Synthesis and Functionalization of Sulfoximine-Bicyclo[1.1.0]butanes: Functionalizable, Tuneable and Cysteine-Selective Chiral Warheads.

Electrophilic covalent warheads with appropriate reactivity and selectivity are crucial to the investigation of protein function and the discovery of therapeutics. Here we report the synthesis of sulfoximine bicyclo[1.1.

Covalent fragment libraries in drug discovery-Design, synthesis, and screening methods.

As the development of drugs with a covalent mode of action is becoming increasingly popular, well-validated covalent fragment-based drug discovery (FBDD) methods have been comparatively slow to keep up with the demand. In this chapter the principles of covalent fragment reactivity, library design, synthesis, and screening methods are explored in depth, focussing on literature examples with direct applications to practical covalent fragment library design and screening. Further, questions about the future of the field are explored and potential useful advances are proposed.

Precise Installation of Diazo-Tagged Side-Chains on Proteins to Enable In Vitro and In-Cell Site-Specific Labeling.

The chemistry of diazo compounds has generated a huge breadth of applications in the field of organic synthesis. Their versatility combined with their tunable reactivity, stability, and chemoselectivity makes diazo compounds desirable reagents for chemical biologists. Here, we describe a method for the precise installation of diazo handles on proteins and antibodies in a mild and specific approach.

'When the walls come tumbling down': The role of intergroup proximity, threat, and contact in shaping attitudes towards the removal of Northern Ireland's peace walls.

Institutional structures of segregation typically entrench social inequality and sustain wider patterns of intergroup conflict and discrimination. However, initiatives to dismantle such structures may provoke resistance. Executive proposals to dismantle Northern Ireland's peace walls by 2023 provide a compelling case study of the nature of such resistance and may thus provide important clues about how it might be overcome.

Parallel lives: Intergroup contact, threat, and the segregation of everyday activity spaces.

Although intergroup contact can reduce prejudice, opportunities to experience such contact are often constrained by systems of segregation. Work on this problem has focused on divisions entrenched within institutions of residence, education, and employment. Our research employed a complementary approach, which treated segregation as the outcome of individuals' movements over time within everyday life spaces.

When should the driver with a history of substance misuse be allowed to return to the wheel? A review of the substance misuse section of the Australian national guidelines.

Assessing fitness to drive in applicants with a historical or current substance use disorder presents a specific clinical challenge. The Australian guidelines require evidence of remission and absence of cognitive change when considering applications for re-licensing driver or individuals applying to reengage in safety-sensitive work. This paper reviews some of the clinical and biochemical indicators that determine whether a particular person is in 'remission' and meets the criteria for return to driving or other safety-sensitive occupation.

Heterodimerization of Arabidopsis calcium/proton exchangers contributes to regulation of guard cell dynamics and plant defense responses.

Arabidopsis thaliana cation exchangers (CAX1 and CAX3) are closely related tonoplast-localized calcium/proton (Ca2+/H+) antiporters that contribute to cellular Ca2+ homeostasis. CAX1 and CAX3 were previously shown to interact in yeast; however, the function of this complex in plants has remained elusive. Here, we demonstrate that expression of CAX1 and CAX3 occurs in guard cells.

A calmodulin-like protein regulates plasmodesmal closure during bacterial immune responses.

Plants sense microbial signatures via activation of pattern recognition receptors (PPRs), which trigger a range of cellular defences. One response is the closure of plasmodesmata, which reduces symplastic connectivity and the capacity for direct molecular exchange between host cells. Plasmodesmal flux is regulated by a variety of environmental cues but the downstream signalling pathways are poorly defined, especially the way in which calcium regulates plasmodesmal closure.

Fruit Calcium: Transport and Physiology.

Calcium has well-documented roles in plant signaling, water relations and cell wall interactions. Significant research into how calcium impacts these individual processes in various tissues has been carried out; however, the influence of calcium on fruit ripening has not been thoroughly explored. Here, we review the current state of knowledge on how calcium may impact the development, physical traits and disease susceptibility of fruit through facilitating developmental and stress response signaling, stabilizing membranes, influencing water relations and modifying cell wall properties through cross-linking of de-esterified pectins.

Psychosis prevalence and physical, metabolic and cognitive co-morbidity: data from the second Australian national survey of psychosis.

Background: There are insufficient data from nationwide surveys on the prevalence of specific psychotic disorders and associated co-morbidities.

Method: The 2010 Australian national psychosis survey used a two-phase design to draw a representative sample of adults aged 18-64 years with psychotic disorders in contact with public treatment services from an estimated resident population of 1 464 923 adults. This paper is based on data from 1642 participants with an International Classification of Diseases (ICD)-10 psychotic disorder.

Protocol: optimising hydroponic growth systems for nutritional and physiological analysis of Arabidopsis thaliana and other plants.

Background: Hydroponic growth systems are a convenient platform for studying whole plant physiology. However, we found through trialling systems as they are described in the literature that our experiments were frequently confounded by factors that affected plant growth, including algal contamination and hypoxia. We also found the way in which the plants were grown made them poorly amenable to a number of common physiological assays.

People living with psychotic illness in 2010: the second Australian national survey of psychosis.

Objective: The 2010 Survey of High Impact Psychosis (SHIP) is Australia's second national psychosis survey. This paper provides an overview of its findings, including comparisons with the first psychosis survey and general population data.

Methods: The survey covered 1.

Calcium delivery and storage in plant leaves: exploring the link with water flow.

Calcium (Ca) is a unique macronutrient with diverse but fundamental physiological roles in plant structure and signalling. In the majority of crops the largest proportion of long-distance calcium ion (Ca(2+)) transport through plant tissues has been demonstrated to follow apoplastic pathways, although this paradigm is being increasingly challenged. Similarly, under certain conditions, apoplastic pathways can dominate the proportion of water flow through plants.

Bipolar disorder: new understandings, emerging treatments.

The role of general practitioners in managing bipolar disorder is gaining increasing recognition.

Prospective study of early bereavement on psychological and behavioural cardiac risk factors.

Background: Increasing evidence supports the role of emotional stress in the onset of cardiovascular disease. Although bereavement is a major emotional stress with both acute and more long-term features, the mechanism of its association with cardiovascular risk is not well understood, in particular because of limited studies of acute bereavement. The aim of the study was to identify psychological and behavioural changes in acute bereavement and potential modifiers of these changes.

Guidance note: risk management of workers with medical electronic devices and metallic implants in electromagnetic fields.

Medical electronic devices and metallic implants are found in an increasing number of workers. Industrial applications requiring intense electromagnetic fields (EMF) are growing and the potential risk of injurious interactions arising from EMF affecting devices or implants needs to be managed. Potential interactions include electromagnetic interference, displacement, and electrostimulation or heating of adjacent tissue, depending on the device or implant and the frequency of the fields.