Liquid-induced colour change in a beetle: the concept of a photonic cell

PubMed Central

Mouchet, Sébastien R.; Van Hooijdonk, Eloise; Welch, Victoria L.; Louette, Pierre; Colomer, Jean-François; Su, Bao-Lian; Deparis, Olivier

2016-01-01

The structural colour of male Hoplia coerulea beetles is notable for changing from blue to green upon contact with water. In fact, reversible changes in both colour and fluorescence are induced in this beetle by various liquids, although the mechanism has never been fully explained. Changes enacted by water are much faster than those by ethanol, in spite of ethanol’s more rapid spread across the elytral surface. Moreover, the beetle’s photonic structure is enclosed by a thin scale envelope preventing direct contact with the liquid. Here, we note the presence of sodium, potassium and calcium salts in the scale material that mediate the penetration of liquid through putative micropores. The result leads to the novel concept of a “photonic cell”: namely, a biocompatible photonic structure that is encased by a permeable envelope which mediates liquid-induced colour changes in that photonic structure. Engineered photonic cells dispersed in culture media could revolutionize the monitoring of cell-metabolism. PMID:26758681

Dynamic structure mediates halophilic adaptation of a DNA polymerase from the deep-sea brines of the Red Sea.

PubMed

Takahashi, Masateru; Takahashi, Etsuko; Joudeh, Luay I; Marini, Monica; Das, Gobind; Elshenawy, Mohamed M; Akal, Anastassja; Sakashita, Kosuke; Alam, Intikhab; Tehseen, Muhammad; Sobhy, Mohamed A; Stingl, Ulrich; Merzaban, Jasmeen S; Di Fabrizio, Enzo; Hamdan, Samir M

2018-01-24

The deep-sea brines of the Red Sea are remote and unexplored environments characterized by high temperatures, anoxic water, and elevated concentrations of salt and heavy metals. This environment provides a rare system to study the interplay between halophilic and thermophilic adaptation in biologic macromolecules. The present article reports the first DNA polymerase with halophilic and thermophilic features. Biochemical and structural analysis by Raman and circular dichroism spectroscopy showed that the charge distribution on the protein's surface mediates the structural balance between stability for thermal adaptation and flexibility for counteracting the salt-induced rigid and nonfunctional hydrophobic packing. Salt bridge interactions via increased negative and positive charges contribute to structural stability. Salt tolerance, conversely, is mediated by a dynamic structure that becomes more fixed and functional with increasing salt concentration. We propose that repulsive forces among excess negative charges, in addition to a high percentage of negatively charged random coils, mediate this structural dynamism. This knowledge enabled us to engineer a halophilic version of KOD DNA polymerase.-Takahashi, M., Takahashi, E., Joudeh, L. I., Marini, M., Das, G., Elshenawy, M. M., Akal, A., Sakashita, K., Alam, I., Tehseen, M., Sobhy, M. A., Stingl, U., Merzaban, J. S., Di Fabrizio, E., Hamdan, S. M. Dynamic structure mediates halophilic adaptation of a DNA polymerase from the deep-sea brines of the Red Sea.

Negative refraction of acoustic waves using a foam-like metallic structure

NASA Astrophysics Data System (ADS)

Hladky-Hennion, A.-C.; Vasseur, J. O.; Haw, G.; Croënne, C.; Haumesser, L.; Norris, A. N.

2013-04-01

A phononic crystal (PC) slab made of a single metallic phase is shown, theoretically and experimentally, to display perfect negative index matching and focusing capability when surrounded with water. The proposed PC slab is a centimeter scale hollow metallic foam-like structure in which acoustic energy is mediated via the metal lattice. The negative index property arises from an isolated branch of the dispersion curves corresponding to a mode that can be coupled to incident acoustic waves in surrounding water. This band also intercepts the water sound line at a frequency in the ultrasonic range. The metallic structure is consequently a candidate for the negative refraction of incident longitudinal waves.

Water-soluble mercury ion sensing based on the thymine-Hg2+-thymine base pair using retroreflective Janus particle as an optical signaling probe.

PubMed

Chun, Hyeong Jin; Kim, Saemi; Han, Yong Duk; Kim, Dong Woo; Kim, Ka Ram; Kim, Hyo-Sop; Kim, Jae-Ho; Yoon, Hyun C

2018-05-01

Herein, we report an optical sensing platform for mercury ions (Hg 2+ ) in water based on the integration of Hg 2+ -mediated thymine-thymine (T-T) stabilization, a biotinylated stem-loop DNA probe, and a streptavidin-modified retroreflective Janus particle (SA-RJP). Two oligonucleotide probes, including a stem-loop DNA probe and an assistant DNA probe, were utilized. In the absence of Hg 2+ , the assistant DNA probe does not hybridize with the stem-loop probe due to their T-T mismatch, so the surface-immobilized stem-loop DNA probe remains a closed hairpin structure. In the presence of Hg 2+ , the DNA forms a double-stranded structure with the loop region via Hg 2+ -mediated T-T stabilization. This DNA hybridization induces stretching of the stem-loop DNA probe, exposing biotin. To translate these Hg 2+ -mediated structural changes in DNA probe into measurable signal, SA-RJP, an optical signaling label, is applied to recognize the exposed biotin. The number of biospecifically bound SA-RJPs is proportional to the concentration of Hg 2+ , so that the concentration of Hg 2+ can be quantitatively analyzed by counting the number of RJPs. Using the system, a highly selective and sensitive measurement of Hg 2+ was accomplished with a limit of detection of 0.027nM. Considering the simplified optical instrumentation required for retroreflection-based RJP counting, RJP-assisted Hg 2+ measurement can be accomplished in a much easier and inexpensive manner. Moreover, the detection of Hg 2+ in real drinking water samples including tap and commercial bottled water was successfully carried out. Copyright © 2018 Elsevier B.V. All rights reserved.

Significance of wall structure, macromolecular composition, and surface polymers to the survival and transport of Cryptosporidium parvum Oocysts

USDA-ARS?s Scientific Manuscript database

The structure and composition of the oocyst wall are primary factors determining the survival of Cryptosporidium parvum oocysts outside the host. An external polymer matrix (glycocalyx) may mediate interactions with environmental surfaces and, thus, affect the transport of oocysts in water, soil, an...

Conserved water-mediated H-bonding dynamics of catalytic Asn 175 in plant thiol protease.

PubMed

Nandi, Tapas K; Bairagya, Hridoy R; Mukhopadhyay, Bishnu P; Sekar, K; Sukul, Dipankar; Bera, Asim K

2009-03-01

The role of invariant water molecules in the activity of plant cysteine protease is ubiquitous in nature. On analysing the 11 different Protein DataBank (PDB) structures of plant thiol proteases, the two invariant water molecules W1 and W2 (W220 and W222 in the template 1PPN structure) were observed to form H-bonds with the O b atom of Asn 175. Extensive energy minimization and molecular dynamics simulation studies up to 2 ns on all the PDB and solvated structures clearly revealed the involvement of the H-bonding association of the two water molecules in fixing the orientation of the asparagine residue of the catalytic triad. From this study,it is suggested that H-bonding of the water molecule at the W1 invariant site better stabilizes the Asn residue at the active site of the catalytic triad.

Role of solvent-mediated carbodiimide cross-linking in fabrication of electrospun gelatin nanofibrous membranes as ophthalmic biomaterials.

PubMed

Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang; Ma, David Hui-Kang

2017-02-01

Due to their ability to mimic the structure of extracellular matrix, electrospun gelatin nanofibers are promising cell scaffolding materials for tissue engineering applications. However, the hydrophilic gelatin molecules usually need stabilization before use in aqueous physiological environment. Considering that biomaterials cross-linked via film immersion technique may have a more homogeneous cross-linked structure than vapor phase cross-linking, this work aims to investigate the chemical modification of electrospun gelatin nanofibrous membranes by liquid phase carbodiimide in the presence of ethanol/water co-solvents with varying ethanol concentrations ranging from 80 to 99.5vol%. The results of characterization showed that increasing water content in the binary reaction solvent system increases the extent of cross-linking of gelatin nanofibers, but simultaneously promotes the effect of biopolymer swelling and distortion in fiber mat structure. As compared to non-cross-linked counterparts, carbodiimide treated gelatin nanofibrous mats exhibited better thermal and biological stability where the shrinkage temperature and resistance to enzymatic degradation varied in response to ethanol/water solvent composition-mediated generation of cross-links. Irrespective of their cross-linking density, all studied membrane samples did not induce any responses in ocular epithelial cell cultures derived from cornea, lens, and retina. Unlike many other cross-linking agents and/or methods (e.g., excessive vapor phase cross-linking) that may pose a risk of toxicity, our study demonstrated that these nanofibrous materials are well tolerated by anterior segment tissues. These findings also indicate the safety of using ethanol/water co-solvents for chemical cross-linking of gelatin to engineer nanofibrous materials with negligible biological effects. In summary, the present results suggest the importance of solvent-mediated carbodiimide cross-linking in modulating structure-property relationship without compromising in vitro and in vivo biocompatibility of electrospun gelatin nanofibers for future ophthalmic applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Water-mediated electron transfer between protein redox centers.

PubMed

Migliore, Agostino; Corni, Stefano; Felice, Rosa Di; Molinari, Elisa

2007-04-12

Recent experimental and theoretical investigations show that water molecules between or near redox partners can significantly affect their electron-transfer (ET) properties. Here we study the effects of intervening water molecules on the electron self-exchange reaction of azurin (Az), by performing a conformational sampling on the water medium and by using a newly developed ab initio method to calculate transfer integrals between molecular redox sites. We show that the insertion of water molecules at the interface between the copper active sites of Az dimers slightly increases the overall ET rate, while some favorable water conformations can considerably enhance the ET kinetics. These features are traced back to the interplay of two competing factors: the electrostatic interaction between the water and protein subsystems (mainly opposing the ET process for the water arrangements drawn from MD simulations) and the effectiveness of water in mediating ET coupling pathways. Such an interplay provides a physical basis for the found absence of correlation between the electronic couplings derived through ab initio electronic structure calculations and the related quantities obtained through the Empirical Pathways (EP) method. In fact, the latter does not account for electrostatic effects on the transfer integrals. Thus, we conclude that the water-mediated electron tunneling is not controlled by the geometry of a single physical pathway. We discuss the results in terms of the interplay between different ET pathways controlled by the conformational changes of one of the water molecules via its electrostatic influence. Finally, we examine the dynamical effects of the interfacial water and check the validity of the Condon approximation.

