Mitochondrial-derived vesicles retain membrane potential and contain a functional ATP synthase.

Vesicular transport is a means of communication. While cells can communicate with each other via secretion of extracellular vesicles, less is known regarding organelle-to organelle communication, particularly in the case of mitochondria. Mitochondria are responsible for the production of energy and for essential metabolic pathways in the cell, as well as fundamental processes such as apoptosis and aging. Here, we show that functional mitochondria isolated from Saccharomyces cerevisiae release vesicles, independent of the fission machinery. We isolate these mitochondrial-derived vesicles (MDVs) and find that they are relatively uniform in size, of about 100 nm, and carry selective protein cargo enriched for ATP synthase subunits. Remarkably, we further find that these MDVs harbor a functional ATP synthase complex. We demonstrate that these vesicles have a membrane potential, produce ATP, and seem to fuse with naive mitochondria. Our findings reveal a possible delivery mechanism of ATP-producing vesicles, which can potentially regenerate ATP-deficient mitochondria and may participate in organelle-to-organelle communication.

A combination of Class-I fumarases and metabolites (α-ketoglutarate and fumarate) signal the DNA damage response in Escherichia coli.

Class-II fumarases (fumarate hydratase, FH) are dual-targeted enzymes occurring in the mitochondria and cytosol of all eukaryotes. They are essential components in the DNA damage response (DDR) and, more specifically, protect cells from DNA double-strand breaks. Similarly, the gram-positive bacterium Bacillus subtilis class-II fumarase, in addition to its role in the tricarboxylic acid cycle, participates in the DDR. Escherichia coli harbors three fumarase genes: class-I fumA and fumB and class-II fumC Notably, class-I fumarases show no sequence similarity to class-II fumarases and are of different evolutionary origin. Strikingly, here we show that E. coli fumarase functions are distributed between class-I fumarases, which participate in the DDR, and the class-II fumarase, which participates in respiration. In E. coli, we discover that the signaling molecule, alpha-ketoglutarate (α-KG), has a function, complementing DNA damage sensitivity of fum-null mutants. Excitingly, we identify the E. coli α-KG-dependent DNA repair enzyme AlkB as the target of this interplay of metabolite signaling. In addition to α-KG, fumarate (fumaric acid) is shown to affect DNA damage repair on two different levels, first by directly inhibiting the DNA damage repair enzyme AlkB demethylase activity, both in vitro and in vivo (countering α-KG). The second is a more global effect on transcription, because fum-null mutants exhibit a decrease in transcription of key DNA damage repair genes. Together, these results show evolutionary adaptable metabolic signaling of the DDR, in which fumarases and different metabolites are recruited regardless of the evolutionary enzyme class performing the function.

Microbial induced carbonate precipitation for remediation of heavy metals, ions and radioactive elements: A comprehensive exploration of prospective applications in water and soil treatment.

Improper disposal practices have caused environmental disruptions, possessing by heavy metal ions and radioactive elements in water and soil, where the innovative and sustainable remediation strategies are significantly imperative in last few decades. Microbially induced carbonate precipitation (MICP) has emerged as a pioneering technology for remediating contaminated soil and water. Generally, MICP employs urease-producing microorganisms to decompose urea (NH2CONH2) into ammonium (NH4+and carbon dioxide (CO2), thereby increasing pH levels and inducing carbonate precipitation (CO32-), and effectively removing remove contaminants. Nonetheless, the intricate mechanism underlying heavy metal mineralization poses a significant challenge, constraining its application in contaminants engineering, particularly in the context of prolonged heavy metal leaching over time and its efficacy in adverse environmental conditions. This review provides a comprehensive idea of recent development of MICP and its application in environmental engineering, examining metabolic pathways, mineral precipitation mechanisms, and environmental factors as well as providing future perspectives for commercial utilization. The use of ureolytic bacteria in MICP demonstrates cost-efficiency, environmental compatibility, and successful pollutant abatement over tradition bioremediation techniques, and bio-synthesis of nanoparticles. limitations such as large-scale application, elevated Ca2+levels in groundwater, and gradual contaminant release need to be overcome. The possible future research directions for MICP technology, emphasizing its potential in conventional remediation, CO2 sequestration, bio-material synthesis, and its role in reducing environmental impact for long-term economic benefits.

