Dibutyl phthalate degradation by Paenarthrobacter ureafaciens PB10 through downstream product myristic acid and its bioremediation potential in contaminated soil.

Dibutyl phthalate (DBP) is a widely used plasticizer to make plastic flexible and long-lasting. It is easily accessible in a broad spectrum of environments as a result of the rising level of plastic pollution. This compound is considered a top-priority toxicant and persistent organic pollutant by international environmental agencies for its endocrine disruptive and carcinogenic propensities. To mitigate the DBP in the soil, one DBP-degrading bacterial strain was isolated from a plastic-polluted landfill and identified as Paenarthrobacter ureafaciens PB10 by 16S rRNA gene sequence-based homology. The strain was found to develop a distinct transparent halo zone around grown colonies on an agar plate supplemented with DBP. The addition of yeast extract (100 mg/L) as a nutrient source accelerated cell biomass production and DBP degradation rate; however, the presence of glucose suppressed DBP degradation by the PB10 strain without affecting its ability to proliferate. The strain PB10 was efficient in eliminating DBP under various pH conditions (5.0-8.0). Maximum cell growth and degradation of 99.49% at 300 mg/L DBP were achieved in 72 h at the optimized mineral salt medium (MS) conditions of pH 7.0 and 32 °C. Despite that, when the concentration of DBP rose to 3000 mg/L, the DBP depletion rate was measured at 79.34% in 72 h. Some novel intermediate metabolites, like myristic acid, hexadecanoic acid, stearic acid, and the methyl derivative of 4-hydroxyphenyl acetate, along with monobutyl phthalate and phthalic acid, were detected in the downstream degradation process of DBP through GC-MS profiling. Furthermore, in synchronization with native soil microbes, this PB10 strain successfully removed a notable amount of DBP (up to 54.11%) from contaminated soil under microcosm study after 10 d. Thus, PB10 has effective DBP removal ability and is considered a potential candidate for bioremediation in DBP-contaminated sites.

Silver-doped hydroxyapatite laden chitosan-gelatin nanocomposite scaffolds for bone tissue engineering: an in-vitro and in-ovo evaluation.

Despite the advancements in bone tissue engineering, the majority of implant failures are caused due to microbial contamination. So, efforts are being made to develop biomaterial with antimicrobial property enhancing the regeneration of damaged bone tissue. In the present study, chitosan-gelatin (CG) scaffolds containing silver-doped hydroxyapatite (AgHAP) nanoparticles at 0.5%, 1.0% and 1.5% (w/v) were fabricated by lyophilization technique. The results confirmed the synthesis of AgHAP nanoparticles and showed interconnected porous structure of the nanocomposite scaffolds with 89%-75% porosity. Similarly, the swelling percentage, degradation behavior and compressive modulus of CG-AgHAP nanocomposite scaffolds were 1666%, 40% and 0.7 MPa, respectively. The developed nanocomposite scaffolds revealed better antimicrobial properties and bioactivity. The cell culture studies showed favorable viability of Wharton's jelly stem cells on CG-AgHAP nanocomposite scaffolds. CAM (chorioallantoic membrane) assay determined the angiogenic potential with better visualization of blood vessels in the CAM area. Hence, the obtained results confirmed that CG-AgHAP3 nanocomposite scaffold was the most suitable for bone tissue engineering applications among all scaffolds.

Hepatitis C virus non-structural proteins modulate cellular kinases for increased cytoplasmic abundance of host factor HuR and facilitate viral replication.

Host protein HuR translocation from nucleus to cytoplasm following infection is crucial for the life cycle of several RNA viruses including hepatitis C virus (HCV), a major causative agent of hepatocellular carcinoma. HuR assists the assembly of replication-complex on the viral-3'UTR, and its depletion hampers viral replication. Although cytoplasmic HuR is crucial for HCV replication, little is known about how the virus orchestrates the mobilization of HuR into the cytoplasm from the nucleus. We show that two viral proteins, NS3 and NS5A, act co-ordinately to alter the equilibrium of the nucleo-cytoplasmic movement of HuR. NS3 activates protein kinase C (PKC)-δ, which in-turn phosphorylates HuR on S318 residue, triggering its export to the cytoplasm. NS5A inactivates AMP-activated kinase (AMPK) resulting in diminished nuclear import of HuR through blockade of AMPK-mediated phosphorylation and acetylation of importin-α1. Cytoplasmic retention or entry of HuR can be reversed by an AMPK activator or a PKC-δ inhibitor. Our findings suggest that efforts should be made to develop inhibitors of PKC-δ and activators of AMPK, either separately or in combination, to inhibit HCV infection.