Selecting an optimal number of binding site waters to improve virtual screening enrichments against the adenosine A2A receptor.

PubMed

Lenselink, Eelke B; Beuming, Thijs; Sherman, Woody; van Vlijmen, Herman W T; IJzerman, Adriaan P

2014-06-23

A major challenge in structure-based virtual screening (VS) involves the treatment of explicit water molecules during docking in order to improve the enrichment of active compounds over decoys. Here we have investigated this in the context of the adenosine A2A receptor, where water molecules have previously been shown to be important for achieving high enrichment rates with docking, and where the positions of some binding site waters are known from a high-resolution crystal structure. The effect of these waters (both their presence and orientations) on VS enrichment was assessed using a carefully curated set of 299 high affinity A2A antagonists and 17,337 decoys. We show that including certain crystal waters greatly improves VS enrichment and that optimization of water hydrogen positions is needed in order to achieve the best results. We also show that waters derived from a molecular dynamics simulation - without any knowledge of crystallographic waters - can improve enrichments to a similar degree as the crystallographic waters, which makes this strategy applicable to structures without experimental knowledge of water positions. Finally, we used decision trees to select an ensemble of structures with different water molecule positions and orientations that outperforms any single structure with water molecules. The approach presented here is validated against independent test sets of A2A receptor antagonists and decoys from the literature. In general, this water optimization strategy could be applied to any target with waters-mediated protein-ligand interactions.

Morphological evidence of mechanoreceptive gravity perception in a water flea - Daphnia magna

NASA Technical Reports Server (NTRS)

Meyers, D. G.

1985-01-01

Hair-like structures or setae located in the basal membrane of the swimming antennae of the water flea, D. magna, were observed by scanning electron microscopy and compared to mechanoreceptors in the Higher Order Crustacea. Similarities in anatomy, size, attachment, number, length, and orientation support the hypothesis that the setae are rheoceptive mechanoreceptors which mediate gravity perception through deflection by water currents during the sink phase of hop-and-sink swimming behavior.

High-resolution crystal structure of Streptococcus pyogenes β-NAD⁺ glycohydrolase in complex with its endogenous inhibitor IFS reveals a highly water-rich interface.

PubMed

Yoon, Ji Young; An, Doo Ri; Yoon, Hye Jin; Kim, Hyoun Sook; Lee, Sang Jae; Im, Ha Na; Jang, Jun Young; Suh, Se Won

2013-11-01

One of the virulence factors produced by Streptococcus pyogenes is β-NAD(+) glycohydrolase (SPN). S. pyogenes injects SPN into the cytosol of an infected host cell using the cytolysin-mediated translocation pathway. As SPN is toxic to bacterial cells themselves, S. pyogenes possesses the ifs gene that encodes an endogenous inhibitor for SPN (IFS). IFS is localized intracellularly and forms a complex with SPN. This intracellular complex must be dissociated during export through the cell envelope. To provide a structural basis for understanding the interactions between SPN and IFS, the complex was overexpressed between the mature SPN (residues 38-451) and the full-length IFS (residues 1-161), but it could not be crystallized. Therefore, limited proteolysis was used to isolate a crystallizable SPNct-IFS complex, which consists of the SPN C-terminal domain (SPNct; residues 193-451) and the full-length IFS. Its crystal structure has been determined by single anomalous diffraction and the model refined at 1.70 Å resolution. Interestingly, our high-resolution structure of the complex reveals that the interface between SPNct and IFS is highly rich in water molecules and many of the interactions are water-mediated. The wet interface may facilitate the dissociation of the complex for translocation across the cell envelope.

Crystal structural analysis of protein–protein interactions drastically destabilized by a single mutation

PubMed Central

Urakubo, Yoshiaki; Ikura, Teikichi; Ito, Nobutoshi

2008-01-01

The complex of barnase (bn) and barstar (bs), which has been widely studied as a model for quantitative analysis of protein–protein interactions, is significantly destabilized by a single mutation, namely, bs Asp39 → Ala, which corresponds to a change of 7.7 kcal·mol−1 in the free energy of binding. However, there has been no structural information available to explain such a drastic destabilization. In the present study, we determined the structure of the mutant complex at 1.58 Å resolution by X-ray crystallography. The complex was similar to the wild-type complex in terms of overall and interface structures; however, the hydrogen bond network mediated by water molecules at the interface was significantly different. Several water molecules filled the cavity created by the mutation and consequently caused rearrangement of the hydrated water molecules at the interface. The water molecules were redistributed into a channel-like structure that penetrated into the complex. Furthermore, molecular dynamics simulations showed that the mutation increased the mobility of water molecules at the interface. Since such a drastic change in hydration was not observed in other mutant complexes of bn and bs, the significant destabilization of the interaction may be due to this channel-like structure of hydrated water molecules. PMID:18441234

Anticorrosive Microbial Polysaccharides: Structure-Function Relationships

USDA-ARS?s Scientific Manuscript database

Water-soluble microbial polysaccharides are often implicated in biofilm formation and are believed to mediate cell-cell aggregation and adhesion to surfaces. Generally, biofilm formation is considered harmful or undesirable, as it leads to increased drag, plugging of pores, dimished heat transfer, ...

Structural, mutagenic and in silico studies of xyloglucan fucosylation in Arabidopsis thaliana suggest a water-mediated mechanism

DOE PAGES

Urbanowicz, Breeanna R.; Bharadwaj, Vivek S.; Alahuhta, Markus; ...

2017-07-03

The mechanistic underpinnings of the complex process of plant polysaccharide biosynthesis are poorly understood, largely due to the resistance of glycosyltransferase (GT) enzymes to structural characterization. In Arabidopsis thaliana, a glycosyl transferase family 37 (GT37) fucosyltransferase-1 (AtFUT1) catalyzes the regiospecific transfer of terminal 1,2-fucosyl residues to xyloglucan side chains - a key step in the biosynthesis of fucosylated sidechains of galactoxyloglucan. We unravel the mechanistic basis for fucosylation by AtFUT1 with a multipronged approach involving protein expression, X-ray crystallography, mutagenesis experiments and molecular simulations. Mammalian cell culture expressions enable sufficient production of the enzyme for X-ray crystallography, which reveals themore » structural architecture of AtFUT1 in complex with bound donor and acceptor substrate analogs. Here, the lack of an appropriately positioned active site residue as a catalytic base leads us to propose an atypical water-mediated fucosylation mechanism facilitated by an H-bonded network, which is corroborated by mutagenesis experiments as well as detailed atomistic simulations.« less

Structural, mutagenic and in silico studies of xyloglucan fucosylation in Arabidopsis thaliana suggest a water-mediated mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Urbanowicz, Breeanna R.; Bharadwaj, Vivek S.; Alahuhta, Markus

The mechanistic underpinnings of the complex process of plant polysaccharide biosynthesis are poorly understood, largely due to the resistance of glycosyltransferase (GT) enzymes to structural characterization. In Arabidopsis thaliana, a glycosyl transferase family 37 (GT37) fucosyltransferase-1 (AtFUT1) catalyzes the regiospecific transfer of terminal 1,2-fucosyl residues to xyloglucan side chains - a key step in the biosynthesis of fucosylated sidechains of galactoxyloglucan. We unravel the mechanistic basis for fucosylation by AtFUT1 with a multipronged approach involving protein expression, X-ray crystallography, mutagenesis experiments and molecular simulations. Mammalian cell culture expressions enable sufficient production of the enzyme for X-ray crystallography, which reveals themore » structural architecture of AtFUT1 in complex with bound donor and acceptor substrate analogs. Here, the lack of an appropriately positioned active site residue as a catalytic base leads us to propose an atypical water-mediated fucosylation mechanism facilitated by an H-bonded network, which is corroborated by mutagenesis experiments as well as detailed atomistic simulations.« less

Sensory Hair Cells: An Introduction to Structure and Physiology.

PubMed

McPherson, Duane R

2018-06-18

Sensory hair cells are specialized secondary sensory cells that mediate our senses of hearing, balance, linear acceleration, and angular acceleration (head rotation). In addition, hair cells in fish and amphibians mediate sensitivity to water movement through the lateral line system, and closely related electroreceptive cells mediate sensitivity to low-voltage electric fields in the aquatic environment of many fish species and several species of amphibian.Sensory hair cells share many structural and functional features across all vertebrate groups, while at the same time they are specialized for employment in a wide variety of sensory tasks. The complexity of hair cell structure is large, and the diversity of hair cell applications in sensory systems exceeds that seen for most, if not all, sensory cell types. The intent of this review is to summarize the more significant structural features and some of the more interesting and important physiological mechanisms that have been elucidated thus far. Outside vertebrates, hair cells are only known to exist in the coronal organ of tunicates. Electrical resonance, electromotility, and their exquisite mechanical sensitivity all contribute to the attractiveness of hair cells as a research subject.

Peroxidase-mediated polymerization of 1-naphthol: impact of solution pH and ionic strength.

PubMed

Bhandari, Alok; Xu, Fangxiang; Koch, David E; Hunter, Robert P

2009-01-01

Peroxidase-mediated oxidation has been proposed as a treatment method for naphthol-contaminated water. However, the impact of solution chemistry on naphthol polymerization and removal has not been documented. This research investigated the impact of pH and ionic strength on peroxidase-mediated removal of 1-naphthol in completely mixed batch reactors. The impact of hydrogen peroxide to 1-naphthol ratio and activity of horseradish peroxidase was also studied. Size exclusion chromatography was used to estimate the molecular weight distribution of oligomeric products, and liquid chromatography/mass spectrometry was used to estimate product structure. Naphthol transformation decreased with ionic strength, and substrate removal was lowest at neutral pHs. Solution pH influenced the size and the composition of the oligomeric products. An equimolar ratio of H(2)O(2):naphthol was sufficient for optimal naphthol removal. Polymerization products included naphthoquinones and oligomers derived from two, three, and four naphthol molecules. Our results illustrate the importance of water chemistry when considering a peroxidase-based approach for treatment of naphthol-contaminated waters.

Ultrafast infrared spectroscopy reveals water-mediated coherent dynamics in an enzyme active site.

