Functional nervous diseases:

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NMR imaging of the diffusion of water at 37 degrees C into poly(2-hydroxyethyl methacrylate) containing aspirin or vitamin B-12

The ingress of water into poly(2-hydroxyethyl methacrylate), PHEMA, loaded with either one of two model drugs, vitamin B-12 or aspirin, was studied at 37 degreesC using three-dimensional NMR imaging. PHEMA was loaded with 5 and 10 wt % of the drugs. From the imaging profiles, it was observed that incorporation of vitamin B-12 into PHEMA resulted in enhanced crack formation on sorption of water and the crack healing behind the diffusion front was slower than for PHEMA without added drug. This was accounted for by the anti-plasticization of PHEMA by vitamin B-12. Crack formation was inhibited in the P-HEMA-aspirin systems because of the plasticizing effect of the aspirin on the PHEMA matrix. All of the polymers were found to absorb water according to an underlying Fickian diffusion mechanism. For PHEMA loaded with 5 wt % of aspirin or vitamin B-12, the best values of the water diffusion coefficients were both found to be 1.3 +/- 0.1 x 10(-11) m(2) s(-1) at 37 degreesC, while the values for the polymer loaded with 10 wt % of the drugs were slightly higher, 1.5 +/- 0.1 x 10(-11) m(2) s(-1).

Ms. Ff. Mus. 1135 - Am 1. Advent : Hosianna dem Sohne David! ; gelobet sey p. ; C. C. A. T. B., 2 oboe et flauti, 2 violini, 1 viola, violoncello et organo

von Telemann. [Textdichter: Gottfried Simonis]

25-hydroxycholesterol, 7β-hydroxycholesterol and 7-ketocholesterol upregulate interleukin-8 expression independently of Toll-like receptor 1, 2, 4 or 6 signalling in human macrophages

Recent studies have shown that Toll-like receptor (TLR)- signalling contributes significantly to the inflammatory events of atherosclerosis. As products of cholesterol oxidation (oxysterols) accumulate within atherosclerotic plaque and have been proposed to contribute to inflammatory signalling in the diseased artery, we investigated the potential of 7-ketocholesterol (7-KC), 7β-hydroxycholesterol (7β-HC) and 25-hydroxycholesterol (25-HC) to stimulate inflammatory signalling via the lipid-recognising TLRs 1, 2, 4 and 6. Each oxysterol stimulated secretion of the inflammatory chemokine interleukin-8 (IL-8), but not I?B degradation or tumour necrosis factor- release from monocytic THP-1 cells. Transfection of TLR-deficient HEK-293 cells with TLRs 1, 2, 4 or 6 did not increase sensitivity to the tested oxysterols. Moreover, blockade of TLR2 or TLR4 with specific inhibitors did not reduce 25-hydroxycholesterol (25-HC) induced IL-8 release from THP-1 cells. We conclude that although the oxysterols examined in this study may contribute to increased expression of certain inflammatory genes, this occurs by mechanisms independent of TLR signalling.

A study of T = 2 states in ^(12)B, ^(12)C, ^(20)F and ^(28)Al

The lowest T = 2 states have been identified and studied in the nuclei ¹²C, 12</sup>B, 20F and and 28Al. The first two of these were produced in the reactions 14C(p,t)12</sup>C and 14C (p,3He)12</sup>B, at 50.5 and 63.4 MeV incident proton energy respectively, at the Oak Ridge National Laboratory. The T = 2 states in 20F and 28Al were observed in (3He,p) reactions at 12-MeV incident energy, with the Caltech Tandem accelerator.</sup>

The results for the four nuclei studied are summarized below:

(1) ¹²C: the lowest T = 2 state was located at an excitation energy of 27595 ± 20 keV, and has a width less than 35 keV.</sup>

(2) ¹²B: the lowest T = 2 state was found at an excitation energy of 12710 ± 20 keV. The width was determined to be less than 54 keV and the spin and parity were confirmed to be 0+. A second 12</sup>B state (or doublet) was observed at an excitation energy of 14860 ± 30 keV with a width (if the group corresponds to a single state) of 226 ± 30 keV.</sup>

(3) ²⁰F: the lowest T = 2 state was observed at an excitation of 6513 ± 5 keV; the spin and parity were confirmed to be 0⁺. A second state, tentatively identified as T = 2 from the level spacing, was located at 8210 ± 6 keV.

