The ADAMTS1 protease gene is required for mammary tumor growth and metastasis

A disintegrin and metalloprotease with thrombospondin motifs protein 1 (ADAMTS1) is a protease commonly up-regulated in metastatic carcinoma. Its overexpression in cancer cells promotes experimental metastasis, but whether ADAMTS1 is essential for metastatic progression is unknown. To address this question, we investigated mammary cancer progression and spontaneous metastasis in the MMTV-PyMT mouse mammary tumor model in Adamts1 knockout mice. Adamts1−/−/PyMT mice displayed significantly reduced mammary tumor and lung metastatic tumor burden and increased survival, compared with their wild-type and heterozygous littermates. Histological examination revealed an increased proportion of tumors with ductal carcinoma in situ and a lower proportion of high-grade invasive tumors in Adamts1−/−/PyMT mice, compared with Adamts1+/+/PyMT mice. Increased apoptosis with unaltered proliferation and vascular density in the Adamts1−/−/PyMT tumors suggested that reduced cell survival accounts for the lower tumor burden in ADAMTS1-deficient mice. Furthermore, Adamts1−/− tumor stroma had significantly lesser amounts of proteolytically cleaved versican and increased numbers of CD45+ leukocytes. Characterization of immune cell gene expression indicated that cytotoxic cell activation was increased in Adamts1−/− tumors, compared with Adamts1+/+ tumors. This finding is supported by significantly elevated IL-12+ cell numbers in Adamts1−/− tumors. Thus, in vivo ADAMTS1 may promote mammary tumor growth and progression to metastasis in the PyMT model and is a potential therapeutic target to prevent metastatic breast cancer.

The ACNC's new governance rules

Australian charities have a new regulator in the form of the Australian Charities and Not-for-profits Commission (ACNC) which began operations in December 2012; and new governance rules which applied from 1 July 2013. While there is some uncertainty over the ACNC's future, the new legislative framework currently applies to approximately 58,000 charities which seek federal tax concessions and other benefits, and includes governance standards that apply across charitable organisational forms (company, trust and association) with some exceptions. The governance standards are a minimum benchmark that many charities will already meet, if they are companies or incorporated associations.

Emerging Planning Frameworks for Climate Adaptation

This chapter focuses on the more strategic activities that lead people in the regional community to decide how they want to respond to climate change. Such strategic activities include analysing, prioritising and deciding upon the best course of action. Planning for climate adaptation (usually seen to include the setting of visions and objectives, the determination of key strategies and the monitoring of broad outcomes) encompasses the strategic activities involved in the system of governance for climate adaptation. Planning occurs at all scales from global to the business, property, family and even individual scales. Applying a rapid appraisal technique, this chapter analyses the system of planning for climate adaptation as it relates to the achievement of adaptation outcomes within the Wet Tropics Cluster. It finds that some aspects of the system are healthier than others, and identifies several actions that regional NRM bodies may consider (either collectively or individually) to enhance adaptation outcomes by improving the planning system within the cluster.

A prostitute's progress : male prostitution in scientific discourse

This paper examines discourses of male prostitution through an analysis of scientific texts. A contrast is drawn between nineteenth-century understandings of male prostitution and twentieth-century accounts of male prostitution. In contrast to female prostitution, male prostitution was not regarded as a significant social problem throughout the nineteenth century, despite its close association with gender deviation and social disorder. Changing conceptions of sexuality, linked with the emergence of the ‘adolescent’, drew scientific attention to male prostitution during the 1940s and 1950s. Research suggested that male prostitution was a problem associated with the development of sexual identity. Through the application of scientific techniques, which tagged and differentiated male prostitute populations, a language developed about male prostitution that allowed for normative assessments and judgements to be made concerning particular classes of male prostitute. The paper highlights how a broad distinction emerged between public prostitutes, regarded as heterosexual/masculine, and private prostitutes, regarded as homosexual/effeminate. This distinction altered the way in which male prostitution was understood and governed, allowing for male prostitution to be constituted as a public health concern.

The effect of repeated loading and freeze-thaw cycling on immature bovine thoracic motion segment stiffness

