Uniaxial pressure control of competing orders in a high-temperature superconductor.

Cuprates exhibit antiferromagnetic, charge density wave (CDW), and high-temperature superconducting ground states that can be tuned by means of doping and external magnetic fields. However, disorder generated by these tuning methods complicates the interpretation of such experiments. Here, we report a high-resolution inelastic x-ray scattering study of the high-temperature superconductor YBa2Cu3O6.67 under uniaxial stress, and we show that a three-dimensional long-range-ordered CDW state can be induced through pressure along the a axis, in the absence of magnetic fields. A pronounced softening of an optical phonon mode is associated with the CDW transition. The amplitude of the CDW is suppressed below the superconducting transition temperature, indicating competition with superconductivity. The results provide insights into the normal-state properties of cuprates and illustrate the potential of uniaxial-pressure control of competing orders in quantum materials.

Engineering Human Microbiota: Influencing Cellular and Community Dynamics for Therapeutic Applications.

The complex relationship between microbiota, human physiology, and environmental perturbations has become a major research focus, particularly with the arrival of culture-free and high-throughput approaches for studying the microbiome. Early enthusiasm has come from results that are largely correlative, but the correlative phase of microbiome research has assisted in defining the key questions of how these microbiota interact with their host. An emerging repertoire for engineering the microbiome places current research on a more experimentally grounded footing. We present a detailed look at the interplay between microbiota and host and how these interactions can be exploited. A particular emphasis is placed on unstable microbial communities, or dysbiosis, and strategies to reestablish stability in these microbial ecosystems. These include manipulation of intermicrobial communication, development of designer probiotics, fecal microbiota transplantation, and synthetic biology.

Influence of the conserved active site residues of histidyl tRNA synthetase on the mechanism of aminoacylation reaction.

The relation between the conservation of active site residues and the molecular mechanism of aminoacylation reaction is an unexplored problem. In the present paper, the influences of the conserved active site residues on the reaction mechanism as well as the electrostatic potential near the reaction center are analyzed for Histidyl tRNA synthetase from Escherichia coli, Thermus thermophilus and Staphylococcus aureus. While the primary structures show both convergence as well as divergence, the secondary level structures of the active sites of the three species show considerable conservation in the respective structural organizations. The conserved active site residues near the reaction center, which have a major role in the reaction mechanism and catalysis, retain their specific position and orientation relative to the substrate in the three species. In order to understand the influence of different conserved and nonconserved residues near the reaction center, two different models are considered. First, a large model of active site with the substrates, Mg(2+) ions and water is constructed in which the first shell residues (including both conserved as well as nonconserved) near the reaction center are studied. From the large model, a smaller model is constructed for reaction path modeling individually for three species. Validation of the smaller model is carried out by comparing the energy surfaces of large and small models as a function of reaction coordinates. Further, the electrostatic potential near the reaction center for the large and small model are compared. The transition state structures of the activation step of aminoacylation reaction for E. coli, T. thermophilus and S. aureus are calculated using the combined ab-initio/semi-empirical calculation. The similarity of the energy profiles as a function of the relevant reaction coordinate and the orientation of the catalytic residue, Arg259, indicate that the reaction mechanisms are identical which are guided by the strikingly similar structural pattern formed by conserved residues for three species. The energy surfaces have close resemblance in three species and present a clear perspective that how the reaction proceeds with the aid of different conserved residues. The study of electrostatic potential confirms this view. The present study provides an understanding of the relationship between the conservation of residues and the efficient reaction mechanism of aminoacylation reaction.

Nanoaggregate shapes at the air/water interface.

Chiral interfaces and molecular recognition phenomena are of special interest not only for the understanding of biological recognition processes but also for the potential application in material science. Langmuir monolayers at the air-water interface have successfully been used as simple models to mimic biological phenomena. Recent experimental studies revealed that both chirality and molecular recognition processes of amphiphiles are controlling the features of the nano-aggregates at the air/water interface. The objective of experimental studies has been to gain information about the properties of mesoscopic length scale aggregates obtained on the basis of chiral discrimation effects and the formation of supramolecular entities by molecular recognition of non-surface active species dissolved in the aqueous subphase. Differences in the two-dimensional morphology and lattice structures of the nano-aggregates cannot be explained by macroscopic theories and needed information about the detailed orientation and distance dependence of the intermolecular interaction within the aggregates. First new bottom-up studies have been directed toward understanding the driving forces for the aggregation processes of monolayers. Different types of interactions have been successfully considered using semi-empirical quantum chemical methods. The possibilities of Langmuir-Blodgett (LB) patterning to be an alternative paradigm for large-area patterning with mesostructured features are discussed.

