Probing the effect of nitro groups in nitramine based energetic molecules: a DFT and charge density study

The structure, electron density distribution, energetic and electrostatic properties of simple nitramine based energetic TMA, DMNA, MDA and TNA molecules were determined using density functional theory (B3LYP) with the 6-311G^** and aug-cc-pVDZ basis sets coupled with Bader's theory of atoms in molecules. In the NO₂ group substituted molecules, the N–N bond distance increases with the increase of NO₂ groups, whereas in C–N bonds, this effect is relatively less, and the distances are almost equal. The topological analysis of electron density reveals that the electron density ρ_bcp(r) of C–N and N–N bonds are significantly decreasing with the increase of NO₂ groups in the nitramine molecules. The Laplacian of electron density ▽²ρ_bcp(r) of N–NO₂ bonds [DMNA: ? 16.7 eÅ^? 5, MDA: ? 12.8 eÅ^? 5 and TNA: ? 7.9 eÅ^? 5] of the molecules are relatively less negative, and the values also decrease with the increase of NO₂ groups; this implies that the charge concentration decreases with the increase of NO₂ groups, which leads to weakening the N–N bonds of the molecules. The isosurface of molecular electrostatic potential displays high electronegative regions around the NO₂ groups. The oxygen balance OB₁₀₀ of the molecules increases as the number of NO₂ group increases in the molecules, in which, the TNA molecule having maximum OB₁₀₀ value [+7.89]. The band gap, heat of detonation, bond dissociation energy and charge imbalance are predominantly depends on the number of NO₂ group present in the molecule. The charge imbalance parameter (ν) has been calculated for all molecules, which reveals that TNA is a highly sensitive molecule, the corresponding ν value is 0.047.     

A Protein Disulfide Isomerase Controls Neuronal Migration through Regulation of Wnt Secretion

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Down-regulation of polysialic acid is required for efficient myelin formation

Oligodendrocyte precursor cells modify the neural cell adhesion molecule (NCAM) by the attachment of polysialic acid (PSA). Upon further differentiation into mature myelinating oligodendrocytes, however, oligodendrocyte precursor cells down-regulate PSA synthesis. In order to address the question of whether this down-regulation is a necessary prerequisite for the myelination process, transgenic mice expressing the polysialyltransferase ST8SiaIV under the control of the proteolipid protein promoter were generated. In these mice, postnatal down-regulation of PSA in oligodendrocytes was abolished. Most NCAM-120, the characteristic NCAM isoform in oligodendrocytes, carried PSA in the transgenic mice at all stages of postnatal development. Polysialylated NCAM-120 partially co-localized with myelin basic protein and was present in purified myelin. The permanent expression of PSA-NCAM in oligodendrocytes led to a reduced myelin content in the forebrains of transgenic mice during the period of active myelination and in the adult animal. In situ hybridizations indicated a significant decrease in the number of mature oligodendrocytes in the forebrain. Thus, down-regulation of PSA during oligodendrocyte differentiation is a prerequisite for efficient myelination by mature oligodendrocytes. Furthermore, myelin of transgenic mice exhibited structural abnormalities like redundant myelin and axonal degeneration, indicating that the down-regulation of PSA is also necessary for myelin maintenance.     

Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion

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Plant latex thrombin-like cysteine proteases alleviates bleeding by bypassing factor VIII in murine model

Hemostasis is a tightly regulated process which maintains a fluid state of blood within the vasculature and provides thrombotic response upon tissue injury. Various scientific studies have implicated the role of plant latex proteases in hemostasis using in vitro experiments. However, in vivo models substantiate their role in hemostasis. Therefore, in the present study, the effect of plant latex thrombin-like proteases (PTLPs) on hemostasis was investigated systematically using mice tail bleeding as a preclinical model. In this direction, latex protease fractions (LPFs), which showed potent thrombin-like activity, were selected as they act directly on fibrinogen to form clot and quickly stop bleeding. Thrombin-like activity was exhibited mainly by cysteine proteases. Calotropis gigantea, Carica papaya, Jatropha curcas, Oxystelma esculentum, Tabernaemontana divaricata, and Vallaris solanacea LPFs and papain from C. papaya latex significantly reduced bleeding on a topical application in normal and aspirin administered mice. In addition, PTLPs accelerated the clotting of factor VIII deficient plasma, while, papain brought back the clotting time to normal levels acting like a bypassing agent. Further, papain failed to show activity in the presence of specific cysteine protease inhibitor iodoacetic acid; confirming protease role in all the activities exhibited. At the tested dose, PTLPs except C. gigantea did not show toxicity. Further, structural and sequence comparison between PTLPs and human thrombin revealed structural and sequence dissimilarity indicating their unique nature. The findings of the present study may open up a new avenue for considering PTLPs including papain in the treatment of bleeding wounds.     

High fidelity epigenetic inheritance: Information theoretic model predicts threshold filling of histone modifications post replication

During cell devision, maintaining the epigenetic information encoded in histone modification patterns is crucial for survival and identity of cells. The faithful inheritance of the histone marks from the parental to the daughter strands is a puzzle, given that each strand gets only half of the parental nucleosomes. Mapping DNA replication and reconstruction of modifications to equivalent problems in communication of information, we ask how well enzymes can recover the parental modifications, if they were ideal computing machines. Studying a parameter regime where realistic enzymes can function, our analysis predicts that enzymes may implement a critical threshold filling algorithm which fills unmodified regions of length at most k. This algorithm, motivated from communication theory, is derived from the maximum à posteriori probability (MAP) decoding which identifies the most probable modification sequence based on available observations. Simulations using our method produce modification patterns similar to what has been observed in recent experiments. We also show that our results can be naturally extended to explain inheritance of spatially distinct antagonistic modifications.     

Influence of Water Hyacinth Cover on the Physico-chemical Characteristics of Water and Phytoplankton Composition in a Reservoir near Jaipur (India)

Water hyacinth (Eichhornia crassipes (Mart.) Solms.) invaded a eutrophic reservoir receiving domestic sewage near Jaipur (India) during 1975 and gradually developed a complete thick cover over the whole water body during Sept.–Oct. 1978. The physico-chemical characteristics of the water and the phytoplankton composition were studied during Sept. 1977–Sept. 1979 by fortnightly sampling. The changes observed during the second year of study are ascribed to the water hyacinth cover. The important changes were: lowering of water temperature, pH, dissolved oxygen content and nitrate nitrogen, and increase in total alkalinity, free carbon dioxide, chemical oxygen demand, ammonia nitrogen, sulphides, calcium, magnesium and phosphate phosphorus. The changes in the phytoplankton were both qualitative and quantitative. The green algae, particularly the species of Ankistrodesmus, Chlorella, Crucigenia and Selenastrum, increased considerably and replaced the blue-green algae, of which Oscillatoria and Microcystis disappeared totally. The densities of several other taxa changed significantly.