Herbicide mixtures at high doses slow the evolution of resistance in experimentally evolving populations of Chlamydomonas reinhardtii

The widespread evolution of resistance to herbicides is a pressing issue in global agriculture. Evolutionary principles and practices are key to the management of this threat to global food security. The application of mixtures of herbicides has been advocated as an anti-resistance strategy, without substantial empirical support for its validation. We evolved experimentally populations of the unicellular green chlorophyte, Chlamydomonas reinhardtii, to minimum inhibitory concentrations (MICs) of single-herbicide modes of action and to pair-wise and three-way mixtures between different herbicides at various total combined doses. Herbicide mixtures were most effective when each component was applied at or close to its MIC. When doses were high, increasing the number of mixture components was also effective in reducing the evolution of resistance. Employing mixtures at low combined doses did not retard resistance evolution, even accelerating the evolution of resistance to some components. At low doses, increasing the number of herbicides in the mixture tended to select for more generalist resistance (cross-resistance). Our results reinforce findings from the antibiotic resistance literature and confirm that herbicide mixtures can be very effective for resistance management, but that mixtures should only be employed where the economic and environmental context permits the applications of high combined doses

Modifications of Gait as Predictors of Natural Osteoarthritis Progression in STR/Ort Mice

OBJECTIVE: Osteoarthritis (OA) is a common chronic disease for which disease-modifying therapies are not currently available. Studies to seek new targets for slowing the progress of OA rely on mouse models, but these do not allow for longitudinal monitoring of disease development. This study was undertaken to determine whether gait can be used to measure disease severity in the STR/Ort mouse model of spontaneous OA and whether gait changes are related to OA joint pain. METHODS: Gait was monitored using a treadmill-based video system. Correlations between OA severity and gait at 3 treadmill speeds were assessed in STR/Ort mice. Gait and pain behaviors of STR/Ort mice and control CBA mice were analyzed longitudinally, with monthly assessments. RESULTS: The best speed to identify paw area changes associated with OA severity in STR/Ort mice was found to be 17 cm · seconds(−1). Paw area was modified with age in CBA and STR/Ort mice, but this began earlier in STR/Ort mice and correlated with the onset of OA at 20 weeks of age. In addition, task noncompliance appeared at 20 weeks. Surprisingly, STR/Ort mice did not show any signs of pain with OA development, even when treated with the opioid antagonist naloxone, but did exhibit normal pain behaviors in response to complete Freund's adjuvant–induced arthritis. CONCLUSION: The present results identify an animal model in which OA severity and OA pain can be studied in isolation from one another. The findings suggest that paw area and treadmill noncompliance may be useful tools to longitudinally monitor nonpainful OA development in STR/Ort mice. This will help in providing a noninvasive means of assessing new therapies to slow the progression of OA

Spiral ground state against ferroelectricity in the frustrated magnet BiMnFe2O6

The spiral magnetic structure and underlying spin lattice of BiMnFe2O6 are investigated by low-temperature neutron powder diffraction and density functional theory band structure calculations. In spite of the random distribution of the Mn3+ and Fe3+ cations, this compound undergoes a transition into an incommensurate antiferromagnetically ordered state below TN ~ 220 K. The magnetic structure is characterized by the propagation vector k=[0,beta,0] with beta ~ 0.14 and the P22_12_11'(0 \beta 0)0s0s magnetic superspace symmetry. It comprises antiferromagnetic helixes propagating along the b-axis. The magnetic moments lie in the ac plane and rotate about pi*(1+beta) ~ 204.8 deg angle between the adjacent magnetic atoms along b. The spiral magnetic structure arises from the peculiar frustrated arrangement of exchange couplings in the ab plane. The antiferromagnetic coupling along the c-axis leads to the cancellation of electric polarization, and results in the lack of ferroelectricity in BiMnFe2O6.Comment: 11 pages, 8 figures, 8 table

Large ferroelectric polarization in the new double perovskite NaLaMnWO6_{6} induced by non-polar instabilities

Based on density functional theory calculations and group theoretical analysis, we have studied NaLaMnWO$_{6}$ compound which has been recently synthesized [Phys. Rev. B 79, 224428 (2009)] and belongs to the $AA'BB'{\rm O}_{6}$ family of double perovskites. At low temperature, the structure has monoclinic $P2_{1}$ symmetry, with layered ordering of the Na and La ions and rocksalt ordering of Mn and W ions. The Mn atoms show an antiferromagnetic (AFM) collinear spin ordering, and the compound has been reported as a potential multiferroic. By comparing the low symmetry structure with a parent phase of $P4/nmm$ symmetry, two distortion modes are found dominant. They correspond to MnO$_{6}$ and WO$_{6}$ octahedron \textit{tilt} modes, often found in many simple perovskites. While in the latter these common tilting instabilities yield non-polar phases, in NaLaMnWO$_{6}$ the additional presence of the $A$-$A^{'}$ cation ordering is sufficient to make these rigid unit modes as a source of the ferroelectricity. Through a trilinear coupling with the two unstable tilting modes, a significant polar distortion is induced, although the system has no intrinsic polar instability. The calculated electric polarization resulting from this polar distortion is as large as $\sim$ 16 ${\mu}{\rm C/cm^{2}}$. Despite its secondary character, this polarization is coupled with the dominant tilting modes and its switching is bound to produce the switching of one of two tilts, enhancing in this way a possible interaction with the magnetic ordering. The transformation of common non-polar purely steric instabilities into sources of ferroelectricity through a controlled modification of the parent structure, as done here by the cation ordering, is a phenomenon to be further explored.Comment: Physical Chemistry Chemical physics (in press

Methionine adenosyltransferase S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target thiol

S-Adenosylmethionine serves as the methyl donor for many biological methylation reactions and provides the propylamine group for the synthesis of polyamines. S-Adenosylmethionine is synthesized from methionine and ATP by the enzyme methionine adenosyltransferase. The cellular factors regulating S-adenosylmethionine synthesis have not been well defined. Here we show that in rat hepatocytes S-nitrosoglutathione monoethyl ester, a cell-permeable nitric oxide donor, markedly reduces cellular S-adenosylmethionine content via inactivation of methionine adenosyltransferase by S-nitrosylation. Removal of the nitric oxide donor from the incubation medium leads to the denitrosylation and reactivation of methionine adenosyltransferase and to the rapid recovery of cellular S-adenosylmethionine levels. Nitric oxide inactivates methionine adenosyltransferase via S-nitrosylation of cysteine 121. Replacement of the acidic (aspartate 355) or basic (arginine 357 and arginine 363) amino acids located in the vicinity of cysteine 121 by serine leads to a marked reduction in the ability of nitric oxide to S-nitrosylate and inactivate hepatic methionine adenosyltransferase. These results indicate that protein S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target cysteine