Plasma membrane intrinsic protein OsPIP2;6 is involved in root-to-shoot arsenic translocation in rice (Oryza sativa L.).

KEY MESSAGE: This study demonstrates the crucial role of OsPIP2;6 for translocation of arsenic from roots to shoots, which can decrease arsenic accumulation in rice for improved food safety. Arsenic (As) contamination in food and water, primarily through rice consumption, poses a significant health risk due to its natural tendency to accumulate inorganic arsenic (iAs). Understanding As transport mechanisms is vital for producing As-free rice. This study investigates the role of rice plasma membrane intrinsic protein, OsPIP2;6, for AsIII tolerance and accumulation. RNAi-mediated suppression of OsPIP2;6 expression resulted in a substantial (35-65%) reduction in As accumulation in rice shoots, while root arsenic levels remained largely unaffected. Conversely, OsPIP2;6 overexpression led to 15-76% higher arsenic accumulation in shoots, with no significant change in root As content. In mature plants, RNAi suppression caused (19-26%) decrease in shoot As, with flag leaves and grains showing a 16% reduction. OsPIP2;6 expression was detected in both roots and shoots, with higher transcript levels in shoots. Localization studies revealed its presence in vascular tissues of both roots and shoots. Overall, our findings highlight OsPIP2;6's role in root-to-shoot As translocation, attributed to its specific localization in the vascular tissue of roots and leaves. This knowledge can facilitate the development of breeding programs to mitigate As accumulation in rice and other food crops for improved food safety and increasing productivity on As-contaminated soils.

Performance prediction of a circularly polarized graphene-dielectric resonator-based antenna for THz frequency application using machine learning algorithms.

In this article, a graphene-dielectric resonator-based antenna is designed in the THz frequency regime. Circular polarization is achieved by feeding the cylindrical-shaped ceramic using a perturbed square-shaped aperture. Graphene loading over the alumina ceramic provides the frequency reconfigurable feature. In order to overcome the difficulty of simulating the THz antenna (i.e., very large simulation time), machine learning algorithms such as the artificial neural network (ANN) and random forest are used to effectively predict the performance of the designed antenna. The proposed antenna works effectively in between 5.0 and 5.5 THz with a 3 dB axial ratio frequency range from 5.1 to 5.35 THz. There is good correlation found between the predicted, measured, and simulated reflection coefficient and axial ratio. Due to stable radiation properties and good diversity performance within the operating frequency band, the proposed antenna can be employable for different wireless applications in the THz frequency regime.

Origin of Enhancement of Orbital Magnetic Moment in SiO2-Coated Fe3O4 Nanocomposites Studied by X-ray Magnetic Circular Dichroism.

In this study, magnetic Fe3O4 nanoparticles (NPs) were dispersed uniformly by varying the thickness of the SiO2 coating, and their electronic and magnetic properties were investigated. X-ray diffraction confirmed the structural configuration of monophase inverse-spinel Fe3O4 NPs in nanometer size. Scanning electron microscopy revealed the formation of proper nonporous crystallite particles with a clear core-shell structure with silica on the surface of Fe3O4 NPs. The absorption mechanism studied through the zeta potential indicates that SiO2-coated Fe3O4 nanocomposites (SiO2@Fe3O4 NCs) possess electrostatic interactions to control their agglomeration in stabilizing suspensions by providing a protective shield of amorphous SiO2 on the oxide surface. High-resolution transmission electron microscopy images demonstrate a spherical morphology having an average grain diameter of ∼11-17 nm with increasing thickness of SiO2 coating with the addition of a quantitative presence and proportion of elements determined through elemental mapping and electron energy loss spectroscopy studies. Synchrotron-based element-specific soft X-ray absorption spectroscopy and X-ray magnetic circular dichroism (XMCD) techniques have been involved in the bulk-sensitive total fluorescence yield mode to understand the origin of magnetization in SiO2@Fe3O4 NCs. The magnetization hysteresis of Fe3O4 was determined by XMCD. At room temperature, the magnetic coercivity (Hc) is as high as 1 T, which is about 2 times more than the value of the thin film and about 5 times more pronounced than that of NPs. For noninteracting single-domain NPs with the Hc spread from 1 to 3 T, the Stoner-Wohlfarth model provided an intriguing explanation for the hysteresis curve. These curves determine the different components of Fe oxides present in the samples that derive the remnant magnetization involved in each oxidation state of Fe and clarify which Fe component is responsible for the resultant magnetism and magnetocrystalline anisotropy based on noninteracting single-domain particles.

