An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling

Focal adhesion kinase (FAK) transduces cell adhesion to the extracellular matrix into proliferative signals. We show that FAK overexpression induced proliferation in endothelial cells, which are normally growth arrested by limited adhesion. Interestingly, displacement of FAK from adhesions by using a FAK−/− cell line or by expressing the C-terminal fragment FRNK also caused an escape of adhesion-regulated growth arrest, suggesting dual positive and negative roles for FAK in growth regulation. Expressing kinase-dead FAK-Y397F in FAK−/− cells prevented uncontrolled growth, demonstrating the antiproliferative function of inactive FAK. Unlike FAK overexpression–induced growth, loss of growth control in FAK−/− or FRNK-expressing cells increased RhoA activity, cytoskeletal tension, and focal adhesion formation. ROCK inhibition rescued adhesion-dependent growth control in these cells, and expression of constitutively active RhoA or ROCK dysregulated growth. These findings demonstrate the ability of FAK to suppress and promote growth, and underscore the importance of multiple mechanisms, even from one molecule, to control cell proliferation

Genome-Wide Analysis of Neuroblastomas using High-Density Single Nucleotide Polymorphism Arrays

BACKGROUND: Neuroblastomas are characterized by chromosomal alterations with biological and clinical significance. We analyzed paired blood and primary tumor samples from 22 children with high-risk neuroblastoma for loss of heterozygosity (LOH) and DNA copy number change using the Affymetrix 10K single nucleotide polymorphism (SNP) array. FINDINGS: Multiple areas of LOH and copy number gain were seen. The most commonly observed area of LOH was on chromosome arm 11q (15/22 samples; 68%). Chromosome 11q LOH was highly associated with occurrence of chromosome 3p LOH: 9 of the 15 samples with 11q LOH had concomitant 3p LOH (P = 0.016). Chromosome 1p LOH was seen in one-third of cases. LOH events on chromosomes 11q and 1p were generally accompanied by copy number loss, indicating hemizygous deletion within these regions. The one exception was on chromosome 11p, where LOH in all four cases was accompanied by normal copy number or diploidy, implying uniparental disomy. Gain of copy number was most frequently observed on chromosome arm 17q (21/22 samples; 95%) and was associated with allelic imbalance in six samples. Amplification of MYCN was also noted, and also amplification of a second gene, ALK, in a single case. CONCLUSIONS: This analysis demonstrates the power of SNP arrays for high-resolution determination of LOH and DNA copy number change in neuroblastoma, a tumor in which specific allelic changes drive clinical outcome and selection of therapy

Fatigue of Materials II: Advances and Emergences in Understanding

The Second International Symposium of Fatigue of Materials: Advances and Emergences in Understanding is a five-session symposium held in conjunction with the Materials Science and Technology Conference 2012 (MS&T 2012) at Pittsburgh, Pennsylvania, during October 7-11, 2012. The abstracts that were submitted for presentation at this symposium cover a diverse range of topics. We have made an attempt to group these papers into sessions that focus on closely-related topics. However, as can be expected, many of the papers could fit into more than one session. In the ensuing discussion, we provide a cohesive, complete and compelling overview of the symposium as well as a summary of the abstracts that were submitted. Session 1 (Overview 1) and Session 2 (Overview II) contain papers that (i) Review the current state of knowledge both related and relevant to the subject of fatigue behavior of materials, and (ii) New, innovative, and emerging techniques for experimental evaluation of the fatigue behavior. In concurrence the papers attempt to analyze the data for aspects relevant to design and simultaneously predicting the useful life of components and structures. Session 3 (Aerospace Materials I) and Session 4 (Aerospace Materials II) focus on advanced materials that are used in performance-critical applications in the aerospace and automotive industries, such as the alloys of titanium, nickel, aluminum, and magnesium. Session 5 is a collection of papers relating to other materials of engineering interest, such as iron and steel, polymer, rubber, and even composites. In the summary presented below, the session number and paper number are identified by S and P. Topics related to the influence of both processing and the environment are covered in papers presented in all the sessions of this symposium, and are briefly summarized here as a group with additional discussion included in the individual sessions.https://corescholar.libraries.wright.edu/books/1042/thumbnail.jp

