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1.
Chem Asian J ; 19(9): e202400135, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38503696

RESUMO

The introduction of a higher arene unit as a structural motif is unprecedented in calixphyrin chemistry. Herein, the syntheses, spectral and structural characterization of heretofore anonymous terphenylene unit (o-p-o) incorporated calixphyrin with fused sp2 meso carbons is reported. The explicitly tailored macrocyclic core is utilized to stabilize the Cu(II) metal ion. The molecular structures of the calixbenziphyrin and Cu(II) complex are unambiguously confirmed by single-crystal X-ray analysis. Moreover, theoretical supports uphold experimental conclusions.

2.
Arch Microbiol ; 206(1): 6, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38015256

RESUMO

Paracoccus species are metabolically versatile gram-negative, aerobic facultative methylotrophic bacteria showing enormous promise for environmental and bioremediation studies. Here we report, the complete genome analysis of Paracoccus sp. strain DMF (P. DMF) that was isolated from a domestic wastewater treatment plant in Kanpur, India (26.4287 °N, 80.3891 °E) based on its ability to degrade a recalcitrant organic solvent N, N-dimethylformamide (DMF). The results reveal a genome size of 4,202,269 base pairs (bp) with a G + C content of 67.9%. The assembled genome comprises 4141 coding sequences (CDS), 46 RNA sequences, and 2 CRISPRs. Interestingly, catabolic operons related to the conventional marine-based methylated amines (MAs) degradation pathway were functionally annotated within the genome of an obligated aerobic heterotroph that is P. DMF. The genomic data-based characterization presented here for the novel heterotroph P. DMF aims to improve the understanding of the phenotypic gene products, enzymes, and pathways involved with greater emphasis on facultative methylotrophic motility-based latent pathogenicity.


Assuntos
Paracoccus , Paracoccus/genética , Dimetilformamida , Bactérias , Genômica , Água
3.
Environ Sci Pollut Res Int ; 30(60): 125947-125964, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38010547

RESUMO

Paracoccus sp. strain DMF (P. DMF from henceforth) is a gram-negative heterotroph known to tolerate and utilize high concentrations of N,N-dimethylformamide (DMF). The work presented here elaborates on the metabolic pathways involved in the degradation of C1 compounds, many of which are well-known pollutants and toxic to the environment. Investigations on microbial growth and detection of metabolic intermediates corroborate the outcome of the functional genome analysis. Several classes of C1 compounds, such as methanol, methylated amines, aliphatic amides, and naturally occurring quaternary amines like glycine betaine, were tested as growth substrates. The detailed growth and kinetic parameter analyses reveal that P. DMF can efficiently aerobically degrade trimethylamine (TMA) and grow on quaternary amines such as glycine betaine. The results show that the mechanism for halotolerant adaptation in the presence of glycine betaine is dissimilar from those observed for conventional trehalose-mediated halotolerance in heterotrophic bacteria. In addition, a close genomic survey revealed the presence of a Co(I)-based substrate-specific corrinoid methyltransferase operon, referred to as mtgBC. This demethylation system has been associated with glycine betaine catabolism in anaerobic methanogens and is unknown in denitrifying aerobic heterotrophs. This report on an anoxic-specific demethylation system in an aerobic heterotroph is unique. Our finding exposes the metabolic potential for the degradation of a variety of C1 compounds by P. DMF, making it a novel organism of choice for remediating a wide range of possible environmental contaminants.


Assuntos
Dimetilformamida , Paracoccus , Dimetilformamida/metabolismo , Amidas , Betaína , Paracoccus/genética , Redes e Vias Metabólicas
4.
J Inorg Biochem ; 249: 112369, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37776829