PubMed

Adamczyk, Katrin; Simpson, Niall; Greetham, Gregory M; Gumiero, Andrea; Walsh, Martin A; Towrie, Michael; Parker, Anthony W; Hunt, Neil T

2015-01-01

Understanding the impact of fast dynamics upon the chemical processes occurring within the active sites of proteins and enzymes is a key challenge that continues to attract significant interest, though direct experimental insight in the solution phase remains sparse. Similar gaps in our knowledge exist in understanding the role played by water, either as a solvent or as a structural/dynamic component of the active site. In order to investigate further the potential biological roles of water, we have employed ultrafast multidimensional infrared spectroscopy experiments that directly probe the structural and vibrational dynamics of NO bound to the ferric haem of the catalase enzyme from Corynebacterium glutamicum in both H 2 O and D 2 O. Despite catalases having what is believed to be a solvent-inaccessible active site, an isotopic dependence of the spectral diffusion and vibrational lifetime parameters of the NO stretching vibration are observed, indicating that water molecules interact directly with the haem ligand. Furthermore, IR pump-probe data feature oscillations originating from the preparation of a coherent superposition of low-frequency vibrational modes in the active site of catalase that are coupled to the haem ligand stretching vibration. Comparisons with an exemplar of the closely-related peroxidase enzyme family shows that they too exhibit solvent-dependent active-site dynamics, supporting the presence of interactions between the haem ligand and water molecules in the active sites of both catalases and peroxidases that may be linked to proton transfer events leading to the formation of the ferryl intermediate Compound I. In addition, a strong, water-mediated, hydrogen bonding structure is suggested to occur in catalase that is not replicated in peroxidase; an observation that may shed light on the origins of the different functions of the two enzymes.

Theoretical vibrational sum-frequency generation spectroscopy of water near lipid and surfactant monolayer interfaces.

PubMed

Roy, S; Gruenbaum, S M; Skinner, J L

2014-11-14

Understanding the structure of water near cell membranes is crucial for characterizing water-mediated events such as molecular transport. To obtain structural information of water near a membrane, it is useful to have a surface-selective technique that can probe only interfacial water molecules. One such technique is vibrational sum-frequency generation (VSFG) spectroscopy. As model systems for studying membrane headgroup/water interactions, in this paper we consider lipid and surfactant monolayers on water. We adopt a theoretical approach combining molecular dynamics simulations and phase-sensitive VSFG to investigate water structure near these interfaces. Our simulated spectra are in qualitative agreement with experiments and reveal orientational ordering of interfacial water molecules near cationic, anionic, and zwitterionic interfaces. OH bonds of water molecules point toward an anionic interface leading to a positive VSFG peak, whereas the water hydrogen atoms point away from a cationic interface leading to a negative VSFG peak. Coexistence of these two interfacial water species is observed near interfaces between water and mixtures of cationic and anionic lipids, as indicated by the presence of both negative and positive peaks in their VSFG spectra. In the case of a zwitterionic interface, OH orientation is toward the interface on the average, resulting in a positive VSFG peak.

Insight towards the conserved water mediated recognition of catalytic and structural Zn(+2) ions in human Matrix Metalloproteinase-8 enzyme: A study by MD-simulation methods.

PubMed

Chakrabarti, Bornali; Bairagya, Hridoy R; Mishra, Deepak Kr; Chatterjee, Pradip Kumar; Mukhopadhyay, Bishnu P

2013-01-01

Human matrix metalloproteinase-8 (hMMP-8) plays a important role in the progression of colorectal cancer, metastasis, multiple sclerosis and rheumetoid arthritis. Extensive MD-simulation of the PDB and solvated structures of hMMP-8 has revealed the presence of few conserved water molecules around the catalytic and structural zinc (ZnC and ZnS) ions. The coordination of two conserved water molecules (W and WS) to ZnS and the H-bonding interaction of WS to S151 have indicated the plausible involvement of that metal ion in the catalytic process. Beside this the coupling of ZnC and ZnS metal ions (ZnC - W(H) (W(1))…..W(2) ….H(162) - ZnS) through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of two zinc ions which were separated by ~13 Å in their X-ray structures. This unique recognition of both the Zn(+2) ions in the enzyme through conserved water molecules may be implemented/ exploited for the design of antiproteolytic agent using water mimic drug design protocol.

The role of ZA channel water-mediated interactions in the design of bromodomain-selective BET inhibitors.

PubMed

Bharatham, Nagakumar; Slavish, Peter J; Shadrick, William R; Young, Brandon M; Shelat, Anang A

2018-05-01

The Bromodomain and Extra-Terminal domain (BET) family of proteins are involved in the regulation of gene transcription, and their dysregulation is implicated in several diseases including cancer. BET proteins contain two tandem bromodomains (BD1 and BD2) that independently recognize acetylated-lysine residues and appear to have distinct biological roles. We compared several published co-crystal structures and found five positions near the substrate binding pocket that vary between BET bromodomains. One position located in the ZA loop has unique properties. In BRD2-4, this residue is glutamine in BD1 and lysine in BD2; in BRDT, this residue is arginine in BD1 and asparagine in BD2. Using molecular modeling, we identified differences in the water-mediated network at this position between bromodomains. Molecular dynamics simulations helped rationalize the observed bromodomain selectivity for exemplar BET inhibitors and a congeneric series of tetrahydroquinolines (THQ) that differed by a single heteroatom near the ZA channel. The 2-furan SJ830599, the most BD2-selective THQ analog, did not disrupt the water-mediated networks in either domain, but was electrostatically-repulsed by the specific arrangement of the W5 water dipole in BD1. Our work underscores the value of exploring water-mediated interactions to study ligand binding, and highlights the difficulty of optimizing polar interactions due to high desolvation penalties. Finally, we suggest further modifications to THQ-based BET inhibitors that would increase BD2-selectivity in BRD2-4, while minimizing affinity for one or both bromodomains of BRDT. Copyright © 2018 Elsevier Inc. All rights reserved.

Structure-based cleavage mechanism of Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage

PubMed Central

Sheng, Gang; Zhao, Hongtu; Wang, Jiuyu; Rao, Yu; Tian, Wenwen; Swarts, Daan C.; van der Oost, John; Patel, Dinshaw J.; Wang, Yanli

2014-01-01

We report on crystal structures of ternary Thermus thermophilus Argonaute (TtAgo) complexes with 5′-phosphorylated guide DNA and a series of DNA targets. These ternary complex structures of cleavage-incompatible, cleavage-compatible, and postcleavage states solved at improved resolution up to 2.2 Å have provided molecular insights into the orchestrated positioning of catalytic residues, a pair of Mg2+ cations, and the putative water nucleophile positioned for in-line attack on the cleavable phosphate for TtAgo-mediated target cleavage by a RNase H-type mechanism. In addition, these ternary complex structures have provided insights into protein and DNA conformational changes that facilitate transition between cleavage-incompatible and cleavage-compatible states, including the role of a Glu finger in generating a cleavage-competent catalytic Asp-Glu-Asp-Asp tetrad. Following cleavage, the seed segment forms a stable duplex with the complementary segment of the target strand. PMID:24374628

The structure of the yeast plasma membrane SNARE complex reveals destabilizing water-filled cavities.

PubMed

Strop, Pavel; Kaiser, Stephen E; Vrljic, Marija; Brunger, Axel T

2008-01-11

SNARE proteins form a complex that leads to membrane fusion between vesicles, organelles, and plasma membrane in all eukaryotic cells. We report the 1.7A resolution structure of the SNARE complex that mediates exocytosis at the plasma membrane in the yeast Saccharomyces cerevisiae. Similar to its neuronal and endosomal homologues, the S. cerevisiae SNARE complex forms a parallel four-helix bundle in the center of which is an ionic layer. The S. cerevisiae SNARE complex exhibits increased helix bending near the ionic layer, contains water-filled cavities in the complex core, and exhibits reduced thermal stability relative to mammalian SNARE complexes. Mutagenesis experiments suggest that the water-filled cavities contribute to the lower stability of the S. cerevisiae complex.

Covalent docking of selected boron-based serine beta-lactamase inhibitors

NASA Astrophysics Data System (ADS)

Sgrignani, Jacopo; Novati, Beatrice; Colombo, Giorgio; Grazioso, Giovanni

2015-05-01

AmpC β-lactamase is a hydrolytic enzyme conferring resistance to β-lactam antibiotics in multiple Gram-negative bacteria. Therefore, identification of non-β-lactam compounds able to inhibit the enzyme is crucial for the development of novel antibacterial therapies. In general, AmpC inhibitors have to engage the highly solvent-exposed catalytic site of the enzyme. Therefore, understanding the implications of ligand-protein induced-fit and water-mediated interactions behind the inhibitor-enzyme recognition process is fundamental for undertaking structure-based drug design process. Here, we focus on boronic acids, a promising class of beta-lactamase covalent inhibitors. First, we optimized a docking protocol able to reproduce the experimentally determined binding mode of AmpC inhibitors bearing a boronic group. This goal was pursued (1) performing rigid and flexible docking calculations aiming to establish the role of the side chain conformations; and (2) investigating the role of specific water molecules in shaping the enzyme active site and mediating ligand protein interactions. Our calculations showed that some water molecules, conserved in the majority of the considered X-ray structures, are needed to correctly predict the binding pose of known covalent AmpC inhibitors. On this basis, we formalized our findings in a docking and scoring protocol that could be useful for the structure-based design of new boronic acid AmpC inhibitors.

Role of Interfacial Water Molecules in Proline-rich Ligand Recognition by the Src Homology 3 Domain of Abl*

PubMed Central

Palencia, Andres; Camara-Artigas, Ana; Pisabarro, M. Teresa; Martinez, Jose C.; Luque, Irene

2010-01-01

The interaction of Abl-Src homology 3 domain (SH3) with the high affinity peptide p41 is the most notable example of the inconsistency existing between the currently accepted description of SH3 complexes and their binding thermodynamic signature. We had previously hypothesized that the presence of interfacial water molecules is partially responsible for this thermodynamic behavior. We present here a thermodynamic, structural, and molecular dynamics simulation study of the interaction of p41 with Abl-SH3 and a set of mutants designed to alter the water-mediated interaction network. Our results provide a detailed description of the dynamic properties of the interfacial water molecules and a molecular interpretation of the thermodynamic effects elicited by the mutations in terms of the modulation of the water-mediated hydrogen bond network. In the light of these results, a new dual binding mechanism is proposed that provides a better description of proline-rich ligand recognition by Abl-SH3 and that has important implications for rational design. PMID:19906645

Role of interfacial water molecules in proline-rich ligand recognition by the Src homology 3 domain of Abl.

