Coordination of Cell Polarity during Xenopus Gastrulation

Cell polarity is an essential feature of animal cells contributing to morphogenesis. During Xenopus gastrulation, it is known that chordamesoderm cells are polarized and intercalate each other allowing anterior-posterior elongation of the embryo proper by convergent extension (CE). Although it is well known that the cellular protrusions at both ends of polarized cells exert tractive force for intercalation and that PCP pathway is known to be essential for the cell polarity, little is known about what triggers the cell polarization and what the polarization causes to control intracellular events enabling the intercalation that leads to the CE. In our research, we used EB3 (end-binding 3), a member of +TIPs that bind to the plus end of microtubule (MT), to visualize the intracellular polarity of chordamesoderm cells during CE to investigate the trigger of the establishment of cell polarity. We found that EB3 movement is polarized in chordamesoderm cells and that the notochord-somite tissue boundary plays an essential role in generating the cell polarity. This polarity was generated before the change of cell morphology and the polarized movement of EB3 in chordamesoderm cells was also observed near the boundary between the chordamesoderm tissue and naïve ectoderm tissue or lateral mesoderm tissues induced by a low concentration of nodal mRNA. These suggest that definitive tissue separation established by the distinct levels of nodal signaling is essential for the chordamesodermal cells to acquire mediolateral cell polarity

Prognostic Tools in Patients with Advanced Cancer: A Systematic Review

Purpose: In 2005, the European Association for Palliative Care (EAPC) made recommendations for prognostic markers in advanced cancer. Since then, prognostic tools have been developed, evolved and validated. The aim of this systematic review was to examine the progress in the development and validation of prognostic tools. Methods: Medline, Embase Classic + and Embase were searched. Eligible studies met the following criteria: patients with incurable cancer; >18 years; original studies; population n>100; published after 2003. Descriptive and quantitative statistical analyses were performed. Results: Forty-nine studies were eligible, assessing seven prognostic tools across different care settings, primary cancer types and statistically assessed survival prediction. The (PPS) Palliative Performance Scale was the most studied (n=21,082), composed of 6 parameters (6 subjective), was externally validated and predicted survival. The Palliative Prognostic Score (PaP) composed of 6 parameters (4 subjective, 2 objective), the Palliative Prognostic Index (PPI) composed of 9 parameters (9 subjective), and the Glasgow Prognostic Score (GPS) composed of 2 parameters (2 objective), and were all externally validated in more than 2000 patients with advanced cancer and predicted survival. Conclusion: Various prognostic tools have been validated, but vary in their complexity, subjectivity and therefore clinical utility. The GPS would seem the most favourable as it uses only two parameters (both objective) and has prognostic value complementary to the gold standard measure, which is performance status. Further studies comparing all proven prognostic markers in a single cohort of patients with advanced cancer, are needed to determine the optimal prognostic tool

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtype-specific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe