Immunohistochemical evidence for the NO cGMP signaling pathway in respiratory ciliated epithelia of rat.

Airway epithelia play a crucial role in protecting the lung from the external environment. Ciliated airway epithelial cells contribute to mucociliary transport systems via ciliary beating and electrolyte transport mechanisms to defend against respiratory tract infection. Both of these activities are regulated by nitric oxide (NO)-dependent mechanisms. To better understand the role of the NO-cGMP signal transduction cascade in these responses, we investigated the localization of endothelial nitric oxide synthase (eNOS), soluble guanylyl cyclase (sGC), cGMP-dependent protein kinase (PKG) I-alpha, and PKG I-beta in the tracheas and lungs of normal rats by immunohistochemistry. Mouse anti-eNOS, rabbit anti-sGC, PKG I-alpha, and PKG I-beta antibodies were used. Strong immunostaining for eNOS was detected in ciliated tracheal, bronchial, and bronchiolar epithelia, in Clara cells, and in Type II alveolar cells. The pattern of sGC and PKG I-beta immunostaining showed striking parallels with that of eNOS staining. No staining was detectable in ciliated epithelium with the anti-PKG I-alpha antibody. Taken together, these observations suggest that PKG I-beta might transduce NO-sGC signaling into biological responses in ciliated respiratory epithelia.(J Histochem Cytochem 47:1369-1374, 1999)     

Cloning and characterization of E-dlg, a novel splice variant of mouse homologue of the Drosophila discs large tumor suppressor binds preferentially to SAP102

Membrane-associated guanylate kinases (MAGUKs) act as scaffolds to coordinate signaling events through their multiple domains at the plasma membrane. The MAGUK SH3 domain is noncanonical and its function remains unclear. To identify potential binding partners of MAGUK SH3, the synapse-associated protein 102 (SAP102) SH3 domain was used as bait in a yeast two-hybrid screen of a mouse embryonic cDNA library. A mouse homologue of the Drosophila discs large tumor suppressor (Dlg, also known as SAP97) bound preferentially to SAP102 SH3. The 4347bp cDNA sequence encoded an 893 amino acid protein with 94% identity to mouse SAP97. A deleted region (33-aa) strongly suggests this is a novel splice variant, which we call Embryonic-dlg/SAP97 (E-dlg). The interaction of SAP102 and E-dlg was confirmed in mammalian cells. E-dlg can also bind to potassium channel Kv1.4 in a pull-down assay. E-dlg was highly expressed in embryonic and some adult mouse tissues, such as brain, kidney, and ovary. Furthermore, in situ hybridization showed that E-dlg was mostly expressed in olfactory bulb and cerebellum.     

Towards optimum permeability reduction in porous media using biofilm growth simulations

While biological clogging of porous systems can be problematic in numerous processes (e.g., microbial enhanced oil recovery—MEOR), it is targeted during bio‐barrier formation to control sub‐surface pollution plumes in ground water. In this simulation study, constant pressure drop (CPD) and constant volumetric flow rate (CVF) operational modes for nutrient provision for biofilm growth in a porous system are considered with respect to optimum (minimum energy requirement for nutrient provision) permeability reduction for bio‐barrier applications. Biofilm growth is simulated using a Lattice‐Boltzmann (LB) simulation platform complemented with an individual‐based biofilm model (IbM). A biomass detachment technique has been included using a fast marching level set (FMLS) method that models the propagation of the biofilm–liquid interface with a speed proportional to the adjacent velocity shear field. The porous medium permeability reduction is simulated for both operational modes using a range of biofilm strengths. For stronger biofilms, less biomass deposition and energy input are required to reduce the system permeability during CPD operation, whereas CVF is more efficient at reducing the permeability of systems containing weaker biofilms. Biotechnol. Bioeng. 2009;103: 767–779. © 2009 Wiley Periodicals, Inc.     

Sex biased intra-tree oviposition site selection and larval foraging behavior of a specialist herbivore

Heterogeneity in the quality of oviposition and feeding sites within plants can significantly influence the distribution and abundance of herbivorous insects, but remains poorly understood. Field surveys and a manipulative study were conducted to evaluate the influence of variation within the crown of black spruce, Picea mariana (Mill.) B.S.P. (Pinaceae), on adult oviposition and larval feeding behavior of yellowheaded spruce sawfly, Pikonema alaskensis Rohwer (Hymenoptera: Tenthredinidae). Most eggs were laid in the mid to lower crown of 1.5–2 m tall trees. However, most of the few eggs that were laid in the upper crown (i.e., whorl 2) were female. Fourth and fifth instars dispersed acropetally, from the mid and lower to the upper crown, causing high defoliation in the upper crown. Late-instar females were generally more abundant than males on the leader, the most apical shoot on a tree where eggs and early instars rarely occurred, strongly suggesting that more females than males disperse acropetally. This hypothesis was supported in a manipulative experiment, where only 15–20% of larvae in all-male broods, but almost three-quarters of larvae in mixed broods, dispersed to the upper crown. To our knowledge, this is only the second study to explicitly demonstrate preferential allocation of progeny sex through oviposition site selection by a herbivorous insect, and the first study to unambiguously demonstrate sex-biased dispersal by the juveniles of an insect whose adult females can fly. This study emphasizes the important role of intra-plant variation in shaping both oviposition site selection and the dispersal behavior of juvenile phytophagous insects within their hosts, and suggests that sex-biased foraging behaviors may be necessary for some insects to accommodate the respective needs of immature females and males within heterogeneous host plants.     

1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position

The use of a 1,3,4-oxadiazole in combination with an 8-hydroxy-1,6-naphthyridine ring system has been shown to deliver potent enzyme and antiviral activity through inhibition of viral DNA integration. This report presents a detailed structure–activity investigation of the C5 position resulting in low nM potency for several analogs with an excellent therapeutic index.     

The use of oxadiazole and triazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 1: Establishing the pharmacophore

A series of HIV-1 integrase inhibitors containing a novel metal binding motif consisting of the 8-hydroxy-1,6-naphthyridine core and either an oxadiazole or triazole has been identified. The design of the key structural components was based on a two-metal coordination pharmacophore. This report presents initial structure–activity data that shows the new chelation architecture delivers potent inhibition in both enzymatic and antiviral assays.     

Pyrazolopyrimidines and pyrazolotriazines with potent activity against herpesviruses

Synthesis of several pyrazolo[1,5-c]pyrimidines, pyrazolo[1,5-a]pyrimidines and pyrazolo[1,5-a][1,3,5]triazines with potent activity against herpes simplex viruses is described. Synthetic approaches allowing for variation of the substitution pattern are outlined and resulting changes in antiviral activity are highlighted. Several compounds with in vitro antiviral activity similar or better than acyclovir are described.     

Integrating gene expression and GO classification for PCA by preclustering

Background  

Gene expression data can be analyzed by summarizing groups of individual gene expression profiles based on GO annotation information. The mean expression profile per group can then be used to identify interesting GO categories in relation to the experimental settings. However, the expression profiles present in GO classes are often heterogeneous, i.e., there are several different expression profiles within one class. As a result, important experimental findings can be obscured because the summarizing profile does not seem to be of interest. We propose to tackle this problem by finding homogeneous subclasses within GO categories: preclustering.