Polystyrene Nano- and Microplastic Particles Induce an Inflammatory Gene Expression Profile in Rat Neural Stem Cell-Derived Astrocytes In Vitro.

Microplastics are considered an emerging environmental pollutant due to their ubiquitous presence in the environment. However, the potential impact of microplastics on human health warrants further research. Recent studies have reported neurobehavioral and neurotoxic effects in marine and rodent models; however, their impact on the underlying cellular physiology in mammals remains unclear.

Distinct roles for the RNA-binding protein Staufen1 in prostate cancer.

Background: Prostate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients.

Overexpression of Staufen1 in DM1 mouse skeletal muscle exacerbates dystrophic and atrophic features.

In myotonic dystrophy type 1 (DM1), the CUG expansion (CUGexp) in the 3' untranslated region of the dystrophia myotonica protein kinase messenger ribonucleic acid affects the homeostasis of ribonucleic acid-binding proteins, causing the multiple symptoms of DM1. We have previously reported that Staufen1 is increased in skeletal muscles from DM1 mice and patients and that sustained Staufen1 expression in mature mouse muscle causes a progressive myopathy. Here, we hypothesized that the elevated levels of Staufen1 contributes to the myopathic features of the disease.

Cystatin C promotes tau protein phosphorylation and causes microtubule instability by inhibiting intracellular turnover of GSK3β in neurons.

In Alzheimer's disease (AD) tau protein hyperphosphorylation causes neurofibrillary tangle formation, microtubule instability and neurodegeneration. Determining the mechanism of tau hyperphosphorylation will provide a better understanding of AD pathology. Cystatin C (CysC) is a risk factor for late-onset AD and its level is upregulated in the brains of AD patients.

Novel Roles for Staufen1 in Embryonal and Alveolar Rhabdomyosarcoma via c-myc-dependent and -independent events.

Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle beds, and express key myogenic regulatory factors. However, their developmental program remains blocked in the proliferative phase with cells unable to exit the cell cycle to fuse into myotubes.

The p53 protein induces stable miRNAs that have the potential to modify subsequent p53 responses.

The p53 tumour suppressor is a transcription factor that can increase the expression of mRNAs and microRNAs (miRNAs). HT29-tsp53 cells expressing a temperature sensitive variant of p53 have provided a useful model to rapidly and reversibly control p53 activity. In this model, the majority of p53-responsive mRNAs were upregulated rapidly but they were short-lived leading to rapid decay of the p53 response at the restrictive temperature.

A Temperature Sensitive Variant of p53 Drives p53-Dependent MicroRNA Expression without Evidence of Widespread Post-Transcriptional Gene Silencing.

The p53 tumour suppressor is a transcription factor that can regulate the expression of numerous genes including many encoding proteins and microRNAs (miRNAs). The predominant outcomes of a typical p53 response are the initiation of apoptotic cascades and the activation of cell cycle checkpoints. HT29-tsp53 cells express a temperature sensitive variant of p53 and in the absence of exogenous DNA damage, these cells preferentially undergo G1 phase cell cycle arrest at the permissive temperature that correlates with increased expression of the cyclin-dependent kinase inhibitor p21WAF1.

A novel cis-acting element from the 3'UTR of DNA damage-binding protein 2 mRNA links transcriptional and post-transcriptional regulation of gene expression.

The DNA damage-binding protein 2 (DDB2) is an adapter protein that can direct a modular Cul4-DDB1-RING E3 Ligase complex to sites of ultraviolet light-induced DNA damage to ubiquitinate substrates during nucleotide excision repair. The DDB2 transcript is ultraviolet-inducible; therefore, its regulation is likely important for its function. Curiously, the DDB2 mRNA is reportedly short-lived, but the transcript does not contain any previously characterized cis-acting determinants of mRNA stability in its 3' untranslated region (3'UTR).

Modelling tauopathies in Drosophila: insights from the fruit fly.

Drosophila melanogaster is an experimentally tractable model organism that has been used successfully to model aspects of many human neurodegenerative diseases. Drosophila models of tauopathy have provided valuable insights into tau-mediated mechanisms of neuronal dysfunction and death. Here we review the findings from Drosophila models of tauopathy reported over the past ten years and discuss how they have furthered our understanding of the pathogenesis of tauopathies.

The role of mRNA decay in p53-induced gene expression.

The p53 tumor suppressor is a DNA-damage-responsive sequence-specific transcriptional activator. The sustained activation of the p53 response is incompatible with cell growth and viability. To circumvent this issue, a variety of negative feedback loops exist to limit the duration of p53 activation.