Degradation performance and mechanism toward methyl orange via nanoporous copper powders fabricated by dealloying of ZrCuNiAl metallic glassy precursors

The catalyst of nanoporous Cu (NP-Cu) powders, with the chemical composition of Cu79.63Ni6.85O13.53 (at.%), was successfully fabricated by dealloying of Zr-Cu-Ni-Al metallic glassy precursors. The as-prepared NP-Cu powders, co-existing with Cu2O phase on Cu ligament surface, had a three-dimensional (3D) network porous structure. The NP-Cu powders/H2O2 system showed superior catalytic degradation efficiency toward azo dyes in both acidic (pH 2) and neutral (pH 7) environments. Moreover, the cyclic tests indicated that this powder catalyst also exhibited good durability. A novel degradation mechanism of NP-Cu powders/H2O2 was proposed: the high degradation performance in acidic environment was mainly derived from heterogeneous reaction involved with a specific pathway related to Cu3+ to produce HO•, while in neutral environment it was primarily resulted from homogeneous reaction with the generation of HO• from the classical Cu-based Fenton-like process. This work indicates that the NP-Cu powders have great potential applications as catalysts for wastewater treatments.

Experimental Study on Sdccag3 Regulating Osteogenesis and Adipogenic Differentiation of Rats Bone Marrow Mesenchymal Stem Cells

Background Bone marrow mesenchymal stem cells have a metabolic balance between osteogenic and adipogenic differentiation. Sdccag3 is differentially expressed in hyperlipidemia rats, and it can be beneficial to the osteogenesis disorder caused by dyslipidemia, but the pathway mechanism and its influence on the differentiation have not been studied. Methods Here, we designed RT-PCR and Western Blot to determine the expression of Osteogenic and lipid gene, including ALP, Runx2, PPARγ FABP4 and so on, and then we performed microarray to evaluate the bone formation, calculate BV/TV. Simultaneously, we detected mRNA from the hyperlipidemia rat model we established to find the specific pathway mechanism. Results In this experiment, we found that high fat environment influences BMSCs differentiation. Sdccag3 overexpression upregulates the osteogenic differentiation of BMSCs and increased new bone formation. Conclusion Therefore, our findings show that Sdccag3 regulates osteogenesis and adipogenic differentiation of BMSCs.

The Lotus japonicus ROP3 Is Involved in the Establishment of the Nitrogen-Fixing Symbiosis but Not of the Arbuscular Mycorrhizal Symbiosis

Legumes form root mutualistic symbioses with some soil microbes promoting their growth, rhizobia, and arbuscular mycorrhizal fungi (AMF). A conserved set of plant proteins rules the transduction of symbiotic signals from rhizobia and AMF in a so-called common symbiotic signaling pathway (CSSP). Despite considerable efforts and advances over the past 20 years, there are still key elements to be discovered about the establishment of these root symbioses. Rhizobia and AMF root colonization are possible after a deep cell reorganization. In the interaction between the model legume Lotus japonicus and Mesorhizobium loti, this reorganization has been shown to be dependent on a SCAR/Wave-like signaling module, including Rho-GTPase (ROP in plants). Here, we studied the potential role of ROP3 in the nitrogen-fixing symbiosis (NFS) as well as in the arbuscular mycorrhizal symbiosis (AMS). We performed a detailed phenotypic study on the effects of the loss of a single ROP on the establishment of both root symbioses. Moreover, we evaluated the expression of key genes related to CSSP and to the rhizobial-specific pathway. Under our experimental conditions, rop3 mutant showed less nodule formation at 7- and 21-days post inoculation as well as less microcolonies and a higher frequency of epidermal infection threads. However, AMF root colonization was not affected. These results suggest a role of ROP3 as a positive regulator of infection thread formation and nodulation in L. japonicus. In addition, CSSP gene expression was neither affected in NFS nor in AMS condition in rop3 mutant. whereas the expression level of some genes belonging to the rhizobial-specific pathway, like RACK1, decreased in the NFS. In conclusion, ROP3 appears to be involved in the NFS, but is neither required for intra-radical growth of AMF nor arbuscule formation.