(4) ²⁸Al: the lowest T = 2 state was identified at an excitation of 5997 ± 6 keV; the spin and parity were confirmed to be 0⁺. A second state at an excitation energy of 7491 ± 11 keV is tentatively identified as T = 2, with a corresponding (tentative) spin and parity assignment J^π = 2<sup>+.

The results of the present work and the other known masses of T = 2 states and nuclei for 8 ≤ A ≤ 28 are summarized, and massequation coefficients have been extracted for these multiplets. These coefficients were compared with those from T = 1 multiplets, and then used to predict the mass and stability of each of the unobserved members of the T = 2 multiplets.

Arctic oscillation or North Atlantic oscillation?

The definition and interpretation of the Arctic oscillation (AO) are examined and compared with those of the North Atlantic oscillation (NAO). It is shown that the NAO reflects the correlations between the surface pressure variability at its centers of action, whereas this is not the case for the AO. The NAO pattern can be identified in a physically consistent way in principal component analysis applied to various fields in the Euro-Atlantic region. A similar identification is found in the Pacific region for the Pacific–North American (PNA) pattern, but no such identification is found here for the AO. The AO does reflect the tendency for the zonal winds at 35° and 55°N to anticorrelate in both the Atlantic and Pacific regions associated with the NAO and PNA. Because climatological features in the two ocean basins are at different latitudes, the zonally symmetric nature of the AO does not mean that it represents a simple modulation of the circumpolar flow. An increase in the AO or NAO implies strong, separated tropospheric jets in the Atlantic but a weakened Pacific jet. The PNA has strong related variability in the Pacific jet exit, but elsewhere the zonal wind is similar to that related to the NAO. The NAO-related zonal winds link strongly through to the stratosphere in the Atlantic sector. The PNA-related winds do so in the Pacific, but to a lesser extent. The results suggest that the NAO paradigm may be more physically relevant and robust for Northern Hemisphere variability than is the AO paradigm. However, this does not disqualify many of the physical mechanisms associated with annular modes for explaining the existence of the NAO.

TLR4/MYD88-dependent, LPS-induced synthesis of PGE(2) by macrophages or dendritic cells prevents anti-CD3-mediated CD95L upregulation in T cells

Antigen-presenting cells (APCs) control T-cell responses by multiple mechanisms, including the expression of co-stimulatory molecules and the production of cytokines and other mediators that control T-cell proliferation, survival and differentiation. Here, we demonstrate that soluble factor(s) produced by Toll-like receptor (TLR)-activated APCs suppress activation-induced cell death (AICD). This effect was observed in non-stimulated APCs, but it was significantly increased after lipopolysaccharide (LPS) treatment. Using different KO mice, we found that the LPS-induced protective factor is dependent on TLR4/MyD88. We identified the protective factor as prostaglandin E-2(PGE(2)) and showed that both APC-derived supernatants and PGE(2) prevented CD95L upregulation in T cells in response to TCR/CD3 stimulation, thereby avoiding both AICD and activated T cell killing of target macrophages. The PGE(2) receptors, EP2 and EP4, appear to be involved since pharmacological stimulation of these receptors mimics the protective effect on T cells and their respective antagonists interfere with the protection induced by either APCs derived or synthetic PGE(2). Finally, the engagement of EP2 and EP4 synergistically activates protein kinase A (PKA) and exchange protein directly activated by cAMP pathways to prevent AICD. Taken together, these results indicate that APCs can regulate T-cell levels of CD95L by releasing PGE2 in response to LPS through a TLR4/MyD88-dependent pathway, with consequences for both T cell and their own survival.

