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Mapping the human record in the British early Palaeolithic: evidence from the Solent River system
The lithic record from the Solent River and its tributaries is re-examined in the light of recent interpretations about the changing demography of Britain during the Lower and early Middle Palaeolithic. Existing models of the terrace stratigraphies in the Solent and its tributary areas are reviewed and the corresponding archaeological record (specifically handaxes) for each terrace is assessed to provide models for the relative changes in human occupation through time. The Bournemouth area is studied in detail to examine the effects of quarrying and urbanisation on collection history and on the biases it introduces to the record. In addition, the effects of reworking of artefacts from higher into lower terraces are assessed, and shown to be a significant problem. Although there is very little absolute dating available for the Solent area, a cautious interpretation of the results from these analyses would suggest a pre-Marine Isotope Stage (MIS) 12 date for the first appearance of humans, a peak in population between MIS 12 and 10, and a decline in population during MIS 9 and 8. Owing to poor contextual data and small sample sizes, it is not clear when Levallois technology was introduced. This record is compared and contrasted to that from the Thames Valley. It is suggested that changes in the palaeogeography of Britain, in particular land connections to the continent, might have contributed to differences in the archaeological records from the Solent and Thames regions
Objectifying processes: The use of geometric morphometrics and multivariate analyses on Acheulean tools
Nowadays, the fruitful discussion regarding the morphological variability of handaxes during the Middle Pleistocene has reached a decisive moment with the use of more accurate statistical methods, such as geometric morphometrics (GM) and multivariate analyses (MA). This paper presents a preliminary methodological approach for checking the utility of these new approaches on the analysis of the tools’ shape. It goes beyond the simple description of morphology and isolates the variables which define the final morphology of a tool. We compared two Middle Pleistocene sites, Boxgrove and Swanscombe, which are morphologically very different. Then, we applied the GM analysis on 1) 2D images, with two semi-landmark distributions: 28 semi-landmarks, specially concentrated on the tip and butt, and 60 equally spaced points; and 2) on 3D models using new software (AGMT3-D Software) including 5000 semi-landmarks. The more points used to define the tool’s outline, the more accurate will be the interpretation of the variables affecting shape. On the other hand, if the semi-landmarks are localized on specific sectors of the tool, a bias is created, by concentrating on those sectors, rather than the general tool shape. The 3D models offer a new dimension on the shape analysis, as their results mean the combination of plan-shape, profile-shape and the tool’s topography
Ex Vivo Modeling of Chemical Synergy in Prenatal Kidney Cystogenesis
Cyclic adenosine monophosphate (cAMP) drives genetic polycystic kidney disease (PKD) cystogenesis. Yet within certain PKD families, striking differences in disease severity exist between affected individuals, and genomic and/or environmental modifying factors have been evoked to explain these observations. We hypothesized that PKD cystogenesis is accentuated by an aberrant fetal milieu, specifically by glucocorticoids. The extent and nature of cystogenesis was assessed in explanted wild-type mouse embryonic metanephroi, using 8-Br-cAMP as a chemical to mimic genetic PKD and the glucocorticoid dexamethasone as the environmental modulator. Cysts and glomeruli were quantified by an observer blinded to culture conditions, and tubules were phenotyped using specific markers. Dexamethasone or 8-Br-cAMP applied on their own produced cysts predominantly arising in proximal tubules and descending limbs of loops of Henle. When applied together, however, dexamethasone over a wide concentration range synergized with 8-Br-cAMP to generate a more severe, glomerulocystic, phenotype; we note that prominent glomerular cysts have been reported in autosomal dominant PKD fetal kidneys. Our data support the idea that an adverse antenatal environment exacerbates renal cystogenesis
Making a U-turn on the Purfleet Interchange: Stone Tool Technology in Marine Isotope Stage 9 Britain and the Emergence of the Middle Palaeolithic in Europe
