Iridium-catalyzed alkane C−H borylation has long suffered from poor atom economy, resulting from both the inclusion of only 1 equiv of boron from the diboron reagent and a requirement for neat substrate. An appropriately substituted dipyridylarylmethane ligand was found to give highly active alkane borylation catalysts that facilitate C−H borylation with improved efficiency. This system provides for complete consumption of the diboron reagent, producing 2 molar equivalents of product at low catalyst loadings. The superior efficacy of this system also enables borylation of unactivated alkanes in hydrocarbon solvent with a reduced excess of substrate and improved functional group compatibility. The effectiveness of this ligand is displayed across a selection of functional groups, both under traditional borylation conditions in neat substrate and under atypical conditions in cyclohexane solvent. The utility of this catalytic system is exemplified by the borylation of substrates containing polar functionality, which are unreactive toward C−H borylation under neat conditions.

A single infusion of Escherichia coli endotoxin into sheep results in structural evidence of pulmonary endothelial injury, increases in both prostacyclin and prostaglandin E2 (PGE2) in lung lymph, and an increase in pulmonary microvascular permeability. Endotoxin-induced lung endothelial damage can also be induced in vitro, but to date these studies have utilized endothelium from large pulmonary vessels. In the present study, we have grown endothelial cells from peripheral lung vessels of cows and sheep and exposed these microvascular endothelial cells to endotoxin. Controls included lung microvascular endothelium without endotoxin and endothelial cells from bovine and sheep main pulmonary artery with and without addition of endotoxin. We found that endotoxin caused significant increases in release of prostacyclin and PGE2 from both bovine and sheep lung microvascular and pulmonary artery endothelium. Normal bovine and sheep pulmonary artery and bovine lung microvascular endothelium released greater levels of prostacyclin than PGE2 (ng/ng); release of PGE2 from the microvascular cells was greater than from the pulmonary artery endothelium in both species. Exposure of endothelial cells from cow and sheep main pulmonary artery to endotoxin results in endothelial cell retraction and pyknosis, a loss of barrier function, increased release of prostacyclin and PGE2 and eventual cell lysis. In lung microvascular cells, the increases in prostanoids were accompanied by changes in cell shape but occurred in the absence of either detectable alterations in barrier function or cytolysis. Thus, while endotoxin causes alterations to endothelial cells from both large and small pulmonary vessels, the effects are not identical suggesting site specific phenotypic expression of endothelial cells even within a single vessel. To determine whether the response of either the large or small pulmonary vessel endothelial cells in culture mimics most closely the in vivo response of the lung to endotoxin requires further study.

Tau dysfunction is common in several neurodegenerative diseases including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Affective symptoms have often been associated with aberrant tau pathology and are commonly comorbid in patients with tauopathies, indicating a connection between tau functioning and mechanisms of depression. The current study investigated depression-like behavior in Mapt−/− mice, which contain a targeted deletion of the gene coding for tau. We show that 6-month Mapt−/− mice are resistant to depressive behaviors, as evidenced by decreased immobility time in the forced swim and tail suspension tests, as well as increased escape behavior in a learned helplessness task. Since depression has also been linked to deficient adult neurogenesis, we measured neurogenesis in the hippocampal dentate gyrus and subventricular zone using 5-bromo-2-deoxyuridine (BrdU) labeling. We found that neurogenesis is increased in the dentate gyrus of 14-month-old Mapt−/− brains compared to wild type, providing a potential mechanism for their behavioral phenotypes. In addition to the hippocampus, an upregulation of proteins involved in neurogenesis was observed in the frontal cortex and amygdala of the Mapt−/− mice using proteomic mass spectrometry. All together, these findings suggest that tau may have a role in the depressive symptoms observed in many neurodegenerative diseases and identify tau as a potential molecular target for treating depression.

The field of catalytic C–H borylation has grown considerably since its founding, providing a means for the preparation of synthetically versatile organoborane products. Although sp2 C–H borylation methods have found widespread and practical use in organic synthesis, the analogous sp3 C–H borylation reaction remains challenging and has seen limited application. Existing catalysts are often hindered by incomplete consumption of the diboron reagent, poor functional-group tolerance, harsh reaction conditions, and the need for excess or neat substrate. These challenges acutely affect the C–H borylation chemistry of unactivated hydrocarbon substrates, which has lagged in comparison to methods for the C–H borylation of activated compounds. Herein, we discuss recent advances in the sp3 C–H borylation of undirected substrates in the context of two particular challenges: (1) utilization of the diboron reagent and (2) the need for excess or neat substrate. Our recent work on the application of dipyridylarylmethane ligands in sp3 C–H borylation has allowed us to make contributions in this space and has presented an additional ligand scaffold to supplement traditional phenanthroline ligands.