Biological management of the invasive Vachellia nilotica ssp. indica (Benth.) Kyal. & Boatwr. (Fabales: Mimosoideae) in tropical Australia: stress-inducing potential of Anomalococcus indicus Ramakrishna (Insecta: Hemiptera: Coccoidea: Lecanodiaspididae), an agent of promise

Vachellia nilotica ssp. indica (hereafter, V. n. indica) is an important tree weed in Australia. Its dense populations induce undesirable changes in the vast areas of northern Australia. Because chemical and mechanical management options appear unviable for various reasons, biological management of this tree is considered a better option. Among the many trialled arthropods in Australian context, Anomalococcus indicus, a lecanodiaspid native to India, has been identified as a potent-candidate, since in India, its native terrain, it is the most widespread and occurs throughout the year. Severe infestations of A. indicus cause defoliation, wilting and death of branches, and occasionally the tree. Populations of A. indicus have been brought into Australia and are being tested for its host specificity under quarantine conditions. This article reports the physiological damage and stress it inflicts in the shoots of V. n. indica. Younger-nymphal instars of A. indicus feed on cortical-parenchyma cells of young stems, whereas the older instars and adults feed from the phloem of old stems. Two conspicuous responses of V. n. indica arising in response to the feeding action of A. indicus are changes in the cell-wall dynamics and irregular cell divisions. The feeding action of A. indicus elicits a sequence of reactions in the stem tissues of V. n. indica such as differentiation of thick-walled elements in the outer cortical parenchyma, differential thickening of cells with supernumerary layers of either suberin or lignin, proliferations of parenchyma and phloem, wall thickening and obliteration of inner lumen of phloem cells, and the sieve plates plugged with callosic deposits. The responses are the culminations of interaction between the virulence factor (one or more of the salivary proteins?) from A. indicus and the resistance factor in V. n. indica. We have analysed structural changes in the context of their functions, by comparing the feeding action of A. indicus with that of other hemipteroids. From the level of stress it induces, this study confirms that A. indicus has the potential to be an effective biological management of V. n. indica in Australia. © 2014 © 2014 Taylor & Francis and Aboricultural Association.

Creating healthy food environments in NSW: A knowledge and evidence synthesis to inform advocacy and action. Seven separate documents across the domains: Overview

Summaries evidence across seven domains of potential food policy action to improve food environments and food supply to prevent obesity for NSW Health

Mechanism of action of selenious acid in the electrodeposition of manganese

The effect of selenious acid as an addition agent in the electrodeposition of manganese was studied by analysing the current-potential curves for manganese deposition. The mechanism of action of this addition agent was found to be essentially similar to that proposed for sulphur dioxide, namely to affect the manganese deposition indirectly by influencing the hydrogen evolution reaction which is a parallel reaction at the electrode surface.

Educational action research in Singapore: To prove or improve?

The rise of educational action research amongst schools in Singapore can be attributed to the government’s belief that educational research and reform can improve school performance and help Singapore keep pace with the impact of globalization. However, against a backdrop of neo-liberal educational reform where efficiency, accountability and demonstrable outcomes are valued, the underlying intent of the action research projects would seem to be inconsistent with the emancipatory intent normally associated with action research. A systematic review was conducted of 71 action research projects submitted to a local educational conference in 2006. Of concern to us is how action research has been narrowly interpreted and recruited simply as an evaluative tool with the emancipatory potential largely ignored. The paper is theoretically framed by governmentality and performativity to explore the embedded power relations that may “fabricate” the action research projects. The findings and discussions suggest a need for the government, schools and teacher-researchers to reflexively question the current expectation of action research and to be clear about its broader purpose

Bustle behind the scenes of action : nemosis as a model for fibroblast inflammatory activation

