Binary specification of nonsense codons by splicing and cytoplasmic translation.

Premature translation termination codons resulting from nonsense or frameshift mutations are common causes of genetic disorders. Complications arising from the synthesis of C-terminally truncated polypeptides can be avoided by 'nonsense-mediated decay' of the mutant mRNAs. Premature termination codons in the beta-globin mRNA cause the common recessive form of beta-thalassemia when the affected mRNA is degraded, but the more severe dominant form when the mRNA escapes nonsense-mediated decay. We demonstrate that cells distinguish a premature termination codon within the beta-globin mRNA from the physiological translation termination codon by a two-step specification mechanism. According to the binary specification model proposed here, the positions of splice junctions are first tagged during splicing in the nucleus, defining a stop codon operationally as a premature termination codon by the presence of a 3' splicing tag. In the second step, cytoplasmic translation is required to validate the 3' splicing tag for decay of the mRNA. This model explains nonsense-mediated decay on the basis of conventional molecular mechanisms and allows us to propose a common principle for nonsense-mediated decay from yeast to man.

[Functions and tasks of the psychological rehabilitation of patients with malignant brain tumors]. / Funktionen und Aufgaben der psychischen Rehabilitation von Patienten mit maligner Hirntumorerkrankung.

Based on a holistic understanding of rehabilitation, overall objectives in rehabilitating patients with malignant brain tumour are outlined. On the background of demands to orient rehabilitational efforts more than hitherto on the specific needs of those affected, results obtained from interviewing 36 brain tumour patients are set out, regarding their anxieties as well as factors that were experienced as helpful in the process of coping with the disease. The rank of assistance in adjusting to impending death in rehabilitative work with patients who have malignant brain tumours is discussed. Also, possible reasons are outlined for patients hardly ever talking about their condition's life-threatening nature on their own initiative. A patient-centered approach is advocated for the psychoemotional support of this patient group, implications for training and further education of hospital workers are discussed briefly.