Analyzing the cation-aromatic interactions in proteins: Cation-aromatic database V2.0.

The cation-aromatic database (CAD) is a comprehensive repository of cation-aromatic motifs found in experimentally determined protein structures, first reported in 2007 [Proteins, 2007, 67, 1179]. The present article is an update of CAD that contains information of approximately 27.26 million cation-aromatic motifs. CAD uses three distance parameters (r, d1, and d2) to determine the position of the cation relative to the centroid of the aromatic residue and classifies the motifs as cation-π or cation-σ interactions. As of June 2023, about 193 936 protein structures were retrieved from Protein Data Bank, and this resulted in the identification of an impressive number of 27 255 817 cation-aromatic motifs. Among these motifs, spherical motifs constituted 94.09%, while cylindrical motifs made up the remaining 5.91%. When considering the interaction of metal ions with aromatic residues, 965 564 motifs are identified. Remarkably, 82.08% of these motifs involved the binding of metal ions to the amino acid HIS. Moreover, the analysis of binding preferences between cations and aromatic residues revealed that the HIS-HIS, PHE-ARG, and TRP-ARG pairs exhibited a preferential geometry. The motif pair HIS-HIS was the most prevalent, accounting for 19.87% of the total, closely followed by TYR-LYS at 10.17%. Conversely, the motif pair TRP-HIS had the lowest occurrence, representing only 4.20% of the total. The data generated help in revealing the characteristics and biological functions of cation-aromatic interactions in biological molecules. The updated version of CAD (Cation-Aromatic Database V2.0) can be accessed at https://acds.neist.res.in/cadv2.

Dengue virus pathogenesis and host molecular machineries.

Dengue viruses (DENV) are positive-stranded RNA viruses belonging to the Flaviviridae family. DENV is the causative agent of dengue, the most rapidly spreading viral disease transmitted by mosquitoes. Each year, millions of people contract the virus through bites from infected female mosquitoes of the Aedes species. In the majority of individuals, the infection is asymptomatic, and the immune system successfully manages to control virus replication within a few days. Symptomatic individuals may present with a mild fever (Dengue fever or DF) that may or may not progress to a more critical disease termed Dengue hemorrhagic fever (DHF) or the fatal Dengue shock syndrome (DSS). In the absence of a universally accepted prophylactic vaccine or therapeutic drug, treatment is mostly restricted to supportive measures. Similar to many other viruses that induce acute illness, DENV has developed several ways to modulate host metabolism to create an environment conducive to genome replication and the dissemination of viral progeny. To search for new therapeutic options, understanding the underlying host-virus regulatory system involved in various biological processes of the viral life cycle is essential. This review aims to summarize the complex interaction between DENV and the host cellular machinery, comprising regulatory mechanisms at various molecular levels such as epigenetic modulation of the host genome, transcription of host genes, translation of viral and host mRNAs, post-transcriptional regulation of the host transcriptome, post-translational regulation of viral proteins, and pathways involved in protein degradation.

Modulation of various host cellular machinery during COVID-19 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) emerged in December 2019, causing a range of respiratory infections from mild to severe. This resulted in the ongoing global COVID-19 pandemic, which has had a significant impact on public health. The World Health Organization declared COVID-19 as a global pandemic in March 2020. Viruses are intracellular pathogens that rely on the host's machinery to establish a successful infection. They exploit the gene expression machinery of host cells to facilitate their own replication. Gaining a better understanding of gene expression modulation in SARS-CoV2 is crucial for designing and developing effective antiviral strategies. Efforts are currently underway to understand the molecular-level interaction between the host and the pathogen. In this review, we describe how SARS-CoV2 infection modulates gene expression by interfering with cellular processes, including transcription, post-transcription, translation, post-translation, epigenetic modifications as well as processing and degradation pathways. Additionally, we emphasise the therapeutic implications of these findings in the development of new therapies to treat SARS-CoV2 infection.

Rhodium catalysed intramolecular benzannulation for the formation of tetracyclic carbazoles.

Rhodium catalyzed alkyne-tethered intramolecular annulation has been demonstrated for the synthesis of tetracyclic carbazole skeletons and a series of five to eight-membered pyrido[3,2,1-jk]carbazoles were successfully obtained. The present atom economical annulation proceeded under mild reaction conditions, offering a broad substrate scope.

Synergistic effect of barium titanate nanoparticles and graphene quantum dots on the dielectric properties and conductivity of poly(vinylidenefluoride-co-hexafluoroethylene) films.

