The lyotropic liquid crystalline phases of surfactants exhibit a rich polymorphism of structures that have long-range periodicities and whose characteristic repeat distances range from 2 to 15 ...nanometers. The electrochemical reduction of platinum salts confined to the aqueous environments of these phases leads to the deposition of platinum films that have a well-defined long-ranged porous nanostructure and high specific surface areas. These results suggest that the use of liquid crystalline plating solutions could be a versatile way to create mesoporous electrodes for batteries, fuel cells, electrochemical capacitors, and sensors.
In the preparation of mesoporous materials it has been shown that the liquid crystalline properties of the surfactant are an important factor in determining the morphology of the mesostructures. In ...this study the regularity and morphology of the mesopore structure was examined by X-ray diffraction, transmission electron microscopy and BET surface area analysis as a function of surfactant concentration for the TMOS/Brij 56/HCl (0.5 M) system. The preparation of ordered HI mesoporous silica was shown to take place from both a dilute solution of surfactant (1Brij 56:1000HCl (0.5 M)) and a concentrated surfactant solution (1Brij 56:1HCl (0.5 M)). Ordered HI silica monoliths were prepared with 3.6 nm diameter pores and 1.7 nm thick walls from concentrated Brij 56 mixtures. Similarly ordered HI silica micron sized powders were prepared with 3.8 nm diameter pores and 2.1 nm thick walls from dilute Brij 56 mixtures. Comparison of the mesostructure of the silicas with the liquid crystal phase behaviour of the binary Brij 56/water system showed a correlation between the order of the mesoporous material and the phase behaviour of the surfactant at the high concentration of surfactant. At the low concentrations of surfactant the binary Brij 56/water phase diagram does not exhibit liquid crystalline behaviour. However, phase separation of the micellar solution, induced by the presence of silica species, resulted in micron sized domains of liquid crystalline material. These tiny domains acted as moulds for the formation of mesoporous silica.
Efforts to prevent depression, the leading cause of disability worldwide, have focused on a limited number of candidate factors. Using phenotypic and genomic data from over 100,000 UK Biobank ...participants, the authors sought to systematically screen and validate a wide range of potential modifiable factors for depression.
Baseline data were extracted for 106 modifiable factors, including lifestyle (e.g., exercise, sleep, media, diet), social (e.g., support, engagement), and environmental (e.g., green space, pollution) variables. Incident depression was defined as minimal depressive symptoms at baseline and clinically significant depression at follow-up. At-risk individuals for incident depression were identified by polygenic risk scores or by reported traumatic life events. An exposure-wide association scan was conducted to identify factors associated with incident depression in the full sample and among at-risk individuals. Two-sample Mendelian randomization was then used to validate potentially causal relationships between identified factors and depression.
Numerous factors across social, sleep, media, dietary, and exercise-related domains were prospectively associated with depression, even among at-risk individuals. However, only a subset of factors was supported by Mendelian randomization evidence, including confiding in others (odds ratio=0.76, 95% CI=0.67, 0.86), television watching time (odds ratio=1.09, 95% CI=1.05, 1.13), and daytime napping (odds ratio=1.34, 95% CI=1.17, 1.53).
Using a two-stage approach, this study validates several actionable targets for preventing depression. It also demonstrates that not all factors associated with depression in observational research may translate into robust targets for prevention. A large-scale exposure-wide approach combined with genetically informed methods for causal inference may help prioritize strategies for multimodal prevention in psychiatry.
Embryonal precursors of Wilms tumor Coorens, Tim H H; Treger, Taryn D; Al-Saadi, Reem ...
Science,
12/2019, Letnik:
366, Številka:
6470
Journal Article
Recenzirano
Odprti dostop
Adult cancers often arise from premalignant clonal expansions. Whether the same is true of childhood tumors has been unclear. To investigate whether Wilms tumor (nephroblastoma; a childhood kidney ...cancer) develops from a premalignant background, we examined the phylogenetic relationship between tumors and corresponding normal tissues. In 14 of 23 cases studied (61%), we found premalignant clonal expansions in morphologically normal kidney tissues that preceded tumor development. These clonal expansions were defined by somatic mutations shared between tumor and normal tissues but absent from blood cells. We also found hypermethylation of the
locus, a known driver of Wilms tumor development, in 58% of the expansions. Phylogenetic analyses of bilateral tumors indicated that clonal expansions can evolve before the divergence of left and right kidney primordia. These findings reveal embryonal precursors from which unilateral and multifocal cancers develop.
SOST Inhibits Prostate Cancer Invasion Hudson, Bryan D; Hum, Nicholas R; Thomas, Cynthia B ...
PloS one,
11/2015, Letnik:
10, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt ...signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. We found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings.
