Oil and gas companies' corporate social responsibility: Policies and HIV initiatives in Nigeria

This dissertation study describes the health and HIV related initiatives of multinational oil and gas companies that operate in Nigeria, perceptions of oil and gas company employees, oil and gas company leaders, and key informants from government, public health, community and the Nigerian business coalition on HIV. A mixed method approach was used. Study participants include employees and leaders that worked for multinational oil and gas companies operating in Nigeria and key informants residing in Nigeria. The oil and gas companies that were sampled all had initiatives in place that were consistent with accepted recommended best practices for companies responding to HIV. All of the companies provided comprehensive health and HIV services to employees and dependents; all had HIV initiatives in the community and had formed partnerships with government or NGO/civil societies. Study participants shared the perception that corporate social responsibility was integral to the oil and gas companies conducting business in Nigeria due to the economic gains of the companies from the country/communities and because of the negative impact that oil and gas exploration activities had on communities. Themes identified that played a role in oil and gas companies' response and how decisions were/should be made were: 'business interest', 'social or government influence', 'pressure to respond', and 'community factors'. The study produced information that can be used to inform and guide oil and gas companies' health and HIV initiatives in Nigeria.^

The role of the conserved N -terminal domain of STAT3 in STAT3 dephosphorylation and nuclear export

Rapid redistribution of STAT subcellular localization is an essential feature of cytokine signaling. To elucidate the molecular basis of STAT3 function, which plays a critical role in controlling innate immune responses in vivo, we initiated studies to determine the mechanisms controlling STAT3 nuclear trafficking. We found that STAT3 is transported to the nucleus in the absence of cytokine treatment, as judged by indirect immunofluorescence studies in the presence of leptomycin B, an inhibitor of CRM1-dependent nuclear export, suggesting that the non-phosphorylated STAT3 protein contains a functional nuclear import signal. An isoform lacking the STAT3 N-terminal domain (Δ133STAT3) retains the ability to undergo constitutive nuclear localization, indicating that this region is not essential for cytokine-independent nuclear import. Δ133STAT3 is also transported to the nucleus following stimulation with interleukin-6 (IL-6). Interestingly, IL-6-dependent tyrosine phosphorylation of Δ133STAT3 appears to be prolonged and the nuclear export of the protein delayed in cells expressing endogenous STAT3, consistent with defective Δ133STAT3 dephosphorylation. Endogenous STAT3 does not promote the nuclear export of Δ133STAT3, although dimerization between endogenous Stat3 and Δ133STAT3 is detected readily. Thus, the STAT3 N-terminal domain is not required for dimerization with full-length STAT3, yet appears to play a role in proper export of Stat3 from the nucleus following cytokine stimulation. STAT3-deficient cells reconstituted with Δ133STAT3 show enhanced and prolonged Stat1 signaling in response to IL-6, suggesting that induction of the STAT3-dependent negative regulator SOCS3 is impaired. In fact, Δ133STAT3 fails to induce SOCS3 mRNA efficiently. These studies collectively indicate that the STAT3 N-terminal region may be important for IL-6-dependent target gene activation and nuclear dephosphorylation, while dispensable for nuclear import. STAT3 is an oncogene. STAT3 is constitutively activated in primary tumors of many types. Thus far, research in the design of STAT3 protein inhibitors has focused on the SH2 and DNA-binding domains of STAT3. Interference with these domains eliminates all signaling through STAT3. If the N-terminal domain is involved in tetramerization on a subset of target genes, inhibition of this region may lead to a more selective inhibition of some STAT3 functions while leaving others intact. ^