Transcriptome Analysis of Pterygium and Pinguecula Reveals Evidence of Genomic Instability Associated with Chronic Inflammation

Solar damage due to ultraviolet radiation (UVR) is implicated in the development of two proliferative lesions of the ocular surface: pterygium and pinguecula. Pterygium and pinguecula specimens were collected, along with adjacent healthy conjunctiva specimens. RNA was extracted and sequenced. Pairwise comparisons were made of differentially expressed genes (DEGs). Computational methods were used for analysis. Transcripts from 18,630 genes were identified. Comparison of two subgroups of pterygium specimens uncovered evidence of genomic instability associated with inflammation and the immune response; these changes were also observed in pinguecula, but to a lesser extent. Among the top DEGs were four genes encoding tumor suppressors that were downregulated in pterygium: C10orf90, RARRES1, DMBT1 and SCGB3A1; C10orf90 and RARRES1 were also downregulated in pinguecula. Ingenuity Pathway Analysis overwhelmingly linked DEGs to cancer for both lesions; however, both lesions are clearly still benign, as evidenced by the expression of other genes indicating their well-differentiated and non-invasive character. Pathways for epithelial cell proliferation were identified that distinguish the two lesions, as well as genes encoding specific pathway components. Upregulated DEGs common to both lesions, including KRT9 and TRPV3, provide a further insight into pathophysiology. Our findings suggest that pterygium and pinguecula, while benign lesions, are both on the pathological pathway towards neoplastic transformation.

PlantPathMarks (PPMdb): an interactive hub for pathways-based markers in plant genomes

AbstractOver the past decade, the problem of finding an efficient gene-targeting marker set or signature for plant trait characterization has remained challenging. Many databases focusing on pathway mining have been released with one major deficiency, as they lack to develop marker sets that target only genes controlling a specific pathway or certain biological process. Herein, we present the PlantPathMarks database (PPMdb) as a comprehensive, web-based, user-friendly, and interactive hub for pathway-based markers in plant genomes. Based on our newly developed pathway gene set mining approach, two novel pathway-based marker systems called pathway gene-targeted markers (PGTMs) and pathway microsatellite-targeted markers (PMTMs) were developed as a novel class of annotation-based markers. In the PPMdb database, 2,690,742 pathway-based markers reflecting 9,894 marker panels were developed across 82 plant genomes. The markers include 691,555 PGTMs and 1,999,187 PMTMs. Across these genomes, 165,378 enzyme-coding genes were mapped against 126 KEGG reference pathway maps. PPMdb is furnished with three interactive visualization tools (Map Browse, JBrowse and Species Comparison) to visualize, map, and compare the developed markers over their KEGG reference pathway maps. All the stored marker panels can be freely downloaded. PPMdb promises to create a radical shift in the paradigm of the area of molecular marker research. The use of PPMdb as a mega-tool represents an impediment for non-bioinformatician plant scientists and breeders. PPMdb is freely available at http://ppmdb.easyomics.org.

Using predictive machine learning models for drug response simulation by calibrating patient-specific pathway signatures

The utility of pathway signatures lies in their capability to determine whether a specific pathway or biological process is dysregulated in a given patient. These signatures have been widely used in machine learning (ML) methods for a variety of applications including precision medicine, drug repurposing, and drug discovery. In this work, we leverage highly predictive ML models for drug response simulation in individual patients by calibrating the pathway activity scores of disease samples. Using these ML models and an intuitive scoring algorithm to modify the signatures of patients, we evaluate whether a given sample that was formerly classified as diseased, could be predicted as normal following drug treatment simulation. We then use this technique as a proxy for the identification of potential drug candidates. Furthermore, we demonstrate the ability of our methodology to successfully identify approved and clinically investigated drugs for four different cancers, outperforming six comparable state-of-the-art methods. We also show how this approach can deconvolute a drugs’ mechanism of action and propose combination therapies. Taken together, our methodology could be promising to support clinical decision-making in personalized medicine by simulating a drugs’ effect on a given patient.

