Unraveling the Metabolic Enigma: A High-Resolution LC-MS Approach to Decipher Two Triazine Herbicides Tolerance in Radish and Rice.

Our study investigated the effects of terbuthylazine (TBA) and metribuzin (MT) on rice and radish at field application concentrations. Both herbicides induced oxidative stress and severely inhibited growth in the two crops. However, the radish cultivar T-33 exhibited significantly lower stress levels compared to the sensitive cultivar S-24, suggesting its higher tolerance to TBA and MT.

De novo missense variants in the PP2A regulatory subunit PPP2R2B in a neurodevelopmental syndrome: potential links to mitochondrial dynamics and spinocerebellar ataxias.

The heterotrimeric protein phosphatase 2A (PP2A) complex catalyzes about half of Ser/Thr dephosphorylations in eukaryotic cells. A CAG repeat expansion in the neuron-specific protein PP2A regulatory subunit PPP2R2B gene causes spinocerebellar ataxia type 12 (SCA12). We established five monoallelic missense variants in PPP2R2B (four confirmed as de novo) as a cause of intellectual disability with developmental delay (R149P, T246K, N310K, E37K, I427T).

Identification of a specific APOE transcript and functional elements associated with Alzheimer's disease.

Background: The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized.

Methods: To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples.

Generation of a human induced pluripotent stem cell line JHUi004-A with heterozygous mutation for spinocerebellar ataxia type 12 using genome editing.

Spinocerebellar ataxia type 12 (SCA12) is caused by a CAG expansion mutation in PPP2R2B, a gene encoding brain-specific regulatory units of protein phosphatase 2A (PP2A); while normal alleles carry 4 to 31 triplets, the disease alleles carry 43 to 78 triplets. Here, by CRISPR/Cas9n genome editing, we have generated a human heterozygous SCA12 iPSC line with 73 triplets for the mutant allele. The heterozygous SCA12 iPSCs have normal karyotype, express pluripotency markers and are able to differentiate into the three germ layers.

Huntington disease-like 2: insight into neurodegeneration from an African disease.

Huntington disease (HD)-like 2 (HDL2) is a rare genetic disease caused by an expanded trinucleotide repeat in the JPH3 gene (encoding junctophilin 3) that shows remarkable clinical similarity to HD. To date, HDL2 has been reported only in patients with definite or probable African ancestry. A single haplotype background is shared by patients with HDL2 from different populations, supporting a common African origin for the expansion mutation.

Identification of a specific APOE transcript and functional elements associated with Alzheimer's disease.

Introduction: The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus have not been fully characterized.

Methods: To identify novel AD-linked functional elements within the locus, we integrated SNP variants with RNA-seq, DNA methylation, and ChIP-seq data from human postmortem brains.

Bidirectional Transcription at the PPP2R2B Gene Locus in Spinocerebellar Ataxia Type 12.

Background: Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by expansion of a CAG repeat in the PPP2R2B gene.

Objective: In this study, we tested the hypothesis that the PPP2R2B antisense (PPP2R2B-AS1) transcript containing a CUG repeat is expressed and contributes to SCA12 pathogenesis.

Methods: Expression of PPP2R2B-AS1 transcript was detected in SCA12 human induced pluripotent stem cells (iPSCs), iPSC-derived NGN2 neurons, and SCA12 knock-in mouse brains using strand-specific reverse transcription polymerase chain reaction.

Bidirectional transcription at the gene locus in spinocerebellar ataxia type 12.

Objective: Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by expansion of a CAG repeat in the . Here we tested the hypothesis that the ( ) transcript containing a CUG repeat is expressed and contributes to SCA12 pathogenesis.

Methods: Expression of transcript was detected in SCA12 human induced pluripotent stem cells (iPSCs), iPSC-derived NGN2 neurons, and SCA12 knock-in mouse brains using strand-specific RT-PCR (SS-RT-PCR).

Generation of a human induced pluripotent stem cell line JHUi003-A with homozygous mutation for spinocerebellar ataxia type 12 using genome editing.

Spinocerebellar ataxia type 12 (SCA12) is caused by a CAG expansion mutation in PPP2R2B, a gene encoding a brain-specific regulatory unit of protein phosphatase 2A (PP2A); while normal alleles carry 4 to 31 triplets, the disease alleles carry 43 to 78 triplets. Here, by CRISPR/Cas9 genome editing, we have generated a human homozygous SCA12 iPSC line with 69 and 72 triplets for each allele. The homozygous SCA12 iPSCs have normal karyotype, express pluripotency markers and are able to differentiate into the three germ layers.

Use of single guided Cas9 nickase to facilitate precise and efficient genome editing in human iPSCs.

Cas9 nucleases permit rapid and efficient generation of gene-edited cell lines. However, in typical protocols, mutations are intentionally introduced into the donor template to avoid the cleavage of donor template or re-cleavage of the successfully edited allele, compromising the fidelity of the isogenic lines generated. In addition, the double-stranded breaks (DSBs) used for editing can introduce undesirable "on-target" indels within the second allele of successfully modified cells via non-homologous end joining (NHEJ).

A high-throughput screening to identify small molecules that suppress huntingtin promoter activity or activate huntingtin-antisense promoter activity.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of huntingtin (HTT). While there are currently no disease-modifying treatments for HD, recent efforts have focused on the development of nucleotide-based therapeutics to lower HTT expression. As an alternative to siRNA or oligonucleotide methods, we hypothesized that suppression of HTT expression might be accomplished by small molecules that either (1) directly decrease HTT expression by suppressing HTT promoter activity or (2) indirectly decrease HTT expression by increasing the promoter activity of HTT-AS, the gene antisense to HTT that appears to inhibit expression of HTT.

[Effects of temperature on leaf lettuce vernalization.].