PVDF-HFP/BaTiO3/GQDs polymer nanocomposite films with good flexibility and high dielectric constant (ϵ) at low frequency were prepared via solution casting technique. Different compositions of BaTiO3 (non-conducting ceramic nanofiller) and Graphene quantum dots (GQDs) (conducting nanofiller) utilized as co-filler were embedded in poly (vinylidene fluoride-co-hexafluoroethylene) (PVDF-HFP) polymer matrix. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) techniques were employed to characterize the prepared nanocomposite films. The mechanical properties of PVDF-HFP/BaTiO3/GQDs nanocomposite films were also investigated. Dielectric properties of nanocomposite films such as dielectric constant (ϵ), dielectric loss (tanδ) and AC conductivity ( σac ) were also determined as a function of frequency and temperature. Highest ϵ with relatively low tanδ obtained at low frequency for maximum temperature in all polymer nanocomposite films. The σac increases from lower (100 Hz) to higher frequency up to 100 kHz and drops to zero for the further increment of frequency. These results suggest that the PVDF-HFP/BaTiO3/GQDs nanocomposites are the most promising materials for energy storage applications.

Structure, morphology and modelling studies of polyvinylalcohol nanocomposites reinforced with nickel oxide nanoparticles and graphene quantum dots.

Nickel oxide (NiO) nanoparticles (NPs) and graphene quantum dots (GQDs) reinforced polyvinyl alcohol (PVA) nanocomposite films were prepared using a solution casting technique. The physicochemical characteristics of PVA/NiO/GQDs (PNG) nanocomposite films were studied using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscopy (FESEM). The obtained PNG nanocomposite films showed good mechanical flexibility and improved tensile strength. The influence of nanofiller concentrations on PNG nanocomposite film. The obtained results demonstrate an increase in the activation energy (Ea) up to PNG3 upon increasing the GQDs concentration and thereafter, its decreases. The fundamental interactions of the constituents of PNG nanocomposite film were investigated using density functional theory (DFT). This study on electronic structure reveals that the PVA model indirectly interacts with GQDs through the NiO model. This configuration is favoured in terms of interaction energy (-78 kJ/mol) compared to the one in which PVA interacts directly with the GQDs model.

Experts' Consensus on Use of Long-Acting Nitroglycerine in the Management of Angina and Chronic Coronary Syndrome in India.

AIM: To address the existing gaps in knowledge about long-acting nitroglycerine (LA-NTG) and provide recommendations to address these issues. METHODOLOGY: Approved LA-NTG questionnaire that included 17 questions related to the role of LA-NTG in the management of angina and chronic coronary syndrome (CCS) was shared with 150 expert cardiologists from different regions from India. Results of these survey questionnaires were further discussed in 12 regional level meetings. The opinions and suggestions from all the meetings were compiled and analyzed. Further, recommendations were made with the help of attending national cardiology experts and a consensus statement was derived. RESULTS: This is the first consensus on LA-NTG, summarizing the clinical evidence from India and suggesting recommendations based on these data. The experts recommended early use of LA-NTG as a first-line antianginal therapy in combination with beta-blocker since it improves exercise tolerance in patients with CCS. A strong consensus was observed for using LA-NTG in patients with co-morbid hypertension, diabetes, chronic kidney disease and post-percutaneous coronary intervention angina. As a part of cardiac rehabilitation, LA-NTG allows patients with angina to exercise to a greater functional capacity. CONCLUSIONS: A national consensus was observed for several aspects of LA-NTG in the management of angina and CCS. The clinical experience of the experts confirmed an extremely satisfied patient perception about the efficacy of LA-NTG.

Prevalence and severity of coronal and radicular caries among patients with type 2 diabetes mellitus: A cross sectional study.

Background: Studies among type 2 diabetes mellitus patients have reported total caries experience; however the severity and clinical consequences of untreated dental caries are often ignored. Methods: For this study, 150 well (I) and poorly controlled (II) diabetic participants were recruited. The spectrum of caries was evaluated using DMFT (Decayed, Missing and Filled Tooth) index, Dental Caries Severity Classification Scale, PUFA (Pulpal involvement, Ulceration, Fistula and Abscess) index, RCI (Root Caries Index) and the severity of radicular caries by Root Surface Caries Severity Index. Results: The prevalence of coronal and root caries was 90.7% and 23.3%, respectively. There was significant difference among caries experiences for D, M and DMFT. In group II, severity of coronal caries and mean rank of P, F, A and PUFA scores were higher, so were prevalence of root caries and severity of RD2, RD3 and RD4. HbA1c level had positive correlation with DMFT and PUFA scores (r = 0.458 and 0.522), so was the duration of diabetes with coronal caries, DMFT, PUFA score, root caries and RCI score (r = 0.235, 0.320, 0.273, 0.308 and 0.323). Conclusion: This is probably the first study to examine the severity of coronal caries, prevalence of untreated dental caries and severity of radicular caries in diabetic patients. Uncontrolled diabetes causes substantial increase in prevalence and severity of coronal and radicular caries.

