The shellfish enigma across the Mesolithic-Neolithic transition in southern Scandinavia

The well-known and widespread replacement of oysters (abundant during the Mesolithic period) by cockles and mussels in many Danish Stone Age shell middens ca. 5900 cal yrs BP coincides with the transition to agriculture in southern Scandinavia. This human resource shift is commonly believed to reflect changing resource availability, driven by environmental and/or climatic change at the Mesolithic-Neolithic transition rather than cultural choice. While several hypotheses have been proposed to explain the “Mesolithic-Neolithic oyster decline”, an explanation based on a sudden freshening of the inner Danish waters has received most attention. Here, for the first time, we test and refute this long-standing hypothesis that declining salinity explains the marked reduction in oysters identified within numerous shell middens across coastal Denmark at the Mesolithic-Neolithic transition using quantitative and qualitative salinity inference from several, independent proxies (diatoms, molluscs and foraminifera) from multiple Danish fjord sites. Alternatively, we attribute the oyster decline to other environmental causes (particularly changing sedimentation), ultimately driven by external climatic forcing. Critical application of such high-quality environmental archives can reinvigorate archaeological debates and can aid in understanding and managing environmental change in increasingly impacted coastal regions

Comparison of phosphorylation variation of sites within different structural categories.

<p><b>A</b>) Sites within ordered regions (blue) show smaller variation of the phosphorylation fold change over the cell cycle than those within disordered regions (red). The significance of the observation has been tested with Kolmogorov-Smirnov test (p-value 6.6E-13). (<b>B</b>) The variation of phosphorylation changes over the cell cycle scales with the structural propensities of the phosphorylated residues: from lowest in regular structures (blue) to highest in disordered regions (red). The observed differences were found to be significant by ANOVA test (p-value 3.02E-09).</p

Kinase motif decomposition based on phosphorylation variability and structural preferences.

<p>The preferences of various kinases for sites with specific structural background and phosphorylation variation were calculated by the 2D Annotation Enrichment technique (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002842#s4" target="_blank">Methods</a>). In general four classes can be distinguished: (i) tyrosine kinases (black squares), (ii) proline-directed kinases (red circles), (iii) non-proline directed kinases with charged residues in their substrate recognition motif (green and blue triangles corresponding to acidophilic and basophilic kinases respectively) and (iv) proline-oriented kinases, which contain a proline residue in their motif at position different from +1 relative to the modification site (red triangles and pentagons). The vertical axis separates the kinases according to their structural preferences. Tyrosine kinases favor sites within ordered regions with small phosphorylation variability. Serine/threonine kinases prefer more disordered regions, but span a larger space of phosphorylation variation. There is a tendency towards increasing disorderedness with higher phosphorylation variation, which clearly separates non proline-directed, proline-oriented and proline-directed kinases, the latter being characterized by the largest variation in phosphorylation. Examples for each class are shown and the data of all kinases can be found in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002842#pcbi-1002842-t002" target="_blank">Table 2</a>.</p

Enrichment of multi-phospho sites in disordered regions.

<p>The enrichment of additional phosphorylation sites at different distances from the central modified residues was computed. The odds ratios were calculated with the Fisher's Exact test implemented in R. Multiple phosphorylation sites were found significantly more often in disordered regions for any of the considered distances.</p

Temporal phosphorylation patterns of phospho-sites with distinct structural properties.

<p>Phosphorylation fold changes of three sites (UniProt accession number and residue identification number are given) during the six time points is shown together with their corresponding local structure. From left to right the phosphorylation variation over the six time points increases, together with the level of disorder: from (<b>A</b>) regular secondary structure (α-helix or β-sheet) through (<b>B</b>) irregular coils and loops to (<b>C</b>) disordered regions. Phospho-serine residues (pS) within regular regions and loops show small fluctuations in their phosphorylation levels, while larger changes occur in disordered regions.</p

Two sample logo of flanking regions of phosphorylation sites of low <i>versus</i> high phosphorylation variation.