Aminoacylation reaction in the histidyl-tRNA synthetase: fidelity mechanism of the activation step.

Aminoacylation is a vital step of natural biosynthesis of peptide. Correct aminoacylation is a necessary prerequisite for the elimination of noncognate amino acids such as D-amino acids. In the present work, we studied the fidelity mechanism of histidine (His) activation (first step of aminoacylation reaction) using a combined quantum mechanical/semiempirical method based on a model of crystal structure of the oligomeric complex of histidyl-tRNA synthetase (HisRS) from Escherichia coli. The study of the variation in the energy during the mutual approach of the His and ATP to form adenylate shows that the surrounding nanospace of synthetase confines the reactants (L-His and ATP) and proximally places in a geometry suitable for the in-line nucleophilic attack. The significantly higher energy of the energy surface of the model containing D-His is due to unfavorable interaction of D-His with ATP and surrounding residues. This indicates that the network of interaction (principally electrostatic) is highly unfavorable when D-amino acid is incorporated. The reorganization of the surrounding nanospace can lower the unfavorable nature of the intermolecular energy surface of D-His and surrounding residues. However, such a rearrangement requires large-scale structural reorganization of the synthetase structure and is unfavorable. The variation in the bond angles and distances in going from the reactant state to the product state via transition state confirms the mechanism of nucleophilic attack and concomitant inversion of oxygen atoms around alpha-phosphorus (alpha-P). Calculation of the electrostatic potential indicates that in addition to the Mg(2+) the Arg residues in the active site facilitate the nucleophilic attack by reducing the negative charge distributed over the oxygen atoms attached to the alpha-P of ATP. Arg 259 residue has a role similar to that played by the two Mg(2+) cations as this residue is in close proximity of the alpha-P of ATP. Arg 113 also facilitates the reduction of the negative charge on the other side of the reaction center. The favorable electrostatic interaction of the Arg 259 with ATP and His is also concluded from the calculation of the binding energy. The Arg 259 anchors the carboxylic acid group of His and the oxygen atom of the alpha-phosphate group during the progress of reaction. Consequently, Arg 259 plays an important catalytic role in the activation step rather than merely reducing the negative charge density over the ATP.

Orientation and distance dependent chiral discrimination in the first step of the aminoacylation reaction: integrated molecular orbital and semi-empirical method (ONIOM) based calculation.

Aminoacylation is a vital step in natural biosynthesis process of peptide and is the key step in correlating the realm of protein with the RNA world. Incorrect aminoacylation might lead to misacylation of d-amino acid in the tRNA which might cause synthesis of a hetero-peptide rather than natural homopeptide leading to the altered functionality of the peptide. However, the accuracy of this process is remarkable and leads to the attachment of the correct enantiomer of the amino acid with their cognate tRNA. Thus, the chiral discrimination is stringent. In the present work, we presented a combined ONIOM (ab initio/semi-empirical) study of the chiral discrimination in the first step of aminoacylation reaction based on a model of crystal structure of the oligomeric complex of histidyl-tRNA synthetase (HisRS) from Escherichia coli complexed with ATP and histidinol and histidyl-adenylate. The study reveals that the molecular mechanism of the chiral discrimination involves the amino acid, ATP as well as surrounding residues of the synthetase. Several factors are noted to be responsible for discrimination and explain the high level of stereospecificity of the process. The chirality of the amino acid of the substrate and its (principally) electrostatic interaction with the ATP is important for discrimination. The distance and orientational changes involved in the approach of the d-His towards the ATP is energetically unfavorable. The charge distributions on the His and ATP are important for the discrimination. Removal of the charges in the model drastically reduces the discrimination. Restricted nature of the mutual orientation within the cavity of the active site where the His and ATP are located during the change in orientation for the approach to form the adenylate makes the resultant interaction profile as different for l-His and d-His also influences chiral discrimination. The analysis of the transition state structure revealed that alteration of the chirality of the His destabilize the transition state by removing the favorable electrostatic interaction between the Glu-83 and NH(3)(+) group of the His substrate. The proximity of the surrounding residues as present in the active site of the synthetase with the His and ATP (the separation is of nanometer range) has influence of discrimination. The study provides a molecular mechanism of the retention of biological homochirality.

Chiral discrimination in stearoyl amine glycerol monolayers.