RESUMO

Quinalizarin, an analogue of anthracycline anticancer agents, is an anticancer agent itself. A CuII complex was prepared and characterized by elemental analysis, UV-Vis & IR spectroscopy, mass spectrometry, EPR and DFT. The intention behind the preparation of the complex was to increase cellular uptake, compare its binding with DNA against that of quinalizarin, modulation of semiquinone formation, realization of human DNA topoisomerase I & human DNA topoisomerase II inhibition and observation of anticancer activity. While the first two attributes of complex formation lead to increased efficacy, decrease in semiquinone generation could results in a compromise with efficacy. Inhibition of human DNA topoisomerase makes up this envisaged compromise in free radical activity since the complex shows remarkable ability to disrupt activities of human DNA topoisomerase I and II. The complex unlike quinalizarin, does not catalyze flow of electrons from NADH to O2 to the extent known for quinalizarin. Hence, decrease in semiquinone or superoxide radical anion could make modified quinalizarin [as CuII complex] less efficient in free radical pathway. However, it would be less cardiotoxic and that would be advantageous to qualify it as a better anticancer agent. Although binding to calf thymus DNA was comparable to quinalizarin, it was weaker than anthracyclines. Low cost of quinalizarin could justify consideration as a substitute for anthracyclines but the study revealed IC50 of quinalizarin/CuII-quinalizarin was much higher than anthracyclines or their complexes. Even then, there is a possibility that CuII-quinalizarin could be an improved and less costly form of quinalizarin as anticancer agent.


Assuntos
Antineoplásicos , Complexos de Coordenação , Humanos , DNA Topoisomerases Tipo I/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antibióticos Antineoplásicos , Inibidores da Topoisomerase II/farmacologia , Superóxidos/metabolismo , Antraciclinas , Radicais Livres/metabolismo , Cobre/química , Complexos de Coordenação/química
5.
NPJ Vaccines ; 8(1): 134, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37709772

RESUMO

Detailed characterisation of immune responses induced by COVID-19 vaccines rolled out in India: COVISHIELDTM (CS) and COVAXIN® (CO) in a pre-exposed population is only recently being discovered. We addressed this issue in subjects who received their primary series of vaccination between November 2021 and January 2022. Both vaccines are capable of strongly boosting Wuhan Spike-specific neutralising antibody, polyfunctional Th1 cytokine producing CD4+ T-cells and single IFN-γ + CD8+ T-cells. Consistent with inherent differences in vaccine platform, the vector-based CS vaccine-induced immunity was of greater magnitude, breadth, targeting Delta and Omicron variants compared to the whole-virion inactivated vaccine CO, with CS vaccinees showing persistent CD8+ T-cells responses until 3 months post primary vaccination. This study provides detailed evidence on the magnitude and quality of CS and CO vaccine induced responses in subjects with pre-existing SARS-CoV-2 immunity in India, thereby mitigating vaccine hesitancy arguments in such a population, which remains a global health challenge.

6.
PLoS One ; 18(2): e0280636, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36763612

RESUMO

Various faulty farming practices and low-performance cultivars selection are reducing crop yields, factor productivity, and soil fertility. Therefore, there is an urgent need to achieve better nutrient dynamics and sustainable production by selecting more nutrient-responsive cultivars using efficient nutrient management. The present experiment aimed to enhance crop productivity, seed quality, nutrient efficiency, and soil nutrient dynamics through efficient nutrient management under different lentil cultivars. The experiment was laid out in a split-plot design, assigning three cultivars (viz. Sapna, Garima, and HM-1) in the main plots and ten nutrient management practices in the sub-plots, replicating them thrice. Results revealed that cultivar HM-1 recorded significantly higher seed yield (1.59-1.61 Mg ha-1) and the uptake of N (67.2-67.6 kg ha-1), P (6.8-7.0 kg ha-1), K (13.8-13.9 kg ha-1), Zn (60.4-61.1 g ha-1), and Fe (162.5-165.2 g ha-1) in seed compared to Sapna and Garima. Also, the cultivar HM-1 was more efficient in terms of partial factor productivity for NPK (PFP; 24.27-24.59 kg kg-1), partial nutrient balance (PNB; 2.09-2.13 kg kg-1) and internal utilisation efficiency (IUE; 11.64-11.85 kg kg-1). The study showed that the lentil cultivar HM-1 could be successfully grown by substituting 50% RDN with organic manures, i.e., vermicompost, without compromising crop productivity and soil fertility, thereby sustaining soil-human-environment health.


