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Homo sapiens

ABSTRACT: Deletion of 11q in neuroblastomas drives sensitivity to PARP inhibition [SEQ]

PROVIDER: PRJNA396156 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5877550.fastq.gz	Fastqsanger.gz
	SRR5877560.fastq.gz	Fastqsanger.gz
	SRR5877551.fastq.gz	Fastqsanger.gz
	SRR5877561.fastq.gz	Fastqsanger.gz
	SRR5877552.fastq.gz	Fastqsanger.gz

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Homo sapiens

Project description:Deletion of 11q in neuroblastomas drives sensitivity to PARP inhibition [SNP array]

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Deletion of 11q in neuroblastomas drives sensitivity to PARP inhibition

Project description:Deletion of 11q in neuroblastomas drives sensitivity to PARP inhibition

| PRJNA396155 | ENA

Deletion of 11q in neuroblastomas drives sensitivity to PARP inhibition [SNP array]

Project description:SNP arrays were combined with next generation sequencing (NGS) to precisely define the deleted region in 17 primary 11q-loss neuroblastomas and identify allelic variants in genes relevant for neuroblastoma aetiology. We assessed PARP inhibitor olaparib in combination with other chemotherapy medications using both in vitro and in vivo models.

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Deletion of 11q in neuroblastomas drives sensitivity to PARP inhibition [SEQ]

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Affymetrix CytoScan HD data on neuroblastoma cell lines

Project description:Neuroblastomas are characterized by recurrent segmental and/or numerical chromosomal abberations such as MYCN-amplification or 11q-deletion. To further elucidate recurrent chromosomal alterations, 16 neuroblastoma cell lines were investigated.

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Homo sapiens Raw sequence reads-ferroptosis resistance

Project description:To study pathways associated with ferroptosis sensitivity

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11q deletion or ALK activity curbs DLG2 expression to maintain an undifferentiated state in neuroblastoma.

Project description:High-risk 11q deleted neuroblastomas (NBs) typically display an undifferentiated/poorly differentiated morphology. NB is thought to develop from Schwann cell precursors (SCPs) and un-differentiated neural crest derived cells (NCC). It is therefore vital to understand the mechanisms involved in the block of differentiation. We showed that an important and novel role for oncogenic ALK-ERK1/2-SP1 signaling may be the maintenance of an undifferentiated state of transformed NC-derived progenitors that is achieved by repression of DLG2, a tumor suppressor in NB. DLG2 is expressed in the ‘bridge signature’ that represents the transcriptional transition state when neural crest cells or Schwann Cell Precursors (SCP) become chromaffin cells of the adrenal gland. The importance of SP1 and DLG2 in this process is highlighted by our findings that restoring DLG2 expression spontaneously drives NB differentiation. Further, genetic analysis of high-risk 11q deletion NB patient identified genetic lesions in the DLG2 gene, Our data also suggest that further exploration of other ‘bridge genes’ may help to better understand the mechanisms underlying the differentiation of NC-derived progenitors and their contribution to NB.

2020-11-25 | PXD017946 | Pride

Crystal structure of Homo sapiens kynureninase.

Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.

| S-EPMC2531291 | biostudies-literature

Homo sapiens whole blood.

Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.

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The evolution of Homo sapiens denisova and Homo sapiens neanderthalensis miRNA targeting genes in the prenatal and postnatal brain.

Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.

| S-EPMC4686780 | biostudies-literature

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