Chiral discrimination in Langmuir monolayers of amphiphilic 1-stearylamine-glycerol is studied using the hybrid quantum mechanical/molecular mechanical method. Using the experimental information about the lattice structure [D. Vollhardt, U. Gehlert, J. Phys. Chem. B. 2002, 106, 4419], the intermolecular interaction profiles for enantiomeric and racemic pair are studied as a function of mutual tilt and azimuth for different values of intermolecular separation. The present study reveals that, at shorter separation, the interaction profile of the racemic pair has deeper minima than the enantiomeric pair, whereas at larger separation the minimum of the enantiomeric pair is deeper. Thus, the theoretical studies reveal an interesting crossover from heterochiral preference to homochiral preference in 1-stearylamine-glycerol monolayers, with the increase in the intermolecular separation corresponding to a larger area per molecule in the monolayer. This predicts that, with gradual compression, the interactions between racemic pair dominate the experimental features, whereas, under nonequilibrium conditions at the beginning of the formation of the condensed phase, the experimental characteristics of homochirality are observable. The study conclusively shows that the chiral structure of the molecule and the lattice packing drive the chiral preference at the mesoscopic level.

Role of dipolar interaction in the mesoscopic domains of phospholipid monolayers: dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylethanolamine.

The role of dipolar interactions in determining the lipid domain shapes at the air-water interface with a change in the chemical structure of the head groups of lipids is theoretically studied. The phospholipids considered are dipalmitoylphosphatidylcholine (D,L-DPPC) and dipalmitoylphosphatidylethanolamine (DPPE). Despite closely similar chemical structures, the domains of the two lipids are strikingly different. The DPPC domains exhibit elongated arms, while the DPPE domains are nearly round-shaped. To compare the dipolar repulsions in the domains of the two phospholipids, different energy-minimized conformers of DPPC and DPPE are studied using the semiempirical quantum chemical method (PM3). It is found that the dipole moment of DPPC is significantly larger than that of DPPE. The in-plane and out-of-plane components of the dipole moments are calculated using grazing incidence X-ray diffraction data at different surface pressure values, as used in the experiment. The result indicates that the magnitude of the dipolar interaction is significantly larger in DPPC than that in DPPE over the surface pressure range considered. The enhanced dipolar repulsion corroborates well with the difference in the domain shapes in the two phospholipid monolayers. The larger dipolar repulsion in DPPC leads to development of elongated domain arms, while relatively less dipolar repulsion allows a closed shape of the condensed-phase DPPE domains.

Semiempirical quantum mechanical calculations of dipolar interaction between dipyridamole and dipalmitoyl phosphatidyl choline in Langmuir monolayers.

Recent studies have shown that dipalmitoyl phosphatidyl choline (DPPC) monolayers respond cooperatively to the presence of dipyridamole (DIP) guest molecules even at small concentrations, which is a signature of molecular recognition. Using semiempirical quantum mechanical calculations for the DIP-DPPC system, we show that the incorporation of DIP causes large changes in the vertical dipole moment of the DIP-DPPC system, which can explain why measurable changes in surface potential are observed experimentally even at very low DIP concentrations. The calculations are also consistent with the anomalous concentration dependence of the surface pressure and surface potential isotherms for DIP-DPPC monolayers. Rather than saturation or a continuous increase in the effects caused by the incorporation of increasing amounts of DIP, the experimentally observed inversion in the behavior of the surface potential as the DIP concentration reaches 0.5 mol % would be caused by a change in DIP conformation, from a vertical arrangement for the DIP rings to a horizontal or intermediate arrangement. The strong dipolar interactions indicated in the calculations may also be the origin of the drastic changes in monolayer morphology seen in fluorescence microscopy images, with triskellion-shaped domains being formed for condensed DIP-DPPC monolayers.

Role of electrostatic interactions for the domain shapes of Langmuir monolayers of monoglycerol amphiphiles.

The role of electrostatic interaction in the domain morphology of amide, ether, ester, and amine monoglycerol monolayers (abbreviated as ADD, ETD, ESD, and AMD, respectively) with systematic variation in the molecular structure of the headgroup region is investigated. Experimental studies using Brewster angle microscopy (BAM) and grazing incidence X-ray diffraction (GIXD) show that the characteristic features of the condensed monolayer phase, such as domain morphology, crystallinity, and lattice parameters, are very different for these monoglycerols. Therefore, the intermolecular interactions of the four amphiphilic monoglycerols are investigated in detail. First, the dipole moments of four monoglycerols of similar structure but with different functional groups are calculated by a semiempirical quantum mechanical technique. The dipole moments for monoglycerols follow the sequence AMD < ETD < ESD < ADD for the population of conformers of compounds investigated. The dipolar repulsion energies for the amphiphilic monoglycerols are also calculated for different possible mutual orientations between the dipoles. The calculated dipolar energies also follow the same trend for different possible headgroup orientations. These results can explain the domain shape of the monoglycerols observed experimentally. Second, ab initio calculations on the basis of the HF/6-31G** method are performed for representative monoglycerol headgroup segments. The results show that the intermolecular interaction energy related to dimer formation follows the order ETD < ESD < AMD < ADD segments, similar to that observed in experiment except in the case of the AMD segment. The relative importance of intra- and intermolecular hydrogen bonding in dimers is analyzed. The enhanced role of the intermolecular interaction relative to intramolecular interaction in the case of AMD contributes to the relatively high intermolecular interaction energy for the particular conformation of the dimer of AMD segment as observed from ab initio calculation. The present work shows that the variations in headgroup molecular structure alter drastically the domain shape, and the theoretical calculations conclusively reveal the important role of the electrostatic interactions for the mesoscopic domain architecture.

