Polynomial mechanics and optimal control

We describe a new algorithm for trajectory optimization of mechanical systems. Our method combines pseudo-spectral methods for function approximation with variational discretization schemes that exactly preserve conserved mechanical quantities such as momentum. We thus obtain a global discretization of the Lagrange-d'Alembert variational principle using pseudo-spectral methods. Our proposed scheme inherits the numerical convergence characteristics of spectral methods, yet preserves momentum-conservation and symplecticity after discretization. We compare this algorithm against two other established methods for two examples of underactuated mechanical systems; minimum-effort swing-up of a two-link and a three-link acrobot.Comment: Final version to EC

The Mechanism and Modulation of H-NS Mediated Repression in Escherichia coli.

The histone-like nucleoid structuring protein H-NS acts as a global repressor of genes that are expressed in response to environmental stimuli and stress conditions. Repression by H-NS is presumably mediated by binding of H NS to primary "nucleation sites" close to promoters, and the formation of extended nucleoprotein complex from these nucleation sites to inhibit transcription initiation. Modulation of H-NS mediated repression is a complex process involving specific transcription factors and physiology dependent structural alterations. The E. coli bgl and proU operons are model systems that are repressed by H-NS with exceptional specificity. Both of these systems possess upstream and downstream regulatory elements (URE and DRE) bound by H-NS for efficient repression. The present study demonstrates that repression by H-NS binding upstream and downstream is synergistic in proU (as shown in a parallel study for bgl), and that H-NS when bound within the transcription unit represses transcription initiation at the bgl promoter, as reported before for proU. Repression by binding of H-NS downstream is known to be modulated. Common to both proU and bgl is that an increase in the promoter activity abrogates repression. For bgl it is known, that the H-NS mediated repression of the promoter is counteracted by transcription factors BglJ and LeuO. Further, termination factor Rho and the protease Lon are known to modulate repression by H-NS through the DRE, and as shown here the DnaKJ chaperone system is essential for this repression. In case of proU, the promoter is osmoregulated; the RNA polymerase is poised at the promoter at low osmolarity, while it clears the promoter with better efficiency at high osmolarity. Furthermore, the proU operon is subject to post-transcriptional osmoregulation. The proU mRNA is processed by RNAse III within a stretch of highly conserved sequence, suggesting a common mechanism of regulation among Enterobacteria. In summary, the present study demonstrates that the mechanism of H-NS mediated repression of the bgl and proU operons is very similar. However, its modulation is complex involving numerous additional factors specific to the two systems, and thus is achieved in a context specific manner

Scc2 counteracts a Wapl-independent mechanism that releases cohesin from chromosomes during G1

Acknowledgements Maria Demidova conducted initial experiments that this study expanded on. We are grateful to Tomo Tanaka and Seiji Tanaka for supplying reagents. We thank all members of the Nasmyth group for valuable discussions, technical assistance and critical reading of the manuscript. This work was funded by the Wellcome Trust Senior Investigator Award, Grant Ref 107935/Z/15/Z and Cancer Research UK Programme Grant, Grant Ref 26747 to KN. BH is funded by (202062/Z/16/Z).Peer reviewedPublisher PD

Releasing activity disengages Cohesin’s Smc3/Scc1 interface in a process blocked by Acetylation

Sister chromatid cohesion conferred by entrapment of sister DNAs within a tripartite ring formed between cohesin’s Scc1, Smc1, and Smc3 subunits is created during S and destroyed at anaphase through Scc1 cleavage by separase. Cohesin’s association with chromosomes is controlled by opposing activities: loading by Scc2/4 complex and release by a separase- independent releasing activity as well as by cleavage. Coentrapment of sister DNAs at replication is accompanied by acetylation of Smc3 by Eco1, which blocks releasing activity and ensures that sisters remain connected. Because fusion of Smc3 to Scc1 prevents release and bypasses the requirement for Eco1, we suggested that release is mediated by disengagement of the Smc3/Scc1 interface. We show that mutations capable of bypassing Eco1 in Smc1, Smc3, Scc1, Wapl, Pds5, and Scc3 subunits reduce dissociation of N-terminal cleavage fragments of Scc1 (NScc1) from Smc3. This process involves interaction between Smc ATPase heads and is inhibited by Smc3 acetylation

The cohesin ring uses its hinge to organize DNA using non-topological as well as topological mechanisms

As predicted by the notion that sister chromatid cohesion is mediated by entrapment of sister DNAs inside cohesin rings, there is perfect correlation between co-entrapment of circular minichromosomes and sister chromatid cohesion. In most cells where cohesin loads without conferring cohesion, it does so by entrapment of individual DNAs. However, cohesin with a hinge domain whose positively charged lumen is neutralized loads and moves along chromatin despite failing to entrap DNAs. Thus, cohesin engages chromatin in non-topological, as well as topological, manners. Since hinge mutations, but not Smc-kleisin fusions, abolish entrapment, DNAs may enter cohesin rings through hinge opening. Mutation of three highly conserved lysine residues inside the Smc1 moiety of Smc1/3 hinges abolishes all loading without affecting cohesin’s recruitment to CEN loading sites or its ability to hydrolyze ATP. We suggest that loading and translocation are mediated by conformational changes in cohesin’s hinge driven by cycles of ATP hydrolysis

Constitutive expression of Arabidopsis NPR1 confers enhanced resistance to the early instars of Spodoptera litura in transgenic tobacco

In Arabidopsis, NPR1 (AtNPR1) regulates salicylic acid (SA)-mediated activation of PR genes at the onset of systemic acquired resistance. AtNPR1 also modulates SA-induced suppression of jasmonic acid-responsive gene expression, and npr1 mutants manifest enhanced herbivore resistance. We have raised stable transgenic tobacco lines, expressing AtNPR1 constitutively, which showed elevated expression of PR1 and PR2 genes upon SA treatment. Herbivore bioassays with a generalist polyphagous pest, Spodoptera litura, revealed that the transgenic lines exhibited enhanced resistance compared to the wild-type plants, particularly with respect to younger larval populations. Insect-mediated injury induced several protease inhibitors (PIs), more significantly a 40-kDa serine PI in all the tobacco lines, but the induction was higher in the transgenic plants. We show in this communication that heterologous expression of AtNPR1 provides enhanced resistance to early larval populations of the herbivore, Spodoptera in transgenic tobacco plants