Wound healing is a complex process that requires an interplay between several cell types. Classically, fibroblasts have been viewed as producers of extracellular matrix, but more recently they have been recognized as orchestrators of the healing response, promoting and directing, inflammation and neovascularization processes. Compared to those from healthy tissue, inflammation-associated fibroblasts display a dramatically altered phenotype and have been described as sentinel cells, able to switch to an immunoregulatory profile on cue. However, the activation mechanism still remains largely uncharacterized. Nemosis is a model for stromal fibroblast activation. When normal human primary fibroblasts are deprived of growth support they cluster, forming multicellular spheroids. Clustering results in upregulation of proinflammatory markers such as cyclooxygenase-2 and secretion of prostaglandins, proteinases, cytokines, and growth factors. Fibroblasts in nemosis induce wound healing and tumorigenic responses in many cell types found in inflammatory and tumor microenvironments. This study investigated the effect of nemotic fibroblasts on two components of the vascular system, leukocytes and endothelium, and characterized the inflammation-promoting responses that arose in these cell types. Fibroblasts in nemosis were found to secrete an array of chemotactic cytokines and attract leukocytes, as well as promote their adhesion to the endothelium. Nuclear factor-kB, the master regulator of many inflammatory responses, is activated in nemotic fibroblasts. Nemotic fibroblasts are known to produce large amounts of hepatocyte growth factor, a motogenic and angiogenic factor. Also, as shown in this study, they produce vascular endothelial growth factor. These two factors induced migratory and sprouting responses in endothelial cells, both required for neovascularization. Nemotic fibroblasts also caused a decrease in the expression of adherens and tight junction components on the surface of endothelial cells. The results allow the conclusion that fibroblasts in nemosis share many similarities with inflammation-associated fibroblasts. Both inflammation and stromal fibroblasts are known to be involved in tumorigenesis and tumor progression. Nemosis may be viewed as a model for stromal fibroblast activation, or it may correlate with cell-cell interactions between adjacent fibroblasts in vivo. Nevertheless, due to nemosis-derived production of proinflammatory cytokines and growth factors, fibroblast nemosis may have therapeutic potential as an inducer of controlled tissue repair. Knowledge of stromal fibroblast activation gained through studies of nemosis, could provide new strategies to control unwanted inflammation and tumor progression.

Customer asset management in action: using customers portfolio for allocating resources across business-to-business relationships for improved shareholder value

Suvi Nenonen Customer asset management in action: using customer portfolios for allocating resources across business-to-business relationships for improved shareholder value Customers are crucial assets to all firms as customers are the ultimate source of all cash flows. Regardless this financial importance of customer relationships, for decades there has been a lack of suitable frameworks explaining how customer relationships contribute to the firm financial performance and how this contribution can be actively managed. In order to facilitate a better understanding of the customer asset, contemporary marketing has investigated the use of financial theories and asset management practices in the customer relationship context. Building on this, marketing academics have promoted the customer lifetime value concept as a solution for valuating and managing customer relationships for optimal financial outcomes. However, the empirical investigation of customer asset management lags behind the conceptual development steps taken. Additionally, the practitioners have not embraced the use of customer lifetime value in guiding managerial decisions - especially in the business-to-business context. The thesis points out that there are fundamental differences between customer relationships and investment instruments as investment targets, effectively eliminating the possibility to use financial theories in a customer relationships context or to optimize the customer base as a single investment portfolio. As an alternative, the thesis proposes the use of customer portfolio approach for allocating resources across the customer base for improved shareholder value. In the customer portfolio approach, the customer base of a firm is divided into multiple portfolios based on customer relationships’ potential to contribute to the shareholder value creation. After this, customer management concepts are tailored to each customer portfolio, designed to improve the shareholder value in their own respect. Therefore, effective customer asset management with the customer portfolio approach necessitates that firms are able to manage multiple parallel customer management concepts, or business models, simultaneously. The thesis is one of the first empirical studies on customer asset management, bringing empirical evidence from multiple business-to-business case studies on how customer portfolio models can be formed, how customer portfolios can be managed, and how customer asset management has contributed to the firm financial performance.