Acute coronary syndrome in young males after a prolonged stay at high altitude.

The Indian population is predisposed to acute coronary syndrome at a younger age, but very few cases are reported at high altitude. Acute coronary syndrome is frequently associated with multiple cardiovascular risk factors. During management of seven young patients with acute coronary syndrome, it was found that none of them had conventional cardiovascular risk factors including recent physical exertion. It is a known fact that the risk of vascular thrombosis increases by 30 times in Indian soldiers after a long stay at high altitude. Therefore, it is necessary to carry out the tests for procoagulant markers to know whether the acute coronary syndrome was because of the prothrombotic state, and if yes, was high altitude responsible for the procoagulant state or whether the person per se had a procoagulant syndrome. With the absence of these tests at hospitals at high-altitude areas, it becomes difficult to ascertain the exact cause of acute coronary syndrome. This study highlights the importance of aggressively testing for procoagulant markers in young patients presenting with chest pain at high altitude, even in the absence of traditional risk factors.

G-Quadruplex-Specific Cell-Permeable Guanosine-Anthracene Conjugate Inhibits Telomere Elongation and Induces Apoptosis by Repressing the c-MYC Gene.

We herein report a cell-membrane-permeable molecular probe ADG, prepared by conjugating guanosine with anthracene, selectively interacts with c-MYC G-quadruplex over other promoter and telomeric quadruplexes as well as duplex DNA. NMR spectroscopy suggests that ADG interacts with terminal G-quartets as well as with the nearby G-rich tract (G13-G14-G15 and G8-G9-G10) of c-MYC quadruplex. In vitro cellular studies indicate that ADG represses c-MYC expression by stabilizing its promoter G-quadruplex and alters c-MYC-related cellular events. ADG suppresses hTERT and BCL2 gene expressions in a promoter-independent manner, inhibits elongation of telomere length, and activates apoptotic cascades in cancer cells.

Evaluation of vacuum impregnation as a novel approach for soaking of fried Gulabjamun balls.

Vacuum impregnation of sugar syrup into sub-baric fried Gulabjamun was evaluated as a technological approach to prepare a product of most acceptable quality. Sugar syrup concentrations (40, 50 and 60 °Brix) in combination with process time (2, 4 and 6 min) were analyzed for their effect on product quality in terms of its overall acceptability, expansion ratio, hardness, juiciness and sugar content. The effect of the process conditions on the five listed responses during the vacuum impregnation process was evaluated using response surface methodology and modelled using a second order polynomial equation. The optimum combination was obtained as soaking in a syrup of 55 °Brix for 5 min and was experimentally validated for its real time adequacy. The experimental values of the quality parameters thus obtained were found to be in close agreement with the predicted values.

Self-Assembly of a Guanosine Derivative To Form Nanostructures and Transmembrane Channels.

We herein report the self-assembly of a lipophilic bromoguanosine derivative (G1) in homogeneous solution, in the solid state and in planar bilayer membranes. The self-assembly of G1, driven by H-bonding and π-π stacking interactions can form different nano-structures depending on incubation time. The G1 nanostructure is able to bind a bioactive dye like Rose Bengal. In crystal state, it shows ribbon type H-bonding pattern and exhibits birefringence in polarized light. And further, the self-assembled nanostructure of G1 can form discrete transmembrane ion channels in lipid bilayer membranes, enabling passage of potassium ions.

Interferometric focal length measurement of positive and negative lenses using a lateral-shearing cyclic path optical configuration setup and polarization phase-shifting interferometry.

We present a simple interferometric focal length measurement technique for measuring the focal length of positive and negative lenses using a lateral-shearing cyclic path optical configuration (CPOC) setup and polarization phase-shifting interferometry (PPSI). The technique requires an auxiliary lens, whose focal length need not be known accurately, for generating a focused point source at its focal plane. The focal point of the test lens is adjusted to be in the vicinity of the focus of the auxiliary lens. The radii of the resulting spherical wave fronts emerging from the test lens, due to the defocus, for two different longitudinal shifted positions of the test lens are measured using the lateral-shearing CPOC setup and PPSI. Focal length of the test lens is determined from the known longitudinal shift and from the measured radii of the spherical wave fronts. Results obtained for 200.0 mm convex and 100.0 mm concave test lenses are presented.

