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Background and objective Pulmonary Hypertension (pH) is a chronic progressive disease. Endothelial cells (EC) play a central and critical role in the initiation and progression of pH. The NF-κB family (NF-κB1 (p50/p105), NF-κB2 (p52/p100), RelA (p65), RelB, and C-Rel) regulates a wide array of genes involved in inflammatory responses, cell proliferation, and survival. The involvement of specific NF-κB family members in the pathogenesis of hypoxia-induced pH remains to be determined. The objective of this study was to assess the specific role of individual NF-κB family members in mediating endothelial cell responses to hypoxia and its downstream effect on smooth muscle cell proliferation. Methods and results NF-κB family members’ expression were selectively reduced by siRNA in human pulmonary microvascular endothelial cells. Cells were then exposed to hypoxia (1%) for 24 h. Endothelin1, ICAM1 gene expression and Stat1 and Stat3 phosphorylation were assessed. Smooth muscle cells (SMC) proliferation was assessed by culturing them with EC conditioned media. Reduction of either NF-κB2 or RelA in EC, led to a significant decrease in Endothelin1 and ICAM1 gene expression. C-Rel knockdown resulted in a significant increase in phosphorylated STAT1; both C-Rel and RelA knockdown significantly decreased phosphorylated STAT3 in EC. There was a significant reduction in SMC proliferation, and AKT/ERK phosphorylation in SMC, when cultured in RelA knockdown, EC conditioned media. Conclusion RelA in EC plays crucial role in hypoxia induced vascular remodeling and development of pH. Targeting RelA in EC alleviates SMC proliferation as well as inflammation related processes.

Current animal models of chronic intermittent hypoxia (CIH)-induced atherosclerosis have limitations. Mechanisms of CIH-induced atherosclerosis are poorly understood. This study tested new mouse models of CIH-induced atherosclerosis and defined the role of NF-κB p50 in CIH-induced atherosclerosis. Mice deficient in apolipoprotein E (ApoE-KO) or in both ApoE and p50 genes (ApoE-p50-DKO) were exposed to sham or CIH. Atherosclerotic lesions on aortic preparations were analyzed. CIH exposure caused atherosclerosis in ApoE-KO mice fed a normal chow diet and with no preexisting atherosclerotic condition in an exposure time-dependent manner. CIH caused more pronounced atherosclerotic lesions in ApoE-p50-DKO mice on a normal chow diet without preexisting atherosclerosis. ApoE-KO and ApoE-p50-DKO mice exposed to CIH for 30 and 9 weeks, respectively, displayed similar areas of atherosclerotic lesions on cross sections of aortic root. P50 gene deletion in ApoE-p50-DKO mice significantly augmented CIH-induced serum levels of tumor necrosis factor-α and IL-6, aortic tumor necrosis factor-α, and inducible nitric oxide synthase expression and aortic infiltration of Mac3-positive macrophages. CIH caused a greater elevation in serum cholesterol level in ApoE-p50-DKO than in ApoE-KO mice. CIH down-regulated hepatic low-density lipoprotein receptor and HMG-CoA reductase expression in ApoE-p50-DKO but not in ApoE-KO mice. We found two new mouse models that are useful for studying mechanisms and pathways of CIH-induced atherosclerosis. We showed that NF-κB p50 protects against CIH-induced atherosclerosis by inhibiting vascular inflammation and hypercholesterolemia.

The cDNA library of an ovary from Small Tail Han sheep before estrus was constructed by switching mechanism at 5 end of RNA transcript (SMART) approach. This library had a plaque liter of 1 × 109 pfu mL−1 and a 96% recombinant ratio of which the fragment length of inserted average cDNA sequences was 1.0 kb. Based on bioinformatics analysis of the sequences, we obtained 338 expressed sequence tags (ESTs) from 380 cDNA clones which indicated 191 contigs. These contigs consist of 89 unmatched ESTs, 9 homologous known genes in sheep, and 93 homologous sequences in species of mouse, bovine, and human beings, including 19 sequences expressed in the ovary or follicle and 14 unknown sequences. Several candidate genes associated with sheep reproduction trait such as epidermal growth factor (EGF), estrogen receptor (ESR), Inhibin, follicle stimulating hormone receptor (FSHR), prostaglandin (PG), and transforming growth factor-β (TGF-β) were identified and the homologous were cloned from this library, which will contribute to compile expression profiles and find the major genes of prolificacy of Small Tail Han sheep.