RNA-Protein Interactome at the Hepatitis E Virus Internal Ribosome Entry Site.

Multiple processes exist in a cell to ensure continuous production of essential proteins either through cap-dependent or cap-independent translation processes. Viruses depend on the host translation machinery for viral protein synthesis. Therefore, viruses have evolved clever strategies to use the host translation machinery. Earlier studies have shown that genotype 1 hepatitis E virus (g1-HEV) uses both cap-dependent and cap-independent translation machineries for its translation and proliferation. Cap-independent translation in g1-HEV is driven by an 87-nucleotide-long RNA element that acts as a noncanonical, internal ribosome entry site-like (IRESl) element. Here, we have identified the RNA-protein interactome of the HEV IRESl element and characterized the functional significance of some of its components. Our study identifies the association of HEV IRESl with several host ribosomal proteins, demonstrates indispensable roles of ribosomal protein RPL5 and DHX9 (RNA helicase A) in mediating HEV IRESl activity, and establishes the latter as a bona fide internal translation initiation site. IMPORTANCE Protein synthesis is a fundamental process for survival and proliferation of all living organisms. The majority of cellular proteins are produced through cap-dependent translation. Cells also use a variety of cap-independent translation processes to synthesize essential proteins during stress. Viruses depend on the host cell translation machinery to synthesize their own proteins. Hepatitis E virus (HEV) is a major cause of hepatitis worldwide and has a capped positive-strand RNA genome. Viral nonstructural and structural proteins are synthesized through a cap-dependent translation process. An earlier study from our laboratory reported the presence of a fourth open reading frame (ORF) in genotype 1 HEV, which produces the ORF4 protein using a cap-independent internal ribosome entry site-like (IRESl) element. In the current study, we identified the host proteins that associate with the HEV-IRESl RNA and generated the RNA-protein interactome. Through a variety of experimental approaches, our data prove that HEV-IRESl is a bona fide internal translation initiation site.

Cerium oxide nanoparticles disseminated chitosan gelatin scaffold for bone tissue engineering applications.

Cell-free and cell-loaded constructs are used to bridge the critical-sized bone defect. Oxidative stress at the site of the bone defects is a major interference that slows bone healing. Recently, there has been an increase in interest in enhancing the properties of three-dimensional scaffolds with free radical scavenging materials. Cerium oxide nanoparticles (CNPs) can scavenge free radicals due to their redox-modulating property. In this study, freeze-drying was used to fabricate CG-CNPs nanocomposite scaffolds using gelatin (G), chitosan (C), and cerium oxide nanoparticles. Physico-chemical, mechanical, and biological characterization of CG-CNPs scaffolds were studied. CG-CNPs scaffolds demonstrated better results in terms of physicochemical, mechanical, and biological properties as compared to CG-scaffold. CG-CNPs scaffolds were cyto-friendly to MC3T3-E1 cells studied by performing in-vitro and in-ovo studies. The scaffold's antimicrobial study revealed high inhibition zones against Gram-positive and Gram-negative bacteria. With 79 % porosity, 45.99 % weight loss, 178.25 kPa compressive modulus, and 1.83 Ca/P ratio, the CG-CNP2 scaffold displays the best characteristics. As a result, the CG-CNP2 scaffolds are highly biocompatible and could be applied to repair bone defects.

Scaffold Fabrication Techniques of Biomaterials for Bone Tissue Engineering: A Critical Review.

Bone tissue engineering (BTE) is a promising alternative to repair bone defects using biomaterial scaffolds, cells, and growth factors to attain satisfactory outcomes. This review targets the fabrication of bone scaffolds, such as the conventional and electrohydrodynamic techniques, for the treatment of bone defects as an alternative to autograft, allograft, and xenograft sources. Additionally, the modern approaches to fabricating bone constructs by additive manufacturing, injection molding, microsphere-based sintering, and 4D printing techniques, providing a favorable environment for bone regeneration, function, and viability, are thoroughly discussed. The polymers used, fabrication methods, advantages, and limitations in bone tissue engineering application are also emphasized. This review also provides a future outlook regarding the potential of BTE as well as its possibilities in clinical trials.

