Immune pathogenic response landscape of acute posterior multifocal placoid pigment epitheliopathy revealed by scRNA sequencing.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an exceptionally rare inflammatory disorder affecting choroid and retinal pigment epithelial (RPE) cells. Although recent studies suggest an immune-driven nature, the underlying etiology of APMPPE remains elusive. In this study, we conducted a comprehensive investigation on the peripheral blood mononuclear cells (PBMCs) profile of an APMPPE patient using single-cell RNA sequencing.

Novel biallelic variants in IREB2 cause an early-onset neurodegenerative disorder in a Chinese pedigree.

Background: Cellular iron metabolism is essential for maintaining various biological processes in organisms, and this is influenced by the function of iron-responsive element-binding protein 2 (IRP2), encoded by the IREB2 gene. Since 2019, three cases of a genetic neurodegenerative syndrome resulting from compound heterozygous mutations in IREB2 have been documented, highlighting the crucial role of IRP2 in regulating iron metabolism homeostasis. This study aims to investigate the molecular basis in a single proband born to non-consanguineous healthy parents, presenting with severe psychomotor developmental abnormalities and microcytic anemia.

Novel autosomal recessive SINO syndrome-associated variants provide insight into the genotype-phenotype correlation.

Background: encodes a transmembrane scaffold protein, kinase D-interacting substrate of 220 kDa, that regulates neurotrophin signaling. Variants in have been linked to spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome or prenatal fatal cerebral ventriculomegaly and arthrogryposis (VENARG). This study aimed to investigate the genotype-phenotype correlation of pathogenic variants.

Methyltransferase METTL3 governs the modulation of SH3BGR expression through m6A methylation modification, imparting influence on apoptosis in the context of Down syndrome-associated cardiac development.

Down syndrome (DS), caused by an additional chromosome 21, has a high risk of congenital heart defects (CHD), one of the primary causes of mortality in DS newborns. To elucidate the pathogenetic mechanisms underlying this condition, we explored the role of RNA m6A methylation, regulated by METTL3, in DS cardiac development and its impact on the expression of SH3BGR, a gene located at Down syndrome congenital heart disease (DS-CHD) minimal region. We analyzed DS fetal cardiac tissues to assess RNA m6A methylation levels and identify potential contributors.

Transcriptome research of human amniocytes identifies hub genes associated with developmental dysplasia in down syndrome.

Trisomy 21, or Down syndrome (DS), is the most frequent human autosomal chromosome aneuploidy, which leads to multiple developmental disorders, especially mental retardation in individuals. The presence of an additional human chromosome 21 (HSA21) could account for the pathological manifestations in DS. In this study, we analyzed the mRNA gene expression profile of DS-derived amniocytes compared with normal amniocytes, aiming to evaluate the relationship between candidate dysregulated HSA21 genes and DS developmental phenotypes.

Integration of ATAC-seq and RNA-seq identifies MX1-mediated AP-1 transcriptional regulation as a therapeutic target for Down syndrome.

Background: Growing evidence has suggested that Type I Interferon (I-IFN) plays a potential role in the pathogenesis of Down Syndrome (DS). This work investigates the underlying function of MX1, an effector gene of I-IFN, in DS-associated transcriptional regulation and phenotypic modulation.

Methods: We performed assay for transposase-accessible chromatin with high-throughout sequencing (ATAC-seq) to explore the difference of chromatin accessibility between DS derived amniocytes (DSACs) and controls.

Functional analysis of a novel nonsense variant c.91A>T of the gene in a Chinese family with X-linked recessive autosomal spondyloepiphyseal dysplasia tarda.

Spondyloepiphyseal dysplasia tarda (SEDT) is a condition involving late-onset, X-linked recessive skeletal dysplasia caused by mutations in the gene. In this paper, we identified a novel nonsense variant in a SEDT pedigree and analyzed the function of the variant in an attempt to explain the new pathogenesis of the TRAPPC2 protein in SEDT. Briefly, DNA and RNA samples from the peripheral blood of SEDT individuals were prepared.

Three-way contact analysis characterizes the higher order organization of the Tcra locus.

The generation of highly diverse antigen receptors in T and B lymphocytes relies on V(D)J recombination. The enhancer Eα has been implicated in regulating the accessibility of Vα and Jα genes through long-range interactions during rearrangements of the T-cell antigen receptor gene Tcra. However, direct evidence for Eα physically mediating the interaction of Vα and Jα genes is still lacking.

Chromatin organizer SATB1 controls the cell identity of CD4 CD8 double-positive thymocytes by regulating the activity of super-enhancers.

CD4 and CD8 double-positive (DP) thymocytes play a crucial role in T cell development in the thymus. DP cells rearrange the T cell receptor gene Tcra to generate T cell receptors with TCRβ. DP cells differentiate into CD4 or CD8 single-positive (SP) thymocytes, regulatory T cells, or invariant nature kill T cells (iNKT) in response to TCR signaling.

Inhibition of NOS1 promotes the interferon response of melanoma cells.

Background: NOS1 expression predicts poor prognosis in patients with melanoma. However, the molecular function of NOS1 in the type I IFN response and immune escape of melanoma is still unknown.

Methods: The CRISPR/Cas9 system was used to generate NOS1-knockout melanoma cells and the biological characteristics of NOS1-knockout cells were evaluated by MTT assay, clonogenic assay, EdU assay, and flow cytometric assay.

Case Report: Twin Pregnancy Gives Birth to a Girl with Partial Trisomy 21 Mosaicism after Fertilization and Embryo Transfer.

To report a rare case in which an IVF-ET twin pregnancy gave birth to a partial trisomy 21 chimera girl. Case report. University hospital.

Epicardium-Derived Tbx18 CDCs Transplantation Improve Heart Function in Infarcted Mice.

Cardiosphere-derived cells (CDCs) constitute a cardiac stem cell pool, a promising therapeutics in treating myocardial infarction (MI). However, the cell source of CDCs remains unclear. In this study, we isolated CDCs directly from adult mouse heart epicardium named primary epicardium-derived CDCs (pECDCs), which showed a different expression profile compared with primary epicardial cells (pEpiCs).

A Novel Variant of the KIF11 Gene, c.2922G>T, Is Associated with Microcephaly by Affecting RNA Splicing.

Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) is an inherited disorder characterized by severe microcephaly and abnormal facial features. Kinesin family member 11 (KIF11) mutations have been reported closely related to microcephaly in different cases, while the pathogenicity was still unclear. Here, we report a de novo heterozygous mutation in exon 20 of the KIF11 (c.

Phase separation of Epstein-Barr virus EBNA2 protein reorganizes chromatin topology for epigenetic regulation.

Epstein-Barr virus nuclear antigen 2 (EBNA2) is a transactivator of viral and cellular gene expression, which plays a critical role in the Epstein-Barr virus-associated diseases. It was reported that EBNA2 regulates gene expression by reorganizing chromatin and manipulating epigenetics. Recent studies showed that liquid-liquid phase separation plays an essential role in epigenetic and transcriptional regulation.

Downregulation by CNNM2 of ATP5MD expression in the 10q24.32 schizophrenia-associated locus involved in impaired ATP production and neurodevelopment.

Genome-wide association studies (GWAS) have accelerated the discovery of numerous genetic variants associated with schizophrenia. However, most risk variants show a small effect size (odds ratio (OR) <1.2), suggesting that more functional risk variants remain to be identified.

METTL3-Mediated N6-Methyladenosine Modification Is Involved in the Dysregulation of NRIP1 Expression in Down Syndrome.

Down syndrome (DS) is a common genetic condition in which a person is born with an extra copy of chromosome 21. Intellectual disability is the most common characteristic of DS. N6-methyladenosine (m6A) is a common RNA modification that is implicated in many biological processes.

The role of S-nitrosylation of PFKM in regulation of glycolysis in ovarian cancer cells.

One of the malignant transformation hallmarks is metabolism reprogramming, which plays a critical role in the biosynthetic needs of unchecked proliferation, abrogating cell death programs, and immunologic escape. However, the mechanism of the metabolic switch is not fully understood. Here, we found that the S-nitrosoproteomic profile of endogenous nitrogen oxide in ovarian cancer cells targeted multiple components in metabolism processes.

Intravitreal Injection of an Exosome-Associated Adeno-Associated Viral Vector Enhances Retinoschisin 1 Gene Transduction in the Mouse Retina.

To investigate whether exosome-associated adeno-associated virus (AAV) retinoschisin 1 (1) vector improved the transduction efficiency of 1 in the mouse retina. pAAV2-RS1-ZsGreen plasmid was constructed by homologous recombination. Exosome-associated AAV vectors containing human 1 gene (exosome-associated AAV [exo-AAV]2-RS1-ZsGreen) were isolated from producer cells' supernatant, and confirmed by transmission electron microscopy, nanoparticle tracking analysis, and western blotting.

The role of chromatin organizer Satb1 in shaping TCR repertoire in adult thymus.

T cells recognize the universe of foreign antigens with a diverse repertoire of T cell receptors generated by V(D)J recombination. Special AT-rich binding protein 1 (Satb1) is a chromatin organizer that plays an essential role in T cell development. Previous study has shown that Satb1 regulates the re-induction of recombinase Rag1 and Rag2 in CD4CD8 thymocytes, affecting the secondary rearrangement of the gene.

Integrative Analysis Extracts a Core ceRNA Network of the Fetal Hippocampus With Down Syndrome.

Accumulating evidence suggests that circular RNAs (circRNAs)-miRNA-mRNA ceRNA regulatory network-may play an important role in neurological disorders, such as Alzheimer's disease (AD). Interestingly, neuropathological changes that closely resemble AD have been found in nearly all Down syndrome (DS) cases > 35 years. However, few studies have reported circRNA transcriptional profiling in DS cases, which is caused by a chromosomal aberration of trisomy 21.

The Ig heavy chain protein but not its message controls early B cell development.

Development of progenitor B cells (ProB cells) into precursor B cells (PreB cells) is dictated by immunoglobulin heavy chain checkpoint (IgHCC), where the IgHC encoded by a productively rearranged allele assembles into a PreB cell receptor complex (PreBCR) to generate signals to initiate this transition and suppressing antigen receptor gene recombination, ensuring that only one productive allele is expressed, a phenomenon known as allelic exclusion. In contrast to a productively rearranged allele, the messenger RNA (mRNA) () from a nonproductively rearranged allele is degraded by nonsense-mediated decay (NMD). This fact prohibited firm conclusions regarding the contribution of stable to the molecular and developmental changes associated with the IgHCC.