Bipyridyldicarboxamides and f-metals: the influence of electron effects on the structure, stability, separation, and photophysical properties of their complexes.

In this work, three isomeric fluorinated bipyridyldicarboxamides were studied to evaluate the impact of the fluorine atom position on the structure, stability, Am(III)/Ln(III) separation, and photophysical properties of their complexes. The complexes of the fluorinated amides have a metal-to-ligand composition of 1 : 1, which is independent of the fluorine atom position or lanthanide metal. The bipyridyl fragments in the fluorinated complexes are flattened compared with those in unsubstituted ones.

Towards High-Temperature MEMS: Two-Step Annealing Suppressed Recrystallization in Thin Multilayer Pt-Rh/Zr Films.

Platinum-based thin films are widely used to create microelectronic devices operating at temperatures above 500 °C. One of the most effective ways to increase the high-temperature stability of platinum-based films involves incorporating refractory metal oxides (e.g.

Multi-Omics Immune Interaction Networks in Lung Cancer Tumorigenesis, Proliferation, and Survival.

There are currently no effective biomarkers for prognosis and optimal treatment selection to improve non-small cell lung cancer (NSCLC) survival outcomes. This study further validated a seven-gene panel for diagnosis and prognosis of NSCLC using RNA sequencing and proteomic profiles of patient tumors. Within the seven-gene panel, expression combined with dendritic cell activities defined NSCLC patient subgroups ( = 966) with distinct survival outcomes ( = 0.

A Multi-Omics Network of a Seven-Gene Prognostic Signature for Non-Small Cell Lung Cancer.

There is an unmet clinical need to identify patients with early-stage non-small cell lung cancer (NSCLC) who are likely to develop recurrence and to predict their therapeutic responses. Our previous study developed a qRT-PCR-based seven-gene microfluidic assay to predict the recurrence risk and the clinical benefits of chemotherapy. This study showed it was feasible to apply this seven-gene panel in RNA sequencing profiles of The Cancer Genome Atlas (TCGA) NSCLC patients ( = 923) in randomly partitioned feasibility-training and validation sets ( < 0.

Molecular Analysis of in Non-Small-Cell Lung Cancer.

Our previous study found that zinc finger protein 71 (ZNF71) mRNA expression was associated with chemosensitivity and its protein expression was prognostic of non-small-cell lung cancer (NSCLC). The Krüppel associated box (KRAB) transcriptional repression domain is commonly present in human zinc finger proteins, which are linked to imprinting, silencing of repetitive elements, proliferation, apoptosis, and cancer. This study revealed that had a significantly higher expression than the -less isoform in NSCLC tumors ( = 197) and cell lines ( = 117).

Functional Hierarchy and Cooperation of EMT Master Transcription Factors in Breast Cancer Metastasis.

Several master transcription factors (TF) can activate the epithelial-to-mesenchymal transition (EMT). However, their individual and combinatorial contributions to EMT in breast cancer are not defined. We show that overexpression of EMT-TFs individually in epithelial cells upregulated endogenous SNAI2, ZEB1/2, TCF4, and TWIST1/2 as a result of positive feedback mediated in part by suppression of their negative regulator miRNAs miR200s/203/205.

Effect of Heterocyclic Ring on Ln Coordination, Luminescence and Extraction of Diamides of 2,2'-Bipyridyl-6,6'-Dicarboxylic Acid.

We have synthesized and examined several complexes of lanthanides with diamides of 2,2'-bipyridyl-6,6'-dicarboxylic acid bearing various hetaryl-based side chains for the elucidation of the effect of the heterocycle on the structure and properties of the ligands. The multigram scale methods for the preparation of various -alkyl-hetaryls and their diamides were developed. The solid state structure of 6-methyl-2-pyridylamide of 2,2'-bipyridyl-6,6'-dicarboxylic acid possesses a flat structure where the conformation is completely different from that previously observed for -alkylated 2,2'-bipyridyl-6,6'-dicarboxamides and 2,6-pyridinedicarboxamides.

The lanthanide complexes of 2,2'-bipyridyl-6,6'-dicarboxylic dimethylanilides: the influence of a secondary coordination sphere on the stability, structure, luminescence and f-element extraction.

Four of the six possible isomeric 2,2'-bipyridyl-6,6'-dicarboxylic dimethylanilides were studied from the point of view of the impact of a secondary coordination sphere on the formation of complexes with lanthanides in solution, as well as the crystal structure and photophysical properties of the complexes. All ligands form complexes with a 1 : 1 metal-to-ligand ratio with an lg β1 in the range of 6.0-8.