Human gut microbiota and Parkinson's disease.

The bidirectional communication between the gut and the brain has come up very fascinating in recent years. Many studies have reported that the onset of gastrointestinal issues appears long before the actual manifestation of Parkinson's disease (PD) symptoms. Disturbances in the gut-brain axis have been found to be linked with PD. PD-linked neuropathological changes in the enteric nervous system and significant alteration of gut microbiota suggest a vital role of gut microbiota in PD pathogenesis. Studies have also suggested that aggregation of α-synuclein, one of the major proteins associated with PD neuropathology, might start from the gut and move to the central nervous system (CNS) through the vagus nerve and olfactory bulb. Inflammation in the gut has been suggested to be associated with PD initiation and progression. The flushing out of healthy gut microbiota and replacing with pathogens induces gut inflammation and promotes neuroinflammation in the CNS. Therefore, it is intriguing to understand the mechanism of gut-brain communications associated with the development of PD. This review sheds light on the PD pathology, the gut dysbiosis that is associated with PD and its medications, altered gene expression, pathways and microbial metabolites during PD.

Development of a Systematic Strategy toward Promotion of α-Synuclein Aggregation Using 2-Hydroxyisophthalamide-Based Systems.

Establishing a potent scheme against α-synuclein aggregation involved in Parkinson's disease has been evaluated as a promising route to identify compounds that either inhibit or promote the aggregation process of α-synuclein. In the last two decades, this perspective has guided a dramatic increase in the efforts, focused on developing potent drugs either for retardation or promotion of the self-assembly process of α-synuclein. To address this issue, using a chemical kinetics platform, we developed a strategy that enabled a progressively detailed analysis of the molecular events leading to protein aggregation at the microscopic level in the presence of a recently synthesized 2-hydroxyisophthalamide class of small organic molecules based on their binding affinity. Furthermore, qualitatively, we have developed a strategy of disintegration of α-synuclein fibrils in the presence of these organic molecules. Finally, we have shown that these organic molecules effectively suppress the toxicity of α-synuclein oligomers in neuron cells.

Investigation on Carbonation and Permeability of Concrete with Rice Hush Ash and Shop Solution Addition.

The goal of this study was to determine the coefficient of permeability as well as the rate of carbonation of concrete constructed with rice husk ash (RHA) as a partial replacement for cement (i.e., 5%, 10%, and 15%) and two different concentrations of soap solutions (i.e., 1 percent and 2 percent). The microstructural studies of RHA, and carbonated samples have been conducted by using Scanning Electron Microscope (SEM) and X-Ray Diffraction (XRD) analysis. According to this study, the carbonation depth of concrete made with 1% and 2% soap solution concentration and without rice husk ash decreased by 11.89% and 46.55%, respectively. From the results, it may also be observed that the carbonation depth of concrete made with up to 10% replacement of cement by rice husk ash led to maximum carbonation resistance, while more than 10% replacement of cement showed higher carbonation depth. It is also observed that the coefficient of permeability of concrete with 2% soap solution significantly decreased as compared to the 1% soap solution and control mix. It may be observed from the SEM images that 0% soap solution (M1) concrete has a very rough concrete surface which may indicate more voids. However, 2% soap solution concrete has a much smoother surface, which indicates a smaller number of voids. Furthermore, the SEM images showed that the soap solution helps in filling the voids of concrete which ultimately helps in reduction in permeability. Energy Dispersive X-Ray Analysis (EDX) of concrete with 0% (M1) and 2% (M6) soap solution disclosed that the concrete with 2% soap solution (M6) exhibited more silica element formation than the concrete with no soap solution (M1).

Phthalates - A family of plasticizers, their health risks, phytotoxic effects, and microbial bioaugmentation approaches.

