Mesoscopic order and the dimentionality of long-range resonance energy transfer in supramolecular semiconductors

We present time-resolved photoluminescence measurements on two series of oligo-p-phenylenevinylene materials that self-assemble into supramolecular nanostructures with thermotropic reversibility in dodecane. One set of derivatives form chiral, helical stacks while the second set form less organised, frustrated stacks. Here we study the effects of supramolecular organisation on the resonance energy transfer rates. We measure these rates in nanoassemblies formed with mixed blends of oligomers and compare them with the rates predicted by Foerster theory. Our results and analysis show that control of supramolecular order in the nanometre lengthscale has a dominant effect on the efficiency and dimentionality of resonance energy transfer.Comment: 17 Pages, 5 Figures, Submitted to J. Chem. Phy

Stromal mesenchyme cell genes of the human prostate and bladder

BACKGROUND: Stromal mesenchyme cells play an important role in epithelial differentiation and likely in cancer as well. Induction of epithelial differentiation is organ-specific, and the genes responsible could be identified through a comparative genomic analysis of the stromal cells from two different organs. These genes might be aberrantly expressed in cancer since cancer could be viewed as due to a defect in stromal signaling. We propose to identify the prostate stromal genes by analysis of differentially expressed genes between prostate and bladder stromal cells, and to examine their expression in prostate cancer. METHODS: Immunohistochemistry using antibodies to cluster designation (CD) cell surface antigens was first used to characterize the stromas of the prostate and bladder. Stromal cells were prepared from either prostate or bladder tissue for cell culture. RNA was isolated from the cultured cells and analyzed by DNA microarrays. Expression of candidate genes in normal prostate and prostate cancer was examined by RT-PCR. RESULTS: The bladder stroma was phenotypically different from that of the prostate. Most notable was the presence of a layer of CD13(+ )cells adjacent to the urothelium. This structural feature was also seen in the mouse bladder. The prostate stroma was uniformly CD13(-). A number of differentially expressed genes between prostate and bladder stromal cells were identified. One prostate gene, proenkephalin (PENK), was of interest because it encodes a hormone. Secreted proteins such as hormones and bioactive peptides are known to mediate cell-cell signaling. Prostate stromal expression of PENK was verified by an antibody raised against a PENK peptide, by RT-PCR analysis of laser-capture microdissected stromal cells, and by database analysis. Gene expression analysis showed that PENK expression was down-regulated in prostate cancer. CONCLUSION: Our findings show that the histologically similar stromas of the prostate and bladder are phenotypically different, and express organ-specific genes. The importance of these genes in epithelial development is suggested by their abnormal expression in cancer. Among the candidates is the hormone PENK and the down-regulation of PENK expression in cancer suggests a possible association with cancer development

HFF-DeepSpace photometric catalogs of the 12 Hubble frontier fields, clusters, and parallels : photometry, photometric redshifts, and stellar masses

We present Hubble multi-wavelength photometric catalogs, including (up to) 17 filters with the Advanced Camera for Surveys and Wide Field Camera 3 from the ultra-violet to near-infrared for the Hubble Frontier Fields and associated parallels. We have constructed homogeneous photometric catalogs for all six clusters and their parallels. To further expand these data catalogs, we have added ultra-deep KS-band imaging at 2.2. mu m from the Very Large Telescope HAWK-I and Keck-I MOSFIRE instruments. We also add post-cryogenic Spitzer imaging at 3.6 and 4.5. mu m with the Infrared Array Camera (IRAC), as well as archival IRAC 5.8 and 8.0. mu m imaging when available. We introduce the public release of the multi-wavelength (0.2-8 mu m) photometric catalogs, and we describe the unique steps applied for the construction of these catalogs. Particular emphasis is given to the source detection band, the contamination of light from the bright cluster galaxies (bCGs), and intra-cluster light (ICL). In addition to the photometric catalogs, we provide catalogs of photometric redshifts and stellar population properties. Furthermore, this includes all the images used in the construction of the catalogs, including the combined models of bCGs and ICL, the residual images, segmentation maps, and more. These catalogs are a robust data set of the Hubble Frontier Fields and will be an important aid in designing future surveys, as well as planning follow-up programs with current and future observatories to answer key questions remaining about first light, reionization, the assembly of galaxies, and many more topics, most notably by identifying high-redshift sources to target