Customer asset management in action: using customers portfolio for allocating resources across business-to-business relationships for improved shareholder value

Suvi Nenonen Customer asset management in action: using customer portfolios for allocating resources across business-to-business relationships for improved shareholder value Customers are crucial assets to all firms as customers are the ultimate source of all cash flows. Regardless this financial importance of customer relationships, for decades there has been a lack of suitable frameworks explaining how customer relationships contribute to the firm financial performance and how this contribution can be actively managed. In order to facilitate a better understanding of the customer asset, contemporary marketing has investigated the use of financial theories and asset management practices in the customer relationship context. Building on this, marketing academics have promoted the customer lifetime value concept as a solution for valuating and managing customer relationships for optimal financial outcomes. However, the empirical investigation of customer asset management lags behind the conceptual development steps taken. Additionally, the practitioners have not embraced the use of customer lifetime value in guiding managerial decisions - especially in the business-to-business context. The thesis points out that there are fundamental differences between customer relationships and investment instruments as investment targets, effectively eliminating the possibility to use financial theories in a customer relationships context or to optimize the customer base as a single investment portfolio. As an alternative, the thesis proposes the use of customer portfolio approach for allocating resources across the customer base for improved shareholder value. In the customer portfolio approach, the customer base of a firm is divided into multiple portfolios based on customer relationships’ potential to contribute to the shareholder value creation. After this, customer management concepts are tailored to each customer portfolio, designed to improve the shareholder value in their own respect. Therefore, effective customer asset management with the customer portfolio approach necessitates that firms are able to manage multiple parallel customer management concepts, or business models, simultaneously. The thesis is one of the first empirical studies on customer asset management, bringing empirical evidence from multiple business-to-business case studies on how customer portfolio models can be formed, how customer portfolios can be managed, and how customer asset management has contributed to the firm financial performance.

Kinetic decomposition of Ni2SiO4 in oxygen potential gradients

Nickel orthosilicate (Ni2SiO4) has been found to decompose into its component binary oxides in oxygen potential gradients at 1373 K. Nickel oxide was formed at the high oxygen potential boundary, while silica was detected at the low oxygen potential side. Significant porosity and fissures were observed near the Ni2SiO4/SiO2 interface and the SiO2 layer. The critical oxygen partial pressure ratio required for decomposition varied from 1.63 to 2.15 as the oxygen pressures were altered from 1.01 ⊠ 105 to 2.7X 10−4 Pa, well above the dissociation pressure of Ni2SiO4. Platinum markers placed at the boundaries of the Ni2SiO4 sample indicated growth of NiO at the higher oxygen potential boundary, without any apparent transport of material to the low oxygen potential side. However, significant movement of the bulk Ni2SiO4 crystal with respect to the marker was not observed. The decomposition of the silicate occurs due to the unequal rates of transport of Ni and Si. The critical oxygen partial pressure ratio required for decomposition is related both to the thermodynamic stability of Ni2SiO4 with respect to component oxides and the ratio of diffusivities of nickel and silicon. Kinetic decomposition of multicomponent oxides, first discovered by Schmalzried, Laqua, and co-workers [H. Schmalzried, W. Laqua, and P. L. Lin, Z. Natur Forsch. Teil A 34, 192 (1979); H. Schmalzried and W. Laqua, Oxid. Met. 15, 339 (1981); W. Laqua and H. Schmalzried, Chemical Metallurgy—A Tribute to Carl Wagner (Metallurgical Society of the AIME, New York, 1981), p. 29] has important consequences for their use at high temperatures and in geochemistry.

The biological and structural characterization of Mycobacterium tuberculosis UvrA provides novel insights into its mechanism of action

Mycobacterium tuberculosis is an extremely well adapted intracellular human pathogen that is exposed to multiple DNA damaging chemical assaults originating from the host defence mechanisms. As a consequence, this bacterium is thought to possess highly efficient DNA repair machineries, the nucleotide excision repair (NER) system amongst these. Although NER is of central importance to DNA repair in M. tuberculosis, our understanding of the processes in this species is limited. The conserved UvrABC endonuclease represents the multi-enzymatic core in bacterial NER, where the UvrA ATPase provides the DNA lesion-sensing function. The herein reported genetic analysis demonstrates that M. tuberculosis UvrA is important for the repair of nitrosative and oxidative DNA damage. Moreover, our biochemical and structural characterization of recombinant M. tuberculosis UvrA contributes new insights into its mechanism of action. In particular, the structural investigation reveals an unprecedented conformation of the UvrB-binding domain that we propose to be of functional relevance. Taken together, our data suggest UvrA as a potential target for the development of novel anti-tubercular agents and provide a biochemical framework for the identification of small-molecule inhibitors interfering with the NER activity in M. tuberculosis.