Phthalates are a family of reprotoxicant compounds, predominantly used as a plasticizer to improve the flexibility and longevity of consumable plastic goods. After their use these plastic products find their way to the waste disposal sites where they leach out the hazardous phthalates present within them, into the surrounding environment, contaminating soil, groundwater resources, and the nearby water bodies. Subsequently, phthalates move into the living system through the food chain and exhibit the well-known phenomenon of biological magnification. Phthalates as a primary pollutant have been classified as 1B reprotoxicants and teratogens by different government authorities and they have thus imposed restrictions on their use. Nevertheless, the release of these compounds in the environment is unabated. Bioremediation has been suggested as one of the ways of mitigating this menace, but studies regarding the field applications of phthalate utilizing microbes for this purpose are limited. Through this review, we endeavor to make a deeper understanding of the cause and concern of the problem and to find out a possible solution to it. The review critically emphasizes the various aspects of phthalates toxicity, including their chemical nature, human health risks, phytoaccumulation and entry into the food chain, microbial role in phthalate degradation processes, and future challenges.

Zirconia- and ceria-based electrolytes for fuel cell applications: critical advancements toward sustainable and clean energy production.

Solid oxide fuel cells (SOFCs) are emerging as energy conversion devices for large-scale electrical power generation because of their high energy conversion efficiency, excellent ability to minimize air pollution, and high fuel flexibility. In this context, this critical review has focussed on the recent advancements in developing a suitable electrolyte for SOFCs which has been required for the commercialization of SOFC technology after emphasizing the literature from the prior studies. In particular, the significant developments in the field of solid oxide electrolytes for SOFCs, particularly zirconia- and ceria-based electrolytes, have been highlighted as important advancements toward the production of sustainable and clean energy. It has been reported that among various electrolyte materials, zirconia-based electrolytes have the potential to be utilized as the electrolyte in SOFC because of their high thermal stability, non-reducing nature, and high mechanical strength, along with acceptable oxygen ion conductivity. However, some studies have proved that the zirconia-based electrolytes are not suitable for low and intermediate-temperature working conditions because of their poor ionic conductivity to below 850 °C. On the other hand, ceria-based electrolytes are being investigated at a rapid pace as electrolytes for intermediate and low-temperature SOFCs due to their higher oxygen ion conductivity with good electrode compatibility, especially at lower temperatures than stabilized zirconia. In addition, the most emerging advancements in electrolyte materials have demonstrated that the intermediate temperature SOFCs as next-generation energy conversion technology have great potential for innumerable prospective applications.

Proteomic analysis reveals USP7 as a novel regulator of palmitic acid-induced hepatocellular carcinoma cell death.

Nutrient surplus and consequent free fatty acid accumulation in the liver cause hepatosteatosis. The exposure of free fatty acids to cultured hepatocyte and hepatocellular carcinoma cell lines induces cellular stress, organelle adaptation, and subsequent cell death. Despite many studies, the mechanism associated with lipotoxicity and subsequent cell death still remains poorly understood. Here, we have used the proteomics approach to circumvent the mechanism for lipotoxicity using hepatocellular carcinoma cells as a model. Our quantitative proteomics data revealed that ectopic lipids accumulation in cells severely affects the ubiquitin-proteasomal system. The palmitic acid (PA) partially lowered the expression of deubiquitinating enzyme USP7 which subsequently destabilizes p53 and promotes mitotic entry of cells. Our global phosphoproteomics analysis also provides strong evidence of an altered cell cycle checkpoint proteins' expression that abrogates early G2/M checkpoints recovery with damaged DNA and induced mitotic catastrophe leading to hepatocyte death. We observe that palmitic acid prefers apoptosis-inducing factor (AIF) mediated cell death by depolarizing mitochondria and translocating AIF to the nucleus. In summary, the present study provides evidence of PA-induced hepatocellular death mediated by deubiquitinase USP7 downregulation and subsequent mitotic catastrophe.

S-Nitrosylation of OTUB1 Alters Its Stability and Ubc13 Binding.

