Replicative activity of lung type 2 cells following lung X irradiation

We investigated the replicative activity of type 2 cells in the lungs of mice at various times from 3 to 22 weeks after 18 Gy of X rays to the thorax. No significant changes were found until 11 weeks after thoracic X irradiation. Thereafter the replicative index of type 2 cells was significantly elevated, rising four to sixfold above that of control, sham-irradiated mice. During the period when the replicative activity of type 2 cells was elevated, the breathing frequency increased and there was histologic evidence of the presence of radiation pneumonitis. The magnitude of each of these indices of pneumonitis correlated significantly with the type 2 cell replicative index, suggesting that type 2 cell replication is related to pneumonitis in extent as well as in chronology. How these changes relate to the pathogenesis of radiation pneumonitis is unclear.     

Attenuation of pattern recognition receptor signaling is mediated by a MAP kinase kinase kinase

Pattern recognition receptors (PRRs) play a key role in plant and animal innate immunity. PRR binding of their cognate ligand triggers a signaling network and activates an immune response. Activation of PRR signaling must be controlled prior to ligand binding to prevent spurious signaling and immune activation. Flagellin perception in Arabidopsis through FLAGELLIN‐SENSITIVE 2 (FLS2) induces the activation of mitogen‐activated protein kinases (MAPKs) and immunity. However, the precise molecular mechanism that connects activated FLS2 to downstream MAPK cascades remains unknown. Here, we report the identification of a differentially phosphorylated MAP kinase kinase kinase that also interacts with FLS2. Using targeted proteomics and functional analysis, we show that MKKK7 negatively regulates flagellin‐triggered signaling and basal immunity and this requires phosphorylation of MKKK7 on specific serine residues. MKKK7 attenuates MPK6 activity and defense gene expression. Moreover, MKKK7 suppresses the reactive oxygen species burst downstream of FLS2, suggesting that MKKK7‐mediated attenuation of FLS2 signaling occurs through direct modulation of the FLS2 complex.     

Crystallization and phase behavior of fatty acid esters of 1,3-propanediol I: pure systems

Six pure fatty acid esters of 1,3-propanediol (PADE) molecules were investigated. A careful analysis of XRD, DSC as well as SFC results has allowed the determination of their structure and phase behavior. Two beta polymorphs were observed for C10-C18 and three beta polymorphs for C8. The same first polymorph (beta1) was observed for all the samples. The second polymorph (beta2) observed for C12-C18 was different from the second beta-form observed for C8 and C10. For all properties, the short chain length C8 and C10 samples were distinguished from the C12 to C18 samples and this explained much of the observed trends in behavior. Their lamellar packing was similar and has been explained by a simple addition of multiples of the length of a carbon bond to a primitive structure. The estimated long-range order highlighted a geometric effect that enabled the small chain molecules to better order than the longest molecules. The XRD results have been confirmed by DSC. The difference in property between the short and long chain molecules has also been clearly verified by the evolution of the energy of activation for nucleation as well as the enthalpy of melting and confirmed by microscopy measurements. For all the samples, the hardness which increased with increasing chain length is correlated with final %SFC. Avrami analysis of SFC versus time indicated heterogeneous nucleation and spherulitic crystal development from sporadic nuclei, and suggested that the rate of nucleation was higher for longer chain molecules.     

A tale of two controversies: defining both the role of peroxidases in nitrotyrosine formation in vivo using eosinophil peroxidase and myeloperoxidase-deficient mice, and the nature of peroxidase-generated reactive nitrogen species