PubMed

Palencia, Andres; Camara-Artigas, Ana; Pisabarro, M Teresa; Martinez, Jose C; Luque, Irene

2010-01-22

The interaction of Abl-Src homology 3 domain (SH3) with the high affinity peptide p41 is the most notable example of the inconsistency existing between the currently accepted description of SH3 complexes and their binding thermodynamic signature. We had previously hypothesized that the presence of interfacial water molecules is partially responsible for this thermodynamic behavior. We present here a thermodynamic, structural, and molecular dynamics simulation study of the interaction of p41 with Abl-SH3 and a set of mutants designed to alter the water-mediated interaction network. Our results provide a detailed description of the dynamic properties of the interfacial water molecules and a molecular interpretation of the thermodynamic effects elicited by the mutations in terms of the modulation of the water-mediated hydrogen bond network. In the light of these results, a new dual binding mechanism is proposed that provides a better description of proline-rich ligand recognition by Abl-SH3 and that has important implications for rational design.

Mechanistic basis of adaptive maternal effects: egg jelly water balance mediates embryonic adaptation to acidity in Rana arvalis.

PubMed

Shu, Longfei; Suter, Marc J-F; Laurila, Anssi; Räsänen, Katja

2015-11-01

Environmental stress, such as acidification, can challenge persistence of natural populations and act as a powerful evolutionary force at ecological time scales. The ecological and evolutionary responses of natural populations to environmental stress at early life-stages are often mediated via maternal effects. During early life-stages, maternal effects commonly arise from egg coats (the extracellular structures surrounding the embryo), but the role of egg coats has rarely been studied in the context of adaptation to environmental stress. Previous studies on the moor frog Rana arvalis found that the egg coat mediated adaptive divergence along an acidification gradient in embryonic acid stress tolerance. However, the exact mechanisms underlying these adaptive maternal effects remain unknown. Here, we investigated the role of water balance and charge state (zeta potential) of egg jelly coats in embryonic adaptation to acid stress in three populations of R. arvalis. We found that acidic pH causes severe water loss in the egg jelly coat, but that jelly coats from an acid-adapted population retained more water than jelly coats from populations not adapted to acidity. Moreover, embryonic acid tolerance (survival at pH 4.0) correlated with both water loss and charge state of the jelly, indicating that negatively charged glycans influence jelly water balance and contribute to embryonic adaptation to acidity. These results indicate that egg coats can harbor extensive intra-specific variation, probably facilitated in part via strong selection on water balance and glycosylation status of egg jelly coats. These findings shed light on the molecular mechanisms of environmental stress tolerance and adaptive maternal effects.

Structure of the thermophilic l-Arabinose isomerase from Geobacillus kaustophilus reveals metal-mediated intersubunit interactions for activity and thermostability.

PubMed

Choi, Jin Myung; Lee, Yong-Jik; Cao, Thinh-Phat; Shin, Sun-Mi; Park, Min-Kyu; Lee, Han-Seung; di Luccio, Eric; Kim, Seong-Bo; Lee, Sang-Jae; Lee, Sang Jun; Lee, Sung Haeng; Lee, Dong-Woo

2016-04-15

Thermophilic l-arabinose isomerase (AI), which catalyzes the interconversion of l-arabinose and l-ribulose, can be used to produce d-tagatose, a sugar substitute, from d-galactose. Unlike mesophilic AIs, thermophilic AIs are highly dependent on divalent metal ions for their catalytic activity and thermostability at elevated temperatures. However, the molecular basis underlying the substrate preferences and metal requirements of multimeric AIs remains unclear. Here we report the first crystal structure of the apo and holo forms of thermophilic Geobacillus kaustophilus AI (GKAI) in hexamer form. The structures, including those of GKAI in complex with l-arabitol, and biochemical analyses revealed not only how the substrate-binding site of GKAI is formed through displacement of residues at the intersubunit interface when it is bound to Mn(2+), but also revealed the water-mediated H-bonding networks that contribute to the structural integrity of GKAI during catalysis. These observations suggest metal-mediated isomerization reactions brought about by intersubunit interactions at elevated temperatures are responsible for the distinct active site features that promote the substrate specificity and thermostability of thermophilic AIs. Copyright © 2016 Elsevier Inc. All rights reserved.

Ligand-Mediated Ring → Cube Transformation in a Catalytic Subnanocluster: Co4O4(MeCN)n with n = 1-6.

PubMed

Luo, Sijie; Dibble, Collin J; Duncan, Michael A; Truhlar, Donald G

2014-08-07

We studied the Co4O4 subnanocluster and its MeCN-coated species using density functional theory, and we found that the Co4O4 core presents distinctive structures in bare and ligand-coated species. We propose a possible ligand-mediated ring → cube transformation mechanism during the ligand-coating process of the Co4O4 core due to the stronger binding energies of the MeCN ligands to the 3D distorted cube structure than to the 2D ring and ladder structures; theory indicates that three ligands are sufficient to stabilize the cube structure. Both ring and cube structures are ferromagnetic. Our finding is potentially useful for understanding the catalysis mechanism of Co4O4 species, which have important applications in solar energy conversion and water splitting; these catalysis reactions usually involve frequent addition and subtraction of various ligands and thus possibly involve core rearrangement processes similar to our findings.

Escherichia coli growth changes by the mediated effects after low-intensity electromagnetic irradiation of extremely high frequencies.

PubMed

Torgomyan, Heghine; Hovnanyan, Karlen; Trchounian, Armen

2013-04-01

Water is the major constituent of environmental medium and biological systems. The effects occurring in water as a result of low-intensity electromagnetic irradiation (EMI) in extremely high frequencies are supposed to be the primary mechanism to create conditions for biological responses. The EMI effects on Escherichia coli, after irradiation of their suspension, are most probably water-mediated. Indirect effects of EMI at 51.8, 53, 70.6, and 73 GHz frequencies on bacteria, through water, assay buffer (Tris-phosphate buffer with inorganic salts at low or moderate concentrations), or peptone growth medium were studied. The mediated effects of 70.6 and 73 GHz irradiated water, assay buffer, and growth medium on E. coli growth characteristics were insignificant. But the results were different for 51.8 and 53 GHz. EMI mediated effects on bacterial growth were clearly demonstrated. The effects were more strongly expressed with 53 GHz. Moreover, it was shown that 70.6 and 73 GHz similarly suppressed the cell growth after direct irradiation of E. coli in water or on solid medium. Interestingly, for 51.8 and 53 GHz the bacterial growth decreases after suspension irradiation was less, compared to the direct irradiation of bacteria on solid medium. Especially, it was also more expressed in case of 53 GHz. Also with electron microscopy, EMI-induced bacterial cell sizes and structure different changes were detected. In addition, the distinguished changes in surface tension, oxidation-reduction potential and pH of water, assay buffer, growth medium, and bacterial suspension were determined. They depended on EMI frequency used. The differences could be associated with the partial absorbance of EMI energy by the surrounding medium, which depends on a specific frequency. The results are crucial to understand biophysical mechanisms of EMI effects on bacteria.

Psychosocial Factors Mediating the Effect of the CHoBI7 Intervention on Handwashing With Soap: A Randomized Controlled Trial.

PubMed

George, Christine Marie; Biswas, Shwapon; Jung, Danielle; Perin, Jamie; Parvin, Tahmina; Monira, Shirajum; Saif-Ur-Rahman, K M; Rashid, Mahamud-Ur; Bhuyian, Sazzadul Islam; Thomas, Elizabeth D; Dreibelbis, Robert; Begum, Farzana; Zohura, Fatema; Zhang, Xiaotong; Sack, David A; Alam, Munirul; Sack, R Bradley; Leontsini, Elli; Winch, Peter J

2017-08-01

Inadequate hand hygiene is estimated to result in nearly 300,000 deaths annually, with the majority of deaths being among children younger than 5 years. In an effort to promote handwashing with soap and water treatment behaviors among highly susceptible household members of cholera patients, we recently developed the Cholera-Hospital-Based Intervention-for-7-Days (CHoBI7); chobi means picture in Bengali. This 1-week handwashing with soap and water treatment intervention is delivered by a promoter in the hospital and the home to cholera patients and their household members. In our randomized controlled trial of this intervention, we observed a significant reduction in symptomatic cholera infections during the 1-week intervention period compared to the control arm and sustained high uptake of observed handwashing with soap behaviors up to 12 months postintervention. The aim of the present study was to assess the underlying mechanism of change that led to the high handwashing with soap behavior observed among participants who received the CHoBI7 intervention. Handwashing with soap was measured using 5-hour structured observation, and psychosocial factors were assessed using a structured questionnaire among 170 intervention and 174 control household members enrolled in the CHoBI7 trial. To investigate potential mediators of the CHoBI7 intervention effect, mediation models were performed. Response efficacy was found to mediate the intervention's effect on habit formation for handwashing with soap at the 1-week follow-up, and disgust, convenience, and cholera awareness were mediators of habit maintenance at the 6- to 12-month follow-up. These results support the use of theory-driven approaches for the development and implementation of handwashing with soap interventions.

Ag(I)-mediated homo and hetero pairs of guanosine and cytidine: monitoring by circular dichroism spectroscopy.

PubMed

Goncharova, Iryna

2014-01-24

Ag(I)-containing compounds are attractive as antibacterial and antifungal agents. The renewed interest in the application of silver(I) compounds has led to the need for detailed knowledge of the mechanism of their action. One of the possible ways is the coordination of Ag(I) to G-C pairs of DNA, where Ag(+) ions form Ag(I)-mediated base pairs and inhibit the transcription. Herein, a systematic chiroptical study on silver(I)-mediated homo and mixed pairs of the C-G complementary-base derivatives cytidine(C) and 5'-guanosine monophosphate(G) in water is presented. Ag(I)-mediated homo and hetero pairs of G and C and their self-assembled species were studied under two pH levels (7.0 and 10.0) by vibrational (VCD) and electronic circular dichroism(ECD). VCD was used for the first time in this field and showed itself to be a powerful method for obtaining specific structural information in solution. Based on results of the VCD experiments, the different geometries of the homo pairs were proposed under pH 7.0 and 10.0. ECD was used as a diagnostic tool to characterize the studied systems and as a contact point between the previously defined structures of the metal or proton mediated pairs of nucleobases and the systems studied here. On the basis of the obtained data, the formation of the self-assembled species of cytidine with a structure similar to the i-motif structure in DNA was proposed at pH 10.0. Copyright © 2013 Elsevier B.V. All rights reserved.