Fatigue of Materials II: Advances and Emergences in Understanding

The Second International Symposium of Fatigue of Materials: Advances and Emergences in Understanding is a five-session symposium held in conjunction with the Materials Science and Technology Conference 2012 (MS&T 2012) at Pittsburgh, Pennsylvania, during October 7-11, 2012. The abstracts that were submitted for presentation at this symposium cover a diverse range of topics. We have made an attempt to group these papers into sessions that focus on closely-related topics. However, as can be expected, many of the papers could fit into more than one session. In the ensuing discussion, we provide a cohesive, complete and compelling overview of the symposium as well as a summary of the abstracts that were submitted. Session 1 (Overview 1) and Session 2 (Overview II) contain papers that (i) Review the current state of knowledge both related and relevant to the subject of fatigue behavior of materials, and (ii) New, innovative, and emerging techniques for experimental evaluation of the fatigue behavior. In concurrence the papers attempt to analyze the data for aspects relevant to design and simultaneously predicting the useful life of components and structures. Session 3 (Aerospace Materials I) and Session 4 (Aerospace Materials II) focus on advanced materials that are used in performance-critical applications in the aerospace and automotive industries, such as the alloys of titanium, nickel, aluminum, and magnesium. Session 5 is a collection of papers relating to other materials of engineering interest, such as iron and steel, polymer, rubber, and even composites. In the summary presented below, the session number and paper number are identified by S and P. Topics related to the influence of both processing and the environment are covered in papers presented in all the sessions of this symposium, and are briefly summarized here as a group with additional discussion included in the individual sessions

Statistical Analyses on the Seasonal Rainfall Trend and Annual Rainfall Variability in Bhutan

10.2151/sola.2021-035Scientific Online Letters on the Atmosphere17202-20

Investigating drought over the Central Highland, Vietnam, using regional climate models

10.1016/j.jhydrol.2014.11.006Journal of Hydrology526265-27

TSpred: a web server for the rational design of temperature-sensitive mutants

Temperature sensitive (Ts) mutants of proteins provide experimentalists with a powerful and reversible way of conditionally expressing genes. The technique has been widely used in determining the role of gene and gene products in several cellular processes. Traditionally, Ts mutants are generated by random mutagenesis and then selected though laborious large-scale screening. Our web server, TSpred (http://mspc.bii.a-star.edu.sg/TSpred/), now enables users to rationally design Ts mutants for their proteins of interest. TSpred uses hydrophobicity and hydrophobic moment, deduced from primary sequence and residue depth, inferred from 3D structures to predict/identify buried hydrophobic residues. Mutating these residues leads to the creation of Ts mutants. Our method has been experimentally validated in 36 positions in six different proteins. It is an attractive proposition for Ts mutant engineering as it proposes a small number of mutations and with high precision. The accompanying web server is simple and intuitive to use and can handle proteins and protein complexes of different sizes

Regional model simulations of the Bodélé low-level jet of Northern Chad during the Bodélé Dust Experiment (BoDEx 2005)

The low-level jet (LLJ) over the Bodélé depression in northern Chad is a newly identified feature. Strong LLJ events are responsible for the emission of large quantities of mineral dust from the depression, the world¿s largest single dust source, and its subsequent transport to West Africa, the tropical Atlantic, and beyond. Accurate simulation of this key dust-generating atmospheric feature is, therefore, an important requirement for dust models. The objectives of the present study are (i) to evaluate the ability of regional climate models (RCMs) and global analyses/reanalyses to represent this feature, and (ii) to determine the driving mechanisms of the LLJ and its strong diurnal cycle. Observational data obtained during the Bodélé Dust Experiment (BoDEx 2005) are utilized for comparison. When suitably configured, the fifth-generation Pennsylvania State University NCAR Mesoscale Model (MM5) RCM can represent very accurately many of the key features of the jet including the structure, diurnal cycle, and day-to-day variability. Surface winds are also well reproduced, including the peak winds, which activate dust emission. Model fidelity is, however, strongly dependent on the boundary layer parameterization scheme, surface roughness, and vertical resolution in the lowest layers. A model horizontal resolution of a few tens of kilometers is sufficient to resolve most of the key features of the LLJ, while in global analyses/reanalyses many features of the LLJ are not adequately represented. Idealized RCM simulations indicate that under strong synoptic forcing the surrounding orography of the Tibesti and Ennedi Mountains acts to focus the LLJ onto the Bodélé and to accelerate the jet by ~40%. From the RCM experiments it is diagnosed that the pronounced diurnal cycle of the Bodélé LLJ is largely a result of varying eddy viscosity, with elevated heating/cooling over the Tibesti Mountains to the north as a second-order contribution

Hydro-meteorological drought assessment under climate change impact over the Vu Gia-Thu Bon river basin, Vietnam

10.1080/02626667.2017.1346374Hydrological Sciences Journal62101654-166