The omnivorous Tyrolean Iceman: colon contents (meat, cereals, pollen, moss and whipworm) and stable isotope analyses

The contents of the colon of the Tyrolean Iceman who lived Ga. 5300 years ago include muscle fibres, cereal remains, a diversity of pollen, and most notably that of the hop hornbeam (Ostrya carpinifolia) retaining cellular contents, as well as a moss leaf (Neckera complanata) and eggs of the parasitic whipworm (Trichuris trichiura). Based almost solely on stable isotope analyses and ignoring the work on the colon contents, two recently published papers on the Iceman's diet draw ill- founded conclusions about vegetarianism and even veganism. Neither the pollen nor the moss is likely to have been deliberately consumed as food by the Iceman. All the available evidence concerning the Iceman's broad-based diet is reviewed and the significance of the colon contents for matters other than assessment of food intake is outlined

Improved diagnostics targeting c-MET in non-small cell lung cancer: expression, amplification and activation?

Background: Several c-MET targeting inhibitory molecules have already shown promising results in the treatment of patients with Non-small Cell Lung Cancer (NSCLC). Combination of EGFR-and c-MET-specific molecules may overcome EGFR tyrosine kinase inhibitor (TKI) resistance. The aim of this study was to allow for the identification of patients who might benefit from TKI treatments targeting MET and to narrow in on the diagnostic assessment of MET. Methods: 222 tumor tissues of patients with NSCLC were analyzed concerning c-MET expression and activation in terms of phosphorylation (Y1234/1235 and Y1349) using a microarray format employing immunohistochemistry (IHC). Furthermore, protein expression and MET activation was correlated with the amplification status by Fluorescence in Situ Hybridization (FISH). Results: Correlation was observed between phosphorylation of c-MET at Y1234/1235 and Y1349 (spearman correlation coefficient r(s) = 0.41;p 0.05). c-MET gene amplification was detected in eight of 214 patients (3.7 %). No significant association was observed between c-MET amplification, c-MET protein expression and phosphorylation. Conclusion: Our data indicate, that neither expression of c-MET nor the gene amplification status might be the best way to select patients for MET targeting therapies, since no correlation with the activation status of MET was observed. We propose to take into account analyzing the phosphorylation status of MET by IHC to select patients for MET targeting therapies. Signaling of the receptor and the activation of downstream molecules might be more crucial for the benefit of therapeutics targeting MET receptor tyrosine kinases than expression levels alone

All-fibre source of amplitude-squeezed light pulses

An all-fibre source of amplitude squeezed solitons utilizing the self-phase modulation in an asymmetric Sagnac interferometer is experimentally demonstrated. The asymmetry of the interferometer is passively controlled by an integrated fibre coupler, allowing for the optimisation of the noise reduction. We have carefully studied the dependence of the amplitude noise on the asymmetry and the power launched into the Sagnac interferometer. Qualitatively, we find good agreement between the experimental results, a semi-classical theory and earlier numerical calculations [Schmitt etl.al., PRL Vol. 81, p.2446, (1998)]. The stability and flexibility of this all-fibre source makes it particularly well suited to applications in quantum information science

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

Supersymmetric contributions to Bˉs→ϕπ0\bar{B}_s \to \phi \pi^0 and Bˉs→ϕρ0\bar{B}_s \to \phi \rho^0 decays in SCET

We study the decay modes $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$ using Soft Collinear Effective Theory. Within Standard Model and including the error due to the SU(3) breaking effect in the SCET parameters we find that BR $\bar{B}_s\to \phi \pi^0 =7_{-1-2}^{+1+2}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \pi^0=9_{-1-4}^{+1+3}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively.For the decay mode $\bar{B}_s\to \phi \rho^0$, we find that BR $\bar{B}_s\to \phi \rho^0 = 20.2^{+1+9}_{-1-12}\times 10^{-8}$ and BR $\bar{B}_s\to \phi \rho^0 = 34.0^{+1.5 + 15}_{-1.5-22}\times 10^{-8}$ corresponding to solution 1 and solution 2 of the SCET parameters respectively. We extend our study to include supersymmetric models with non-universal A-terms where the dominant contributions arise from diagrams mediated by gluino and chargino exchanges. We show that gluino contributions can not lead to an enhancement of the branching ratios of $\bar{B}_s\to \phi \pi^0$ and $\bar{B}_s\to \phi \rho^0$. In addition, we show that SUSY contributions mediated by chargino exchange can enhance the branching ratio of $\bar{B}_s\to \phi \pi^0$ by about 14% with respect to the SM prediction. For the branching ratio of $\bar{B}_s\to \phi \rho^0$, we find that SUSY contributions can enhance its value by about 1% with respect to the SM prediction.Comment: 25 pages,5 figures, version accepted for publicatio

Overexpression of podocalyxin-like protein is an independent factor of poor prognosis in colorectal cancer

Background:Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and poor prognosis in several forms of cancer. In this study, we investigated the prognostic impact of PODXL expression in colorectal cancer (CRC).Methods:Using tissue microarrays and immunohistochemistry, PODXL expression was evaluated in 536 incident CRC cases from a prospective, population-based cohort study. Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the impact of PODXL expression on cancer-specific survival (CSS) and overall survival (OS).Results:High PODXL expression was significantly associated with unfavourable clinicopathological characteristics, a shorter CSS (hazard ratio (HR)=1.98; 95% confidence interval (CI) 1.38-2.84, P<0.001) and 5-year OS (HR=1.85; 95% CI 1.29-2.64, P=0.001); the latter remaining significant in multivariate analysis (HR=1.52; 95% CI 1.03-2.25, P=0.036). In addition, in curatively resected stage III (T1-4, N1-2, M0) patients (n=122) with tumours with high PODXL expression, a significant benefit from adjuvant chemotherapy was demonstrated (p(interaction) =0.004 for CSS and 0.015 for 5-year OS in multivariate analysis).Conclusion:Podocalyxin-like 1 expression is an independent factor of poor prognosis in CRC. Our results also suggest that PODXL may be a useful marker to stratify patients for adjuvant chemotherapy

Monsters, Laws of Nature, and Teleology in Late Scholastic Textbooks

In the period of emergence of early modern science, ‘monsters’ or individuals with physical congenital anomalies were considered as rare events which required special explanations entailing assumptions about the laws of nature. This concern with monsters was shared by representatives of the new science and Late Scholastic authors of university textbooks. This paper will reconstruct the main theses of the treatment of monsters in Late Scholastic textbooks, by focusing on the question as to how their accounts conceived nature’s regularity and teleology. It shows that they developed a naturalistic teratology in which, in contrast to the naturalistic explanations usually offered by the new science, finality was at central stage. This general point does not impede our noticing that some authors were closer to the views emerging in the Scientific Revolution insofar as they conceived nature as relatively autonomous from God and gave a relevant place to efficient secondary causation. In this connection, this paper suggests that the concept of the laws of nature developed by the new science –as exception-less regularities—transferred to nature’s regularity the ‘strong’ character that Late Scholasticism attributed to finality and that the decline of the Late Scholastic view of finality played as an important concomitant factor permitting the transformation of the concept of laws of nature