A micro-geoarchaeological view on stratigraphy and site formation processes in the Middle, Upper and Epi-Paleolithic layers of Sefunim Cave, Mt. Carmel, Israel

This paper presents a micro-geoarchaeological study carried out on the sedimentary sequence exposed at the entrance of Sefunim Cave, Israel, a sequence that spans from the Middle Paleolithic to the early Epipaleolithic periods. Using FTIR and micromorphological techniques, we investigated the stratigraphic sequence to reconstruct patterns of site use and archaeological formation processes. We identified formation processes that are common among Paleolithic caves sites in the Southern Levant, mainly the deposition of local terra rossa through colluvial sedimentation. Taphonomic disturbances of the deposits range from minimal to moderate, exhibited mainly by root and burrowing activity, but with no evidence for significant transport of archaeological materials. While the upper layers (II–III) are decalcified, the precipitation of secondary calcite results in increasing cementation of the sediments with depth in the lower layers (V–VII). We observed variation at the microscopic scale and identified an inverse correlation between human and carnivore activity throughout the layers. We observed human activity by the presence of micro-archaeological materials such as chert, bone, charcoal, rubified clay, burnt bone and shell, and wood ash. We observed carnivore activity by the presence of phosphatic grains and coprolite fragments as well as chewed and digested bones. We conclude that human activity at the site was characterized by episodes of varying intensity, based on the frequency of archaeological finds within the different layers. The alternating episodes of human and carnivore activity at Sefunim Cave may demonstrate the close-knit interactions and reciprocal relations that humans and carnivore shared at Paleolithic caves.publishedVersio

Human sterile alpha motif domain 9, a novel gene identified as down-regulated in aggressive fibromatosis, is absent in the mouse

BACKGROUND: Neoplasia can be driven by mutations resulting in dysregulation of transcription. In the mesenchymal neoplasm, aggressive fibromatosis, subtractive hybridization identified sterile alpha motif domain 9 (SAMD9) as a substantially down regulated gene in neoplasia. SAMD9 was recently found to be mutated in normophosphatemic familial tumoral calcinosis. In this study, we studied the gene structure and function of SAMD9, and its paralogous gene, SAMD9L, and examined these in a variety of species. RESULTS: SAMD9 is located on human chromosome 7q21.2 with a paralogous gene sterile alpha motif domain 9 like (SAMD9L) in the head-to-tail orientation. Although both genes are present in a variety of species, the orthologue for SAMD9 is lost in the mouse lineage due to a unique genomic rearrangement. Both SAMD9 and SAMD9L are ubiquitously expressed in human tissues. SAMD9 is expressed at a lower level in a variety of neoplasms associated with β-catenin stabilization, such as aggressive fibromatosis, breast, and colon cancers. SAMD9 and SAMD9L contain an amino-terminal SAM domain, but the remainder of the predicted protein structure does not exhibit substantial homology to other known protein motifs. The putative protein product of SAMD9 localizes to the cytoplasm. In vitro data shows that SAMD9 negatively regulates cell proliferation. Over expression of SAMD9 in the colon cancer cell line, SW480, reduces the volume of tumors formed when transplanted into immune-deficient mice. CONCLUSION: SAMD9 and SAMD9L are a novel family of genes, which play a role regulating cell proliferation and suppressing the neoplastic phenotype. This is the first report as far as we know about a human gene that exists in rat, but is lost in mouse, due to a mouse specific rearrangement, resulting in the loss of the SAMD9 gene

Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development

Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133− cells isolated from LM fluids. CD133− LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133− LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs

Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development

Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133− cells isolated from LM fluids. CD133− LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133− LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs.</p

The earliest evidence for Upper Paleolithic occupation in the Armenian Highlands at Aghitu-3 Cave

