Reconsolidation involves histone acetylation depending on the strength of the memory.

Gene expression is a necessary step for memory re-stabilization after retrieval, a process known as reconsolidation. Histone acetylation is a fundamental mechanism involved in epigenetic regulation of gene expression and has been implicated in memory consolidation. However, few studies are available in reconsolidation, all of them in vertebrate models. Additionally, the recruitment of histone acetylation as a function of different memory strengths has not been systematically analyzed before. Here we studied the role of histone acetylation in reconsolidation using a well-characterized memory model in invertebrate, the context-signal memory in the crab Chasmagnathus. Firstly, we found an increase in histone H3 acetylation 1h after memory reactivation returning to basal levels at 3 h. Strikingly, this increment was only detected during reconsolidation of a long-term memory induced by a strong training of 30 trials, but not for a short-term memory formed by a weak training of five trials or for a long-term memory induced by a standard training of 15 trials. Furthermore, we showed that a weak memory which was enhanced during consolidation by histone deacetylases inhibition, also recruited histone H3 acetylation in reconsolidation as the strong training does. Accordingly, we found the first evidence that the administration of a histone acetyl transferase inhibitor during memory reconsolidation impairs long-term memory re-stabilization. Finally, we found that strong training memory, at variance with the standard training memory, was resistant to extinction, indicating that such strong training induced in fact a stronger memory. In conclusion, the results presented here support that the participation of histone acetylation during reconsolidation is an evolutionary conserved feature and constitutes a specific molecular characteristic of strong memories.

Bilateral microtia and cleft palate in cousins with Diamond-Blackfan anemia.

We report on maternal first cousins with bilateral microtia, micrognathia, cleft palate and hematologic findings of Diamond-Blackfan anemia (DBA). The similarity of findings shared between our cases and a female reported by Hasan and Inoue [1993] suggests that this is a distinctive syndrome, rather than a chance association. DBA is a heterogeneous disorder, caused in about 25% of cases by heterozygous mutations in the RPS19 gene (DBA1). Mutation analysis in our cases did not show an RPS19 mutation, and 2 alleles were present in each. Segregation analysis for DBA1 on chromosome 19 and DBA2 on 8p23 was not consistent with linkage. We conclude that this syndrome of microtia, cleft palate and DBA is not allelic to known DBA loci.

Hematopoietic stem cell transplantation for Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry.

The Diamond Blackfan Anemia (DBA) Registry of North America is a detailed database of patients with DBA from the United States and Canada. To date, 354 patients have been registered. From this database an analysis of the outcome of hematopoietic stem cell transplantation for DBA was undertaken. Of the 20 transplanted patients who met criteria for the diagnosis of DBA, eight underwent an allogeneic HLA-matched sibling hematopoietic stem cell transplant (SCT) and 12 an alternative donor SCT. The median age at transplant for all patients was 6 years 2 months; 3 years 10 months vs 9 years 1 month for HLA-matched sibling and alternative donor SCT, respectively. All of the HLA-matched sibling transplants were done using a non-irradiation-containing regimen, whereas the majority of alternative donor transplants were performed using total body irradiation. The survival for HLA-matched sibling vsalternative donor transplant was 87.5% +/- 11.7% vs 14.1% +/- 12.1% at greater than 5 years from SCT (P = 0.015). The use of HLA-matched sibling SCT should be considered for all patients with suitable donors. However, alternative donor SCT in DBA must be approached cautiously, the potential for severe aplastic anemia (SAA) or hematopoietic malignancy not withstanding.

Osteogenic sarcoma associated with Diamond-Blackfan anemia: a report from the Diamond-Blackfan Anemia Registry.

PURPOSE: Diamond-Blackfan anemia (DBA) is a congenital pure red cell aplasia, usually presenting in infancy or early childhood. A review of the literature strongly supports a predisposition to hematopoietic malignancy. Recently, solid tumors have been reported, some attributable to hemosiderosis and/or androgen therapy. Two cases of osteogenic sarcoma have also been documented. An analysis from the Diamond-Blackfan Anemia Registry was performed to evaluate the cancer risk in patients with DBA. METHODS: The Diamond-Blackfan Anemia Registry of North America (DBAR) is a comprehensive database of patients with DBA enrolled, after informed consent, through outreach to pediatric hematologists and family groups. The patients and/or their families complete a detailed questionnaire, and a review of medical records and telephone interviews are performed to complete and clarify the information provided. RESULTS: Of the 354 patients registered in the DBAR, there were six patients meeting the accepted diagnostic criteria for DBA who were found to have malignancies. Three patients had osteogenic sarcoma diagnosed, one with myelodysplastic syndrome, one with colon carcinoma, and one with a soft tissue sarcoma. CONCLUSION: There appears to be an association of osteogenic sarcoma with DBA. A young age at presentation may be a feature of DBA-associated osteogenic sarcoma. Because of the immaturity of the database, the actuarial risk for osteogenic sarcoma and other cancers in individuals with DBA cannot be ascertained. Speculation is made regarding the nature of the molecular defect leading to the association of DBA and osteogenic sarcoma.