A 4,500‐Year‐Long Record of Southern Rocky Mountain Dust Deposition

Dust emissions from southwestern North America (Southwest) impact human health and water resources. Whereas a growing network of regional dust reconstructions characterizes the long‐term natural variability of dustiness in the Southwest, short‐term fluctuations remain unexplored. We present a 4.5‐millennia near‐annual record of dust mass accumulation rates from the southern Rocky Mountains, CO. Using microscanning X‐ray fluorescence and a geochemical end‐member mixing model, the record confirms dust increased with human disturbance beginning around 1880 CE, reversing a long‐term decreasing trend potentially related to changes in effective moisture, wind, and vegetation. However, increases in dust mass accumulation rates do not correspond to years or periods of drought, as characterized by tree rings. This result suggests sediment supply and transport mechanisms have a strong influence on dust deposition. The record shows the Southwest is naturally prone to dustiness; however, human disturbances have a large influence on dust emissions, which can be mitigated by changing land use.Plain Language SummaryWe use a sediment record to characterize the long‐term naturally driven changes in dust deposition over the past 4.5 millennia. The record shows a long‐term trend toward decreasing dust deposition, which was reversed with human‐induced land disturbance beginning in the middle nineteenth century. The long‐term trend may be related to effective moisture, wind, and vegetation. Nonetheless, there appears to be little relationship between known drought events and increased dust deposition, suggesting the controls on dust deposition include factors such as sediment source and transport mechanisms acting independently of drought.Key PointsA new 4,500‐year‐long record of natural dust deposition shows a long‐term decreasing trendDrought variability, as characterized by tree rings, is not closely linked with dust mass accumulationHuman disturbance substantially increased dust deposition since 1880 CEPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151372/1/grl59278.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151372/2/grl59278_am.pd

Survival of Late Pleisticene Hunter-gatherer ancestry in the Iberian Peninsula

The Iberian Peninsula in southwestern Europe represents an important test case for the study of human population movements during prehistoric periods. During the Last Glacial Maximum (LGM), the peninsula formed a periglacial refugium for hunter-gatherers (HGs) and thus served as a potential source for the re-peopling of northern latitudes. The post-LGM genetic signature was previously described as a cline from Western HG (WHG) to Eastern HG (EHG), further shaped by later Holocene expansions from the Near East and the North Pontic steppes. Western and central Europe were dominated by ancestry associated with the 14,000-year-old individual from Villabruna, Italy, which had largely replaced earlier genetic ancestry, represented by 19,000-15,000-year-old individuals associated with the Magdalenian culture. However, little is known about the genetic diversity in southern European refugia, the presence of distinct genetic clusters, and correspondence with geography. Here, we report new genome-wide data from 11 HGs and Neolithic individuals that highlight the late survival of Paleolithic ancestry in Iberia, reported previously in Magdalenian-associated individuals. We show that all Iberian HGs, including the oldest, a 19,000-year-old individual from El Mirón in Spain, carry dual ancestry from both Villabruna and the Magdalenian-related individuals. Thus, our results suggest an early connection between two potential refugia, resulting in a genetic ancestry that survived in later Iberian HGs. Our new genomic data from Iberian Early and Middle Neolithic individuals show that the dual Iberian HG genomic legacy pertains in the peninsula, suggesting that expanding farmers mixed with local HGs

Clinical pharmacogenomic testing of KRAS, BRAF and EGFR mutations by high resolution melting analysis and ultra-deep pyrosequencing

BACKGROUND: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. METHODS: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform. RESULTS: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations. CONCLUSIONS: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.This work was supported by grants from Spanish Health Ministry (FIS) network RIRAAF (RD 07/0064).Ye

Releyendo el fenómeno de la neolitización en el Bajo Aragón a la luz de la excavación del Cingle de Valmayor XI (Mequinenza, Zaragoza)

Este trabajo presenta los resultados preliminares obtenidos en la excavación del Cingle de Valmayor XI, desarrollada dentro del proyecto de investigación ‘Los caminos del Neolítico’. A través del análisis de las dataciones radiocarbónicas y de una detallada lectura estratigráfica se han podido establecer tres horizontes de ocupación diferentes con cronologías que corresponden a distintos momentos del vi milenio cal bc. Se ofrece una descripción general de los eventos arqueológicos documentados en cada una de estas fases, así como de gran parte del material recuperado –cerámica, lítica, industria ósea, elementos de adorno, fauna y restos carpológicos–. Por otra parte, a la luz de las nuevas dataciones presentadas, se propone una revisión del fenómeno de la neolitización en la región del Bajo Aragón y, por extensión, en todo el valle del Ebro; también se cuestiona la identificación de contextos como propios de economías productoras simplemente a través de la presencia de ciertos elementos materiales considerados tradicionalmente como ‘marcadores neolíticos’, sin que existan variaciones con respecto a las estrategias subsistenciales o de explotación del territorio

