The promoter of filamentation (POF1) protein from <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> is an ATPase involved in the protein quality control process

Background

The gene YCL047C, which has been renamed promoter of filamentation gene (POF1), has recently been described as a cell component involved in yeast filamentous growth. The objective of this work is to understand the molecular and biological function of this gene.

Results

Here, we report that the protein encoded by the POF1 gene, Pof1p, is an ATPase that may be part of the Saccharomyces cerevisiae protein quality control pathway. According to the results, Δpof1 cells showed increased sensitivity to hydrogen peroxide, tert-butyl hydroperoxide, heat shock and protein unfolding agents, such as dithiothreitol and tunicamycin. Besides, the overexpression of POF1 suppressed the sensitivity of Δpct1, a strain that lacks a gene that encodes a phosphocholine cytidylyltransferase, to heat shock. In vitro analysis showed, however, that the purified Pof1p enzyme had no cytidylyltransferase activity but does have ATPase activity, with catalytic efficiency comparable to other ATPases involved in endoplasmic reticulum-associated degradation of proteins (ERAD). Supporting these findings, co-immunoprecipitation experiments showed a physical interaction between Pof1p and Ubc7p (an ubiquitin conjugating enzyme) in vivo.

Conclusions

Taken together, the results strongly suggest that the biological function of Pof1p is related to the regulation of protein degradation.

     

Prediction and expression analysis of deleterious nonsynonymous SNPs of Arabidopsis ACD11 gene by combining computational algorithms and molecular docking approach

Accelerated cell death 11 (ACD11) is an autoimmune gene that suppresses pathogen infection in plants by preventing plant cells from becoming infected by any pathogen. This gene is widely known for growth inhibition, premature leaf chlorosis, and defense-related programmed cell death (PCD) in seedlings before flowering in Arabidopsis plant. Specific amino acid changes in the ACD11 protein’s highly conserved domains are linked to autoimmune symptoms including constitutive defensive responses and necrosis without pathogen awareness. The molecular aspect of the aberrant activity of the ACD11 protein is difficult to ascertain. The purpose of our study was to find the most deleterious mutation position in the ACD11 protein and correlate them with their abnormal expression pattern. Using several computational methods, we discovered PCD vulnerable single nucleotide polymorphisms (SNPs) in ACD11. We analysed the RNA-Seq data, identified the detrimental nonsynonymous SNPs (nsSNP), built genetically mutated protein structures and used molecular docking to assess the impact of mutation. Our results demonstrated that the A15T and A39D mutations in the GLTP domain were likely to be extremely detrimental mutations that inhibit the expression of the ACD11 protein domain by destabilizing its composition, as well as disrupt its catalytic effectiveness. When compared to the A15T mutant, the A39D mutant was more likely to destabilize the protein structure. In conclusion, these mutants can aid in the better understanding of the vast pool of PCD susceptibilities connected to ACD11 gene GLTP domain activation.     

BEVSIM: Battery electric vehicle sustainability impact assessment model

To achieve climate neutrality ambitions, greenhouse gas emissions from the transport sector need to be reduced by at least 90% by 2050. To support industry and policy makers on mitigating actions on climate goals it is important to holistically compare and reduce life cycle environmental impacts of road passenger vehicles. A web-based sustainability assessment tool named battery electric vehicle sustainability impact assessment model, BEVSIM, is developed to assess the environmental, circularity, and economic performance of the materials, sub-systems, parts, and individual components of battery electric vehicles and internal combustion engine vehicles. This tool allows to measure and compare impacts resulting from recycling technologies, end-of-life scenarios, and future scenarios resulting from changes in grid mixes. This paper explains the purpose of the tool, its functionality and design as well as the underlying assumptions.     

miR-200c-3p upregulation and ACE2 downregulation via bacterial LPS and LTA as interesting aspects for COVID-19 treatment and immunity

Molecular Biology Reports -     

Incorporation of SPION-casein core-shells into silk-fibroin nanofibers for cardiac tissue engineering

Mimicking the structure of extracellular matrix (ECM) of myocardium is necessary for fabrication of functional cardiac tissue. The superparamagnetic iron oxide nanoparticles (SPIONs, Fe₃O₄), as new generation of magnetic nanoparticles (NPs), are highly intended in biomedical studies. Here, SPION NPs (1 wt%) were synthesized and incorporated into silk-fibroin (SF) electrospun nanofibers to enhance mechanical properties and topography of the scaffolds. Then, the mouse embryonic cardiac cells (ECCs) were seeded on the scaffolds for in vitro studies. The SPION NPs were studied by scanning electron microscope (SEM), X-ray diffraction (XRD), and transmission electron microscope (TEM). SF nanofibers were characterized after incorporation of SPIONs by SEM, TEM, water contact angle measurement, and tensile test. Furthermore, cytocompatibility of scaffolds was confirmed by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. SEM images showed that ECCs attached to the scaffolds with elongated morphologies. Also, the real-time PCR and immunostaining studies approved upregulation of cardiac functional genes in ECCs seeded on the SF/SPION-casein scaffolds including GATA-4, cardiac troponin T, Nkx 2.5, and alpha-myosin heavy chain, compared with the ones in SF. In conclusion, incorporation of core-shells in SF supports cardiac differentiation, while has no negative impact on ECCs' proliferation and self-renewal capacity.     