Transformative and sustainable insights of agricultural waste-based adsorbents for water defluoridation: Biosorption dynamics, economic viability, and spent adsorbent management.

With the progression of civilization, the harmony within nature has been disrupted, giving rise to various ecocidal activities that are evident in every spheres of the earth. These activities have had a profound and far-reaching impact on global health. One significant example of this is the presence of fluoride in groundwater exceeding acceptable limits, resulting in the widespread occurrence of "Fluorosis" worldwide. It is imperative to mitigate the concentration of fluoride in drinking water to meet safety standards. While various defluoridation techniques exist, they often have drawbacks. Biosorption, being a simple, affordable and eco-friendly method, has gained preference for defluoridation. However, its limited commercialization underscores the pressing need for further research in this domain. This comprehensive review article offers a thorough examination of the defluoridation potential of agro-based adsorbents, encompassing their specific chemical compositions and preparation methods. The review presents an in-depth discussion of the factors influencing fluoride biosorption and conducts a detailed exploration of adsorption isotherm and adsorption kinetic models to gain a comprehensive understanding of the nature of the adsorption process. Furthermore, it evaluates the commercial viability through an assessment of regeneration potential and a cost analysis of these agro-adsorbents, with the aim of facilitating the scalability of the defluoridation process. The elucidation of the adsorption mechanism and recommendations for overcoming challenges in large-scale implementation offer a comprehensive outlook on this eco-friendly and sustainable approach to fluoride removal. In summary, this review article equips readers with a lucid understanding of agro-adsorbents, elucidates their ideal conditions for improved performance, offers a more profound insight into the fluoride biosorption mechanism, and introduces the concept of effective spent adsorbent management.

Evaluation and mitigation of potentially toxic elements contamination in mangrove ecosystem: Insights into phytoremediation and microbial perspective.

Mangroves, essential coastal ecosystems, are threatened by human-induced Potentially-toxic-elements (PTEs) pollution. This study analyzed PTEs distribution, phytoremediation potential, and rhizosphere microbial communities in Taiwan's Xinfeng mangrove forest. Significant variations in physicochemical and PTEs concentrations were observed across adjacent water bodies, with moderate contamination in the river, estuary, and overlying water of mangroves sediment. The partition-coefficient showed the mobility of Bi, Pb, Co, and Sr at the water-sediment interface. The geochemical-indices revealed high Bi and Pb contamination and moderate Zn, Sr, Cu, and Cd contamination in sediment. The overall pollution indices indicated the significant contamination, while moderate ecological risk was found for Cd (40 ≤ Eri < 80). Mangroves Kandelia obovata and Avicennia marina exhibited promising PTEs phytoremediation potential (Bi, Cd, Mn, Sr, and Co). Metagenomics indicated a diverse microbial community with N-fixation, P-solubilization, IAA synthesis, and PTEs-resistance genes. These findings underscore the need for targeted conservation to protect these critical habitats.

Systematic Approaches to Study Eclipsed Targeting of Proteins Uncover a New Family of Mitochondrial Proteins.

Dual localization or dual targeting refers to the phenomenon by which identical, or almost identical, proteins are localized to two (or more) separate compartments of the cell. From previous work in the field, we had estimated that a third of the mitochondrial proteome is dual-targeted to extra-mitochondrial locations and suggested that this abundant dual targeting presents an evolutionary advantage. Here, we set out to study how many additional proteins whose main activity is outside mitochondria are also localized, albeit at low levels, to mitochondria (eclipsed). To do this, we employed two complementary approaches utilizing the α-complementation assay in yeast to uncover the extent of such an eclipsed distribution: one systematic and unbiased and the other based on mitochondrial targeting signal (MTS) predictions. Using these approaches, we suggest 280 new eclipsed distributed protein candidates. Interestingly, these proteins are enriched for distinctive properties compared to their exclusively mitochondrial-targeted counterparts. We focus on one unexpected eclipsed protein family of the Triose-phosphate DeHydrogenases (TDH) and prove that, indeed, their eclipsed distribution in mitochondria is important for mitochondrial activity. Our work provides a paradigm of deliberate eclipsed mitochondrial localization, targeting and function, and should expand our understanding of mitochondrial function in health and disease.

