Macquarie University

About: Macquarie University is a education organization based out in Sydney, New South Wales, Australia. It is known for research contribution in the topics: Population & Context (language use). The organization has 14075 authors who have published 47673 publications receiving 1416184 citations. The organization is also known as: Macquarie uni.

Site-specific insertion of gene cassettes into integrons.

Abstract: Summary Site-specific insertion of gene cassettes into the insert region of integrons has been demonstrated. Insertion was only observed if the integron DNA integrase was expressed in the recipient cell and if the cassette DNA was ligated prior to transformation. The essential ligation products were resistant to treatment with exonuclease III, indicating that they were closed circular molecules. Insertion of cassettes into integron fragments containing either no insert (one recombination site), or one gene cassette (two recombination sites), was demonstrated. In the latter case, insertion occurred predominantly at the core site located 5′ to the resident cassette, which corresponds to the only site available when no insert is present in the recipient. When DNA molecules including two gene cassettes were used, insertion of only one of the gene cassettes was generally observed, suggesting that resolution of the circular molecule to generate two independent circular cassettes occurred more rapidly than insertion into the recipient integron.

Late DNA replication in the paternally derived X chromosome of female kangaroos.

Abstract: The mode of dose compensation for X chromosomes in kangaroos seems to be inactivation of the paternal X, in contrast to the random X inactivation characteristic of eutherian mammals.

Social Stories for Children with Disabilities

Abstract: A review of the empirical research literature on Social Stories™ is presented, including a descriptive review and single-subject meta-analysis of appropriate studies. Examination of data suggests the effects of Social Stories™ are highly variable. Interpretations of extant studies are frequently confounded by inadequate participant description and the use of Social Stories™ in combination with other interventions. It is unclear whether particular components of Social Stories™ are central to their efficacy. Data on maintenance and generalization are also limited. Social Stories™ stand as a promising intervention, being relatively straightforward and efficient to implement with application to a wide range of behaviors. Further research is needed to determine the exact nature of their contribution and the components critical to their efficacy.

Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists.

Abstract: Biased agonism at G protein–coupled receptors describes the phenomenon whereby some drugs can activate some downstream signaling activities to the relative exclusion of others. Descriptions of biased agonism focusing on the differential engagement of G proteins versus β-arrestins are commonly limited by the small response windows obtained in pathways that are not amplified or are less effectively coupled to receptor engagement, such as β-arrestin recruitment. At the μ-opioid receptor (MOR), G protein–biased ligands have been proposed to induce less constipation and respiratory depressant side effects than opioids commonly used to treat pain. However, it is unclear whether these improved safety profiles are due to a reduction in β-arrestin–mediated signaling or, alternatively, to their low intrinsic efficacy in all signaling pathways. Here, we systematically evaluated the most recent and promising MOR-biased ligands and assessed their pharmacological profile against existing opioid analgesics in assays not confounded by limited signal windows. We found that oliceridine, PZM21, and SR-17018 had low intrinsic efficacy. We also demonstrated a strong correlation between measures of efficacy for receptor activation, G protein coupling, and β-arrestin recruitment for all tested ligands. By measuring the antinociceptive and respiratory depressant effects of these ligands, we showed that the low intrinsic efficacy of opioid ligands can explain an improved side effect profile. Our results suggest a possible alternative mechanism underlying the improved therapeutic windows described for new opioid ligands, which should be taken into account for future descriptions of ligand action at this important therapeutic target.