Instabilities and self-organization in spatiotemporal epidemic dynamics driven by nonlinearity and noise.

Theoretical analysis of epidemic dynamics has attracted significant attention in the aftermath of the COVID-19 pandemic. In this article, we study dynamic instabilities in a spatiotemporal compartmental epidemic model represented by a stochastic system of coupled partial differential equations (SPDE). Saturation effects in infection spread-anchored in physical considerations-lead to strong nonlinearities in the SPDE. Our goal is to study the onset of dynamic, Turing-type instabilities, and the concomitant emergence of steady-state patterns under the interplay between three critical model parameters-the saturation parameter, the noise intensity, and the transmission rate. Employing a second-order perturbation analysis to investigate stability, we uncover both diffusion-driven and noise-induced instabilities and corresponding self-organized distinct patterns of infection spread in the steady state. We also analyze the effects of the saturation parameter and the transmission rate on the instabilities and the pattern formation. In summary, our results indicate that the nuanced interplay between the three parameters considered has a profound effect on the emergence of dynamical instabilities and therefore on pattern formation in the steady state. Moreover, due to the central role played by the Turing phenomenon in pattern formation in a variety of biological dynamic systems, the results are expected to have broader significance beyond epidemic dynamics.

EEG Correlates of Suggestion-Induced Stroop Interference Reduction in High-Suggestible Individuals: A Systematic Review and Meta-Analysis.

Studies have explored the impact of suggestion on the Stroop effect, aiming to understand how effective suggestion is in modulating this phenomenon. The suggestion effect has been replicated in multiple studies, supporting its robustness, but lacks systematic evaluation. We conducted a systematic review and meta-analysis of relevant English-language studies from PubMed, Web of Science, PsycINFO, Scopus, and ScienceDirect since databases inception until January 2023. Quality of included studies was evaluated using the Joanna Briggs Institute (JBI) appraisal checklist, and potential publication biases were assessed. Subgroup analyses were also performed, and effect sizes were estimated using Hedges' g and analyzed using random effects model. The systematic review was comprised of 19 studies. For the meta-analysis, 14 studies examined the suggestion effect on Stroop interference effect (SIE), while six studies investigated suggestion effects on accuracy. Results have revealed significant overall effects of suggestion on Stroop performance in participants, as evidenced by SIE and accuracy. Subgroup analysis based on types of suggestion demonstrated a significant effect on SIE. Six EEG/ERP studies have also been discussed in the context of the review.

Performance monitoring and error detection: The role of mid frontal theta and error-related negativity (ERN) among Indian adolescents from different socioeconomic background.

The aim of the study was to investigate the relationship between socioeconomic status (SES) and executive functioning, focusing specifically on performance monitoring, error detection, and their association with mid-frontal theta and error-related negativity (ERN). Employing the widely used flanker task, the research involved two phases with participants aged 10-16 years (15 individuals in the pilot phase and 35 in the second phase). Electroencephalogram (EEG) recordings from distinct brain regions were analyzed during various conditions. The study revealed a notable increase in both absolute and relative theta power at Fcz during the flanker task, with a stronger effect observed during incorrect trials. Furthermore, it underscored the influence of socioeconomic status (SES) on mid-frontal theta, highlighting interactions between SES, gender, and experimental conditions impacting both absolute and relative theta. Intriguingly, the research disclosed a positive correlation between parental occupation and error-related negativity (ERN), as well as between age and ERN. These findings underscore the significance of SES, gender, and age in shaping the neural mechanisms associated with performance monitoring and executive functions. The study contributes valuable insights into the intricate interplay between socio-demographic factors and cognitive processes, shedding light on their impact on goal-directed behaviors and brain activity.

Recent Advances in the Treatment Strategies of Friedreich's Ataxia: A Review of Potential Drug Candidates and their Underlying Mechanisms.

BACKGROUND: Friedreich's Ataxia (FRDA) is a rare hereditary neurodegenerative disorder characterized by progressive ataxia, cardiomyopathy, and diabetes. The disease is caused by a deficiency of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and iron metabolism. OBJECTIVE: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action. METHODS: A comprehensive literature search was conducted using various authentic scientific databases to identify studies published in the last decade that investigated potential treatment strategies for FRDA. The search terms used included "Friedreich's ataxia", "treatment", "drug candidates", and "mechanisms of action". RESULTS: To date, only one drug got approval from US-FDA in the year 2023; however, significant developments were achieved in FRDA-related research focusing on diverse therapeutic interventions that could potentially alleviate the symptoms of this disease. Several promising drug candidates have been identified for the treatment of FRDA, which target various aspects of frataxin deficiency and aim to restore frataxin levels, reduce oxidative stress, and improve mitochondrial function. Clinical trials have shown varying degrees of success, with some drugs demonstrating significant improvements in neurological function and quality of life in FRDA patients. CONCLUSION: While there has been significant progress in the development of treatment strategies for FRDA, further research is needed to optimize these approaches and identify the most effective and safe treatment options for patients. The integration of multiple therapeutic strategies may be necessary to achieve the best outcomes in FRDA management.

