Search

In this content analysis, researchers examine articles published from 2000 to 2015 in three family therapy journals, yielding a total of 948 empirical articles. The purpose is to provide an overview of the research being published, assess who is publishing, and investigate the current state of clinical effectiveness research in marriage and family therapy (MFT). Most first authors were affiliated with MFT programs and primarily included diversity and couples in their research. There was a significant increase of research on clinical process-though the number of clinical outcome studies held steady. There were no significant changes with regard to research funding. Implications support the use of innovative research methods to provide evidence of clinical effectiveness., (© 2018 American Association for Marriage and Family Therapy.)

Generally, the long-range electronic communication between spatially orthogonal orbitals is inefficient and limited to field and inductive effects. In this work, we provide experimental evidence that such communication can be achieved via intramolecular electron transfer between two degenerate and mutually orthogonal frontier molecular orbitals (MOs) at the transition state. Interaction between orthogonal orbitals is amplified when the energy gap between these orbitals approaches zero, or at an "orbital crossing". The crossing between two empty or two fully occupied MOs, which do not lead to stabilization, can be "activated" when one of the empty MOs is populated (i.e., electron injection) or one of the filled MOs is depopulated (i.e., hole injection). In reductive cycloaromatization reactions, such crossings define transition states with energies defined by both the in-plane and out-of-plane π-systems. Herein, we provide experimental evidence for the utility of this concept using orbital crossings in reductive C1-C5 cycloaromatization reactions of enediynes. Communication with remote substituents via orbital crossings greatly enhances regioselectivity of the ring closure step in comparison to the analogous radical cyclizations. We also present photophysical data pertaining to the efficiency of electron injection into the benzannelated enediynes.

We examined the encapsulation of CH4, C2H6, C3H8 and iso-C4H10 in water, using four molecular baskets [1]-[4]. The baskets were shown to bind to hydrocarbon gases by forming favourable C-H···π contacts and, concurrently, adjusting the size of their cup-shaped platform.

We prepared eleven amino-acid functionalized baskets and used (1) H NMR spectroscopy to quantify their affinity for entrapping dimethyl methylphosphonate (DMMP, 118 Å(3) ) in aqueous phosphate buffer at pH=7.0±0.1; note that DMMP guest is akin in size to chemical nerve agent sarin (132 Å(3) ). The binding interaction (Ka ) was found to vary with the size of substituent groups at the basket's rim. In particular, the degree of branching at the first carbon of each substituent had the greatest effect on the host-guest interaction, as described with the Verloop's B1 steric parameter. The branching at the remote carbons, however, did not perturb the encapsulation, which is important for guiding the design of more effective hosts and catalysts in future., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The para-OMe functional group, usually regarded as a conjugative p-donor, acts as an efficient hyperconjugative σ-acceptor in reductive cycloaromatization reactions. This apparent reversal of electronic properties is associated with a conformational change that aligns the σ*(O-C) orbital with the adjacent aromatic system and provides stabilization to the developing negative charge in the TS of the dianionic cyclization of enediynes. The chameleonic character of the OMe group illustrates the important role of negative hyperconjugation in anionic processes.

Topiramate is a newer anticonvulsant used to treat epilepsy, migraines, bipolar disorder, posttraumatic stress, and other conditions. Serum topiramate concentrations are measured to determine optimal levels, address therapeutic failure or drug-drug interactions, and assess compliance. Two high-throughput assays for serum topiramate measurement were compared: the Seradyn fluorescence polarization immunoassay (FPIA) on an Abbott TDx/FLx instrument and a new immunoassay from ARK Diagnostics performed on an Olympus AU680 automated analyzer. Precision, linearity, limit of quantitation, carryover, spike recovery, and endogenous interferences were found to be acceptable for the ARK assay. These studies were complemented by comparison of 120 patient samples analyzed using both methods. The ARK immunoassay performed comparably to FPIA with minimal difference in serum topiramate concentrations within the therapeutic range (2.0-20 microg/mL). A slight systematic discordance was observed at higher concentrations (greater than 30 microg/mL) with ARK immunoassay results being on average 6% higher than FPIA. Thus, the ARK immunoassay appears to provide acceptable analytical performance and comparability to FPIA; furthermore, the assay is compatible with high-throughput autoanalyzers.