Assuntos
Lens (Planta) , Humanos , Produtos Agrícolas , Fertilizantes/análise , Solo , Nutrientes , Índia
7.
Front Immunol ; 13: 985938, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268023

RESUMO

This proof-of-concept study tested if prior BCG revaccination can qualitatively and quantitively enhance antibody and T-cell responses induced by Oxford/AstraZeneca ChAdOx1nCoV-19 or COVISHIELD™, an efficacious and the most widely distributed vaccine in India. We compared COVISHIELD™ induced longitudinal immune responses in 21 BCG re-vaccinees (BCG-RV) and 13 BCG-non-revaccinees (BCG-NRV), all of whom were BCG vaccinated at birth; latent tuberculosis negative and SARS-CoV-2 seronegative prior to COVISHIELD™ vaccination. Compared to BCG-NRV, BCG-RV displayed significantly higher and persistent spike-specific neutralizing (n) Ab titers and polyfunctional CD4+ and CD8+ T-cells for eight months post COVISHIELD™ booster, including distinct CD4+IFN-γ+ and CD4+IFN-γ- effector memory (EM) subsets co-expressing IL-2, TNF-α and activation induced markers (AIM) CD154/CD137 as well as CD8+IFN-γ+ EM,TEMRA (T cell EM expressing RA) subset combinations co-expressing TNF-α and AIM CD137/CD69. Additionally, elevated nAb and T-cell responses to the Delta mutant in BCG-RV highlighted greater immune response breadth. Mechanistically, these BCG adjuvant effects were associated with elevated markers of trained immunity, including higher IL-1ß and TNF-α expression in CD14+HLA-DR+monocytes and changes in chromatin accessibility highlighting BCG-induced epigenetic changes. This study provides first in-depth analysis of both antibody and memory T-cell responses induced by COVISHIELD™ in SARS-CoV-2 seronegative young adults in India with strong evidence of a BCG-induced booster effect and therefore a rational basis to validate BCG, a low-cost and globally available vaccine, as an adjuvant to enhance heterologous adaptive immune responses to current and emerging COVID-19 vaccines.


Assuntos
Vacina BCG , Vacinas contra COVID-19 , COVID-19 , Humanos , Adulto Jovem , Adjuvantes Imunológicos , Cromatina , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Imunidade , Interleucina-2 , SARS-CoV-2 , Fator de Necrose Tumoral alfa , Vacinação
8.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-505791

RESUMO

During the COVID-19 pandemic, large differences in susceptibility and mortality due to SARS-CoV-2 infection have been reported between populations in Europe and South Asia. While both host and environmental factors (including BCG vaccination) have been proposed to explain this, the potential biological substrate of these differences is unknown. We purified peripheral blood mononuclear cells from individuals living in India and the Netherlands at baseline and 10-12 weeks after BCG vaccination. We compared chromatin accessibility between the two populations at baseline, as well as gene transcription profiles and cytokine production capacities upon viral stimulation with influenza and SARS-CoV-2. The chromatin accessibility of genes important for adaptive immunity was higher in Indians compared to Europeans, while the latter had more accessible chromatin regions in genes of the innate immune system. At the transcriptional level, we observed that Indian volunteers displayed a more tolerant immune response to viral stimulation, in contrast to a more exaggerated response in Europeans. BCG vaccination strengthened the tolerance program in Indians, but not in Europeans. These differences may partly explain the different impact of COVID-19 on the two populations.

9.
PLoS One ; 17(2): e0262652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35176054

RESUMO

Present investigation was conducted at the Research Farm of Indian Institute of Soil Science, Bhopal during 2017-18 and 2018-19 to study the performance of chickpea crop under various nutrient management modules in a Vertisol. The field experiment was set up in a randomized block design with three replications of twelve different INM modules. During the rabi seasons of 2017-18 and 2018-19, the chickpea (cv. JG-315) was grown with a set of treatments. The crop's performance was evaluated in terms of growth, yield (grain and straw), nutritional content, and nutrient uptake under different treatments. At crop harvest, the physic-chemical characteristics of the soil were also evaluated. Finally, the relationship between the numerous examined parameters was determined. The results showed that integrated nutrient management modules had a positive impact on chickpea crop performance and productivity when compared to using only inorganic fertilizer. The INM modules dramatically increased soil organic carbon and improved soil health in terms of physical and chemical qualities, in addition to higher crop performance. Among the various modules, (1) application of 75% STCR dose + FYM @ 5t ha-1to maize followed by 100% P only to chickpea and (2) application of FYM @ 20t ha-1to maize followed by FYM @ 5t ha-1 to chickpea increased the productivity and nutrient uptake in chickpea, improved soil physico-chemical properties and reflected as viable technique in improving soil nutrient availability on sustainable basis.


