Evaluation of assay technologies for the identification of protein-Peptide interaction antagonists

An increasing number of assay detection technologies are routinely used in small molecule drug discovery and lead optimization. These assays range from solid-phase heterogeneous assays such as enzyme-linked immunosorbent assay and dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA, PerkinElmer Life and Analytical Sciences, Boston, MA) to solution phase, bead-based assays such as electrochemiluminescence assay (BioVeris [Gaithersburg, MD] technology) and amplified luminescent proximity homogeneous assay (AlphaScreen, PerkinElmer Life and Analytical Sciences) to completely solution-based homogeneous assays such as time-resolved fluorescence resonance energy transfer and fluorescence polarization. The aim of this study is to compare these assay technologies and assess the advantages and disadvantages of each in the context of our efforts to develop small molecule antagonists to the melanoma inhibitor of apoptosis protein. In this study, seven peptides have been evaluated for their potencies in each assay format. Our results indicate that these assay technologies produce similar relative potencies; however, some methods may be more susceptible to interference than others. Consequently, the choice of the method used frequently depends on a number of factors in addition to assay reproducibility and performance, such as throughput of the assay, cost, compound interference, and ease of use.     

Long-term effects of spinal cord injury on sexual function in men: implications for neuroplasticity

STUDY DESIGN: Secure, web-based survey.Objectives:Elicit specific information about sexual function from men with spinal cord injuries (SCI). SETTING: World-wide web.Methods:Individuals 18 years or older living with SCI obtained a pass-code to enter a secure website and then answered survey questions. RESULTS: The presence of genital sensation was positively correlated with the ability to feel a build up of sexual tension in the body during sexual stimulation and in the feeling that mental arousal translates to the genitals as physical sensation. There was an inverse relationship between developing new areas of arousal above the level of lesion and not having sensation or movement below the lesion. A positive relationship existed between the occurrence of spasticity during sexual activity and erectile ability. Roughly 60% of the subjects had tried some type of erection enhancing method. Only 48% had successfully achieved ejaculation postinjury and the most commonly used methods were hand stimulation, sexual intercourse, and vibrostimulation. The most commonly cited reasons for trying to ejaculate were for pleasure and for sexual intimacy. Less than half reported having experienced orgasm postinjury and this was influenced by the length of time postinjury and sacral sparing. CONCLUSION: SCI not only impairs male erectile function and ejaculatory ability, but also alters sexual arousal in a manner suggestive of neuroplasticity. More research needs to be pursued in a manner encompassing all aspects of sexual function.     

Five Dimensions of Therapy Process

Building on previous conceptual and methodological discussions, a five-dimensional model of the process of psychotherapy is proposed. The five dimensions are (1) Perspective of Observation (who observes the process: client, therapist, or researcher); (2) Person/Focus (who is observed: client, therapist, or dyad); (3) Aspect of Process (What communication feature is observed: content, action, style, or quality); (4) Unit Level (the hierarchical order or scale at which observation occurs, e.g., sentence/idea, speaking turn, episode, session, stage or treatment); and (5) Sequential Phase (the temporal orientation or purpose of observation: to understand context, process, or impact). The model and its potential value for identifying problems in existing process measures are illustreated using fifteen major process rating systems (Greenberg & Pinsof, 1986). The comprehensiveness of the model and its implications for research and theory are also discussed.     

Resilience and distress among young adults with chronic health conditions: A longitudinal study

Objectives

To test the beneficial associations of a resilient personality prototype among emerging adults with chronic health conditions (CHC) over an 8-year period.

Design

Longitudinal, prospective observation study.

Methods

Data obtained from emerging adults in the Add Health project with a CHC and completed study measures at two time points (286 men, 459 women) were examined. Cluster analysis was used to identify a resilient personality prototype at the first time point, as defined in the Block model of personality. Differences between those with a resilient and non-resilient prototype were examined. A structural equation model (SEM) tested the association of a resilience prototype with positive affect, perceived control and family relationships in predicting distress over time.

Results

A resilient personality profile was identified (n = 256). These individuals reported higher positive affect, greater perceived control and less distress at both measurement occasions than those without this profile (n = 489). Women reported more distress than men. SEM revealed the relationship of a resilient prototype to distress was explained by its beneficial association with positive affect and perceived control at the first assessment, and through its beneficial association with perceived control 8 years later. Gender independently predicted distress.

Conclusions

A resilient personality prototype appears to operate through its beneficial association with perceived control to prospectively predict distress reported by emerging adults with CHC. The self-regulatory properties theoretically associated with a resilient personality prototype may function through perceptions of control which, in turn, prevent prolonged experiences of distress. Clinical implications are considered.