Mutations in the human adenomatous polyposis coli (APC) gene are thought to initiate colorectal tumorigenesis. The tumor suppressor function of APC is attributed primarily to its ability to regulate the WNT pathway by targeting the destruction of beta-catenin. We report here a novel role for APC in regulating degradation of the transcriptional co-repressor C-terminal-binding protein-1 (CtBP1) through a proteasome-dependent process. Further, CtBP1 suppresses the expression of intestinal retinol dehydrogenases, which are required for retinoic acid production and intestinal differentiation. In support of a role for CtBP1 in initiation of colorectal cancer, adenomas taken from individuals with familial adenomatous polyposis contain high levels of CtBP1 protein in comparison with matched, uninvolved tissue. The relationship between APC and CtBP1 is conserved between humans and zebrafish and provides a mechanistic model explaining APC control of intestinal retinoic acid biosynthesis.

Congenital hypertrophy/hyperplasia of the retinal pigmented epithelium is an ocular lesion found in patients harboring mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. We report that Apc-deficient zebrafish display developmental abnormalities of both the lens and retina. Injection of dominant-negative Lef reduced Wnt signaling in the lens but did not rescue retinal differentiation defects. In contrast, treatment of apc mutants with all-trans retinoic acid rescued retinal differentiation defects but had no apparent effect on the lens. We identified Rdh5 as a retina-specific retinol dehydrogenase controlled by APC. Morpholino knockdown of Rdh5 phenocopied the apc mutant retinal differentiation defects and was rescued by treatment with exogenous all-trans retinoic acid. Microarray analyses of apc mutants and Rdh5 morphants revealed a profound overlap in the transcriptional profile of these embryos. These findings support a model wherein Apc serves a dual role in regulating Wnt and retinoic acid signaling within the eye and suggest retinoic acid deficiency as an explanation for APC mutation-associated retinal defects such as congenital hypertrophy/hyperplasia of the retinal pigmented epithelium.

Mutations in the adenomatous polyposis coli (APC) gene result in uncontrolled proliferation of intestinal epithelial cells and are associated with the earliest stages of colorectal carcinogenesis. Cyclooxygenase-2 (COX-2) is elevated in human colorectal cancers and plays an important role in colorectal tumorigenesis; however, the mechanisms by which APC mutations result in increased COX-2 expression remain unclear. We utilized APC mutant zebrafish and human cancer cells to investigate how APC modulates COX-2 expression. We report that COX-2 is up-regulated in APC mutant zebrafish because of a deficiency in retinoic acid biosynthesis. Treatment of both APC mutant zebrafish and human carcinoma cell lines with retinoic acid significantly reduces COX-2 expression. Retinoic acid regulates COX-2 levels by a mechanism that involves participation of the transcription factor C/EBP-beta. APC mutant zebrafish express higher levels of C/EBP-beta than wild-type animals, and retinoic acid supplementation reduces C/EBP-beta expression to basal levels. Both morpholino knockdown of C/EBP-beta in APC mutant zebrafish and silencing of C/EBP-beta using small interfering RNA in HT29 colon cancer cells robustly decrease COX-2 expression. Our findings support a sequence of events in which mutations in APC result in impaired retinoic acid biosynthesis, elevated levels of C/EBP-beta, up-regulation of COX-2, increased prostaglandin E(2) accumulation, and activation of Wnt target genes.

Development of normal colon epithelial cells proceeds through a systematic differentiation of cells that emerge from stem cells within the base of colon crypts. Genetic mutations in the adenomatous polyposis coli (APC) gene are thought to cause colon adenoma and carcinoma formation by enhancing colonocyte proliferation and impairing differentiation. We currently have a limited understanding of the cellular mechanisms that promote colonocyte differentiation. Herein, we present evidence supporting a lack of retinoic acid biosynthesis as a mechanism contributing to the development of colon adenomas and carcinomas. Microarray and reverse transcriptase-PCR analyses revealed reduced expression of two retinoid biosynthesis genes: retinol dehydrogenase 5 (RDH5) and retinol dehydrogenase L (RDHL) in colon adenomas and carcinomas as compared with normal colon. Consistent with the adenoma and carcinomas samples, seven colon carcinoma cell lines also lacked expression of RDH5 and RDHL. Assessment of RDH enzymatic activity within these seven cell lines showed poor conversion of retinol into retinoic acid when compared with normal cells such as normal human mammary epithelial cells. Reintroduction of wild type APC into an APC-deficient colon carcinoma cell line (HT29) resulted in increased expression of RDHL without affecting RDH5. APC-mediated induction of RDHL was paralleled by increased production of retinoic acid. Investigations into the mechanism responsible for APC induction of RDHL indicated that beta-catenin fails to repress RDHL. The colon-specific transcription factor CDX2, however, activated an RDHL promoter construct and induced endogenous RDHL. Finally, the induction of RDHL by APC appears dependent on the presence of CDX2. We propose a novel role for APC and CDX2 in controlling retinoic acid biosynthesis and in promoting a retinoid-induced program of colonocyte differentiation.

