Implementing efficient selective quantum process tomography of superconducting quantum gates on IBM quantum experience.

The experimental implementation of selective quantum process tomography (SQPT) involves computing individual elements of the process matrix with the help of a special set of states called quantum 2-design states. However, the number of experimental settings required to prepare input states from quantum 2-design states to selectively and precisely compute a desired element of the process matrix is still high, and hence constructing the corresponding unitary operations in the lab is a daunting task. In order to reduce the experimental complexity, we mathematically reformulated the standard SQPT problem, which we term the modified SQPT (MSQPT) method. We designed the generalized quantum circuit to prepare the required set of input states and formulated an efficient measurement strategy aimed at minimizing the experimental cost of SQPT. We experimentally demonstrated the MSQPT protocol on the IBM QX2 cloud quantum processor and selectively characterized various two- and three-qubit quantum gates.

NMR-based metabolomic profiling of the differential concentration of phytomedicinal compounds in pericarp, skin and seeds of Momordica charantia (bitter melon).

Momordica charantia is a medicinal plant which is widely used in different traditional medicinal systems to treat several diseases. We have identified the differential distribution of phytomedicinally important metabolites in the pericarp, skin and seeds of M. charantia fruit via NMR spectroscopy. Multivariate statistical analysis showed a clustering of the metabolic profiles of seeds and pericarp, and their clear separation from the metabolic profile of the skin. The total phenolic and flavonoid content of the fruit extracts were estimated via bioassays, the radical scavenging activity was estimated via in vitro DPPH and ABTS assays and an inhibitory activity test of α-glucosidase was also performed. The pericarp and seeds contained significant amounts of phenolic compounds and flavonoids, indicating that they are a good source for antioxidants. The skin contained a significantly higher amount of phytosterols such as Charantin and momordicine, which are known to correlate with antidiabetic activity.

DNA demethylation overcomes attenuation of colchicine biosynthesis in an endophytic fungus Diaporthe.

Fungal endophytes, a major component of the plant host microbiome, are known to synthesize plant-derived metabolites in vitro. However, attenuation of metabolite production upon repeated sub-culturing is a major drawback towards utilizing them as an alternative for plant-derived metabolites. In this study, we isolated Diaporthe perseae, a fungal endophyte from Gloriosa superba tubers, which showed the production of colchicine in axenic cultures. Mass spectrometry, Nuclear Magnetic Resonance spectroscopy, and tubulin polymerization assays confirmed the compound to be colchicine. Repeated sub-culturing of the endophyte for 10 generations led to a reduction in the yield of the metabolite from 55.25 µg/g to 2.32 µg/g of mycelial dry weight. Treatment of attenuated cultures with DNA methylation inhibitor 5-azacytidine resulted in increased metabolite concentration (39.68 µg/g mycelial dry weight) in treated samples compared to control (2.61 µg/g mycelial dry weight) suggesting that 5-azacytidine can induce demethylation of the fungal genome to overcome the phenomenon of attenuation of metabolite synthesis. Reduced levels of global methylation were observed upon 5-azacytidine treatment in attenuated cultures (0.41 % of total cytosines methylated) as compared to untreated control (0.78 % of total cytosines methylated). The results provide a significant breakthrough in utilizing fungal endophytes as a veritable source of plant-derived metabolites from critically endangered plants.

Structural and dynamical aspects of PEG/LiClO4 in solvent mixtures via NMR spectroscopy.

Motivated by the potential usefulness of polyethylene glycol (PEG)/Li+ salt mixtures in several industrial applications, we investigated the structure and dynamics of PEG/LiClO4 mixtures in D2 O and its mixtures with CD3 CN and DMSO-d6 , in a series of PEG-based polymers with a wide variation in their molecular weights. 1 H NMR chemical shifts, T1 /T2 relaxation rates, pulsed-field gradient NMR diffusion experiments, and 2D HOESY NMR studies have been performed to understand the structural and dynamical aspects of these mixtures. Increasing the temperature of the medium results in a significant perturbation in the H-bonded structure of PEG in its PEG/LiClO4 /D2 O mixtures as observed from the increase in chemical shifts. On the other hand, the addition of molecular cosolvents has a negligible effect. The hydrodynamic structure of PEG shows a pronounced variation at low temperature with increasing molecular weight, which, however, disappears at higher temperatures. Increasing the temperature leads to a decrease in the hydrodynamic structure of PEG, which can be explained on the basis of solvation-desolvation phenomena. The 2D HOESY NMR spectra reveal a new finding of Li+ -water binding in the PEG/LiClO4 /D2 O mixtures with the addition of molecular solvents, suggesting that the Li+ cation diffuses freely in the D2 O mixtures of polymers as compared with the polymer mixtures with DMSO or CD3 CN.