Ag(I)-mediated homo and hetero pairs of guanosine and cytidine: Monitoring by circular dichroism spectroscopy

NASA Astrophysics Data System (ADS)

Goncharova, Iryna

2014-01-01

Ag(I)-containing compounds are attractive as antibacterial and antifungal agents. The renewed interest in the application of silver(I) compounds has led to the need for detailed knowledge of the mechanism of their action. One of the possible ways is the coordination of Ag(I) to G-C pairs of DNA, where Ag+ ions form Ag(I)-mediated base pairs and inhibit the transcription. Herein, a systematic chiroptical study on silver(I)-mediated homo and mixed pairs of the C-G complementary-base derivatives cytidine(C) and 5‧-guanosine monophosphate(G) in water is presented. Ag(I)-mediated homo and hetero pairs of G and C and their self-assembled species were studied under two pH levels (7.0 and 10.0) by vibrational (VCD) and electronic circular dichroism(ECD). VCD was used for the first time in this field and showed itself to be a powerful method for obtaining specific structural information in solution. Based on results of the VCD experiments, the different geometries of the homo pairs were proposed under pH 7.0 and 10.0. ECD was used as a diagnostic tool to characterize the studied systems and as a contact point between the previously defined structures of the metal or proton mediated pairs of nucleobases and the systems studied here. On the basis of the obtained data, the formation of the self-assembled species of cytidine with a structure similar to the i-motif structure in DNA was proposed at pH 10.0.

Active site dynamics of ribonuclease.

PubMed Central

Brünger, A T; Brooks, C L; Karplus, M

1985-01-01

The stochastic boundary molecular dynamics method is used to study the structure, dynamics, and energetics of the solvated active site of bovine pancreatic ribonuclease A. Simulations of the native enzyme and of the enzyme complexed with the dinucleotide substrate CpA and the transition-state analog uridine vanadate are compared. Structural features and dynamical couplings for ribonuclease residues found in the simulation are consistent with experimental data. Water molecules, most of which are not observed in crystallographic studies, are shown to play an important role in the active site. Hydrogen bonding of residues with water molecules in the free enzyme is found to mimic the substrate-enzyme interactions of residues involved in binding. Networks of water stabilize the cluster of positively charged active site residues. Correlated fluctuations between the uridine vanadate complex and the distant lysine residues are mediated through water and may indicate a possible role for these residues in stabilizing the transition state. Images PMID:3866234

Thermodynamic Characterization of Hydration Sites from Integral Equation-Derived Free Energy Densities: Application to Protein Binding Sites and Ligand Series.

PubMed

Güssregen, Stefan; Matter, Hans; Hessler, Gerhard; Lionta, Evanthia; Heil, Jochen; Kast, Stefan M

2017-07-24

Water molecules play an essential role for mediating interactions between ligands and protein binding sites. Displacement of specific water molecules can favorably modulate the free energy of binding of protein-ligand complexes. Here, the nature of water interactions in protein binding sites is investigated by 3D RISM (three-dimensional reference interaction site model) integral equation theory to understand and exploit local thermodynamic features of water molecules by ranking their possible displacement in structure-based design. Unlike molecular dynamics-based approaches, 3D RISM theory allows for fast and noise-free calculations using the same detailed level of solute-solvent interaction description. Here we correlate molecular water entities instead of mere site density maxima with local contributions to the solvation free energy using novel algorithms. Distinct water molecules and hydration sites are investigated in multiple protein-ligand X-ray structures, namely streptavidin, factor Xa, and factor VIIa, based on 3D RISM-derived free energy density fields. Our approach allows the semiquantitative assessment of whether a given structural water molecule can potentially be targeted for replacement in structure-based design. Finally, PLS-based regression models from free energy density fields used within a 3D-QSAR approach (CARMa - comparative analysis of 3D RISM Maps) are shown to be able to extract relevant information for the interpretation of structure-activity relationship (SAR) trends, as demonstrated for a series of serine protease inhibitors.

Water mediated synthesis, spectral and structural studies of ethyl 6-amino-4-aryl-5-cyano-2-propyl-4H-pyran-3-carboxylates: Single crystal X-ray structure of ethyl 6-amino-4-(2-chlorophenyl)-5-cyano-2-propyl-4H-pyran-3-carboxylate

NASA Astrophysics Data System (ADS)

Udhaya Kumar, C.; Sethukumar, A.; Agilandeshwari, R.; Arul Prakasam, B.; Vidhyasagar, T.; Sillanpää, Mika

2014-02-01

An efficient and multifunctional three component synthetic protocol was developed to synthesize ethyl 6-amino-4-aryl-5-cyano-2-propyl-4H-pyran-3-carboxylates from ethyl 3-oxohexanoate, malononitrile and corresponding aldehydes (1a-11a) using K2CO3 as a catalyst under water solvent in good yields. The derived compounds have been analyzed by IR and NMR (1D and 2D) spectra. Single crystal X-ray structural analysis of 2a, evidences the flattened-boat conformation of pyran ring and the phenyl group is nearly perpendicular to the pyran ring.

Direct and terrestrial vegetation-mediated effects of environmental change on aquatic ecosystem processes

Treesearch

Becky A. Ball; John S. Kominoski; Heather E. Adams; Stuart E. Jones; Evan S. Kane; Terrance D. Loecke; Wendy M. Mahaney; Jason P. Martina; Chelse M. Prather; Todd M.P. Robinson; Christopher T. Solomon

2010-01-01

Global environmental changes have direct effects on aquatic ecosystems, as well as indirect effects through alterations of adjacent terrestrial ecosystem structure and functioning. For example, shifts in terrestrial vegetation communities resulting from global changes can affect the quantity and quality of water, organic matter, and nutrient inputs to aquatic...

Altered snowfall and soil disturbance influence the early life stage transitions and recruitment of a native and invasive grass in a cold desert

USDA-ARS?s Scientific Manuscript database

Climate change effects on plants are expected to be primarily mediated through early life stage transitions. Snowfall variability, in particular, may have profound impacts on seedling recruitment; structuring plant populations and communities, especially in mid-latitude systems. These water-limi...

A single Watson-Crick G x C base pair in water: aqueous hydrogen bonds in hydrophobic cavities.

PubMed

Sawada, Tomohisa; Fujita, Makoto

2010-05-26

Hydrogen bond (H-bond) formation in water has been a challenging task because water molecules are constant competitors. In biological systems, however, stable H-bonds are formed by shielding the H-bonding sites from the competing water molecules within hydrophobic pockets. Inspired by the nature's elaborated way, we found that even mononucleotides (G and C) can form the minimal G x C Watson-Crick pair in water by simply providing a synthetic cavity that efficiently shields the Watson-Crick H-bonding sites. The minimal Watson-Crick structure in water was elucidated by NMR study and firmly characterized by crystallographic analysis. The crystal structure also displays that, within the cavity, coencapsulated anions and solvents efficiently mediate the minimal G x C Watson-Crick pair formation. Furthermore, the competition experiments with the other nucleobases clearly revealed the evident selectivity for the G x C base pairing in water. These results show the fact that a H-bonded nucleobase pair was effectively induced and stabilized in the local environment of an artificial hydrophobic cavity.

DRoP: a water analysis program identifies Ras-GTP-specific pathway of communication between membrane-interacting regions and the active site.

PubMed

Kearney, Bradley M; Johnson, Christian W; Roberts, Daniel M; Swartz, Paul; Mattos, Carla

2014-02-06

Ras GTPase mediates several cellular signal transduction pathways and is found mutated in a large number of cancers. It is active in the GTP-bound state, where it interacts with effector proteins, and at rest in the GDP-bound state. The catalytic domain is tethered to the membrane, with which it interacts in a nucleotide-dependent manner. Here we present the program Detection of Related Solvent Positions (DRoP) for crystallographic water analysis on protein surfaces and use it to study Ras. DRoP reads and superimposes multiple Protein Data Bank coordinates, transfers symmetry-related water molecules to the position closest to the protein surface, and ranks the waters according to how well conserved and tightly clustered they are in the set of structures. Coloring according to this rank allows visualization of the results. The effector-binding region of Ras is hydrated with highly conserved water molecules at the interface between the P-loop, switch I, and switch II, as well as at the Raf-RBD binding pocket. Furthermore, we discovered a new conserved water-mediated H-bonding network present in Ras-GTP, but not in Ras-GDP, that links the nucleotide sensor residues R161 and R164 on helix 5 to the active site. The double mutant RasN85A/N86A, where the final link between helix 5 and the nucleotide is not possible, is a severely impaired enzyme, while the single mutant RasN86A, with partial connection to the active site, has a wild-type hydrolysis rate. DRoP was instrumental in determining the water-mediated connectivity networks that link two lobes of the catalytic domain in Ras. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hydration in drug design. 3. Conserved water molecules at the ligand-binding sites of homologous proteins

NASA Astrophysics Data System (ADS)

Poornima, C. S.; Dean, P. M.

1995-12-01

Water molecules are known to play an important rôle in mediating protein-ligand interactions. If water molecules are conserved at the ligand-binding sites of homologous proteins, such a finding may suggest the structural importance of water molecules in ligand binding. Structurally conserved water molecules change the conventional definition of `binding sites' by changing the shape and complementarity of these sites. Such conserved water molecules can be important for site-directed ligand/drug design. Therefore, five different sets of homologous protein/protein-ligand complexes have been examined to identify the conserved water molecules at the ligand-binding sites. Our analysis reveals that there are as many as 16 conserved water molecules at the FAD binding site of glutathione reductase between the crystal structures obtained from human and E. coli. In the remaining four sets of high-resolution crystal structures, 2-4 water molecules have been found to be conserved at the ligand-binding sites. The majority of these conserved water molecules are either bound in deep grooves at the protein-ligand interface or completely buried in cavities between the protein and the ligand. All these water molecules, conserved between the protein/protein-ligand complexes from different species, have identical or similar apolar and polar interactions in a given set. The site residues interacting with the conserved water molecules at the ligand-binding sites have been found to be highly conserved among proteins from different species; they are more conserved compared to the other site residues interacting with the ligand. These water molecules, in general, make multiple polar contacts with protein-site residues.

