Storage and release of hydrogen cyanide in a chelicerate ().

Cyanogenesis denotes a chemical defensive strategy where hydrogen cyanide (HCN, hydrocyanic or prussic acid) is produced, stored, and released toward an attacking enemy. The high toxicity and volatility of HCN requires both chemical stabilization for storage and prevention of accidental self-poisoning. The few known cyanogenic animals are exclusively mandibulate arthropods (certain myriapods and insects) that store HCN as cyanogenic glycosides, lipids, or cyanohydrins.

Structure and activity of contryphan-Vc2: Importance of the d-amino acid residue.

In natural proteins and peptides, amino acids exist almost invariably as l-isomers. There are, however, several examples of naturally-occurring peptides containing d-amino acids. In this study we investigated the role of a naturally-occurring d-amino acid in a small peptide identified in the transcriptome of a marine cone snail.

Structure and Characterisation of a Key Epitope in the Conserved C-Terminal Domain of the Malaria Vaccine Candidate MSP2.

Merozoite surface protein 2 (MSP2) is an intrinsically disordered antigen that is abundant on the surface of the malaria parasite Plasmodium falciparum. The two allelic families of MSP2, 3D7 and FC27, differ in their central variable regions, which are flanked by highly conserved C-terminal and N-terminal regions. In a vaccine trial, full-length 3D7 MSP2 induced a strain-specific protective immune response despite the detectable presence of conserved region antibodies.

Late-onset Neonatal Sepsis-A 10-year Review From North Queensland, Australia.

Objective: Late-onset sepsis (LOS) in neonates contributes significantly to both morbidity and mortality. To determine the incidence of LOS, risk factors for disease and the impact on subsequent hospital course, we evaluated a cohort of 6340 neonates admitted to the neonatal intensive care unit and of neonates (3-28 days) admitted from the community between January 2005 and January 2016.

Methods: This was a retrospective case review of all neonates admitted with suspected LOS who had positive blood culture and/or cerebrospinal fluid cultures, for an organism determined to be a pathogen.

Identifying Strategies to Cope with HIV-Related Stigma in a Group of Women Living with HIV/AIDS in the Dominican Republic: A Qualitative Study.

Internalized HIV-related stigma negatively impacts the mental and physical health of women living with HIV/AIDS (WLWHA). Yet, some women can successfully confront stigma. The present work uses qualitative methods to investigate the successful stigma coping strategies displayed by 19 WLWHA who reported the least internalized stigma possible on the Internalized AIDS-Related Stigma Scale out of a larger pool of 233 WLWHA in San Felipe de Puerto Plata, Dominican Republic.

Protocol-based management of older adults with hip fractures in Delhi, India: a feasibility study.

Background: Worldwide hip fractures are projected to increase from 1.7 million in 1990 to 6.3 million in 2050.

Antimalarial drug discovery targeting apical membrane antigen 1.

Malaria continues to frustrate humanity's attempts to eradicate this deadly disease. Although gains have been made over the last 15 years, drug resistance to malaria continues to be a major concern. The lack of new antimalarials with novel mechanisms of action continues to challenge the scientific community to find innovative targets to combat this persistent disease.

Home-based versus centre-based cardiac rehabilitation: abridged Cochrane systematic review and meta-analysis.

Objective: To update the Cochrane review comparing the effects of home-based and supervised centre-based cardiac rehabilitation (CR) on mortality and morbidity, quality of life, and modifiable cardiac risk factors in patients with heart disease.

Methods: Systematic review and meta-analysis. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and CINAHL were searched up to October 2014, without language restriction.

Primary amoebic meningoencephalitis in North Queensland: the paediatric experience.

Primary amoebic meningoencephalitis (PAM) is a fulminant, diffuse haemorrhagic meningoencephalitis caused by Naegleria fowleri, with an almost invariably fatal outcome. In Australia and the developed world, PAM remains a rare disease, although it is very likely that large numbers of cases go undetected in developing countries. N.

A minimized human insulin-receptor-binding motif revealed in a Conus geographus venom insulin.

Insulins in the venom of certain fish-hunting cone snails facilitate prey capture by rapidly inducing hypoglycemic shock. One such insulin, Conus geographus G1 (Con-Ins G1), is the smallest known insulin found in nature and lacks the C-terminal segment of the B chain that, in human insulin, mediates engagement of the insulin receptor and assembly of the hormone's hexameric storage form. Removal of this segment (residues B23-B30) in human insulin results in substantial loss of receptor affinity.

Selenoprotein K regulation of palmitoylation and calpain cleavage of ASAP2 is required for efficient FcγR-mediated phagocytosis.

Effective activation of macrophages through phagocytic Fcγ receptors (FcγR) has been shown to require selenoprotein K (Selk). We set out to determine whether the FcγR-mediated uptake process itself also requires Selk and potential underlying mechanisms. Macrophages from Selk knockout (KO) mice were less efficient compared with wild-type (WT) controls in engulfing IgG-coated fluorescent beads.

The ways and means of fragment-based drug design.

Fragment-based drug design (FBDD) has emerged as a mainstream approach for the rapid and efficient identification of building blocks that can be used to develop high-affinity ligands against protein targets. One of the strengths of FBDD is the relative ease and low cost of the primary screen to identify fragments that bind. However, the fragments that emerge from primary screens often have low affinities, with K values in the high μM to mM range, and a significant challenge for FBDD is to develop the initial fragments into more potent ligands.