Evolution of dispersal syndrome and its corresponding metabolomic changes.

Dispersal is one of the strategies for organisms to deal with climate change and habitat degradation. Therefore, investigating the effects of dispersal evolution on natural populations is of considerable interest to ecologists and conservation biologists. Although it is known that dispersal itself can evolve due to selection, the behavioral, life-history and metabolic consequences of dispersal evolution are not well understood. Here, we explore these issues by subjecting four outbred laboratory populations of Drosophila melanogaster to selection for increased dispersal. The dispersal-selected populations had similar values of body size, fecundity, and longevity as the nonselected lines (controls), but evolved significantly greater locomotor activity, exploratory tendency, and aggression. Untargeted metabolomic fingerprinting through NMR spectroscopy suggested that the selected flies evolved elevated cellular respiration characterized by greater amounts of glucose, AMP, and NAD. Concurrent evolution of higher level of Octopamine and other neurotransmitters indicate a possible mechanism for the behavioral changes in the selected lines. We discuss the generalizability of our findings in the context of observations from natural populations. To the best of our knowledge, this is the first report of the evolution of metabolome due to selection for dispersal and its connection to dispersal syndrome evolution.

Mechanism of Resistance to Camptothecin, a Cytotoxic Plant Secondary Metabolite, by Lymantria sp. Larvae.

Camptothecin (CPT), a monoterpene indole alkaloid, is a potent inhibitor of eukaryotic topoisomerase I (Top 1). Because of this property, several derivatives of CPT are widely used as chemotherapeutic agents. The compound is produced by several plant species, including Nothapodytes nimmoniana (Family: Icacinaceae) presumably as a deterrent to insect pests. Here, we report, a lepidopteran larva, Lymantria sp. of Lymantriidae family which feeds voraciously on the leaves of N. nimmoniana, without any adverse consequences. Larval body weight and molting period were unaffected despite captive feeding of the larva with CPT enriched leaves. Mass spectrometric analysis indicated that nearly 46% of the ingested CPT was excreted while the rest was sequestered predominantly in the exuviae and setae (~35%). Although most of the CPT was in the parental form as found in the plant, traces of inactive, sulfated forms of CPT were recovered from the larva. Compared to that in plant, there were no critical mutations at the CPT binding domain of the insect's Top 1. The gut pH of the larva was alkaline (pH 10.0). The alkaline gut environment converts CPT from its active, lactone form to inactive, carboxylate form. It is likely that such conversion might help the larva to reduce the overall burden of CPT in its gut. We discuss the results in the context of the mechanisms of resistance adapted by insects to plant toxins.

Evolution of the metabolome in response to selection for increased immunity in populations of Drosophila melanogaster.

We used NMR-based metabolomics to test two hypotheses-(i) there will be evolved differences in the metabolome of selected and control populations even under un-infected conditions and (ii) post infection, the metabolomes of the selected and control populations will respond differently. We selected replicate populations of Drosophila melanogaster for increased survivorship (I) against a gram-negative pathogen. We subjected the selected (I) and their control populations (S) to three different treatments: (1) infected with heat-killed bacteria (i), (2) sham infected (s), and (3) untreated (u). We performed 1D and 2D NMR experiments to identify the metabolic differences. Multivariate analysis of the metabolic profiles of the untreated (Iu and Su) flies yielded higher concentrations of lipids, organic acids, sugars, amino acids, NAD and AMP in the Iu treatment as compared to the Su treatment, showing that even in the absence of infection, the metabolome of the I and S regimes was different. In the S and I regimes, post infection/injury, concentration of metabolites directly or indirectly associated with energy related pathways (lipids, organic acids, sugars) declined while the concentration of metabolites that are probably associated with immune response (amino acids) increased. However, in most cases, the I regime flies had a higher concentration of such metabolites even under un-infected conditions. The change in the metabolite concentration upon infection/injury was not always comparable between I and S regimes (in case of lactate, alanine, leucine, lysine, threonine) indicating that the I and S regimes had evolved to respond differentially to infection and to injury.