Histone H4 dosage modulates DNA damage response in the pathogenic yeast Candida glabrata via homologous recombination pathway.

Candida glabrata, a nosocomial fungal bloodstream pathogen, causes significant morbidity and mortality in hospitals worldwide. The ability to replicate in macrophages and survive a high level of oxidative stress contributes to its virulence in the mammalian host. However, the role of DNA repair and recombination mechanisms in its pathobiology is still being discovered. Here, we have characterized the response of C. glabrata to the methyl methanesulfonate (MMS)-induced DNA damage. We found that the MMS exposure triggered a significant downregulation of histone H4 transcript and protein levels, and that, the damaged DNA was repaired by the homologous recombination (HR) pathway. Consistently, the reduced H4 gene dosage was associated with increased HR frequency and elevated resistance to MMS. The genetic analysis found CgRad52, a DNA strand exchange-promoter protein of the HR system, to be essential for this MMS resistance. Further, the tandem-affinity purification and mass spectrometry analysis revealed a substantially smaller interactome of H4 in MMS-treated cells. Among 23 identified proteins, we found the WD40-repeat protein CgCmr1 to interact genetically and physically with H4, and regulate H4 levels, HR pathway and MMS stress survival. Controlling H4 levels tightly is therefore a regulatory mechanism to survive MMS stress in C. glabrata.

Tracking an Underwater Object with Unknown Sensor Noise Covariance Using Orthogonal Polynomial Filters.

In this manuscript, an underwater target tracking problem with passive sensors is considered. The measurements used to track the target trajectories are (i) only bearing angles, and (ii) Doppler-shifted frequencies and bearing angles. Measurement noise is assumed to follow a zero mean Gaussian probability density function with unknown noise covariance. A method is developed which can estimate the position and velocity of the target along with the unknown measurement noise covariance at each time step. The proposed estimator linearises the nonlinear measurement using an orthogonal polynomial of first order, and the coefficients of the polynomial are evaluated using numerical integration. The unknown sensor noise covariance is estimated online from residual measurements. Compared to available adaptive sigma point filters, it is free from the Cholesky decomposition error. The developed method is applied to two underwater tracking scenarios which consider a nearly constant velocity target. The filter's efficacy is evaluated using (i) root mean square error (RMSE), (ii) percentage of track loss, (iii) normalised (state) estimation error squared (NEES), (iv) bias norm, and (v) floating point operations (flops) count. From the simulation results, it is observed that the proposed method tracks the target in both scenarios, even for the unknown and time-varying measurement noise covariance case. Furthermore, the tracking accuracy increases with the incorporation of Doppler frequency measurements. The performance of the proposed method is comparable to the adaptive deterministic support point filters, with the advantage of a considerably reduced flops requirement.

Applications of Sentinel-2 satellite data for spatio-temporal mapping of deep pools for monitoring the riverine connectivity and assessment of ecological dynamics: a case from Godavari, a tropical river in India (2016-2021).

Rivers are dynamic ecosystems with diverse habitats that require ample connectivity to ensure the flow of ecosystem services, thus empowering the sustainable development of an entire basin. Geo-spatial tools offer powerful prospects for monitoring of aquatic ecosystems. The usefulness of Sentinel-2 datasets to assess river connectivity has been explored for an un-gauged seasonal river system. The present study was undertaken in five ecologically unique river reaches viz. Wainganga, Wardha, Pranhita, Godavari-mid and Manair in Godavari Basin in the Indian Deccan Plateau to map water spread dynamics at various time scales, i.e., fortnightly, monthly, seasonal, annual and demi-decadal during 2016-2021. The maximum value of perennial water spread per square kilometre of total floodplain area (2016-2021), determined using Sentinel-2 imageries, was observed in river Wardha (0.18) followed by Pranhita (0.12) and Wainganga (0.11). The water spread showed a decreasing trend, while the number of patches in the river corridor increased over time from post-monsoon to pre-monsoon season. The copious perennial habitat with relatively larger patches, incessant flow in river Pranhita and obstructed flow, large-sized patches reported in river Wardha during summer months, hold importance in terms of providing refuge to aquatic biota. This study provides evidence for the impact of water projects on spatio-temporal water spread dynamics in Godavari Basin. The demonstrated utility of Sentinel-2 imagery coupled with gauge station measurements for river continuity assessment and deep pool mapping would aid in enhancing our understanding on environmental flow at a spatial scale, which in turn would aid in effective river management to achieve the Sustainable Development Goals. The implications of this study for sustainable environmental management and limitations are also discussed.

