwin-winâ for production by promoting high crop yields with low variability. Despite lower yields, and greater yield variability, organic systems had similar costs to conventional systems and were more profitable due to organic premiums. Our results suggest certification guidelines for organic farms successfully promote reliable environmental benefits, but greater reliance on ecological processes may reduce predictability of crop production
Treating breast cancer through novel inhibitors of the phosphatidylinositol 3'-kinase pathway
Recent studies indicate that constitutive signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway is a cause of treatment resistance in breast cancer patients. This implies that patients with tumors that exhibit aberrant PI3K signaling may benefit from targeted pathway inhibitors. The first agents to make it to the clinic are the rapamycin analogs. These compounds inhibit the downstream PI3K effector mTOR (mammalian target of rapamycin). A study presented in this issue of Breast Cancer Research suggests that recently developed inhibitors of phosphoinositide-dependent protein kinase 1, a more proximal target of the PI3K pathway, may provide an alternative route to effective PI3K pathway inhibition for breast cancer treatment
Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer
Identifying Farming Strategies Associated With Achieving Global Agricultural Sustainability
Sustainable agroecosystems provide adequate food while supporting environmental and human wellbeing and are a key part of the United Nations Sustainable Development Goals (SDGs). Some strategies to promote sustainability include reducing inputs, substituting conventional crops with genetically modified (GM) alternatives, and using organic production. Here, we leveraged global databases covering 121 countries to determine which farming strategiesâthe amount of inputs per area (fertilizers, pesticides, and irrigation), GM crops, and percent agriculture in organic productionâare most correlated with 12 sustainability metrics recognized by the United Nations Food and Agriculture Organization. Using quantile regression, we found that countries with higher Human Development Indices (HDI) (including education, income, and lifespan), higher-income equality, lower food insecurity, and higher cereal yields had the most organic production and inputs. However, input-intensive strategies were associated with greater agricultural greenhouse gas emissions. In contrast, countries with more GM crops were last on track to meeting the SDG of reduced inequalities. Using a longitudinal analysis spanning 2004â2018, we found that countries were generally decreasing inputs and increasing their share of agriculture in organic production. Also, in disentangling correlation vs. causation, we hypothesize that a country's development is more likely to drive changes in agricultural strategies than vice versa. Altogether, our correlative analyses suggest that countries with greater progress toward the SDGs of no poverty, zero hunger, good health and wellbeing, quality education, decent work, economic growth, and reduced inequalities had the highest production of organic agriculture and, to a lesser extent, intensive use of inputs
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