Geoffrey M. Smith

Correcting human mitochondrial mutations with targeted RNA import

Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects, and aging. An efficient and simple mechanism for neutralizing deleterious mitochondrial DNA (mtDNA) alterations has unfortunately remained elusive. Here, we report that a 20-ribonucleotide stem-loop sequence from the H1 RNA, the RNA component of the human RNase P enzyme, appended to a nonimported RNA directs the import of the resultant RNA fusion transcript into human mitochondria. The methodology is effective for both noncoding RNAs, such as tRNAs, and mRNAs. The RNA import component, polynucleotide phosphorylase (PNPASE), facilitates transfer of this hybrid RNA into the mitochondrial matrix. In addition, nucleus-encoded mRNAs for mitochondrial proteins, such as the mRNA of human mitochondrial ribosomal protein S12 (MRPS12), contain regulatory sequences in their 3′-untranslated region (UTR) that confers localization to the mitochondrial outer membrane, which is postulated to aid in protein translocation after translation. We show that for some mitochondrial-encoded transcripts, such as COX2, a 3′-UTR localization sequence is not required for mRNA import, whereas for corrective mitochondrial-encoded tRNAs, appending the 3′-UTR localization sequence was essential for efficient fusion-transcript translocation into mitochondria. In vivo, functional defects in mitochondrial RNA (mtRNA) translation and cell respiration were reversed in two human disease lines. Thus, this study indicates that a wide range of RNAs can be targeted to mitochondria by appending a targeting sequence that interacts with PNPASE, with or without a mitochondrial localization sequence, providing an exciting, general approach for overcoming mitochondrial genetic disorders.

A continuous climatic impact on Holocene human population in the Rocky Mountains.

Ancient cultural changes have often been linked to abrupt climatic events, but the potential that climate can exert a persistent influence on human populations has been debated. Here, independent population, temperature, and moisture history reconstructions from the Bighorn Basin in Wyoming (United States) show a clear quantitative relationship spanning 13 ka, which explains five major periods of population growth/decline and ∼45% of the population variance. A persistent ∼300-y lag in the human demographic response conforms with either slow (∼0.3%) intrinsic annual population growth rates or a lag in the environmental carrying capacity, but in either case, the population continuously adjusted to changing environmental conditions.

Footprints Across the Black Rock: Temporal Variability in Prehistoric Foraging Territories and Toolstone Procurement Strategies in the Western Great Basin

Mobility is a common theme in Paleoindian research throughout North America including in the Great Basin. One recent model based on results from the X-ray fluorescence (XRF) analysis of Paleoindian artifacts holds that early groups occupied geographically discrete foraging territories throughout the Great Basin during the terminal Pleistocene/early Holocene, ca. 11,500–7500 radiocarbon years ago (14C B.P.), that covered between 46,000 and 107,000 km2. While this model is innovative, its implications regarding Paleoindian mobility are difficult to reconcile with our knowledge of foraging populations. In this article, I evaluate the model using XRF data for 260 Paleoindian projectile points from northwest Nevada. The results fail to support the hypothesis that a single, expansive foraging territory once covered the western Great Basin. However, when compared to a sample of 1,085 projectile points from later periods (ca. 7000 14C B.P. to the historic era), data from the Paleoindian sample indicate that the foraging territories of early groups differed from those of later groups living in the same region. I suggest that these dissimilarities reflect differences in how groups moved across the landscape and procured lithic raw materials.

Points in Time: Direct Radiocarbon Dates on Great Basin Projectile Points

Abstract Typological cross-dating is the primary means by which archaeological sites are placed into chronological frameworks. This approach relies on the assumption that artifacts at undated sites—usually projectile points—are coeval with similar artifacts found at Other, dated sites. While typological cross-dating is necessary in regions dominated by open-air lithic scatters, the approach can be problematic when undated and dated sites are separated by significant distances. Here, we present radiocarbon dates on projectile points with organic hafting material still attached or found within organic storage bags. Our results provide unequivocal ages for various morphological projectile point types at several Great Basin locales and should be useful to researchers seeking local age estimates for those point types, which often involves relying on chronological data from more distant sites. The results also highlight potential issues with uncritically applying typological cross-dating using typologies based on metric attributes, and in two cases, suggest the need to revise the age ranges for certain point styles in the western Great Basin.