Hydrocarbon stapled temporin-L analogue as potential antibacterial and antiendotoxin agents with enhanced protease stability.

Antimicrobial resistance (AMR) is a serious global concern and a huge burden on the healthcare system. Antimicrobial peptides (AMPs) are considered as a solution of AMR due to their membrane-lytic and intracellular mode of action and therefore resistance development against AMPs is less frequent. One such AMPs, temporin-L (TL) is a 13-mer peptide reported as a potent and broad-spectrum antibacterial agent with significant immunomodulatory activity. However, TL is toxic to human erythrocytes at their antibacterial concentrations and therefore various analogues were synthesized with potent antimicrobial activity and lower hemolytic activity. In this work, we have selected a non-toxic engineered analogue of TL (eTL) and performed hydrocarbon stapling of amino acid residues at i to i + 4 positions at different part of sequence. The synthesized peptides were investigated against both the gram-positive and gram-negative bacteria as well as methicillin resistant S. aureus, its MIC was measured in the concentrations range of 0.9-15.2 µM. All analogues were found equal or better antibacterial as compared to parent peptide. Interestingly one analogue eTL [5-9] was found to be non-cytotoxic and stable in presence of the human serum. Mode of action studies revealed membrane depolarizing and disruptive mode of action with live MRSA. Further in vivo studies of antimicrobial against MRSA infection and anti-endotoxin activities in mice model revealed potential activity of the stapled peptide analogue. Overall, this reports on stapled analogue of the AMPs highlights an important strategy for the development of new antibacterial therapeutics against AMR.

Pediatric oncology services in Nepal: A special focus on pharmacy practice.

The role of clinical pharmacists or oncology pharmacists in pediatric oncology has been established as important in anticancer regimen review, dose calculation, recommendation, chemocounseling, identification of drug-related problems, its resolution, and, prevention and monitoring of adverse drug reactions within high-income countries. With several hospitals providing pediatric oncology services in Nepal, clinical pharmacist involvement in these hospitals is very poor. Upon reviewing the reputed organization and association focused on pediatric oncology pharmacy practice, it looks imperative for Nepal to initiate clinical pharmacy services which will further help in improving patient health outcomes. As such in this commentary, we try to accentuate the pediatric oncology services and pediatric pharmacy practice within Nepal and try to pinpoint the potential areas for clinical pharmacists to focus if they intend to provide services in pediatric oncology pharmacy practice.

Tracing the serendipitous genesis of radiation resistance.

Free-living organisms frequently encounter unfavorable abiotic environmental factors. Those who adapt and cope with sudden changes in the external environment survive. Desiccation is one of the most common and frequently encountered stresses in nature. On the contrary, ionizing radiations are limited to high local concentrations of naturally occurring radioactive materials and related anthropogenic activities. Yet, resistance to high doses of ionizing radiation is evident across the tree of life. The evolution of desiccation resistance has been linked to the evolution of ionizing radiation resistance, although, evidence to support the idea that the evolution of desiccation tolerance is a necessary precursor to ionizing radiation resistance is lacking. Moreover, the presence of radioresistance in hyperthermophiles suggests multiple paths lead to radiation resistance. In this minireview, we focus on the molecular aspects of damage dynamics and damage response pathways comprising protective and restorative functions with a definitive survival advantage, to explore the serendipitous genesis of ionizing radiation resistance.

Andrographis paniculata and Andrographolide - A Snapshot on Recent Advances in Nano Drug Delivery Systems against Cancer.