Lineage relationship of prostate cancer cell types based on gene expression

<p>Abstract</p> <p>Background</p> <p>Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells.</p> <p>Methods</p> <p>Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology) and pattern 4 (aglandular) sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype) and LuCaP 49 (neuroendocrine/small cell carcinoma) grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts.</p> <p>Results</p> <p>Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like) grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness.</p> <p>Conclusions</p> <p>Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.</p

Posttranscriptional regulation of PARG mRNA by HuR facilitates DNA repair and resistance to PARP inhibitors

The majority of pancreatic ductal adenocarcinomas (PDAC) rely on the mRNA stability factor HuR (ELAV-L1) to drive cancer growth and progression. Here, we show that CRISPR-Cas9–mediated silencing of the HuR locus increases the relative sensitivity of PDAC cells to PARP inhibitors (PARPi). PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus to the cytoplasm, specifically promoting stabilization of a new target, poly (ADP-ribose) glycohydrolase (PARG) mRNA, by binding a unique sequence embedded in its 30 untranslated region. HuR-dependent upregulation of PARG expression facilitated DNA repair via hydrolysis of polyADP-ribose on related repair proteins. Accordingly, strategies to inhibit HuR directly promoted DNA damage accumulation, inefficient PAR removal, and persistent PARP-1 residency on chromatin (PARP-1 trapping). Immunoprecipitation assays demonstrated that the PARP-1 protein binds and posttranslationally modifies HuR in PARPi-treated PDAC cells. In a mouse xenograft model of human PDAC, PARPi monotherapy combined with targeted silencing of HuR significantly reduced tumor growth compared with PARPi therapy alone. Our results highlight the HuR–PARG axis as an opportunity to enhance PARPi-based therapies. ©2017 AACR

Los aportes de aerosoles afectan las propiedades ópticas de la materia orgánica disuelta en las aguas costeras del Mediterráneo Noroccidental

Aeolian inputs of organic and inorganic nutrients to the ocean are important as they can enhance biological production in surface waters, especially in oligotrophic areas like the Mediterranean. The Mediterranean littoral is particularly exposed to both anthropogenic and Saharan aerosol depositions on a more or less regular basis. During the last few decades experimental studies have been devoted to examining the effect of inorganic nutrient inputs from dust on microbial activity. In this study, we performed experiments at two different locations of the NW Mediterranean, where we evaluated the changes in the quality and quantity of dissolved organic matter due to atmospheric inputs of different origin (Saharan and anthropogenic) and its subsequent transformations mediated by microbial activities. In both experiments the humic-like and protein-like substances, and the fluorescence quantum yield increased after addition. In general, these changes in the quality of dissolved organic matter did not significantly affect the prokaryotes. The recalcitrant character of the fluorescent dissolved organic matter (FDOM) associated with aerosols was confirmed, as we found negligible utilization of chromophoric compounds over the experimental period. We framed these experiments within a two-year time series data set of atmospheric deposition and coastal surface water analyses. These observations showed that both Saharan and anthropogenic inputs induced changes in the quality of organic matter, increasing the proportion of FDOM substances. This increase was larger during Saharan dust events than in the absence of Saharan influence.Los aportes atmosféricos de nutrientes orgánicos e inorgánicos al océano son importantes ya que pueden aumentar la producción biológica en aguas superficiales, especialmente en las zonas oligotróficas como el Mediterráneo. El litoral del Mediterráneo está particularmente expuesto a aportes de origen antropogénico y a deposiciones de polvo sahariano de forma más o menos regular. Durante las últimas décadas los estudios experimentales se han dedicado, sobre todo, a examinar el efecto de la entrada de nutrientes inorgánicos atmosféricos sobre la actividad microbiana. En este estudio, se realizaron experimentos con comunidades microbianas procedentes de dos zonas del Mediterráneo noroccidental. Se evaluaron los cambios en la calidad y cantidad de la materia orgánica disuelta debido a aportes atmosféricos de distinto origen y sus posteriores transformaciones mediadas por actividades microbianas. En ambos experimentos las sustancias orgánicas fluorescentes y el rendimiento cuántico de fluorescencia aumentaron después de la adición de material atmosférico. En general, estos cambios en la calidad de la materia orgánica no afectaron significativamente a los organismos procariotas. El carácter recalcitrante de la materia orgánica disuelta fluorescente (FDOM) contenida en los aerosoles se confirmó ya que la utilización de compuestos cromóforos durante el período experimental fue insignificante. Los resultados obtenidos se contextualizan en relación con una serie temporal de dos años de datos adquiridos de deposición atmosférica y análisis de agua superficial costera. La variabilidad temporal de estas dos variables mostró que tanto los aportes saharianos como antropogénicos provocaron cambios en la calidad de la materia orgánica disuelta en aguas superficiales, incrementando la fracción fluorescente. Éste aumento resultó ser mayor durante eventos de polvo sahariano que en ausencia de ellos

