Emergence of persistent institutionalized inequality at the Bridge River site, British Columbia: the roles of managerial mutualism and coercion.

Persistent institutionalized inequality (PII) emerged at the Bridge River site by 1200-1300 years ago. Research confirms that PII developed at a time of population packing associated with unstable fluctuations in a critical food resource (anadromous salmon) and persisted across multiple generations. While we understand the demographic and ecological conditions under which this history unfolded, we have yet to address details of the underlying social process.

Evolution of the Okvik/Old Bering Sea culture of the Bering Strait as a major transition.

Great transitions are thought to embody major shifts in locus of selection, labour diversification and communication systems. Such expectations are relevant for biological and cultural systems as decades of research has demonstrated similar dynamics within the evolution of culture. The evolution of the Neo-Inuit cultural tradition in the Bering Strait provides an ideal context for examination of cultural transitions.

Children and innovation: play, play objects and object play in cultural evolution.

Cultural evolutionary theory conceptualises culture as an information-transmission system whose dynamics take on evolutionary properties. Within this framework, however, innovation has been likened to random mutations, reducing its occurrence to chance or fortuitous transmission error. In introducing the special collection on children and innovation, we here place object play and play objects - especially functional miniatures - from carefully chosen archaeological contexts in a niche construction perspective.

The C9orf72 protein interacts with Rab1a and the ULK1 complex to regulate initiation of autophagy.

A GGGGCC hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). C9orf72 encodes two C9orf72 protein isoforms of unclear function. Reduced levels of C9orf72 expression have been reported in C9ALS/FTD patients, and although C9orf72 haploinsufficiency has been proposed to contribute to C9ALS/FTD, its significance is not yet clear.

Invited review: decoding the pathophysiological mechanisms that underlie RNA dysregulation in neurodegenerative disorders: a review of the current state of the art.

Altered RNA metabolism is a key pathophysiological component causing several neurodegenerative diseases. Genetic mutations causing neurodegeneration occur in coding and noncoding regions of seemingly unrelated genes whose products do not always contribute to the gene expression process. Several pathogenic mechanisms may coexist within a single neuronal cell, including RNA/protein toxic gain-of-function and/or protein loss-of-function.

Sequestration of multiple RNA recognition motif-containing proteins by C9orf72 repeat expansions.

GGGGCC repeat expansions of C9orf72 represent the most common genetic variant of amyotrophic lateral sclerosis and frontotemporal degeneration, but the mechanism of pathogenesis is unclear. Recent reports have suggested that the transcribed repeat might form toxic RNA foci that sequester various RNA processing proteins. Consensus as to the identity of the binding partners is missing and whole neuronal proteome investigation is needed.

Ribosome-inactivating proteins: potent poisons and molecular tools.

Ribosome-inactivating proteins (RIPs) were first isolated over a century ago and have been shown to be catalytic toxins that irreversibly inactivate protein synthesis. Elucidation of atomic structures and molecular mechanism has revealed these proteins to be a diverse group subdivided into two classes. RIPs have been shown to exhibit RNA N-glycosidase activity and depurinate the 28S rRNA of the eukaryotic 60S ribosomal subunit.

Chtop is a component of the dynamic TREX mRNA export complex.

The TREX complex couples nuclear pre-mRNA processing with mRNA export and contains multiple protein components, including Uap56, Alyref, Cip29 and the multi-subunit THO complex. Here, we have identified Chtop as a novel TREX component. We show that both Chtop and Alyref activate the ATPase and RNA helicase activities of Uap56 and that Uap56 functions to recruit both Alyref and Chtop onto mRNA.

An interaction between KSHV ORF57 and UIF provides mRNA-adaptor redundancy in herpesvirus intronless mRNA export.

The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway.

Structure and function of mRNA export adaptors.

The mRNA export adaptors provide an important link between multiple nuclear mRNA processing events and the mRNA export receptor TAP/NXF1/Mex67p. They are recruited to mRNA through transcriptional and post-transcriptional events, integrating this information to licence mRNA for export. Subsequently they hand mRNA over to TAP and switch TAP to a higher-affinity RNA-binding state, ensuring its stable association with mRNA destined for export.

UIF, a New mRNA export adaptor that works together with REF/ALY, requires FACT for recruitment to mRNA.

Messenger RNA (mRNA) export adaptors play an important role in the transport of mRNA from the nucleus to the cytoplasm. They couple early mRNA processing events such as 5' capping and 3' end formation with loading of the TAP/NXF1 export receptor onto mRNA. The canonical adaptor REF/ALY/Yra1 is recruited to mRNA via UAP56 and subsequently delivers the mRNA to NXF1 [1].