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NF-[kappa]B is constitutively active in many solid tumors, including breast cancer. However, the role of NF-[kappa]B in breast carcinogenesis is unknown. [Ikk[alpha].sup.AA/AA] 'knockin' mice in which activation of I[kappa]B kinase [alpha] (IKK[alpha]) is prevented by replacement of activation loop serines with alanines exhibit delayed mammary gland growth during pregnancy, because IKK[alpha] activity is required for cyclin D1 induction and proliferation of Iobuloalveolar epithelial cells. Given the role of cyclin D1 in breast and mammary cancer, we examined involvement of IKK[alpha] in mammary carcinogenesis induced by oncogenes or a chemical carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). The [Ikk[alpha].sup.AA] mutation retarded tumor development in response to either 7,12-dimethylbenzaanthracene or the MMTV-c-neu (ErbB2/Her2) transgene but had no effect on MMTV-v-Haras-induced cancer, although both oncogenes rely on cyclin D1. Strikingly, primary [Ikk[alpha].sup.A/AA]/MMTV-c-neu carcinoma cells exhibited diminished self-renewal capacity, resulting in the inability to establish secondary tumors. [Ikk[alpha].sup.AA/AA]/MMTV-c-neu carcinoma cells underwent premature senescence when cultured under conditions used for propagation of mammary gland stem cells. Thus, IKK[alpha] is not only a regulator of mammary epithelial proliferation, but is also an important contributor to ErbB2-induced oncogenesis, providing signals that maintain mammary tumor-initiating cells. IKK[alpha] may represent a novel and specific target for treatment of ErbB2-positive breast cancer. breast cancer | NF-[kappa]B

Research has been conducted on the functions of the IKK(alpha) subunit of I (sub)k B kinase. The generation of the IKK(alpha) (super)AA knockin allele which contains alanines instead of serines in the activation loop has been carried out in identifying these functions and the results are described.

The gelation behavior of cationic surfactants with different counterions, Br−, [FeCl3Br]−, and [CeCl3Br]−, in imidazolium ionic liquids (ILs) and protic ethylammonium nitrate was investigated. Small-angle X-ray scattering measurements and freeze-fracture transmission electron microscopy observations revealed the lamellar phases of metallosurfactant ionogels. The characteristics of imidazolium ILs, including the size and type, have effects on metallosurfactant ionogel properties, such as transformation temperatures, interlayer spacing, and mechanical strength. Cubic fluorite structured cerium oxide nanoparticles (CeO2 NPs) were produced by using metallosurfactant ionogels as precursors. Cubic fluorite CeO2 exhibited good catalase mimetic activity toward H2O2 to generate O2, providing more multiple mimetic enzyme activities of CeO2 NPs for H2O2. [ABSTRACT FROM AUTHOR]

Nuclear factor of κB (NF-κB)is a sequence-specific transcription factor that is known to be involved in the inflammatory and innate immune responses. Although the importance of NF-κB in immunity is undisputed, recent evidence indicates that NF-κB and the signalling pathways that are involved in its activation are also important for tumour development. NF-κB should therefore receive as much attention from cancer researchers as it has already from immunologists. [ABSTRACT FROM AUTHOR]

Investigates the role of enzyme IKB kinase (IKK) alpha in canonical nuclear factor kappa B (NF-[sub K]B) activation pathway. B cells maturation; Formation of secondary lymphoid organs; Expression of NF-[sub k]B target genes; Processing of NF-[sub K]B2 precursors; Phosphorylation of NF-[sub K]B2.

Snf/Swi, a nucleosome remodeling complex, is important for overcoming nucleosome-mediated repression of transcription in Saccharomyces cerevisiae. We have addressed the mechanism by which Snf/Swi controls transcription in vivo of an Snf/Swi-dependent promoter, that of the SUC2 gene. By single-cell analysis, our results show that Snf/Swi is required for activated levels of SUC2 expression in every cell of a population. In addition, Snf/Swi is required for maintenance of SUC2 transcription, suggesting that continuous chromatin remodeling is necessary to maintain an active transcriptional state. Finally, Snf/Swi and Gcn5, a histone acetyltransferase, have partially redundant roles in the control of SUC2 transcription, suggesting a functional overlap between two different mechanisms believed to overcome repression by nucleosomes, nucleosome remodeling and histone acetylation. [ABSTRACT FROM AUTHOR]

The gelation behavior of cationic surfactants with different counterions, Br−, [FeCl3Br]−, and [CeCl3Br]−, in imidazolium ionic liquids (ILs) and protic ethylammonium nitrate was investigated. Small-angle X-ray scattering measurements and freeze-fracture transmission electron microscopy observations revealed the lamellar phases of metallosurfactant ionogels. The characteristics of imidazolium ILs, including the size and type, have effects on metallosurfactant ionogel properties, such as transformation temperatures, interlayer spacing, and mechanical strength. Cubic fluorite structured cerium oxide nanoparticles (CeO2 NPs) were produced by using metallosurfactant ionogels as precursors. Cubic fluorite CeO2 exhibited good catalase mimetic activity toward H2O2 to generate O2, providing more multiple mimetic enzyme activities of CeO2 NPs for H2O2. [ABSTRACT FROM AUTHOR]

The transient receptor potential melastatin 7 channel (TRPM7) is a nonselective cation channel highly expressed in some human cancer tissues. TRPM7 is involved in the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cancer cells. Modulation of TRPM7 could be a promising therapeutic strategy for treating cancer; however, efficient and selective pharmacological TRPM7 modulators are lacking. In this study we investigated N- [4- (4, 6-dimethyl- 2-pyrimidinyloxy) - 3- methylphenyl] -N' - [2 -(dimethylamino)] benzoylurea (SUD), a newly synthesized benzoylurea derivative, for its effects on cancer cell migration and EMT and on functional expression of TRPM7. Our previous studies showed that SUD induces cell cycle arrest and apoptosis of MCF-7 and BGC-823 cells (human breast cancer and gastric cancer cell lines, respectively). Here, we show that SUD significantly decreased the migration of both types of cancer cells. Moreover, SUD decreased vimentin expression and increased E-cadherin expression in both cell types, indicating that EMT is also decreased by SUD. Importantly, SUD potentially reduced the TRPM7-like current in a concentration-dependent manner and decreased TRPM7 expression through the PI3K/Akt signaling pathway. Finally, molecular docking simulations were used to investigate potential SUD binding sites on TRPM7. In summary, our research demonstrated that SUD is an effective TRPM7 inhibitor and a potential agent to suppress the metastasis of breast and gastric cancer by inhibiting TRPM7 expression and function.

The hybrid quadrupole ion trap/time-of-flight mass spectrometry (QIT/TOFMS) device is popular because of its advantages of high sensitivity, high resolution, and MS/MS capability. However, the analytical performance of QIT/TOFMS is severely limited by the parameters of the ion trap, as QIT is typically used as a TOF pulser because the ion initial distributions of space, velocity, and angle change dynamically with the phase angle of rf voltage. In this work, a square waveform phase modulation strategy was proposed to eliminate the influence of the rf phase angle, and the dependence of QIT/TOFMS performance on the phase angle was studied. It was found that the mass resolution and signal intensity showed a "W" trend with the increase of the ion extraction phase angle from 0° to 360°, where the best resolution and sensitivity were obtained at 0°, 180°, and 360° while the worst resolution and sensitivity were obtained at 90° and 270°. Moreover, the optimum phase angle was independent of m / z . As a result, the mass resolution for m / z 106, 164, and 258 was improved by 162%, 160%, and 210% respectively, while the signal intensities for m / z 106, 164, and 258 were enhanced by 25 ± 1, 10 ± 1, and 21 ± 1 fold, respectively, and a limit of detection down to 0.015 ppbv for m / z 164 was obtained. The experiment results indicated that the square waveform phase modulation strategy could be used to simultaneously improve the resolution and sensitivity of QIT/TOFMS.