Insight interactions of engineered nanoparticles with aquatic higher plants for phytoaccumulation, phytotoxicity, and phytoremediation applications: A review.

With the growing age of human civilization, industrialization has paced up equally which is followed by the innovation of newer concepts of science and technology. One such example is the invention of engineered nanoparticles and their flagrant use in widespread applications. While ENPs serve their intended purposes, they also disrupt the ecological balance by contaminating pristine aquatic ecosystems. This review encompasses a comprehensive discussion about the potent toxicity of ENPs on aquatic ecosystems, with a particular focus on their impact on aquatic higher plants. The discussion extends to elucidating the fate of ENPs upon release into aquatic environments, covering aspects ranging from morphological and physiological effects to molecular-level phytotoxicity. Furthermore, this level of toxicity has been correlated with the determination of competent plants for the phytoremediation process towards the mitigation of this ecological stress. However, this review further illustrates the path of future research which is yet to be explored. Determination of the genotoxicity level of aquatic higher plants could explain the entire process comprehensively. Moreover, to make it suitable to be used in natural ecosystems phytoremediation potential of co-existing plant species along with the presence of different ENPs need to be evaluated. This literature will undoubtedly offer readers a comprehensive understanding of the stress induced by the irresponsible release of engineered nanoparticles (ENP) into aquatic environments, along with insights into the resilience characteristics of these pristine ecosystems.

Biologically-induced synthetic manganese carbonate precipitate (BISMCP) for potential applications in heavy metal removal.

Heavy metal pollution of water is a burning issue of today's world. Among several strategies involved for heavy metal remediation purpose, biomineralization has shown great potential. Of late, research has been focused on developing effective mineral adsorbents with reduced time and cost consumption. In this present paper, the Biologically-Induced Synthetic Manganese Carbonate Precipitate (BISMCP) was produced based on the biologically-induced mineralization method, employing Sporosarcina pasteurii in aqueous solutions containing urea and MnCl2. The prepared adsorbent was characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), SEM-energy dispersive X-ray spectroscopy (SEM-EDX), X-ray diffraction (XRD) and BET surface area analyzer. EDX analysis showed the elements in the crystal BISMCP were Mn, C, and O. XRD result of BISMCP determined the crystal structure, which is close to rhodochrosite (MnCO3). Spectral peaks of FTIR at 1641.79 cm-1 confirmed the appearance of C[bond, double bond]O binding, with strong stretching of CO32- in Amide I. From the six kinds of BISMCP produced, sample MCP-6 has the higher specific surface area by BET analysis at 109.01 m2/g, with pore size at 8.76 nm and higher pore volume at 0.178 cm3/g. These specifications will be suitable as an adsorbent for heavy metal removal by adsorption process. This study presents a preliminary analysis of the possibility of BISMCP for heavy metals adsorption using ICP multi-element standard solution XIII (As, Cr, Cd, Cu, Ni, and Zn). BISMCP formed from 0.1 MnCl2 and 30 ml of bacteria volume (MCP-6) produced a better adsorbent material than others concentrations, with the adsorption efficiency of total As at 98.9%, Cr at 97.0%, Cu at 94.7%, Cd at 88.3%, Zn at 48.6%, and Ni at 29.5%. Future work could be examined its efficiency adsorbing individual heavy metals.

Insights into the Formations of Host-Guest Complexes Based on the Benzimidazolium Based Ionic Liquids-ß-Cyclodextrin Systems.

