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Effect of drying and storage on the content of provitamin A of orange fleshed sweet potato (Ipomoa batatas): direct sun radiations do not have significant impact
[Introduction] Sweetpotato is an important crop that is widely consumed in sub-Saharan Africa. Sun drying of sweetpotatoes is a traditional practice: after drying on rocks crushed or sliced dried sweetpotato are stored in granaries; re-hydrated and boiled to be eaten like fresh roots, or milled into flour to make porridge. Orange
fleshed sweetpotato is being promoted in Africa to tackle vitamin A deficiency. There are inconsistent reports on the effect of sun-drying on pro-vitamin A retention. High losses have been reported which may be associated with the unsaturated instable provitamin A carotenoids easily degraded by light, oxygen and heat (Rodriguez Amaya 1997). This poster describes work to understand the effects of sun/solar drying and storage on pro-vitamin A retention
Effect of drying and storage on the content of provitamin A of orange fleshed sweet potato (Ipomoa batatas) Direct sun radiations do not have significant impact
Suicides in public places: findings from one English county
Little is known about where suicides take place. We collected data from coroners’ files on all suicides and undetermined deaths in one large English county from 2000 to 2004. The data show that >30% of suicides occurred in public places. A quarter of these involved jumping from a height and nearly a quarter involved car exhaust poisoning. Several sites were associated with multiple methods of suicide. Identifying and managing high-risk locations should be an important part of an overall suicide prevention strategy and is best tackled at local level
Overexpression of Full-Length ETV1 Transcripts in Clinical Prostate Cancer Due to Gene Translocation
ETV1 is overexpressed in a subset of clinical prostate cancers as a fusion transcript with many different partners. However, ETV1 can also be overexpressed as a full-length transcript. Full-length ETV1 protein functions differently from truncated ETV1 produced by fusion genes. In this study we describe the genetic background of full-length ETV1 overexpression and the biological properties of different full-length ETV1 isoforms in prostate cancer. Break-apart FISH showed in five out of six patient samples with overexpression of full-length ETV1 a genomic rearrangement of the gene, indicating frequent translocation. We were able to study the rearrangements in more detail in two tumors. In the first tumor 5′-RACE on cDNA showed linkage of the complete ETV1 transcript to the first exon of a prostate-specific two exon ncRNA gene that maps on chromosome 14 (EST14). This resulted in the expression of both full-length ETV1 transcripts and EST14-ETV1 fusion transcripts. In chromosome spreads of a xenograft derived from the second prostate cancer we observed a complex ETV1 translocation involving a chromosome 7 fragment that harbors ETV1 and fragments of chromosomes 4 and 10. Further studies revealed the overexpression of several different full-length transcripts, giving rise to four protein isoforms with different N-terminal regions. Even the shortest isoform synthesized by full-length ETV1 stimulated in vitro anchorage-independent growth of PNT2C2 prostate cells. This contrasts the lack of activity of even shorter N-truncated ETV1 produced by fusion transcripts. Our findings that in clinical prostate cancer overexpression of full-length ETV1 is due to genomic rearrangements involving different chromosomes and the identification of a shortened biologically active ETV1 isoform are highly relevant for understanding the mechanism of ETV1 function in prostate cancer
YK-4-279 Inhibits ERG and ETV1 Mediated Prostate Cancer Cell Invasion
Background: Genomic rearrangements involving the ETS family of transcription factors occur in 40–70 % of prostate cancer cases. ERG and ETV1 are the most common ETS members observed in these genetic alterations. The high prevalence of these rearrangements and their biological significance represents a novel therapeutic target for the treatment of prostate cancer. Methods and Findings: We recently reported the development of YK-4-279, a small molecule inhibitor of EWS-FLI1 oncoprotein in Ewing’s Sarcoma. Since ERG and ETV1 belong to the same class of ETS factors as FLI1, we tested the ability of YK-4-279 to inhibit biological functions of ERG and ETV1 proteins in prostate cancer. YK-4-279 inhibited ERG and ETV1 mediated transcriptional activity in a luciferase assay. YK-4-279 also decreased ERG and ETV1 downstream target mRNA and protein expression in ETV1-fusion positive LNCaP and ERG fusion positive VCaP cells. YK-4-279 reduced the motility of LNCaP cells in a scratch assay and the invasive phenotype of both LNCaP and VCaP cells in a HUVEC invasion assay. Fusion-negative PC3 cells were unresponsive to YK-4-279. SiRNA mediated ERG knockdown in VCaP cells resulted in a loss of drug responsiveness. Concurrently, transient ERG expression in PC-3 cells resulted in increased invasive potential, which was reduced by YK-4-279. Conclusion: These data demonstrate that YK-4-279 inhibits ERG and ETV1 biological activity in fusion-positive prostat
At the intersection of primary pulmonary myxoid sarcoma and pulmonary angiomatoid fibrous histiocytoma: observations from three new cases
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107555/1/his12354.pd
Quantum optical coherence tomography of a biological sample
Quantum optical coherence tomography (QOCT) makes use of an entangled-photon
light source to carry out dispersion-immune axial optical sectioning. We
present the first experimental QOCT images of a biological sample: an
onion-skin tissue coated with gold nanoparticles. 3D images are presented in
the form of 2D sections of different orientations.Comment: 16 Pages, 6 Figure
Messina: A Novel Analysis Tool to Identify Biologically Relevant Molecules in Disease
BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package
Comprehensive serial molecular profiling of an “N of 1” exceptional non-responder with metastatic prostate cancer progressing to small cell carcinoma on treatment
Abstract
Importance
Small cell carcinoma/neuroendocrine prostate cancer (NePC) is a lethal, poorly understood prostate cancer (PCa) subtype. Controversy exists about the origin of NePC in this setting.
Objective
To molecularly profile archived biopsy specimens from a case of early-onset PCa that rapidly progressed to NePC to identify drivers of the aggressive course and mechanisms of NePC origin and progression.
Design, setting, and participants
A 47-year-old patient presented with metastatic prostatic adenocarcinoma (Gleason score 9). After a 6-month response to androgen deprivation therapy, the patient developed jaundice and liver biopsy revealed exclusively NePC. Targeted next generation sequencing (NGS) from formalin-fixed paraffin-embedded (FFPE)-isolated DNA was performed from the diagnostic prostate biopsy and the liver biopsy at progression.
Intervention
Androgen deprivation therapy for adenocarcinoma followed by multiagent chemotherapy for NePC.
Main outcomes and measures
Identification of the mutational landscape in primary adenocarcinoma and NePC liver metastasis. Whether the NePC arose independently or was derived from the primary adenocarcinoma was considered based on mutational profiles.
Results
A deleterious somatic SMAD4 L535fs variant was present in both prostate and liver specimens; however, a TP53 R282W mutation was exclusively enriched in the liver specimen. Copy number analysis identified concordant, low-level alterations in both specimens, with focal MYCL amplification and homozygous PTEN, RB1, and MAP2K4 losses identified exclusively in the NePC specimen. Integration with published genomic profiles identified MYCL as a recurrently amplified in NePC.
Conclusions and relevance
NGS of routine biopsy samples from an exceptional non-responder identified SMAD4 as a driver of the aggressive course and supports derivation of NePC from primary adenocarcinoma (transdifferentiation).http://deepblue.lib.umich.edu/bitstream/2027.42/113670/1/13045_2015_Article_204.pd
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