Proteasome isoforms in human thymi and mouse models.

The thymus is the organ where functional and self-tolerant T cells are selected through processes of positive and negative selection before migrating to the periphery. The antigenic peptides presented on MHC class I molecules of thymic epithelial cells (TECs) in the cortex and medulla of the thymus are key players in these processes. It has been theorized that these cells express different proteasome isoforms, which generate MHC class I immunopeptidomes with features that differentiate cortex and medulla, and hence positive and negative CD8 T cell selection.

DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer.

Despite clinical benefits of tyrosine kinase inhibitors (TKIs) in cancer, most tumors can reactivate proliferation under TKI therapy. Here we present transcriptional profiling of HER2+ breast cancer cells transitioning from dormant drug tolerant cells to re-proliferating cells under continuous HER2 inhibitor (HER2i) therapy. Focusing on phosphatases, expression of dual-specificity phosphatase DUSP6 was found inhibited in dormant cells, but strongly induced upon regrowth.

Mammalian oocytes store proteins for the early embryo on cytoplasmic lattices.

Mammalian oocytes are filled with poorly understood structures called cytoplasmic lattices. First discovered in the 1960s and speculated to correspond to mammalian yolk, ribosomal arrays, or intermediate filaments, their function has remained enigmatic to date. Here, we show that cytoplasmic lattices are sites where oocytes store essential proteins for early embryonic development.

Weight loss with very-low-calorie diet and cardiovascular risk factors in moderately obese women: one-year follow-up study including ambulatory blood pressure monitoring.

Objective: The beneficial effects of weight loss with a very-low-calorie diet (VLCD) on cardiovascular risk factors have been reported at the end of energy restriction. As the effects, especially on blood pressure, may not remain constant during weight maintenance, we studied the longer-term effects of weight loss on 24h ambulatory blood pressure (ABP), lipids, glucose and insulin.

Design: Prospective study of a 17-week weight loss programme containing an eight-week VLCD period and follow-up visit at one-year.

Two year maintenance of weight loss after a VLCD and behavioural therapy for obesity: correlation to the scores of questionnaires measuring eating behaviour.

Objective: To investigate changes in weight, Three Factor Eating Questionnaire and Binge eating scores during a two-year period from the start of a VLCD (Nutrilett) and behavioural modification therapy for obesity.

Design: Prospective study of a 17-weeks weight loss programme with one- and two-year follow-up visits.

Subjects: 62 healthy, overweight subjects without previous eating disorders.