Nitrotyrosine is widely used as a marker of post-translational modification by the nitric oxide ((.)NO, nitrogen monoxide)-derived oxidant peroxynitrite (ONOO(-)). However, since the discovery that myeloperoxidase (MPO) and eosinophil peroxidase (EPO) can generate nitrotyrosine via oxidation of nitrite (NO(2)(-)), several questions have arisen. First, the relative contribution of peroxidases to nitrotyrosine formation in vivo is unknown. Further, although evidence suggests that the one-electron oxidation product, nitrogen dioxide ((*)NO(2)), is the primary species formed, neither a direct demonstration that peroxidases form this gas nor studies designed to test for the possible concomitant formation of the two-electron oxidation product, ONOO(-), have been reported. Using multiple distinct models of acute inflammation with EPO- and MPO-knockout mice, we now demonstrate that leukocyte peroxidases participate in nitrotyrosine formation in vivo. In some models, MPO and EPO played a dominant role, accounting for the majority of nitrotyrosine formed. However, in other leukocyte-rich acute inflammatory models, no contribution for either MPO or EPO to nitrotyrosine formation could be demonstrated. Head-space gas analysis of helium-swept reaction mixtures provides direct evidence that leukocyte peroxidases catalytically generate (*)NO(2) formation using H(2)O(2) and NO(2)(-) as substrates. However, formation of an additional oxidant was suggested since both enzymes promote NO(2)(-)-dependent hydroxylation of targets under acidic conditions, a chemical reactivity shared with ONOO(-) but not (*)NO(2). Collectively, our results demonstrate that: 1) MPO and EPO contribute to tyrosine nitration in vivo; 2) the major reactive nitrogen species formed by leukocyte peroxidase-catalyzed oxidation of NO(2)(-) is the one-electron oxidation product, (*)NO(2); 3) as a minor reaction, peroxidases may also catalyze the two-electron oxidation of NO(2)(-), producing a ONOO(-)-like product. We speculate that the latter reaction generates a labile Fe-ONOO complex, which may be released following protonation under acidic conditions such as might exist at sites of inflammation.     

Monoterpenoid indole alkaloids from Palicourea crocea

A new monoterpenoid indole alkaloid N-oxide, 3,4-dihydro-1-(1-β-d-glucopyranosyloxy-1,4a,5,7a-tetrahydro-4-methoxycarbonylcyclopenta[c]pyran-7-yl)-β-carboline-N²-oxide (3) and two known monoterpenoid indole alkaloids, croceaine A (1) and psychollatine (2), were isolated from Palicourea crocea (Rubiaceae) from Trinidad. The structures of 1–3 were determined on the basis of spectral and other physical data. Compounds 1 and 2 were previously isolated from plants of different genera viz. Palicourea crocea and Psychotria umbellata, respectively, both collected in Brazil. The results support the proposal that the genus Palicourea and the subgenus Heteropsychotria should be combined into a single genus.     

Neuropsychopharmacology and Neurogenetic Aspects of Executive Functioning: Should Reward Gene Polymorphisms Constitute a Diagnostic Tool to Identify Individuals at Risk for Impaired Judgment?

Executive functions are processes that act in harmony to control behaviors necessary for maintaining focus and achieving outcomes. Executive dysfunction in neuropsychiatric disorders is attributed to structural or functional pathology of brain networks involving prefrontal cortex (PFC) and its connections with other brain regions. The PFC receives innervations from different neurons associated with a number of neurotransmitters, especially dopamine (DA). Here we review findings on the contribution of PFC DA to higher-order cognitive and emotional behaviors. We suggest that examination of multifactorial interactions of an individual's genetic history, along with environmental risk factors, can assist in the characterization of executive functioning for that individual. Based upon the results of genetic studies, we also propose genetic mapping as a probable diagnostic tool serving as a therapeutic adjunct for augmenting executive functioning capabilities. We conclude that preservation of the neurological underpinnings of executive functions requires the integrity of complex neural systems including the influence of specific genes and associated polymorphisms to provide adequate neurotransmission.     

Synthesis and characterization of highly functionalized symmetric aromatic hexa-ol intermediates from oleic acid

A novel highly functionalized aromatic hexa-ol was synthesized by palladium-catalyzed cyclotrimerization of an alkyne fatty acid ester followed by LAH reduction. This polyol product is a novel monomer made from a renewable lipid raw material for the production of polyurethanes, polyesters and polyamides.     

Synthesis of aromatic triols and triacids from oleic and erucic acid: separation and characterization of the asymmetric and symmetric isomers

Hexasubstituted benzene derivatives, aromatic triols 4, 9 and triacids 5, 10 have been synthesized from oleic and erucic acid derivatives followed by a cyclotrimerization step catalyzed by palladium-on-carbon (Pd/C) and chlorotrimethylsilane (TMSCl). The asymmetric isomer, which is the main product, was isolated from its symmetric isomer by flash chromatography. All the products were fully characterized by IR, (1)H NMR, (13)C NMR and mass spectrometry. The products are suitable monomers for the production of polyurethanes, polyesters and polyamides.