Application of Microalgal Physiological Response as Biomarker for Evaluating the Toxicity of the Textile Dye Alizarin Red S.

Textile dyes are becoming a growing threat to the environment. This report presents the findings of the study on the toxicity of the textile dye Alizarin Red S on two freshwater microalgae. The acute toxicity assay revealed that 96-h EC50 values of Chlorella vulgaris and Spirulina platensis were 29.81 mg/L and 18.94 mg/L respectively. The pigments chlorophyll-a, b and carotenoids in C. vulgaris on 96-h exposure to the dye were 2.91, 3.29 and 3.01 times lower in analogy to control whereas Spirulina platensis showed 2.89and 2.56 fold decrease in chlorophyll-a and carotenoid content than control. After the test period of 96-h with dye, the protein content of C. vulgaris and S. platensis were 2.33 and 1.77 times lower compared to the control. The growth inhibition rate, pigment as well as the protein content declined in compliance with the rise in dye concentration, which anticipate paradigm about the toxic effects of the textile dye.

A Superfamily-wide Activity Atlas of Serine Hydrolases in Drosophila melanogaster.

The serine hydrolase (SH) superfamily is, perhaps, one of the largest functional enzyme classes in all forms of life and consists of proteases, peptidases, lipases, and carboxylesterases as representative members. Consistent with the name of this superfamily, all members, without any exception to date, use a nucleophilic serine residue in the enzyme active site to perform hydrolytic-type reactions via a two-step ping-pong mechanism involving a covalent enzyme intermediate. Given the highly conserved catalytic mechanism, this superfamily has served as a classical prototype in the development of several platforms of chemical proteomics techniques, activity-based protein profiling (ABPP), to globally interrogate the functions of its different members in various native, yet complex, biological settings. While ABPP-based proteome-wide activity atlases for SH activities are available in numerous organisms, including humans, to the best of our knowledge, such an analysis for this superfamily is lacking in any insect model. To address this, we initially report a bioinformatics analysis toward the identification and categorization of nonredundant SHs in Drosophila melanogaster. Following up on this in silico analysis, leveraging discovery chemoproteomics, we identify and globally map the full complement of SH activities during various developmental stages and in different adult tissues of Drosophila. Finally, as a proof of concept of the utility of this activity atlas, we highlight sexual dimorphism in SH activities across different tissues in adult D. melanogaster, and we propose new research directions, resources, and tools that this study can provide to the fly community.

Two Functionally Redundant FK506-Binding Proteins Regulate Multidrug Resistance Gene Expression and Govern Azole Antifungal Resistance.

Increasing resistance to antifungal therapy is an impediment to the effective treatment of fungal infections. Candida glabrata is an opportunistic human fungal pathogen that is inherently less susceptible to cost-effective azole antifungals. Gain-of-function mutations in the Zn-finger pleiotropic drug resistance transcriptional activator-encoding gene CgPDR1 are the most prevalent causes of azole resistance in clinical settings. CgPDR1 is also transcriptionally activated upon azole exposure; however, factors governing CgPDR1 gene expression are not yet fully understood. Here, we have uncovered a novel role for two FK506-binding proteins, CgFpr3 and CgFpr4, in the regulation of the CgPDR1 regulon. We show that CgFpr3 and CgFpr4 possess a peptidyl-prolyl isomerase domain and act redundantly to control CgPDR1 expression, as a Cgfpr3Δ4Δ mutant displayed elevated expression of the CgPDR1 gene along with overexpression of its target genes, CgCDR1, CgCDR2, and CgSNQ2, which code for ATP-binding cassette multidrug transporters. Furthermore, CgFpr3 and CgFpr4 are required for the maintenance of histone H3 and H4 protein levels, and fluconazole exposure leads to elevated H3 and H4 protein levels. Consistent with the role of histone proteins in azole resistance, disruption of genes coding for the histone demethylase CgRph1 and the histone H3K36-specific methyltransferase CgSet2 leads to increased and decreased susceptibility to fluconazole, respectively, with the Cgrph1Δ mutant displaying significantly lower basal expression levels of the CgPDR1 and CgCDR1 genes. These data underscore a hitherto unknown role of histone methylation in modulating the most common azole antifungal resistance mechanism. Altogether, our findings establish a link between CgFpr-mediated histone homeostasis and CgPDR1 gene expression and implicate CgFpr in the virulence of C. glabrata.

