Modeling the Toxicokinetics of Suspensions of Soluble Metallic Nanomaterials.

Proper risk assessment of the many new nanoforms (NFs) that are currently being developed and marketed is hindered by constraints in time and resources for testing their fate and (eco) toxicity profile. This problem has also been encountered in conventional chemical risk assessments, where the definition of related chemical groups can facilitate risk assessment for all class members. Whereas grouping and read-across methods are well established, such approaches are in the early stages of development for NFs.

An integrative approach unveils a distal encounter site for rPTPε and phospho-Src complex formation.

The structure determination of protein tyrosine phosphatase (PTP): phospho-protein complexes, which is essential to understand how specificity is achieved at the amino acid level, remains a significant challenge for protein crystallography and cryoEM due to the transient nature of binding interactions. Using rPTPεD1 and phospho-SrcKD as a model system, we have established an integrative workflow to address this problem, by means of which we generate a protein:phospho-protein complex model using predetermined protein structures, SAXS and pTyr-tailored MD simulations. Our model reveals transient protein-protein interactions between rPTPεD1 and phospho-SrcKD and is supported by three independent experimental validations.

The deubiquitinase Leon/USP5 interacts with Atg1/ULK1 and antagonizes autophagy.

Accumulating evidence has shown that the quality of proteins must be tightly monitored and controlled to maintain cellular proteostasis. Misfolded proteins and protein aggregates are targeted for degradation through the ubiquitin proteasome (UPS) and autophagy-lysosome systems. The ubiquitination and deubiquitinating enzymes (DUBs) have been reported to play pivotal roles in the regulation of the UPS system.

Internal relative potency factors based on immunotoxicity for the risk assessment of mixtures of per- and polyfluoroalkyl substances (PFAS) in human biomonitoring.

Relative potency factors (RPFs) for per- and polyfluoroalkyl substances (PFAS) have previously been derived based on liver effects in rodents for the purpose of performing mixture risk assessment with primary input from biomonitoring studies. However, in 2020, EFSA established a tolerable weekly intake for four PFAS assuming equal toxic potency for immune suppressive effects in humans. In this study we explored the possibility of deriving RPFs for immune suppressive effects using available data in rodents and humans.

Development of a quantitative structure-activity relationship model for predicting quantum yield of hydroxyl radical generation from organic compounds.

Organic compounds are capable of generating hydroxyl radicals (˙OH) through their excited triplet states in natural water. It is of significance to reveal the underlying mechanism of the generation and obtain the generation quantum yield of ˙OH from organic compounds for better understanding of its involvement in indirect photochemical processes in the environment. In this study, the ˙OH quantum yields () of 20 organic compounds were determined by photochemical experiments.

Regulation of oxidative stress-induced autophagy by ATG9A ubiquitination.

High levels of reactive oxygen species (ROS) result in oxidative stress, which damages cells and leads to the development of many diseases. Macroautophagy/autophagy plays an important role in protecting cells from diverse stress stimuli including oxidative stress. However, the molecular mechanisms of autophagy activation in response to oxidative stress remain largely unclear.

K48/K63-linked polyubiquitination of ATG9A by TRAF6 E3 ligase regulates oxidative stress-induced autophagy.

Excessive generation and accumulation of highly reactive oxidizing molecules causes oxidative stress and oxidative damage to cellular components. Accumulating evidence indicates that autophagy diminishes oxidative damage in cells and maintains redox homeostasis by degrading and recycling intracellular damaged components. Here, we show that TRAF6 E3 ubiquitin ligase and A20 deubiquitinase coordinate to regulate ATG9A ubiquitination and autophagy activation in cells responding to oxidative stress.

Drosophila as a model to study autophagy in neurodegenerative diseases and digestive tract.

Autophagy regulates cellular homeostasis by degrading and recycling cytosolic components and damaged organelles. Disruption of autophagic flux has been shown to induce or facilitate neurodegeneration and accumulation of autophagic vesicles is overt in neurodegenerative diseases. The fruit fly Drosophila has been used as a model system to identify new factors that regulate physiology and disease.

Enhanced enzymatic production of cholesteryl 6'-acylglucoside impairs lysosomal degradation for the intracellular survival of Helicobacter pylori.

Background: During autophagy defense against invading microbes, certain lipid types are indispensable for generating specialized membrane-bound organelles. The lipid composition of autophagosomes remains obscure, as does the issue of how specific lipids and lipid-associated enzymes participate in autophagosome formation and maturation. Helicobacter pylori is auxotrophic for cholesterol and converts cholesterol to cholesteryl glucoside derivatives, including cholesteryl 6'-O-acyl-α-D-glucoside (CAG).

Electrocatalytic inactivation of antibiotic resistant bacteria and control of antibiotic resistance dissemination risk.

Antibiotic resistance in environmental matrices becomes urgently significant for public health and has been considered as an emerging environmental contaminant. In this work, the ampicillin-resistant Escherichia coli (AR E. coli) and corresponding resistance genes (bla) were effectively eliminated by the electrocatalytic process, and the dissemination risk of antibiotic resistance was also investigated.

VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism.