There is growing interest in the biomechanics of ‘fusionless’ implant constructs used for deformity correction in the thoracic spine, however, there are questions over the comparability of in vitro biomechanical studies from different research groups due to the various methods used for specimen preparation, testing and data collection. The aim of this study was to identify the effect of two key factors on the stiffness of immature bovine thoracic spine motion segments: (i) repeated cyclic loading and (ii) multiple freeze-thaw cycles, to aid in the planning and interpretation of in vitro studies. Two groups of thoracic spine motion segments from 6-8 week old calves were tested in flexion/extension, right/left lateral bending, and right/left axial rotation under moment control. Group (A) were tested with continuous repeated cyclic loading for 500 cycles with data recorded at cycles 3, 5, 10, 25, 50, 100, 200, 300, 400 and 500. Group (B) were tested after each of five freeze-thaw sequences, with data collected from the 10th load cycle in each sequence. Group A: Flexion/extension stiffness reduced significantly over the 500 load cycles (-22%; P=0.001), but there was no significant change between the 5th and 200th load cycles. Lateral bending stiffness decreased significantly (-18%; P=0.009) over the 500 load cycles, but there was no significant change in axial rotation stiffness (P=0.137). Group B: There was no significant difference between mean stiffness over the five freeze-thaw sequences in flexion/extension (P=0.813) and a near significant reduction in mean stiffness in axial rotation (-6%; P=0.07). However, there was a statistically significant increase in stiffness in lateral bending (+30%; P=0.007). Comparison of in vitro testing results for immature thoracic bovine spine segments between studies can be performed with up to 200 load cycles without significant changes in stiffness. However, when testing protocols require greater than 200 cycles, or when repeated freeze-thaw cycles are involved, it is important to account for the effect of cumulative load and freeze-thaw cycles on spine segment stiffness.

DroplIT, an improved image analysis method for droplet identification in high-throughput crystallization trials

The application of robotics to protein crystallization trials has resulted in the production of millions of images. Manual inspection of these images to find crystals and other interesting outcomes is a major rate-limiting step. As a result there has been intense activity in developing automated algorithms to analyse these images. The very first step for most systems that have been described in the literature is to delineate each droplet. Here, a novel approach that reaches over 97% success rate and subsecond processing times is presented. This will form the seed of a new high-throughput system to scrutinize massive crystallization campaigns automatically. © 2010 International Union of Crystallography Printed in Singapore-all rights reserved.

On the need for an international effort to capture, share and use crystallization screening data

When crystallization screening is conducted many outcomes are observed but typically the only trial recorded in the literature is the condition that yielded the crystal(s) used for subsequent diffraction studies. The initial hit that was optimized and the results of all the other trials are lost. These missing results contain information that would be useful for an improved general understanding of crystallization. This paper provides a report of a crystallization data exchange (XDX) workshop organized by several international large-scale crystallization screening laboratories to discuss how this information may be captured and utilized. A group that administers a significant fraction of the worlds crystallization screening results was convened, together with chemical and structural data informaticians and computational scientists who specialize in creating and analysing large disparate data sets. The development of a crystallization ontology for the crystallization community was proposed. This paper (by the attendees of the workshop) provides the thoughts and rationale leading to this conclusion. This is brought to the attention of the wider audience of crystallographers so that they are aware of these early efforts and can contribute to the process going forward. © 2012 International Union of Crystallography All rights reserved.

Strange and stranger ruralities: Social constructions of rural crime in Australia

Rural crime has largely been understood through social disorganization theory. The dominance of this perspective has meant that most research into rural crime has tried to resolve perceived strains in communities, rather than analyze how social problems are constituted in rural places. Using Elias and Scotson's (1994) account of established-outsider relations, the paper examines how the organizational capacity of specific social groups is significant in determining the quality of crime-talk and responses to crime in isolated and rural settings. In particular social 'oldness' and notions of what constitutes 'community' are significant in determining what activities and individuals or groups are marked as features of crime-talk in these settings.

Incentivising tenants to stay the term – will clawbacks be enforceable?

Incentives are commonly offered by commercial landlords to tenants in the form of short term rent deductions or contributions to the tenant’s fitout. Usually these incentives are conditional upon the lessee remaining in the premises for the term of the lease with an obligation on the tenant to repay a proportion of the fitout contribution and rent deductions upon early termination or assignment. While the enforceability of clawback provisions has always been unclear, there was commercial benefit to landlords in maintaining high rentals on the face of the lease and attracting good quality tenants through fitout contributions. The use of clawback provisions as part of these incentives was recently analysed by the Queensland Supreme Court through the lens of the penalties doctrine in GWC Property Group Pty Ltd v Higginson & Ors [2014] QSC 264, with a negative outcome for the landlord. Unless the decision is overturned on appeal, the salient message for landlords is that repayment of incentives for any reason, not just a breach of the lease, is unlikely to be enforceable.

Sectional analysis of stormwater treatment performance of a constructed wetland

Constructed wetlands are among the most common Water Sensitive Urban Design (WSUD) measures for stormwater treatment. These systems have been extensively studied to understand their performance and influential treatment processes. Unfortunately, most past studies have been undertaken considering a wetland system as a lumped system with a primary focus on the reduction of the event mean concentration (EMC) values of specific pollutant species or total pollutant load removal. This research study adopted an innovative approach by partitioning the inflow runoff hydrograph and then investigating treatment performance in each partition and their relationships with a range of hydraulic factors. The study outcomes confirmed that influenced by rainfall characteristics, the constructed wetland displays different treatment characteristics for the initial and later sectors of the runoff hydrograph. The treatment of small rainfall events (<15 mm) is comparatively better at the beginning of runoff events while the trends in pollutant load reductions for large rainfall events (>15 mm) are generally lower at the beginning and gradually increase towards the end of rainfall events. This highlights the importance of ensuring that the inflow into a constructed wetland has low turbulence in order to achieve consistent treatment performance for both, small and large rainfall events.