Cancer is one of the deadliest illnesses of the 21st century. Chemotherapy and radiation therapies both have considerable side effects. Antitumor antibiotics are one of them. Coughs, common colds, fevers, laryngitis, and infectious disorders have all been treated with Andrographis paniculata for centuries. Extracts of Andrographis effectively treat various ailments, as well as cancer. The most active molecule in Andrographis paniculata is andrographolide a, diterpene, and lactone. Andrographis paniculata and its derivatives have long been used to treat various ailments. Anti-inflammatory and cancerfighting characteristics have been observed in Andrographolide. Andrographolide, a diterpene lactone separated from Andrographis paniculata, has also been shown to have important criticalessential biological protective properties. It has also been suggested that it could be used to treat major human diseases like-rheumatoid like rheumatoid, colitis, and Parkinsons disease. This summary aims to highlight Andrographolide as a promising cancer treatment option. Several databases were searched for andrographolides cytotoxic/anti-cancer effects in pre-clinical and clinical research to serve this purpose. Several studies have shown that Andrographolide is helpful in cancer medication, as detailed in this review.

Deinococcus lineage and Rad52 family-related protein DR0041 is involved in DNA protection and compaction.

DR0041 ORF encodes an uncharacterized Deinococcus lineage protein. We earlier reported presence of DR0041 protein in DNA repair complexes of Ssb and RecA in Deinococcus radiodurans. Here, we systematically examined the role of DR0041 in DNA metabolism using various experimental methodologies including electrophoretic mobility assays, nuclease assays, strand exchange assays and transmission electron microscopy. Interaction between DR0041 and the C-terminal acidic tail of Ssb was assessed through co-expression and in vivo cross-linking studies. A knockout mutant was constructed to understand importance of DR0041 ORF for various physiological processes. Results highlight binding of DR0041 protein to single-stranded and double-stranded DNA, interaction with Ssb-coated single-stranded DNA without interference with RecA-mediated strand exchange, protection of DNA from exonucleases, and compaction of high molecular weight DNA molecules into tightly condensed forms. Bridging and compaction of sheared DNA by DR0041 protein might have implications in the preservation of damaged DNA templates to maintain genome integrity upon exposure to gamma irradiation. Our results suggest that DR0041 protein is dispensable for growth under standard growth conditions and following gamma irradiation but contributes to protection of DNA during transformation. We discuss the role of DR0041 protein from the perspective of protection of broken DNA templates and functional redundancy.

Enantioselective Synthesis of Octahydrofuranoindole Core of Aspidosperma Alkaloids via a Diels-Alder/Reduction/Fluoroetherification Reaction Sequence.

Herein, we disclose the enantioselective synthesis of novel tricyclic fluorooctahydrofuranoindole spirooxindoles bearing five contiguous stereocenters via an organocatalytic sequential Diels-Alder/Reduction/Fluoroetherifiction reaction strategy. The potential of the developed approach was witnessed by generating vast examples (up to 20 examples) of library molecules embedding natural product core with good yields and phenomenal diastereo- and enantioselectivities (up to 77 % overall yield, up to 99 % ee and 10 : 1 dr). The synthetic utility of our protocol was further demonstrated by synthesizing tricyclic iodooctahydroindole spirooxindole framework through sequential Diels-Alder/reduction/iodoetherification reaction in 65 % overall yield and excellent stereoselectivity (99 % ee and 4 : 1 dr).

Biochemical and histopathological alterations in freshwater fish, Labeo rohita (Hamilton, 1822) upon chronic exposure to a commonly used hopper insecticide, triflumezopyrim.

The present study has been carried out to see the long-term effects of triflumezopyrim in an Indian major carp, Labeo rohita. Fishes were exposed to sub-lethal concentrations triflumezopyrim insecticide, 1.41 ppm (Treatment 1), 3.27 ppm (Treatment 2) and 4.97 ppm (Treatment 3), respectively for 21 days. The liver, kidney, gills, muscle, and brain tissues of the fish were examined for physiological parameters and biochemical parameters such as catalase (CAT), superoxide dismutase (SOD), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), acetylcholinessterase (AChE), and hexokinase. After 21 days of exposure, the activity CAT, SOD, LDH, MDH and ALT got increased and a drop in the activity of total protein was found in all treatment groups in comparison to the control group. Long-term triflumezopyrim exposure increased ROS production, ultimately leading to oxidative cell damage and inhibiting the antioxidant capabilities of the fish tissues. Histopathological analysis showed alteration in different tissues structures of pesticide treated fishes. Fishes exposed to highest sublethal concentration of the pesticide showed higher damage rate. The present study demonstrated that chronic exposure of fish to different sublethal concentration of triflumezopyrim exerts detrimental effect on the organism.

Poly- and Perfluoroalkyl Substances (PFAS): Do They Matter to Aquatic Ecosystems?