To investigate the effects of different temperatures on the vernalization of leaf lettuce, and declare their type, two easy bolting leaf lettuce varieties of GB-30 and GB-31 were selected as material, which were treated by 4 ℃, 20 ℃ and 25 ℃ for 20 d respectively and afterwards treated by high temperature stress. The process of flower bud differentiation was observed by using paraffin section technology, and combined the condition of bolting and flowering to estimate whether or not it underwent vernalization, and defined its vernalization type. The results showed that, two varieties of GB-30 and GB-31 appeared bolting to different degrees at the 8 day under high temperature stress after temperature treatments in the early stage.

ATXN2-AS, a gene antisense to ATXN2, is associated with spinocerebellar ataxia type 2 and amyotrophic lateral sclerosis.

Objective: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by a CAG repeat expansion in the gene ataxin-2 (ATXN2). ATXN2 intermediate-length CAG expansions were identified as a risk factor for amyotrophic lateral sclerosis (ALS). The ATXN2 CAG repeat is translated into polyglutamine, and SCA2 pathogenesis has been thought to derive from ATXN2 protein containing an expanded polyglutamine tract.

Assessing a peptidylic inhibitor-based therapeutic approach that simultaneously suppresses polyglutamine RNA- and protein-mediated toxicities in patient cells and Drosophila.

Polyglutamine (polyQ) diseases represent a group of progressive neurodegenerative disorders that are caused by abnormal expansion of CAG triplet nucleotides in disease genes. Recent evidence indicates that not only mutant polyQ proteins, but also their corresponding mutant RNAs, contribute to the pathogenesis of polyQ diseases. Here, we describe the identification of a 13-amino-acid peptide, P3, which binds directly and preferentially to long-CAG RNA within the pathogenic range.

Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65.

Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin (HTT) gene. Recent evidence suggests that HD is a consequence of multimodal, non-mutually exclusive mechanisms of pathogenesis that involve both HTT protein- and HTT RNA-triggered mechanisms. Here we provide further evidence for the role of expanded HTT (expHTT) RNA in HD by demonstrating that a fragment of expHTT is cytotoxic in the absence of any translation and that the extent of cytotoxicity is similar to the cytotoxicity of an expHTT protein fragment encoded by a transcript of similar length and with a similar repeat size.

Phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. Disease pathogenesis derives, at least in part, from the long polyglutamine tract encoded by mutant HTT. Therefore, considerable effort has been dedicated to the development of therapeutic strategies that significantly reduce the expression of the mutant HTT protein.

Reciprocal regulation of axonal Filopodia and outgrowth during neuromuscular junction development.

Background: The assembly of the vertebrate neuromuscular junction (NMJ) is initiated when nerve and muscle first contact each other by filopodial processes which are thought to enable close interactions between the synaptic partners and facilitate synaptogenesis. We recently reported that embryonic Xenopus spinal neurons preferentially extended filopodia towards cocultured muscle cells and that basic fibroblast growth factor (bFGF) produced by muscle activated neuronal FGF receptor 1 (FGFR1) to induce filopodia and favor synaptogenesis. Intriguingly, in an earlier study we found that neurotrophins (NTs), a different set of target-derived factors that act through Trk receptor tyrosine kinases, promoted neuronal growth but hindered presynaptic differentiation and NMJ formation.

Regulation of axonal growth and neuromuscular junction formation by neuronal phosphatase and tensin homologue signaling.

During the development of the vertebrate neuromuscular junction (NMJ), motor axon tips stop growing after contacting muscle and transform into presynaptic terminals that secrete the neurotransmitter acetylcholine and activate postsynaptic ACh receptors (AChRs) to trigger muscle contraction. The neuron-intrinsic signaling that retards axonal growth to facilitate stable nerve-muscle interaction and synaptogenesis is poorly understood. In this paper, we report a novel function of presynaptic signaling by phosphatase and tensin homologue (PTEN) in mediating a growth-to-synaptogenesis transition in neurons.

Differential regulation of axonal growth and neuromuscular junction assembly by HGF/c-Met signaling.

Background: During vertebrate neuromuscular junction (NMJ) development, contact between motor axons and muscle fibers is followed by pre- and post-synaptic specialization. Using Xenopus nerve-muscle cocultures, we recently showed that spinal neurons initially contacted muscle cells by means of filopodial processes, and that muscle-derived basic fibroblast growth factor induced axonal filopodia and slowed axonal advance to promote nerve-muscle interaction and NMJ establishment. In contrast, neurotrophins enhanced axonal growth but suppressed the extension of axonal filopodia and blocked NMJ formation.

The function of p120 catenin in filopodial growth and synaptic vesicle clustering in neurons.

At the developing neuromuscular junction (NMJ), physical contact between motor axons and muscle cells initiates presynaptic and postsynaptic differentiation. Using Xenopus nerve-muscle cocultures, we previously showed that innervating axons induced muscle filopodia (myopodia), which facilitated interactions between the synaptic partners and promoted NMJ formation. The myopodia were generated by nerve-released signals through muscle p120 catenin (p120ctn), a protein of the cadherin complex that modulates the activity of Rho GTPases.

Axonal filopodial asymmetry induced by synaptic target.

During vertebrate neuromuscular junction (NMJ) assembly, motor axons and their muscle targets exchange short-range signals that regulate the subsequent steps of presynaptic and postsynaptic specialization. We report here that this interaction is in part mediated by axonal filopodia extended preferentially by cultured Xenopus spinal neurons toward their muscle targets. Immunoblotting and labeling experiments showed that basic fibroblast growth factor (bFGF) was expressed by muscle and associated with the cell surface, and treatment of cultured spinal neurons with recombinant bFGF nearly doubled the normal density of filopodia in neurites.