Inclusion complexation is one of the best strategies for developing a controlled release of a toxic drug without unexpected side effects from the very beginning of the administration to the target site. In this study, three benzimidazolium based ionic liquids (ILs) having bromide anion and cation bearing long alkyl chains, hexyl- ([C6CFBim]Br), octyl- ([C8CFBim]Br), and decyl- ([C10CFBim]Br) were designed and synthesized as antibacterial drugs. Inclusion complexes (ICs) of studied ILs have been prepared by the combination of ß-cyclodextrin (ß-CD), considering these conjugations should enhance the benignity of ILs and make them potential candidates for the controlled drug release. Characterizations and structural analysis of studied ICs have been performed by 1H NMR, 2D-ROESY NMR, FT-IR, HRMS, TGA, DSC, surface tension, ionic conductivity, dynamic light scattering (DLS), and isothermal titration calorimetry (ITC). Further, the morphology of the ICs has been analyzed by SEM and TEM. Furthermore, neat ILs and ICs have been treated against Escherichia coli and Bacillus subtilis to investigate their antibacterial activity, which confirms the prevention of bacterium growth and the shrinkage of the bacterial cell wall. The findings of this work provide the proof of concept that studied benzimidazolium based ILs-ß-CD host-guest complexes should act as a potential candidate in controlled drug delivery and other biomedical applications.

Ubiquitination Occurs in the Mitochondrial Matrix by Eclipsed Targeted Components of the Ubiquitination Machinery.

Ubiquitination is a critical type of post-translational modification in eukaryotic cells. It is involved in regulating nearly all cellular processes in the cytosol and nucleus. Mitochondria, known as the metabolism heart of the cell, are organelles that evolved from bacteria. Using the subcellular compartment-dependent α-complementation, we detect multiple components of ubiquitination machinery as being eclipsed distributed to yeast mitochondria. Ubiquitin conjugates and mono-ubiquitin can be detected in lysates of isolated mitochondria from cells expressing HA-Ub and treated with trypsin. By expressing MTS (mitochondrial targeting sequence) targeted HA-tagged ubiquitin, we demonstrate that certain ubiquitination events specifically occur in yeast mitochondria and are independent of proteasome activity. Importantly, we show that the E2 Rad6 affects the pattern of protein ubiquitination in mitochondria and provides an in vivo assay for its activity in the matrix of the organelle. This study shows that ubiquitination occurs in the mitochondrial matrix by eclipsed targeted components of the ubiquitin machinery, providing a new perspective on mitochondrial and ubiquitination research.

New aspects of lipopeptide-incorporated nanoparticle synthesis and recent advancements in biomedical and environmental sciences: a review.

The toxicity of metal nanoparticles has introduced promising research in the current scenario since an enormous number of people have been potentially facing this problem in the world. The extensive attention on green nanoparticle synthesis has been focussed on as a vital step in bio-nanotechnology to improve biocompatibility, biodegradability, eco-friendliness, and huge potential utilization in various environmental and clinical assessments. Inherent influence on the study of green nanoparticles plays a key role to synthesize the controlled and surface-influenced molecule by altering the physical, chemical, and biological assets with the provision of various precursors, templating/co-templating agents, and supporting solvents. However, in this article, the dominant characteristics of several kinds of lipopeptide biosurfactants are discussed to execute a critical study of factors affecting synthesis procedure and applications. The recent approaches of metal, metal oxide, and composite nanomaterial synthesis have been deliberated as well as the elucidation of the reaction mechanism. Furthermore, this approach shows remarkable boosts in the production of nanoparticles with the very less employed harsh and hazardous processes as compared to chemical or physical method-based nanoparticle synthesis. This study also shows that the advances in strain selection for green nanoparticle production could be a worthwhile and strong economical approach in futuristic medical science research.

Two novel cell culture models of buccal mucosal oral cancer from patients with no risk-habits of tobacco smoking or chewing.