Home-based cardiac rehabilitation for people with heart failure: A systematic review and meta-analysis.

Aims: To assess the effectiveness of home-based cardiac rehabilitation (CR) for heart failure compared to either usual medical care (i.e. no CR) or centre-based CR on mortality, morbidity, exercise capacity, health-related quality of life, drop out, adherence rates, and costs.

Applications of (19)F-NMR in Fragment-Based Drug Discovery.

(19)F-NMR has proved to be a valuable tool in fragment-based drug discovery. Its applications include screening libraries of fluorinated fragments, assessing competition among elaborated fragments and identifying the binding poses of promising hits. By observing fluorine in both the ligand and the target protein, useful information can be obtained on not only the binding pose but also the dynamics of ligand-protein interactions.

A global call for action to include gender in research impact assessment.

Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably).

Structure-Activity Studies of β-Hairpin Peptide Inhibitors of the Plasmodium falciparum AMA1-RON2 Interaction.

The interaction between apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2) plays a key role in the invasion of red blood cells by Plasmodium parasites. Disruption of this critical protein-protein interaction represents a promising avenue for antimalarial drug discovery. In this work, we exploited a 13-residue β-hairpin based on the C-terminal loop of RON2 to probe a conserved binding site on Plasmodium falciparum AMA1.

Overrepresentation of Diabetes in Soft Tissue Nontuberculous Mycobacterial Infections.

Diabetes predisposes patients to bacterial infections. Although diabetes confers susceptibility to tuberculosis, the association between nontuberculous mycobacterial (NTM) infections and diabetes remains unknown. A retrospective chart analysis of patients in northern Australia during a 20-year period with soft tissue NTM infections revealed that patients with diabetes were three times overrepresented in comparison to the general population (odds ratio = 3.

Improving Rice Zinc Biofortification Success Rates Through Genetic and Crop Management Approaches in a Changing Environment.

Though rice is the predominant source of energy and micronutrients for more than half of the world population, it does not provide enough zinc (Zn) to match human nutritional requirements. Moreover, climate change, particularly rising atmospheric carbon dioxide concentration, reduces the grain Zn concentration. Therefore, rice biofortification has been recognized as a key target to increase the grain Zn concentration to address global Zn malnutrition.

Enabling Noninvasive Systemic Delivery of the Kv1.3-Blocking Peptide HsTX1[R14A] via the Buccal Mucosa.

The peptide HsTX1[R14A] is a potent and selective blocker of the voltage-gated potassium channel Kv1.3, a well-recognized therapeutic target for autoimmune diseases. To overcome the poor oral absorption and consequent need for regular injections, the potential of the buccal mucosa for systemic delivery of HsTX1[R14A] was investigated.

More parasitic myositis cases in humans in Australia, and the definition of genetic markers for the causative agents as a basis for molecular diagnosis.

Since 1998, there have been six reported human cases of myositis in Australia, attributable to infection with the nematode Haycocknema perplexum. However, an unequivocal diagnosis of H. perplexum infection and associated disease has been seriously compromised by a lack of molecular markers for this nematode.

Design, Synthesis, and Characterization of Cyclic Peptidomimetics of the Inducible Nitric Oxide Synthase Binding Epitope That Disrupt the Protein-Protein Interaction Involving SPRY Domain-Containing Suppressor of Cytokine Signaling Box Protein (SPSB) 2 and Inducible Nitric Oxide Synthase.

SPRY domain-containing suppressor of cytokine signaling box protein (SPSB) 2-deficient macrophages have been found to exhibit prolonged expression of inducible nitric oxide synthase (iNOS) and enhanced killing of persistent pathogens, suggesting that inhibitors of the SPSB2-iNOS interaction have potential as novel anti-infectives. In this study, we describe the design, synthesis, and characterization of cyclic peptidomimetic inhibitors of the SPSB2-iNOS interaction constrained by organic linkers to improve stability and druggability. SPR, ITC, and (19)F NMR analyses revealed that the most potent cyclic peptidomimetic bound to the iNOS binding site of SPSB2 with low nanomolar affinity (KD 29 nM), a 10-fold improvement over that of the linear peptide DINNN (KD 318 nM), and showed strong inhibition of SPSB2-iNOS interaction in macrophage cell lysates.

Women's health: a new global agenda.

Robyn Norton is co-founder and Principal Director of The George Institute for Global Health (Australia), a not-for-profit medical research institute that aims to increase the provision of safe, effective and affordable healthcare, especially for disadvantaged populations worldwide. She is Professor of Global Health and James Martin Fellow at the University of Oxford (UK), Professor of Public Health at the University of Sydney (Australia) and Honorary Professor at Peking University (China). Professor Norton is internationally regarded for her research on the causes, prevention and management of injuries and the management of various critical conditions in surgical and intensive care settings.

Cryptococcosis-the impact of delay to diagnosis.

Cryptococcosis is a mycotic disease caused by the yeast Cryptococcus sp. It is associated with significant mortality and morbidity, including long-term neurological sequelae. It is not known whether the high morbidity observed is related to a delay in diagnosis.