AlacatDesigner─Computational Design of Peptide Concatamers for Protein Quantitation.

Protein quantitation via mass spectrometry relies on peptide proxies for the parent protein from which abundances are estimated. Owing to the variability in signal from individual peptides, accurate absolute quantitation usually relies on the addition of an external standard. Typically, this involves stable isotope-labeled peptides, delivered singly or as a concatenated recombinant protein. Consequently, the selection of the most appropriate surrogate peptides and the attendant design in recombinant proteins termed QconCATs are challenges for proteome science. QconCATs can now be built in a "a-la-carte" assembly method using synthetic biology: ALACATs. To assist their design, we present "AlacatDesigner", a tool that supports the peptide selection for recombinant protein standards based on the user's target protein. The user-customizable tool considers existing databases, occurrence in the literature, potential post-translational modifications, predicted miscleavage, predicted divergence of the peptide and protein quantifications, and ionization potential within the mass spectrometer. We show that peptide selections are enriched for good proteotypic and quantotypic candidates compared to empirical data. The software is freely available to use either via a web interface AlacatDesigner, downloaded as a Desktop application or imported as a Python package for the command line interface or in scripts.

The sugar-responsive circadian clock regulator bZIP63 modulates plant growth.

Adjustment to energy starvation is crucial to ensure growth and survival. In Arabidopsis thaliana (Arabidopsis), this process relies in part on the phosphorylation of the circadian clock regulator bZIP63 by SUCROSE non-fermenting RELATED KINASE1 (SnRK1), a key mediator of responses to low energy. We investigated the effects of mutations in bZIP63 on plant carbon (C) metabolism and growth. Results from phenotypic, transcriptomic and metabolomic analysis of bZIP63 mutants prompted us to investigate the starch accumulation pattern and the expression of genes involved in starch degradation and in the circadian oscillator. bZIP63 mutation impairs growth under light-dark cycles, but not under constant light. The reduced growth likely results from the accentuated C depletion towards the end of the night, which is caused by the accelerated starch degradation of bZIP63 mutants. The diel expression pattern of bZIP63 is dictated by both the circadian clock and energy levels, which could determine the changes in the circadian expression of clock and starch metabolic genes observed in bZIP63 mutants. We conclude that bZIP63 composes a regulatory interface between the metabolic and circadian control of starch breakdown to optimize C usage and plant growth.

What things make people with a learning disability happy and satisfied with their lives: an inclusive research project.

BACKGROUND: We looked at the research that other people have done about what makes people with a learning disability happy and satisfied with their lives. Researchers call being happy and satisfied with your life 'subjective well-being'. They found out that having things like money and good health does not always mean people are happy. They also found that some people are really happy, even if there are things in their lives they would like to change. None of the people who have done research about 'subjective well-being' have interviewed people with a learning disability about what makes them happy with their lives. MATERIALS AND METHODS: We have carried out a study about what makes people with a learning disability happy and satisfied with their lives. This report talks about the research that we did, and what we found out. We interviewed 20 people with a learning disability who said they were very happy and satisfied. We asked them about what things helped them feel like this. RESULTS: The people we spoke to said things like relationships, choice and independence, activities and valuable social roles made them feel satisfied with their lives. They told us about the things that enable them to lead happy lives, and the things that disable them. We also found out about the importance of personal characteristics. These are things like looking on the bright side of life or having ways to manage difficult emotions like sadness or anger. CONCLUSIONS: We found out that it is important for people with a learning disability to have good things in their lives, but it is also important to be enabled to access these good things.

A naturalistic comparison of the effectiveness of trainee and qualified clinical psychologists.

OBJECTIVE: To compare the effect of clinician type on the outcome for adult mental health clients treated by trainee and qualified clinical psychologists. DESIGN: Naturalistic, non-random between-participants group design: a group of 60 adult mental health out-patients treated by trainees and a matched group of 60 patients treated by qualified clinical psychologists. METHOD: Participants completed a range of established measures at assessment and outcome of their treatment during routine clinical practice. RESULTS: Significant improvements in mental health were made for both groups from assessment to outcome; however, no significant effect of clinician type was evident. CONCLUSIONS: A variety of factors (e.g. quantity of supervision) contributing to trainee effectiveness are identified and discussed.

Analysis of assimilation during psychotherapy with people who have mental retardation.

The assimilation model provides a structured account of changes occurring within psychotherapy. The model proposes that clients assimilate their problematic experience through the development of schema observable in psychotherapeutic settings. The research procedure involved applying the Assimilation of Problematic Experiences Scale (APES) to transcripts from 8 clients. Quantitative methods were applied to examine whether clients with mental retardation illustrate changes in level of assimilation within and across sessions. Results suggest that people with mental retardation do assimilate problematic experiences during psychotherapy. Methodological issues and clinical implications are discussed. Our goal was to provide a clinically relevant account, applicable to the achievements of people with mental retardation, in the context of psychotherapy.

Measuring interpersonal problems in people with mental retardation.

Despite interpersonal problems being commonplace in the clinical presentations of people with mental retardation, previous efforts to index interpersonal difficulties have tended to unsatisfactorily rely on external ratings. The Inventory of Interpersonal Problems-32 is a psychometrically robust self-report measure of interpersonal problems in adult populations. We found that this instrument retained many of its psychometric properties when used with a sample of 255 respondents with mild mental retardation. Results indicate four usable subscales alongside the full-scale when employed with this population. The subscales produced generally satisfactory internal and test-retest reliabilities and sound concurrent and internal-external criterion-related validities. Results are discussed with reference to further development of the measure in relation to people with mental retardation.