Ion-molecule reactions reveal facile radical migration in peptides

Ion-molecule reactions between molecular oxygen and peptide radicals in the gas phase demonstrate that radical migration occurs easily within large biomolecules without addition of collisional activation energy.

Teachers in early childhood policy

This paper examines teacher accountability and authority in early childhood policy. It reports on data from a study that investigated the influences affecting early childhood teacher decision-making at the preschool level in Victoria, Australia. Using a question raised by Ball ‘Where are the teachers in all this [policy]?’ provided a starting point for the critical discourse analysis into how forms of control, teacher authority, obligation and constraint within policies potentially influenced teachers’ curriculum decisions. The study found that despite no government-mandated curriculum framework at the time, teachers were held accountable for their curricular practice. Yet as professionals, early childhood teachers were denied public acknowledgement of their expertise as they were almost invisible in policy. In the four policies analysed, proprietors of early childhood settings and preschool agencies held authority over curriculum. Subsequently, teachers’ authority as professionals with curricular knowledge was diminished.

Anionic migration reactions in aromatic systems effected by collisional activation : Deprotonated anilides containing methoxycarbonyl substituents

Long-range cross-ring reactions are of minor importance in the collision-induced mass spectra (MS/MS) of [M - H]- ions of CH2OCO-C6H4-NHCOR systems: e.g. the loss of 'CD3CO2CH3' from CH3OCO-C6H4-(N) over bar COCD3. Major processes involve (i) losses of radicals to form stable radical anions, e.g. loss of a ring hydrogen atom and losses from the ester (CH3 ., CH3O . and . CO2CH3), (ii) losses of neutral molecules from the amide moiety [e.g. CO (R = H) and CH2CO (R = CH3), and proximity effects when the two substituents are ortho [e.g. loss of (CH3OD+CO2) from o-CH3OCO-C6H4 (N) over bar COCD3].

Health governance : law, regulation and policy

This special issue of Public Health is devoted to health governance, examining the role of law, regulation and policy in safeguarding the public's health. Each of us has devoted a career to thinking carefully about the role of law as a tool to prevent injury and disease and to promote the population's health and wellbeing. 1, 2, 3 and 4 In this Guest Editorial we first explain what we mean by the term ‘governance’, as well as the role of law in a well-regulated society. Next, we explore the increasingly important, and challenging, concept of what we call national and global federalism—the inter-relationships among the various levels of governance (local, national, supranational and transnational) and among various actors in national and global health. Third, we explain the origins of this journal symposium, which arises from three conferences on the topic in Hong Kong and Sydney. Finally, we offer a brief introduction to the articles that follow.

A new national women's health policy : legal, ethical and policy initiatives to support women's health

In 1989 the first National Women's Health Policy was launched in Australia. Now, 20 years later, the Federal Government has announced plans for the development of a new National Women's Health Policy to address the health needs of Australian women. The Policy will be based on five principles: gender equity; health equity between women; a focus on prevention; an evidence base for interventions; and a life course approach. This editorial examines the role for law in the development of a new National Women's Health Policy. It considers the relevance of regulatory frameworks for health research in supporting an evidence base for health interventions and analyses the requirement in the National Health and Medical Research Council's National Statement on Ethical Conduct in Human Research for "fair inclusion" of research participants. The editorial argues for a holistic approach to women's health that includes regulatory frameworks for research, identification of funding priorities for research, and the need for a dedicated government department or agency to promote women's health.

Reproductive technology, public policy and single motherhood

In mid 2000, the Australian community engaged in a national debate over access to infertility treatment services. The debate was sparked by a Federal Court decision in late July. That decision, by Justice Sundberg in the case of McBain v State of Victoria 1 held that the provisions of the Infertility Treatment Act 1995 (Vic) which limited eligibility for infertility treatment to women who were married or in heterosexual de facto relationships, were inconsistent with section 22 of the Commonwealth Sex Discrimination Act 1984 (Cth) which prohibits discrimination on the basis of marital status. Justice Sundberg held that, by virtue of section 109 of the Constitution, 2 the provisions of the Victorian Act were inoperative to the extent of the inconsistency between the State and Commonwealth legislation.

Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense matrices

Background The behaviour of tumour cells depends on factors such as genetics and the tumour microenvironment. The latter plays a crucial role in normal mammary gland development and also in breast cancer initiation and progression. Breast cancer tissues tend to be highly desmoplastic and dense matrix as a pre-existing condition poses one of the highest risk factors for cancer development. However, matrix influence on tumour cell gene expression and behaviour such as cell migration is not fully elucidated. Results We generated high-density (HD) matrices that mimicked tumour collagen content of 20 mg/cm3 that were ~14-fold stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cell imaging showed breast cancer cells utilizing cytoplasmic streaming and cell body contractility for migration within HD matrix. Cell migration was blocked in the presence of both the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugs individually. This suggests roles for ROCK1 and MMP in cell migration are complicated by compensatory mechanisms. ROCK1 expression and protein activity, were significantly upregulated in HD matrix but these were blocked by treatment with a histone deacetylase (HDAC) inhibitor, MS-275. In HD matrix, the inhibition of ROCK1 by MS-275 was indirect and relied upon protein synthesis and Notch1. Inhibition of Notch1 using pooled siRNA or DAPT abrogated the inhibition of ROCK1 by MS-275. Conclusion Increased matrix density elevates ROCK1 activity, which aids in cell migration via cell contractility. The upregulation of ROCK1 is epigenetically regulated in an indirect manner involving the repression of Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an upregulation of Notch1 levels leading to blockade of ROCK1 expression.

Bimolecular interaction of Insulin-Like Growth Factor (IGF) binding protein-2 with αvβ3 negatively modulates IGF-I-Mediated migration and tumor growth

Both the integrin and insulin-like growth factor binding protein (IGFBP) families independently play important roles in modulating tumor cell growth and progression. We present evidence for a specific cell surface localization and a bimolecular interaction between the αvβ3 integrin and IGFBP-2. The interaction, which could be specifically perturbed using vitronectin and αvβ3 blocking antibodies, was shown to modulate IGF-mediated cellular migration responses. Moreover, this interaction was observed in vivo and correlated with reduced tumor size of the human breast cancer cells, MCF-7β3, which overexpressed the αvβ3 integrin. Collectively, these results indicate that αvβ3 and IGFBP-2 act cooperatively in a negative regulatory manner to reduce tumor growth and the migratory potential of breast cancer cells.

Epidermal growth factor promotes MDA-MB-231 breast cancer cell migration through a phosphatidylinositol 3'-kinase and phospholipase C-dependent mechanism

Epidermal growth factor receptor (EGFR) levels predict a poor outcome in human breast cancer and are most commonly associated with proliferative effects of epidermal growth factor (EGF), with little emphasis placed on motogenic responses to EGF. We found that MDA-MB-231 human breast cancer cells elicited a potent chemotactic response despite their complete lack of a proliferative response to EGF. Antagonists of EGFR ligation, the EGFR kinase, phosphatidylinositol 3'-kinase, and phospholipase C, but not the mitogen- activated protein kinases (extracellular signal-regulated protein kinase 1 and 2), blocked MDA-MB-231 chemotaxis. These findings suggest that EGF may influence human breast cancer progression via migratory pathways, the signaling for which appears to be dissociated, at least in part, from the proliferative pathways.

Hidden innovation : Policy, industry and the creative sector

The term ‘two cultures’ was coined more than 50 years ago by scientist and novelist C.P. Snow to describe the divergence in the world views and methods of scientists and the creative sector. This divergence has meant that innovation systems and policies have focused for decades on science, engineering, technology and medicine and the industries that depend on them. The humanities, arts and social sciences have been bit players at best; their contributions hidden from research agendas, policy and program initiatives, and the public mind. But structural changes to advanced economies and societies have brought services industries and the creative sector to greater prominence as key contributors to innovation. Hidden Innovation peels back the veil, tracing the way innovation occurs through new forms of screen production enabled by social media platforms as well as in public broadcasting. It shows that creative workers are contributing fresh ideas across the economy and how creative cities debates need reframing. It traces how policies globally are beginning to catch up with the changing social and economic realities. In his new book, Cunningham argues that the innovation framework offers the best opportunity in decades to reassess and refresh the case for the public role of the humanities, particularly the media, cultural and communication studies disciplines.

Transfection of MDA-MB-231 human breast carcinoma cells with bone sialoprotein (BSP) stimulates migration and invasion in vitro and growth of primary and secondary tumors in nude mice

We have investigated the role of bone sialoprotein (BSP), a secreted glycoprotein normally found in bone, in breast cancer progression. To explore functions for BSP in human breast cancer invasion and metastasis, the full-length BSP cDNA was transfected into the MDA-MB-231-BAG human breast cancer cell line under the control of the CMV promoter. Clones expressing BSP and vector control clones were isolated. BSP producing clones showed increased monolayer wound healing, a faster rate of stellate outgrowth in Matrigel and increased rate of invasion into a collagen matrix when compared to control clones. Clones were also examined in models of breast cancer growth and metastasis in vivo. BSP transfected clones showed an increased rate of primary tumor growth following mammary fat pad injection of nude mice. BSP transfected clones and vector control clones metastasized to soft organs and bone at a similar rate after intra-cardiac injection as determined by real-time PCR and X-ray analysis. Although these organs were targets for both BSP transfected and non-transfected cells, the size of the metastatic lesion was shown to be significantly larger for BSP expressing clones. This was determined by real-time PCR analysis for soft organs and by X-ray analysis of bone lesions. For bone this was confirmed by intra-tibial injections of cells in nude mice. We conclude that BSP acts to drive primary and secondary tumor growth of breast cancers in vivo.

