Poly(thioether) vitrimers via transalkylation of trialkylsulfonium salts

Vitrimers are permanently cross-linked organic polymers that can be reshaped, molded, and recycled without loss of network integrity. Herein, we report poly(thioether) networks, prepared through a straightforward thiol-ene photopolymerization, that can be turned into catalyst-free vitrimer materials by partial alkylation of the thioethers (1-10%) to the corresponding trialkylsulfonium salts. Based on a classical S(N)2-type substitution, the resulting polyionic networks can be reshaped upon heating via swift transalkylation reactions. This novel exchange reaction for the design of vitrimers was studied both on low MW model compounds as well as on a material level. In addition, we demonstrated the recycling of these networks without significant loss of mechanical properties

A randomized controlled trial of three years growth hormone and gonadotropin-releasing hormone agonist treatment in children with idiopathic short stature and intrauterine growth retardation

We assessed the effectiveness and safety of 3 yr combined GH and GnRH agonist (GnRHa) treatment in a randomized controlled study in children with idiopathic short stature (ISS) or intrauterine growth retardation (IUGR). Gonadal suppression, GH reserve, and adrenal development were assessed by hormone measurements in both treated children and controls during the study period. Thirty-six short children, 24 girls (16 ISS/8 IUGR) and 12 boys (8 ISS/4 IUGR), with a height SD score of -2 SD or less in early puberty (girls, B2-3; boys, G2-3), were randomly assigned to treatment (n = 18) with GH (genotropin 4 IU/m(2). day) and GnRHa (triptorelin, 3.75 mg/28 days) or no treatment (n = 18). At the start of the study mean (SD) age was 11.4 (0.56) or 12.2 (1.12) yr whereas bone age was 10.7 (0.87) or 10.9 (0.63) yrs in girls and boys, respectively. During 3 yr of study height SD score for chronological age did not change in both treated children and controls, whereas a decreased rate of bone maturation after treatment was observed [mean (SD) 0.55 (0.21) 'yr'/yr vs. 1.15 (0.37) 'yr'/yr in controls, P < 0.001, girls and boys together]. Height SD score for bone age and predicted adult height increased significantly after 3 yr of treatment; compared with controls the predicted adult height gain was 8.0 cm in girls and 10.4 cm in boys. Furthermore, the ratio between sitting height/height SD score decreased significantly in treated children, whereas body mass index was not influenced by treatment. Puberty was effectively arrested in the treated children, as was confirmed by physical examination and prepubertal testosterone and estradiol levels. GH-dependent hormones including serum insulin-like growth factor I and II, carboxy terminal propeptide of type I collagen, amino terminal propeptide of type III collagen, alkaline phosphatase, and osteocalcin were not different between treated children and controls during the study period. Thus, a GH dose of 4 IU/m(2) seems adequate for stabilization of the GH reserve and growth in these GnRHa-treated children. We conclude that 3 yr treatment with GnRHa was effective in suppressing pubertal development and skeletal maturation, whereas the addition of GH preserved growth velocity during treatment. This resulted in a considerable gain in predicted adult height, without demonstrable side effects. Final height results will provide the definite answer on the effectiveness of this combined treatment

A novel strategy for the comprehensive analysis of the biomolecular composition of isolated plasma membranes

A methodology for rapid, high-purity isolation of plasma membranes using superparamagnetic nanoparticles is described. The method is illustrated with high-resolution proteomic, glycomic and lipidomic analyses of presenilin-deficient cells

Lipid degradation promotes prostate cancer cell survival

Prostate cancer is the most common male cancer and androgen receptor (AR) is the major driver of the disease. Here we show that Enoyl-CoA delta isomerase 2 (ECI2) is a novel AR-target that promotes prostate cancer cell survival. Increased ECI2 expression predicts mortality in prostate cancer patients (p = 0.0086). ECI2 encodes for an enzyme involved in lipid metabolism, and we use multiple metabolite profiling platforms and RNA-seq to show that inhibition of ECI2 expression leads to decreased glucose utilization, accumulation of fatty acids and down-regulation of cell cycle related genes. In normal cells, decrease in fatty acid degradation is compensated by increased consumption of glucose, and here we demonstrate that prostate cancer cells are not able to respond to decreased fatty acid degradation. Instead, prostate cancer cells activate incomplete autophagy, which is followed by activation of the cell death response. Finally, we identified a clinically approved compound, perhexiline, which inhibits fatty acid degradation, and replicates the major findings for ECI2 knockdown. This work shows that prostate cancer cells require lipid degradation for survival and identifies a small molecule inhibitor with therapeutic potential.</p

Les fouilles de Pessinonte : le temple

Les quatre collaborateurs, partant chacun d'un point de vue spécial, se sont efforcés de résoudre deux problèmes relatifs au temple trouvé à Pessinonte, lors des fouilles archéologiques qui ont eu lieu en cet endroit depuis 1967. Le résultat de leurs recherches est que le temple en question a été construit au début du Ier siècle après J.-C., probablement à l'époque de Tibère, et qu'il desservait le culte impérial.Lambrechts P., Strubbe J., Waelkens M., Stoops G. Les fouilles de Pessinonte : le temple. In: L'antiquité classique, Tome 41, fasc. 1, 1972. pp. 156-173