The solvation structure of alprazolam.

PubMed

Sridhar, Akshay; Johnston, Andrew J; Varathan, Luxmmi; McLain, Sylvia E; Biggin, Philip C

2016-08-10

Alprazolam is a benzodiazepine that is commonly prescribed for the treatment of anxiety and other related disorders. Like other benzodiazepines, it is thought to exert its effect through interaction with GABAA receptors. However, it has also been described as a potent and selective protein interaction inhibitor of bromodomain and extra-terminal (BET) proteins. Indeed, the only crystal structure of alprazolam bound to a protein is a complex between alprazolam and the BRD4 bromodomain. The structure shows that the complex also involves many water interactions that mediate contacts between the drug and the protein, a scenario that exists in many drug-protein complexes. How such waters relate to solvation patterns of small molecules may improve our understanding of what dictates their appearance or absence in bridging positions within complexes and thus will be important in terms of future rational drug-design. Here, we use neutron diffraction in conjunction with molecular dynamics simulations to provide a detailed analysis of how water molecules interact with alprazolam in methanol/water mixtures. The agreement between the neutron diffraction and the molecular dynamics is extremely good. We discuss the results in the context of drug design.

Plasticity of vulnerability to leaf hydraulic dysfunction during acclimation to drought in grapevines: an osmotic-mediated process.

PubMed

Martorell, Sebastian; Medrano, Hipolito; Tomàs, Magdalena; Escalona, José M; Flexas, Jaume; Diaz-Espejo, Antonio

2015-03-01

Previous studies have reported correlation of leaf hydraulic vulnerability with pressure-volume parameters related to cell turgor. This link has been explained on the basis of the effects of turgor on connectivity among cells and tissue structural integrity, which affect leaf water transport. In this study, we tested the hypothesis that osmotic adjustment to water stress would shift the leaf vulnerability curve toward more negative water potential (Ψ leaf ) by increasing turgor at low Ψ leaf . We measured leaf hydraulic conductance (K leaf ), K leaf vulnerability [50 and 80% loss of K leaf (P50 and P80 ); |Ψ leaf | at 50 and 80% loss of K leaf , respectively), bulk leaf water relations, leaf gas exchange and sap flow in two Vitis vinifera cultivars (Tempranillo and Grenache), under two water treatments. We found that P50 , P80 and maximum K leaf decreased seasonally by more than 20% in both cultivars and watering treatments. However, K leaf at 2 MPa increased threefold, while osmotic potential at full turgor and turgor loss point decreased. Our results indicate that leaf resistance to hydraulic dysfunction is seasonally plastic, and this plasticity may be mediated by osmotic adjustment. © 2014 Scandinavian Plant Physiology Society.

Microphase Separation in Oil-Water Mixtures Containing Hydrophilic and Hydrophobic Ions

NASA Astrophysics Data System (ADS)

Tasios, Nikos; Samin, Sela; van Roij, René; Dijkstra, Marjolein

2017-11-01

We develop a lattice-based Monte Carlo simulation method for charged mixtures capable of treating dielectric heterogeneities. Using this method, we study oil-water mixtures containing an antagonistic salt, with hydrophilic cations and hydrophobic anions. Our simulations reveal several phases with a spatially modulated solvent composition, in which the ions partition between water-rich and water-poor regions according to their affinity. In addition to the recently observed lamellar phase, we find tubular and droplet phases, reminiscent of those found in block copolymers and surfactant systems. Interestingly, these structures stem from ion-mediated interactions, which allows for tuning of the phase behavior via the concentrations, the ionic properties, and the temperature.

Influence of root-water-uptake parameterization on simulated heat transport in a structured forest soil

NASA Astrophysics Data System (ADS)

Votrubova, Jana; Vogel, Tomas; Dohnal, Michal; Dusek, Jaromir

2015-04-01

Coupled simulations of soil water flow and associated transport of substances have become a useful and increasingly popular tool of subsurface hydrology. Quality of such simulations is directly affected by correctness of its hydraulic part. When near-surface processes under vegetation cover are of interest, appropriate representation of the root water uptake becomes essential. Simulation study of coupled water and heat transport in soil profile under natural conditions was conducted. One-dimensional dual-continuum model (S1D code) with semi-separate flow domains representing the soil matrix and the network of preferential pathways was used. A simple root water uptake model based on water-potential-gradient (WPG) formulation was applied. As demonstrated before [1], the WPG formulation - capable of simulating both the compensatory root water uptake (in situations when reduced uptake from dry layers is compensated by increased uptake from wetter layers), and the root-mediated hydraulic redistribution of soil water - enables simulation of more natural soil moisture distribution throughout the root zone. The potential effect on heat transport in a soil profile is the subject of the present study. [1] Vogel T., M. Dohnal, J. Dusek, J. Votrubova, and M. Tesar. 2013. Macroscopic modeling of plant water uptake in a forest stand involving root-mediated soil-water redistribution. Vadose Zone Journal, 12, 10.2136/vzj2012.0154. The research was supported by the Czech Science Foundation Project No. 14-15201J.

Active-site solvent replenishment observed during human carbonic anhydrase II catalysis.

PubMed

Kim, Jin Kyun; Lomelino, Carrie L; Avvaru, Balendu Sankara; Mahon, Brian P; McKenna, Robert; Park, SangYoun; Kim, Chae Un

2018-01-01

Human carbonic anhydrase II (hCA II) is a zinc metalloenzyme that catalyzes the reversible hydration/dehydration of CO 2 /HCO 3 - . Although hCA II has been extensively studied to investigate the proton-transfer process that occurs in the active site, its underlying mechanism is still not fully understood. Here, ultrahigh-resolution crystallographic structures of hCA II cryocooled under CO 2 pressures of 7.0 and 2.5 atm are presented. The structures reveal new intermediate solvent states of hCA II that provide crystallographic snapshots during the restoration of the proton-transfer water network in the active site. Specifically, a new intermediate water (W I ') is observed next to the previously observed intermediate water W I , and they are both stabilized by the five water molecules at the entrance to the active site (the entrance conduit). Based on these structures, a water network-restructuring mechanism is proposed, which takes place at the active site after the nucleophilic attack of OH - on CO 2 . This mechanism explains how the zinc-bound water (W Zn ) and W1 are replenished, which are directly responsible for the reconnection of the His64-mediated proton-transfer water network. This study provides the first 'physical' glimpse of how a water reservoir flows into the hCA II active site during its catalytic activity.

Terrain and subsurface influences on runoff generation in a steep, deep, highly weathered system

NASA Astrophysics Data System (ADS)

Mallard, J. M.; McGlynn, B. L.; Richter, D. D., Jr.

2017-12-01

Our understanding of runoff generation in regions characterized by deep, highly weathered soils is incomplete, despite the prevalence occupation of these landscapes worldwide. To address this, we instrumented a first-order watershed in the Piedmont of South Carolina, USA, a region that extends east of the Appalachians from Maryland to Alabama, and home to some of the most rapid population growth in the country. Although regionally the relief is modest, the landscape is often highly dissected and local slopes can be steep and highly varied. The typical soils of the region are kaolinite dominated ultisols, with hydrologic properties controlled by argillic Bt horizons, often with >50% clay-size fraction. The humid subtropical climate creates relatively consistent precipitation intra-annually and seasonally variable energy availability. Consequently, the mixed deciduous and coniferous tree cover creates a strong evapotranspiration-mediated hydrologic dynamic. While moist soils and extended stream networks are typical from late fall through spring, relatively dry soils and contracting stream networks emerge in the summer and early fall. Here, we seek to elucidate the relative influence of the vertical soil and spatial terrain structure of this region on watershed hillslope hydrology and subsequent runoff generation. We installed a network of nested, shallow groundwater wells and soil water content probes within an ephemeral to first-order watershed to continuously measure soil and groundwater dynamics across soil horizons and landscape position. We also recorded local precipitation and discharge from this watershed. Most landscape positions exhibited minimal water table response to precipitation throughout dry summer periods, with infrequently observed responses rarely coincident with streamflow generation. In contrast, during the wetter late fall through early spring period, streamflow was driven by the interaction between transient perched water tables and topographically mediated redistribution of shallow groundwater downslope. Our findings suggest that understanding streamflow generation in regions possessing both complex terrain and complex vertical soil structure requires synchronous characterization of terrain mediated water redistribution and subsurface soil hydrology.

Plant Survival and Mortality during Drought Can be Mediated by Co-occurring Species' Physiological and Morphological Traits: Results from a Model

NASA Astrophysics Data System (ADS)

Tai, X.; Mackay, D. S.

2015-12-01

Interactions among co-occurring species are mediated by plant physiology, morphology and environment. Without proper mechanisms to account for these factors, it remains difficult to predict plant mortality/survival under changing climate. A plant ecophysiological model, TREES, was extended to incorporate co-occurring species' belowground interaction for water. We used it to examine the interaction between two commonly co-occurring species during drought experiment, pine (Pinus edulis) and juniper (Juniperus monosperma), with contrasting physiological traits (vulnerability to cavitation and leaf water potential regulation). TREES was parameterized and validated using field-measured plant physiological traits. The root architecture (depth, profile, and root area to leaf area ratio) of juniper was adjusted to see how root morphology could affect the survival/mortality of its neighboring pine under both ambient and drought conditions. Drought suppressed plant water and carbon uptake, as well increased the average percentage loss of conductivity (PLC). Pine had 59% reduction in water uptake, 48% reduction in carbon uptake, and 38% increase in PLC, while juniper had 56% reduction in water uptake, 50% reduction in carbon and 29% increase in PLC, suggesting different vulnerability to drought as mediated by plant physiological traits. Variations in juniper root architecture further mediated drought stress on pine, from negative to positive. Different juniper root architecture caused variations in response of pine over drought (water uptake reduction ranged 0% ~63%, carbon uptake reduction ranged 0% ~ 70%, and PLC increase ranged 2% ~ 91%). Deeper or more uniformly distributed roots of juniper could effectively mitigate stress experienced by pine. In addition, the total water and carbon uptake tended to increase as the ratio of root area to leaf area increased while PLC showed non-monotonic response, suggesting the potential trade-off between maximizing resource uptake and susceptibility to cavitation. The results showed that co-occurring species' morphological traits could alleviate or aggravate stress imposed by drought and should therefore be considered together with plant physiological traits in predicting plant mortality and ecosystem structural shift under future climate conditions.

