Arylazo sulfones: multifaceted photochemical reagents and beyond.

The photochemical action of arylazo sulfones under visible light irradiation has recently gained considerable attention for the construction of carbon-carbon and carbon-heteroatom bonds in organic synthesis. The inherent dyedauxiliary group (-N2SO2R) embedded in the reagent is responsible for the absorption of visible light even in the absence of a photocatalyst, additive or oxidant, leading to the generation of three different radicals, viz. aryl (carbon-centred), sulfonyl (sulphur-centred) and diazenyl (nitrogen-centred) radicals, under different reaction conditions. Encountering a reagent with such a versatile behaviour is quite rare, which makes arylazo sulfones a highly interesting class of compounds. The mild reaction conditions under which these reagents can operate are an added advantage. Recently, they are also being used as non-ionic photoacid generators (PAGs), electron acceptors, and hydrogen atom transfer (HAT) and imination reagents in a number of synthetic transformations. They have displayed substantial damaging effect on the structure of DNA in the presence of light which can lead to their use as phototoxic pharmaceuticals for cancer treatment. Moreover, their photochemistry is also being exploited in polymerization reactions (as photoinitiators) and in materials chemistry (surface modification).

Paving the way to environment-friendly greener anesthesia.

Health-care settings have an important responsibility toward environmental health and safety. The operating room is a major source of environmental pollution within a hospital. Inhalational agents and nitrous oxide are the commonly used gases during general anesthesia for surgeries, especially in the developing world. These greenhouse gases contribute adversely to the environmental health both inside the operating room and in the outside atmosphere. Impact of these anesthetic agents depends on the total consumption, characteristics of individual agents, and gas flows, with higher levels increasing the environmental adverse effects. The inimical impact of nitrous oxide is higher due to its longer atmospheric half-life and potential for destruction of the ozone layer. Anesthesiologist of today has a choice in the selection of anesthetic agents. Prudent decisions will help in mitigating environmental pollution and contributing positively to a greener planet. Therefore, a shift from inhalational to intravenous-based technique will reduce the carbon footprint of anesthetic agents and their impact on global climate. Propofol forms the mainstay of intravenous anesthesia technique and is a proven drug for anesthetic induction and maintenance. Anesthesiologists should appreciate growing concerns about the role of inhalational anesthetics on the environment and join the cause of environmental responsibility. In this narrative review, we revisit the pharmacological and pharmacokinetic considerations, clinical uses, and discuss the merits of propofol-based intravenous anesthesia over inhalational anesthesia in terms of environmental effects. Increased awareness about the environmental impact and adoption of newer, versatile, and user-friendly modalities of intravenous anesthesia administration will pave the way for greener anesthesia practice.

Discovery of differentially expressed novel miRNAs in breast normal cells and their putative targets.

MicroRNAs (miRNAs) play critical role in normal breast development and their altered expression may lead to breast cancer. Identification of new miRNAs allows us to understand the normal physiological process and associated disease pathophysiology. In the present study we identify the novel miRNAs in withaferin A treated breast normal cells (MCF-10A) using small RNA sequencing. The pathophysiological potential of the identified miRNAs was checked by studying their expression pattern in MDA-MB-231 and MCF-7 breast cancer cells using qRT-PCR technique. The secondary/tertiary structure of the identified miRNAs, target gene enrichment in Gene Ontology terms and KEGG pathway, miRNA-mRNA interaction of the sorted target genes, miRNA-mRNA/miRNA-argonaute protein/miRNA-mRNA-argonaute protein interaction and stability, were studied using bioinformatics tools/software, and molecular dynamics simulations. Hsa-miR-N88585 and hsa-miR-N461089 were identified and validated as novel miRNAs in normal breast cells. Up-expression of identified miRNAs in MDA-MB-231 and MCF-7 cells indicates their oncogenic nature. Identified target genes were enriched in classical signaling pathways (AMPK and Ras) and important GO terms. PLXDC2, BHLHE40, ARMC8, and PECAM1, CDC27, KCNK3 genes were sorted as putative targets for hsa-miR-N88585 and hsa-miR-N461089, respectively. MD simulation revealed stable hsa-miR-N88585/hsa-miR-N461089-AGO protein complex formation which indicates their further processing. In conclusion, the study identifies hsa-miR-N88585 and hsa-miR-N461089 as novel miRNAs in breast normal cells which are significantly inversely expressed in breast cancer cells. Further experiments are required to study the role of identified novel miRNAs in normal breast development and pathophysiology of breast cancer.

