Transcriptomic Analyses of Brains of RBM8A Conditional Knockout Mice at Different Developmental Stages Reveal Conserved Signaling Pathways Contributing to Neurodevelopmental Diseases.

RNA-binding motif 8A (RBM8A) is a core component of the exon junction complex (EJC) that binds pre-mRNAs and regulates their splicing, transport, translation, and nonsense-mediated decay (NMD). Dysfunction in the core proteins has been linked to several detriments in brain development and neuropsychiatric diseases. To understand the functional role of in brain development, we have generated brain-specific knockout mice and used next-generation RNA-sequencing to identify differentially expressed genes (DEGs) in mice with heterozygous, conditional knockout (cKO) of in the brain at postnatal day 17 (P17) and at embryonic day 12.

A Suite of New Strain Construction Vectors for Gene Expression Knockdown in Budding Yeast.

Numerous tools for gene expression knockdown have been developed and characterized in the model organism and extended to facilitate studies in multicellular models. To comparatively evaluate the efficacy of these approaches, we systematically applied seven such published constitutive and inducible knockdown strategies to a panel of essential genes encoding nuclear-localized proteins. In this effort, we created the CEAS (C-SWAT for Essential Allele Strains) collection, a suite of tagging vectors for improved utility and ease of strain construction.

Measuring transcription factor binding and gene expression using barcoded self-reporting transposon calling cards and transcriptomes.

Calling cards technology using self-reporting transposons enables the identification of DNA-protein interactions through RNA sequencing. Although immensely powerful, current implementations of calling cards in bulk experiments on populations of cells are technically cumbersome and require many replicates to identify independent insertions into the same genomic locus. Here, we have drastically reduced the cost and labor requirements of calling card experiments in bulk populations of cells by introducing a DNA barcode into the calling card itself.

Schizophrenia risk ZNF804A interacts with its associated proteins to modulate dendritic morphology and synaptic development.

Schizophrenia (SZ) is a devastating brain disease that affects about 1% of world population. Among the top genetic associations, zinc finger protein 804A (ZNF804A) gene encodes a zinc finger protein, associated with SZ and biolar disorder (BD). Copy number variants (CNVs) of ZNF804A have been observed in patients with autism spectrum disorders (ASDs), anxiety disorder, and BD, suggesting that ZNF804A is a dosage sensitive gene for brain development.

Full function of exon junction complex factor, Rbm8a, is critical for interneuron development.

The formation of the nervous system requires a balance between proliferation, differentiation, and migration of neural progenitors (NPs). Mutations in genes regulating development impede neurogenesis and lead to neuropsychiatric diseases, including autism spectrum disorders (ASDs) and schizophrenia (SZ). Recently, mutations in nonsense-mediated mRNA decay genes have been associated with ASDs, intellectual disability (ID), and SZ.

Gluconate suppresses seizure activity in developing brains by inhibiting CLC-3 chloride channels.

Neonatal seizures are different from adult seizures, and many antiepileptic drugs that are effective in adults often fail to treat neonates. Here, we report that gluconate inhibits neonatal seizure by inhibiting CLC-3 chloride channels. We detect a voltage-dependent outward rectifying Cl current mediated by CLC-3 Cl channels in early developing brains but not adult mouse brains.

Chemical Conversion of Human Fetal Astrocytes into Neurons through Modulation of Multiple Signaling Pathways.

We have previously developed a cocktail of nine small molecules to convert human fetal astrocytes into neurons, but a nine-molecule recipe is difficult for clinical applications. Here, we identify a chemical formula with only three to four small molecules for astrocyte-to-neuron conversion. We demonstrate that modulation of three to four signaling pathways among Notch, glycogen synthase kinase 3, transforming growth factor β, and bone morphogenetic protein pathways is sufficient to change an astrocyte into a neuron.

Control of CNS functions by RNA-binding proteins in neurological diseases.

Purpose Of Review: This review summarizes recent studies on the molecular mechanisms of RNA binding proteins (RBPs) that control neurological functions and pathogenesis in various neurodevelopmental and neurodegenerative diseases, including autism spectrum disorders, schizophrenia, Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and spinocerebellar ataxia.

Recent Findings: RBPs are critical players in gene expression that regulate every step of posttranscriptional modifications. Recent genome-wide approaches revealed that many proteins associate with RNA, but do not contain any known RNA binding motifs.

The complete chloroplast genome sequence of , a species with an extremely small population.

is an endemic species to China and is only distributed in Jiande, Zhejiang Province. The species is on the verge of extinction. The chloroplast genome of was determined from Illumina pair-end sequencing data.

Self-Assembly of Extracellular Vesicle-like Metal-Organic Framework Nanoparticles for Protection and Intracellular Delivery of Biofunctional Proteins.