The ubiquitin-proteasome system (UPS) and autophagy are two major quality control processes whose impairment is linked to a wide variety of diseases. The coordination between UPS and autophagy remains incompletely understood. Here, we show that ubiquitin ligase UBE3C and deubiquitinating enzyme TRABID reciprocally regulate K29/K48-branched ubiquitination of VPS34.

PTPN9-mediated dephosphorylation of VTI1B promotes ATG16L1 precursor fusion and autophagosome formation.

Macroautophagy/autophagy is an evolutionarily conserved intracellular pathway for the degradation of cytoplasmic materials. Under stress conditions, autophagy is upregulated and double-membrane autophagosomes are formed by the expansion of phagophores. The ATG16L1 precursor fusion contributes to development of phagophore structures and is critical for the biogenesis of autophagosomes.

Development of a quantitative structure-activity relationship model for mechanistic interpretation and quantum yield prediction of singlet oxygen generation from dissolved organic matter.

Singlet oxygen (O) is capable of degrading organic contaminants and inducing cell damage and inactivation of viruses. It is mainly generated through the interaction of dissolved oxygen with excited triplet states of dissolved organic matter (DOM) in natural waters. The present study aims at revealing the underlying mechanism of O generation and providing a potential tool for predicting the quantum yield of O (Φ) generation from DOM by constructing a quantitative structure-activity relationship (QSAR) model.

Disentanglement of the chemical, physical, and biological processes aids the development of quantitative structure-biodegradation relationships for aerobic wastewater treatment.

Attenuation of organic compounds in sewage treatment plants (STPs) is affected by a complex interplay between chemical (e.g. ionization, hydrolysis), physical (e.

PTPN3 suppresses lung cancer cell invasiveness by counteracting Src-mediated DAAM1 activation and actin polymerization.

Cancer cell migration plays a crucial role during the metastatic process. Reversible tyrosine phosphorylation by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs) have been implicated in the regulation of cancer cell migration and invasion. However, the underlying mechanisms have not been fully elucidated.

Autophagy, Inflammation, and Metabolism (AIM) Center in its second year.

The NIH-funded center for autophagy research named Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center is now completing its second year as a working center with a mission to promote autophagy research locally, nationally, and internationally. The center has thus far supported a cadre of 6 junior faculty (mentored PIs; mPIs) at a near-R01 level of funding. Two mPIs have graduated by obtaining their independent R01 funding and 3 of the remaining 4 have won significant funding from NIH in the form of R21 and R56 awards.

Clinical efficacy of celecoxib for osteoarthritis and bone anchor assisted knee extensor reconstruction.

Celecoxib is the most recent non steroidal anti-inflammatory analgesic, and has been gradually used in the treatment of acute pain, rheumatism and osteoarthritis. This paper analyzes the analgesic effect of celecoxib in the treatment of knee osteoarthritis and put forward a new mechanism of knee joint extensor reconstruction assisted by bone anchor. The experimental group was given celecoxib 200 mg/ time and 1 time /d.

Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence: supporting the next generation of autophagy researchers and fostering international collaborations.

Recently, NIH has funded a center for autophagy research named the Autophagy, Inflammation, and Metabolism (AIM) Center of Biomedical Research Excellence, located at the University of New Mexico Health Science Center (UNM HSC), with aspirations to promote autophagy research locally, nationally, and internationally. The center has 3 major missions: (i) to support junior faculty in their endeavors to develop investigations in this area and obtain independent funding; (ii) to develop and provide technological platforms to advance autophagy research with emphasis on cellular approaches for high quality reproducible research; and (iii) to foster international collaborations through the formation of an International Council of Affiliate Members and through hosting national and international workshops and symposia. Scientifically, the AIM center is focused on autophagy and its intersections with other processes, with emphasis on both fundamental discoveries and applied translational research.

Atg9 antagonizes TOR signaling to regulate intestinal cell growth and epithelial homeostasis in .

Autophagy is essential for maintaining cellular homeostasis and survival under various stress conditions. Autophagy-related gene 9 (Atg9) encodes a multipass transmembrane protein thought to act as a membrane carrier for forming autophagosomes. However, the molecular regulation and physiological importance of Atg9 in animal development remain largely unclear.

A Review of Recent Advances towards the Development of (Quantitative) Structure-Activity Relationships for Metallic Nanomaterials.

Gathering required information in a fast and inexpensive way is essential for assessing the risks of engineered nanomaterials (ENMs). The extension of conventional (quantitative) structure-activity relationships ((Q)SARs) approach to nanotoxicology, i.e.

Impact of water chemistry on the particle-specific toxicity of copper nanoparticles to Daphnia magna.

Toxicity of metallic nanoparticle suspensions (NP) is generally assumed to result from the combined effect of the particles present in suspensions (NP) and their released ions (NP). Evaluation and consideration of how water chemistry affects the particle-specific toxicity of NP are critical for environmental risk assessment of nanoparticles. In this study, it was found that the toxicity of Cu NP to Daphnia magna, in line with the trends in toxicity for Cu NP, decreased with increasing pH and with increasing concentrations of divalent cations and dissolved organic carbon (DOC).