A fraction isolated from Ehrlich ascites carcinoma as an antitumor and differentiating agent against human leukemic cell ML-2.

Lipopolysaccharide fraction isolated from Ehrlich ascites carcinoma (E-LPS) was investigated as an antitumor agent against human leukemia cell ML-2. Marked cell growth inhibition was observed with ML-2 cell accompanied by inhibition of DNA synthesis and perturbation of cell cycle. Induction of differentiation in treated ML-2 cells was observed as indicated by morphological maturation, NBT reducing activity and indirect immunofluorescence.

Parasympatholytic activity of psychoactive drugs in rat brain mitochondria.

Chlorpromazine, imipramine and amphetamine at a concentration of 0.66, 1.33 and 13.3 x 10(4) M in vitro inhibited acetyl cholinesterase activity by 16, 23 and 31% respectively in rat brain mitochondria. No change in enzyme activity was induced by these drugs in vivo. There is little cholinergic facilitation through acetylcholinesterase inhibition in the presence of psychoactive drugs.

Chlorpromazine and other psychoactive drug induced alterations of a membrane bound enzyme in rat brain.

Psychoactive drugs like chlorpromazine (CPZ), imipramine, lithium and amphetamine in one way or another affect behaviour. The drug responses are presumably mediated by inducing a change in the activity of membrane bound enzymes. CPZ is very potent in inhibiting the alkaline phosphatase activity in rat brain. The combined effect of CPZ with other drugs shows that CPZ and imipramine together inhibit the enzyme activity significantly greater than the individual inhibition either by CPZ or by imipramine alone. Effective inhibition of the alkaline phosphatase activity with a single drug or combined drugs may lead to a change in neuronal permeability through glucocorticoids thereby affecting mood.

Effect of three organophosphates on respiration in rat brain and liver tissue.

The effects of three organophosphate pesticides, i.e. monocrotophos, dichlorvos, and phosphamidon on respiration in rat brain and liver tissue slices have been studied. Among these pesticides dichlorvos causes significant inhibition of respiration both in brain and liver.

Antidepressants and brain respiration.

Imipramine and clorgyline, at concentrations of 0.002 M, inhibit the respiration of brain tissue by 82 and 71 per cent respectively, while chloropromazine and tranylcypromine, at concentrations of 0.01 M, inhibit it about 25 per cent. Deprenyl and amphetamine at a concentration of 0.002 M inhibit brain tissue respiration by 12 and 18 per cent respectively. Respiration in brain is least affected by lithium chloride (only 5 per cent inhibition).

In vitro and in vivo effect of organophosphate pesticides on monoamine oxidase activity in rat brain.

The effects of some organophosphate pesticides, e.g. lebaycid, metacid and metasystox on the monoamine oxidase (MAO) activity in rat brain mitochondria have been studied. These pesticides cause significant inhibition of MAO activity in vitro but have negligible effects on its activity in vivo.

In vitro and in vivo effect of chloropromazine, imipramine and lithium chloride on monoamine oxidase activity in rat brain mitochondria.

Chloropromazine (CPZ) and imipramine at a concentration of 1 x 10(-3) M inhibit rat brain mitochondrial monoamine oxidase activity in vitro by 70 and 55% respectively, while lithium, even at a concentration of 0.05 M, inhibits the activity of this enzyme very negligibly (4%). In vivo, these drugs at a dose level of 56 mg CPZ, 76 mg imipramine and 76 mg lithium chloride/Kg body wt., did not cause any observable variation from normal in brain mitochondrial monoamine oxidase activity.

Laryngeal leiomyoma.

A case of leiomyoma arising from the left false cord is reported. In the larynx the lesion is very rare and the literature reports only 14 cases. Among those reported we were unable to find any case reported from India.