Dataset Information

Palaeoproteomic evidence identifies archaic hominins associated with the Châtelperronian at the Grotte du Renne.

ABSTRACT: The project aimed to characterize the protein composition from 3 Pleistocene bone specimens (AR-7, AR-16, AR-30). Analysed extracts concern standard ZooMS tryptic digests (AR-7, AR-16, AR-30) and additional palaeoproteomic extracts (AR-30A and AR-30B). The latter concern two biological duplicates. All extractions were performed at the Department of Human Evolution, MPI-EVA (Germany) under sterile conditions. Analyses took place on a Q-Exactive Hybrid Quadrupole-Orbitrap MS.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo

TISSUE(S): Bone

SUBMITTER: Frido Welker

LAB HEAD: Matthew Collins

PROVIDER: PXD003208 | Pride | 2016-09-27

REPOSITORIES: Pride

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Palaeoproteomic evidence identifies archaic hominins associated with the Châtelperronian at the Grotte du Renne.

Welker Frido F Hajdinjak Mateja M Talamo Sahra S Jaouen Klervia K Dannemann Michael M David Francine F Julien Michèle M Meyer Matthias M Kelso Janet J Barnes Ian I Brace Selina S Kamminga Pepijn P Fischer Roman R Kessler Benedikt M BM Stewart John R JR Pääbo Svante S Collins Matthew J MJ Hublin Jean-Jacques JJ

Proceedings of the National Academy of Sciences of the United States of America 20160916 40

In Western Europe, the Middle to Upper Paleolithic transition is associated with the disappearance of Neandertals and the spread of anatomically modern humans (AMHs). Current chronological, behavioral, and biological models of this transitional period hinge on the Châtelperronian technocomplex. At the site of the Grotte du Renne, Arcy-sur-Cure, morphological Neandertal specimens are not directly dated but are contextually associated with the Châtelperronian, which contains bone points and beads. ...[more]

PMID: 27638212

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Project description:For a long time, Neanderthals were considered hunters of large mammals, whereas the diversification of the exploited faunal spectrum to include smaller taxa, including birds, was assumed to be specific to anatomically modern humans. In recent decades, archaeozoological analyses of faunal remains from layers associated with Middle Palaeolithic lithic industries have revealed traces of human manipulation of small taxa, indicating the exploitation of a wider range of animals than previously thought, including small or fast-moving animals such as molluscs, leporids and birds. These new data have challenged the view that Neanderthals did not exploit small animals, thereby narrowing the behavioral gap with anatomically modern humans. Nevertheless, the information currently available comes almost exclusively from southern Europe and the nature of Neanderthal small fauna exploitation in northern Europe remains largely unknown. The present study aims to fill this gap by applying archaeozoological methods, including detailed taphonomic and traceological analyses, to 118 bird remains recovered from levels containing Middle Palaeolithic industries at Scladina cave, southern Belgium. Analyses of proteomics were applied to clarify the taxonomic identity of two morphologically non-diagnostic elements. Compared to mammal remains, bird bones, most of which belong to the order Galliformes, are scarce at Scladina Cave. This is likely due to conservation bias. Traces of non-human predators or scavengers, suggest that mammalian carnivores are responsible for accumulating a considerable portion of the avian assemblage. In total, seven bird bones exhibit anthropogenic traces, and one element presents questionable traces. Various Galliformes and a cormorant were exploited likely for their meat, during MIS 5 and/or 6 and MIS 6. The terminal posterior phalanx (talon) of a raptor of the size of a pomarine eagle displays intense polishing that could be linked to human manipulation of this element (MIS 5 and/or 6), although in the absence of tool marks this remains hypothetical at this stage. On the radius of a Western capercaillie, two deep incisions may indicate bone working, and intense use-wear on one of the fractured ends indicates that the bone has been utilized, potentially on soft organic material (MIS 6). This study provides the first evidence of the exploitation of birds during the Middle Palaeolithic in Belgium and constitutes the only detailed archaeozoological analysis of bird material in northwestern Europe. The likely transformation and use of a bird bone is only the second example recovered from Neanderthal occupations. The novel taxa identified as Neanderthal prey highlight the plasticity of Neanderthal ecological behavior, adapting to different landscapes and climates and exploiting the full spectrum of locally available prey.

