Excavations in the Acheulean Levels at the Earlier Stone Age site of Canteen Koppie, Northern Province, South Africa

The fluvial gravels of the river Vaal in South Africa have long been known as a source for Earlier Stone Age (ESA) artefacts. Most were discovered through the open cast mining for diamonds that has left very little in situ fluvial sediment remaining today. The site of Canteen Koppie is an internationally famous location with a reputation for prolific Acheulean artefacts, especially handaxes and the enigmatic prepared core and Levallois-like technology known as Victoria West. Our understanding of this site, and most other Vaal locations, is almost solely based on highly selected artefact collections. Here, we report on the first controlled excavations ever to be conducted at Canteen Koppie. The deposits are likely to date to the Early and Middle Pleistocene, and our excavations sample the full depth of the stratigraphic sequence. The lower units, first identified in these excavations, add a considerable time depth to the Acheulean occupation of the site, making this the longest chrono-stratigraphic sequence in South Africa to our knowledge. Given the current international interest in the origins of Levallois/prepared core technology (PCT), its occurrence in Unit 2b Upper, and its presence alongside Victoria West technology in Unit 2a has significant implications for debates on the role of Victoria West in the origins of PCT. From the Canteen Koppie evidence, Levallois and Victoria West are clearly rooted in the Acheulean.RésuméOn sait depuis longtemps que les graviers fluviaux de la rivière Vaal en Afrique du Sud sont une source d'artefacts de l'âge de pierre ancien (ESA). Ils ont été découverts pour la plupart au cours de l'extraction de diamants dans des mines à ciel ouvert, ce qui fait qu'il ne reste que très peu de sédiments fluviaux in situ aujourd'hui. Le site de Canteen Koppie est un lieu célèbre dans le monde entier, réputé pour l'abondance de ses artefacts acheuléens, en particulier les bifaces et la technologie enigmatique des nucléus préparés semblable au Levallois connue sous le nom de Victoria West. Notre compréhension de ce site, et de la plupart des autres lieux du Vaal, repose presque uniquement sur des collections d'artefacts extrèmement sélectionnés. Ici, nous faisons le compte rendu des premières fouilles contrôlées jamais menées à Canteen Koppie. Les dépôts datent probablement du début et du milieu du pléistocène et nos excavations prennent des échantillons de l'ensemble de la profondeur de la séquence stratigraphique. Les unités les plus basses, identifiées pour la première fois au cours de ces fouilles, ajoutent une profondeur temporelle considérable à l'occupation acheuléenne du site, elles en font la plus longue séquence chronostratigraphique d'Afrique du Sud à notre connaissance. Etant donné l'actuel intérêt international pour les origines de la technologie Levallois/nucléus préparé (PCT), sa rencontre dans l'Unité 2b Supérieure, et sa présence à côté de la technologie Victoria West dans l'Unité 2a ont d'importantes implications pour les débats sur le rôle de Victoria West dans les origines de PCT. D'après les témoignages de Canteen Koppie,il est clair que Levallois et Victoria West ont leurs racines dans l'acheuléen.ZusammenfassungDie Schwemmkiese des Flusses Vaal in Südafrika sind seit langem als Fundort altsteinzeitlicher Artefakte bekannt. Meist wurden sie während des Diamanttagebaus gefunden, durch den heute sehr wenige Sedimente noch in situ erhalten sind. Der Fundplatz Canteen Koppie ist ein international weithin bekannter Ort, der berühmt ist für reiche Artefakte des Acheuléen, insbesondere Faustkeile und die rätselhafte, an Levallois erinnernde Kerntechnologie, die als Victoria West bekannt ist. Unser Verständnis dieses Fundplatzes, wie auch der meisten anderen Orte entlang des Vaal, basiert fast ausschließlich auf einer eng begrenzten Auswahl von Artefaktensembles. Hier berichten wir über die erste systematische Ausgrabung, die je in Canteen Koppie durchgeführt wurde. Die Schichten datieren wahrscheinlich ins Früh- und Mittelpleistozän; unsere Grabungen erfassten die gesamte Ausdehnung der stratigraphischen Abfolge. Die unteren Einheiten, die zuerst in den Grabungen identifiziert werden konnten, vergrößern die zeitliche Tiefe der Acheuléen-zeitlichen Nutzung des Ortes erheblich, wodurch dies nach unserem Wissen die längste chrono-stratigraphische Sequenz in Südafrika ist. Aufgrund des gegenwärtigen Interesses an den Ursprüngen der Levallois-Technik bzw. Technik der vorbereiteten Kerne (prepared core technology, PCT) ist ihr Auftreten in Unit 2b Upper und das Vorhandensein in Unit 2a, gemeinsam mit Victoria West-Technologie, von besonderer Bedeutung für die Diskussionen über die Rolle, die Victoria West bei der Entstehung von PCT spielt. Anhand der Beobachtungen in Canteen Koppie können wir festhalten, dass Levallois und Victoria West sicher im Acheuléen wurzeln.RésuménLas gravas fluviales del Rio Vaal en Sudáfrica han sido conocidas desde antiguo como una fuente de artefactos de la Primera Edad de Piedra (ESA en su acrónimo inglés). La mayoría han sido descubiertos al buscar diamantes al aire libre que ha dejado muy pocos sedientos fluviales in situ hoy en día. El yacimiento de Canteen Koppie es un emplazamiento internacionalmente famoso con una reputación de ser especialmente prolijo en artefactos del Achelense, especialmente hachas de mano y los enigmáticos núcleos preparados y la tecnología de estilo Levallois conocida como ‘Victoria West’. Nuestra comprensión de este yacimiento, y de la mayoría de los otros yacimientos en el Vaal, se basa casi exclusivamente en una serie de colecciones de artefactos altamente seleccionados. Este trabajo informa sobre las primeras excavaciones controladas jamás realizadas en Canteen Koppie. Los depósitos datan más probablemente al Pleistoceno Alto y Medio, y nuestra excavación cató toda la profundidad de la secuencia estratigráfica. Las capas más bajas, identificadas por primera vez en esta excavación, añaden una considerable profundidad temporal a la ocupación Achelense del yacimiento, y lo convierten, que sepamos, en la secuencia crono-estratigráfica más larga de Sudáfrica. Dado el interés internacional actual en los orígenes de la tecnología Levallois/núcleos preparados (PCT en su acrónimo inglés), su aparición en el Nivel 2b Superior, y su presencia junto con la tecnología Victoria West en el Nivel 2a tiene significativas consecuencias para los debates sobre el papel de Victoria West en los orígenes del PCT. Por lo que indica la evidencia de Canteen Koppie, las tecnologías Levallois y Victoria West están ambas claramente enraizadas en el Achelense