Subfornical organ mediates pressor effect of angiotensin: Influence of nitric oxide synthase inhibitors, AT(1) and AT(2) angiotensin antagonist's receptors

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Insights into the role of oligomeric state on the biological activities of crotoxin: crystal structure of a tetrameric phospholipase A(2) formed by two isoforms of crotoxin B from Cratalus durissus terrificus venom

Crotoxin B (CB or Cdt PLA(2)) is a basic Asp49-PLA(2) found in the venom of Crotalus durissus terrificus and it is one of the subunits that constitute the crotoxin (Cro). This heterodimeric toxin, main component of the C. d. terrificus venom, is completed by an acidic, nontoxic, and nonenzymatic component (crotoxin A, CA or crotapotin), and it is related to important envenomation effects such as neurological disorders, myotoxicity, and renal failure. Although Cro has been crystallized since 1938, no crystal structure of this toxin or its subunits is currently available. In this work, the authors present the crystal structure of novel tetrameric complex formed by two dimers of crotoxin B isoforms (CB1 and CB2). The results suggest that these assemblies are stable in solution and show that Ser1 and Glu92 of CB1 and CB2, respectively, play an important role in the oligomerization. The tetrameric and dimeric conformations resulting from the association of the isoforms may increase the neurotoxicity of the toxin CB by the creation of new binding sites, which could improve the affinity of the molecular complexes to the presynaptic membrane.

Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation.

Clearance of allergic inflammatory cells from the lung through matrix metalloproteinases (MMPs) is necessary to prevent lethal asphyxiation, but mechanistic insight into this essential homeostatic process is lacking. In this study, we have used a proteomics approach to determine how MMPs promote egression of lung inflammatory cells through the airway. MMP2- and MMP9-dependent cleavage of individual Th2 chemokines modulated their chemotactic activity; however, the net effect of complementing bronchoalveolar lavage fluid of allergen-challenged MMP2(-/-)/MMP9(-/-) mice with active MMP2 and MMP9 was to markedly enhance its overall chemotactic activity. In the bronchoalveolar fluid of MMP2(-/-)/MMP9(-/-) allergic mice, we identified several chemotactic molecules that possessed putative MMP2 and MMP9 cleavage sites and were present as higher molecular mass species. In vitro cleavage assays and mass spectroscopy confirmed that three of the identified proteins, Ym1, S100A8, and S100A9, were substrates of MMP2, MMP9, or both. Function-blocking Abs to S100 proteins significantly altered allergic inflammatory cell migration into the alveolar space. Thus, an important effect of MMPs is to differentially modify chemotactic bioactivity through proteolytic processing of proteins present in the airway. These findings provide a molecular mechanism to explain the enhanced clearance of lung inflammatory cells through the airway and reveal a novel approach to target new therapies for asthma.

Climatological observations from ship logbooks between 1750 and 1854 (release 2.1)

The Climatological Database for the World's Oceans: 1750-1854 (CLIWOC) project, which concluded in 2004, abstracted more than 280,000 daily weather observations from ships' logbooks from British, Dutch, French, and Spanish naval vessels engaged in imperial business in the eighteenth and nineteenth centuries. These data, now compiled into a database, provide valuable information for the reconstruction of oceanic wind field patterns for this key period that precedes the time in which anthropogenic influences on climate became evident. These reconstructions, in turn, provide evidence for such phenomena as the El Niño-Southern Oscillation and the North Atlantic Oscillation. Of equal importance is the finding that the CLIWOC database the first coordinated attempt to harness the scientific potential of this resource represents less than 10 percent of the volume of data currently known to reside in this important but hitherto neglected source.

The Dabistan, or, School of manners /

Includes index.

NMR imaging of the diffusion of water at 310 K into poly[(2-hydroxyethyl methacrylate)-co-(tetrahydrofurfuryl methacrylate)] containing vitamin B12 or aspirin

The ingress of water into copolymers of 2-hydroxyethyl methacrylate (HEMA) and tetrahydrofurfuryl methacrylate (THFMA) loaded with either one of two model drugs, ie vitamin B-12 or aspirin, was studied at 310 K using three-dimensional nuclear magnetic resonance (3D NMR) imaging. The poly(HEMA) was loaded with 5 wt% of the drugs. From the imaging profiles it was observed that incorporation of vitamin B-12 into the polymers rich in HEMA resulted in crack formation at the interface between the rubbery region and the glassy core on sorption of water, although these cracks were 'healed' behind the diffusion front. However, for the copolymers with low HEMA contents and for those containing aspirin, no evidence for similar crack formation was found. For the copolymers loaded with 5 wt% of aspirin or vitamin B-12 the values of the water diffusion coefficients, determined by curve-fitting the relative water concentration profiles from magnetic resonance imaging (MRI) measurements, were found to be smaller than those obtained from a mass uptake study. (C) 2004 Society of Chemical Industry.