Crystal structure of the magnesium salt of the herbicide 2,4-D: pentaaqua[(2,4-dichlorophenoxy)acetato-kO]magnesium (2,4-dichlorophenoxy)acetate hemihydrate

In the structure of the title magnesium complex with the phenoxy herbicide (2,4-dichlorophenoxy)acetic acid (2,4-D), [Mg(H2O)5(C8H5Cl2O3)]+ C8H5Cl2O3)- . 0.5H2O, the discrete cationic MgO6 complex units comprise a carboxyl O-donor from a monodentate 2,4-D cationic ligand and five water molecules in a slightly distorted octahedral coordination. The 2,4-D anions are linked to the complex units through duplex water O-H...O(carboxyl) hydrogen bonds through the coordinated water molecules. In the crystal inter-unit O-H...O hydrogen-bonding interactions involving coordinated water molecules as well as the hemi-hydrate solvate molecule with carboxyl O-atom acceptors, give a two-dimensional layered structure lying parallel (001), in which pi-pi ligand-cation interactions [minimum ring centroid separation, 3.6405(17)A] and a short O-H...Cl interaction [3.345(2)A] are also found.

Crystal structures and hydrogen-bonding in the co-crystalline adducts of 3,5-dinitrobenzoic acid with 4-aminosalicylic acid and 2-hydroxy-3-(1H-indol-3-yl)propenoic acid

The structures of the cocrystalline adducts of 3,5-dinitrobenzoic acid (3,5-DNBA) with 4-aminosalicylic acid (PASA), the 1:1 partial hydrate, C7H4N2O6 .C7H7NO3 . 2H2O, (I) and 2-hydroxy-3-(1H-indol-3-yl)propenoic acid (HIPA) and the 1:1:1 d6-dimethylsulfoxide solvate, C7H4N2O6 . C11H9NO3 . C2D6OS, (II) are reported. The crystal substructure of (I) comprises two centrosymmetric hydrogen-bonded R2/2(8) homodimers, one with 3,5-DNBA, the other with PASA, and an R2/2(8) 3,5-DNBA-PASA heterodimer. In the crystal, inter-unit amine N-H...O and water O-H...O hydrogen bonds generate a three-dimensional supramolecular structure. In (II), the asymmetric unit consists of the three constituent molecules which form an essentially planar cyclic hydrogen-bonded heterotrimer unit [graph set R2/3(17)] through carboxyl, hydroxy and amino groups. These units associate across a crystallographic inversion centre through the HIPA carboxylic acid group in an R2/2~(8) hydrogen-bonding association, giving a zero-dimensional structure lying parallel to (100). In both structures, pi--pi interactions are present [minimum ring centroid separations: 3.6471(18)A in (I) and 3.5819(10)A in (II)].

Crystal structures of the co-crystalline adduct 5-(4-bromophenyl)-1,3,4-thiadiazol-2-amine--4-nitrobenzoic acid (1/1) and the salt 2-amino-5-(4-bromophenyl)-1,3,4-thiadiazol-3-ium 2-carboxy-4,6-dinitrophenolate

The structures of the 1:1 co-crystalline adduct C8H6BrN3S . C7H5NO4 (I) and the salt C8H7BrN3S+ C7H3N2O7- (II) from the interaction of 5-(4-bromophenyl)-1,3,4-thiadiazol-2-amine with 4-nitrobenzoic acid and 3,5-dinitrosalicylic acid, respectively, have been determined. The primary inter-species association in both (I) and (II) is through duplex R2/2(8) (N-H...O/O-H...O) or (N-H...O/N-H...O) hydrogen bonds, respectively, giving heterodimers. In (II), these are close to planar [dihedral angles between the thiadiazole ring and the two phenyl rings are 2.1(3)deg. (intra) and 9.8(2)deg. (inter)], while in (I) these angles are 22.11(15) and 26.08(18)deg., respectively. In the crystal of (I), the heterodimers are extended into a one-dimensional chain along b through an amine N-...N(thiadiazole) hydrogen bond but in (II), a centrosymmetric cyclic heterotetramer structure is generated through N-H...O hydrogen bonds to phenol and nitro O-atom acceptors and features, together with the primary R2/2(8) interaction, conjoined R4/6(12), R2/1(6) and S(6) ring motifs. Also present in (I) are pi--pi interactions between thiadiazole rings [minimum ring centroid separation, 3.4624(16)deg.] as well as short Br...O(nitro) interactions in both (I) and (II) [3.296(3)A and 3.104(3)A, respectively].