Interactions between pharmacologic NFB inhibitors (eg, Bay 11-7082, SN-50) and the checkpoint abrogator UCN-01 have been examined in human multiple myeloma (MM) cells. Exposure of U266 cells to Bay 11-7082 (Bay) in combination with UCN-01 resulted in the abrogation of NFB/DNA binding activity and the synergistic induction of apoptosis. Comparable synergism was observed in other MM cell lines an...

Because of the complexity derived from the existence of various phosphoinositide 3-kinase (PI3K) isoforms and their differential roles in cancers, development of PI3K inhibitors with differential pharmacologic and pharmacokinetic profiles would allow best exploration in different indications, combinations, and dosing regimens. Here, we report BAY 80-6946, a highly selective and potent pan-class...

Multi-locus genotype and sex were used to identify individual bowhead whales Balaena mysticetus from 710 samples collected between 1995 and 2010 at 4 localities in eastern Canada (Foxe Basin, Pelly Bay, Repulse Bay, and Cumberland Sound) and at 1 locality in West Greenland (Disko Bay). In total, 29 recaptures of the same individuals were identified between years, of which 26 individuals were re...

Coronary artery disease is associated with oxidative stress due to the excessive generation of free radicals in the vascular wall. This study investigated the impact of tert-butyl hydroperoxide (t-BuOOH), a peroxyl radical generator, on the redox state of soluble guanylate cyclase (sGC) in isolated monkey coronary arteries. Helically cut strips of endothelium-intact monkey coronary arteries tre...

The RAS-RAF-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway provides numerous opportunities for targeted oncology therapeutics. In particular, the MEK enzyme is attractive due to high selectivity for its target ERK and the central role that activated ERK plays in driving cell proliferation. The structural, pharmacologic, and pharmacokinetic ...

As an estuarine-dependent species, striped bass (Morone saxatilis) demonstrate large plasticity in migration patterns (Secor and Piccoli, 1996). Striped bass in Chesapeake Bay are partial migrants; only a fraction of individuals will leave estuarine habitats for oceanic waters (Kohlenstein, 1981). Never the less, Chesapeake Bay striped bass are the major contributors to interjurisdictional ocea...

In Prince Edward Island (PEI), shellfish (bivalves comprised of mussel and oyster) aquaculture production occurs in sheltered, generally shallow bays. The productive capacity of a bay for shellfish aquaculture is determined by many factors including the hydrodynamics of the bay and input of nutrients. There is considered to be a limit to the production (biomass) that can be extracted from an ar...

There is a net discharge of water and nutrients through Long Key Channel from Florida Bay to the Florida Keys National Marine Sanctuary (FKNMS). There has been speculation that this water and its constituents may be contributing to the loss of coral cover on the Florida Keys Reef tract over the past few decades, as well as speculation that changes in freshwater flow in the upstream Everglades e...

This study evaluated the distribution of polychlorinated biphenyls (PCBs) in 39 surface sediment samples and four cores collected in Toulon Bay, a semiclosed area submitted to various anthropogenic inputs. The concentration of PCBs in the superficial sediment samples ranged from 1.7 to 2530 ng g(-1) dry weight. The spatial distribution of these compounds suggested that the high concentrations o...

Atrial secretion of atrial natriuretic peptide (ANP) has been shown to be regulated by atrial workload. Although modulating factors for the secretion of ANP have been reported, the role for intracellular Ca(2+) on the secretion of ANP has been controversial. The purpose of the present study was to define roles for L- and T-type Ca(2+) channels in the regulation of ANP secretion in perfused beat...