Anionic migration in aromatic systems effected by collisional activation. Unusual fragmentations of deprotonated anilides containing methoxyl and ethoxyl substituents

Long-range cross-ring reactions occur when (M - H)(-) ions of methoxy- and ethoxy-C6H4-(-)NCOR (R = H, CH3, C6H5 and CH3O) are subjected to collisional activation, These reactions are generally minor processes: a particular example is the cross-ring elimination p-C2H5O-C6H4-(NCOCH3)-N-- --> [CH3-(p-C2H5O-C6H4-NCO)] --> p-(O--)-C6H4-NCO + C2H4 + CH4. Major processes of these (M - H)(-) ions involve (i) losses of radicals to form stabilised radical anions, e.g. (a) loss of a ring H-. or (b) CH3. (or C2H5.) from the alkoxy group, and (ii) proximity effects when the two substituents are ortho, e.g. loss of CH3OH from o-CH3O-C6H4-(NCHO)-N-- yields deprotonated benzoxazole. Another fragmentation of an arylmethoxyl anion involves loss of CH2O. It is proposed that losses of CH2O are initiated by anionic centres but the actual mechanisms in the cases studied depend upon the substitution pattern of the methoxyanilide: o- and p-methoxyanilides may undergo ipso proton transfer/elimination reactions, whereas the in-analogues undergo proton transfer reactions to yield an o-CH3O substituted aryl carbanion followed by proton transfer from CH3O to the carbanion site with concomitant loss of CH2O.

Effects of child care policy and environment on physical activity

Child care centers differ systematically with respect to the quality and quantity of physical activity they provide, suggesting that center-level policies and practices, as well as the center's physical environment, are important influences on children's physical activity behavior. Purpose To summarize and critically evaluate the extant peer-reviewed literature on the influence of child care policy and environment on physical activity in preschool-aged children. Methods A computer database search identified seven relevant studies that were categorized into three broad areas: cross-sectional studies investigating the impact of selected center-level policies and practices on moderate-to-vigorous physical activity (MVPA), studies correlating specific attributes of the outdoor play environment with the level and intensity of MVPA, and studies in which a specific center-level policy or environmental attribute was experimentally manipulated and evaluated for changes in MVPA. Results Staff education and training, as well as staff behavior on the playground, seem to be salient influences on MVPA in preschoolers. Lower playground density (less children per square meter) and the presence of vegetation and open play areas also seem to be positive influences on MVPA. However, not all studies found these attributes to be significant. The availability and quality of portable play equipment, not the amount or type of fixed play equipment, significantly influenced MVPA levels. Conclusions Emerging evidence suggests that several policy and environmental factors contribute to the marked between-center variability in physical activity and sedentary behavior. Intervention studies targeting these factors are thus warranted.

Bone sialoprotein supports breast cancer cell adhesion proliferation and migration through differential usage of the αvβ3 and αvβ5 integrins

Bone sialoprotein (BSP), a secreted glycoprotein found in bone matrix, has been implicated in the formation of mammary microcalcifications and osteotropic metastasis of human breast cancer (HBC). BSP possesses an integrin-binding RGD (Arg-Gly-Asp) domain, which may promote interactions between HBC cells and bone extracellular matrix. Purified BSP, recombinant human BSP fragments and BSP-derived RGD peptides are shown to elicit migratory, adhesive, and proliferative responses in the MDA-MB-231 HBC cell line. Recombinant BSP fragment analysis localized a significant component of these activities to the RGD domain of the protein, and synthetic RGD peptides with BSP flanking sequences (BSPRGD) also conferred these responses. The fibronectin-derived RGD counterpart, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro), could not support these cellular responses, emphasizing specificity of the BSP configuration. Although most of the proliferative and adhesive responses could be attributed to RGD interactions, these interactions were only partly responsible for the migrational responses. Experiments with integrin-blocking antibodies demonstrated that BSP-RGD-induced migration utilizes the αvβ3 vitronectin receptor, whereas adhesion and proliferation responses were αvβ5-mediated. Using fluorescence activated cell sorting, we selected two separate subpopulations of MDA-MB-231 cells enriched for αvβ3 or αvβ5 respectively. Although some expression of the alternate αv integrin was still retained, the αvβ5-enriched MDA-MB-231 cells showed enhanced proliferative and adhesive responses, whereas the αvβ3-enriched subpopulation was suppressed for proliferation and adhesion, but showed enhanced migratory responses to BSP-RGD. In addition, similar analysis of two other HBC cell lines showed less marked, but similar RGD-dependent trends in adhesion and proliferation to the BSP fragments. Collectively, these data demonstrate BSP effects on proliferative, migratory, and adhesive functions in HBC cells and that the RGD-mediated component differentially employs αvβ3 and αvβ5 integrin receptors.