Expression profile of CREB knockdown in myeloid leukemia cells.

BackgroundThe cAMP Response Element Binding Protein, CREB, is a transcription factor that regulates cell proliferation, differentiation, and survival in several model systems, including neuronal and hematopoietic cells. We demonstrated that CREB is overexpressed in acute myeloid and leukemia cells compared to normal hematopoietic stem cells. CREB knockdown inhibits leukemic cell proliferation in vitro and in vivo, but does not affect long-term hematopoietic reconstitution.MethodsTo understand downstream pathways regulating CREB, we performed expression profiling with RNA from the K562 myeloid leukemia cell line transduced with CREB shRNA.ResultsBy combining our expression data from CREB knockdown cells with prior ChIP data on CREB binding we were able to identify a list of putative CREB regulated genes. We performed extensive analyses on the top genes in this list as high confidence CREB targets. We found that this list is enriched for genes involved in cancer, and unexpectedly, highly enriched for histone genes. Furthermore, histone genes regulated by CREB were more likely to be specifically expressed in hematopoietic lineages. Decreased expression of specific histone genes was validated in K562, TF-1, and primary AML cells transduced with CREB shRNA.ConclusionWe have identified a high confidence list of CREB targets in K562 cells. These genes allow us to begin to understand the mechanisms by which CREB contributes to acute leukemia. We speculate that regulation of histone genes may play an important role by possibly altering the regulation of DNA replication during the cell cycle

Potassium bis­(1,1,1,5,5,5-hexa­fluoro­pentane-2,4-dionato)bis­(4,4,4-trifluoro-1-phenyl­butane-1,3-dionato)europate(III)

In the crystal structure of the title complex, K[Eu(C5HF6O2)2(C10H6F3O2)2], the EuIII ion is in a slightly distorted square-anti­prismatic coordination geometry which is defined by eight O atoms of the anionic β-diketone ligands. The two K+ ions lie on crystallographic inversion centers. The Eu—O bond distances are in the range 2.294 (5)–2.413 (5) Å. The crystal used was a non-merohedral twin, the ratio of the twin domains being 0.5236 (5):0.4764 (5)

{N,N-Bis 2-(Diphenylphosphanyl)Ethyl Aniline}(Eta(2)-Dibenzylideneaceton E)Palladium(0)

In the title complex, [Pd(C34H33NP2)(C17H14O)], the Pd-0 atom is coordinated in a trigonal planar geometry formed by two P atoms of a bis[(diphenylphosphino)ethyl] aniline ligand and a C=C (eta(2)) bond involving the C atoms that are in the alpha,beta positions relative to the central ketone of the dibenzylideneacetone ligand.Robert A. Welch Foundation F-1631National Science Foundation CHE-0741973, CHE-0847763Texas Higher Education Coordinating Board 01916-090-2010American Heart Association 0765078YUT-AustinICDDSigma-Xi, the Scientific Research SocietyChemistryBiochemistr

A Comparison Of 3,4,6A,7,10,10A-Hexahydro-7,10-Epoxypyrimido 2,1-A Isoindol-6(2H)-One And 2-(2-Aminoethyl)-3A,4,7,7A-Tetrahydro-1H-4,7-Epoxyisoindole-1,3(2H)-Dion E: Structural And Reactivity Differences Of Two Homologous Tricyclic Imides

The crystal structures of 3,4,6a,7,10,10a-hexahydro-7,10-epoxypyrimido[2,1-a]isoindol-6(2H)-one, C11H12N2O2, and 2-(2-aminoethyl)-3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione, C10H12N2O3, two tricyclic imides, show one and two molecules in the asymmetric unit, respectively. Intermolecular hydrogen-bonding interactions are observed in both compounds.National Science Foundation (grant No. CHE-0741973)The Welch Foundation (grant No. F-1631)National Science Foundation (grant No. CHE-0847763)ChemistryBiochemistr

Inhibition of delta-like ligand 4 induces luteal hypervascularization followed by functional and structural luteolysis in the primate ovary

Using specific inhibitors established that angiogenesis in the ovarian follicle and corpus luteum is driven by vascular endothelial growth factor. Recently, it has been demonstrated that the Notch ligand, delta-like ligand 4 (Dll4) negatively regulates vascular endothelial growth factor-mediated vessel sprouting and branching. To investigate the role of Dll4 in regulation of the ovarian vasculature, we administered a neutralizing antibody to Dll4 to marmosets at the periovulatory period. The vasculature was examined on luteal d 3 or d 10: angiogenesis was determined by incorporation of bromodeoxyuridine, staining for CD31 and cell death by staining for activated caspase-3. Ovulatory progesterone rises were monitored to determine effects of treatment on luteal function and time to recover normal cycles in a separate group of animals. Additionally, animals were treated in the follicular or midluteal phase to determine effects of Dll4 inhibition on follicular development and luteal function. Controls were treated with human IgG (Fc). Corpora lutea from marmosets treated during the periovulatory period exhibited increased angiogenesis and increased vascular density on luteal d 3, but plasma progesterone was significantly suppressed. By luteal d 10, corpora lutea in treated ovaries were significantly reduced in size, with involution of luteal cells, increased cell death, and suppressed plasma progesterone concentrations. In contrast, initiation of anti-Dll4 treatment during the midluteal phase produced only a slight suppression of progesterone for the remainder of the cycle. Moreover, Dll4 inhibition had no appreciable effect on follicular development. These results show that Dll4 has a specific and critical role in the development of the normal luteal vasculature