Assuntos
Carbono/química , Cicer/crescimento & desenvolvimento , Fertilizantes/análise , Nutrientes/análise , Estações do Ano , Solo/química , Zea mays/crescimento & desenvolvimento , Cicer/efeitos dos fármacos , Índia , Nutrientes/administração & dosagem , Zea mays/efeitos dos fármacos
10.
Bioinformation ; 18(9): 757-763, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37426511

RESUMO

Data on the microbial composition among tobacco chewers and oral cancer patients in Rajasthan, India is of interest. NGS analysis from tobacco chewers and oral cancer comprised the most abundant and core microbial taxa in the oral cavity. It shows that highly pathogenic phylum consisting of 6% Fusobacteria and 9% Firmicutes are observed in oral cancer samples; whereas, 0.6% Treponema, 34% Firmicutes, 0.02% Mollicutes, and 4% Fusobacteria are seen in tobacco chewers. Thus, data shows that the most abundant and core microbial taxa are found in the oral cavity of tobacco chewers and oral cancer patients in Rajasthan, India.

11.
Front Microbiol ; 13: 1041124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36817102

RESUMO

Pulses are an important source of energy and protein, essential amino acids, dietary fibers, minerals, and vitamins, and play a significant role in addressing global nutritional security. The global pulse area, production, and average productivity increased from 1961 to 2020 (60 years). Pulses are usually grown under rainfed, highly unstable, and complex production environments, with substantial variability in soil and environmental factors, high year-to-year output variability, and variation in soil moisture. Since the last six decades, there is not much satisfactory improvement in the yield of pulses because of their cultivation in harsh environments, coupled with their continuous ignorance of the farmers and governments in policy planning. As a result, the global food supplies through pulses remained negligible and amounted to merely ~1.0% of the total food supply and 1.2% of the vegan food system. In this situation, protein-rich food is still a question raised at the global level to make a malnutrition-free world. Pulses are a vital component of agricultural biological diversity, essential for tackling climate change, and serve as an energy diet for vegetarians. Pulses can mitigate climate change by reducing the dependence on synthetic fertilizers that artificially introduce nitrogen (N) into the soil. The high demand and manufacture of chemical fertilizers emit greenhouse gases (GHGs), and their overuse can harm the environment. In addition, the increasing demand for the vegetal protein under most global agroecosystems has to be met with under a stressed rainfed situation. The rainfed agroecosystem is a shelter for poor people from a significant part of the globe, such as Africa, South Asia, and Latin America. Nearly, 83% [over 1,260 million hectares (ha)] of cultivated land comes under rainfed agriculture, contributing significantly to global food security by supplying over 60% of the food. In rainfed areas, the limitation of natural resources with the shrinking land, continuous nutrient mining, soil fertility depletion, declining productivity factor, constantly depleting water availability, decreasing soil carbon (C) stock, augmented weed menace, ecological instability, and reduced system productivity are creating a more challenging situation. Pulses, being crops of marginal and semi-marginal soils of arid and semi-arid climates, require less input for cultivation, such as water, nutrients, tillage, labor, and energy. Furthermore, accommodation of the area for the cultivation of pulses reduces the groundwater exploitation, C and N footprints, agrochemical application in the cropping systems, and ill effects of climate change due to their inherent capacity to withstand harsh soil to exhibit phytoremediation properties and to stand well under stressed environmental condition. This article focuses on the role of pulses in ecological services, human wellbeing, soil, environmental health, and economic security for advanced sustainability. Therefore, this study will enhance the understanding of productivity improvement in a system-based approach in a rainfed agroecosystem through the involvement of pulses. Furthermore, the present study highlighted significant research findings and policy support in the direction of exploring the real yield potential of pulses. It will provide a road map to producers, researchers, policymakers, and government planners working on pulses to promote them in rainfed agroecosystems to achieve the United Nations (UN's) Sustainable Development Goals (SDGs).

