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Kdm1a is a histone demethylase linked to intellectual disability with essential roles during gastrulation and the terminal differentiation of specialized cell types, including neurons, that remains highly expressed in the adult brain. To explore Kdm1a’s function in adult neurons, we develop inducible and forebrain-restricted Kdm1a knockouts. By applying multi-omic transcriptome, epigenome and chromatin conformation data, combined with super-resolution microscopy, we find that Kdm1a elimination causes the neuronal activation of nonneuronal genes that are silenced by the polycomb repressor complex and interspersed with active genes. Functional assays demonstrate that the N-terminus of Kdm1a contains an intrinsically disordered region that is essential to segregate Kdm1a-repressed genes from the neighboring active chromatin environment. Finally, we show that the segregation of Kdm1a-target genes is weakened in neurons during natural aging, underscoring the role of Kdm1a safeguarding neuronal genome organization and gene silencing throughout life.Kdm1a is a histone demethylase implicated in intellectual disability. Here, the authors show that removing Kdm1a in neurons of the adult mouse forebrain disrupts silencing of nonneuronal genes and chromatin organization, emphasizing its role in preserving neuronal genome integrity. [ABSTRACT FROM AUTHOR]

Objective: Adenoid hypertrophy may coexist, and often does, with rhinitis. Therefore, in some cases, adenoidectomy alone, despite the fact that it reduces nasal resistance, may be insufficient to restore nasal breathing. Juliusson et al. suggested using rhinomanometry with and without nasal decongestant as a method for selecting patients for adenoidectomy. In this study, we aim to assess whether the decongestant test, when using normative data, is useful to select children for adenoidectomy. Methods: Children between 4 and 15 years old undergoing adenoidectomy were selected from two tertiary referral university hospitals. Participants underwent anterior active rhinomanometry with and without nasal decongestant before and after surgery. Parents fill in the sinus and nasal quality-of-life survey (SN5). Results: 47 participants were included, and mean age 6.5 ± 2.15. 2 cohorts were defined according to the result of the nasal decongestant test (> 40% improvement in nasal resistance or not). There is a statistically significant difference between groups, with a higher improvement in nasal resistance and airflow after adenoidectomy in the group with less than 40% improvement in nasal resistance. Conclusions: In conclusion, this study supports the use of the decongestant test with rhinomanometry to select children for adenoidectomy; especially as it has proven to be a simple technique, harmless, fast, and easily performed on collaborative children. [ABSTRACT FROM AUTHOR]

This paper aims to analyse the ductility of existing buildings to evaluate its influence in their seismic performance. This has been achieved through the retrospective analysis of an existing building in accordance with current seismic codes. This study has revealed the lack of guidance in the NCSE02 and the EC8 regarding the assessment of the ductility of existing buildings. This manuscript proposes a methodology to assess the ductility of Spanish existing buildings. For this purpose, this paper has implemented the American code procedure combined with the EC8 and the Spanish seismic code (NCSE02) requirements. A two-storey RC frame school located in the Spanish region of Huelva has been selected as a case study. Different versions of this school have been compared: as built, designed according to current best practice, EC8 provisions and NCSE02 provisions. To do so, different constructive features have been varied according to each of the ductility class requirements: geometrical properties and the reinforcement ratio of the structural elements. Nonlinear static analyses have been carried out to obtain the displacement ductility factor (μ) and the behaviour factor (q) of each model. Construction costs and the expected damage index have been determined and compared. Results have shown that the best performance, regarding the ductility and the costs, has been obtained with the models designed with deep beams. Conversely, models with wide beams, and where only the reinforcement ratios have been varied, have merely shown a slight enhancement of the resistant and ductile capacity. It has been concluded that the ductility affects the shear capacity, the seismic performance and the expected damage of RC buildings. [ABSTRACT FROM AUTHOR]

The lysine acetyltransferases type 3 (KAT3) family members CBP and p300 are important transcriptional co-activators, but their specific functions in adult post-mitotic neurons remain unclear. Here, we show that the combined elimination of both proteins in forebrain excitatory neurons of adult mice resulted in a rapidly progressing neurological phenotype associated with severe ataxia, dendritic retraction and reduced electrical activity. At the molecular level, we observed the downregulation of neuronal genes, as well as decreased H3K27 acetylation and pro-neural transcription factor binding at the promoters and enhancers of canonical neuronal genes. The combined deletion of CBP and p300 in hippocampal neurons resulted in the rapid loss of neuronal molecular identity without de- or transdifferentiation. Restoring CBP expression or lysine acetylation rescued neuronal-specific transcription in cultured neurons. Together, these experiments show that KAT3 proteins maintain the excitatory neuron identity through the regulation of histone acetylation at cell type-specific promoter and enhancer regions. Neuronal identity maintenance is highly regulated. Here, the authors showed that CBP and p300 safeguard neuronal identity through histone acetylation at promoters and enhancers of neuronal specific genes. The loss of both CBP and p300 impairs gene expression, circuit activity, and behavior in mice. [ABSTRACT FROM AUTHOR]

The development of inhibitory circuits depends on the action of a network of transcription factors and epigenetic regulators that are critical for interneuron specification and differentiation. Although the identity of many of these transcription factors is well established, much less is known about the specific contribution of the chromatin-modifying enzymes that sculpt the interneuron epigenome. Here, we generated a mouse model in which the lysine acetyltransferase CBP is specifically removed from neural progenitors at the median ganglionic eminence (MGE), the structure where the most abundant types of cortical interneurons are born. Ablation of CBP interfered with the development of MGE-derived interneurons in both sexes, causing a reduction in the number of functionally mature interneurons in the adult forebrain. Genetic fate mapping experiments not only demonstrated that CBP ablation impacts on different interneuron classes, but also unveiled a compensatory increment of interneurons that escaped recombination and cushion the excitatory-inhibitory imbalance. Consistent with having a reduced number of interneurons, CBP-deficient mice exhibited a high incidence of spontaneous epileptic seizures, and alterations in brain rhythms and enhanced low gamma activity during status epilepticus. These perturbations led to abnormal behavior including hyperlocomotion, increased anxiety and cognitive impairments. Overall, our study demonstrates that CBP is essential for interneuron development and the proper functioning of inhibitory circuitry in vivo. [ABSTRACT FROM AUTHOR]