The evidence for services to avoid or delay residential aged care admission: A systematic review

Background Interventions that enable people to remain in their own home as they age are of interest to stakeholders, yet detailed information on effective interventions is scarce. Our objective was to systematically search and synthesise evidence for the effectiveness of community-based, aged care interventions in delaying or avoiding admission to residential aged care. Method Nine databases were searched from January 2000 to February 2018 for English publications. Reference lists of relevant publications were searched. The databases yielded 55,221 citations and 50 citations were gleaned from other sources. Where there was sufficient homogeneity of study design, population, intervention and measures, meta-analyses were performed. Studies were grouped by the type of intervention: complex multifactorial interventions, minimal/single focus interventions, restorative programs, or by the target population (e.g. participants with dementia). Results Data from 31 randomised controlled trials (32 articles) that met our inclusion criteria were extracted and analysed. Compared to controls, complex multifactorial interventions in community aged care significantly improved older adults’ ability to remain living at home (risk difference − 0.02; 95% CI -0.03, − 0.00; p = 0.04). Commonalities in the 13 studies with complex interventions were the use of comprehensive assessment, regular reviews, case management, care planning, referrals to additional services, individualised interventions, frequent client contact if required, and liaison with General Practitioners. Complex interventions did not have a significantly different effect on mortality. Single focus interventions did not show a significant effect in reducing residential aged care admissions (risk difference 0, 95% CI -0.01, 0.01; p = 0.71), nor for mortality or quality of life. Subgroup analysis of complex interventions for people with dementia showed significant risk reduction for residential aged care admissions (RD -0.05; 95% CI -0.09, -0.01; p = 0.02). Compared to controls, only interventions targeting participants with dementia had a significant effect on improving quality of life (SMD 3.38, 95% CI 3.02, 3.74; p \u3c 0.000001). Conclusions Where the goal is to avoid residential aged care admission for people with or without dementia, there is evidence for multifactorial, individualised community programs. The evidence suggests these interventions do not result in greater mortality and hence are safe. Minimal, single focus interventions will not achieve the targeted outcomes. Trial registration PROSPERO Registration CRD42016050086

Exploring stakeholders\u27 perceptions of the acceptability, usability, and dissemination of the australian 24-hour movement guidelines for the early years

Background: Australian 24-Hour Movement Guidelines for the Early Years were recently developed. To maximize the uptake of the guidelines, perceptions of key stakeholders were sought. Methods: Thirty-five stakeholders (11% Aboriginal or Torres Strait Islander descent) participated in focus groups or key informant interviews. Stakeholders included parents of children aged 0-5 years, early childhood educators, and health and policy professionals, recruited using convenience and snowballing techniques. Focus groups and interviews were audio-recorded and transcribed verbatim. Data were analyzed inductively using thematic analysis. Results: There was general acceptance of the Movement Guidelines. The stakeholders suggested that the Guidelines were highly aspirational and needed to be carefully messaged, so parents did not feel guilty if their child was not meeting them. Stakeholders identified that the messaging needed to be culturally appropriate and visually appealing. Dissemination strategies differed depending on the stakeholder. Conclusion: Seeking stakeholder perceptions is an important process in the development of national Movement Guidelines. This study successfully examined stakeholders\u27 perceptions regarding the acceptability, usability, and dissemination of the Australian 24-Hour Movement Guidelines. Effective and innovative strategies for maximizing compliance and uptake of the Guidelines should be prioritized

{μ-6,6′-Dimeth­oxy-2,2′-[butane-1,4-diylbis(nitrilo­methyl­idyne)]diphenolato-1:2κ8 O 6,O 1,O 1′,O 6′:O 1,N,N′,O 1′}tris­(nitrato-1κ2 O,O′)copper(II)gadolinium(III)

In the title dinuclear complex, [CuGd(C20H22N2O4)(NO3)3], the CuII ion is located in the inner N2O2 cavity of the Schiff base ligand and adopts a distorted square-planar geometry. The GdIII ion is ten-coordinate being bound to ten O atoms, four from the Schiff base ligand and six from three bidentate nitrate anions. The CuII and GdIII ions are linked by two phenolate O atoms of the Schiff base ligand, with a separation of 3.5185 (9) Å