12.
Bioinformation ; 18(8): 724-729, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37323560

RESUMO

Oral cancer is becoming more common, and it threatens to be a serious worldwide medical issue. Hence, it is of interest to elucidate the networks between proteins and biologically active compounds, as well as their functional annotations, and cell signaling pathways. The online STRING software was used to create a molecular genetics interaction network named AZURIN on oral bacterial proteins. We also used the cystoscope software to identify 11 nodes and 16 edges with an average node order of 2.91. Thus, we document data on the interaction of protein networks with other proteins for identifying potential therapeutic drug candidates linked to oral disease.

13.
Nucleic Acids Res ; 49(20): 11834-11854, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34751402

RESUMO

RECQ1 is the shortest among the five human RecQ helicases comprising of two RecA like domains, a zinc-binding domain and a RecQ C-terminal domain containing the winged-helix (WH). Mutations or deletions on the tip of a ß-hairpin located in the WH domain are known to abolish the unwinding activity. Interestingly, the same mutations on the ß-hairpin of annealing incompetent RECQ1 mutant (RECQ1T1) have been reported to restore its annealing activity. In an attempt to unravel the strand annealing mechanism, we have crystallized a fragment of RECQ1 encompassing D2-Zn-WH domains harbouring mutations on the ß-hairpin. From our crystal structure data and interface analysis, we have demonstrated that an α-helix located in zinc-binding domain potentially interacts with residues of WH domain, which plays a significant role in strand annealing activity. We have shown that deletion of the α-helix or mutation of specific residues on it restores strand annealing activity of annealing deficient constructs of RECQ1. Our results also demonstrate that mutations on the α-helix induce conformational changes and affects DNA stimulated ATP hydrolysis and unwinding activity of RECQ1. Our study, for the first time, provides insight into the conformational requirements of the WH domain for efficient strand annealing by human RECQ1.


Assuntos
DNA de Cadeia Simples/química , RecQ Helicases/química , Sítios de Ligação , DNA de Cadeia Simples/metabolismo , Humanos , Simulação de Dinâmica Molecular , Mutação , Ligação Proteica , Conformação Proteica em alfa-Hélice , RecQ Helicases/genética , RecQ Helicases/metabolismo , Zinco/metabolismo
14.
Int J Biol Macromol ; 192: 574-589, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653440

RESUMO

Taro is a major root crop utilized widely for diverse food and non-food applications. Taro corms are processed into various forms before consumption, which makes them digestible and palatable, extends the shelf life and reduces post-harvest losses. Taro corm contains starch as the major carbohydrate, accounting up to 70-80% of the whole dry matter. The starches obtained from different cultivars and sources significantly differ in physical, chemical, thermal, morphological, and functional properties, which can be explored for varied applications. Starch quality also controls the end-quality of food and industrial products. Several starch modification methods have been studied to improve its positive attributes and to eliminate deficiencies in its native characteristics. These modification methods, which can be categorised into physical, chemical and enzymatic, have proved to improve the characteristics and applications of starch. This review aims to compile the information about the chemical composition, characterization, isolation and modification methods, with an objective of its increased use in food or non-food industries. In addition, challenges and issues in the small-scale processing of taro are discussed. The information available in this review may help in a better understanding and utilization of taro starch.


Assuntos
Colocasia/química , Amido/química , Amido/isolamento & purificação , Amilose/química , Engenharia Química , Fracionamento Químico , Fenômenos Químicos , Produção Agrícola , Estrutura Molecular , Valor Nutritivo , Compostos Fitoquímicos , Raízes de Plantas/química , Solubilidade , Amido/análise , Relação Estrutura-Atividade
16.
J Arthroplasty ; 36(5): 1633-1637, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33468344