Interplay between geo-population factors and hierarchy of cities in multilayer urban networks.

Only taking into consideration the interplay between processes occurring at different levels of a country can provide the complete social and geopolitical plot of its urban system. We study the interaction of the administrative structure and the geographical connectivity between cities with the help of a multiplex network approach. We found that a spatially-distributed geo-network imposes its own ranking to the hierarchical administrative network, while the latter redistributes the shortest paths between nodes in the geographical layer.

On the strong difference in reactivity of acyclic and cyclic diazodiketones with thioketones: experimental results and quantum-chemical interpretation.

The 1,3-dipolar cycloaddition of acyclic 2-diazo-1,3-dicarbonyl compounds (DDC) and thioketones preferably occurs with Z,E-conformers and leads to the formation of transient thiocarbonyl ylides in two stages. The thermodynamically favorable further transformation of C=S ylides bearing at least one acyl group is identified as the 1,5-electrocyclization into 1,3-oxathioles. However, in the case of diazomalonates, the dominating process is 1,3-cyclization into thiiranes followed by their spontaneous desulfurization yielding the corresponding alkenes.

KAP1 promotes proliferation and metastatic progression of breast cancer cells.

KAP1 (TRIM28) is a transcriptional regulator in embryonic development that controls stem cell self-renewal, chromatin organization, and the DNA damage response, acting as an essential corepressor for KRAB family zinc finger proteins (KRAB-ZNF). To gain insight into the function of this large gene family, we developed an antibody that recognizes the conserved zinc fingers linker region (ZnFL) in multiple KRAB-ZNF. Here, we report that the expression of many KRAB-ZNF along with active SUMOlyated KAP1 is elevated widely in human breast cancers.

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones - First evidence for the 1,3-oxathiole-thiocarbonyl ylide interconversion.

Acyclic diazodicarbonyl compounds react at room temperature with cycloaliphatic thioketones, e.g. 2,2,4,4-tetramethyl-3-thioxocyclobutanе-1-one and adamantanethione, via a cascade process in which the key step is a 1,5-electrocyclization of the intermediate thiocarbonyl ylide leading to tetrasubstituted spirocyclic 1,3-oxathioles.

The microRNA-200 family targets multiple non-small cell lung cancer prognostic markers in H1299 cells and BEAS-2B cells.

Lung cancer remains the leading cause of cancer-related mortality for both men and women. Tumor recurrence and metastasis is the major cause of lung cancer treatment failure and death. The microRNA‑200 (miR-200) family is a powerful regulator of the epithelial-mesenchymal transition (EMT) process, which is essential in tumor metastasis.

NEDD9 depletion destabilizes Aurora A kinase and heightens the efficacy of Aurora A inhibitors: implications for treatment of metastatic solid tumors.

Aurora A kinase (AURKA) is overexpressed in 96% of human cancers and is considered an independent marker of poor prognosis. While the majority of tumors have elevated levels of AURKA protein, few have AURKA gene amplification, implying that posttranscriptional mechanisms regulating AURKA protein levels are significant. Here, we show that NEDD9, a known activator of AURKA, is directly involved in AURKA stability.

Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2.

Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMT) occurring in wound-healing processes and the cancer stem cell-like compartment of tumors, including TGF-β dependence, we investigated the role of the Grainyhead gene, Grainyhead-like-2 (GRHL2) in oncogenic EMT. GRHL2 was downregulated specifically in the claudin-low subclass breast tumors and in basal-B subclass breast cancer cell lines.

The ATM substrate KAP1 controls DNA repair in heterochromatin: regulation by HP1 proteins and serine 473/824 phosphorylation.

The repair of DNA damage in highly compact, transcriptionally silent heterochromatin requires that repair and chromatin packaging machineries be tightly coupled and regulated. KAP1 is a heterochromatin protein and co-repressor that binds to HP1 during gene silencing but is also robustly phosphorylated by Ataxia telangiectasia mutated (ATM) at serine 824 in response to DNA damage. The interplay between HP1-KAP1 binding/ATM phosphorylation during DNA repair is not known.

A KLF4-miRNA-206 autoregulatory feedback loop can promote or inhibit protein translation depending upon cell context.