S-Nitrosylation is a reversible post-translational modification that regulates protein function involving the covalent attachment of the nitric oxide (NO) moiety to sulfhydryl residues of the protein. It is an important regulator in the cell signaling process under physiological conditions. However, the release of an excess amount of NO due to dysregulated NOS machinery causes aberrant S-nitrosylation of proteins, which affects protein folding, localization, and activity. Here, we have shown that OTUB1, a deubiquitinating enzyme, undergoes S-nitrosylation under redox stress conditions in vivo and in vitro. Previously, we have shown that OTUB1 forms an amyloid-like structure that promotes phosphorylation of α-synuclein and neuronal toxicity. However, the mechanistic insight into OTUB1 aggregation remains elusive. Here, we identified that OTUB1 undergoes S-nitrosylation in SH-SY5Y neuroblastoma cells under rotenone-induced stress, as well as excitotoxic conditions, and in rotenone-treated mouse brains. The in vitro S-nitrosylation of OTUB1 followed by mass-spectrometry analysis has identified cysteine-23 and cysteine-91 as S-nitrosylation sites. S-Nitrosylated OTUB1 (SNO-OTUB1) diminished its catalytic activity, impaired its native structure, promoted amyloid-like aggregation, and compromised its binding with Ubc13. Thus, our results demonstrated that nitrosylation of OTUB1 might play a crucial role in regulating the ubiquitin signaling and Parkinson's disease pathology.

Molecular insight into arsenic uptake, transport, phytotoxicity, and defense responses in plants: a critical review.

MAIN CONCLUSION: A critical investigation into arsenic uptake and transportation, its phytotoxic effects, and defense strategies including complex signaling cascades and regulatory networks in plants. The metalloid arsenic (As) is a leading pollutant of soil and water. It easily finds its way into the food chain through plants, more precisely crops, a common diet source for humans resulting in serious health risks. Prolonged As exposure causes detrimental effects in plants and is diaphanously observed through numerous physiological, biochemical, and molecular attributes. Different inorganic and organic As species enter into the plant system via a variety of transporters e.g., phosphate transporters, aquaporins, etc. Therefore, plants tend to accumulate elevated levels of As which leads to severe phytotoxic damages including anomalies in biomolecules like protein, lipid, and DNA. To combat this, plants employ quite a few mitigation strategies such as efficient As efflux from the cell, iron plaque formation, regulation of As transporters, and intracellular chelation with an array of thiol-rich molecules such as phytochelatin, glutathione, and metallothionein followed by vacuolar compartmentalization of As through various vacuolar transporters. Moreover, the antioxidant machinery is also implicated to nullify the perilous outcomes of the metalloid. The stress ascribed by the metalloid also marks the commencement of multiple signaling cascades. This whole complicated system is indeed controlled by several transcription factors and microRNAs. This review aims to understand, in general, the plant-soil-arsenic interaction, effects of As in plants, As uptake mechanisms and its dynamics, and multifarious As detoxification mechanisms in plants. A major portion of this article is also devoted to understanding and deciphering the nexus between As stress-responsive mechanisms and its underlying complex interconnected regulatory networks.

A potent cadmium bioaccumulating Enterobacter cloacae strain displays phytobeneficial property in Cd-exposed rice seedlings.

In agricultural soil, cadmium (Cd) pollution compromises soil health, reduces crop yield, and produces Cd-contaminated crops. Bio-based approaches are necessary as an eco-friendly and sustainable solution to mitigate Cd-polluted areas. A heavy metal-resistant rhizobacterial strain (AS10) has been isolated from a heavy metal-defiled rice field. The 16S rDNA sequence and MALDI-TOF MS analyses of ribosomal protein reveal its identity closely similar to Enterobacter cloacae. The strain was found to withstand up to 4000 µg/ml Cd2+, 3312 µg/ml Pb2+ and 1500 µg/ml As3+. The Cd2+ removal efficiency was recorded as high as 72.11% when grown in 4000 µg/ml Cd2+. The strain's Cd-accumulation efficiency was also apprehended by TEM-EDAX followed by XRD-XRF-FTIR analyses. Besides, the strain showed solubilization of inorganic phosphate, ACC deaminase activity, nitrogen fixation and IAA production ability. Added further, the strain, as an efficient bioinoculant, significantly improved rice plant growth at the seedling stage through Cd immobilization. It prevented the surge of stress ethylene and oxidative stress in rice seedlings, resulting in overall plant growth improvement. Hence, the strain AS10 as potent plant growth-promoting rhizobacteria (PGPR) may be beneficial, especially in heavy metal-contaminated crop fields.

Enzyme producing insect gut microbes: an unexplored biotechnological aspect.