DNA barcoding and NMR spectroscopy-based assessment of species adulteration in the raw herbal trade of Saraca asoca (Roxb.) Willd, an important medicinal plant.

Saraca asoca (Roxb.) Willd, commonly known as "Asoka" or "Ashoka," is one of the most important medicinal plants used in raw herbal trade in India. The bark extracts of the tree are used in the treatment of leucorrhea and other uterine disorders besides also having anti-inflammatory, anti-bacterial, anti-pyretic, anti-helminthic, and analgesic activity. The indiscriminate and rampant extraction of the wood to meet the ever-increasing market demand has led to a sharp decline in naturally occurring populations of the species in the country. Consequently, the species has recently been classified as "vulnerable" by the International Union for Conservation of Nature (IUCN). Increasing deforestation and increasing demand for this medicinal plant have resulted in a limited supply and suspected widespread adulteration of the species in the raw herbal trade market. Adulteration is a serious concern due to: (i) reduction in the efficacy of this traditional medicine, (ii) considerable health risk to consumers, and (iii) fraudulent product substitution that impacts the economy for the Natural Health Product (NHP) Industry and consumers. In this paper, we provide the first attempt to assess the extent of adulteration in the raw herbal trade of S. asoca using DNA barcoding validated by NMR spectroscopic techniques. Analyzing market samples drawn from 25 shops, mostly from peninsular India, we show that more than 80 % of the samples were spurious, representing plant material from at least 7 different families. This is the first comprehensive and large-scale study to demonstrate the widespread adulteration of market samples of S. asoca in India. These results pose grave implications for the use of raw herbal drugs, such as that of S. asoca, on consumer health and safety. Based on these findings, we argue for a strong and robust regulatory framework to be put in place, which would ensure the quality of raw herbal trade products and reassure consumer confidence in indigenous medicinal systems. Graphical Abstract DNA barcoding and NMR spectroscopy-based assessment of adulteration in Saraca asoca.

NMR-based investigation of the Drosophila melanogaster metabolome under the influence of daily cycles of light and temperature.

We utilized an NMR-based metabolomic approach to profile the metabolites in Drosophila melanogaster that cycle with a daily rhythm. 1H 1D and 2D NMR experiments were performed on whole-body extracts sampled from flies that experienced strong time cues in the form of both light and temperature cycles. Multivariate and univariate statistical analysis was used to identify those metabolites whose concentrations oscillate diurnally. We compared metabolite levels at two time points twelve hours apart, one close to the end of the day and the other close to the end of the night, and identified metabolites that differed significantly in their relative concentrations. We were able to identify 14 such metabolites whose concentrations differed significantly between the two time points. The concentrations of metabolites such as sterols, fatty acids, amino acids such as leucine, valine, isoleucine, alanine and lysine as well as other metabolites such as creatine, glucose, AMP and NAD were higher close to the end of the night, whereas the levels of lactic acid, and a few amino acids such as histidine and tryptophan were higher close to the end of the day. We compared signal intensities across 12 equally spaced time points for these 14 metabolites, in order to profile the changes in their levels across the day, since the NMR metabolite peak intensity is directly proportional to its molar concentration. Through this report we establish NMR-based metabolomics combined with multivariate statistical analysis as a useful method for future studies on the interactions between circadian clocks and metabolic processes.

Metabolomic profiling of the phytomedicinal constituents of Carica papaya L. leaves and seeds by 1H NMR spectroscopy and multivariate statistical analysis.