Inhibitors of DNA methyltransferase, typified by 5-aza-2'-deoxycytidine (5-Aza-CdR), induce the expression of genes transcriptionally down-regulated by de novo methylation in tumor cells. We utilized gene expression microarrays to examine the effects of 5-Aza-CdR treatment in HT29 colon adenocarcinoma cells. This analysis revealed the induction of a set of genes that implicated IFN signaling in the HT29 cellular response to 5-Aza-CdR. Subsequent investigations revealed that the induction of this gene set correlates with the induction of signal transducer and activator of transcription (STAT) 1, 2, and 3 genes and their activation by endogenous IFN-alpha. These observations implicate the induction of the IFN-response pathway as a major cellular response to 5-Aza-CdR and suggests that the expression of STATs 1, 2, and 3 can be regulated by DNA methylation. Consistent with STAT's limiting cell responsiveness to IFN, we found that 5-Aza-CdR treatment sensitized HT29 cells to growth inhibition by exogenous IFN-alpha2a, indicating that 5-Aza-CdR should be investigated as a potentiator of IFN responsiveness in certain IFN-resistant tumors.

We have isolated a novel mutation that caused variegated leaf color in a tomato plant which had multiple maize Ac transposable elements and the tomato Xa allele. Xa is a previously characterized semi-dominant mutation that causes tomato leaves to be bright yellow when heterozygous (Xa/xa+). The mutation responsible for the new phenotype was named Mox (Modifier of Xa). The Mox mutation modified the Xa/xa+ yellow leaf phenotype in two ways: it compensated for the Xa allele resulting in a plant with a wildtype green color, and it caused somatic variegation which appeared as white and yellow sectors on the green background. Somatic variegation was visible only if the plant contained both the Mox and Xa loci. Genetic studies indicated that the Mox locus was linked in repulsion to Xa and that the Mox locus was genetically transmitted at a reduced frequency through the male gamete. Molecular characterization of the Ac elements in lines segregating for Mox identified an Ac insertion that appeared to cosegregate with Mox variegation. We propose a model in which the Mox mutation consists of a duplication of the xa+ allele and subsequent Ac-induced breakage of the duplicated region causes variegation.

We have assayed the transposition activity of the maize transposable element Ac in transgenic tomato plants that had a single copy of Ac. We found that Ac elements were in either a high or low activity state and that an Ac insertion could cycle from low to high activity within a generation. The different transposition activities were not simply due to the chromosomal position of the element, because the same Ac insertion had different levels of activity in sibling plants. Transposition activity was measured by two methods, one genetic and one physical; both assays gave similar results for each plant studied. Notably, plants with active Ac elements had progeny with amplified Ac copy number, while no amplification was detected in lines containing Ac in a low activity state. Analysis of lines with amplified elements revealed that the elements could be either clustered or dispersed. Our results were consistent with amplification being the result of transposition.

To detect genomic instability caused by Ac elements in transgenic tomatoes, we used the incompletely dominant mutation Xanthophyllic-1 (Xa-1) as a whole plant marker gene. Xa-1 is located on chromosome 10 and in the heterozygote state causes leaves to be yellow. Transgenic Ac-containing tomato plants which differed in the location and number of their Ac elements were crossed to Xa-1 tester lines and F1 progeny were scored for aberrant somatic sectoring. Of 800 test and control F1 progeny screened, only four plants had aberrantly high levels of somatic sectors. Three of the plants had twin sectors consisting of green tissue adjacent to white tissue, and the other had twin sectors comprised of green tissue adjacent to tissue more yellow than the heterozygote background. Sectoring was inherited and the two sectoring phenotypes mapped to opposite homologs of chromosome 10; the green/yellow sectoring phenotype mapped in coupling to Xa-1 while the green/white sectoring phenotype mapped in repulsion. The two sectoring phenotypes cosegregated with different single, non-rearranged Acs, and loss of these Acs from the genome corresponded to the loss of sectoring. Sectoring was still observed after transposition of the Ac to a new site which indicated that sectoring was not limited to a single locus. In both sectored lines, meiotic recombination of the sectoring Ac to the opposite homolog caused the phenotype to switch between the green/yellow and the green/white phenotypes. Thus the two different sectoring phenotypes arose from the same Ac-induced mechanism; the phenotype depended on which chromosome 10 homolog the Ac was on. We believe that the twin sectors resulted from chromosome breakage mediated by a single intact, transposition-competent Ac element.