Influences on catch-up growth using relative versus absolute metrics : evidence from the MAL-ED cohort study

Acknowledgements The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development Project (MAL-ED) was a collaborative project led by the Foundation for the National Institutes of Health and the National Institutes of Health, Fogarty International Center. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. National Institutes of Health or Department of Health and Human Services. Funding The MAL-ED study was supported by the Bill & Melinda Gates Foundation, through grants to the Foundation for the National Institutes of Health, and with additional support from the National Institutes of Health, Fogarty Inter- national Center. The funder had no direct role in the writing of the manu- script or in the study design, data collection, analysis or interpretation of study results. We are grateful to the children and caregivers who participated in the study for their invaluable contributions.Peer reviewedPublisher PD

Mechanical cell competition kills cells via induction of lethal p53 levels.

Cell competition is a quality control mechanism that eliminates unfit cells. How cells compete is poorly understood, but it is generally accepted that molecular exchange between cells signals elimination of unfit cells. Here we report an orthogonal mechanism of cell competition, whereby cells compete through mechanical insults. We show that MDCK cells silenced for the polarity gene scribble (scrib(KD)) are hypersensitive to compaction, that interaction with wild-type cells causes their compaction and that crowding is sufficient for scrib(KD) cell elimination. Importantly, we show that elevation of the tumour suppressor p53 is necessary and sufficient for crowding hypersensitivity. Compaction, via activation of Rho-associated kinase (ROCK) and the stress kinase p38, leads to further p53 elevation, causing cell death. Thus, in addition to molecules, cells use mechanical means to compete. Given the involvement of p53, compaction hypersensitivity may be widespread among damaged cells and offers an additional route to eliminate unfit cells.This work was supported by a Cancer Research UK Programme Grant (EP and LW A12460), a Royal Society University Research fellowship to EP (UF0905080), a Wellcome Trust PhD studentship to I.K, a Cambridge Cancer Centre PhD studentship to MG and Core grant funding from the Wellcome Trust (092096) and CRUK (C6946/A14492).This is the final version of the article. It first appeared from Nature Publishing Group via https://doi.org/10.1038/ncomms1137

The urologic epithelial stem cell database (UESC) – a web tool for cell type-specific gene expression and immunohistochemistry images of the prostate and bladder

Background: Public databases are crucial for analysis of high-dimensional gene and protein expression data. The Urologic Epithelial Stem Cells (UESC) database http://scgap.systemsbiology.net/ is a public database that contains gene and protein information for the major cell types of the prostate, prostate cancer cell lines, and a cancer cell type isolated from a primary tumor. Similarly, such information is available for urinary bladder cell types. Description: Two major data types were archived in the database, protein abundance localization data from immunohistochemistry images, and transcript abundance data principally from DNA microarray analysis. Data results were organized in modules that were made to operate independently but built upon a core functionality. Gene array data and immunostaining images for human and mouse prostate and bladder were made available for interrogation. Data analysis capabilities include: (1) CD (cluster designation) cell surface protein data. For each cluster designation molecule, a data summary allows easy retrieval of images (at multiple magnifications). (2) Microarray data. Single gene or batch search can be initiated with Affymetrix Probeset ID, Gene Name, or Accession Number together with options of coalescing probesets and/or replicates. Conclusion: Databases are invaluable for biomedical research, and their utility depends on data quality and user friendliness. UESC provides for database queries and tools to examine cell typespecific gene expression (normal vs. cancer), whereas most other databases contain only whole tissue expression datasets. The UESC database provides a valuable tool in the analysis of differential gene expression in prostate cancer genes in cancer progression.This work was supported by grant 1U01 DK63630 from NIDDK. Additional funding came from grants CA85859, CA98699 and CA111244 from NCI