Poly- and perfluoroalkyl substances (PFASs) are a group of anthropogenic chemicals with an aliphatic fluorinated carbon chain. Due to their durability, bioaccumulation potential, and negative impacts on living organisms, these compounds have drawn lots of attention across the world. The negative impacts of PFASs on aquatic ecosystems are becoming a major concern due to their widespread use in increasing concentrations and constant leakage into the aquatic environment. Furthermore, by acting as agonists or antagonists, PFASs may alter the bioaccumulation and toxicity of certain substances. In many species, particularly aquatic organisms, PFASs can stay in the body and induce a variety of negative consequences, such as reproductive toxicity, oxidative stress, metabolic disruption, immunological toxicity, developmental toxicity, cellular damage and necrosis. PFAS bioaccumulation plays a significant role and has an impact on the composition of the intestinal microbiota, which is influenced by the kind of diet and is directly related to the host's well-being. PFASs also act as endocrine disruptor chemicals (EDCs) which can change the endocrine system and result in dysbiosis of gut microbes and other health repercussions. In silico investigation and analysis also shows that PFASs are incorporated into the maturing oocytes during vitellogenesis and are bound to vitellogenin and other yolk proteins. The present review reveals that aquatic species, especially fishes, are negatively affected by exposure to emerging PFASs. Additionally, the effects of PFAS pollution on aquatic ecosystems were investigated by evaluating a number of characteristics, including extracellular polymeric substances (EPSs) and chlorophyll content as well as the diversity of the microorganisms in the biofilms. Therefore, this review will provide crucial information on the possible adverse effects of PFASs on fish growth, reproduction, gut microbial dysbiosis, and its potential endocrine disruption. This information aims to help the researchers and academicians work and come up with possible remedial measures to protect aquatic ecosystems as future works need to be focus on techno-economic assessment, life cycle assessment, and multi criteria decision analysis systems that screen PFAS-containing samples. New innovative methods requires further development to reach detection at the permissible regulatory limits.

Significant destabilization of human telomeric G-quadruplex upon peptide binding: dramatic effect of flanking bases.

Human telomere is composed of highly repeated hexanucleotide sequence TTAGGG and a 3' single-stranded DNA tail. Many telomere G4 topologies characterized at atomic level by X-ray crystallography and NMR studies. Until now, various small ligands developed to interact with G-quadruplex mainly to stabilize the structure and least is known for its destabilization. In this study, we provide the first evidence of human telomeric G4 destabilization upon peptide binding in dilute and cell-mimicking molecular crowing conditions due to the changes in flanking bases of human telomeric sequences. Hence, our findings will open the new ways to target diseases related with increasing the efficiency of DNA replication, transcription or duplex reannealing.Communicated by Ramaswamy H. Sarma.

Outcome of Malnourished Children Admitted in the Nutritional Rehabilitation Home.

BACKGROUND: Globally, the burden of malnutrition, especially undernutrition, as well as the consequences of malnutrition is of the rise which is especially of significant concern for underdeveloped countries. Countries like Nepal are also facing a similar problem of malnutrition. In Madhesh province, among the under 5 children the incidence of chronic malnutrition is 29.3%. Our aim is to assess the malnourishment in the children of Madhesh province in Nepal. METHODS: This cross-sectional quantitative study was carried out among 409 malnourished children who were admitted from July 17, 2018 to July 16, 2022 at NRH in Gajendra Narayan Singh Hospital. Collected data were fed into Microsoft-excel and analyzed using SPSS software, version-2016. As data were normally distributed, frequency, percentage, mean and standard deviation were calculated for descriptive analysis. To find out the association of categorical variables, the Chi-square test or Fisher's Exact test was used where appropriate. P-value <0.05 was significant. RESULTS: Out of 409 malnourished cases, 145 cases were SAM (SD<-3) and 264 cases were MAM (-2 to -3SD) at the time of admission. The mean increment in the weight was 1.14±0.44  kg.  The average length of stay was 19.82±8.73 days. There is a significant difference (p<0.001) in the length of stay among the SAM and MAM cases of our study and a difference in the increment of weight in comparison to mean weight gain (1.14±0.44  kg) with respect to the length of stay of the malnourished child who stayed for more than 28 days and less. CONCLUSIONS: There is significant weight gain in malnourished children after management at the Nutritional Rehabilitation Center.

Recognition and unfolding of human telomeric G-quadruplex by short peptide binding identified from the HRDC domain of BLM helicase.