Simulations reveal that the HIV-1 gp120-CD4 complex dissociates via complex pathways and is a potential target of the polyamidoamine (PAMAM) dendrimer

The polyamidoamine (PAMAM) dendrimer prevents HIV-1 entry into target cells in vitro. Its mechanism of action, however, remains unclear and precludes the design of potent dendrimers targeting HIV-1 entry. We employed steered molecular dynamics simulations to examine whether the HIV-1 gp120-CD4 complex is a target of PAMAM. Our simulations mimicked single molecule force spectroscopy studies of the unbinding of the gp120-CD4 complex under the influence of a controlled external force. We found that the complex dissociates via complex pathways and defies the standard classification of adhesion molecules as catch and slip bonds. When the force loading rate was large, the complex behaved as a slip bond, weakening gradually. When the loading rate was small, the complex initially strengthened, akin to a catch bond, but eventually dissociated over shorter separations than with large loading rates. PAMAM docked to gp120 and destabilized the gp120-CD4 complex. The rupture force of the complex was lowered by PAMAM. PAMAM disrupted salt bridges and hydrogen bonds across the gp120-CD4 interface and altered the hydration pattern of the hydrophobic cavity in the interface. In addition, intriguingly, PAMAM suppressed the distinction in the dissociation pathways of the complex between the small and large loading rate regimes. Taken together, our simulations reveal that PAMAM targets the gp120-CD4 complex at two levels: it weakens the complex and also alters its dissociation pathway, potentially inhibiting HIV-1 entry.

Suramin is a potent and selective inhibitor of Mycobacterium tuberculosis RecA protein and the SOS response: RecA as a potential target for antibacterial drug discovery

In eubacteria, RecA is essential for recombinational DNA repair and for stalled replication forks to resume DNA synthesis. Recent work has implicated a role for RecA in the development of antibiotic resistance in pathogenic bacteria. Consequently, our goal is to identify and characterize small-molecule inhibitors that target RecA both in vitro and in vivo. We employed ATPase, DNA strand exchange and LexA cleavage assays to elucidate the inhibitory effects of suramin on Mycobacterium tuberculosis RecA. To gain insights into the mechanism of suramin action, we directly visualized the structure of RecA nucleoprotein filaments by atomic force microscopy. To determine the specificity of suramin action in vivo, we investigated its effect on the SOS response by pull-down and western blot assays as well as for its antibacterial activity. We show that suramin is a potent inhibitor of DNA strand exchange and ATPase activities of bacterial RecA proteins with IC50 values in the low micromolar range. Additional evidence shows that suramin inhibits RecA-catalysed proteolytic cleavage of the LexA repressor. The mechanism underlying such inhibitory actions of suramin involves its ability to disassemble RecA-single-stranded DNA filaments. Notably, suramin abolished ciprofloxacin-induced recA gene expression and the SOS response and augmented the bactericidal action of ciprofloxacin. Our findings suggest a strategy to chemically disrupt the vital processes controlled by RecA and hence the promise of small molecules for use against drug-susceptible as well as drug-resistant strains of M. tuberculosis for better infection control and the development of new therapies.

2-(4-Chlorobenzyl)-6-arylimidazo2,1-b]1,3,4]thiadiazoles: Synthesis, cytotoxic activity and mechanism of action

The cytotoxic activity of a new series of 2-(4'-chlorobenzyl)-5,6-disubstituted imidazo2,1-b]1,3,4]wthiadiazoles against different human and murine cancer cell lines is reported. Among the tested compounds, two derivatives namely 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo2,1-1)]1,3,4]th iadiazole-5-carbaldehyde 4i and 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-ypimidazo2,1-1)]1,3,4]thi adiazol-5-yl thiocyanate 5i emerged as the most potent against all the cell lines. To investigate the mechanism of action, we selected compounds 4i for cell cycle study, analysis of mitochondrial membrane potential and Annexin V-FITC flow cytometric analysis and DNA fragmentation assay. Results showed that 4i induced cytotoxicity by inducing apoptosis without arresting the cell cycle. (C) 2014 Elsevier Masson SAS. All rights reserved.