Role of temperature and co-infection in mediating the immune response of goldfish.

Aquatic Pathogens are expected to encounter tremendous levels of variation in their environment - both abiotic and biotic. Here we examined the change in innate immune parameters and mortality pattern of Carassius auratus during the interaction of co-infection due to an ectoparasite, Argulus and bacteria Aeromonas hydrophila, along with a temperature gradient. Experimental fish were assigned randomly to six treatment groups (T1-T6). Fish of groups T1, T3 and T5 are assigned for healthy fishes kept at 23, 28 and 33°c temperature and served as control. T2, T4 and T6 groups are the co-infected groups kept at temperature gradient. For the haematological and enzyme parameter analysis, sampling was done at 24 h, 72 h and 168 h post challenge from 4 fish in all experimental groups. A temperature dependent increase in intensity of Argulus was observed in the experimental group. Both in control group and co-infected group a temperature dependent mortality pattern was observed, showing an increased mortality of 60% in T6 and 20% in T5 group. A significant decrease of RBC, Hb, and PCV values was observed in co-infected group when compared with control fish in each of the experimental group. Also a temperature dependent increase in WBC, neutrophil and monocyte value was observed in control fish. Whereas, a significant reduction in WBC, neutrophil and monocyte was observed in co-infected fish exposed to 33 °C during the progression of infection. Furthermore, T4 group showed a significantly higher Nitroblue tetrazolium test, Myelo peroxidase and lyzozyme activity compared to other co-infection group. A significantly increased activity of Superoxide dismutase, Glutathione peroxidise and catalase activity was recorded in control fish exposed to 33 °C (T5) whereas, there was no significant difference observed in the activity of catalase and Glutathione peroxidise in the other control fish (T1 and T3 group). This result implies that increase in temperature not only accelerates the intensity of co-infection but also imbalance the health status of the fish by hampering the immunological and physiological parameters towards more detrimental side.

Molecular insights into the role of plant transporters in salt stress response.

Salt stress disturbs the cellular osmotic and ionic balance, which then creates a negative impact on plant growth and development. The Na+ and Cl- ions can enter into plant cells through various membrane transporters, including specific and non-specific Na+ , K+ , and Ca2+ transporters. Therefore, it is important to understand Na+ and K+ transport mechanisms in plants along with the isolation of genes, their characterization, the structural features, and their post-translation regulation under salt stress. This review summarizes the molecular insights of plant ion transporters, including non-selective cation transporters, cyclic nucleotide-gated cation transporters, glutamate-like receptors, membrane intrinsic proteins, cation proton antiporters, and sodium proton antiporter families. Further, we discussed the K+ transporter families such as high-affinity K+ transporters, HAK/KUP/KT transporters, shaker type K+ transporters, and K+ efflux antiporters. Besides the ion transport process, we have shed light on available literature on epigenetic regulation of transport processes under salt stress. Recent advancements of salt stress sensing mechanisms and various salt sensors within signaling transduction pathways are discussed. Further, we have compiled salt-stress signaling pathways, and their crosstalk with phytohormones.

Dose-dependent co-infection of Argulus sp. and Aeromonas hydrophila in goldfish (Carassius auratus) modulates innate immune response and antioxidative stress enzymes.