To explore the unmapped biotechnologically important microbial platforms for human welfare, the insect gut system is such a promising arena. Insects, the inhabitant of all ecological niches, harbor a healthy diversified microbial population in their versatile gut environment. This deep-rooted symbiotic relationship between insects and gut microbes is the result of several indispensable microbial performances that include: enzyme production, detoxification of plant defense compounds and insecticides, maintenance of life cycle, host fertility, bioremediation, pest biocontrol, production of antimicrobial compounds, and in addition provide vitamins, amino acids, and lactic acids to their hosts. Insects have developed such symbiotic interactions with different microorganisms for nutritional benefits like the digestion of dietary compounds by the production of several key hydrolytic enzymes viz: amylase, cellulase, lignocellulase, protease, lipase, xylanase, pectinase, chitinase, laccase, etc. The nutritional enrichment offered by these microbes to insects may be the key factor in the evolutionary attainment of this group. Around one million insect species are grouped under 31 orders, however, only ten of such groups' have been studied in relation to enzyme-producing gut microbes. Moreover, insect gut symbionts are a potential source of biotechnologically active biomolecules as these microbes go through a course of selection pressures in their host gut environment. As symbiosis has pronounced potential regarding the production of novel compounds, especially enzymes with multidimensional industrial capabilities, so there are ample scopes to explore this treasure box for human welfare. Biological significance as well as industrially compatible capabilities can categorize these insect gut symbionts as an unexplored biotechnological aspect.

Identification of diphenyl furan derivatives via high throughput and computational studies as ArgA inhibitors of Mycobacterium tuberculosis.

Microbial amino acid biosynthetic pathways are underexploited for the development of anti-bacterial agents. N-acetyl glutamate synthase (ArgA) catalyses the first committed step in L-arginine biosynthesis and is essential for M. tuberculosis growth. Here, we have purified and optimized assay conditions for the acetylation of l-glutamine by ArgA. Using the optimized conditions, high throughput screening was performed to identify ArgA inhibitors. We identified 2,5-Bis (2-chloro-4-guanidinophenyl) furan, a dicationic diaryl furan derivatives, as ArgA inhibitor, with a MIC99 values of 1.56 µM against M. tuberculosis. The diaryl furan derivative displayed bactericidal killing against both M. bovis BCG and M. tuberculosis. Inhibition of ArgA by the lead compound resulted in transcriptional reprogramming and accumulation of reactive oxygen species. The lead compound and its derivatives showed micromolar binding with ArgA as observed in surface plasmon resonance and tryptophan quenching experiments. Computational and dynamic analysis revealed that these scaffolds share similar binding site residues with L-arginine, however, with slight variations in their interaction pattern. Partial restoration of growth upon supplementation of liquid cultures with either L-arginine or N-acetyl cysteine suggests a multi-target killing mechanism for the lead compound. Taken together, we have identified small molecule inhibitors against ArgA enzyme from M. tuberculosis.