Specific Genetic Polymorphisms Contributing in Differential Binding of Gliadin Peptides to HLA-DQ and TCR to Elicit Immunogenicity in Celiac Disease.

Immunogenicity of gliadin peptides in celiac disease (CD) is majorly determined by the pattern of molecular interactions with HLA-DQ and T-cell receptors (TCR). Investigation of the interactions between immune-dominant gliadin peptides, DQ protein, and TCR are warranted to unravel the basis of immunogenicity and variability contributed by the genetic polymorphisms. Homology modeling of HLA and TCR done using Swiss Model and iTASSER, respectively. Molecular interactions of eight common deamidated immune-dominant gliadin with HLA-DQ allotypes and specific TCR gene pairs were evaluated. Docking of the three structures was performed with ClusPro2.0 and ProDiGY was used to predict binding energies. Effects of known allelic polymorphisms and reported susceptibility SNPs were predicted on protein-protein interactions. CD susceptible allele, HLA-DQ2.5 was shown to have considerable binding affinity to 33-mer gliadin (ΔG = - 13.9; Kd = 1.5E - 10) in the presence of TRAV26/TRBV7. Higher binding affinity was predicted (ΔG = - 14.3, Kd = 8.9E - 11) when TRBV28 was replaced with TRBV20 paired with TRAV4 suggesting its role in CD predisposition. SNP rs12722069 at HLA-DQ8 that codes Arg76α forms three H-bonds with Glu12 and two H-bonds with Asn13 of DQ2 restricted gliadin in the presence of TRAV8-3/TRBV6. None of the HLA-DQ polymorphisms was found to be in linkage disequilibrium with reported CD susceptibility markers. Haplotypic presentations of rs12722069-G, rs1130392-C, rs3188043-C and rs4193-A with CD reported SNPs were observed in sub-ethnic groups. Highly polymorphic sites of HLA alleles and TCR variable regions could be utilized for better risk prediction models in CD. Therapeutic strategies by identifying inhibitors or blockers targeting specific gliadin:HLA-DQ:TCR binding sites could be investigated.

Flavonoids as emerging notch signaling pathway modulators in cancer.

Notch signaling is an evolutionary conserved pathway important for the developmental processes and implicated in the tumor formation. Notch signaling pathway (NSP) inhibitors have been tested in clinical trials alone or in combination with the chemotherapy but none got clinical approval due to severe toxicity in patients. Flavonoids inhibit NSP by inhibiting notch receptor cleavage and/or inhibiting transcriptional regulation by Notch intracellular domain (NICD). Interestingly, some flavonoids are reported to inhibit NSP by mediating the microRNA expression. NSP inhibitory flavonoid(s) in combination with standard therapy is might be an effective strategy in cancer treatment.

Every lid swelling is not stye: A rare presentation of scrub typhus eschar.

A 17-year-old female patient presented to us with complaints of diffuse swelling in her left upper eyelid with preauricular lymphadenopathy for three days. She was diagnosed with a case of hordeolum externum and was treated on the same line. However, during follow-up, she developed a mild- to moderate-grade fever, which did not subside with treatment. On further investigation, her IgM rapid ELISA for Scrub typhus was positive, which was further confirmed by the Weil-Fellix test (OXK=1:360). She was treated with systemic doxycycline. Within a week, her fever returned to normal baseline, with resolution of local eye lid swelling, and her black scab was also gone. We have reported a case of scrub typhus as a rare manifestation with lid swelling and subsequently eschar formation on the upper eye lid. The patient was promptly treated with oral antibiotics without any morbidity.

Phytochemicals present in Indian ginseng possess potential to inhibit SARS-CoV-2 virulence: A molecular docking and MD simulation study.