This paper re-examines earlier Palaeolithic core technology from British sites assigned to MIS 11, 9, and 7 using primarily a châine opératoire approach, with the objective of better understanding the earliest occurrence and distribution of Levallois and other prepared-core technologies across the Old World. Contrary to previous interpretations (White and Ashton in Current Anthropology, 44: 598–609, 2003), we find no evidence for a true Levallois concept in MIS 11 or MIS 9 in Britain. Cores previously described as ‘simple prepared cores’ or ‘proto-Levallois’ cores show neither evidence of core management nor predetermination of the resulting flakes. They can instead be explained as the coincidental result of a simpler technological scheme aimed at exploiting the largest surface area of a core, thereby maximising the size of the flakes produced from it. This may be a more widespread practice, or a local solution derived from existing principles. Levallois appears fully formed in Britain during terminal MIS 8/initial MIS 7. Consequently, Britain does not provide evidence for an in situ evolution of Levallois, rather we argue it was introduced by new settlers after a glacial abandonment: the solution to the emergence and significance of Levallois lies in southern Europe, the Levant and Africa
Longitudinal Metabolomic Profiling of Amino Acids and Lipids across Healthy Pregnancy
Pregnancy is characterized by a complexity of metabolic processes that may
impact fetal development and ultimately, infant health outcomes. However, our
understanding of whole body maternal and fetal metabolism during this critical
life stage remains incomplete. The objective of this study is to utilize
metabolomics to profile longitudinal patterns of fasting maternal metabolites
among a cohort of non-diabetic, healthy pregnant women in order to advance our
understanding of changes in protein and lipid concentrations across gestation,
the biochemical pathways by which they are metabolized and to describe
variation in maternal metabolites between ethnic groups. Among 160 pregnant
women, amino acids, tricarboxylic acid (TCA) cycle intermediates, keto-bodies
and non-esterified fatty acids were detected by liquid chromatography coupled
with mass spectrometry, while polar lipids were detected through flow-injected
mass spectrometry. The maternal plasma concentration of several essential and
non-essential amino acids, long-chain polyunsaturated fatty acids, free
carnitine, acetylcarnitine, phosphatidylcholines and sphingomyelins
significantly decreased across pregnancy. Concentrations of several TCA
intermediates increase as pregnancy progresses, as well as the keto-body
β-hydroxybutyrate. Ratios of specific acylcarnitines used as indicators of
metabolic pathways suggest a decreased beta-oxidation rate and increased
carnitine palmitoyltransferase-1 enzyme activity with advancing gestation.
Decreasing amino acid concentrations likely reflects placental uptake and
tissue biosynthesis. The absence of any increase in plasma non-esterified
fatty acids is unexpected in the catabolic phase of later pregnancy and may
reflect enhanced placental fatty acid uptake and utilization for fetal tissue
growth. While it appears that energy production through the TCA cycle
increases as pregnancy progresses, decreasing patterns of free carnitine and
acetylcarnitine as well as increased carnitine palmitoyltransferase-1 rate and
β-hydroxybutyrate levels suggest a concomitant upregulation of ketogenesis to
ensure sufficient energy supply in the fasting state. Several differences in
metabolomic profiles between Hispanic and non-Hispanic women demonstrate
phenotypic variations in prenatal metabolism which should be considered in
future studies
Renal Action of Acute Chloroquine and Paracetamol Administration in the Anesthetized, Fluid-Balanced Rat
Prolonged low flow reduces reactive hyperemia and augments low flow mediated constriction in the brachial artery independent of the menstrual cycle
© 2013 Rakobowchuk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Non-invasive forearm ischemia-reperfusion injury and low flow induced vascular dysfunction models provide methods to
evaluate vascular function. The role of oestrogen, an endogenous anti-oxidant on recovery from ischemia-reperfusion injury
has not been evaluated nor has the impact of prolonged low flow on vascular function been established. Eight healthy women (33610 yr) attended the lab during the follicular, ovulatory and mid-luteal phases of their menstrual cycles. After 30 minutes of rest, brachial artery vascular function was assessed by ultrasound measurements of diameter changes during 5 minutes of forearm ischemia and 3 minutes after. Subsequently, a 20-minute forearm ischemia period was completed. Further, vascular function assessments were completed 15, 30 and 45 minutes into recovery. Flow-mediated dilation, lowflow-mediated constriction, and reactive hyperaemia proximal to the area of ischemia were determined. Flow-mediated dilation was reduced at 15 minutes of recovery but recovered at 30 and 45 minutes (PRE: 7.161.0%, POST15:4.560.6%, POST30:5. 560.7% POST45:5.960.4%, p,0.01). Conversely, low-flow mediated constriction increased (PRE: 21.360.4%, POST15: 23.360.6%, POST30: 22.560.5% POST45: 21.560.12%, p,0.01). Reactive hyperaemia was reduced throughout recovery (p,0.05). Data were unaffected by menstrual phase. Prolonged low flow altered vascular function and may relate as much to increased vasoconstriction as with decreased vasodilation. Reductions in anterograde shear and greater retrograde shear likely modulate the brachial artery response, but the reduced total shear also plays an important role. The data suggest substantial alterations in vascular function proximal to areas of ischemia with potential clinical implications following reperfusion.British Heart Foundation (PG/08/060/25340),a Physiological Society summer studentship to SG, and a Wellcome Trust Vacation Studentship to EP