Parkinsonian gait effects with DBS are associated with pallido-peduncular axis activation

Background: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) often shows variable outcomes on treating gait dysfunction in Parkinson's disease (PD). Such variability may stem from which specific neuronal pathways are modulated by DBS and the extent to which those pathways are modulated relative to one another. Objective: Leveraging ultra-high-field (7T) imaging data and subject-specific computational models, this study investigated how activation of seven distinct pathways in and around STN, including the pallidopeduncular and pedunculopallidal pathways, affect step length at clinically-optimized STN-DBS settings. Methods: Personalized computational models were developed for 10 subjects with a clinical diagnosis of PD and with bilateral STN-DBS implants. Results: The subject-specific pathway activation models showed a significant positive association between activation of the pedunculopallidal pathway and increased step length, and negative association on step length with pallidopeduncular pathway and hyperdirect pathway activation. Conclusions: The STN region includes multiple pathways, including fibers of passage to and from the mesencephalic locomotor area. Future clinical optimization of STN-DBS should consider these fibers of passage in the context of treating parkinsonian gait.

Loss of the mitochondrial phosphate carrier SLC25A3 induces remodeling of the cardiac mitochondrial protein acylome

Mitochondria are recognized as signaling organelles because, under stress, mitochondria can trigger various signaling pathways to coordinate the cell's response. The specific pathway(s) engaged by mitochondria in response to mitochondrial energy defects in vivo and in high-energy tissues like the heart are not fully understood. Here, we investigated cardiac pathways activated in response to mitochondrial energy dysfunction by studying mice with cardiomyocyte-specific loss of the mitochondrial phosphate carrier (SLC25A3), an established model that develops cardiomyopathy as a result of defective mitochondrial ATP synthesis. Mitochondrial energy dysfunction induced a striking pattern of acylome remodeling, with significantly increased post-translational acetylation and malonylation. Mass spectrometry-based proteomics further revealed that energy dysfunction-induced remodeling of the acetylome and malonylome preferentially impacts mitochondrial proteins. Acetylation and malonylation modified a highly interconnected interactome of mitochondrial proteins, and both modifications were present on the enzyme isocitrate dehydrogenase 2 (IDH2). Intriguingly, IDH2 activity was enhanced in SLC25A3-deleted mitochondria, and further study of IDH2 sites targeted by both acetylation and malonylation revealed that these modifications can have site-specific and distinct functional effects. Finally, we uncovered a novel crosstalk between the two modifications, whereby mitochondrial energy dysfunction-induced acetylation of sirtuin 5 (SIRT5), inhibited its function. Because SIRT5 is a mitochondrial deacylase with demalonylase activity, this finding suggests that acetylation can modulate the malonylome. Together, our results position acylations as an arm of the mitochondrial response to energy dysfunction and suggest a mechanism by which focal disruption to the energy production machinery can have an expanded impact on global mitochondrial function.

Chemical inhibition of lycopene β-cyclases unmask operation of phytoene synthase 2 in ripening tomato fruits

In ripening tomato fruits, the leaf-specific carotenoids biosynthesis mediated by phytoene synthase 2 (PSY2) is replaced by a fruit-specific pathway by the expression of two chromoplast-specific genes: phytoene synthase 1 (PSY1) and lycopene-β-cyclase (CYCB). Consequently, mutations in those two and other genes contributing to intermediate steps render the ripened tomato fruits bereft of lycopene. To decipher whether PSY2-mediated pathway also operates in ripening fruits, we blocked the in vivo activity of lycopene-β-cyclases by injecting CPTA (2-(4-Chlorophenylthio) triethylamine hydrochloride), an inhibitor of lycopene-β-cyclases. The injection of CPTA induced accumulation of lycopene in leaves, immature-green and ripening fruits. Even, in tomato mutants deficient in fruit-specific carotenoid biosynthesis such as V7 and r (PSY1), and ζ-carotene isomerase (ZISO), CPTA triggered lycopene accumulation. The CPTA-treated ziso mutant fruits, where PSY1 remains functional, accumulated phytoene and phytofluene. Conversely, CPTA-treated PSY1-knockout mutant (r3756) fruits did not accumulate phytoene and phytofluene. CPTA-treated fruits were enriched in lycopene-derived volatiles and had reduced ABA levels. The lycopene accumulation was associated with the partial transformation of chloroplasts to chromoplasts bearing thread-like crystalline structures, indicating lycopene accumulation. Our study shows that inhibition of lycopene β-cyclases unmasks the operation of a parallel carotenoid biosynthetic pathway mediated by PSY2 in ripening tomato fruits.