With its well-preserved archaeological and environmental records, Aghitu-3 Cave permits us to examine the settlement patterns of the Upper Paleolithic (UP) people who inhabited the Armenian Highlands. We also test whether settlement of the region between ∼39–24,000 cal BP relates to environmental variability. The earliest evidence occurs in archaeological horizon (AH) VII from ∼39–36,000 cal BP during a mild, moist climatic phase. AH VI shows periodic occupation as warm, humid conditions prevailed from ∼36–32,000 cal BP. As the climate becomes cooler and drier at ∼32– 29,000 cal BP (AH V-IV), evidence for occupation is minimal. However, as cooling continues, the deposits of AH III demonstrate that people used the site more intensively from ∼29–24,000 cal BP, leaving behind numerous stone artifacts, faunal remains, and complex combustion features. Despite the climatic fluctuations seen across this 15,000-year sequence, lithic technology remains attuned to one pattern: unidirectional reduction of small cores geared towards the production of bladelets for tool manufacture. Subsistence patterns also remain stable, focused on medium-sized prey such as ovids and caprids, as well as equids. AH III demonstrates an expansion of social networks to the northwest and southwest, as the transport distance of obsidian used to make stone artifacts increases. We also observe the addition of bone tools, including an eyed needle, and shell beads brought from the east, suggesting that these people manufactured complex clothing and wore ornaments. Remains of micromammals, birds, charcoal, pollen, and tephra relate the story of environmental variability. We hypothesize that UP behavior was linked to shifts in demographic pressures and climatic changes. Thus, by combining archaeological and environmental data, we gain a clearer picture about the first UP inhabitants of the Armenian Highlands

Impaired bidirectional synaptic plasticity and procedural memory formation in striatum-specific cAMP response element-binding protein-deficient mice

The striatum has a well documented role in procedural learning and memory. However, the synaptic and molecular mechanisms of acquisition and storage of this form of memory remain poorly understood. We examined procedural memory and plasticity in transgenic mice reversibly expressing a dominant-negative cAMP response element-binding protein (CREB) mutant in the dorsal striatum. In these transgenic mice, corticostriatal long-term potentiation and depression are abolished, indicating that CREB function is essential for bidirectional long-term synaptic plasticity in this structure. Importantly, CREB-deficient animals show reversible alterations in several forms of striatum-dependent memory, including footshock avoidance learning and "response" learning in the cross maze. These findings implicate transcriptional regulation by CREB family transcription factors in striatum-dependent information processing and provide the first clear correlation between procedural learning and memory and synaptic plasticity at the corticostriatal synapse

Relaxation time for a dimer covering with height representation

This paper considers the Monte Carlo dynamics of random dimer coverings of the square lattice, which can be mapped to a rough interface model. Two kinds of slow modes are identified, associated respectively with long-wavelength fluctuations of the interface height, and with slow drift (in time) of the system-wide mean height. Within a continuum theory, the longest relaxation time for either kind of mode scales as the system size N. For the real, discrete model, an exact lower bound of O(N) is placed on the relaxation time, using variational eigenfunctions corresponding to the two kinds of continuum modes.Comment: 12 pages, LaTeX; 1 figure in PostScript file; to appear, J. Stat. Phys. Sections and subsections were reshuffled to improve presentation, some text added on quantum-dimer model, fully-frustrated Ising model, and application to general class of "height" model

The open-air site of Tolbor 16 (Northern Mongolia): Preliminary results and perspectives.

Numerous questions remain regarding the timing and the context of Upper Paleolithic emergence in Northeast Asia. Available data allow the recognition of a form of Initial Upper Paleolithic (IUP) documented in the Altai circa 45e40 ka 14C BP, and in the Cis- and Transbaikal around �37 ka 14C BP. In Northern Mongolia, a series of assemblages show intriguing similarities with IUP laminar assemblages from South Siberia and suggest long distance contact/movements of population during the first half of MIS3. These contacts are potentially enabled by the main river that drains into Lake Baikal, the Selenga. By cutting through the Sayan and the Yablonovy mountain ranges, the Selenga drainage system provides a potential corridor connecting South Siberia with the plains of Mongolia. The Tolbor 16 site (Ikh Tulberiin Gol, Northern Mongolia) is located circa 13 km from the confluence with the Selenga. The first results presented here suggest that the lithic assemblage and the ornaments discovered at Tolbor 16 document the early appearance of Upper Paleolithic in the region. This newly discovered site offers the possibility to generate high-resolution contextual data on the first appearance of the blade assemblages in Mongolia and to test the ‘Selenga corridor hypothesis’