RESUMO

BACKGROUND: Periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is a rare but major complication. Owing to an increasing antibiotic resistance in bacteria causing PJI, vancomycin has been investigated as a prophylactic agent. Intraosseous regional administration (IORA) of vancomycin achieves significantly higher local tissue concentrations than systemic administration. There are limited data on IORA of vancomycin with respect to vancomycin-associated complications. METHODS: Single-surgeon retrospective review of primary TKA was performed between January 2015 and May 2019. All patients received 500 mg of IORA of vancomycin after tourniquet inflation and 3 × 1 g intravenous cefazolin in 24 hrs. Preoperative data collected included age, gender, body mass index, American Society of Anesthesiologists (ASA) score, diabetes, and chronic kidney disease (CKD). We documented in-hospital complications and complications requiring readmission within 12 months. Primary outcome measures were the incidence of acute kidney injury (AKI), 'red man syndrome' (RMS), and neutropenia. The secondary outcome measure was PJI incidence. RESULTS: We identified 631 primary TKAs in 556 patients, of which 331 received IORA. The mean age was 67.7 ± 8.7 years, and 57.8% were women. CKD was prevalent in 17.2% of the cohort. AKI occurred in 25 (3.9%) cases. After controlling for covariates, CKD was the only significant predictor of AKI (odds ratio = 3.035, P = .023). RMS and neutropenia were not observed in this cohort. The 90-day PJI rate was 0%, and the 1-year PJI rate was 0.2%. CONCLUSIONS: Low-dose IORA of vancomycin in addition to standard intravenous systemic cefazolin prophylaxis in TKA is safe without significant adverse effects of vancomycin such as AKI, RMS, or neutropenia.


Assuntos
Artroplastia do Joelho , Infecções Relacionadas à Prótese , Idoso , Antibacterianos/efeitos adversos , Antibioticoprofilaxia , Artroplastia do Joelho/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/prevenção & controle , Estudos Retrospectivos , Vancomicina/efeitos adversos
17.
Prog Biophys Mol Biol ; 160: 66-78, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32735943

RESUMO

Dimethylformamidase (DMFase) catalyzes the hydrolysis of dimethylformamide, an industrial solvent, introduced into the environment by humans. Recently, we determined the structures of dimethylformamidase by electron cryo microscopy and X-ray crystallography revealing a tetrameric enzyme with a mononuclear iron at the active site. DMFase from Paracoccus sp. isolated from a waste water treatment plant around the city of Kanpur in India shows maximal activity at 54 °C and is halotolerant. The structures determined by both techniques are mostly identical and the largest difference is in a loop near the active site. This loop could play a role in co-operativity between the monomers. A number of non-protein densities are observed in the EM map, which are modelled as water molecules. Comparison of the structures determined by the two methods reveals conserved water molecules that could play a structural role. The higher stability, unusual active site and negligible activity at low temperature makes this a very good model to study enzyme mechanism by cryoEM.


Assuntos
Amidoidrolases/química , Microscopia Crioeletrônica/métodos , Cristalografia por Raios X/métodos , Amidoidrolases/metabolismo , Conformação Proteica , Multimerização Proteica/fisiologia , Transdução de Sinais , Água/química
18.
Front Microbiol ; 11: 1668, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849344

RESUMO

Pseudomonas aeruginosa is among the top three gram-negative bacteria according to the WHO's critical priority list of pathogens against which newer antibiotics are urgently needed and considered a global threat due to multiple drug resistance. This situation demands unconventional antimicrobial strategies such as the inhibition of quorum sensing to alleviate the manifestation of classical resistance mechanisms. Here, we report that 2,4-di-tert-butylphenol (2,4-DBP), isolated from an endophytic fungus, Daldinia eschscholtzii, inhibits the quorum-sensing properties of P. aeruginosa. We have found that treating P. aeruginosa with 2,4-DBP substantially reduced the secretion of virulence factors as well as biofilm, and its associated factors that are controlled by quorum sensing, in a dose-dependent manner. Concomitantly, 2,4-DBP also significantly reduced the expression of quorum sensing-related genes, i.e., lasI, lasR, rhlI, and rhlR significantly. Importantly, 2,4-DBP restricted the adhesion and invasion of P. aeruginosa to the A549 lung alveolar carcinoma cells. In addition, bactericidal assay with 2,4-DBP exhibited synergism with ampicillin to kill P. aeruginosa. Furthermore, our computational studies predicted that 2,4-DBP could bind to the P. aeruginosa quorum-sensing receptors LasR and RhlR. Collectively, these data suggest that 2,4-DBP can be exploited as a standalone drug or in combination with antibiotic(s) as an anti-virulence and anti-biofilm agent to combat the multidrug resistant P. aeruginosa infection.