The intracellular delivery of biofunctional enzymes or therapeutic proteins through systemic administration is of great importance in therapeutic intervention of various diseases. However, current strategies face substantial challenges owing to various biological barriers, including susceptibility to protein degradation and denaturation, poor cellular uptake, and low transduction efficiency into the cytosol. Here, we developed a biomimetic nanoparticle platform for systemic and intracellular delivery of proteins.

Displacement and hybridization reactions in aptamer-functionalized hydrogels for biomimetic protein release and signal transduction.

A variety of hydrogels have been synthesized for controlling the release of signaling molecules in applications such as drug delivery and regenerative medicine. However, it remains challenging to synthesize hydrogels with the ability to control the release of signaling molecules sequentially or periodically under physiological conditions as living cells do in response to the variation of metabolism. The purpose of this work was to study a novel biomimetic hydrogel system with the ability of recapitulating the procedure of cellular signal transduction and controlling the sequential release of signaling molecules under physiological conditions.

A prenatal interruption of DISC1 function in the brain exhibits a lasting impact on adult behaviors, brain metabolism, and interneuron development.

Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 (), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life.

Polycistronic tRNA and CRISPR guide-RNA enables highly efficient multiplexed genome engineering in human cells.

CRISPR/Cas9 has been widely used for genomic editing in many organisms. Many human diseases are caused by multiple mutations. The CRISPR/Cas9 system provides a potential tool to introduce multiple mutations in a genome.

Transient enhancement of proliferation of neural progenitors and impairment of their long-term survival in p25 transgenic mice.

Cyclin-dependent kinase 5 (CDK5) regulates important neuronal functions via p35. p35 undergoes cleavage in response to neuronal activity and neurotoxic conditions to release its subunit p25. Although p25 has been implicated in various neurodegenerative diseases, the mechanisms by which p25 mediates neurodegenerative impairment have not been fully elucidated.

Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects.

Mutations in β-catenin (CTNNB1) have been implicated in cancer and mental disorders. Recently, loss-of-function mutations of CTNNB1 were linked to intellectual disability (ID), and rare mutations were identified in patients with autism spectrum disorder (ASD). As a key regulator of the canonical Wnt pathway, CTNNB1 plays an essential role in neurodevelopment.

A critical role of RBM8a in proliferation and differentiation of embryonic neural progenitors.

Background: Nonsense mediated mRNA decay (NMD) is an RNA surveillance mechanism that controls RNA stability and ensures the speedy degradation of erroneous and unnecessary transcripts. This mechanism depends on several core factors in the exon junction complex (EJC), eIF4A3, RBM8a, Magoh, and BTZ, as well as peripheral factors to distinguish premature stop codons (PTCs) from normal stop codons in transcripts. Recently, emerging evidence has indicated that NMD factors are associated with neurodevelopmental disorders such as autism spectrum disorder (ASD) and intellectual disability (ID).

Concise review: mesenchymal stem cells and translational medicine: emerging issues.

Mesenchymal stem cells (MSCs) are emerging as a promising therapeutic approach of cell-based therapy for a wide range of autoimmune disorders and degenerative diseases. In preclinical and clinical studies, MSCs have been shown to be highly efficient in treating graft-versus-host disease, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, myocardial infarction, liver cirrhosis, inflammatory bowel disease, and other disorders. The underlying therapeutic mechanisms of MSCs include their homing efficiency to the tissue injury sites, their differentiation potential, their capability to produce a large amount of trophic factors, and their immunomodulatory effect.

Generation of human inner ear prosensory-like cells via epithelial-to-mesenchymal transition.

Aim: To identify human hair cell progenitors from adult inner ear sensory epithelium.

Materials & Methods: We collected discarded utricles from translabyrinthine surgery and isolated human utricular sensory epithelial cells (HUCs) to explore whether they can proliferate and obtain features of stem/progenitor cells in vitro using reverse transcription PCR and immunofluorescence.

Results: When cultured in vitro, HUCs expressed genes and proteins that are usually present in prosensory cells and stem cells.

[The influence of virtual reality both on biology experiment and teaching].

Based on the characters of virtual laboratory of biology and bioinformation, this article suggested that the development of the technique would lead to great influence and reform on both the experiments of biology and its teaching. Furthermore, the technique had an important impact on the traditional studies in Biology and its thinking model of students.

[Multicolor FISH analysis of rDNA and telomere on spin-ach].

In this study, multicolor FISH analysis on metaphase chromosomes of spinach with biotin-labeled 25S rDNA, DIG-labeled telomere sequences and biotin-labeled and DIG-labeled 5S rDNA was performed. There were six 25S rDNA loci, which were located on the satellites of the third, the fifth and the sixth chromosomes, four 5S rDNA loci, which were located on the long arms of the third and the fifth chromosomes. The telomere loci were located on the end of the sixth chromosome and also on both the end and centromeric regions of other chromosomes.