Societal changes in the Bereket valley during the Roman Imperial period Results from the Sagalassos Territorial Archaeological Survey 2008 (southwest Turkey)

status: publishe

Numerically derived evidence for late-Holocene climate change and its impact on human presence in the southwest Taurus Mountains, Turkey

A well-dated pollen diagram from Gravgaz marsh, near the archaeological site of Sagalassos (western Taurus Mountains, Turkey), provides the first detailed record of vegetation change in southwest Turkey during the last two millennia. A newly developed numerical analysis disentangles the climatic and anthropogenic influences on vegetation and reveals for the first time for southwest Turkey the timing and influence of late-Holocene climate change. Results show that sudden vegetation changes, driven by changes in moisture availability, co-occurred with well-defined European climate shifts. A trend towards dry conditions, from c. ad 640 to 940, coincides with the cold early Middle Ages in Europe. During this period, human presence in the region diminished and agricultural activity switched focus from crop cultivation to pastoralism while signs of cereal cultivation temporarily ceased. This period was followed by a return to moister conditions from ad 940 to 1280, coinciding with the ‘Medieval Climate Anomaly’. During this period there was a resurgence of human activity in the basin. Another trend towards dry conditions occurred at c. ad 1280, corresponding with the start of the ‘Little Ice Age’ in Europe and another disappearance of cereal pollen until the present day. The numerical analyses suggest that human impact around Gravgaz during the last two millennia is primarily driven by climatic changes.status: publishe

Sensitivity of the Eastern Mediterranean geomorphic system towards environmental change during the Late Holocene: a chronological perspective

Alluvial and colluvial sediment deposition provide a vital record of environmental change during the Holocene. Firm chronological control on these archives is necessary to enable us to relate sediment dynamics to human activity and climate variability. In the Eastern Mediterranean, such relationships are hard to establish due to the lack of spatially well-distributed sediment archives with good chronological control. This scarcity is problematic with respect to regional-scale reconstructions of the temporal variation of sediment dynamics. Here, we present a radiocarbon database (n=178) of geomorphological activity collected from multiple distinct sediment archives within the territory of Sagalassos in south-western Turkey. The data were grouped according to their sedimentary facies for analysis using cumulative probability distributions (CPDs) and sedimentation rate (SR) modelling. Two small-scale colluvial valleys, where chronological information was abundant, were investigated in more detail. Results show that sedimentation chronology differs between individual, nearby cores, as it depends strongly on the local geomorphic situation. A generalizing approach combining multiple core results yields more widely valid conclusions. High sedimentation rates coincided with the initial major anthropogenic disturbance of the landscape and decreased afterwards, probably due to hillslope soil depletion. CPD and SR analysis indicates that in general colluvial sedimentation rates did not change much from 2000 BC onwards. River floodplain sedimentation, in contrast, increased markedly during the first millennium BC and during recent times, and a significant time lag in enhanced sediment deposition between the upper and lower reaches of the river valleys was observed. © 2012 John Wiley & Sons, Ltd.status: publishe

Man, vegetation and climate during the Holocene in the territory of Sagalassos, Western Taurus Mountains, SW Turkey

Past vegetation change and the influence of climate change and anthropogenic pressure during the Holocene is constructed from a series of palynological records sampled from three locations within the territory of the antique site of Sagalassos. The disappearance of the original deciduous oak woodlands and increases in anthropogenic indicator species around 5300 and 4300 BC, correspond with an increase in settlements in the region. A period of drought, following the deforestation may have hampered the recovery of deciduous oak. The timing of the onset of the Beysehir Occupation Phase (BO-Phase) in the territory differs between locations, estimates ranging from c. 1000-800 BC to the start of the Hellenistic period (334 BC). The most intense period of arboriculture coincides with the Roman and late-Roman periods. Increases in human pressure on the landscape as reflected in the pollen record correspond with an increased rate of sedimentation and fire activity. The timing of the end of the BO-Phase again differs between locations. Estimates range from the 4th century AD to the mid 7th century AD, when a region-wide shift to dry environmental conditions is observed. Numerical analyses show that post BO-Phase vegetation change is largely driven by climate and displays a succession of dry and wet periods that coincided with well-defined European climate shifts, including the Medieval Climate Anomaly and the Little Ice Age. Current agricultural activities in the region are of a very recent (20th century) origin.status: publishe

Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation

The protein kinase D (PKD) family is regulated through multi-site phosphorylation, including autophosphorylation. For example, PKD displays in vivo autophosphorylation on Ser-742 (and Ser-738 in vitro) in the activation loop and Ser-910 in the C-tail (hPKD1 numbering). In this paper, we describe the surprising observation that PKD also displays in vitro autocatalytic activity towards a Tyr residue in the P + 1 loop of the activation segment. We define the molecular determinants for this unusual activity and identify a Cys residue (C705 in PKD1) in the catalytic loop as of utmost importance. In cells, PKD Tyr autophosphorylation is suppressed through the association of an inhibitory factor. Our findings provide important novel insights into PKD (auto)regulation.status: publishe