The interfacial character of antibody paratopes: analysis of antibody-antigen structures.

PubMed

Nguyen, Minh N; Pradhan, Mohan R; Verma, Chandra; Zhong, Pingyu

2017-10-01

In this study, computational methods are applied to investigate the general properties of antigen engaging residues of a paratope from a non-redundant dataset of 403 antibody-antigen complexes to dissect the contribution of hydrogen bonds, hydrophobic, van der Waals contacts and ionic interactions, as well as role of water molecules in the antigen-antibody interface. Consistent with previous reports using smaller datasets, we found that Tyr, Trp, Ser, Asn, Asp, Thr, Arg, Gly, His contribute substantially to the interactions between antibody and antigen. Furthermore, antibody-antigen interactions can be mediated by interfacial waters. However, there is no reported comprehensive analysis for a large number of structured waters that engage in higher ordered structures at the antibody-antigen interface. From our dataset, we have found the presence of interfacial waters in 242 complexes. We present evidence that suggests a compelling role of these interfacial waters in interactions of antibodies with a range of antigens differing in shape complementarity. Finally, we carry out 296 835 pairwise 3D structure comparisons of 771 structures of contact residues of antibodies with their interfacial water molecules from our dataset using CLICK method. A heuristic clustering algorithm is used to obtain unique structural similarities, and found to separate into 368 different clusters. These clusters are used to identify structural motifs of contact residues of antibodies for epitope binding. This clustering database of contact residues is freely accessible at http://mspc.bii.a-star.edu.sg/minhn/pclick.html. minhn@bii.a-star.edu.sg, chandra@bii.a-star.edu.sg or zhong_pingyu@immunol.a-star.edu.sg. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Elucidating the influence of polymorph-dependent interfacial solvent structuring at chitin surfaces.

PubMed

Brown, Aaron H; Walsh, Tiffany R

2016-10-20

Interfacial solvent structuring is thought to be influential in mediating the adsorption of biomolecules at aqueous materials interfaces. However, despite the enormous potential for exploitation of aqueous chitin interfaces in industrial, medical and drug-delivery applications, little is known at the molecular-level about such interfacial solvent structuring for chitin. Here we use molecular simulation to predict the structure of the [100] and [010] interfaces of α-chitin and β-chitin dihydrate in contact with liquid water and saline solution. We find the α-chitin [100] interface supports lateral high-density regions in the first water layer at the interface, which are also present, but not as pronounced, for β-chitin. The lateral structuring of interfacial ions at the saline/chitin interface is also more pronounced for α-chitin compared with β-chitin. Our findings provide a foundation for the systematic design of biomolecules with selective binding affinity for different chitin polymorphs. Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of commitment strength in enhancing safe water consumption: mediation analysis of a cluster-randomized trial.

PubMed

Inauen, Jennifer; Tobias, Robert; Mosler, Hans-Joachim

2014-11-01

The objectives of this study were to investigate the importance of commitment strength in the theory of planned behaviour (TPB) and to test whether behaviour change techniques (BCTs) aimed at increasing commitment strength indeed promote switching to arsenic-safe wells by changing commitment strength. A cluster-randomized controlled trial with four arms was conducted to compare an information-only intervention to information plus one, two, or three commitment-enhancing BCTs. Randomly selected households (N = 340) of Monoharganj, Bangladesh, in seven geographically separate areas, whose members were drinking arsenic-contaminated water at baseline and had access to arsenic-safe wells, participated in this trial. The areas were randomly allocated to the four intervention arms. Water consumption behaviour, variables of the TPB, commitment strength, and socio-demographic characteristics were assessed at baseline and at 3-month follow-up by structured face-to-face interviews. Mediation analysis was used to investigate the mechanisms of behaviour change. Changes in commitment strength significantly increased the explanatory power of the TPB to predict well-switching. Commitment-enhancing BCTs - public self-commitment, implementation intentions, and reminders - increased the behaviour change effects of information by up to 50%. Mediation analyses confirmed that the BCTs indeed increased well-switching by increasing commitment strength. Unexpectedly, however, mediation via changes in behavioural intentions was the strongest mechanism of the intervention effects. Commitment is an important construct to consider in water- and health-related behaviour change and may be for other health behaviours as well. BCTs that alter behavioural intentions and commitment strength proved highly effective at enhancing the behaviour change effects of information alone. Statement of contribution What is already known on this subject? Millions of people drink contaminated water even if they have access to safe water alternatives and despite increased awareness of the consequences to health. The theory of planned behaviour (TPB) and commitment strength are predictive of safe water consumption. The potentially commitment-enhancing behaviour change techniques (BCTs) - reminders, implementation intentions, and public self-commitment - can promote health behaviours, including safe water consumption. What does this study add? Changes in commitment strength significantly added to the prediction of switching to arsenic-safe wells by the TPB. Information-plus-BCTs aimed at increasing commitment strength led to >50% more well-switching than information alone. Behaviour change effects of the BCTs were mediated by changes in commitment strength and behavioural intentions. © 2013 The British Psychological Society.

Physicochemical hydrodynamics of porous structures in vascular plants

NASA Astrophysics Data System (ADS)

Ryu, Jeongeun; Ahn, Sungsook; Kim, Seung-Gon; Kim, Taejoo; Lee, Sang Joon

2013-11-01

Transport of sap flow through xylem conduits of vascular plants has been considered as a passive process, because the xylem conduits are regarded as inert, dead wood. However, plants can actively regulate water transport using ion-mediated response for adapting to environmental changes. In order to understand the active regulation mechanism of physicochemical hydrodynamics of porous structures in vascular plants, the effects of specific ion types and their ionic ratios on the water transport were experimentally investigated under in vivocondition. Based on the experimental results, the principle of ionic effects will be explained through in-vitro comparative experiments and theoretical considerations. This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MSIP) (No. 2008-0061991).

Rheoceptive mediators of graviperception in a water flea: Morphological implications of antennal-socket setae in daphnia magna

NASA Technical Reports Server (NTRS)

Meyers, D. G.

1984-01-01

Aquatic microcrustaceans of the genus Daphnia are known to orient to light during the day. At night, in the absence of visual cues, daphnids were suspected of maintaining equilibrium by monitoring the direction of gravity through their swimming antennae. Recent investigations using simulated, weightlessness conditions coupled with absence of illumination revealed hair like structures or setae on the basal, articulating socket of the antennae that, when surgically removed, resulted in disorientation. Given the simulated weightlessness or neutrally buoyant condition that eliminated sinking of the normally negatively buoyant Daphnia, it was proposed that the antennal socket setae function as rheoceptors stimulated by the upward rush of water currents during gravity induced, sinking phase of daphnid swimming movements. This rheoceptively mediated, gravity perception hypothesis is further supported by morphological investigations. Scanning electron micrographs indicate that antennal socket setae are anatomically similar to proprioceptors used by higher crustaceans to monitor gravitational direction.

Effects of short-term hypothermal and contrast exposure on immunophysiological parameters of laboratory animals.

PubMed

Kalenova, L F; Fisher, T A; Suhovey, J G; Besedin, I M

2009-05-01

Experiments on inbred animals showed that short-term exposure in cold water significantly modified structural and functional parameters of the immune system at different levels of its organization, from bone marrow hemopoiesis to effector stage of the immune response to antigen. The thermal factor caused changes in nonspecific and specific mechanisms of the immune system. Hypothermal exposure (7-9 degrees C, 5 sec) increased the thymic index and bone marrow lymphocyte count, reduced absorption capacity and stimulated metabolic activity of phagocytes, stimulated cell-mediated and suppressed humoral immunity. Contrast exposure in cold and hot water (7-9 degrees C, 5 sec/40-42 degrees C, 30 sec) increased monocyte count in bone marrow and reduced it in the their peripheral blood, reduced metabolic activity of phagocytes, stimulated cell-mediated and suppressed humoral immunity. These data demonstrate physiological mechanisms of interactions between the thermoregulatory and immune systems.

Throughfall-mediated alterations to soil microbial community structure in a forest plot of homogenous soil texture, litter, and plant species composition

NASA Astrophysics Data System (ADS)

Van Stan, John; Rosier, Carl; Moore, Leslie; Gay, Trent; Reichard, James; Wu, Tiehang; Kan, Jinjun

2015-04-01

Identifying spatiotemporal influences on soil microbial community (SMC) structure is critical to our understanding of patterns in biogeochemical cycling and related ecological services (e.g., plant community structure, water quality, response to environmental change). Since forest canopy structure alters the spatiotemporal patterning of precipitation water and solute supplies to soils (via "throughfall"), is it possible that changes in SMC structure could arise from modifications in canopy elements? Our study investigates this question by monitoring throughfall water and dissolved ion supply to soils beneath a continuum of canopy structure: from large gaps (0% cover), to bare Quercus virginiana Mill. (southern live oak) canopy (~50-70%), to heavy Tillandsia usneoides L. (Spanish moss) canopy (>90% cover). Throughfall water supply diminished with increasing canopy cover, yet increased washoff/leaching of Na+, Cl-, PO43-, and SO42- from the canopy to the soils. Presence of T. usneoides diminished throughfall NO3-, but enhanced NH4+, concentrations supplied to subcanopy soils. The mineral soil horizon (0-10 cm) sampled in triplicate from locations receiving throughfall water and solutes from canopy gaps, bare canopy, and T. usneoides-laden canopy significantly differed in soil chemistry parameters (pH, Ca2+, Mg2+, CEC). Polymerase Chain Reaction-Denaturant Gradient Gel Electrophoresis (PCR-DGGE) banding patterns beneath similar canopy covers (experiencing similar throughfall dynamics) also produced high similarities per ANalyses Of SIMilarity (ANO-SIM), and clustered together when analyzed by Nonmetric Multidimensional Scaling (NMDS). These results suggest that modifications of forest canopy structures are capable of affecting mineral-soil horizon SMC structure via throughfall when canopies' biomass distribution is highly heterogeneous. As SMC structure, in many instances, relates to functional diversity, we suggest that future research seek to identify functional diversity shifts (e.g., nitrogen transformation) in response to canopy structural alterations of throughfall water/solute concentration

Estimating Effects of Arsenic Exposure During Pregnancy on Perinatal Outcomes in a Bangladeshi Cohort

PubMed Central

Cardenas, Andres; Rodrigues, Ema; Mazumdar, Maitreyi; Dobson, Christine; Golam, Mostofa; Quamruzzaman, Quazi; Rahman, Mahmudar; Christiani, David C.

