Contextualizing the Upper Paleolithic of the Armenian Highlands: New data from Solak-1, central Armenia.

As a potential corridor connecting Southwest Asia with western and northern Europe, the Armenian Highlands and southern Caucasus hold great potential for increasing our understanding of Upper Paleolithic behavioral and cultural variability. However, given the dearth of Upper Paleolithic sites, we lack the data necessary to answer basic questions regarding the timing and nature of the Upper Paleolithic in this region. Solak-1 is an open-air site located along the upper Hrazdan Valley (1635 m above sea level) in central Armenia.

Novel use of a servosphere to study apodous insects: Investigation of blow fly post-feeding larval dispersal.

Blow flies (Diptera: Calliphoridae) are arguably the most important providers of an estimate of minimum post-mortem interval in forensic investigations. They usually undergo a post-feeding dispersal from the body. While previous studies have looked at dispersal of groups of larvae, recording the dispersal activity of individual larvae has not previously been demonstrated.

Aggregation and Prion-Inducing Properties of the G-Protein Gamma Subunit Ste18 are Regulated by Membrane Association.

Yeast prions and mnemons are respectively transmissible and non-transmissible self-perpetuating protein assemblies, frequently based on cross-β ordered detergent-resistant aggregates (amyloids). Prions cause devastating diseases in mammals and control heritable traits in yeast. It was shown that the de novo formation of the prion form [] of yeast release factor Sup35 is facilitated by aggregates of other proteins.

Geochemical Evidence for the Control of Fire by Middle Palaeolithic Hominins.

The use of fire played an important role in the social and technological development of the genus Homo. Most archaeologists agree that this was a multi-stage process, beginning with the exploitation of natural fires and ending with the ability to create fire from scratch. Some have argued that in the Middle Palaeolithic (MP) hominin fire use was limited by the availability of fire in the landscape.

Yeast Models for Amyloids and Prions: Environmental Modulation and Drug Discovery.

Amyloids are self-perpetuating protein aggregates causing neurodegenerative diseases in mammals. Prions are transmissible protein isoforms (usually of amyloid nature). Prion features were recently reported for various proteins involved in amyloid and neural inclusion disorders.

Prion-based memory of heat stress in yeast.

Amyloids and amyloid-based prions are self-perpetuating protein aggregates which can spread by converting a normal protein of the same sequence into a prion form. They are associated with diseases in humans and mammals, and control heritable traits in yeast and other fungi. Some amyloids are implicated in biologically beneficial processes.

Yeast Short-Lived Actin-Associated Protein Forms a Metastable Prion in Response to Thermal Stress.

Self-perpetuating ordered protein aggregates (amyloids and prions) are associated with a variety of neurodegenerative disorders. Although environmental agents have been linked to certain amyloid diseases, the molecular basis of their action remains unclear. We have employed endogenous yeast prions as a model system to study environmental control of amyloid formation.

Prions, Chaperones, and Proteostasis in Yeast.

Prions are alternatively folded, self-perpetuating protein isoforms involved in a variety of biological and pathological processes. Yeast prions are protein-based heritable elements that serve as an excellent experimental system for studying prion biology. The propagation of yeast prions is controlled by the same Hsp104/70/40 chaperone machinery that is involved in the protection of yeast cells against proteotoxic stress.

Middle Palaeolithic toolstone procurement behaviors at Lusakert Cave 1, Hrazdan valley, Armenia.

Strategies employed by Middle Palaeolithic hominins to acquire lithic raw materials often play key roles in assessing their movements through the landscape, relationships with neighboring groups, and cognitive abilities. It has been argued that a dependence on local resources is a widespread characteristic of the Middle Palaeolithic, but how such behaviors were manifested on the landscape remains unclear. Does an abundance of local toolstone reflect frequent encounters with different outcrops while foraging, or was a particular outcrop favored and preferentially quarried? This study examines such behaviors at a finer geospatial scale than is usually possible, allowing us to investigate hominin movements through the landscape surrounding Lusakert Cave 1 in Armenia.

Quantitative analysis of protein-protein interactions.

Numerous authors, including contributors to this volume, have described methods to detect protein-protein interactions. Many of these approaches are now accessible to the inexperienced investigator thanks to core facilities and/or affordable instrumentation. This chapter discusses some common design considerations that are necessary to obtain valid measurements, as well as the assumptions and analytical methods that are relevant to the quantitation of these interactions.

Satsurblia: new insights of human response and survival across the Last Glacial Maximum in the southern Caucasus.

The region of western Georgia (Imereti) has been a major geographic corridor for human migrations during the Middle and Upper Palaeolithic (MP/UP). Knowledge of the MP and UP in this region, however, stems mostly from a small number of recent excavations at the sites of Ortvale Klde, Dzudzuana, Bondi, and Kotias Klde. These provide an absolute chronology for the Late MP and MP-UP transition, but only a partial perspective on the nature and timing of UP occupations, and limited data on how human groups in this region responded to the harsh climatic oscillations between 37,000-11,500 years before present.

