Double Mu Research Articles

Genetic Analysis of the Heparan Modification Network in Caenorhabditis elegans

Heparan sulfates (HS) are highly modified sugar polymers in multicellular organisms that function in cell adhesion and cellular responses to protein signaling. Functionally distinct, cell type-dependent HS modification patterns arise as the result of a conserved network of enzymes that catalyze deacetylations, sulfations, and epimerizations in specific positions of the sugar residues. To understand the genetic interactions of the enzymes during the HS modification process, we have measured the composition of HS purified from mutant strains of Caenorhabditis elegans. From these measurements we have developed a genetic network model of HS modification. We find the interactions to be highly recursive positive feed-forward and negative feedback loops. Our genetic analyses show that the HS C-5 epimerase hse-5, the HS 2-O-sulfotransferase hst-2, or the HS 6-O-sulfotransferase hst-6 inhibit N-sulfation. In contrast, hse-5 stimulates both 2-O- and 6-O-sulfation and, hst-2 and hst-6 inhibit 6-O- and 2-O-sulfation, respectively. The effects of hst-2 and hst-6 on N-sulfation, 6-O-sulfation, and 2-O-sulfation appear largely dependent on hse-5 function. This core of regulatory interactions is further modulated by 6-O-endosulfatase activity (sul-1). 47% of all 6-O-sulfates get removed from HS and this editing process is dependent on hst-2, thereby providing additional negative feedback between 2-O- and 6-O-sulfation. These findings suggest that the modification patterns are highly sensitive to the relative composition of the HS modification enzymes. Our comprehensive genetic analysis forms the basis of understanding the HS modification network in metazoans.

One-dimensional metal-azido complex constructed by a double EO azido bridged trinuclear nickel(ii) unit: synthesis, structure and magnetic properties

The hydrothermal reaction of Ni(NO(3))(2).6H(2)O, NaN(3) phenanthroline and nicotinic acid yielded a one-dimensional (1D) complex, [Ni(1.5)(N(3))(2)(phen)(nic)](n) (1) (phen = phenanthroline, nic = nicotinate), which is a new example of the named orbital countercomplementarity-like complex. In 1, the nicotinate shows mu(3)-nic-N,O,O coordination mode, and the azide groups adopt mu(1,1) bridging mode linking Ni(II) ions to form a rare trinuclear Ni(II) unit bridged by a double mu(1,1) azido.

Magnetic Structure of the Large-Spin Mn10 and Mn19 Complexes: A Theoretical Complement to an Experimental Milestone

High-spin molecules have been proposed as candidates for the storage of information at the molecular level. The electronic structure of two complex magnetic molecular systems, Mn 10 and Mn 19, is characterized by means of a computational study based on density functional theory. All the exchange interactions in the recently reported Mn 19 complex with the highest known spin value of 83/2, and in its highly symmetric Mn 10 parent compound, are ferromagnetic. In these complexes, there are two kinds of ferromagnetic coupling: the first one corresponds to Mn (II)-Mn (III) interactions through a double mu 2-alkoxo-mu 4-oxo bridge where the high coordination number of the Mn (II) cations results in long Mn (II)-O bond distances, while the second one involves Mn (III)-Mn (III) interactions through mu 2-alkoxo-mu 3-eta (1):eta (1):eta (1) azido bridging ligands with long Mn (III)-N distances due to a Jahn-Teller effect.

Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice.

Several studies have shown a functional relationship between the endogenous cannabinoid and opioid systems. However, acute effects of Delta9-tetrahydrocannabinol (THC) and physical dependence were not modified in knockout mice with single deletion of mu (MOR), delta (DOR) or kappa (KOR) opioid receptors. To further investigate the neurobiological basis of cannabinoid dependence, we have evaluated acute pharmacological responses, rewarding effects, tolerance and dependence to THC in double MOR/DOR knockout mice. Antinociception and hypolocomotion induced by acute THC administration remained unaffected, whereas the hypothermic effect was slightly attenuated in these double knockout mice. During chronic THC treatment, knockout mice developed slower tolerance to the hypothermic effect, but the development of tolerance to antinociceptive and hypolocomotor effects was unchanged. The rewarding properties of THC, measured in the conditioned place preference paradigm, were reduced in knockout mice. Interestingly, the somatic manifestations of THC withdrawal were also significantly attenuated in mutant mice, suggesting that a cooperative action of MOR and DOR is required for the entire expression of THC dependence.

Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice

Cannabinoid withdrawal syndrome is reduced in double mu and delta opioid receptor knockout mice

Two new one-dimensional compounds with end-to-end dicyanamide as a bridging ligand: syntheses and structural characterization of trans-[Mn(4-bzpy)2(N(CN)2)2]n and cis-[Mn(Bpy)(N(CN)2)2]n, (4-bzpy = 4-benzoylpyridine; bpy = 2,2'-bipyridyl).

Two new one-dimensional compounds, trans-[Mn(4-bzpy)2(N(CN)2)2]n (1) and cis-[Mn(bpy)(N(CN)2)2]n (2), have been synthesized and studied from a magnetic point of view (4-bzpy = 4-benzoylpyridine; bpy = 2,2'-bipyridyl). The crystal structures of 1 and 2 have been solved. Compound 1 crystallizes in the monoclinic system, P2(1)/n group, a = 6.374(2) A, b = 7.584(2) A, c = 26.766(5) A, beta = 91.87 degrees, and Z = 2, whereas compound 2 crystallizes in the monoclinic system, C2/c group, a = 6.707(2) A, b = 17.188(5) A, c = 13.096(5) A, beta = 90.54 degrees, and Z = 4. The two compounds consist of chains with double mu 1,5-dicyanamide bridges between neighboring manganese(II) atoms. The weak antiferromagnetic coupling found for the two compounds (J = -0.3 cm-1 for 1 and -0.4 cm-1 for 2) has been studied by MO analysis, and the superexchange pathway through the mu 1,5-(NCNCN-) bridge has been compared with the shorter mu 1,3-(NNN-).

A Note on Doubles of 4-Manifolds

If M is a simply-connected 4-manifold with boundary, let D(M) denote its double MU∂M(-M). If M is closed, let D(M) denote M#-M. In either case, D(M) is a simply-connected 4-manifold of index zero, and so by a theorem of Wall [8], M#k(S2xS2) must be standard for k sufficiently large, where by standard we mean diffeomorphic to the connected sum of copies of S2 x S2 and S2×S2, the non-trivial S2 bundle over S2 (which is itself diffeomorphic to ℂP2#-ℂP2 [7]). In this paper we give abound on k, in the case where M has no 3-handles.