Research in recent decades has revealed that the guanine (G)-quadruplex secondary structure in DNA modulates a variety of cellular events that are mostly related to serious diseases. Systems capable of regulating DNA G-quadruplex structures would therefore be useful for the modulation of various cellular events to produce biological effects. A high specificity for recognition of telomeric G-quadruplex has been observed for BLM helicase. We identified peptides from the HRDC domain of BLM using a molecular docking approach with various available solutions and crystal structures of human telomeres and recently created a peptide library. Herein, we tested one peptide (BLM HRDC peptide) from the library and examined its interaction with human telomeric variant-1 (HTPu-var-1) to understand the basis of G4-protein interactions. Our circular dichroism (CD) data showed that HTPu-var-1 folded into an anti-parallel G-quadruplex, and the CD intensity significantly decreased upon increasing the peptide concentration. There was a significant decrease in hypochromicity due to the formation of G-quadruplex-peptide complex at 295 nm, which indicated the unfolding of structure due to the decrease in stacking interactions. The fluorescence data showed quenching upon titrating the peptide with HTPu-var-1-G4. Electrophoretic mobility shift assay confirmed the unfolding of the G4 structure. Cell viability was significantly reduced in the presence of the BLM peptide, with IC50 values of 10.71 µM and 11.83 µM after 72 and 96 hours, respectively. These results confirmed that the selected peptide has the ability to bind to human telomeric G-quadruplex and unfold it. This is the first report in which a peptide was identified from the HRDC domain of the BLM G4-binding protein for the exploration of the G4-binding motif, which suggests a novel strategy to target G4 using natural key peptide segments.

SNPs in miRNAs and Target Sequences: Role in Cancer and Diabetes.

miRNAs are fascinating molecular players for gene regulation as individual miRNA can control multiple targets and a single target can be regulated by multiple miRNAs. Loss of miRNA regulated gene expression is often reported to be implicated in various human diseases like diabetes and cancer. Recently, geneticists across the world started reporting single nucleotide polymorphism (SNPs) in seed sequences of miRNAs. Similarly, SNPs are also reported in various target sequences of these miRNAs. Both the scenarios lead to dysregulated gene expression which may result in the progression of diseases. In the present paper, we explore SNPs in various miRNAs and their target sequences reported in various human cancers as well as diabetes. Similarly, we also present evidence of these mutations in various other human diseases.

Identification of vaccine targets in pathogens and design of a vaccine using computational approaches.

Antigen identification is an important step in the vaccine development process. Computational approaches including deep learning systems can play an important role in the identification of vaccine targets using genomic and proteomic information. Here, we present a new computational system to discover and analyse novel vaccine targets leading to the design of a multi-epitope subunit vaccine candidate. The system incorporates reverse vaccinology and immuno-informatics tools to screen genomic and proteomic datasets of several pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Vibrio cholerae to identify potential vaccine candidates (PVC). Further, as a case study, we performed a detailed analysis of the genomic and proteomic dataset of T. cruzi (CL Brenner and Y strain) to shortlist eight proteins as possible vaccine antigen candidates using properties such as secretory/surface-exposed nature, low transmembrane helix (< 2), essentiality, virulence, antigenic, and non-homology with host/gut flora proteins. Subsequently, highly antigenic and immunogenic MHC class I, MHC class II and B cell epitopes were extracted from top-ranking vaccine targets. The designed vaccine construct containing 24 epitopes, 3 adjuvants, and 4 linkers was analysed for its physicochemical properties using different tools, including docking analysis. Immunological simulation studies suggested significant levels of T-helper, T-cytotoxic cells, and IgG1 will be elicited upon administration of such a putative multi-epitope vaccine construct. The vaccine construct is predicted to be soluble, stable, non-allergenic, non-toxic, and to offer cross-protection against related Trypanosoma species and strains. Further, studies are required to validate safety and immunogenicity of the vaccine.

An in vivo Interaction Network of DNA-Repair Proteins: A Snapshot at Double Strand Break Repair in Deinococcus radiodurans.

