Chronology and Ecology of Late Pleistocene Megafauna in the Northern Willamette Valley, Oregon

This study is an investigation of the timing of extinction of late Pleistocene, large bodied mammalian herbivores (megafauna) and of the environment in which they lived. The demise of the megafauna near the end of the Pleistocene remains unexplained. Owing to potential human involvement in the extinctions, archaeologists have been particularly concerned to understand the causes for faunal losses. Our current lack of understanding of the timing and the causes of the extinctions in North America may result from a deficiency in understanding the histories of each individual species of extinct animal on a local level. Detailed regional chronologies of fauna are necessary for comparison with paleoenvironmental and archaeological data to help sort out causes for extinction. The Willamette Valley of western Oregon has long been noted for finds of megafauna, though records have not been synthesized since the early 20th century and these materials have remained largely unstudied. In this thesis, I first create a catalog of extinct megafauna recovered from the Willamette Valley. Next, using material from the northern valley, I employ AMS radiocarbon dating, stable isotope δ¹³C and δ¹⁵N analyses, and gross inferences based on the dietary specializations and habitat preferences of taxa in order to reconstruct environments and to develop a local chronology of events that is then arrayed against archaeological and paleoenvironmental data. The results of this study indicate that megafaunal populations in the northern Willamette Valley were contemporaneous with the earliest known human populations of the Pacific Northwest, as well as later populations associated with the Clovis Paleoindian Horizon. Consistent with the overkill hypothesis, radiocarbon ages span the length of the Clovis window, but no ages are younger than Clovis. Moreover, all radiocarbon ages are older than or contemporaneous to the onset of the Younger Dryas Stadial. No age ranges fall exclusively within the Younger Dryas. Comparison of megafaunal ages and paleoenvironmental records support the view that climate change contributed to local animal population declines. Prior to ~13,000 cal BP, the Willamette Valley was an open environment; herbivores mainly consumed C₃ vegetation. The timing of the loss of megafauna coincides with increased forested conditions as indicated by regional paleoenvironmental reconstruction. As the timing of megafaunal decline correlates with Clovis, the onset of the Younger Dryas, and increased forested conditions, it is not possible with the data currently available to distinguish the cause of extinction in the Willamette Valley. The age ranges of the fauna coupled with taphonomic and geologic context indicate that the fauna are autochthonous to the Willamette Valley; they do not represent ice rafted carcasses or isolated skeletal elements transported from elsewhere during late Pleistocene glacial outburst floods

Telomerecat: A ploidy-agnostic method for estimating telomere length from whole genome sequencing data.

Telomere length is a risk factor in disease and the dynamics of telomere length are crucial to our understanding of cell replication and vitality. The proliferation of whole genome sequencing represents an unprecedented opportunity to glean new insights into telomere biology on a previously unimaginable scale. To this end, a number of approaches for estimating telomere length from whole-genome sequencing data have been proposed. Here we present Telomerecat, a novel approach to the estimation of telomere length. Previous methods have been dependent on the number of telomeres present in a cell being known, which may be problematic when analysing aneuploid cancer data and non-human samples. Telomerecat is designed to be agnostic to the number of telomeres present, making it suited for the purpose of estimating telomere length in cancer studies. Telomerecat also accounts for interstitial telomeric reads and presents a novel approach to dealing with sequencing errors. We show that Telomerecat performs well at telomere length estimation when compared to leading experimental and computational methods. Furthermore, we show that it detects expected patterns in longitudinal data, repeated measurements, and cross-species comparisons. We also apply the method to a cancer cell data, uncovering an interesting relationship with the underlying telomerase genotype

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Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

The Radiocarbon Record of the Western Stemmed Tradition on the Southern Columbia Plateau of Western North America

The late Pleistocene–early Holocene archaeological record of the interior Pacific Northwest is dominated by what has been regionally referred to as the Western Stemmed Tradition (WST). While various efforts have attempted to clarify the chronology of this tradition, these have largely focused on data from the Great Basin and have been disproportionately preoccupied with establishing the beginning of the tradition due to its temporal overlap with Clovis materials. Specifically focusing on the Columbia Plateau, we apply a series of Bayesian chronological models to create concise estimates of the most likely beginning, end, and span of the WST. We then further explore its chronology by modeling its temporal span under various parameters and criteria so as to better identify places in the chronology that need further work and those that are robust regardless of data iteration. Our analysis revealed four major findings: (1) WST conservatively dates between 13,000 and 11,000 cal BP, likely extending to ~13,500 cal BP; (2) the most problematic period for WST is its termination; (3) the WST is incredibly long-lived compared to roughly contemporary Paleoindian traditions; and (4) the WST was seemingly unaffected by the onset of the Younger Dryas

Chronology and Ecology of Late Pleistocene Megafauna in the Northern Willamette Valley, Oregon

Since the mid-19th century, western Oregon\u27s Willamette Valley has been a source of remains from a wide variety of extinct megafauna. Few of these have been previously described or dated, but new chronologic and isotopic analyses in conjunction with updated evaluations of stratigraphic context provide substantial new information on the species present, timing of losses, and paleoenvironmental conditions. Using subfossil material from the northern valley, we use AMS radiocarbon dating, stable isotope (δ13C and δ15N) analyses, and taxonomic dietary specialization and habitat preferences to reconstruct environments and to develop a local chronology of events that we then compare with continental and regional archaeological and paleoenvironmental data. Analysis of twelve bone specimens demonstrates the presence of bison, mammoth, horse, sloth, and mastodon from ~15,000–13,000 cal yr BP. The latest ages coincide with changing regional climate corresponding to the onset of the Younger Dryas. It is suggested that cooling conditions led to increased forest cover, and, along with river aggradation, reduced the area of preferred habitat for the larger bodied herbivores, which contributed to the demise of local megafauna. Archaeological evidence for megafauna–human interactions in the Pacific Northwest is scarce, limiting our ability to address the human role in causing extinction

Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)

An amendment to this paper has been published and can be accessed via a link at the top of the paper