Proteins which bind methylated lysines ("readers" of the histone code) are important components in the epigenetic regulation of gene expression and can also modulate other proteins that contain methyl-lysine such as p53 and Rb. Recognition of methyl-lysine marks by MBT domains leads to compaction of chromatin and a repressed transcriptional state. Antagonists of MBT domains would serve as probes to interrogate the functional role of these proteins and initiate the chemical biology of methyl-lysine readers as a target class. Small-molecule MBT antagonists were designed based on the structure of histone peptide-MBT complexes and their interaction with MBT domains determined using a chemiluminescent assay and ITC. The ligands discovered antagonize native histone peptide binding, exhibiting 5-fold stronger binding affinity to L3MBTL1 than its preferred histone peptide. The first cocrystal structure of a small molecule bound to L3MBTL1 was determined and provides new insights into binding requirements for further ligand design.
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http://dx.doi.org/10.1021/jm200045v | DOI Listing |
Psychodyn Psychiatry
December 2024
Professor of Psychological Therapies with Children and Young People, University College London, UK; Director of the Child Attachment and Psychological Therapies Research Unit (ChAPTRe); Director of the Child Attachment and Psychological Therapies Research Unit (ChaPTRe), Anna Freud, London.
It is now more than 30 years since Peter Fonagy published his classic 1991 paper introducing the concept of "mentalization" into the psychoanalytic literature, and in the period since then mentalization-based treatment (MBT) has emerged as an important therapeutic approach. In reviewing the history of this treatment, it is often assumed that MBT emerged at the interface between three domains: first, the developmental research on theory of mind; second, the clinical challenges of treating borderline personality disorder; and third, the empirical research on intergenerational patterns of attachment. This article suggests that there was one more domain, which was equally important to the development of MBT and which is perhaps less widely recognized.
View Article and Find Full Text PDFBMC Palliat Care
November 2024
Department of Neurology, PD Hinduja National Hospital and Medical Research Centre, Veer Savarkar Marg, Mahim Mumbai, Maharashtra, 400016, India.
Background: One in five people will be older than 60 by the year 2050 in India. This demographic transition demands integration of geriatric and palliative care. The national level burden of palliative and supportive care needs of the older population is largely unknown in India.
View Article and Find Full Text PDFDig Dis Sci
November 2024
Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, 3500 Civic Center Blvd., Philadelphia, PA, 19104, USA.
Background: Dietary fat malabsorption contributes to poor nutritional status in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI). Prescribing gastric acid-reducing agents such as proton-pump inhibitors (PPI) as an adjunct to pancreatic enzyme replacement therapy (PERT) to improve dietary fat absorption has been accepted in clinical practice despite limited evidence.
Aims: This was a pilot randomized, double-blind, placebo-controlled crossover trial of subjects aged 12 and older with CF and EPI assessed on placebo and omeprazole to determine if PPI improved the efficacy of PERT as indicated by measures of dietary fat absorption.
Int J Appl Posit Psychol
January 2024
Resilience Research Centre, Dalhousie University, 6420 Coburg Road, PO Box 15000, Halifax, Nova Scotia B3H 4R2 Canada.
Unlabelled: Although many positive psychology interventions like mindfulness-based treatments (MBTs) for youth have been used with a wide array of risk exposed populations (children living in poverty, victims of violence, displaced persons, children with disabilities, etc.), the efficacy of MBTs with regard to the level and domain of risk exposure has been largely overlooked. This oversight contributes to a perception of positive psychology as being decontextualized.
View Article and Find Full Text PDFFront Psychol
October 2024
Institute for Psychosocial Prevention, University Hospital Heidelberg, Heidelberg, Germany.
Introduction: Conduct disorder (CD) is a severe mental disorder in youth. Yet, providing psychological interventions for adolescents with CD is challenging. This patient group is often characterized by risk factors for therapy dropout such as, e.
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