The epithelial–mesenchymal transition: new insights in signaling, development, and disease

The conversion of an epithelial cell to a mesenchymal cell is critical to metazoan embryogenesis and a defining structural feature of organ development. Current interest in this process, which is described as an epithelial–mesenchymal transition (EMT), stems from its developmental importance and its involvement in several adult pathologies. Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada (October 1–3, 2005). The meeting, which was hosted by The EMT International Association, was the second international EMT meeting, the first being held in Port Douglas, Queensland, Australia in October 2003. The EMT International Association was formed in 2002 to provide an international body for those interested in EMT and the reverse process, mesenchymal–epithelial transition, and, most importantly, to bring together those working on EMT in development, cancer, fibrosis, and pathology. These themes continued during the recent meeting in Vancouver

Differential effects of two-pore channel protein 1 and 2 silencing in MDA-MB-468 breast cancer cells

Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca. These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells

Microstructure, Elastic and Inelastic Properties of Partially Graphitized Biomorphic Carbons

The microstructural characteristics and amplitude dependences of the Young’s modulus E and internal friction (logarithmic decrement δ) of biocarbon matrices prepared by beech wood carbonization at temperatures Tcarb = 850–1600°C in the presence of a nickelcontaining catalyst have been studied. Using Xray diffraction and electron microscopy, it has been shown that the use of a nickel catalyst during carbon ization results in a partial graphitization of biocarbons at Tcarb ≥ 1000°C: the graphite phase is formed as 50 to 100nm globules at Tcarb = 1000°C and as 0.5 to 3.0μm globules at Tcarb = 1600°C. It has been found that the measured dependences E(Tcarb) and δ(Tcarb) contain three characteristic ranges of variations in the Young’s modulus and logarithmic decrement with a change in the carbonization temperature: E increases and δ decreases in the ranges Tcarb 1300°C; in the range 1000 < Tcarb < 1300°C, E sharply decreases and δ increases. The observed behavior of E(Tcarb) and δ(Tcarb) for biocarbons carbonized in the presence of nickel correlates with the evolution of their microstructure. The largest values of E are obtained for samples with Tcarb = 1000 and 1600°C. However, the samples with Tcarb = 1600°C exhibit a higher suscep tibility to microplasticity due to the presence of a globular graphite phase that is significantly larger in size and total volume.Peer reviewe

Parents’ knowledge of and opinions about healthcare laws and technology in primary care

Purpose Historically, parents have demonstrated poor understanding of adolescent healthcare laws. This study assessed US parents’ current knowledge and opinions about technology facilitated physician–adolescent communication and applicable laws to enhance transition to adult health care.Methods A brief survey in two low-income academic paediatric clinics asked parents about their knowledge of health care and laws, and their opinions about technology facilitated contact between physicians and adolescents.Results Almost all parents (96.7%) have internet access at home, work or via a mobile device. Only 44.1% approved of having a physician directly contact their child about annual examinations, immunisations or to discuss issues of sexuality. Half (55.4%) were aware that adolescents could receive confidential sexuality information and treatment without parents’ permission. Only one-third (32.2%) approved of a specific technology for direct communication.Conclusions Parents are divided about direct physician–adolescent contact. Future plans to engage adolescents to understand their health will require parental education and involvement on the value of physician–adolescent communication

Vocal signals facilitate cooperative hunting in wild chimpanzees

Cooperation and communication likely co-evolved in humans. However, the evolutionary roots of this interdependence remain unclear. We address this issue by investigating the role of vocal signals in facilitating a group cooperative behavior in an ape species: hunting in wild chimpanzees. First, we show that bark vocalizations produced before hunt initiation are reliable signals of behavioral motivation, with barkers being most likely to participate in the hunt. Next, we find that barks are associated with greater hunter recruitment and more effective hunting, with shorter latencies to hunting initiation and prey capture. Our results indicate that the co-evolutionary relationship between vocal communication and group-level cooperation is not unique to humans in the ape lineage, and is likely to have been present in our last common ancestor with chimpanzees