Coronaviruses are deadly and contagious pathogens that affects people in different ways. Researchers have increased their efforts in the development of antiviral agents against coronavirus targeting Mpro protein (main protease) as an effective drug target. The present study explores the inhibitory potential of characteristic and non-characteristic Withania somnifera (Indian ginseng) phytochemicals (n ≈ 100) against SARS-Cov-2 Mpro protein. Molecular docking studies revealed that certain W. somnifera compounds exhibit superior binding potential (-6.16 to -12.27 kcal/mol) compared to the standard inhibitors (-2.55 to -6.16 kcal/mol) including nelfinavir and lopinavir. The non-characteristic compounds (quercetin-3-rutinoside-7-glucoside, rutin and isochlorogenic acid B) exhibited higher inhibitory potential in comparison to characteristic W. somnifera compounds withanolide and withanone. Molecular dynamics (MD) simulation studies of the complex for 100 ns confirm favorable and stable binding of the lead molecule. The MMPBSA calculation of the last 10 ns of the protein-ligand complex trajectory exhibited stable binding of quercetin-3-rutinoside-7-glucoside at the active site of SARS-Cov-2 Mpro. Taken together, the study demonstrates that the non-characteristic compounds present in W. somnifera possess enhanced potential to bind SARS-Cov-2 Mpro active site. We further recommend in vitro and in vivo experimentation to validate the anti-SARS-CoV-2 potential of these lead molecules.

Experimental Biology 2020 Meeting Abstracts.

Bone morphogenetic proteins (BMPs) are growth factors that belong to the transforming growth factor-ß (TGF-ß) superfamily, and till date 15 BMPs have been described. BMPs, first described for their role in bone and cartilage formation, also play a role in renal fibrosis in chronic kidney disease (CKD). There is evidence to indicate that in rodent models of CKD, administration of recombinant BMP1-3 increases renal fibrosis whereas administration of a BMP1-3-neutralizing antibody or BMP-7 antibody reduces renal fibrosis and preserves renal function. The aim of the present study was to investigate changes in gene expression in the renal cortex obtained from cats with kidney disease or calcium oxalate stone formers (CaOx) at necropsy, to identify BMPs associated with renal dysfunction in cats and potential fibrosis. At time of death the circulating levels of creatinine as well as symmetric dimethyl arginine (SDMA), both markers of kidney decline in cats, were significantly higher in cats with renal disease (n=11) or stone-forming cats (CaOx, n=12) when compared to controls (n=19). Using RNAseq in kidney tissue, we found a modest, but significant, increase in the expression of BMP-1 in cats with kidney disease (2.48 fold) and stone formers (1.72 fold), compared to controls (both p<0.01). While the increase in BMP-2 in CaOx cats was significant (1.46 fold; p<0.05 vs Con), the increase in cats with kidney disease was not (1.23 fold; NS). BMP2K, a BMP-2 inducible kinase, was significantly increased in both kidney disease (1.43 fold) and CaOX (1.46 fold) (both p<0.05). In contrast, a significant decrease in BMP4 was observed in both groups (<2.2 fold and 1.68 fold in kidney disease and CaOx, respectively; both p<0.001 vs Con). A decrease was also seen in CRIM 1, a protein associated with podocyte filtration function and whose reduction is associated with fibrosis, in both groups. BMP-7, whose potential therapeutic role in treating CKD and reversing fibrosis has been documented, was modestly decreased in both groups (both less than 1.5 fold) compared to controls. Given that there was an increase in all three forms of TGFß (TGFß1, TGFß2, and TGFß3), a potent initiator of renal fibrosis, in both groups, and a decline in BMP-7, an endogenous inhibitor of TGFß signaling in fibrosis, compared to controls, our results profile the BMPs potentially associated with renal fibrosis in cats that may contribute to kidney dysfunction. In summary, a nutritional therapy to slow the progression of kidney dysfunction may benefit from the inclusion of dietary ingredients that attenuate renal fibrosis in cats. SUPPORT OR FUNDING INFORMATION: This study was funded by Hill's Pet Nutrition, Inc.

Role of ZBTB7A zinc finger in tumorigenesis and metastasis.

The zinc finger and BTB (broad-complex, tramtrack and bric a brac) domain containing protein 7A (ZBTB7A) is a pleiotropic transcription factor that plays an important role in various stages of cell proliferation, differentiation, and other developmental processes. ZBTB7A is a member of the POK family that directly and specifically binds to short DNA recognition sites located near their target genes thereby acting as transcriptional activator or repressor. ZBTB7A overexpression has been associated with tumorigenesis and metastasis in various human cancer types, including breast, prostate, lung, ovarian, and colon cancer. However in some instances downregulation of ZBTB7A results in tumor progression, suggesting its role as a tumor suppressor. ZBTB7A is involved with complicated regulatory networks which include protein-protein and protein-nucleic acid interactions. ZBTB7A involvement in cancer progression and metastasis is perhaps enabled through the regulation of various signaling pathways depending on the type and genetic context of cancer. The association of ZBTB7A with other proteins affects cancer aggressiveness, therapeutic resistance and clinical outcome. This review focuses on the involvement of ZBTB7A in various signaling pathways and its role in cancer progression. We will also review the literature on ZBTB7A and cancer which could be potentially explored for its therapeutic implications.

