Congenital dyserythropoietic anemia type I is caused by mutations in codanin-1

Congenital dyserythropoietic anemias (CDAs) constitute a rare group of inherited red-blood-cell disorders associated with dysplastic changes in late erythroid precursors. CDA type I (CDAI [MIM 224120], gene symbol CDAN1) is characterized by erythroid pathological features such as internuclear chromatin bridges, spongy heterochromatin, and invagination of the nuclear membrane, carrying cytoplasmic organelles into the nucleus. A cluster of 45 highly inbred Israeli Bedouin with CDAI enabled the mapping of the CDAN1 disease gene to a 2-Mb interval, now refined to 1.2 Mb, containing 15 candidate genes on human chromosome 15q15 (Tamary et al. 1998). After the characterization and exclusion of 13 of these genes, we identified the CDAN1 gene through 12 different mutations in 9 families with CDAI. This 28-exon gene, which is transcribed ubiquitously into 4738 nt mRNA, was reconstructed on the basis of gene prediction and homology searches. It encodes codanin-1, a putative o-glycosylated protein of 1,226 amino acids, with no obvious transmembrane domains. Codanin-1 has a 150-residue amino-terminal domain with sequence similarity to collagens and two shorter segments that show weak similarities to the microtubule-associated proteins, MAP1B (neuraxin) and synapsin. These findings, and the cellular phenotype, suggest that codanin-1 may be involved in nuclear envelope integrity, conceivably related to microtubule attachments. The specific mechanisms by which codanin-1 underlies normal erythropoiesis remain to be elucidated

Supporting resilience of older adults with cognitive decline requires a multi-level system approach

The concept of resilience, i.e., the capacity of a system to bounce back after a stressor, is gaining interest across many fields of science, policy and practice. To date, resilience research in people with cognitive decline has predominantly addressed the early stages of decline. We propose that: (1) resilience is a relevant concept in all stages of cognitive decline; and (2) a socioecological, multisystem perspective on resilience is required to advance understanding of, and care and support for people with cognitive decline and their support networks. We substantiate our position with literature and examples. Resilience helps to understand differences in response to risk factors of (further) cognitive decline and informs personalised prevention. In a curative context, interventions to strengthen resilience aim to boost recovery from cognitive decline. In care for people with dementia, resilience focused interventions can strengthen coping mechanisms to maintain functioning and wellbeing of the individual and their support network. A good example of improving resilience in the social and policy context is the introduction of age-friendly cities and dementia-friendly communities. Good care for people with cognitive decline requires a health and social care system that can adapt to changes in demand. Given the interdependency of resilience at micro-, meso- and macro-levels, an integrative socioecological perspective is required. Applying the concept of resilience in the field of cognitive decline opens new horizons for research to improve understanding, predicting, intervening on health and social care needs for the increasing population with cognitive decline