Direct interaction of DNMT inhibitors to PrP C suppresses pathogenic process of prion

The conversion of the normal cellular prion protein (PrP C )to the misfolded pathogenic scrapie prion protein (PrP Sc )is the biochemical hallmark of prion replication. So far, various chemical compounds that inhibit this conformational conversion have been identified. Here, we report the novel anti-prion activity of SGI-1027 and its meta/meta analogue (M/M), previously known only as potent inhibitors of DNA methyltransferases (DNMTs). These compounds effectively decreased the level of PrP Sc in cultured cells with permanent prion infection, without affecting PrP C at the transcriptional or translational levels. Furthermore, SGI-1027 prevented effective prion infection of the cells. In a PrP aggregation assay, both SGI-1027 and M/M blocked the formation of misfolded PrP aggregates, implying that binding of these compounds hinders the PrP conversion process. A series of binding and docking analyses demonstrated that both SGI-1027 and M/M directly interacted with the C-terminal globular domain of PrP C , but only SGI-1027 bound to a specific region of PrP C with high affinity, which correlates with its potent anti-prion efficacy. Therefore, we report SGI-1027 and related compounds as a novel class of potential anti-prion agents that preferentially function through direct interaction with PrP C . © 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences1

Evaluation of the Biodegradation Efficiency of Four Various Types of Plastics by Pseudomonas aeruginosa Isolated from the Gut Extract of Superworms

Plastic waste worldwide is becoming a serious pollution problem for the planet. Various physical and chemical methods have been tested in attempts to remove plastic dumps. However, these have usually resulted in secondary pollution issues. Recently, the biodegradation of plastic by fungal and bacterial strains has been spotlighted as a promising solution to remove plastic wastes without generating secondary pollution. We have previously reported that a Pseudomonas aeruginosa strain isolated from the gut of a superworm is capable of biodegrading polystyrene (PS) and polyphenylene sulfide (PPS). Herein, we demonstrate the extraordinary biodegradative power of P. aeruginosa in efficiently depolymerizing four different types of plastics: PS, PPS, polyethylene (PE) and polypropylene (PP). We further compared biodegradation rates for these four plastic types and found that PE was biodegraded fastest, whereas the biodegradation of PP was the slowest. Moreover, the growth rates of P. aeruginosa were not always proportional to biodegradation rates, suggesting that the rate of bacterial growth could be influenced by the composition and properties of intermediate molecules produced during plastic biodegradation, and these may supply useful cellular precursors and energy. In conclusion, an initial screening system to select the most suitable bacterial strain to biodegrade certain types of plastic is particularly important and may be necessary to solve plastic waste problems both presently and in the future. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.1

Genetics of Resistance to Common Root Rot (Spot Blotch), Fusarium Crown Rot, and Sharp Eyespot in Wheat

Due to soil changes, high density planting, and the use of straw-returning methods, wheat common root rot (spot blotch), Fusarium crown rot (FCR), and sharp eyespot (sheath blight) have become severe threats to global wheat production. Only a few wheat genotypes show moderate resistance to these root and crown rot fungal diseases, and the genetic determinants of wheat resistance to these devastating diseases are poorly understood. This review summarizes recent results of genetic studies of wheat resistance to common root rot, Fusarium crown rot, and sharp eyespot. Wheat germplasm with relatively higher resistance are highlighted and genetic loci controlling the resistance to each disease are summarized

Learning and Memory Alterations Are Associated with Hippocampal N-acetylaspartate in a Rat Model of Depression as Measured by 1H-MRS

It is generally accepted that cognitive processes, such as learning and memory, are affected in depression. The present study used a rat model of depression, chronic unpredictable mild stress (CUMS), to determine whether hippocampal volume and neurochemical changes were involved in learning and memory alterations. A further aim was to determine whether these effects could be ameliorated by escitalopram treatment, as assessed with the non-invasive techniques of structural magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). Our results demonstrated that CUMS had a dramatic influence on spatial cognitive performance in the Morris water maze task, and CUMS reduced the concentration of neuronal marker N-acetylaspartate (NAA) in the hippocampus. These effects could be significantly reversed by repeated administration of escitalopram. However, neither chronic stress nor escitalopram treatment influenced hippocampal volume. Of note, the learning and memory alterations of the rats were associated with right hippocampal NAA concentration. Our results indicate that in depression, NAA may be a more sensitive measure of cognitive function than hippocampal volume