Extreme glacial cooling likely led to hominin depopulation of Europe in the Early Pleistocene
The oldest known hominin remains in Europe [~1.5 to ~1.1 million years ago (Ma)] have been recovered from Iberia, where paleoenvironmental reconstructions have indicated warm and wet interglacials and mild glacials, supporting the view that once established, hominin populations persisted continuously. We report analyses of marine and terrestrial proxies from a deep-sea core on the Portugese margin that show the presence of pronounced millennial-scale climate variability during a glacial period ~1.154 to ~1.123 Ma, culminating in a terminal stadial cooling comparable to the most extreme events of the last 400,000 years. Climate envelope–model simulations reveal a drastic decrease in early hominin habitat suitability around the Mediterranean during the terminal stadial. We suggest that these extreme conditions led to the depopulation of Europe, perhaps lasting for several successive glacial-interglacial cycles
Developmental Exposure of Mice to Dioxin Promotes Transgenerational Testicular Inflammation and an Increased Risk of Preterm Birth in Unexposed Mating Partners
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, commonly known as dioxin) is a ubiquitous environmental contaminant and known endocrine disruptor. Using a mouse model, we previously found that adult female mice exposed in utero to TCDD (F1 generation) as well as multiple subsequent generations (F2-F4) exhibited reduced fertility and an increased incidence of spontaneous preterm birth. Additional studies revealed that male F1 mice with a similar in utero/developmental TCDD exposure also exhibited diminished fertility and conferred an increased risk of preterm birth to their unexposed mating partners. Herein, we extend these previous observations, reporting that reduced fertility in male F1 mice is linked to testicular inflammation which coincides with apoptosis of developing spermatocytes, sub-fertility and an increased risk of preterm birth in their unexposed mating partners. Significantly, in the absence of additional toxicant exposure, testicular inflammation and reduced fertility persisted in F2 and F3 males and their control mating partners also frequently exhibited spontaneous preterm birth. Although a steady, global decline in male fertility has been noted over the last few decades, the reasons for these changes have not been firmly established. Likewise, the PTB rate in the U.S. and other countries has paralleled industrial development, suggesting a possible relationship between environmental toxicant exposure and adverse pregnancy outcomes. Most current clinical strategies to prevent preterm birth are focused solely on the mother and have yielded limited benefits. In contrast, our studies strongly suggest that the preconception testicular health of the father is a critical determinant of pregnancy outcomes in mice. Future clinical studies should examine the potential contribution of the male to gestation length in women and whether efforts to reduce the incidence of preterm birth should be initiated in both parents prior to pregnancy
Human occupation of northern Europe in MIS 13: Happisburgh Site 1 (Norfolk, UK) and its European context
The timing, environmental setting and archaeological signatures of an early human presence in northernEurope have been longstanding themes of Palaeolithic research. In the space of 20 years, the earliestrecord of human occupation in Britain has been pushed back from 500 ka (Boxgrove) to 700 ka (Pakefield)and then to >800 ka (Happisburgh Site 3). Other sites also contribute to this record of humanoccupation; a second locality at Happisburgh, referred to as Site 1, attests to human presence at around500 ka (MIS 13). This paper provides the first comprehensive account of research undertaken at HappisburghSite 1 since 2000. The early human landscape and depositional environment was that of a riverfloodplain, where an active river channel, in which a grey sand was deposited, was abandoned, forming afloodplain lake, with marginal marsh/swamp environments, which was infilled with organic mud. Thissuccession is sealed by Middle Pleistocene glacial deposits. An assemblage of 199 flint flakes, flake toolsand cores was recovered from the grey sand and organic mud. The evidence from Happisburgh Site 1 isplaced in the context of the wider British and European MIS 13 record. The growing evidence for asignificant dispersal of humans into northern Europe around 500 ka raises critical questions concerningthe environmental conditions under which this took place. We also consider the evolutionary andbehavioural changes in human populations that might have enabled the more widespread and persistentperiod of human presence in northern Europe at this time.</p
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