Extracts from the Carica papaya L. plant are widely reported to contain metabolites with antibacterial, antioxidant and anticancer activity. This study aims to analyze the metabolic profiles of papaya leaves and seeds in order to gain insights into their phytomedicinal constituents. We performed metabolite fingerprinting using 1D and 2D 1H NMR experiments and used multivariate statistical analysis to identify those plant parts that contain the most concentrations of metabolites of phytomedicinal value. Secondary metabolites such as phenyl propanoids, including flavonoids, were found in greater concentrations in the leaves as compared to the seeds. UPLC-ESI-MS verified the presence of significant metabolites in the papaya extracts suggested by the NMR analysis. Interestingly, the concentration of eleven secondary metabolites namely caffeic, cinnamic, chlorogenic, quinic, coumaric, vanillic, and protocatechuic acids, naringenin, hesperidin, rutin, and kaempferol, were higher in young as compared to old papaya leaves. The results of the NMR analysis were corroborated by estimating the total phenolic and flavonoid content of the extracts. Estimation of antioxidant activity in leaves and seed extracts by DPPH and ABTS in-vitro assays and antioxidant capacity in C2C12 cell line also showed that papaya extracts exhibit high antioxidant activity.

Functional dynamics in replication protein A DNA binding and protein recruitment domains.

Replication Protein A (RPA) is an essential scaffold for many DNA processing machines; its function relies on its modular architecture. Here, we report (15)N-nuclear magnetic resonance heteronuclear relaxation analysis to characterize the movements of single-stranded (ss) DNA binding and protein interaction modules in the RPA70 subunit. Our results provide direct evidence for coordination of the motion of the tandem RPA70AB ssDNA binding domains. Moreover, binding of ssDNA substrate is found to cause dramatic reorientation and full coupling of inter-domain motion. In contrast, the RPA70N protein interaction domain remains structurally and dynamically independent of RPA70AB regardless of binding of ssDNA. This autonomy of motion between the 70N and 70AB modules supports a model in which the two binding functions of RPA are mediated fully independently, but remain differentially coordinated depending on the length of their flexible tethers. A critical role for linkers between the globular domains in determining the functional dynamics of RPA is proposed.

Investigating correlations in the altered metabolic profiles of obese and diabetic subjects in a South Indian Asian population using an NMR-based metabolomic approach.

It is well known that obesity/high body mass index (BMI) plays a key role in the evolution of insulin resistance and type-2 diabetes mellitus (T2DM). However, the exact mechanism underlying its contribution is still not fully understood. This work focuses on an NMR-based metabolomic investigation of the serum profiles of diabetic, obese South Indian Asian subjects. (1)H 1D and 2D NMR experiments were performed to profile the altered metabolic patterns of obese diabetic subjects and multivariate statistical methods were used to identify metabolites that contributed significantly to the differences in the samples of four different subject groups: diabetic and non-diabetic with low and high BMIs. Our analysis revealed that the T2DM-high BMI group has higher concentrations of saturated fatty acids, certain amino acids (leucine, isoleucine, lysine, proline, threonine, valine, glutamine, phenylalanine, histidine), lactic acid, 3-hydroxybutyric acid, choline, 3,7-dimethyluric acid, pantothenic acid, myoinositol, sorbitol, glycerol, and glucose, as compared to the non-diabetic-low BMI (control) group. Of these 19 identified significant metabolites, the levels of saturated fatty acids, lactate, valine, isoleucine, and phenylalanine are also higher in obese non-diabetic subjects as compared to control subjects, implying that this set of metabolites could be identified as potential biomarkers for the onset of diabetes in subjects with a high BMI. Our work validates the utility of NMR-based metabolomics in conjunction with multivariate statistical analysis to provide insights into the underlying metabolic pathways that are perturbed in diabetic subjects with a high BMI.

Disentangling diffusion information of individual components in a mixture with a 3D COMPACT-IDOSY NMR experiment.

A new 3D diffusion-ordered heteronuclear NMR experiment COMPACT-IDOSY (cross-polarization optimized multisite polarized accelerated time internally encoded diffusion ordered spectroscopy) has been designed and experimentally implemented on a mixture of flavonoids rutin and quercetin. The pulse sequence uses a cross-polarization mixing period and diffusion encoding gradients internally incorporated into the coherence transfer interval of a long-range heteronuclear correlation experiment. Substantial reduction in experimental time, good sensitivity and excellent resolution of signal overlap lead to the accurate determination of translational diffusion coefficients of individual components in the mixture.