<p>Amino acids in the top and bottom parts (<b>A</b>) – central residue serine and <b>B</b>) – central residue threonine) represent residues, which are enriched or depleted correspondingly in the flanking regions of sites with small phosphorylation variation. Strong preferences are found for charged residues such as arginine, aspartate, and glutamate. In contrast, the majority of the amino acids that are more frequent in the negative set (i.e. variable phosphorylation set) are disorder-related e.g. proline, serine and glycine.</p

Conservation of phosphorylated sites versus conservation of control sites taking into account local structure.

<p>Lower values correspond to slower evolutionary rate and higher conservation. Phosphorylation sites predicted to lie within regular structures (in blue, pS/pT/pY regular) appeared to be more conserved than their equivalent non-phosphorylated residues from the same proteins (p-value 2.24e-16). The same tendency was present for modified sites in disordered regions (in red, pS/pT/pY disordered), which were also subjected to a statistically significant slower evolutionary rate than their control set (p-value 3.4E-03). Phosphorylation sites in regular structures showed higher conservation than that of phosphorylation sites in irregular structures (p-value 3.23E-120).</p

Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study-1

<p><b>Copyright information:</b></p><p>Taken from "Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study"</p><p>BMC Cancer 2005;5():8-8.</p><p>Published online 19 Jan 2005</p><p>PMCID:PMC548152.</p><p>Copyright © 2005 Albrethsen et al; licensee BioMed Central Ltd.</p>0 chips. Differences in mean intensities of HNP 1-3 in normal and colon tumor tissue were statistical significant at 5% level (p < 0.0005). FIG. 2B HNP profiles of normal and colon cancer serum. Serum samples (125 colon cancer and 100 normal) were analyzed on IMAC30 chips. The mean intensities were significantly different at 5% level (p < 2.2e-16). The reproducibility was significant for all three peptides in both tissue and serum. The standard deviation of HNP 1, 2 and 3 was 70%, 136% and 57% in normal tissue and 11%, 15% and 8% in tumor tissue. The standard deviation of HNP 1, 2 and 3 was 96%, 154% and 81% in normal serum and 234%, 365% and 282% in cancer serum. The boxplot show the 25th quantile, median, 75th quantile, and whiskers extent to min. and max. values

Metformin, an Anthropogenic Contaminant of <i>Seidlitzia rosmarinus</i> Collected in a Desert Region near the Gulf of Aqaba, Sinai Peninsula

A phytochemical investigation of <i>Seidlitzia rosmarinus</i> collected along the shoreline of the Gulf of Aqaba in the remote southern desert region of the Sinai peninsula has revealed the presence of the registered drug metformin (<b>4</b>). However, analysis of the ¹⁴C content revealed the drug to be an anthropogenic contaminant. Consequently, natural product researchers should be aware that compounds isolated from plants might originate from environmental contamination rather than biosynthesis. The new natural product <i>N</i>-(4-hydroxyphenylethyl)<i>-</i>α<i>-</i>chloroferuloylamide was isolated as a mixture of the <i>E</i> and <i>Z</i> isomers along with a number of other well-established secondary metabolites

Metformin, an Anthropogenic Contaminant of <i>Seidlitzia rosmarinus</i> Collected in a Desert Region near the Gulf of Aqaba, Sinai Peninsula

A phytochemical investigation of <i>Seidlitzia rosmarinus</i> collected along the shoreline of the Gulf of Aqaba in the remote southern desert region of the Sinai peninsula has revealed the presence of the registered drug metformin (<b>4</b>). However, analysis of the ¹⁴C content revealed the drug to be an anthropogenic contaminant. Consequently, natural product researchers should be aware that compounds isolated from plants might originate from environmental contamination rather than biosynthesis. The new natural product <i>N</i>-(4-hydroxyphenylethyl)<i>-</i>α<i>-</i>chloroferuloylamide was isolated as a mixture of the <i>E</i> and <i>Z</i> isomers along with a number of other well-established secondary metabolites