The dispersion method does not affect the in vitro genotoxicity of multi-walled carbon nanotubes despite inducing surface alterations.

Multi-walled carbon nanotubes (MWCNTs) are a desirable class of high aspect ratio nanomaterials (HARNs) owing to their extensive applications. Given their demand, the growing occupational and consumer exposure to these materials has warranted an extensive investigation into potential hazards they may pose towards human health. This study utilised both the in vitro mammalian cell gene mutation and the cytokinesis-blocked micronucleus (CBMN) assays to investigate genotoxicity in human lymphoblastoid (TK6) and 16HBE14o human lung epithelial cells, following exposure to NM-400 and NM-401 MWCNTs for 24 h.

Differentially Induced Autophagy by Engineered Nanomaterial Treatment Has an Impact on Cellular Homeostasis and Cytotoxicity.

Considering the increasing production of engineered nanomaterials (ENMs), new approach methodologies (NAMs) are essential for safe-by-design approaches and risk assessment. Our aim was to enhance screening strategies with a focus on reactivity-triggered toxicities. We applied tests to 10 selected benchmark ENMs in two cell models, lung epithelial A549 and differentiated THP-1 macrophage-like cells.

Towards characterization of cell culture conditions for reliable proteomic analysis: in vitro studies on A549, differentiated THP-1, and NR8383 cell lines.

Proteomic investigations result in high dimensional datasets, but integration or comparison of different studies is hampered by high variances due to different experimental setups. In addition, cell culture conditions can have a huge impact on the outcome. This study systematically investigates the impact of experimental parameters on the proteomic profiles of commonly used cell lines-A549, differentiated THP-1 macrophage-like cells, and NR8383-for toxicity studies.

Governance of advanced materials: Shaping a safe and sustainable future.

The past few decades of managing the uncertain risks associated with nanomaterials have provided valuable insights (knowledge gaps, tools, methods, etc.) that are equally important to promote safe and sustainable development and use of advanced materials. Based on these insights, the current paper proposes several actions to optimize the risk and sustainability governance of advanced materials.

Advancing Nanomaterial Toxicology Screening Through Efficient and Cost-Effective Quantitative Proteomics.

Proteomic investigations yield high-dimensional datasets, yet their application to large-scale toxicological assessments is hindered by reproducibility challenges due to fluctuating measurement conditions. To address these limitations, this study introduces an advanced tandem mass tag (TMT) labeling protocol. Although labeling approaches shorten data acquisition time by multiplexing samples compared to traditional label-free quantification (LFQ) methods in general, the associated costs may surge significantly with large sample sets, for example, in toxicological screenings.

Meta-Analysis of Integrated Proteomic and Transcriptomic Data Discerns Structure-Activity Relationship of Carbon Materials with Different Morphologies.

The Fiber Pathogenicity Paradigm (FPP) establishes connections between fiber structure, durability, and disease-causing potential observed in materials like asbestos and synthetic fibers. While emerging nanofibers are anticipated to exhibit pathogenic traits according to the FPP, their nanoscale diameter limits rigidity, leading to tangling and loss of fiber characteristics. The absence of validated rigidity measurement methods complicates nanofiber toxicity assessment.

A comparative proteomics analysis of four contact allergens in THP-1 cells shows distinct alterations in key metabolic pathways.

Allergic contact dermatitis (ACD) is the predominant form of immunotoxicity in humans. The sensitizing potential of chemicals can be assessed in vitro. However, a better mechanistic understanding could improve the current OECD-validated test battery.

PROTEOMAS: a workflow enabling harmonized proteomic meta-analysis and proteomic signature mapping.

Toxicological evaluation of substances in regulation still often relies on animal experiments. Understanding the substances' mode-of-action is crucial to develop alternative test strategies. Omics methods are promising tools to achieve this goal.

The Contact Allergen NiSO Triggers a Distinct Molecular Response in Primary Human Dendritic Cells Compared to Bacterial LPS.

Dendritic cells (DC) play a central role in the pathogenesis of allergic contact dermatitis (ACD), the most prevalent form of immunotoxicity in humans. However, knowledge on allergy-induced DC maturation is still limited and proteomic studies, allowing to unravel molecular effects of allergens, remain scarce. Therefore, we conducted a global proteomic analysis of human monocyte-derived dendritic cells (MoDC) treated with NiSO, the most prominent cause of ACD and compared proteomic alterations induced by NiSO to the bacterial trigger lipopolysaccharide (LPS).

Proteomic Phosphosite Analysis Identified Crucial NPM-ALK-Mediated NIPA Serine and Threonine Residues.

Anaplastic large-cell lymphoma (ALCL) is an aggressive non-Hodgkin lymphoma that shows in 60% of cases a translocation t(2;5)(p23;q35), which leads to the expression of the oncogenic kinase NPM-ALK. The nuclear interaction partner of ALK (NIPA) defines an E3-SCF ligase that contributes to the timing of mitotic entry. It has been shown that co-expression of NIPA and NPM-ALK results in constitutive NIPA phosphorylation.

Mass Spectrometry-Based Analysis of TRPP2 Phosphorylation.

Differential phosphorylation of proteins is a key regulatory mechanism in biology. Immunoprecipitation-coupled mass spectrometry facilitates the targeted analysis of transient receptor ion potential channel polycystin-2 (TRPP2) phosphorylation. However, empirical testing is required to optimize experimental conditions for immunoprecipitation and mass spectrometry.