RNA-Protein Interaction Analysis of SARS-CoV-2 5' and 3' Untranslated Regions Reveals a Role of Lysosome-Associated Membrane Protein-2a during Viral Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-strand RNA virus. The viral genome is capped at the 5' end, followed by an untranslated region (UTR). There is a poly(A) tail at the 3' end, preceded by a UTR. The self-interaction between the RNA regulatory elements present within the 5' and 3' UTRs and their interaction with host/virus-encoded proteins mediate the function of the 5' and 3' UTRs. Using an RNA-protein interaction detection (RaPID) assay coupled to liquid chromatography with tandem mass spectrometry, we identified host interaction partners of SARS-CoV-2 5' and 3' UTRs and generated an RNA-protein interaction network. By combining these data with the previously known protein-protein interaction data proposed to be involved in virus replication, we generated the RNA-protein-protein interaction (RPPI) network, likely to be essential for controlling SARS-CoV-2 replication. Notably, bioinformatics analysis of the RPPI network revealed the enrichment of factors involved in translation initiation and RNA metabolism. Lysosome-associated membrane protein-2a (Lamp2a), the receptor for chaperone-mediated autophagy, is one of the host proteins that interact with the 5' UTR. Further studies showed that the Lamp2 level is upregulated in SARS-CoV-2-infected cells and that the absence of the Lamp2a isoform enhanced the viral RNA level whereas its overexpression significantly reduced the viral RNA level. Lamp2a and viral RNA colocalize in the infected cells, and there is an increased autophagic flux in infected cells, although there is no change in the formation of autophagolysosomes. In summary, our study provides a useful resource of SARS-CoV-2 5' and 3' UTR binding proteins and reveals the role of Lamp2a protein during SARS-CoV-2 infection. IMPORTANCE Replication of a positive-strand RNA virus involves an RNA-protein complex consisting of viral genomic RNA, host RNA(s), virus-encoded proteins, and host proteins. Dissecting out individual components of the replication complex will help decode the mechanism of viral replication. 5' and 3' UTRs in positive-strand RNA viruses play essential regulatory roles in virus replication. Here, we identified the host proteins that associate with the UTRs of SARS-CoV-2, combined those data with the previously known protein-protein interaction data (expected to be involved in virus replication), and generated the RNA-protein-protein interaction (RPPI) network. Analysis of the RPPI network revealed the enrichment of factors involved in translation initiation and RNA metabolism, which are important for virus replication. Analysis of one of the interaction partners of the 5'-UTR (Lamp2a) demonstrated its role in reducing the viral RNA level in SARS-CoV-2-infected cells. Collectively, our study provides a resource of SARS-CoV-2 UTR-binding proteins and identifies an important role for host Lamp2a protein during viral infection.

Unraveling the role of plant growth-promoting rhizobacteria in the alleviation of arsenic phytotoxicity: A review.

The toxic metalloid arsenic (As), is a major pollutant of soil and water, imposing severe health concerns on human lives. It enters the food chain mainly through As-contaminated crops. The uptake, translocation and accumulation of As in plant tissue are often controlled by certain soil-inhabiting microbial communities. Among them, indigenous, free-living As-resistant plant growth-promoting rhizobacteria (PGPR) plays a pivotal role in As-immobilization. Besides, the plant's inability to withstand As after a threshold level is actively managed by these PGPR increasing As-tolerance in host plants by a synergistic plant-microbe interaction. The dual functionality of As-resistant PGPR i.e., phytostimulation and minimization of As-induced phytotoxic damages are one of the main focal points of this review article. It is known that such PGPR having the functional arsenic-resistant genes (in ars operon) including As-transporters, As-transforming genes contributed to the As accumulation and detoxification/transformation respectively. Apart from assisting in nutrient acquisition and modulating phytohormone levels, As-resistant PGPR also influences the antioxidative defense system in plants by maneuvering multiple enzymatic and non-enzymatic antioxidants. Furthermore, they are effective in reducing membrane damage and electrolyte leakage in plant cells. As-induced photosynthetic damage is also found to be salvaged by As-resistant PGPR. Briefly, the eco-physiological, biochemical and molecular mechanisms of As-resistant PGPR are thus elaborated here with regard to the As-exposed crops.

Ellagic Acid Inhibits α-Synuclein Aggregation at Multiple Stages and Reduces Its Cytotoxicity.

α-Synuclein is a natively unfolded protein and its deposition in the Lewy body and Lewy neurites in the substantia nigra region of the brain is linked to Parkinson's disease (PD). The molecular mechanisms of α-synuclein aggregation and its clearance have not been well understood. Until now, several strategies have been designed to inhibit α-synuclein aggregation and related cytotoxicity. Polyphenols, small molecules, synthetic peptides, and peptide-derived molecules have been considered as potential candidates that inhibit α-synuclein oligomerization and its fibrillation, and a few of them are in clinical trials. We have identified a polyphenolic compound ellagic acid (EA) that inhibits α-synuclein aggregation. Our results demonstrated that EA inhibits primary nucleation, seeded aggregation, and membrane-induced aggregation. The cytotoxicity of α-synuclein oligomers and fibers treated with EA has been investigated and we found that EA treated oligomers and fibrils showed reduced cytotoxicity. Additionally, we also observed inhibition of membrane binding of α-synuclein by EA in SH-SY5Y cells. In conclusion, the present study suggests that small molecules such as ellagic acid have anti-amyloidogenic properties and may have therapeutic potential for Parkinson's disease and other proteinopathies.