Project description:Aberrant activation of androgen receptor (AR)-dependent transcriptional programs is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions (PPIs) involving AR-interacting proteins, which we designate the “AR-interactome”. Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate-tumor cells has not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate-tumor cell line, N-AR, which stably expresses wild-type AR containing the streptavidin-binding peptide epitope tagged at its N-terminus (SBP-AR). A bioanalytical workflow involving streptavidin-chromatography and label-free quantitative mass spectrometry was used to identify SBP-AR and associated ligand-sensitive proteins/protein complexes functionally linked to AR activation in the cytosol of N-AR cells. Functional studies verified that ligand-sensitive streptavidin-copurified proteins encoded modulators of AR-mediated transcription, suggesting that these novel proteins were putative SBP-AR-interacting proteins in N-AR cells. This was supported by biochemical associations between recombinant SBP-AR and the ligand-sensitive COPI retrograde trafficking complex in vitro. Extensive biochemical and molecular experiments showed that the COPI-retrograde complex regulates ligand-mediated AR transcriptional activation through the mobilization of Golgi-localized ARA160 coactivator into the nuclear compartment of prostate-tumor cells. Collectively, this study provides a bioanalytical strategy to validate the AR-interactome and define novel AR-interacting proteins involved in ligand-mediated AR activation in prostate-tumor cells. Moreover, we describe a cellular system to study how compartment-specific AR-interacting proteins influence AR activation and contribute to aberrant AR-dependent transcription that underlies the majority of human prostate cancers.

Project description:Reactivation of androgen receptor (AR) may drive recurrent prostate cancer in castrate patients. Ack1 tyrosine kinase is overexpressed in prostate cancer and promotes castrate resistant xenograft tumor growth and enhances androgen target gene expression and AR recruitment to enhancers. Ack1 phosphorylates AR at Tyr-267 in the N-terminal transactivation domain. In this study, the role of this phosphorylation site was investigated by characterizing the phosphorylation site mutant in the context of full length and truncated AR lacking the ligand-binding domain. The Y267F mutant showed decreased transactivation of reporters. Expression of wild type full length and truncated AR in LNCaP cells increased cell proliferation in androgen-depleted conditions and increased colony formation. However, the Y267F mutant of full length and truncated AR was defective in stimulating cell proliferation. The full length AR Y267F mutant was defective in nuclear translocation induced by androgen or Ack1 kinase. The truncated AR was constitutively localized to the nucleus. Chromatin immunoprecipitation analysis showed that it was recruited to the target enhancers without androgen. The truncated Y267F AR mutant did not exhibit constitutive nuclear localization and androgen enhancer binding activity. Expression of AR responsive genes in cells expressing truncated AR wt and AR-Y267F mutant under androgen deprived conditions was assessed by microarray gene expression analysis. The AR pathway score was increased in cells expressing truncated AR wt and decreased in cells expressing truncated AR-Y267F. These results support the concept that phosphorylation of Tyr-267 is required for AR nuclear translocation and recruitment and DNA binding and transcription of AR responsive genes. Gene expression profiling was performed using RNA samples from LNCaP cells expressing truncated AR-wt and truncated AR-Y267F growing in androgen deprived conditions. The RNA sample from vector control cells were used as reference sample. Two biological replicates were used per each cell line.

			Action	DRS
	AR16_2_ZooMS.raw	Raw
	AR16_Search1.pep.xml	Pepxml
	AR16_Search2.pep.xml	Pepxml
	AR16_Search3.pep.xml	Pepxml
	AR30A.raw	Raw

Dataset Information

Palaeoproteomic evidence identifies archaic hominins associated with the Châtelperronian at the Grotte du Renne.

Dataset's files

Publications

Palaeoproteomic evidence identifies archaic hominins associated with the Châtelperronian at the Grotte du Renne.

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