Fluorescent Dansyl-Guanosine Conjugates that Bind c-MYC Promoter G-Quadruplex and Downregulate c-MYC Expression.

The four-stranded G-quadruplex present in the c-MYC P1 promoter has been shown to play a pivotal role in the regulation of c-MYC transcription. Small-molecule compounds capable of inhibiting the c-MYC promoter activity by stabilising the c-MYC G-quadruplex could potentially be used as anticancer agents. In this context, here we report the synthesis of dansyl-guanosine conjugates through one-pot modular click reactions. The dansyl-guanosine conjugates can selectively detect c-MYC G-quadruplex over other biologically relevant quadruplexes and duplex DNA and can be useful as staining reagents for selective visualisation of c-MYC G-quadruplex over duplex DNA by gel electrophoresis. NMR spectroscopic titrations revealed the preferential binding sites of these dansyl ligands to the c-MYC G-quadruplex. A dual luciferase assay and qRT-PCR revealed that a dansyl-bisguanosine ligand represses the c-MYC expression, possibly by stabilising the c-MYC G-quadruplex.

Proteomic based approach for characterizing 4-hydroxy-2-nonenal induced oxidation of buffalo (Bubalus bubalis) and goat (Capra hircus) meat myoglobins.

BACKGROUND: Myoglobin (Mb) is a sarcoplasmic heme protein primarily responsible for meat color and its chemistry is species specific. 4-hydroxy-2-nonenal (HNE) is a cytotoxic lipid derived aldehyde detected in meat and was reported to covalently adduct with nucleophilic histidine residues of Mb and predispose it to greater oxidation. However, no literature is available on characterization of lipid oxidation induced oxidation of Indian water buffalo (Bubalus bubalis) and goat (Capra hircus) myoglobins. METHODS: Present study characterize the Mb extracted from water buffalo and goat cardiac muscles using two-dimensional gel electrophoresis (2DE), OFFGEL electrophoresis and mass spectrometry (MS). Purified buffalo and goat bright red oxymyoglobin were reacted with HNE in-vitro at physiological pH (7.4) and temperature (37 °C) conditions and the formation of oxidised brown metmyoglobin was measured. The Mb-HNE adducts were detected using MALDI-TOF MS, whereas specific sites of adduction was determined using ESI-QTOF MS/MS. RESULTS: Purified buffalo and goat Mb samples revealed a molecular mass of 17,043.6 and 16,899.9 Daltons, respectively. The 2DE analysis exhibited 65 (sarcoplasmic protein extract) and 6 (pure Mb) differentially expressed (P < 0.05) protein spots between buffalo and goat samples. OFFGEL electrophoresis revealed an isoelectric point of 6.77 and 7.35 respectively, for buffalo and goat Mb's. In-vitro incubation of HNE with bright red buffalo and goat oxymyoglobin's at pH 7.4 and 37 °C resulted in pronounced (P < 0.05) oxidation and formation of brown metmyoglobin. MALDI-TOF MS analysis of Mb-HNE reaction mix revealed covalent binding (via Michael addition) of 3 and 5 molecules of HNE with buffalo and goat Oxy-Mb's, respectively. ESI-QTOF MS/MS identified seven and nine histidine (HIS) residues of Mb that were readily adducted by HNE in buffalo and goat, respectively. CONCLUSION: The study demonstrated better redox stability of buffalo Mb than goat Mb. Our findings confirm the hypothesis that relative effect of HNE was greater for Mb's with 12 ± 1 HIS residues than Mb's with 9 HIS residues and helps meat processors in developing species-specific processing strategies to reduce the color variability.

Conductivity fluctuations in proton-implanted ZnO microwires.

Electric noise can be an important limitation for applications of conducting elements in the nanometer size range. The intrinsic electrical noise of prospective materials for opto-spintronics applications like ZnO has not yet been characterized. In this study, we have investigated the conductivity fluctuations in 10 nm thick current paths produced by proton implantation of ZnO microwires at room temperature. The voltage noise under a constant dc current bias in undoped, as well as in Li-doped microwires, is characterized by [Formula: see text] power spectra with [Formula: see text]. The noise intensity scales with the square of the bias current pointing to bias-independent resistivity fluctuations as a source of the observed noise. The normalized power spectral density appears inversely proportional to the number of carriers in the probed sample volume, in agreement with the phenomenological Hooge law. For the proton-implanted ZnO microwire and at 1 Hz we obtain a normalized power spectral density as low as [Formula: see text] Hz(-1).