Activation of matrix metalloproteinase-2 (MMP-2) by membrane type 1 matrix metalloproteinase through an artificial receptor for ProMMP-2 generates active MMP-2

金沢大学がん研究所がん病態制御The suggested model for pro-matrix metalloproteinase-2 (proMMP-2) activation by membrane type 1 MMP (MT1-MMP) implicates the complex between MT1-MMP and tissue inhibitor of MMP-2 (TIMP-2) as a receptor for proMMP-2. To dissect this model and assess the pathologic significance of MMP-2 activation, an artificial receptor for proMMP-2 was created by replacing the signal sequence of TIMP-2 with cytoplasmic/transmembrane domain of type II transmembrane mosaic serine protease (MSP-T2). Unlike TIMP-2, MSP-T2 served as a receptor for proMMP-2 without inhibiting MT1-MMP, and generated TIMP-2-free active MMP-2 even at a low level of MT1-MMP. Thus, MSP-T2 did not affect direct cleavage of the substrate testican-1 by MT1-MMP, whereas TIMP-2 inhibited it even at the level that stimulates proMMP-2 processing. Expression of MSP-T2 in HT1080 cells enhanced MMP-2 activation by endogenous MT1-MMP and caused intensive hydrolysis of collagen gel. Expression of MSP-T2 in U87 glioma cells, which express a trace level of endogenous MT1-MMP, induced MMP-2 activation and enhanced cell-associated protease activity, activation of extracellular signal-regulated kinase, and metastatic ability into chick embryonic liver and lung. MT1-MMP can exert both maximum MMP-2 activation and direct cleavage of substrates with MSP-T2, which cannot be achieved with TIMP-2. These results suggest that MMP-2 activation by MT1-MMP potentially amplifies protease activity, and combination with direct cleavage of substrate causes effective tissue degradation and enhances tumor invasion and metastasis, which highlights the complex role of TIMP-2. MSP-T2 is a unique tool to analyze physiologic and pathologic roles of MMP-2 and MT1-MMP in comparison with TIMP-2. ©2008 American Association for Cancer Research.全文公開20091

The Mass Distribution and Lifetime of Prestellar Cores in Perseus, Serpens, and Ophiuchus

We present an unbiased census of starless cores in Perseus, Serpens, and Ophiuchus, assembled by comparing large-scale Bolocam 1.1 mm continuum emission maps with Spitzer c2d surveys. We use the c2d catalogs to separate 108 starless from 92 protostellar cores in the 1.1 mm core samples from Enoch et al. (2006), Young et al. (2006), and Enoch et al. (2007). A comparison of these populations reveals the initial conditions of the starless cores. Starless cores in Perseus have similar masses but larger sizes and lower densities on average than protostellar cores, with sizes that suggest density profiles substantially flatter than r^-2. By contrast, starless cores in Serpens are compact and have lower masses than protostellar cores; future star formation will likely result in lower mass objects than the currently forming protostars. Comparison to dynamical masses estimated from the NH_3 survey of Perseus cores by Rosolowsky et al. (2007) suggests that most of the starless cores are likely to be gravitationally bound, and thus prestellar. The combined prestellar core mass distribution includes 108 cores and has a slope of -2.3+/-0.4 for M>0.8 Msun. This slope is consistent with recent measurements of the stellar initial mass function, providing further evidence that stellar masses are directly linked to the core formation process. We place a lower limit on the core-to-star efficiency of 25%. There are approximately equal numbers of prestellar and protostellar cores in each cloud, thus the dense prestellar core lifetime must be similar to the lifetime of embedded protostars, or 4.5x10^5 years, with a total uncertainty of a factor of two. Such a short lifetime suggests a dynamic, rather than quasi-static, core evolution scenario, at least at the relatively high mean densities (n>2x10^4 cm^-3) to which we are sensitive.Comment: 27 pages, 15 figures, 5 tables, accepted for publication in ApJ. Version with full resolution figures available at http://www.astro.caltech.edu/~menoch/corespaper