The gelation behavior of cationic surfactants with different counterions, Br - , [FeCl 3 Br] - , and [CeCl 3 Br] - , in imidazolium ionic liquids (ILs) and protic ethylammonium nitrate was investigated. Small-angle X-ray scattering measurements and freeze-fracture transmission electron microscopy observations revealed the lamellar phases of metallosurfactant ionogels. The characteristics of imidazolium ILs, including the size and type, have effects on metallosurfactant ionogel properties, such as transformation temperatures, interlayer spacing, and mechanical strength. Cubic fluorite structured cerium oxide nanoparticles (CeO 2 NPs) were produced by using metallosurfactant ionogels as precursors. Cubic fluorite CeO 2 exhibited good catalase mimetic activity toward H 2 O 2 to generate O 2 , providing more multiple mimetic enzyme activities of CeO 2 NPs for H 2 O 2 ., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Green and environmentally friendly ionogels formed by a sugar surfactant were prepared in two kinds of imidazolium-based ionic liquids. The phase transition from ribbon structures to lamellar structures induced by temperature and the transition mechanism were investigated in detail by means of freeze-fracture TEM and field-emission SEM observations, as well as small-angle X-ray scattering measurements. The rheological properties and tribological properties of two kinds of ionogels were systematically investigated. The difference in the lubricating properties and antiwear capability can be explained well by the mechanical and viscoelastic properties, as well as the different microstructures of samples destroyed by shear forces. This work provides a better understanding of the relationship between the structures, rheological properties, and tribological properties of ionogels., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

IkappaB Kinase (IKK)alpha is required for activation of an alternative NF-kappaB signaling pathway based on processing of the NF-kappaB2/p100 precursor protein, which associates with RelB in the cytoplasm. This pathway, which activates RelB:p52 dimers, is required for induction of several chemokine genes needed for organization of secondary lymphoid organs. We investigated the basis for the IKKalpha dependence of the induction of these genes in response to engagement of the lymphotoxin beta receptor (LTbetaR). Using chromatin immunoprecipitation, we found that the promoters of organogenic chemokine genes are recognized by RelB:p52 dimers and not by RelA:p50 dimers, the ubiquitous target for the classical NF-kappaB signaling pathway. We identified in the IKKalpha-dependent promoters a novel type of NF-kappaB-binding site that is preferentially recognized by RelB:p52 dimers. This site links induction of organogenic chemokines and other important regulatory molecules to activation of the alternative pathway.

IKK alpha is a component of the I kappa B kinase (IKK) complex that plays a key role in the activation of NF-kappa B. In Ikk alpha mutant mice and mice expressing a transdominant negative mutant of I kappa B alpha (cI kappa B alpha Delta N), molars have abnormal cusps, indicating that Ikk alpha is involved in cusp formation through the NF-kappa B pathway. However, Ikk alpha mutant incisors also have an earlier phenotype where epithelium evaginates outward into the developing oral cavity rather than invaginating into the underlying mesenchyme. A similar evagination of epithelium was also observed in whisker development, suggesting that Ikk alpha contributes to the direction of epithelial growth during the early stages of development in many ectodermal appendages. Since cI kappa B alpha Delta N mice have normal incisor epithelial invagination, Ikk alpha's role appears to be NF-kappa B independent. Changes in Notch1, Notch2, Wnt7b, and Shh expression found in incisor epithelium of Ikk alpha mutants suggest that this NF-kappa B-independent function is mediated by Notch/Wnt/Shh signaling pathways.

The lymphotoxin-beta receptor (LTbetaR) plays critical roles in inflammation and lymphoid organogenesis through activation of NF-kappaB. In addition to activation of the classical NF-kappaB, ligation of this receptor induces the processing of the cytosolic NF-kappaB2/p100 precursor to yield the mature p52 subunit, followed by translocation of p52 to the nucleus. This activation of NF-kappaB2 requires NIK and IKKalpha, while NEMO/IKKgamma is dispensable for p100 processing. IKKbeta-dependent activation of canonical NF-kappaB is required for the expression but not processing of p100 and for the expression of proinflammatory molecules including VCAM-1, MIP-1beta, and MIP-2 in response to LTbetaR ligation. In contrast, IKKalpha controls the induction by LTbetaR ligation of chemokines and cytokines involved in lymphoid organogenesis, including SLC, BLC, ELC, SDF1, and BAFF.