The Ocean 100: Transnational corporations in the ocean economy.

The ocean economy is growing as commercial use of the ocean accelerates, while progress toward achieving international goals for ocean conservation and sustainability is lagging. In this context, the private sector is increasingly recognized as having the capacity to hamper efforts to achieve aspirations of sustainable ocean-based development or alternatively to bend current trajectories of ocean use by taking on the mantle of corporate biosphere stewardship. Here, we identify levels of industry concentration to assess where this capacity rests. We show that the 10 largest companies in eight core ocean economy industries generate, on average, 45% of each industry's total revenues. Aggregating across all eight industries, the 100 largest corporations (the "Ocean 100") account for 60% of total revenues. This level of concentration in the ocean economy presents both risks and opportunities for ensuring sustainability and equity of global ocean use.

A non-oncogenic HPV 16 E6/E7 vaccine enhances treatment of HPV expressing tumors.

Human papillomaviruses (HPVs) are the causative factor for >90% of cervical cancers and 25% of head and neck cancers. The incidence of HPV positive (+) head and neck squamous cell carcinomas has greatly increased in the last 30 years. E6 and E7 are the two key viral oncoproteins that induce and propagate cellular transformation. An immune response generated during cisplatin/radiation therapy improves tumor clearance of HPV(+) cancers. Augmenting this induced response during therapy with an adenoviral HPV16 E6/E7 vaccine improves long-term survival in pre-clinical models. Here, we describe the generation of an HPV16 E6/E7 construct, which contains mutations that render E6/E7 non-oncogenic, while preserving antigenicity. These mutations do not allow E6/E7 to degrade p53, pRb, PTPN13, or activate telomerase. Non-oncogenic E6/E7 (E6(Δ)/E7(Δ)) expressed as a stable integrant, or in the [E1-, E2b-] adenovirus, lacks the ability to transform human cells while retaining the ability to induce an HPV-specific immune response. Moreover, E6(Δ)/E7(Δ) plus chemotherapy/radiation statistically enhances clearance of established HPV(+) cancer in vivo.

Bovine AAV transcytosis inhibition by tannic acid results in functional expression of CFTR in vitro and altered biodistribution in vivo.

Bovine adeno-associated virus (BAAV) can enter a cell either through a transcytosis or transduction pathway. We previously demonstrated that particles entering via the transcytosis pathway can be redirected to transduce the cell by blocking particle exocytosis with tannic acid (TA). To investigate whether this approach is useful in lung gene therapy applications, we tested the effect of TA on BAAV transduction in cystic fibrosis airway epithelia in vitro, and in mouse lung in vivo. Our findings suggest that BAAV transcytosis can occur in vivo and that treatment with TA reduces transcytosis and increases lung transduction. TA treatment did not impair the sorting and the activity of the BAAV expressed cystic fibrosis transmembrane regulator membrane protein.

A functional R domain from cystic fibrosis transmembrane conductance regulator is predominantly unstructured in solution.

Phosphorylation of the regulatory (R) domain initiates cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel activity. To discover how the function of this domain is determined by its structure, we produced an R domain protein (R8) that spanned residues 708-831 of CFTR. Phosphorylated, but not unphosphorylated, R8 stimulated activity of CFTR channels lacking this domain, indicating that R8 is functional. Unexpectedly, this functional R8 was predominantly random coil, as revealed by CD and limited proteolysis. The CD spectra of both phosphorylated and nonphosphorylated R8 were similar in aqueous buffer. The folding agent trimethylamine N-oxide induced only a small increase in the helical content of nonphosphorylated R8 and even less change in the helical content of phosphorylated R8. These data, indicating that the R domain is predominantly random coil, may explain the seemingly complex way in which phosphorylation regulates CFTR channel activity.

Nigerian geophagical clay: a traditional antidiarrheal pharmaceutical.

The chief geophagical clay entering the West African market system comes from the village of Uzalla, Nigeria. Village inhabitants ascribe antidiarrheal properties to the clay, and they use it in traditional medicinal preparations to counteract intestinal problems. Mineralogical analyses demonstrate a striking similarity between the Uzalla village clay and the clay in the commercial pharmaceutical Kaopectate.

Geophagia in rural Mississippi: environmental and cultural contexts and nutritional implications.

We investigated geophagia in the black population of rural Holmes County, Mississippi. Twenty-five sources of geophagical clays were located and most of the sources are associated with rural settlements throughout the county. Clays are taken from subsurface soil horizons, and all but one of the sources come from the upland portion of the county. Geophagia occurs among 57% of women and 16% of children of both sexes, but it is not found among adult males or adolescents. Average daily comsumption of clay is 50 g. Our data indicate geophagia is not correlated with hunger, anemia, or helminthic problems, but it may contribute to the common problem of hypertension. Geophagia has been suggested as one of the factors leading to hyperkalemia, but our data do not support this notion.