Although VEGF-targeted therapies are showing promise, new angiogenesis targets are needed to make additional gains. Here, we show that increased Zeste homolog 2 (EZH2) expression in either tumor ...cells or in tumor vasculature is predictive of poor clinical outcome. The increase in endothelial EZH2 is a direct result of VEGF stimulation by a paracrine circuit that promotes angiogenesis by methylating and silencing vasohibin1 (vash1). Ezh2 silencing in the tumor-associated endothelial cells inhibited angiogenesis mediated by reactivation of VASH1, and reduced ovarian cancer growth, which is further enhanced in combination with ezh2 silencing in tumor cells. Collectively, these data support the potential for targeting ezh2 as an important therapeutic approach.
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► EZH2 is a key regulator of tumor angiogenesis ► VEGF stimulation increases EZH2 levels in endothelial cells ► Ezh2 silencing inhibits angiogenesis by activating vash1 ► Ezh2 targeting is an attractive therapeutic approach
Emerging evidence suggests that the Notch/Delta-like ligand 4 (Dll4) pathway may offer important new targets for antiangiogenesis approaches. In this study, we investigated the clinical and ...biological significance of Dll4 in ovarian cancer. Dll4 was overexpressed in 72% of tumors examined in which it was an independent predictor of poor survival. Patients with tumors responding to anti-VEGF therapy had lower levels of Dll4 than patients with stable or progressive disease. Under hypoxic conditions, VEGF increased Dll4 expression in the tumor vasculature. Immobilized Dll4 also downregulated VEGFR2 expression in endothelial cells directly through methylation of the VEGFR2 promoter. RNAi-mediated silencing of Dll4 in ovarian tumor cells and tumor-associated endothelial cells inhibited cell growth and angiogenesis, accompanied by induction of hypoxia in the tumor microenvironment. Combining Dll4-targeted siRNA with bevacizumab resulted in greater inhibition of tumor growth, compared with control or treatment with bevacizumab alone. Together, our findings establish that Dll4 plays a functionally important role in both the tumor and endothelial compartments of ovarian cancer and that targeting Dll4 in combination with anti-VEGF treatment might improve outcomes of ovarian cancer treatment.
We present the fifth edition of the Sloan Digital Sky Survey (SDSS) Quasar Catalog, which is based upon the SDSS Seventh Data Release. The catalog, which contains 105,783 spectroscopically confirmed ...quasars, represents the conclusion of the SDSS-I and SDSS-II quasar survey. The catalog consists of the SDSS objects that have luminosities larger than Mi = --22.0 (in a cosmology with H 0 = 70 km s--1 Mpc--1, Delta *W M = 0.3, and Delta *W Delta *L = 0.7), have at least one emission line with FWHM larger than 1000 km s--1 or have interesting/complex absorption features, are fainter than i 15.0, and have highly reliable redshifts. The catalog covers an area of 9380 deg2. The quasar redshifts range from 0.065 to 5.46, with a median value of 1.49; the catalog includes 1248 quasars at redshifts greater than 4, of which 56 are at redshifts greater than 5. The catalog contains 9210 quasars with i < 18; slightly over half of the entries have i < 19. For each object the catalog presents positions accurate to better than 01 rms per coordinate, five-band (ugriz) CCD-based photometry with typical accuracy of 0.03 mag, and information on the morphology and selection method. The catalog also contains radio, near-infrared, and X-ray emission properties of the quasars, when available, from other large-area surveys. The calibrated digital spectra cover the wavelength region 3800-9200 A at a spectral resolution of 2000; the spectra can be retrieved from the SDSS public database using the information provided in the catalog. Over 96% of the objects in the catalog were discovered by the SDSS. We also include a supplemental list of an additional 207 quasars with SDSS spectra whose archive photometric information is incomplete.
The diversity and heterogeneity within high-grade serous ovarian cancer (HGSC), which is the most lethal gynecologic malignancy, is not well understood. Here, we perform comprehensive multi-platform ...omics analyses, including integrated analysis, and immune monitoring on primary and metastatic sites from highly clinically annotated HGSC samples based on a laparoscopic triage algorithm from patients who underwent complete gross resection (R0) or received neoadjuvant chemotherapy (NACT) with excellent or poor response. We identify significant distinct molecular abnormalities and cellular changes and immune cell repertoire alterations between the groups, including a higher rate of NF1 copy number loss, and reduced chromothripsis-like patterns, higher levels of strong-binding neoantigens, and a higher number of infiltrated T cells in the R0 versus the NACT groups.
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•High rate of NF1 loss in the R0 compared to neoadjuvant chemotherapy (NACT) group•Lower chromothripsis-like pattern and higher neoantigens in the R0 versus NACT group•Increased number of infiltrated T cells and decreased macrophages in the R0 group•Significant transcriptomic and proteomic variations between HGSC subgroups
High-grade serous ovarian cancer (HGSC) patients with no gross residual disease (R0) after primary surgery have the greatest improvement in clinical outcomes. A deep understanding of molecular and cellular heterogeneity of HGSC is lacking. Findings by Lee et al. highlight major molecular and cellular differences between clinically defined subgroups of HGSC.
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. ...Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently.
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