Cytoplasmic Restriction of Mutated SOD1 Impairs the DNA Repair Process in Spinal Cord Neurons

Amyotrophic lateral sclerosis (ALS) caused by mutation of superoxide dismutase 1 (SOD1), affects various cellular processes and results in the death of motor neurons with fatal defects. Currently, several neurological disorders associated with DNA damage are known to directly induce neurodegenerative diseases. In this research, we found that cytoplasmic restriction of SOD1G93A, which inhibited the nucleic translocation of SOD1WT, was directly related to increasing DNA damage in SOD1- mutated ALS disease. Our study showed that nucleic transport of DNA repair- processing proteins, such as p53, APEX1, HDAC1, and ALS- linked FUS were interfered with under increased endoplasmic reticulum (ER) stress in the presence of SOD1G93A. During aging, the unsuccessful recognition and repair process of damaged DNA, due to the mislocalized DNA repair proteins might be closely associated with the enhanced susceptibility of DNA damage in SOD1- mutated neurons. In addition, the co-expression of protein disulphide isomerase (PDI) directly interacting with SOD1 protein in neurons enhances the nucleic transport of cytoplasmic- restricted SOD1G93A. Therefore, our results showed that enhanced DNA damage by SOD1 mutation-induced ALS disease and further suggested that PDI could be a strong candidate molecule to protect neuronal apoptosis by reducing DNA damage in ALS disease

Influence of overnight orthokeratology lens fitting decentration on corneal topography reshaping

Abstract Background This retrospective study was designed to investigate the sole influence of orthokeratology (OK) lens fitting decentration on the Zernike coefficients of the reshaped anterior corneal surface. Methods This study comprised a review of 106 right eyes and measurements of corneal topography both before OK and at 1-month follow-up visit. A routine was designed to calculate local corneal surface astigmatism and assist the determination of OK lens fitting decentration from pupil center. The pupil-centered corneal Zernike coefficients of baseline (PCCB) and post-treatment (PCCP) were calculated. Meanwhile, the OK-lens-centered corneal Zernike coefficients of post-treatment (OCCP) were also calculated and considered as the presumptive ideal fitting group without decentration. Relationships between lens fitting decentration and the change of Zernike coefficients including (PCCP − PCCB) and (PCCP − OCCP) were analyzed. Results Patients with a mean age of 11 ± 2.36 years old had an average spherical equivalent refractive error of −3.52 ± 1.06 D before OK. One month after treatment, OK lens fitting decentration from pupil center was 0.68 ± 0.35 mm. RMS of 3rd-order (P  0.05). For the high order corneal Zernike coefficients in (PCCP – OCCP), radial distance of decentration was correlated with C3−1 $${C}_3^{-1}$$ (r = −0.296, P < 0.05), C31 $${C}_3^1$$ (r = −0.396, P < 0.001), and C40 $${C}_4^0$$ (r = 0.449, P < 0.001), horizontal decentration was significantly correlated with C31 $${C}_3^1$$ (r = 0.901, P < 0.001) and C51 $${C}_5^1$$ (r = 0.340, P < 0.001), and vertical decentration was significantly correlated with C3−1 $${C}_3^{-1}$$ (r = 0.904, P < 0.001). Conclusions OK lens fitting decentration within 1.5 mm hardly influenced the change of corneal spherical power for myopia correction, but significantly induced additional corneal high order Zernike coefficients including C3−1 $${C}_3^{-1}$$, C31 $${C}_3^1$$, C40 $${C}_4^0$$, and C51 $${C}_5^1$$