Co-infection with parasites and bacteria is of frequent occurrence in aquaculture, leads to growth impedance otherwise mortality in fish depending on the varying degree of a load of primary pathogen either parasite or bacteria. The mechanistic regulation of immune response during co-infection in fish has merely documented. The aim of this study was to determine the impact of co-infection with Aeromonas hydrophila at three exposure doses of Argulus sp. on the innate immune responses and antioxidative stress enzymes of goldfish (Carassius auratus). The experimental fish were randomly distributed into eight treatment groups viz. T1 (control group without Argulus and A. hydrophila infection), T2 (fish exposed to a sub-lethal dose of A. hydrophila), T3 (low Argulus-infested fish), T4 (T3 + sub-lethal dose of A. hydrophila), T5 (moderate Argulus-infested fish), T6 (T5 + sub-lethal dose of A. hydrophila), T7 (high Argulus-infested fish) and T8 (T7+ sub-lethal dose of A. hydrophila) in duplicates. After distributing experimental fish into their respective treatment group, A. hydrophila was injected to T2, T4, T6 and T8. After the bacterial challenge, four fish from each experimental group were randomly sampled on 24, 72, and 168 h and subjected to the hematological, innate immune parameters and enzymatic analysis. In the co-infection group T8, a high degree of enhanced pathogenicity of A. hydrophila was noticed with increased mortalities (84.2%) in comparison to other groups. The current study shows a declining pattern in RBC, PCV and Hb values with the degree of parasite infestation without co-infection groups. Moreover, in the T8 group, exposure of a sub-lethal dose of bacteria resulted in a drastic reduction of the recorded parameters. Furthermore, a decreased value for WBC, monocyte and neutrophil was found in higher parasite group co-infected with a sub-lethal dose of bacteria relative to other co-infected groups during the experimental period. Also, a decrease in innate immune parameters and antioxidative stress enzymes were observed in the T8 group compared to T7 and T2 groups throughout the trial period. These findings indicate that a rise in the dose of Argulus infection improves A. hydrophila colonization in goldfish and contributes to suppression of the innate immune system and increased mortality.

With no lysine kinases: the key regulatory networks and phytohormone cross talk in plant growth, development and stress response.

With No Lysine kinases (WNKs) are a distinct family of Serine/Threonine protein kinase with unique arrangement of catalytic residues in kinase domain. In WNK, an essential catalytic lysine requisite for attaching ATP and phosphorylation reaction is located in subdomain I, instead of subdomain II, which is essentially a typical feature of other Ser/Thr kinases. WNKs are identified in diverse organisms including multicellular and unicellular organisms. Mammalian WNKs are well characterized at structural and functional level, while plant WNKs are not explored much except few recent studies. Plant WNKs role in various physiological processes viz. ion maintenance, osmotic stress, pH homeostasis, circadian rhythms, regulation of flowering time, proliferation and organ development, and abiotic stresses are known, but the mechanisms involved are unclear. Plant WNKs are known to be involved in enhanced drought and salt stress response via ABA-signaling pathway, but the complete signaling cascade is yet to be elucidated. The current review will discuss the interplay between WNKs and growth regulators and their cross talks in plant growth and development. We have also highlighted the link between the stress phytohormones and WNK members in regulating abiotic stress responses in plants. The present review will provide an overall known mechanism on the involvement of WNKs in plant growth and development and abiotic stress response and highlight its role/applications in the development of stress-tolerant plants.

Genome protection: histone H4 and beyond.

Histone proteins regulate cellular factors' accessibility to DNA, and histone dosage has previously been linked with DNA damage susceptibility and efficiency of DNA repair pathways. Surplus histones are known to impede the DNA repair process by interfering with the homologous recombination-mediated DNA repair in Saccharomyces cerevisiae. Here, we discuss the recent finding of association of methyl methanesulfonate (MMS) resistance with the reduced histone H4 gene dosage in the pathogenic yeast Candida glabrata. We have earlier shown that while the low histone H3 gene dosage led to MMS susceptibility, the lack of two H4-encoding ORFs, CgHHF1 and CgHHF2, led to resistance to MMS-induced DNA damage. This resistance was linked with a higher rate of homologous recombination (HR). Taking these findings further, we review the interactome analysis of histones H3 and H4 in C. glabrata. We also report that the arginine residue present at the 95th position in the C-terminal tail of histone H4 protein is required for complementation of the MMS resistance in the Cghhf1Δhhf2Δ mutant, thereby pointing out a probable role of this residue in association with HR factors. Additionally, we present evidence that reduction in H4 protein levels may constitute an important part of varied stress responses in C. glabrata. Altogether, we present an overview of histone H4 dosage, HR-mediated repair of damaged DNA and stress resistance in this opportunistic human fungal pathogen.

Development of novel carbazole derivatives with effective multifunctional action against Alzheimer's diseases: Design, synthesis, in silico, in vitro and in vivo investigation.