Stress-dependent proteolytic processing of the actin assembly protein Lsb1 modulates a yeast prion.

Yeast prions are self-propagating amyloid-like aggregates of Q/N-rich protein that confer heritable traits and provide a model of mammalian amyloidoses. [PSI(+)] is a prion isoform of the translation termination factor Sup35. Propagation of [PSI(+)] during cell division under normal conditions and during the recovery from damaging environmental stress depends on cellular chaperones and is influenced by ubiquitin proteolysis and the actin cytoskeleton.

Analysis of collagen preservation in bones recovered in archaeological contexts using NIR Hyperspectral Imaging.

The scope of this article is to propose an innovative method based on Near Infrared Hyperspectral Chemical Imaging (NIR-HCI) to rapidly and non-destructively evaluate the relative degree of collagen preservation in bones recovered from archaeological contexts. This preliminary study has allowed the evaluation of the potential of the method using bone samples from the Early Upper Palaeolithic, Mesolithic and Neolithic periods at the site of Trou Al'Wesse in Belgium. NIR-HCI, combined with chemometric tools, has identified specific spectral bands characteristic of collagen.

Physiological and environmental control of yeast prions.

Prions are self-perpetuating protein isoforms that cause fatal and incurable neurodegenerative disease in mammals. Recent evidence indicates that a majority of human proteins involved in amyloid and neural inclusion disorders possess at least some prion properties. In lower eukaryotes, such as yeast, prions act as epigenetic elements, which increase phenotypic diversity by altering a range of cellular processes.

BAP1 is phosphorylated at serine 592 in S-phase following DNA damage.

The human BAP1 deubiquitinating enzyme is a chromatin-bound transcriptional regulator and tumor suppressor. BAP1 functions in suppressing cell proliferation, yet its role in the DNA damage response pathway is less understood. In this study we characterized DNA damage-induced phosphorylation of BAP1 at serine 592 (pS592) and the cellular outcomes of this modification.

Regulation of proteolysis by human deubiquitinating enzymes.

The post-translational attachment of one or several ubiquitin molecules to a protein generates a variety of targeting signals that are used in many different ways in the cell. Ubiquitination can alter the activity, localization, protein-protein interactions or stability of the targeted protein. Further, a very large number of proteins are subject to regulation by ubiquitin-dependent processes, meaning that virtually all cellular functions are impacted by these pathways.

Two ZnF-UBP domains in isopeptidase T (USP5).

Human ubiquitin-specific cysteine protease 5 (USP5, also known as ISOT and isopeptidase T), an 835-residue multidomain enzyme, recycles ubiquitin by hydrolyzing isopeptide bonds in a variety of unanchored polyubiquitin substrates. Activation of the enzyme's hydrolytic activity toward ubiquitin-AMC (7-amino-4-methylcoumarin), a fluorogenic substrate, by the addition of free, unanchored monoubiquitin suggested an allosteric mechanism of activation by the ZnF-UBP domain (residues 163-291), which binds the substrate's unanchored diglycine carboxyl tail. By determining the structure of full-length USP5, we discovered the existence of a cryptic ZnF-UBP domain (residues 1-156), which was tightly bound to the catalytic core and was indispensable for catalytic activity.

Structure and recognition of polyubiquitin chains of different lengths and linkage.

The polyubiquitin signal is post-translationally attached to a large number of proteins, often directing formation of macromolecular complexes resulting in the translocation, assembly or degradation of the attached protein. Recent structural and functional studies reveal general mechanisms by which different architectures and length of the signal are distinguished.

Prion induction by the short-lived, stress-induced protein Lsb2 is regulated by ubiquitination and association with the actin cytoskeleton.

Yeast prions are self-perpetuating, QN-rich amyloids that control heritable traits and serve as a model for mammalian amyloidoses. De novo prion formation by overproduced prion protein is facilitated by other aggregated QN-rich protein(s) and is influenced by alterations of protein homeostasis. Here we explore the mechanism by which the Las17-binding protein Lsb2 (Pin3) promotes conversion of the translation termination factor Sup35 into its prion form, [PSI(+)].

An emerging model for BAP1's role in regulating cell cycle progression.

BRCA1-associated protein-1 (BAP1) is a 729 residue, nuclear-localized deubiquitinating enzyme (DUB) that displays tumor suppressor properties in the BAP1-null NCI-H226 lung carcinoma cell line. Studies that have altered BAP1 cellular levels or enzymatic activity have reported defects in cell cycle progression, notably at the G1/S transition. Recently BAP1 was shown to associate with the transcriptional regulator host cell factor 1 (HCF-1).