A Flaked Stone Crescent from a Stratified, Radiocarbon-Dated Site in the Northern Great Basin

Seven sites in the Far West have produced crescents in dated contexts: of these, only two are in the Great Basin. Single dates from both Great Basin sites—the Sunshine Locality and Fort Rock Cave—suggest that crescents date to the terminal Pleistocene. Crescents from dated contexts in California suggest that they were also used during the early Holocene. We report the discovery of a crescent from a stratified, radiocarbon-dated rockshelter in southeast Oregon initially occupied ∼9600 calendar years ago (cal B.P.). Although crescents may date to the terminal Pleistocene elsewhere in the Great Basin, our find indicates that they were also used during the early Holocene. Crossover Immunoelectrophoresis analysis of the crescent produced a positive reaction for pronghorn, suggesting that the tool contacted that taxon during butchering or hafting activities.

Cascade Points in the Northern Great Basin: A Radiocarbon-Dated Foliate Point Assemblage from Warner Valley, Oregon

Although common in the northern Great Basin, foliate points sometimes referred to as Cascade points are generally regarded as poor temporal markers because they are found in early, middle, and even late Holocene contexts. It is unclear whether this broad timespan is a function of prolonged use of the point form, later groups recycling discarded artifacts, or a combination of both. We review the spatial and temporal distribution of foliate points in the northern Great Basin and present new data derived from work at a stratified rockshelter in Oregons Warner Valley. There, we have uncovered foliate projectile points that meet the original definition and more recent refinements of the Cascade point type associated with a late early Holocene and middle Holocene occupation. We present technological and source provenance data for the points and the associated lithic assemblage and reconstruct how prehistoric foragers used the rockshelter.

The Surface Paleoindian Record of Northern Warner Valley, Oregon, and Its Bearing on the Temporal and Cultural Separation of Clovis and Western Stemmed Points in the Northern Great Basin

Abstract The chronological and technological relationships between Clovis and Western Stemmed Tradition (WST) projectile points in the Great Basin are unclear. There are no dated and stratified sites containing both point types. We present data from Oregons Warner Valley, where a rich Paleoindian surface record associated with dated landforms and differences in raw materials represented within each technology allow us to evaluate current hypotheses regarding Clovis and WST points. Our results provide little support for the hypothesis that Clovis and WST points were initially components of the same lithic toolkit in the northern Great Basin. Instead, we suggest that the technologies were separated by a narrow period of time or that two cultural traditions existed during the terminal Pleistocene in the northern Great Basin.

The Age and Origin of Olivella Beads from Oregon’s LSP-1 Rockshelter: The Oldest Marine Shell Beads in the Northern Great Basin

Beads manufactured frommarine shells originating along the Pacific Coast have been found at numerous sites in the western United States. Because they were conveyed across substantial distances and widely exchanged during ethnographic times, researchers generally assume that shell beads were also traded prehistorically. By examining the spatial and temporal distribution of beads, researchers have reconstructed prehistoric exchange networks. In this report, we present stable isotope data and accelerator mass spectrometer (AMS) radiocarbon dates for six Callianax (previously Olivella) biplicata beads from the LSP-1 rockshelter in southcentral Oregon. Most of the beads were deposited during the early Holocene during a series of short-term occupations and the shells used to manufacture them were procured along the northern California, Oregon, or Washington coasts.

A First Look at the Terminal Pleistocene/Early Holocene Record of Guano Valley, Oregon, USA

ABSTRACT Surface sites play a vital role in interpreting terminal Pleistocene/early Holocene (TP/EH) lifeways in the Great Basin. Two years of work in Oregon’s Guano Valley by crews from the University of Nevada, Reno have revealed a rich record of Western Stemmed Tradition occupations associated with an extensive delta system that brought freshwater into the valley from the adjacent tablelands. To date, we have recorded nearly 700 diagnostic TP/EH artifacts within the relatively small delta, making it one of the densest concentrations of Paleoindian artifacts in the region. This paper presents preliminary results from our archaeological and geomorphological investigations in Guano Valley as well as an extensive toolstone source provenance analysis.

Carbon and Oxygen Isotope Composition of Early Holocene Olivella Shell Beads from the Northwest Coast, USA

Archaeological investigations of the age and origins of marine shell beads are important for understanding the emergence and maintenance of long-distance trade networks in prehistory. In this paper we expand upon and re-examine the incremental carbon (C and δC) and oxygen (δO) isotope data from two Olivella biplicata shell beads from the LSP-1 Rockshelter, Oregon, USA, to address two common problems in dating marine shell trade goods: (1) the source region is large, adding to uncertainty regarding the appropriate specification of ΔR; and (2) the C activity within individual specimens is variable. Although this combination of factors severely limits the dating precision that is possible, we recommend a sampling and calibration approach that accounts for these added sources of uncertainty and minimizes the loss of precision. We recommend (1) sequential sampling in order to quantify the range of variability in C within shells; (2) a Bayesian calibration procedure that models the C dates as an ontogenetic sequence, in this case constrained by stable isotope sclerochronology; and (3) specifying ΔR in a manner that accounts for the full range of possible reservoir offsets in the source region.