Carbazole based novel multifunctional agents has been rationally designed and synthesized as potential anti-Alzheimer agents. Multi-functional activity of these derivatives have been assessed by performing various in-vitro assays and these compounds appeared to be potent AChE inhibitors, Aß aggregation inhibitors, anti-oxidant and neuroprotective agents. Among the entire series, MT-1 and MT-6 were most potent multifunctional agents which displayed effective and selective AChE inhibition, Aß disaggregation, anti-oxidant and metal chelation action. Neuroprotective activity of MT-6 has been examined against H2O2 induced toxicity in SHSY-5Y cells and they have shown effective neuroprotection. Additionally, MT-6 did not display any significant toxicity in SHSY-5Y cells, indicating its non-toxic nature. Molecular docking and MD simulation studies have been also performed to explore molecular level interaction with AChE and Aß. Finally, MT-6 was evaluated against scopolamine induced dementia model of mice and this compound actively improved memory deficit and cognition impairment in scopolamine treated mice. Thus, novel carbazole derivative MT-6 has been explored as an effective and safe multifunctional agent against AD and this molecule may be used as a suitable lead for development of effective anti-Alzheimer agents in future.

Triclosan induces immunosuppression and reduces survivability of striped catfish Pangasianodon hypophthalmus during the challenge to a fish pathogenic bacterium Edwardsiella tarda.

Toxicological studies on the emergent pollutant, triclosan (TCS) have established the wide-ranging effects of the compound on fish and other aquatic organisms. Although the available literature describes the standalone effects of TCS on growth and metabolism of fish yet, reports about the combined effects of TCS with microbial pathogens are scarce. In a real environment, a combined exposure to TCS and pathogens is of common occurrence, therefore, such investigation facilitates in developing a better understanding about the gross effects of pollutants and microbial pathogens on aquatic organisms including fish. In this context, the experimental fish (striped catfish, Pangasianodon hypophthalmus) were exposed to three different concentrations of TCS viz. 10, 20 and 30% of 96 h LC50 (1177 µg L-1) for 45 days including two control group firstly solvent control (without TCS) group and another one (without solvent and TCS) group in triplicate. Sampling was performed fortnightly and blood, serum and tissues (liver, and gills) samples were collected for evaluating immunological and biochemical parameters. Following 45 days of the experiments, the experimental fish in each treatment group including controls were challenged with a fish pathogenic bacterium Edwardsiella tarda (LD50 dose) and fish mortality was daily monitored for calculating cumulative mortality till 7 days and further, relative per cent survivable was estimated. A significant reduction in cellular immune responses i.e. respiratory burst activity (RBA), myeloperoxidase activity (MPO), phagocytic activity (PA) and humoral immune components viz. serum lysozyme activity, total immunoglobulin in serum, ceruloplasmin level, serum total protein, albumin and globulin level was evident in TCS exposed groups in comparison to control during the experimental periods. Further, oxidative stress parameters viz. superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) activity in liver and gill tissue exhibited a dose-dependent increase in activity with related to TCS concentration during the experimental periods. A significant reduction in relative percentage survival was observed with increasing TCS concentration. The present study reveals that TCS can inhibit the cellular and humoral components of the innate immune system of the fish and can elevate the mortality due to TCS mediated immunosuppression in fish during the bacterial infection.

Mechanistic elucidation of amphetamine metabolism by tyramine oxidase from human gut microbiota using molecular dynamics simulations.

The human gut harbors diverse bacterial species in the gut, which play an important role in the metabolism of food and host health. Recent studies have also revealed their role in altering the pharmacological properties and efficacy of oral drugs through promiscuous metabolism. However, the atomistic details of the enzyme-drug interactions of gut bacterial enzymes which can potentially carry out the metabolism of drug molecules are still scarce. A well-known example is the FDA drug amphetamine (a central nervous system stimulant), which has been predicted to undergo promiscuous metabolism by gut bacteria. Therefore, to understand the atomistic details and energy landscape of the gut microbial enzyme-mediated metabolism of this drug, molecular dynamics studies were performed. It was observed that amphetamine binds to tyramine oxidase from the Escherichia coli strain present in the human gut microbiota at the binding site harboring polar and nonpolar amino acids. The stability analysis of amphetamine at the binding site showed that the binding is stable and the free energy for the binding of amphetamine was found to be ~ -51.71 kJ/mol. The insights provided by this study on promiscuous metabolism of amphetamine by a gut enzyme will be very useful to improve the efficacy of the drug.

Triclosan exposure induces varying extent of reversible antimicrobial resistance in Aeromonas hydrophila and Edwardsiella tarda.

