Calcitonin receptor plays a physiological role to protect against hypercalcemia in mice

It is well established that calcitonin is a potent inhibitor of bone resorption; however, a physiological role for calcitonin acting through its cognate receptor, the calcitonin receptor (CTR), has not been identified. Data from previous genetically modified animal models have recognized a possible role for calcitonin and the CTR in controlling bone formation; however, interpretation of these data are complicated, in part because of their mixed genetic background. Therefore, to elucidate the physiological role of the CTR in calcium and bone metabolism, we generated a viable global CTR knockout (KO) mouse model using the Cre/loxP system, in which the CTR is globally deleted by >94% but <100%. Global CTRKOs displayed normal serum ultrafiltrable calcium levels and a mild increase in bone formation in males, showing that the CTR plays a modest physiological role in the regulation of bone and calcium homeostasis in the basal state in mice. Furthermore, the peak in serum total calcium after calcitriol [1,25(OH)2D3]-induced hypercalcemia was substantially greater in global CTRKOs compared with controls. These data provide strong evidence for a biological role of the CTR in regulating calcium homeostasis in states of calcium stress.

Identification of broad specificity P450CAM variants by primary screening against indole as substrate

High-throughput screening of cytochrome P450CAM libraries, for their ability to oxidise indole to indigo and indirubin, has resulted in the identification of variants with activity towards the structurally unrelated substrate diphenylmethane.

Tactics of antifeminist backlash against the U. S. battered women's movement

Opposition to men’s violence against women who are their intimate partners has become politically popular in the United States. The Violence Against Women Act (VAWA) has enjoyed broad-based support for over 15 years. VAWA has been refined and expanded with each reauthorization. Resistance to the battered women’s movement is often overlooked in this political context. However, woman abuse and state responses to it are mired in cultural tensions about crime, law, gender, economics, scholarship, and the family. Based on interviews with 35 advocates in the United States, this paper outlines key tactics of antifeminist backlash against the battered women’s movement.

Unidentified vehicle in multi-vehicle accident - failure to notify Nominal Defendant no bar to proceedings against it

In Kumar v Suncorp Metway Insurance Limited [2004] QSC 381 Douglas J examined s37 of the Motor Accident Insurance Act 1994 (Qld) in the context of an accident involving multiple insurers when a notice of accident had not been given to the Nominal Defendant

Personal injuries sustained in the course of employment - claim against employer under Workcover Queensland Act 1996

In Devlin v South Mole Island Resort [2003] QSC 020 the Court concluded the applicant was entitled to pursue a concurrent claim he alleged he had against the respondent under the Personal Injuries Proceedings Act 2002 in respect of injuries sustained in the course of employment, and also that the Workcover Queensland Act 1996 did not abolish the applicant's right to proceed against the respondent.

The role of core protest group members in sustaining protest against controversial construction and engineering projects

Community-based protests against major construction and engineering projects are becoming increasingly common as concerns over issues such as corporate social accountability, climate change and corruption become more prominent in the public's mind. Public perceptions of risk associated with these projects can have a contagious effect, which mismanaged can escalate into long-term and sometimes acrimonious protest stand-offs that have negative implications for the community, firms involved and the construction industry as a whole. This paper investigates the role of core group members in sustaining community-based protest against construction and engineering projects. Using a thematic story telling approach which draws on ethnographic method and social contagion theories, it presents an in-depth analysis of a single case study - one of Australia's longest standing community protests against a construction project. It concludes that core group members play a critical role, within anarchic structures which provide a high degree of spontaneity and improvisation, in sustaining movement continuity by building collective identity, mobilising resources and a moving interface which developers find hard to communicate with.

Party to litigation insolvent company - costs order against non-party liquidator

In Kimtran Pty Ltd v Downie [2003] QDC 043 the court allowed in part an appeal from the refusal by the Queensland Building Tribunal to order the respondent liquidators pay the appellants' costs of proceedings in the Tribunal. The decision involved an examination of authorities which have considered the circumstances in which it is in the interests of justice to make an order for costs against a non-party.

Costs order against company in liquidation unlikely to be effective indemnity

In Kimtran v Downie [2003] QCA 424, the Queensland Court of Appeal allowed an appeal from the decision of a District Court judge who had ordered costs against a non-party liquidator. It held that the court's decision in relation to the awarding of costs against a liquidator was not constrained by the decision of the of the Court of Appeal in Mahaffey v Belar Pty Ltd [1999] QCA 2 in the manner stated in the District Court.

Nonlinear secret sharing immune against cheating

The paper investigates the design of secret sharing that is immune against cheating (as defined by the Tompa-Woll attack). We examine secret sharing with binary shares and secrets. Bounds on the probability of successful cheating are given for two cases. The first case relates to secret sharing based on bent functions and results in a non-perfect scheme. The second case considers perfect secret sharing built on highly nonlinear balanced Boolean functions.

A non-malleable group key exchange protocol robust against active insiders

In this paper we make progress towards solving an open problem posed by Katz and Yung at CRYPTO 2003. We propose the first protocol for key exchange among n ≥2k+1 parties which simultaneously achieves all of the following properties: 1. Key Privacy (including forward security) against active attacks by group outsiders, 2. Non-malleability — meaning in particular that no subset of up to k corrupted group insiders can ‘fix’ the agreed key to a desired value, and 3. Robustness against denial of service attacks by up to k corrupted group insiders. Our insider security properties above are achieved assuming the availability of a reliable broadcast channel.