Induction of apoptosis in breast cancer cells by naphthylisoquinoline alkaloids.

Breast cancer is one of the most common types of cancer in the world and a major cause of mortality. Present therapeutic strategies against breast cancer have severe drawbacks such as allergies, damage to healthy tissues, reoccurrence of cancer, and emergence of drug resistance. Naphthylisoquinoline alkaloids are a group of structurally unique natural products produced by tropical lianas belonging to the plant families Dioncophyllaceae and Ancistrocladaceae indigenous to Asia and Africa. These secondary metabolites have been reported to show anti-infective activity, but they also act against leukemic and pancreatic cancer cells. In the present study we have tested the potential of eleven mono- and dimeric naphthylisoquinoline compounds against two breast cancer cell lines, MCF-7 and MDA-MB-231. Three out of the compounds (agents 1, 4, and 11) showed significant activities against both tested cancer cell lines. Further mechanistic investigations revealed that all of the three substances induce apoptotic cell death via its intrinsic pathway by causing deformation of the nuclear membrane, disruption of the mitochondrial membrane potential (MMP), and elevated reactive oxygen species (ROS) production in both cell lines. Flow cytometric analysis using Annexin V - FITC/PI double staining showed an increased number of apoptotic cells in both, the early and the late phases.

Recent Advances in Radical C-H Activation/Radical Cross-Coupling.

Research and industrial interest in radical C-H activation/radical cross-coupling chemistry has continuously grown over the past few decades. These reactions offer fascinating and unconventional approaches toward connecting molecular fragments with high atom- and step-economy that are often complementary to traditional methods. Success in this area of research was made possible through the development of photocatalysis and first-row transition metal catalysis along with the use of peroxides as radical initiators. This Review provides a brief and concise overview of the current status and latest methodologies using radicals or radical cations as key intermediates produced via radical C-H activation. This Review includes radical addition, radical cascade cyclization, radical/radical cross-coupling, coupling of radicals with M-R groups, and coupling of radical cations with nucleophiles (Nu).

Animal-Use Antibiotics Induce Cross-Resistance in Bacterial Pathogens to Human Therapeutic Antibiotics.

Exposure of bacteria to a sub-lethal dosage of antibiotic is one the major causes for the onset of antibiotic resistance. Therefore, we aimed to assess the emergence of antibiotic cross-resistance in bacteria after exposure to a sub-lethal dose of veterinary feed directive (VFD) antibiotics, tilmicosin, and florfenicol. The minimum inhibitory concentrations (MICs) of tilmicosin and florfenicol against Salmonella enterica serovar Enteritidis, Klebsiella pneumoniae, Staphylococcus aureus, and Listeria monocytogenes were determined. Next, the pathogens were exposed to a sub-inhibitory concentration of tilmicosin (0.5, 5, 20 µg/ml) and florfenicol (1, 20 µg/ml) for 24 h and 48 h, and acquired cross-resistance to human therapeutic antibiotics was measured by determining the increase in MIC values. MICs of ampicillin, tetracycline, nalidixic acid, and meropenem against Salmonella and Klebsiella were in the range of 20-1000 µg/ml, 5-62.5 µg/ml, 5-125 µg/ml, and 0.05-0.1 µg/ml, respectively, whereas MICs against Staphylococcus and Listeria were 2.5-10 µg/ml, 2.5 µg/ml, 62.5-500 µg/ml, and 0.1-0.2 µg/ml, respectively. Pre-exposure of these bacteria to a sub-inhibitory concentration of tilmicosin and florfenicol, increased cross-resistance against ampicillin, tetracycline, and nalidixic acid from 1.25- to 40-fold compared to the antibiotic unexposed bacteria with the exception of meropenem, which did not show increased resistance. This study could serve as a foundation to understand the mechanisms of acquired cross-resistance to traditional therapeutic antibiotics, and to develop strategies to alleviate such problem by using alternative antimicrobials.

Molecular characterisation and transcriptional regulation of muscle growth regulatory factors myogenin and myogenic factor 6 in the Trans-Himalayan cyprinid fish Schizothorax richardsonii.