Triclosan (TCS) is a biocide commonly used in household and personal care items to prevent the microbial growth and is currently considered as an emerging pollutant. It has a ubiquitous distribution which can substantially contribute towards antimicrobial resistance. The present study was designed to evaluate the effect of different concentrations of TCS exposure on the antibiotic sensitivity of aquatic bacteria. Aeromonas hydrophila ATCC® 49140™ and Edwardsiella tarda ATCC® 15947™ exposed to TCS for short (30 min) and long duration (serial passages). The agar-disc diffusion assay during the serial passages of TCS exposure and subsequent exposure withdrawal showed clinically insignificant changes in the zone of inhibition for six selected antibiotics in both bacterial strains at all exposure concentrations. Four folds concentration-dependent increase in the minimum inhibitory concentrations (MICs) of TCS was observed in both the strains following TCS exposure. Similarly, a concentration-dependent increase in the MICs of oxytetracycline (OTC) up to 4 folds in A. hydrophila, and up to 8 folds in E. tarda, was also documented during the TCS exposure. In all the cases, withdrawal of TCS exposure effectively reduced the MICs of TCS and OTC in blank passages suggesting a decline in acquired resistance. The frequencies of mutation during 30 min TCS exposure for E. tarda and A. hydrophila ranged between >10-6 and 10-7 levels. Nevertheless, the TCS exposure did not cause any detectable mutation on the fabV gene of A. hydrophila indicating that the TCS may elicit phenotypic adaptation or other resistance mechanism. Although the reduction in MICs due to exposure withdrawal did not restore the bacterial susceptibility up to the initial level, the study proved that the reduced TCS use could significantly help reduce the antimicrobial-resistance and cross-resistance in pathogenic bacteria.

Physical entrapment of chitosan in fixed-down-flow column bed enhances triclosan removal from water.

Triclosan (TCS) is an emergent pollutant with wide-ranging deleterious effects on aquatic organisms and humans. There is a growing concern about the development of low-cost and efficient treatment systems for the removal of TCS from water. This report describes the performance of a prototype of a continuous flow, fixed bed column device with physically entrapped industrial by-product chitosan. The effects of initial TCS concentration, adsorbent dose in the column matrix, and flow rate were investigated with regard to removal efficiency (%), adsorption capacity and breakthrough time. To understand the thermodynamic properties of the adsorption process, three kinetic models - Thomas, Yoon-Nelson and Adams-Bohart - were applied to the experimental data for the prediction of characteristic parameters of the adsorption process. The Yoon-Nelson model showed the best agreement between the experimental and calculated values. The column showed a near saturation state (Ct/C0 = 0.92; C0 and Ct are the concentration of TCS before and after treatment.) at 90 mg L-1 TCS concentration after 60 minutes. In view of non-availability of a treatment process for the emergent pollutant TCS, the data of the present investigation will facilitate the development of novel prototypes of column bed reactors for the removal of TCS.

Mechanistic and structural insight into promiscuity based metabolism of cardiac drug digoxin by gut microbial enzyme.

The recent advances in microbiome studies have revealed the role of gut microbiota in altering the pharmacological properties of oral drugs, which contributes to patient-response variation and undesired effect of the drug molecule. These studies are essential to guide us for achieving the desired efficacy and pharmacological activity of the existing drug molecule or for discovering novel and more effective therapeutics. However, one of the main limitations is the lack of atomistic details on the binding and metabolism of these drug molecules by gut-microbial enzymes. Therefore, in this study, for a well-known and important FDA-approved cardiac glycoside drug, digoxin, we report the atomistic details and energy economics for its binding and metabolism by the Cgr2 protein of Eggerthella lenta DSM 2243. It was observed that the binding pocket of digoxin to Cgr2 primarily involved the negatively charged polar amino acids and a few non-polar hydrophobic residues. The drug digoxin was found to bind Cgr2 at the same binding site as that of fumarate, which is the proposed natural substrate. However, digoxin showed a much lower binding energy (17.75 ± 2 Kcal mol-1 ) than the binding energy (42.17 ± 2 Kcal mol-1 ) of fumarate. This study provides mechanistic insights into the structural and promiscuity-based metabolism of widely used cardiac drug digoxin and presents a methodology, which could be useful to confirm the promiscuity-based metabolism of other orally administrated drugs by gut microbial enzymes and also help in designing strategies for improving the efficacy of the drugs.