OBJECTIVE: Tobacco consumption is one of the major etiological factors for oral cancer, but it also develops in non-tobacco users, with unknown etiologies. Cellular models for tobacco associated oral cancer are available, however; reports of cellular models for studying non-tobacco associated oral cancer are limiting. We report here the establishment and characterization of two novel buccal mucosal cancer cell lines 'GBC02' and 'GBC035' derived from non-tobacco users. MATERIALS AND METHODS: Short tandem repeats (STR) profiling, Next-generation sequencing for whole-genome, exome and copy number alterations, immunofluorescence, flow-cytometry, proliferation, live-cell chemotaxis, 3D-spheroid formation, chemotherapy response, gene-expression microarray, gene-set enrichment analysis and xenograft development were performed. RESULTS: Sources of the established cultures were matched to their donors through STR profiling. Genome sequence analysis revealed somatic mutations in TP53, CASP8, CDKN2A for GBC02 with deletions and amplifications encompassing CDKN2A, FAT1 and CCND1, PIK3CA, SOX2, EGFR, MYC genes, respectively. GBC035 harbored mutations in FAT1, NOTCH1, HRAS, CDKN2A, HLA-B, HLA-A genes. While GBC035 cells showed higher E-Cadherin positive cell-cell junctions and collective cell migration in chemotaxis; GBC02 cells were vimentin-positive and demonstrated individual cell migration. Further, exhibiting their relevance to preclinical research, GBC02 3D-spheroids demonstrated enrichment of development-related gene-signatures in microarray transcriptome analysis and were resistant to Cisplatin, but showed sensitivity to cancer stem cells-targeting drug, Salinomycin. Additionally, tumorigenic ability of GBC02 was demonstrated. CONCLUSIONS: Altogether, we present here comprehensively characterized unique cell lines established from non-tobacco associated tumors, which may serve as models for preclinical investigations of oral cancers caused independent of tobacco usage.

Evidences for Inclusion and Encapsulation of an Ionic liquid with ß-CD and 18-C-6 in Aqueous Environments by Physicochemical Investigation.

The interface between pyrrolidinium-based ionic liquid, i.e., 1-ethyl-1-methylpyrrolidinium bromide, with ß-cyclodextrin and 18-crown-6 solution have been compared and explored by means of density, viscosity, refractive index, electrical conductance and surface tension, FTIR, 1H nuclear magnetic resonance, 2D ROESY NMR, and high resolution mass spectroscopy studies. Limiting apparent molar volumes (ϕV0), experimental slopes (SV*) interpreted in terms of inclusion and interaction (ion-solvent, ion-ion). Establishment of binding affinity were discussed in molecular terms supported this inclusion complexation and encapsulation interaction process. The result shows that the stability of the resulting complexes of ß-cyclodextrin:[EMPyrr]+ and 18-crown-6:[EMPyrr]+ is based on the geometrical and spectrometric data. Host guest chemistry of the five-membered nitrogen containing cation with two different macro cyclic hosts is supported by studying NMR. HRMS has been used to support the complexation process with the proper stoichiometry ratio. The solid complex formations were established by Fourier transform infrared study.

Study to Probe Subsistence of Host-Guest Inclusion Complexes of α and ß-Cyclodextrins with Biologically Potent Drugs for Safety Regulatory Dischargement.

Host-guest interaction of two significant drugs, phenylephrine hydrochloride and synephrine with α and ß-cyclodextrins were studied systematically. Initially two simple but reliable physicochemical techniques namely conductance and surface tension were employed to find out saturation concentration for the inclusion and its stoichiometry. The obtained 1:1 stoichiometry was further confirmed by two spectrometric methods, UV-Vis study and spectrofluorimetry. Significant shifts in IR stretching frequency also support the inclusion process. Relative stabilities of the inclusion complexes were established by the association constants obtained from UV-Vis spectroscopic measurements, program based mathematical calculation of conductivity data. Calculations of the thermodynamic parameters dictates thermodynamic feasibility of the inclusion process. Spectrofluorometric measurement scaffolds the UV-Vis spectroscopic measurement validating stability of the ICs once again. Mass spectroscopic measurement gives the molecular ion peaks corresponding to the inclusion complex of 1:1 molar ratio of host and guest molecules. The mechanism of inclusion was drawn by 1H-NMR and 2D ROESY spectroscopic analysis. Surface texture of the inclusion complexes was studied by SEM. Finally, the cytotoxic activities of the inclusion complexes were analyzed and found, Cell viability also balances for non-toxic behavior of the ICs. Moreover, all the studies reveal the formation of inclusion complexes of two ephedra free, alternatively emerging drugs (after their banned product having ephedra) SNP, PEH with α and ß-CD which enriches the drug delivery system with their regulatory release without any chemical modification.