Effectiveness of policy against illegal disposal of waste

Our objective is to analyze the effectiveness, against the illegal disposal of waste, of a licensing system that has been introduced in a waste management policy. We theoretically find enforcement leverage in the licensing system, and then examine the theoretical result empirically. The results suggest that extending liability to disposers, which forms the basis of the enforcement leverage, deters illegal disposal more effectively than increasing penalties for illegal disposal. We also obtain evidence of transboundary movement of illegal disposal, and find how the court determines penalties for illegal disposal.

Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection

Early transcriptional activation events that occur in bladder immediately following bacterial urinary tract infection (UTI) are not well defined. In this study, we describe the whole bladder transcriptome of uropathogenic Escherichia coli (UPEC) cystitis in mice using genome-wide expression profiling to define the transcriptome of innate immune activation stemming from UPEC colonization of the bladder. Bladder RNA from female C57BL/6 mice, analyzed using 1.0 ST-Affymetrix microarrays, revealed extensive activation of diverse sets of innate immune response genes, including those that encode multiple IL-family members, receptors, metabolic regulators, MAPK activators, and lymphocyte signaling molecules. These were among 1564 genes differentially regulated at 2 h postinfection, highlighting a rapid and broad innate immune response to bladder colonization. Integrative systems-level analyses using InnateDB (http://www.innatedb.com) bioinformatics and ingenuity pathway analysis identified multiple distinct biological pathways in the bladder transcriptome with extensive involvement of lymphocyte signaling, cell cycle alterations, cytoskeletal, and metabolic changes. A key regulator of IL activity identified in the transcriptome was IL-10, which was analyzed functionally to reveal marked exacerbation of cystitis in IL-10–deficient mice. Studies of clinical UTI revealed significantly elevated urinary IL-10 in patients with UPEC cystitis, indicating a role for IL-10 in the innate response to human UTI. The whole bladder transcriptome presented in this work provides new insight into the diversity of innate factors that determine UTI on a genome-wide scale and will be valuable for further data mining. Identification of protective roles for other elements in the transcriptome will provide critical new insight into the complex cascade of events that underpin UTI.

Phage library screening for the rapid identification and in vivo testing of candidate genes for a DNA vaccine against Mycoplasma mycoides subsp. mycoides small colony biotype

A new strategy for rapidly selecting and testing genetic vaccines has been developed, in which a whole genome library is cloned into a bacteriophage λ ZAP Express vector which contains both prokaryotic (Plac) and eukaryotic (PCMV) promoters upstream of the insertion site. The phage library is plated on Escherichia coli cells, immunoblotted, and probed with hyperimmune and/or convalescent-phase antiserum to rapidly identify vaccine candidates. These are then plaque purified and grown as liquid lysates, and whole bacteriophage particles are then used directly to immunize the host, following which PCMV-driven expression of the candidate vaccine gene occurs. In the example given here, a semirandom genome library of the bovine pathogen Mycoplasma mycoides subsp. mycoides small colony (SC) biotype was cloned into λ ZAP Express, and two strongly immunodominant clones, λ-A8 and λ-B1, were identified and subsequently tested for vaccine potential against M. mycoides subsp. mycoides SC biotype-induced mycoplasmemia. Sequencing and immunoblotting indicated that clone λ-A8 expressed an isopropyl-β-d-thiogalactopyranoside (IPTG)-inducible M. mycoides subsp. mycoides SC biotype protein with a 28-kDa apparent molecular mass, identified as a previously uncharacterized putative lipoprotein (MSC_0397). Clone λ-B1 contained several full-length genes from the M. mycoides subsp. mycoides SC biotype pyruvate dehydrogenase region, and two IPTG-independent polypeptides, of 29 kDa and 57 kDa, were identified on immunoblots. Following vaccination, significant anti-M. mycoides subsp. mycoides SC biotype responses were observed in mice vaccinated with clones λ-A8 and λ-B1. A significant stimulation index was observed following incubation of splenocytes from mice vaccinated with clone λ-A8 with whole live M. mycoides subsp. mycoides SC biotype cells, indicating cellular proliferation. After challenge, mice vaccinated with clone λ-A8 also exhibited a reduced level of mycoplasmemia compared to controls, suggesting that the MSC_0397 lipoprotein has a protective effect in the mouse model when delivered as a bacteriophage DNA vaccine. Bacteriophage-mediated immunoscreening using an appropriate vector system offers a rapid and simple technique for the identification and immediate testing of putative candidate vaccines from a variety of pathogens.

Methylproamine protects against ionizing radiation by preventing DNA double-strand breaks

Purpose The majority of cancer patients will receive radiotherapy (RT), therefore, investigations into advances of this modality are important. Conventional RT dose intensities are limited by adverse responses in normal tissues and a primary goal is to ameliorate adverse normal tissue effects. The aim of these experiments is to further our understanding regarding the mechanism of radioprotection by the DNA minor groove binder, methylproamine, in a cellular context at the DNA level. Materials and methods We used immunocytochemical methods to measure the accumulation of phosphorylated H2AX (γH2AX) foci following ionizing radiation (IR) in patient-derived lymphoblastoid cells exposed to methylproamine. Furthermore, we performed pulsed field gel electrophoresis DNA damage and repair assays to directly interrogate the action of methylproamine on DNA in irradiated cells. Results We found that methylproamine-treated cells had fewer γH2AX foci after IR compared to untreated cells. Also, the presence of methylproamine decreased the amount of lower molecular weight DNA entering the gel as shown by the pulsed field gel electrophoresis assay. Conclusions These results suggest that methylproamine acts by preventing the formation of DNA double-strand breaks (dsbs) and support the hypothesis that radioprotection by methylproamine is mediated, at least in part, by decreasing initial DNA damage.