Synthesis and evaluation of the biological activity of N `-2-oxo-1,2 dihydro-3H-indol-3-ylidene] benzohydrazides as potential anticancer agents

New N'-2-oxo-1,2-dihydro-3H-indol-3-ylidene]benzohydrazide derivatives were synthesized and evaluated for their cytotoxic properties against murine leukemia, L1210, human leukemia, REH and K562, human T-cell leukemia, CEM and human cervix carcinoma, HeLa cells. Among the tested compounds, the 3,4,5-trimethoxy-N'-5-methyl-2-oxo-1,2-dihydro-3H-indol-3-ylidene]ben zohydrazide derivative (5t) emerged as the most potent inhibitor against all the tumor cell lines evaluated. To investigate the mechanism of action, 5t was further studied by cell cycle analysis, mitochondrial membrane potential analysis, DNA fragmentation and Annexin V-FITC flow cytometric analysis, which suggested that 5t was able to induce apoptosis at submicromolar range.

Exploring the potential of adjunct therapy in tuberculosis

A critical unmet need for treatment of drug-resistant tuberculosis (TB) is to find novel therapies that are efficacious, safe, and shorten the duration of treatment. Drug discovery approaches for TB primarily target essential genes of the pathogen Mycobacterium tuberculosis (Mtb) but novel strategies such as host-directed therapies and nonmicrobicidal targets are necessary to bring about a paradigm shift in treatment. Drugs targeting the host pathways and nonmicrobicidal proteins can be used only in conjunction with existing drugs as adjunct therapies. Significantly, host-directed adjunct therapies have the potential to decrease duration of treatment, as they are less prone to drug resistance, target the immune responses, and act via novel mechanism of action. Recent advances in targeting host-pathogen interactions have implicated pathways such as eicosanoid regulation and angiogenesis. Furthermore, several approved drugs such as metformin and verapamil have been identified that appear suitable for repurposing for the treatment of TB. These findings and the challenges in the area of host- and/or pathogen-directed adjunct therapies and their implications for TB therapy are discussed.

Florida's West Coast inlets: shoreline effects and recommended action

This report responds to the 1986 Beaches Bill which, in recognition of the potential deleterious impact on Florida's beaches of inlets modified for navigation, mandated a study of those inlets with identification of recommended action to reduce the impacts. This report addresses west Coast inlets; East Coast inlets are the subject of a companion report. There are 37 inlets along that portion of Florida's West Coast commencing from Pensacola Bay Entrance to Caxambas Pass at the south end of Marco Island. Compared to those on the East Coast, most West Coast inlets have not had the deleterious effects on the adjacent beaches, yet all modified inlets without proper management have the potential of impacting unfavorably on the adjacent shorelines. Moreover, at present there is interest in opening three West Coast entrances which either have been open in the past (Midnight Pass) or which have opened occasionally (Navarre Pass and Entrance to Phillips Lake). A review of inlets in their natural condition demonstrates the presence of a shallow broad outer bar across which the longshore transport Occurs. These shallow and shifting bar features were unsuitable for navigation which in many cases has led to the deepening of the channels and fixing with one or two jetty structures. Inlets in this modified state along with inappropriate maintenance practices have the potential of placing great ero$ional stress along the adjacent beaches. Moreover. channel dredging can reduce wave sheltering of the shoreline by ebb tidal shoals and alter the equilibrium of the affected shoreline segments. The ultimate in poor sand management practice is the placement of good quality beach sand in water depths too great for the sand to reenter the longshore system under natural forces; depths of 12 ft. or less are considered appropriate for Florida in order to maintain the sand in the system. With the interference of the nearshore sediment transport processes by inlets modified for navigation, if the adjacent beaches are to be stabilized there must be an active monitoring program with commitment to placement of dredged material of beach quality on shoreline segments of documented need. Several East Coast inlets have such transfer facilities; however. the quantities of sand transferred should be increased. Although an evolution and improvement in the technical capability to manage sand resources in the vicinity of inlets is expected, an adequate capability exists today and a concerted program should be made to commence a scheduled implementation of this capability at those entrances causing greatest erosional stress on the adjacent shorelines. A brief summary review for each of the 37 West Coast inlets is presented including: a scaled aerial photograph, brief historical information, several items related to sediment losses at each inlet and special characteristics relevant to State responsibilities. For each inlet, where appropriate, the above infor~tion is utilized to develop a recommenced action. (PDF has 101 pages.)