FOXG1 Regulates PRKAR2B Transcriptionally and Posttranscriptionally via miR200 in the Adult Hippocampus.

Rett syndrome is a complex neurodevelopmental disorder that is mainly caused by mutations in MECP2. However, mutations in FOXG1 cause a less frequent form of atypical Rett syndrome, called FOXG1 syndrome. FOXG1 is a key transcription factor crucial for forebrain development, where it maintains the balance between progenitor proliferation and neuronal differentiation.

Influenza A Virus Induces Autophagosomal Targeting of Ribosomal Proteins.

Seasonal epidemics of influenza A virus are a major cause of severe illness and are of high socio-economic relevance. For the design of effective antiviral therapies, a detailed knowledge of pathways perturbed by virus infection is critical. We performed comprehensive expression and organellar proteomics experiments to study the cellular consequences of influenza A virus infection using three human epithelial cell lines derived from human lung carcinomas: A549, Calu-1 and NCI-H1299.

Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney.

Polycystic kidney disease (PKD) and other renal ciliopathies are characterized by cysts, inflammation, and fibrosis. Cilia function as signaling centers, but a molecular link to inflammation in the kidney has not been established. Here, we show that cilia in renal epithelia activate chemokine signaling to recruit inflammatory cells.

Mitochondrial fatty acid biosynthesis and muscle fiber plasticity in very long-chain acyl-CoA dehydrogenase-deficient mice.

The white skeletal muscle of very long-chain acyl-CoA-dehydrogenase-deficient (VLCAD ) mice undergoes metabolic modification to compensate for defective β-oxidation in a progressive and time-dependent manner by upregulating glucose oxidation. This metabolic regulation seems to be accompanied by morphologic adaptation of muscle fibers toward the glycolytic fiber type II with the concomitant upregulation of mitochondrial fatty acid biosynthesis (mFASII) and lipoic acid biosynthesis. Dietary supplementation of VLCAD mice with different medium-chain triglycerides over 1 year revealed that odd-chain species has no effect on muscle fiber switch, whereas even-chain species inhibit progressive metabolic adaptation.

Respiratory status determines the effect of emodin on cell viability.

The anthraquinone emodin has been shown to have antineoplastic properties and a wealth of unconnected effects have been linked to its use, most of which are likely secondary outcomes of the drug treatment. The primary activity of emodin on cells has remained unknown. In the present study we demonstrate dramatic and extensive effects of emodin on the redox state of cells and on mitochondrial homeostasis, irrespectively of the cell type and organism, ranging from the yeast Saccharomyces cerevisiae to human cell lines and primary cells.

Threading Granules in Freiburg. 2 International Symposium on "One Mitochondrion, Many Diseases - Biological and Molecular Perspectives", a FRIAS Junior Researcher Conference, Freiburg im Breisgau, Germany, March 9/10, 2016.

Altered mitochondrial activities play an important role in many different human disorders, including cancer and neurodegeneration. At the Freiburg Institute of Advanced Studies (FRIAS) Junior Researcher Conference "One Mitochondrion, Many Diseases - Biological and Molecular Perspectives" (University of Freiburg, Freiburg, Germany), junior and experienced researches discussed common and distinct mechanisms of mitochondrial contributions to various human disorders.

The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes.

Adult neural stem/precursor cells (NSPCs) of the subventricular zone (SVZ) are an endogenous source for neuronal replacement in CNS disease. However, adult neurogenesis is compromised after brain injury in favor of a glial cell fate, which is mainly attributed to changes in the NSPC environment. Yet, it is unknown how this unfavorable extracellular environment translates into a transcriptional program altering NSPC differentiation.

Modeling non-hereditary mechanisms of Alzheimer disease during apoptosis in yeast.

Impaired protein degradation and mitochondrial dysfunction are believed to contribute to neurodegenerative disorders, including Alzheimer disease (AD). In patients suffering from non-hereditary AD, UBB, the frameshift variant of ubiquitin B, accumulated in neurons affected by neurofibrillary tangles, which is a pathological hallmark. We established a yeast model expressing high levels of UBB, and could demonstrate that UBB interfered with both the ubiquitin-proteasome system (UPS) and mitochondrial function.

Accumulation of Basic Amino Acids at Mitochondria Dictates the Cytotoxicity of Aberrant Ubiquitin.

Neuronal accumulation of UBB, a frameshift variant of ubiquitin B, is a hallmark of Alzheimer's disease (AD). How UBB contributes to neuronal dysfunction remains elusive. Here, we show that in brain regions of AD patients with neurofibrillary tangles UBB co-exists with VMS1, the mitochondrion-specific component of the ubiquitin-proteasome system (UPS).

Metadherin exon 11 skipping variant enhances metastatic spread of ovarian cancer.

Metastatic ovarian cancer has a dismal prognosis and current chemotherapeutic approaches have very limited success. Metadherin (MTDH) is expressed in human ovarian cancer tissue and its expression inversely correlates with patients overall survival. Consistent with these studies, we observed MTDH expression in tissue specimens of FIGO Stage III ovarian carcinomas (72/83 cases).

Altered MCM protein levels and autophagic flux in aged and systemic sclerosis dermal fibroblasts.

Aging is a common risk factor of many disorders. With age, the level of insoluble extracellular matrix increases leading to increased stiffness of a number of tissues. Matrix accumulation can also be observed in fibrotic disorders, such as systemic sclerosis (SSc).