Confronting racially exclusionary practices in the acquisition and analyses of neuroimaging data.

Across the brain sciences, institutions and individuals have begun to actively acknowledge and address the presence of racism, bias, and associated barriers to inclusivity within our community. However, even with these recent calls to action, limited attention has been directed to inequities in the research methods and analytic approaches we use. The very process of science, including how we recruit, the methodologies we utilize and the analyses we conduct, can have marked downstream effects on the equity and generalizability of scientific discoveries across the global population. Despite our best intentions, the use of field-standard approaches can inadvertently exclude participants from engaging in research and yield biased brain-behavior relationships. To address these pressing issues, we discuss actionable ways and important questions to move the fields of neuroscience and psychology forward in designing better studies to address the history of exclusionary practices in human brain mapping.

Combinatorial approaches for treating neuropsychiatric social impairment.

Social behaviour is an essential component of human life and deficits in social function are seen across multiple psychiatric conditions with high morbidity. However, there are currently no FDA-approved treatments for social dysfunction. Since social cognition and behaviour rely on multiple signalling processes acting in concert across various neural networks, treatments aimed at social function may inherently require a combinatorial approach. Here, we describe the social neurobiology of the oxytocin and endocannabinoid signalling systems as well as translational evidence for their use in treating symptoms in the social domain. We leverage this systems neurobiology to propose a network-based framework that involves pharmacology, psychotherapy, non-invasive brain stimulation and social skills training to combinatorially target trans-diagnostic social impairment. Lastly, we discuss the combined use of oxytocin and endocannabinoids within our proposed framework as an illustrative strategy to treat specific aspects of social function. Using this framework provides a roadmap for actionable treatment strategies for neuropsychiatric social impairment. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.

Supplementary prescribing in mental health and learning disabilities.

Nurse prescribing in mental health and learning disability services is a new development. The experiences of nine nurses working in mental health and learning disabilities, who formed part of the first cohort in the U.K. to undertake the supplementary nurse prescribing course, are described. Experiences of the course and implementation of supplementary prescribing in practice are discussed. The attitudes of nurses, other health professionals and patients to nurse prescribing are also explored.

Harnessing the power of the genome in the search for new antibiotics.

Over the past 40 years, the search for new antibiotics has been largely restricted to well-known compound classes active against a standard set of drug targets. Although many effective compounds have been discovered, insufficient chemical variability has been generated to prevent a serious escalation in clinical resistance. Recent advances in genomics have provided an opportunity to expand the range of potential drug targets and have facilitated a fundamental shift from direct antimicrobial screening programs toward rational target-based strategies. The application of genome-based technologies such as expression profiling and proteomics will lead to further changes in the drug discovery paradigm by combining the strengths and advantages of both screening strategies in a single program.

New antibiotic discovery, novel screens, novel targets and impact of microbial genomics.

The clinical need for new classes of antibiotic continues to grow, as drug resistance erodes the efficacy of current therapies. Historically, most antibiotics were discovered by random screening campaigns, but over the past 20 years, this strategy has largely failed to deliver a sufficient range of chemical diversity to keep pace with changing clinical profiles. A more rational approach to drug hunting has been greatly potentiated by the availability of bacterial genomic information. The rapid progress in sequencing and analysis of these small, prokaryotic genomes has enabled the concomitant development of powerful new technologies that are already enhancing the potential utility of genomic information. The future promises versatile and precise tools to understand what makes a successful antibiotic and moreover the means to identify and evaluate novel classes of drug.

Bacterial genome sequencing and drug discovery.

The availability of bacterial genome sequence information has opened up many new strategies for antibacterial drug hunting. There are obvious benefits for the identification and evaluation of new drug targets, but genomic-based technology is also beginning to provide new tools for the downstream, preclinical, optimisation of compounds. The greatest benefit from these new approaches lies in the ability to examine the entire genome (or several genomes) simultaneously and in total. In this way, one potential target can be evaluated against another, and either the total effects of functional impairment can be established or the effects of a compound can be compared across species.

Inhibitors of bacterial signal peptidase: a series of 6-(substituted oxyethyl)penems.

A series of 6-(substituted oxyethyl)penem esters having the (5S) stereochemistry which are potent inhibitors of Escherichia coli leader peptidase is described. Structure-activity relationships are discussed.

On the catalytic mechanism of prokaryotic leader peptidase 1.

The catalytic mechanism of leader peptidase 1 (LP1) of the bacterium Escherichia coli has been investigated by a combination of site-directed mutagenesis, assays of enzyme activity in vivo utilizing a strain of E. coli which has a conditional defect in LP1 activity, and gene cloning. The biological activity of mutant forms of E. coli LP1 demonstrates that this enzyme belongs to a novel class of proteinases. The possibility that LP1 may be an aspartyl proteinase has been excluded on the basis of primary sequence comparison and mutagenesis. Assignment of LP1 to one of the other three recognized classes of proteinases (metalloproteinases, thiol proteinases and the classical serine proteinases) can also be excluded, as it is clearly demonstrated that none of the histidine or cysteine residues within LP1 are required for catalytic activity. The Pseudomonas fluorescens lep gene has been cloned and sequenced and the corresponding amino acid sequence compared with that of E. coli LP1. The E. coli LP1 and P. fluorescens LP1 primary sequences are 50% identical after insertion of gaps. The P. fluorescens LP1 has 39 fewer amino acids, a calculated molecular mass of 31903 Da and functions effectively in vivo in E. coli. None of the cysteine residues and only one of the histidine residues which are present in E. coli LP1 are conserved in sequence position in the P. fluorescens LP1 enzyme. The possibility that LP1 is a novel type of serine proteinase is discussed.

Intergeneric cosynthesis of penicillin by strains of Penicillium chrysogenum, P. chrysogenum/notatum and Aspergillus nidulans.

A number of mutants impaired in penicillin production have previously been isolated from Penicillium chrysogenum and Aspergillus nidulans. During cofermentation of osmotically fragile mycelia derived from these strains, in the presence of inhibitors of cell wall regeneration, intergeneric cosynthesis has been demonstrated between mutants which are probably impaired in different parts of th penicillin biosynthetic pathway.