Krüppel-like factor 4 (KLF4), a transcription factor that regulates cell fate in a context-dependent fashion, is normally induced upon growth arrest or differentiation. In many cancer cells there is dysregulation, with increased expression in proliferating cells. To identify sequence elements that mediate KLF4 suppression in normal epithelial cells, we utilized a luciferase reporter and RK3E cells, which undergo a proliferation-differentiation switch to form an epithelial sheet.

Functional analysis of KAP1 genomic recruitment.

TRIM28 (KAP1) is upregulated in many cancers and has been implicated in both transcriptional activation and repression. Using chromatin immunoprecipitation and sequencing, we show that KAP1 binding sites fall into several categories, specifically, the 3' coding exons of zinc finger (ZNF) genes and promoter regions of ZNFs and other genes. The currently accepted model is that KAP1 is recruited to the genome via interaction of its N-terminal RBCC domain with KRAB ZNFs (KRAB domain containing ZNFs).

Epigenetic gene silencing by the SRY protein is mediated by a KRAB-O protein that recruits the KAP1 co-repressor machinery.

The sex determination transcription factor SRY is a cell fate-determining transcription factor that mediates testis differentiation during embryogenesis. It may function by repressing the ovarian determinant gene, RSPO1, action in the ovarian developmental pathway and activates genes, such as SOX9, important for testis differentiation at the onset of gonadogenesis. Further, altered expression of SRY and related SOX genes contribute to oncogenesis in many human cancers.

Structural insights into human KAP1 PHD finger-bromodomain and its role in gene silencing.

The tandem PHD finger-bromodomain, found in many chromatin-associated proteins, has an important role in gene silencing by the human co-repressor KRAB-associated protein 1 (KAP1). Here we report the three-dimensional solution structure of the tandem PHD finger-bromodomain of KAP1. The structure reveals a distinct scaffold unifying the two protein modules, in which the first helix, alpha(Z), of an atypical bromodomain forms the central hydrophobic core that anchors the other three helices of the bromodomain on one side and the zinc binding PHD finger on the other.

PHD domain-mediated E3 ligase activity directs intramolecular sumoylation of an adjacent bromodomain required for gene silencing.

Tandem PHD and bromodomains are often found in chromatin-associated proteins and have been shown to cooperate in gene silencing. Each domain can bind specifically modified histones: the mechanisms of cooperation between these domains are unknown. We show that the PHD domain of the KAP1 corepressor functions as an intramolecular E3 ligase for sumoylation of the adjacent bromodomain.

MAGE-A, mMage-b, and MAGE-C proteins form complexes with KAP1 and suppress p53-dependent apoptosis in MAGE-positive cell lines.

The MAGE-A, MAGE-B, and MAGE-C protein families comprise the class-I MAGE/cancer testes antigens, a group of highly homologous proteins whose expression is suppressed in all normal tissues except developing sperm. Aberrant expression of class I MAGE proteins occurs in melanomas and many other malignancies, and MAGE proteins have long been recognized as tumor-specific targets; however, their functions have largely been unknown. Here, we show that suppression of class I MAGE proteins induces apoptosis in the Hs-294T, A375, and S91 MAGE-positive melanoma cell lines and that members of all three families of MAGE class I proteins form complexes with KAP1, a scaffolding protein that is known as a corepressor of p53 expression and function.

KAP1, a novel substrate for PIKK family members, colocalizes with numerous damage response factors at DNA lesions.

The DNA damage response requires a coordinated nucleo-cytoplasmic cascade of events, which ultimately converge on damaged DNA packaged in chromatin. Few connections between the proteins that remodel chromatin and the proteins that mediate this damage response have been shown. We have investigated the DNA damage-induced phosphorylation of the KRAB-ZFP-associated protein 1 (KAP1), the dedicated corepressor for Krüppel-associated box (KRAB) zinc finger protein (ZFP) proteins.

Novel gain of function activity of p53 mutants: activation of the dUTPase gene expression leading to resistance to 5-fluorouracil.

Mutated forms of p53 are often expressed in a variety of human tumors. In addition to loss of function of the p53 tumor suppressor, mutant p53s contribute to malignant process by acquisition of novel functions that enhance transformed properties of cells and resistance to anticancer therapy in vitro, and increase tumorigenecity, invasiveness and metastatic ability in vivo. Searching for genes that change expression in response to p53 gain of function mutants may give a clue to the mechanisms underlying their oncogenic effects.