In vertebrates, myogenic regulatory factors (MRFs) play an important role in muscle growth through the processes of cell determination and differentiation. Herein, we report the molecular characterisation of two MRFs, myogenin (myog) and myogenic factor 6 (myf6) in Indian snow trout Schizothorax richardsonii. The full length mRNA sequence of Srmyog and Srmyf6 was 1437 and 1296 bp, with an ORF of 762 and 720 bp, encoding a putative protein of 253 and 239 amino acids, respectively. In silico analysis and predicted tertiary protein structure revealed that both these nuclear localized MRFs contained the highly conserved basic helix loop helix motif, to potentially aid in dimerization with functional partners and DNA binding. Phylogenetically, the deduced protein sequences of Srmyog and Srmyf6 closely clustered with high altitude dwelling cyprinids, suggesting common ancestry. Tissue-wise, transcripts of Srmyog and Srmyf6 were abundant in skeletal muscle, affirming their muscle-specific role. Moreover, Srmyog was highly expressed in females as compared to males, whereas Srmyf6 expression was higher in older-bigger individuals as compared to younger-smaller fish. Nutritional status (fed-starved-refed) and diet composition (protein and lipid levels) had no significant influence on Srmyog expression. But, Srmyf6 expression was elevated in fishes re-fed after 3 weeks of starvation and in those fed low protein diet. Only rearing temperature was found to coherently influence Srmyog and Srmyf6 transcripts, with highest expression at 18 °C, which favoured growth. Overall, molecular characterisation of the structure and regulation of these MRFs is the first step taken towards deciphering slow growth in this important Himalayan cyprinid.

Rapid detection and differentiation of Staphylococcus colonies using an optical scattering technology.

Staphylococcus species are a major pathogen responsible for nosocomial infections and foodborne illnesses. We applied a laser-based BARDOT (bacterial rapid detection using optical scattering technology) for rapid colony screening and detection of Staphylococcus on an agar plate and differentiate these from non-Staphylococcus spp. Among the six growth media tested, phenol red mannitol agar (PRMA) was found most suitable for building the Staphylococcus species scatter image libraries. Scatter image library for Staphylococcus species gave a high positive predictive value (PPV 87.5-100%) when tested against known laboratory strains of Staphylococcus spp., while the PPV against non-Staphylococcus spp. was 0-38%. A total of nine naturally contaminated bovine raw milk and ready-to-eat chicken salad samples were tested, and BARDOT detected Staphylococcus including Staphylococcus aureus with 80-100% PPV. Forty-five BARDOT-identified bacterial isolates from naturally contaminated foods were further confirmed by tuf and nuc gene-specific PCR and 16S rRNA gene sequence. This label-free, non-invasive on-plate colony screening technology can be adopted by the food industries, biotechnology companies, and public health laboratories for Staphylococcus species detection including S. aureus from various samples for food safety and public health management. Graphical abstract.

Investigating essential gene function in Mycobacterium tuberculosis using an efficient CRISPR interference system.

Despite many methodological advances that have facilitated investigation of Mycobacterium tuberculosis pathogenesis, analysis of essential gene function in this slow-growing pathogen remains difficult. Here, we describe an optimized CRISPR-based method to inhibit expression of essential genes based on the inducible expression of an enzymatically inactive Cas9 protein together with gene-specific guide RNAs (CRISPR interference). Using this system to target several essential genes of M. tuberculosis, we achieved marked inhibition of gene expression resulting in growth inhibition, changes in susceptibility to small molecule inhibitors and disruption of normal cell morphology. Analysis of expression of genes containing sequences similar to those targeted by individual guide RNAs did not reveal significant off-target effects. Advantages of this approach include the ability to compare inhibited gene expression to native levels of expression, lack of the need to alter the M. tuberculosis chromosome, the potential to titrate the extent of transcription inhibition, and the ability to avoid off-target effects. Based on the consistent inhibition of transcription and the simple cloning strategy described in this work, CRISPR interference provides an efficient approach to investigate essential gene function that may be particularly useful in characterizing genes of unknown function and potential targets for novel small molecule inhibitors.

Glaucoma awareness Indian military personnel: a tri-service study.