Modulatory effects of statins on the autophagy: A therapeutic perspective

Autophagy is considered as an important mechanism for maintaining homeostasis and responsible for the degradation of superfluous or potentially toxic components and organelles. Autophagy impairment is associated with a number of pathological conditions, such as aging, neurological disorders, cancer, and infection. Autophagy also plays a significant role in cancer chemotherapy. The multiple cancer drugs have been notably developed with the strategy of autophagy modulation. Statins, 3-hydroxy-3-methyl-glutaryl-CoA inhibitors, are known due to their efficacy in decreasing low-density lipoprotein and extensively used for the management of cardiovascular diseases. Statins have other therapeutic and biological activities, such as antioxidant, anti-inflammatory, antitumor, and neuroprotective known as pleiotropic effects. It seems that statins are capable of targeting various signaling pathways in the induction of their great pharmacological effects. At the present study, we demonstrate the therapeutic effects of statins mediated via autophagy regulation.     

Alveolar mimics with periodic strain and its effect on the cell layer formation

We report on the development of a new model of alveolar air–tissue interface on a chip. The model consists of an array of suspended hexagonal monolayers of gelatin nanofibers supported by microframes and a microfluidic device for the patch integration. The suspended monolayers are deformed to a central displacement of 40–80 µm at the air–liquid interface by application of air pressure in the range of 200–1,000 Pa. With respect to the diameter of the monolayers, that is, 500 µm, this displacement corresponds to a linear strain of 2–10% in agreement with the physiological strain range in the lung alveoli. The culture of A549 cells on the monolayers for an incubation time of 1–3 days showed viability in the model. We exerted a periodic strain of 5% at a frequency of 0.2 Hz for 1 hr to the cells. We found that the cells were strongly coupled to the nanofibers, but the strain reduced the coupling and induced remodeling of the actin cytoskeleton, which led to a better tissue formation. Our model can serve as a versatile tool in lung investigations such as in inhalation toxicology and therapy.     

Nanoparticles and cancer therapy: Perspectives for application of nanoparticles in the treatment of cancers

Rapid growth in nanotechnology toward the development of nanomedicine agents holds massive promise to improve therapeutic approaches against cancer. Nanomedicine products represent an opportunity to achieve sophisticated targeting strategies and multifunctionality. Nowadays, nanoparticles (NPs) have multiple applications in different branches of science. In recent years, NPs have repetitively been reported to play a significant role in modern medicine. They have been analyzed for different clinical applications, such as drug carriers, gene delivery to tumors, and contrast agents in imaging. A wide range of nanomaterials based on organic, inorganic, lipid, or glycan compounds, as well as on synthetic polymers has been utilized for the development and improvement of new cancer therapeutics. In this study, we discuss the role of NPs in treating cancer among different drug delivery methods for cancer therapy.     

Forest biodiversity in a changing climate: which logic for conservation strategies?

Climate change has direct and indirect impacts on forest ecosystems worldwide. In this context, changing site conditions and altered disturbance regimes as well as forest management responses are challenging the conservation of biodiversity in forests. Climate-induced dynamics and uncertainties related to future forest ecosystem development are calling into question current conservation strategies and concepts. Given the longevity of trees, slow development rates of forest ecosystems and slow migration rates of many forest species, the planning of adaptation measures in response to climate change are especially difficult though highly important for forest biodiversity conservation. This paper introduces a special issue with eight contributions which deal with a variety of aspects of forest biodiversity conservation in the face of climate change. More specifically, the papers address direct impacts of climate change on forest biodiversity, adaptation measures for forest and conservation management, as well as resulting challenges for conservation strategies and concepts. In conclusion, adaptation measures that enhance diversity and provide different options for future action, thereby maintaining ecosystems’ resilience, as well as conservation management operating on a landscape level, are promoted as being beneficial for coping with uncertainties related to climate change. Adaptive management, which constantly reviews conservation goals and measures, and which takes into account both science-based and local ecological knowledge on climate change can be a valuable tool to inform decisions for forest biodiversity conservation.