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Arboleda-Tham Syndrome (ARTHS) is a rare genetic disorder caused by heterozygous, de novo mutations in Lysine(K) acetyltransferase 6A (KAT6A). ARTHS is clinically heterogeneous and characterized by several common features, including intellectual disability, developmental and speech delay, and hypotonia, and affects multiple organ systems. KAT6A is the enzymatic core of a histone-acetylation protein complex; however, the direct histone targets and gene regulatory effects remain unknown. In this study, we use ARTHS patient (n = 8) and control (n = 14) dermal fibroblasts and perform comprehensive profiling of the epigenome and transcriptome caused by KAT6A mutations. We identified differential chromatin accessibility within the promoter or gene body of 23% (14/60) of genes that were differentially expressed between ARTHS and controls. Within fibroblasts, we show a distinct set of genes from the posterior HOXC gene cluster (HOXC10, HOXC11, HOXC-AS3, HOXC-AS2, and HOTAIR) that are overexpressed in ARTHS and are transcription factors critical for early development body segment patterning. The genomic loci harboring HOXC genes are epigenetically regulated with increased chromatin accessibility, high levels of H3K23ac, and increased gene-body DNA methylation compared to controls, all of which are consistent with transcriptomic overexpression. Finally, we used unbiased proteomic mass spectrometry and identified two new histone post-translational modifications (PTMs) that are disrupted in ARTHS: H2A and H3K56 acetylation. Our multi-omics assays have identified novel histone and gene regulatory roles of KAT6A in a large group of ARTHS patients harboring diverse pathogenic mutations. This work provides insight into the role of KAT6A on the epigenomic regulation in somatic cell types.

Background: Because patients infected with respiratory syncytial virus (RSV) have been reported to be older than patients infected with influenza virus, the more frequent incidence of complications in RSV-infected patients may be age-related. This study compared clinical characteristics and outcomes in hospitalized adults infected with RSV with findings in age- and sex-matched adults infected with influenza virus. Methods: The medical records of hospitalized adult patients infected with RSV or influenza virus at two university hospitals from 2013 to 2022 were retrospectively analyzed. Virus infection was confirmed by real-time polymerase chain reaction. Each RSV-infected patient was matched by age and sex with two influenza virus-infected patients, and their clinical symptoms, laboratory parameters and hospital courses were compared. Results: The study cohort consisted of 552 patients, 184 infected with RSV and 368 infected with influenza virus. Fever (71.2% vs. 79.9%, p =.022) and cough (70.1% vs. 80.4%, p =.007) were significantly less frequent in the RSV than in the influenza group, whereas white blood cell counts (9132/mm3 vs. 7616/mm3, p <.001) and C-reactive protein concentrations (10.25 vs. 8.88 mg/dL, p =.029) were significantly higher in the RSV group. The frequency of oxygen therapy was higher (60.3% vs. 48.6%, p =.010) and hospital stay was longer (8 vs. 6 days, p =.003) in RSV than in influenza virus-infected patients. Conclusions: Clinical symptoms were less frequent, but disease was more severe, in hospitalized adult patients infected with RSV than in age- and sex-matched patients infected with influenza. Greater attention should be paid to diagnosing and preventing RSV infection in adults. [ABSTRACT FROM AUTHOR]

Neuroscience research underscores the critical impact of adverse experiences on brain development. Yet, there is limited understanding of the specific pathways linking adverse experiences to accelerated or delayed brain development and their ultimate contributions to psychopathology. Here, we present new longitudinal data demonstrating that neurocognitive functioning during adolescence, as affected by adverse experiences, predicts psychopathology during young adulthood. The sample included 167 participants (52% male) assessed in adolescence and young adulthood. Adverse experiences were measured by early maltreatment experiences and low family socioeconomic status. Cognitive control was assessed by neural activation and behavioral performance during the Multi-Source Interference Task. Psychopathology was measured by self-reported internalizing and externalizing symptomatology. Results indicated that higher maltreatment predicted heightened frontoparietal activation during cognitive control, indicating delayed neurodevelopment, which, in turn predicted higher internalizing and externalizing symptomatology. Furthermore, higher maltreatment predicted a steeper decline in frontoparietal activation across adolescence, indicating neural plasticity in cognitive control-related brain development, which was associated with lower internalizing symptomatology. Our results elucidate the crucial role of neurocognitive development in the processes linking adverse experiences and psychopathology. Implications of the findings and directions for future research on the effects of adverse experiences on brain development are discussed. [ABSTRACT FROM AUTHOR]

BackgroundSeveral modifiable lifestyle factors have been shown to have potential beneficial effects in slowing cognitive decline. Two such factors that may affect cognitive performance and slow the progression of memory loss into dementia in older adults are cognitive training and physical activity. There are currently no effective treatments for dementia; therefore, preventative strategies to delay or prevent the onset of dementia are of critical importance.ObjectiveThe aim of this study was to determine the relative effectiveness of simultaneous performance of memory training and aerobic exercise to a sequential performance intervention on memory functioning in older adults.Methods55 older adults (aged 60- 75) with subjective memory impairments (non-demented and non-MCI) completed the intervention that consisted of 90-minute small group classes held twice weekly. Participants were randomized to either 4-weeks of supervised strategy-based memory training done simultaneously while stationary cycling (SIM) or sequentially after the stationary cycling (SEQ). Standardized neurocognitive measures of memory, executive functioning, speed of processing, attention, and cognitive flexibility were assessed at baseline and post-intervention.ResultsThe SIM group, but not the SEQ group, had a significant improvement on composite memory following the intervention (t(51) = 2.7, p = 0.01, effect size (ES) = 0.42) and transfer to non-trained reasoning abilities (t(51) = 6.0, ES = 0.49) and complex attention (t(51) = 3.1, p = 0.003, ES = 0.70). Conversely, the SEQ group, but not the SIM, showed significant improvement in executive functioning (t(51) = 5.0, p = 0.0001, ES = 0.96).ConclusionThese findings indicate that a 4-week simultaneous memory training and aerobic exercise program is sufficient to improve memory, attention, and reasoning abilities in older adults.

Since the first reported outbreak in Wuhan, China, on December 31, 2019, severe acute respiratory syndrome coronavirus 2 has infected >210 million persons and resulted in nearly 4.4 million deaths [...]