19.
Angew Chem Int Ed Engl ; 59(39): 16961-16966, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32452120

RESUMO

N,N-dimethyl formamide (DMF) is an extensively used organic solvent but is also a potent pollutant. Certain bacterial species from genera such as Paracoccus, Pseudomonas, and Alcaligenes have evolved to use DMF as a sole carbon and nitrogen source for growth via degradation by a dimethylformamidase (DMFase). We show that DMFase from Paracoccus sp. strain DMF is a halophilic and thermostable enzyme comprising a multimeric complex of the α2 ß2 or (α2 ß2 )2 type. One of the three domains of the large subunit and the small subunit are hitherto undescribed protein folds of unknown evolutionary origin. The active site consists of a mononuclear iron coordinated by two Tyr side-chain phenolates and one carboxylate from Glu. The Fe3+ ion in the active site catalyzes the hydrolytic cleavage of the amide bond in DMF. Kinetic characterization reveals that the enzyme shows cooperativity between subunits, and mutagenesis and structural data provide clues to the catalytic mechanism.


Assuntos
Amidoidrolases/metabolismo , Dimetilformamida/metabolismo , Paracoccus/enzimologia , Tirosina/metabolismo , Amidoidrolases/química , Domínio Catalítico , Dimetilformamida/química , Estrutura Molecular , Tirosina/química
20.
Turk J Pediatr ; 61(2): 250-256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31951335

RESUMO

Nanjegowda CK, Kamath SP, Kamath P, Shah TD, Kulkarni V, Lashkari HP, Baliga BS. Comparison of diastolic function in children with transfusion dependent beta thalassemia major by tissue and conventional doppler imaging indices and its correlation with serum ferritin levels. Turk J Pediatr 2019; 61: 250-259. Regular blood transfusions for children with beta thalassemia major (ß- TM) results in iron overload cardiomyopathy/cardiac failure. Mortality in these children is most often because of heart failure. We compared Tissue Doppler Imaging (TDI) and conventional pulse wave Doppler (PWD) indices in evaluating diastolic function in chronically transfused ß-TM children and correlated the Doppler indices with mean serum ferritin levels. This was a prospective cross-sectional study conducted at tertiary teaching hospital. ß-TM children aged 3 to 18 years were enrolled as per inclusion criteria. PWD parameters at the mitral inflow (E, A, E/A and DT) and TDI parameters at the medial mitral annulus (E'and E/E') were used for estimation of diastolic dysfunction. Of the 66 children with thalassemia, the mean age was 10.2±3.77yrs and 60.6% were boys. The E/E' ratio estimated diastolic dysfunction (34/66, 51.5%) greater than four times that assessed by E/A ratio indices (8/66, 12.1%) in the subjects. Association of serum ferritin levels with E/E' ratio by chi square test was significant statistically (P=0.027), however was not significant with E/A ratio. By Mann Whitney test, the median serum ferritin levels (ng/ml) were higher [4034.50, (IQR-2084-5340.25) in those with diastolic dysfunction (abnormal E/E'), when compared to those with normal E/E'[2037.50(1510.75- 3572.25)], with their difference being significant (p=0.011), however serum ferritin levels were not significant with E/A ratio and DT. E/E' parameter had a sensitivity and specificity of 76.5% and 53.1% respectively at a mean serum ferritin cutoff level of 2076 ng/mL by ROC analysis. In conclusion, TDI is a more reliable modality for diagnosing early diastolic dysfunction when compared to PWD. Threshold level of serum ferritin greater than 2076 ng/mL is associated with increased incidence of diastolic dysfunction.


Assuntos
Transfusão de Sangue , Ecocardiografia Doppler/métodos , Ferritinas/sangue , Ventrículos do Coração/diagnóstico por imagem , Função Ventricular Esquerda/fisiologia , Talassemia beta/fisiopatologia , Adolescente , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos Transversais , Diástole , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Curva ROC , Talassemia beta/sangue , Talassemia beta/diagnóstico
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