CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

The assumption that mesenchymal stromal cell (MSC)-based therapies are capable of augmenting physiological regeneration processes has fostered intensive basic and clinical research activities. However, to achieve sustained therapeutic success in vivo, not only the biological, but also the mechanical microenvironment of MSCs during these regeneration processes needs to be taken into account. This is especially important for e.g., bone fracture repair, since MSCs present at the fracture site undergo significant biomechanical stimulation. This study has therefore investigated cellular characteristics and the functional behaviour of MSCs in response to mechanical loading. Our results demonstrated a reduced expression of MSC surface markers CD73 (ecto-5’-nucleotidase) and CD29 (integrin β1) after loading. On the functional level, loading led to a reduced migration of MSCs. Both effects persisted for a week after the removal of the loading stimulus. Specifi c inhibition of CD73/CD29 demonstrated their substrate dependent involvement in MSC migration after loading. These results were supported by scanning electron microscopy images and phalloidin staining of actin fi laments displaying less cell spreading, lamellipodia formation and actin accumulations. Moreover, focal adhesion kinase and Src-family kinases were identified as candidate downstream targets of CD73/CD29 that might contribute to the mechanically induced decrease in MSC migration. These results suggest that MSC migration is controlled by CD73 CD29, which in turn are regulated by mechanical stimulation of cells. We therefore speculate that MSCs migrate into the fracture site, become mechanically entrapped, and thereby accumulate to fulfil their regenerative functions.

Quantifying variability within technique and performance in elite fast bowlers : is technical variability dysfunctional or functional?

In fast bowling, cricketers are expected to produce a range of delivery lines and lengths while maximising ball speed. From a coaching perspective, technique consistency has been typically associated with superior performance in these areas. However, although bowlers are required to bowl consistently, at the elite level they must also be able to vary line, length and speed to adapt to opposition batters’ strengths and weaknesses. The relationship between technique and performance variability (and consistency) has not been investigated in previous fast bowling research. Consequently, the aim of this study was to quantify both technique (bowling action and coordination) and performance variability in elite fast bowlers from Australian Junior and National Pace Squads. Technique variability was analysed to investigate whether it could be classified as functional or dysfunctional in relation to speed and accuracy.

PCR bias Toward the wild-type k-ras and p53 sequences: Implications for PCR detection of mutations and cancer diagnosis

PCR-based cancer diagnosis requires detection of rare mutations in k- ras, p53 or other genes. The assumption has been that mutant and wild-type sequences amplify with near equal efficiency, so that they are eventually present in proportions representative of the starting material. Work on factor IX suggests that this assumption is invalid for one case of near- sequence identity. To test the generality of this phenomenon and its relevance to cancer diagnosis, primers distant from point mutations in p53 and k-ras were used to amplify wild-type and mutant sequences from these genes. A substantial bias against PCR amplification of mutants was observed for two regions of the p53 gene and one region of k-ras. For k-ras and p53, bias was observed when the wild-type and mutant sequences were amplified separately or when mixed in equal proportions before PCR. Bias was present with proofreading and non-proofreading polymerase. Mutant and wild-type segments of the factor V, cystic fibrosis transmembrane conductance regulator and prothrombin genes were amplified and did not exhibit PCR bias. Therefore, the assumption of equal PCR efficiency for point mutant and wild-type sequences is invalid in several systems. Quantitative or diagnostic PCR will require validation for each locus, and enrichment strategies may be needed to optimize detection of mutants.

Are the ‘cave’ minerals archerite (K,NH4)H2PO4 and biphosphammite (K,NH4)H2PO4 identical? A molecular structural study

The molecular structure of the mineral archerite ((K,NH4)H2PO4) has been determined and compared with that of biphosphammite ((NH4,K)H2PO4). Raman spectroscopy and infrared spectroscopy has been used to characterise these ‘cave’ minerals. Both minerals originated from the Murra-el-elevyn Cave, Eucla, Western Australia. The mineral is formed by the reaction of the chemicals in bat guano with calcite substrates. Raman and infrared bands are assigned to H2PO4-, OH and NH stretching vibrations. The Raman band at 981 cm-1 is assigned to the HOP stretching vibration. Bands in the 1200 to 1800 cm-1 region are associated with NH4+ bending modes. The molecular structure of the two minerals appear to be very similar, and it is therefore concluded that the two minerals are identical.

The role of cross-functional teams on the alignment between technology innovation effectiveness and operational effectiveness

Organisations are increasingly investing in complex technological innovations, such as enterprise information systems, with the aim of improving the operation of the business, and in this way gaining competitive advantage. However, the implementation of technological innovations tends to have an excessive focus on either technology innovation effectiveness, or the resulting operational effectiveness. Focusing on either one of them is detrimental to long-term performance. Cross-functional teams have been used by many organisations as a way of involving expertise from different functional areas in the implementation of technologies. The role of boundary spanning actors is discussed as they bring a common language to the cross-functional teams. Multiple regression analysis has been used to identify the structural relationships and provide an explanation for the influence of cross-functional teams, technology innovation effectiveness and operational effectiveness in the continuous improvement of operational performance. The findings indicate that cross functional teams have an indirect influence on continuous improvement of operational performance through the alignment between technology innovation effectiveness and operational effectiveness.

Functional heterogeneity as a two-dimensional concept : empirical evidence for new venture teams

Previous research on entrepreneurial teams has failed to settle the controversy over whether team heterogeneity helps or hinders new venture performance. Reconciling this inconsistency, this paper suggests a new conceptual approach to disentangle differential effects of team heterogeneity by modeling two separate heterogeneity dimensions, namely knowledge scope and knowledge disparity. Analyzing unique data on functional experiences of the members of 337 start-up teams, we find support for our contention of team heterogeneity as a two-dimensional concept. Results suggest that knowledge disparity negatively relates to both start-ups’ entrepreneurial and innovative performance. In contrast, we find knowledge scope to positively affect entrepreneurial performance, while it shows an inverse U-shaped relationship to innovative start-up performance.

Osteopontin is a downstream effector of the PI3-kinase pathway in melanomas that is inversely correlated with functional PTEN

The tumor suppressor PTEN antagonizes phosphatidylinositol 3-kinase (PI3K), which contributes to tumorigenesis in many cancer types. While PTEN mutations occur in some melanomas, their precise mechanistic consequences have yet to be elucidated. We sought to identify novel downstream effectors of PI3K using a combination of genomic and functional tests. Microarray analysis of 53 melanoma cell lines identified 610 genes differentially expressed (P<0.05) between wild-type lines and those with PTEN aberrations. Many of these genes are known to be involved in the PI3K pathway and other signaling pathways influenced by PTEN. Validation of differential gene expression by qRT-PCR was performed in the original 53 cell lines and an independent set of 18 melanoma lines with known PTEN status. Osteopontin (OPN), a secreted glycophosphoprotein that contributes to tumor progression, was more abundant at both the mRNA and protein level in PTEN mutants. The inverse correlation between OPN and PTEN expression was validated (P<0.02) by immunohistochemistry using melanoma tissue microarrays. Finally, treatment of cell lines with the PI3K inhibitor LY294002 caused a reduction in expression of OPN. These data indicate that OPN acts downstream of PI3K in melanoma and provides insight into how PTEN loss contributes to melanoma development.