Loss of NSD2 causes dysregulation of synaptic genes and altered H3K36 dimethylation in mice

Background: Epigenetic disruptions have been implicated in neurodevelopmental disorders. NSD2 is associated with developmental delay/intellectual disability; however, its role in brain development and function remains unclear.Methods: We performed transcriptomic and epigenetic analyses using Nsd2 knockout mice to better understand the role of NSD2 in the brain.Results and discussion: Transcriptomic analysis revealed that the loss of NSD2 caused dysregulation of genes related to synaptic transmission and formation. By analyzing changes in H3 lysine 36 dimethylation (H3K36me2), NSD2-mediated H3K36me2 mainly marked quiescent state regions and the redistribution of H3K36me2 occurred at transcribed genes and enhancers. By integrating transcriptomic and epigenetic data, we observed that H3K36me2 changes in a subset of dysregulated genes related to synaptic transmission and formation. These results suggest that NSD2 is involved in the regulation of genes important for neural function through H3K36me2. Our findings provide insights into the role of NSD2 and improve our understanding of epigenetic regulation in the brain

Circadian protection against bacterial skin infection by epidermal CXCL14-mediated innate immunity

体内時計は夜間に自然免疫を発動 --皮膚ケモカインによる自然免疫機構--. 京都大学プレスリリース. 2022-06-16.Biological clocks set for skin immunity. 京都大学プレスリリース. 2022-06-21.The epidermis is the outermost layer of the skin and the body’s primary barrier to external pathogens; however, the early epidermal immune response remains to be mechanistically understood. We show that the chemokine CXCL14, produced by epidermal keratinocytes, exhibits robust circadian fluctuations and initiates innate immunity. Clearance of the skin pathogen Staphylococcus aureus in nocturnal mice was associated with CXCL14 expression, which was high during subjective daytime and low at night. In contrast, in marmosets, a diurnal primate, circadian CXCL14 expression was reversed. Rhythmically expressed CXCL14 binds to S. aureus DNA and induces inflammatory cytokine production by activating Toll-like receptor (TLR)9-dependent innate pathways in dendritic cells and macrophages underneath the epidermis. CXCL14 also promoted phagocytosis by macrophages in a TLR9-independent manner. These data indicate that circadian production of the epidermal chemokine CXCL14 rhythmically suppresses skin bacterial proliferation in mammals by activating the innate immune system

Synthesis and application of an N(δ)-acetyl-N(δ)-hydroxyornithine analog: Identification of novel metal complexes of deferriferrichrysin.

Synthesis of Fmoc-protected N(δ)-acetyl-N(δ)-(tert-butoxy)-l-ornithine has revealed it to be a metal-chelating amino-acid precursor. This protected amino acid was compatible with the preparation of ferrichrome peptides by standard Fmoc-based solid-phase peptide synthesis. Evaluation of deferriferrichrysin for metal ion chelation revealed that zirconium(IV) and titanium(IV) formed complexes with deferriferrichrysin

Synthesis and functional analysis of deferriferrichrysin derivatives: Application to colorimetric pH indicators.

Deferriferrichrysin belongs to the siderophore peptide family which are Fe(III)-coordinating cyclic peptides. The common structure of this family is three consecutive hydroxamate moieties, such as N(δ)-acetyl-N(δ)-hydroxy-l-ornithine (Aho). We have designed two deferriferrichrysin derivatives where three Aho residues were arranged as: cyclo(-Aho-Gly-Aho-Gly-Aho-Gly-) and cyclo(-Aho-Ser-Aho-Ser-Aho-Ser-). Comparative evaluation of the physicochemical properties of their Fe(III) complexes revealed that naturally occurring deferriferrichrysin formed a more stable Fe(III) complex when compared with the two derivatives. This result shows that three consecutive Aho residues are indispensable for high affinity Fe(III) binding by deferriferrichrysin. Of note, the observed pH-dependent chromogenic response of the Fe(III) complexes of the derivatives suggests that these two derivatives should function as sensitive pH indicators in acidic environments

A Case of Neuromyelitis Optica Masquerading as Miller Fisher Syndrome

A 22-year-old woman presented with double vision that she had experienced since an infection 2 weeks previously. A neurological examination showed limited bilateral eye abduction, mimicking Miller Fisher syndrome. However, T2-weighted magnetic resonance imaging of her brain revealed hyperintense areas in the tegmentum of the pons, including the abducens nucleus, and her serum anti-aquaporin-4 antibody test was positive. She was finally diagnosed with neuromyelitis optica. Intravenous high-dose steroid therapy immediately improved the patient's abduction palsy, but bilateral optic neuritis manifested during the treatment. Subsequent treatment with plasma exchange improved her optic neuritis symptoms