The study uses Johnson and Johnson's Learning Together approach as a strategy for teaching third-grade learners' information literacy. The study explored the perceptions and attitudes as well as the interactive processes, behavior and patterns of K3 children learning information technology via a cooperative approach. Data collection included a survey, the instructors' observations and reflective journals as well as interviews with the students. The findings of the study are summarized in the following four areas. First, generally speaking, the study showed the positive value of a cooperative approach when effectively integrated into computer curriculums. Second, the study found that group interaction was more procedure-related, including topic choice, duty assignation, content selection, and computer operation. Third, it was found that most learners mastered computer skills, but approached their knowledge-building project with less of a sense of synthesis and integration. Finally, the study found four different forms of interactions (Individual, Authoritative, Argumentative and Consolidated) emerging during the earlier stages of learning with group cohesion increasing at later stages. It can be concluded that learners' attitudes and interactive quality in their group learning is promoted to varying degrees, and most learners are capable of mastering computer skills. However, given the time limitation of four months and that it was the instructors' and learners' first attempt at cooperative learning, there was still much to learn for mastery of the course and much to be desired in scaffolding learners' for highly effective cooperative learning. The paper concludes with some recommendations for the future design of an information technology curriculum for cooperative learning.

The study investigates the value and effectiveness of online workshops as a tool for creating professional learning communities. The pattern of interaction, mentoring quality and attitude of teacher toward participation in a Web-based Teacher's Professional Development Platform were addressed. One hundred and twenty eight participants were co-mentored by three senior elementary mathematics teachers to meet a professional development requirement. Data collection involved content analysis and supplemental surveys. The content analyzed included the participants' message posts, the quality of the dialogue and the quality of mentoring by assistants. A survey was administered to elucidate participants' attitudes towards and perceptions of the Web as a tool for professional development. The study revealed that most participants claimed to have benefited emotionally and intellectually from using telecommunications networks for professional development and support. Positive learning effects on members were satisfactory, yet their participation was not highly interactive or as reflective as the authors would have wished. Closely examining the messages posted by participants revealed that the categories general introduction and organization were most, with the fewest associated queries and responses. The assistants' mentoring strategies mainly included feedback/praise, directing, modeling, questioning, cognitive elaboration and efforts to explore accounted for less than 10% altogether. That is, the assistants focused more on social and organizational functions, and less on intellectual function. The study was significant in that the computer-mediated workshop nurtured the teachers' professional growth, but their participation was neither highly interactive nor and, even though there much anecdotal evidence supported the claim that members enjoyed and valued the online workshops. The paper concludes by offering some recommendations concerning the future design of technology in professional learning.

The pathophysiology of septic shock is characterized by the induction of multiple proinflammatory genes and their products. Transcription factors play key roles in the transcription of these genes. Transcription factors may play important roles in the pathophysiology of septic shock. However, little information is available regarding the in vivo transcription factor activities during sepsis. We have studied the in vivo effects of LPS on the DNA binding activities of transcription factors Sp1 (promoter selective transcription factor), AP-2 (activating protein-2), AP-1 (activating protein-1), NF-κB (nuclear factor kappa B), and CREB (cAMP response element binding protein). We found that LPS up-regulated the DNA binding activity of inducible transcription factors AP-1, NF-κB, and CREB in a time-dependent manner, but down-regulated the DNA binding activity of constitutive transcription factors Sp1 and AP-2. Thus, LPS regulates the inducible and constitutive transcription factors differentially under in vivo conditions.