Positioning of bone marrow hematopoietic and stromal cells relative to blood flow in vivo: Serially reconstituting hematopoietic stem cells reside in distinct nonperfused niches

Hematopoietic stem cell (HSC) niches have been reported at the endosteum or adjacent to bone marrow (BM) vasculature. To investigate functional attributes of these niches, mice were perfused with Hoechst 33342 (Ho) in vivo before BM cell collection in presence of pump inhibitors and antibody stained. We report that the position of phenotypic HSCs, multipotent and myeloid progenitors relative to blood flow, follows a hierarchy reflecting differentiation stage, whereas mesenchymal stromal cells are perivascular. Furthermore, during granulocyte colony-stimulating factor-induced mobilization, HSCs migrated closer to blood flow, whereas stromal cells did not. Interestingly, phenotypic Lin(-)Sca1(+)KIT(+) CD41(+)CD48(+)CD150(+) HSCs segregated into 2 groups (Honeg or Homed), based on degree of blood/Ho perfusion of their niche. HSCs capable of serial transplantation and long-term bromodeoxyuridine label retention were enriched in Ho-neg HSCs, whereas Ho-med HSCs cycled more frequently and only re-constituted a single host. This suggests that the most potent HSC niches are enriched in locally secreted factors and low oxygen tension due to negligible blood flow. Importantly, blood perfusion of niches correlates better with HSC function than absolute distance from vasculature. This technique enables prospective isolation of serially reconstituting HSCs distinct from other less potent HSCs of the same phenotype, based on the in vivo niche in which they reside. (Blood. 2010; 116(3): 375-385

Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium

Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting.; We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults.; rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism.; This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways

Bronchopulmonary Dysplasia and Perinatal Characteristics Predict 1-Year Respiratory Outcomes in Newborns Born at Extremely Low Gestational Age: A Prospective Cohort Study

OBJECTIVE:To assess the utility of clinical predictors of persistent respiratory morbidity in extremely low gestational age newborns (ELGANs). STUDY DESIGN:We enrolled ELGANs (<29 weeks' gestation) at ≤7 postnatal days and collected antenatal and neonatal clinical data through 36 weeks' postmenstrual age. We surveyed caregivers at 3, 6, 9, and 12 months' corrected age to identify postdischarge respiratory morbidity, defined as hospitalization, home support (oxygen, tracheostomy, ventilation), medications, or symptoms (cough/wheeze). Infants were classified as having postprematurity respiratory disease (PRD, the primary study outcome) if respiratory morbidity persisted over ≥2 questionnaires. Infants were classified with severe respiratory morbidity if there were multiple hospitalizations, exposure to systemic steroids or pulmonary vasodilators, home oxygen after 3 months or mechanical ventilation, or symptoms despite inhaled corticosteroids. Mixed-effects models generated with data available at 1 day (perinatal) and 36 weeks' postmenstrual age were assessed for predictive accuracy. RESULTS:Of 724 infants (918 ± 234 g, 26.7 ± 1.4 weeks' gestational age) classified for the primary outcome, 68.6% had PRD; 245 of 704 (34.8%) were classified as severe. Male sex, intrauterine growth restriction, maternal smoking, race/ethnicity, intubation at birth, and public insurance were retained in perinatal and 36-week models for both PRD and respiratory morbidity severity. The perinatal model accurately predicted PRD (c-statistic 0.858). Neither the 36-week model nor the addition of bronchopulmonary dysplasia to the perinatal model improved accuracy (0.856, 0.860); c-statistic for BPD alone was 0.907. CONCLUSION:Both bronchopulmonary dysplasia and perinatal clinical data accurately identify ELGANs at risk for persistent and severe respiratory morbidity at 1 year. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01435187