An extremophile Deinococcus radiodurans survives massive DNA damage by efficiently mending hundreds of double strand breaks through homology-dependent DNA repair pathways. Although DNA repair proteins that contribute to its impressive DNA repair capacity are fairly known, interactions among them or with proteins related to other relevant pathways remain unexplored. Here, we report in vivo cross-linking of the interactomes of key DNA repair proteins DdrA, DdrB, RecA, and Ssb (baits) in D. radiodurans cells recovering from gamma irradiation. The protein-protein interactions were systematically investigated through co-immunoprecipitation experiments coupled to mass spectrometry. From a total of 399 proteins co-eluted with the baits, we recovered interactions among diverse biological pathways such as DNA repair, transcription, translation, chromosome partitioning, cell division, antioxidation, protein folding/turnover, metabolism, cell wall architecture, membrane transporters, and uncharacterized proteins. Among these, about 80 proteins were relevant to the DNA damage resistance of the organism based on integration of data on inducible expression following DNA damage, radiation sensitive phenotype of deletion mutant, etc. Further, we cloned ORFs of 23 interactors in heterologous E. coli and expressed corresponding proteins with N-terminal His-tag, which were used for pull-down assays. A total of 95 interactions were assayed, in which we confirmed 25 previously unknown binary interactions between the proteins associated with radiation resistance, and 2 known interactions between DdrB and Ssb or DR_1245. Among these, five interactions were positive even under non-stress conditions. The confirmed interactions cover a wide range of biological processes such as DNA repair, negative regulation of cell division, chromosome partitioning, membrane anchorage, etc., and their functional relevance is discussed from the perspective of DNA repair. Overall, the study substantially advances our understanding on the cross-talk between different homology-dependent DNA repair pathways and other relevant biological processes that essentially contribute to the extraordinary DNA damage repair capability of D. radiodurans. The data sets generated and analyzed in this study have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the data set identifier PXD021822.

Probing the Interaction of Bovine Serum Albumin with Copper Nanoclusters: Realization of Binding Pathway Different from Protein Corona.

With an aim to understand the interaction mechanism of bovine serum albumin (BSA) with copper nanoclusters (CuNCs), three different types CuNCs having chemically different surface ligands, namely, tannic acid (TA), chitosan, and cysteine (Cys), have been fabricated, and investigations are carried out in the absence and presence of protein (BSA) at ensemble-averaged and single-molecule levels. The CuNCs, capped with different surface ligands, are consciously chosen so that the role of surface ligands in the overall protein-NCs interactions is clearly understood, but, more importantly, to find whether these CuNCs can interact with protein in a new pathway without forming the "protein corona", which otherwise has been observed in relatively larger nanoparticles when they are exposed to biological fluids. Analysis of the data obtained from fluorescence, ζ-potential, and ITC measurements has clearly indicated that the BSA protein in the presence of CuNCs does not attain the binding stoichiometry (BSA/CuNCs > 1) that is required for the formation of "protein corona". This conclusion is further substantiated by the outcome of the fluorescence correlation spectroscopy (FCS) study. Further analysis of data and thermodynamic calculations have revealed that the surface ligands of the CuNCs play an important role in the protein-NCs binding events, and they can alter the mode and thermodynamics of the process. Specifically, the data have demonstrated that the binding of BSA with TA-CuNCs and Chitosan-CuNCs follows two types of binding modes; however, the same with Cys-CuNCs goes through only one type of binding mode. Circular dichroism (CD) measurements have indicated that the basic structure of BSA remains almost unaltered in the presence of CuNCs. The outcome of the present study is expected to encourage and enable better application of NCs in biological applications.

N6-methyladenine and epigenetic immunity of Deinococcus radiodurans.

DNA methylation is ubiquitously found in all three domains of life. This epigenetic modification on adenine or cytosine residues serves to regulate gene expression or to defend against invading DNA in bacteria. Here, we report the significance of N6-methyladenine (6mA) to epigenetic immunity in Deinococcus radiodurans. Putative protein encoded by DR_2267 ORF (Dam2DR) contributed 35% of genomic 6mA in D. radiodurans but did not influence gene expression or radiation resistance. Dam2DR was characterized to be a functional S-adenosyl methionine (SAM)-dependent N6-adenine DNA methyltransferase (MTase) but with no endonuclease activity. Adenine methylation from Dam2DR or Dam1DR (N6-adenine MTase encoded by DR_0643) improved DNA uptake during natural transformation. To the contrary, methylation from Escherichia coli N6-adenine MTase (DamEC that methylates adenine in GATC sequence) on donor plasmid drastically reduced DNA uptake in D. radiodurans, even in presence of Dam2DR or Dam1DR methylated adenines. With these results, we conclude that self-type N6-adenine methylation on donor DNA had a protective effect in absence of additional foreign methylation, a separate methylation-dependent Restriction Modification (R-M) system effectively identifies and limits uptake of G6mATC sequence containing donor DNA. This is the first report demonstrating presence of epigenetic immunity in D. radiodurans.