INTRODUCTION: In India, glaucoma is the third most common cause of blindness, reflecting both its asymptomatic presentation and a lack of knowledge in the general population. No previous published data of glaucoma awareness among the Indian Armed forces personnel exists, who constitute a unique group consisting of people drawn from all parts of the country and society. METHODS: Bilingual questionnaires were distributed to 496 serving Army, Navy and Air Force personnel serving in units local to the Zonal military hospital in North India. Having heard of the term glaucoma resulted in the subject being 'glaucoma aware', while 'knowledge of glaucoma' required at least three out of six questions to be answered correctly. RESULTS: 110/496 (22%) participants were found to be glaucoma aware, while knowledge of glaucoma was found in 60/496 (12%) participants. CONCLUSIONS: This study demonstrates that glaucoma awareness and knowledge is high compared with rural or urban Indian populations. This is likely reflects the frequent health camps conducted by the armed forces and periodic medical examinations. However, these figures are still low compared with developed countries and likely reflects differences in education standards, socioeconomic status and differing influences of the media.

Erratum: Kim, K.-P.; Singh, A.K.; Bai, X.; Leprun, L.; Bhunia, A.K. Novel PCR Assays Complement Laser Biosensor-Based Method and Facilitate Listeria Species Detection from Food. Sensors 2015, 15, 22672-22691.

The authors wish to correct the oligonucleotide sequence of primer E-LAP-F1 and LIS-R1 in Table 1in their paper published in Sensors [1], doi:10.3390/s150922672, http://www.mdpi.com/1424-8220/15/9/22672. The following table should be used.[...].

Photocatalytic Dehydrogenative Cross-Coupling of Alkenes with Alcohols or Azoles without External Oxidant.

Direct cross-coupling between alkenes/R-H or alkenes/RXH is a dream reaction, especially without external oxidants. Inputting energy by photocatalysis and employing a cobalt catalyst as a two-electron acceptor, a direct C-H/X-H cross-coupling with H2 evolution has been achieved for C-O and C-N bond formation. A new radical alkenylation using alkene as the redox compound is presented. A wide range of aliphatic alcohols-even long chain alcohols-are tolerated well in this system, providing a new route to multi-substituted enol ether derivatives using simple alkenes. Additionally, this protocol can also be used for N-vinylazole synthesis. Mechanistic insights reveal that the cobalt catalyst oxidizes the photocatalyst to revive the photocatalytic cycle.

Anti-Markovnikov Oxidation of ß-Alkyl Styrenes with H2O as the Terminal Oxidant.

Oxygenation of alkenes is one of the most straightforward routes for the construction of carbonyl compounds. Wacker oxidation provides a broadly useful strategy to convert the mineral oil into higher value-added carbonyl chemicals. However, the conventional Wacker chemistry remains problematic, such as the poor activity for internal alkenes, the lack of anti-Markovnikov regioselectivity, and the high cost and chemical waste resulted from noble metal catalysts and stoichiometric oxidant. Here, we describe an unprecedented dehydrogenative oxygenation of ß-alkyl styrenes and their derivatives with water under external-oxidant-free conditions by utilizing the synergistic effect of photocatalysis and proton-reduction catalysis that can address these challenges. This dual catalytic system possesses the single anti-Markovnikov selectivity due to the property of the visible-light-induced alkene radical cation intermediate.

Factors affecting redox potential and differential sensitivity of SoxR to redox-active compounds.

SoxR is a [2Fe-2S]-containing sensor-regulator, which is activated through oxidation by redox-active compounds (RACs). SoxRs show differential sensitivity to RACs, partly due to different redox potentials, such that Escherichia coli (Ec) SoxR with lower potential respond to broader range of RACs than Streptomyces coelicolor (Sc) SoxR. In S. coelicolor, the RACs that do not activate ScSoxR did not inhibit growth, suggesting that ScSoxR is tuned to respond to growth-inhibitory RACs. Based on sequence comparison and mutation studies, two critical amino acids around the [2Fe-2S] binding site were proposed as key determinants of sensitivity. ScSoxR-like mutation (R127L/P131V) in EcSoxR changed its sensitivity profile as ScSoxR, whereas EcSoxR-like mutation (L126R/V130P) in ScSoxR caused relaxed response. In accordance, the redox potentials of EcSoxR(R) (127) (L) (/) (P) (131) (V) and ScSoxR(L126R/V130P) were estimated to be -192 ± 8 mV and -273 ± 10 mV, respectively, approaching that of ScSoxR (-185 mV) and EcSoxR (-290 mV). Molecular dynamics simulations revealed that the R127L and P131V substitutions in EcSoxR caused more electropositive environment around [2Fe-2S], making it harder to get oxidized. This reveals a mechanism to modulate redox-potential in [Fe-S]-containing sensors by point mutations and to evolve a sensor with differential sensitivity to achieve optimal cellular physiology.