Resolving overlaps in diffusion encoded spectra using band-selective pulses in a 3D BEST-DOSY experiment.

A novel diffusion-edited 3D NMR experiment that incorporates a BEST-HMQC pulse sequence in its implementation is presented. Heteronuclear 3D DOSY NMR experiments are useful in elucidating the diffusion coefficients of individual constituents of a mixture, especially in cases where the proton NMR 2D DOSY spectra show considerable overlap. The present 3D BEST-DOSY pulse sequence provides a more sensitive and less time-consuming alternative to standard 3D HMQC-DOSY experiments. Cleanly separated subspectra of individual mixture components are obtained, leading to the determination of diffusion coefficients with better accuracy. The feasibility of the technique is demonstrated on a mixture of amino acids, on a mixture of small molecules with similar diffusion coefficients, and on a complex mixture with large dynamic range (commercial gasoline). The implications of using adiabatic decoupling schemes and band-selective shaped pulses for selective BEST-DOSY experiments on proteins are also discussed.

Using the 19F NMR chemical shift anisotropy tensor to differentiate between the zigzag and chiral forms of fluorinated single-walled carbon nanotubes.

The structural characterization of different kinds of zigzag and chiral single-walled carbon nanotubes (SWNTs) has been investigated theoretically using (19)F NMR spectroscopy. The chemical shift anisotropy (CSA) tensor is computed at different levels of theory for the (19)F nuclei in different forms of functionalized fluorinated carbon nanotubes (CNT). A set of fluorine CSA parameters comprising the span, skew, and isotropic chemical shift is computed for each form of the fluoronanotubes and multidimensional CSA parameter correlation maps are constructed. We show that these correlations are able to clearly distinguish between the chiral and zigzag forms of fluorinated carbon nanotubes (F-SWNTs). Implications for solid-state and liquid-state NMR experiments are discussed.

Using the chemical shift anisotropy tensor of carbonyl backbone nuclei as a probe of secondary structure in proteins.

This study seeks to establish that the chemical shift anisotropy (CSA) tensor of the backbone carbonyl ((13)C') nucleus is a useful indicator of secondary structure elements in proteins. The CSA tensors of protein backbone nuclei in different secondary structures were computed for experimentally determined dihedral angles using ab initio methods and by calculating the CSA tensor for a model peptide over the entire dihedral angle space. It is shown that 2D and 3D cluster plots of CSA tensor parameters for (13)C' nuclei are able to distinguish between different secondary structure elements with little to no overlap. As evidenced by multinuclear 2D plots, the CSA of the (13)C' nucleus when correlated with different CSA parameters of the other backbone nuclei (such as C(alpha) or (1)H(alpha)) is also useful in secondary structure identification. The differentiation of alpha-helix versus beta-sheet motifs (the most populated regions of the Ramachandran map) for experimentally determined values of the carbonyl CSA tensor for proteins ubiquitin and binase (obtained from the literature) agrees well with the quantum chemical predictions.

Mapping NMR chemical shift anisotropy parameters of backbone nuclei onto secondary structure elements in proteins.

There has been much recent progress in using NMR chemical shift anisotropy (CSA) parameters to gain information about secondary structure content in proteins. This paper focuses on the comparison of CSA tensors of different backbone nuclei (namely 13C(a), 13C', 15N, 1H(a), 1H(N)) of all twenty amino acids appearing in well- defined secondary structures such as helices and sheets. Dihedral angle information of these backbone nuclei in different secondary structure elements has been extracted from experimentally determined structures of proteins deposited in the protein databank. The CSA tensors of these backbone nuclei have been computed for the corresponding dihedral angles using ab initio quantum chemical methods. It is shown that 2D correlated plots of a novel set of CSA parameters (r,t), that define the magnitude and shape of the anisotropy, are extremely useful in identifying secondary structure content. Further, multinuclear correlations between these CSA parameters can clearly distinguish between various secondary structure elements such as helices and sheets.