A Multiproxy Database of Western North American Holocene Paleoclimate Records

Holocene climate reconstructions are useful for understanding the diverse features and spatial heterogeneity of past and future climate change. Here we present a database of western North American Holocene paleoclimate records. The database gathers paleoclimate time series from 184 terrestrial and marine sites, including 381 individual proxy records. The records span at least 4000 of the last 12 000 years (median duration of 10 725 years) and have been screened for resolution, chronologic control, and climate sensitivity. Records were included that reflect temperature, hydroclimate, or circulation features. The database is shared in the machine readable Linked Paleo Data (LiPD) format and includes geochronologic data for generating site-level time-uncertain ensembles. This publicly accessible and curated collection of proxy paleoclimate records will have wide research applications, including, for example, investigations of the primary features of ocean-atmospheric circulation along the eastern margin of the North Pacific and the latitudinal response of climate to orbital changes. The database is available for download at https://doi.org/10.6084/m9.figshare.12863843.v1 (Routson and McKay, 2020)

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between similar to 10,500 and similar to 400 years ago. We date the most recent common ancestor of all HBV lineages to between similar to 20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for similar to 4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic.Molecular Technology and Informatics for Personalised Medicine and Healt

Late Holocene tephrostratigraphy from Cajas National Park, southern Ecuador

Lakes located downwind of active volcanoes serve as a natural repository for volcanic ash (tephra) produced during eruptive events. In this study, sediment cores from four lakes in Cajas National Park, southern Ecuador, situated approximately 200 km downwind of active volcanoes in the Northern Andes Volcanic Zone, were analysed to document the regional history of tephra fall extending back around 3000 a cal BP. The ages of the lacustrine sedimentary sequences were constrained using a total of 20 AMS radiocarbon ages on plant remains. The tephra layers were correlated among the lakes based on their radiocarbon age, elemental composition, colour, and grain morphology. We found five unique tephra layers, each at least 0.2 cm thick, and further constrained their ages by combining the results from two age-depth modelling approaches (clam and rbacon). The tephra layers were deposited 3034 ± 621, 2027 ± 41, 1557 ± 177, 733 ± 112, and 450 ± 70 a cal BP. The ages of all but the youngest tephra layer overlap with those of known eruptions from Tungurahua. Some tephra layers are missing as macroscopic layers in several cores, with only two of the five tephra layers visible in the sediment of three lakes. Likewise, previous studies of lake sediment cores from the region are missing the four youngest tephra layers, further highlighting the need to sample multiple lakes to reconstruct a comprehensive history of fallout events. The newly documented stratigraphic marker layers will benefit future studies of lake sediments in Cajas National Park

Inhibition of adult hippocampal neurogenesis disrupts contextual learning but spares spatial working memory, long-term conditional rule retention and spatial reversal

Neurogenesis in the adult dentate gyrus (DG) of the hippocampus has been implicated in neural plasticity and cognition but the specific functions contributed by adult-born neurons remain controversial. Here, we have explored the relationship between adult hippocampal neurogenesis and memory function using tasks which specifically require the participation of the DG. In two separate experiments several groups of rats were exposed to fractionated ionizing radiation (two sessions of 7 Gy each on consecutive days) applied either to the whole brain or focally, aiming at a region overlying the hippocampus. The immunocytochemical assays showed that the radiation significantly reduced the expression of doublecortin (DCX), a marker for immature neurons, in the dorsal DG. Ultrastructural examination of the DG region revealed disruption of progenitor cell niches several weeks after the radiation. In the first experiment, whole-brain and focal irradiation reduced DCX expression by 68% and 43%, respectively. Whole-brain and focally-irradiated rats were unimpaired compared with control rats in a matching-to-place (MTP) working memory task performed in the T-maze and in the long-term retention of the no-alternation rule. In the second experiment, focal irradiation reduced DCX expression by 36% but did not impair performance on (1) a standard non-matching-to-place (NMTP) task, (2) a more demanding NMTP task with increasingly longer within-trial delays, (3) a long-term retention test of the alternation rule and (4) a spatial reversal task. However, rats irradiated focally showed clear deficits in a >purely> contextual fear-conditioning task at short and long retention intervals. These data demonstrate that reduced adult hippocampal neurogenesis produces marked deficits in the rapid acquisition of emotionally relevant contextual information but spares spatial working memory function, the long-term retention of acquired spatial rules and the ability to flexibly modify learned spatial strategies. © 2009 IBRO.Peer Reviewe

A multiproxy database of western North American Holocene paleoclimate records

Holocene climate reconstructions are useful for understanding the diverse features and spatial heterogeneity of past and future climate change. Here we present a database of western North American Holocene paleoclimate records. The database gathers paleoclimate time series from 184 terrestrial and marine sites, including 381 individual proxy records. The records span at least 4000 of the last 12 000 years (median duration of 10 725 years) and have been screened for resolution, chronologic control, and climate sensitivity. Records were included that reflect temperature, hydroclimate, or circulation features. The database is shared in the machine readable Linked Paleo Data (LiPD) format and includes geochronologic data for generating site-level time-uncertain ensembles. This publicly accessible and curated collection of proxy paleoclimate records will have wide research applications, including, for example, investigations of the primary features of ocean-atmospheric circulation along the eastern margin of the North Pacific and the latitudinal response of climate to orbital changes. The database is available for download at https://doi.org/10.6084/m9.figshare.12863843.v1 (Routson and McKay, 2020). Water Resource