Measurement of the surface form error of large aperture plane optical surfaces with a polarization phase-shifting liquid reference reflection Fizeau interferometer.

A polarization phase-shifting liquid reference reflection Fizeau interferometer has been proposed. A polarization cyclic path optical configuration along with a concave telescope mirror is used to produce a pair of expanded, collimated p and s polarized beams with a small angular separation between them. The collimated beams are deflected along a vertical direction toward a Fizeau interferometer cavity formed between a liquid surface that acts as a reference surface and a plane test surface. Either the p or s polarized beam is allowed to strike the liquid surface normally and the orientation of the test surface is adjusted to reflect the other beam, having orthogonal linear polarization, in the direction of the normally reflected reference beam from the liquid surface. A combination of a quarter-wave plate and linear polarizer is used to apply polarization phase shift between the test and reference beams, and quantitative surface form error is measured by applying phase-shifting interferometry. A method for elimination of the residual system aberration is discussed. Results obtained for an optically polished BK-7 disk of clear aperture diameter ≈160 mm are presented.

Small roll angle measurement using lateral shearing cyclic path polarization interferometry.

We present a technique for the measurement of roll angular displacement of a rotary stage using a lateral shearing cyclic path optical configuration (CPOC) setup and polarization phase shifting interferometry (PPSI). The CPOC setup, aligned on the rotary stage, laterally shears the input plane polarized spherical beam into a pair of orthogonally polarized beams, which when brought to the same state of polarization by a polarizer produce interference fringes similar to Young's fringes. Rotation of the CPOC setup in its plane introduces a phase change between the orthogonally polarized lateral sheared beams due to the change in angle of incidence of the input beam. The change in the phase results in spatial displacement of the interference fringes. Using PPSI, the phase, or the optical path difference change between the laterally sheared beams that is related to the rotation angle of the CPOC setup, is measured.

Measurement of surface form error of an optical surface with reduced interferometric spatial coherence artifacts using a ring source and polarization phase-shifting interferometry.

We present a technique for the measurement of surface form error of an optical surface using a ring source and polarization phase-shifting interferometry (PPSI). The ring source, generated using a refracting axicon, is projected onto a rotating diffuser to reduce the spatial coherence noise generated by the spatially coherent He-Ne laser and to enhance the interference fringe contrast. PPSI is applied to extract the phase [and hence the optical path difference (OPD)] from the interference fringes formed by a Fizeau cavity using the ring source. The OPD values are least-square fitted to a plane and the surface form errors are evaluated from the deviations of the OPD values from the fitted reference plane. A two-step subtraction method to reduce the system errors and the effect of the ring source diameter on the effective measurement area of the test surface are discussed. The main advantage of the technique is that the perturbations in the Fizeau cavity are negligible during the phase shifts as the phase shifts between the interfering beams are introduced outside the cavity.

Distribution trends & antibiogram pattern of Salmonella enterica serovar Newport in India.

BACKGROUND & OBJECTIVES: Salmonellosis is a major public health concern worldwide. Besides typhoidal salmonellae, infections due to non-typhoidal serovars of Salmonella are also associated with high morbidity and mortality leading to huge economic losses. Among non-typhoidal serovars, Salmonella Newport has been reported as a major cause of foodborne infections resulting in outbreaks due to consumption of contaminated food items. Little data related to this serovar are available from India leading to the scarcity of information on the distribution trends of this important serovar in the country. Therefore, an effort was made in the present study to generate data on distribution trends and antibiogram of S. Newport in the country. METHODS: S. Newport isolates received at the National Salmonella and Escherichia Centre at Kasauli, India, during January 2010 to December 2013 were analysed for their distribution trends and antibiogram data were also generated using standard methods. RESULTS: In the present study, S. Newport isolates were received from eight s0 tates and one union territory of the country and highest proportion of S. Newport isolates were found to be from humans (53.61%) followed by animals (27.84%) and food (18.56%). S. Newport isolates exhibited resistance to all drugs used in the present study except chloramphenicol, ciprofloxacin and cefuroxime. INTERPRETATION & CONCLUSIONS: Considering distribution of this important serovar of Salmonalla and its wide range of reservoirs, steps towards formulation and execution of efficient surveillance programmes should be taken.