2016-01-01

Background: The relationship between arsenic and birth weight is not well understood. The objective was to evaluate the causal relationship between prenatal arsenic exposure and birth weight considering the potential mediation effects of gestational age and maternal weight gain during pregnancy using structural equation models. Methods: A prospectively enrolled cohort of pregnant women was recruited in Bangladesh from 2008 to 2011. Arsenic was measured in personal drinking water at the time of enrollment (gestational age <16 weeks, N = 1,140) and in toenails collected ≤1 month postpartum (N = 624) using inductively coupled plasma mass spectrometry. Structural equation models estimated the direct and indirect effects of arsenic on birth weight with gestational age and maternal weight gain considered as mediating variables. Results: Every unit increase in natural log water arsenic was indirectly associated with decreased birth weight (β = −19.17 g, 95% confidence interval [CI]: −24.64, −13.69) after adjusting for other risk factors. This association was mediated entirely through gestational age (β = −17.37 g, 95% CI: −22.77, −11.98) and maternal weight gain during pregnancy (β = −1.80 g, 95% CI: −3.72, 0.13). When exposure was modeled using toenail arsenic concentrations, similar results were observed. Every increase in natural log toenail arsenic was indirectly associated with decreased birth weight (β = −15.72 g, 95% CI: −24.52, −6.91) which was mediated through gestational age (β = −13.59 g, 95% CI: −22.10, −5.07) and maternal weight gain during pregnancy (β = −2.13 g, 95% CI: −5.24, 0.96). Conclusion: Arsenic exposure during pregnancy was associated with lower birth weight. The effect of arsenic on birth weight appears to be mediated mainly through decreasing gestational age and to a lesser extent by lower maternal weight gain during pregnancy. PMID:26583609

Resistance of tropical seedlings to drought is mediated by neighbourhood diversity.

PubMed

O'Brien, Michael J; Reynolds, Glen; Ong, Robert; Hector, Andy

2017-11-01

Occasional periods of drought are typical of most tropical forests, but climate change is increasing drought frequency and intensity in many areas across the globe, threatening the structure and function of these ecosystems. The effects of intermittent drought on tropical tree communities remain poorly understood and the potential impacts of intensified drought under future climatic conditions are even less well known. The response of forests to altered precipitation will be determined by the tolerances of different species to reduced water availability and the interactions among plants that alleviate or exacerbate the effects of drought. Here, we report the response of experimental monocultures and mixtures of tropical trees to simulated drought, which reveals a fundamental shift in the nature of interactions among species. Weaker competition for water in diverse communities allowed seedlings to maintain growth under drought while more intense competition among conspecifics inhibited growth under the same conditions. These results show that reduced competition for water among species in mixtures mediates community resistance to drought. The delayed onset of competition for water among species in more diverse neighbourhoods during drought has potential implications for the coexistence of species in tropical forests and the resilience of these systems to climate change.

Detection of abnormalities in the superficial zone of cartilage repaired using a tissue engineered construct derived from synovial stem cells.

PubMed

Ando, Wataru; Fujie, Hiromichi; Moriguchi, Yu; Nansai, Ryosuke; Shimomura, Kazunori; Hart, David A; Yoshikawa, Hideki; Nakamura, Norimasa

2012-09-28

The present study investigated the surface structure and mechanical properties of repair cartilage generated from a tissue engineered construct (TEC) derived from synovial mesenchymal stem cells at six months post-implantation compared to those of uninjured cartilage. TEC-mediated repair tissue was cartilaginous with Safranin O staining, and had comparable macro-scale compressive properties with uninjured cartilage. However, morphological assessments revealed that the superficial zone of TEC-mediated tissue was more fibrocartilage-like, in contrast to the middle or deep zones that were more hyaline cartilage-like with Safranin O staining. Histological scoring of the TEC-mediated tissue was significantly lower in the superficial zone than in the middle and deep zones. Scanning electron microscopy showed a thick tangential bundle of collagen fibres at the most superficial layer of uninjured cartilage, while no corresponding structure was detected at the surface of TEC-mediated tissue. Immunohistochemical analysis revealed that PRG4 was localised in the superficial area of uninjured cartilage, as well as the TEC-mediated tissue. Friction testing showed that the lubrication properties of the two tissues was similar, however, micro-indentation analysis revealed that the surface stiffness of the TEC-repair tissue was significantly lower than that of uninjured cartilage. Permeability testing indicated that the TEC-mediated tissue exhibited lower water retaining capacity than did uninjured cartilage, specifically at the superficial zone. Thus, TEC-mediated tissue exhibited compromised mechanical properties at the superficial zone, properties which need improvement in the future for maintenance of long term repair cartilage integrity.

The importance and conservation of ectomycorrizal fungal diversity in forest ecosystems: lessons from Europe and the Pacific Northwest.

Treesearch

Michael P. Amaranthus

1998-01-01

Ectomycorrhizal fungi (EMF) consist of about 5,000 species and profoundly affect forest ecosystems by mediating nutrient and water uptake, protecting roots from pathogens and environmental extremes, and maintaining soil structure and forest food webs. Diversity of EMF likely aids forest ecosystem resilience in the face of changing environmental factors such as...

Improving the efficiency of water splitting in dye-sensitized solar cells by using a biomimetic electron transfer mediator

PubMed Central

Zhao, Yixin; Swierk, John R.; Megiatto, Jackson D.; Sherman, Benjamin; Youngblood, W. Justin; Qin, Dongdong; Lentz, Deanna M.; Moore, Ana L.; Moore, Thomas A.; Gust, Devens; Mallouk, Thomas E.

2012-01-01

Photoelectrochemical water splitting directly converts solar energy to chemical energy stored in hydrogen, a high energy density fuel. Although water splitting using semiconductor photoelectrodes has been studied for more than 40 years, it has only recently been demonstrated using dye-sensitized electrodes. The quantum yield for water splitting in these dye-based systems has, so far, been very low because the charge recombination reaction is faster than the catalytic four-electron oxidation of water to oxygen. We show here that the quantum yield is more than doubled by incorporating an electron transfer mediator that is mimetic of the tyrosine-histidine mediator in Photosystem II. The mediator molecule is covalently bound to the water oxidation catalyst, a colloidal iridium oxide particle, and is coadsorbed onto a porous titanium dioxide electrode with a Ruthenium polypyridyl sensitizer. As in the natural photosynthetic system, this molecule mediates electron transfer between a relatively slow metal oxide catalyst that oxidizes water on the millisecond timescale and a dye molecule that is oxidized in a fast light-induced electron transfer reaction. The presence of the mediator molecule in the system results in photoelectrochemical water splitting with an internal quantum efficiency of approximately 2.3% using blue light. PMID:22547794

Structure, spectroscopy and dynamics of layered H2O and CO2 ices

USGS Publications Warehouse

,; Plattner, Nuria; Meuwly, Markus

2012-01-01

Molecular dynamics simulations of structural, spectroscopic and dynamical properties of mixed water–carbon dioxide (H2O–CO2) ices are discussed over temperature ranges relevant to atmospheric and astrophysical conditions. The simulations employ multipolar force fields to represent electrostatic interactions which are essential for spectroscopic and dynamical investigations. It is found that at the water/CO2 interface the water surface acts as a template for the CO2 component. The rotational reorientation times in both bulk phases agree well with experimental observations. A pronounced temperature effect on the CO2 reorientation time is observed between 100 K and 200 K. At the interface, water reorientation times are nearly twice as long compared to water in the bulk. The spectroscopy of such ices is rich in the far-infrared region of the spectrum and can be related to translational and rotational modes. Furthermore, spectroscopic signatures mediated across the water/CO2 interface are found in this frequency range (around 440 cm−1). These results will be particularly important for new airborne experiments such as planned for SOFIA.

Nitroxide free radicals protect macular carotenoids against chemical destruction (bleaching) during lipid peroxidation

PubMed Central

Zareba, M.; Widomska, J.; Burke, J. M.; Subczynski, W. K.

2016-01-01

Macular xanthophylls (MXs) lutein and zeaxanthin are dietary carotenoids that are selectively concentrated in the human eye retina, where they are thought to protect against age-related macular degeneration (AMD) by multiple mechanisms, including filtration of phototoxic blue light and quenching of singlet oxygen and triplet states of photosensitizers. These physical protective mechanisms require that MXs be in their intact structure. Here, we investigated the protection of the intact structure of zeaxanthin incorporated into model membranes subjected to oxidative modification by water- and/or membrane-soluble small nitroxide free radicals. Model membranes were formed from saturated, monounsaturated, and polyunsaturated phosphatidylcholines (PCs). Oxidative modification involved autoxidation, iron-mediated, and singlet oxygen-mediated lipid peroxidation. The extent of chemical destruction (bleaching) of zeaxanthin was evaluated from its absorption spectra and compared with the extent of lipid peroxidation evaluated using the thiobarbituric acid assay. Nitroxide free radicals with different polarity (membrane/water partition coefficients) were used. The extent of zeaxanthin bleaching increased with membrane unsaturation and correlated with the rate of PC oxidation. Protection of the intact structure of zeaxanthin by membrane-soluble nitroxides was much stronger than that by water-soluble nitroxides. The combination of zeaxanthin and lipid-soluble nitroxides exerted strong synergistic protection against singlet oxygen-induced lipid peroxidation. The synergistic effect may be explained in terms of protection of the intact zeaxanthin structure by effective scavenging of free radicals by nitroxides, therefore allowing zeaxanthin to quench the primary oxidant, singlet oxygen, effectively by the physical protective mechanism. The redox state of nitroxides was monitored using electron paramagnetic resonance spectroscopy. Both nitroxide free radicals and their reduced form, hydroxylamines, were equally effective. Obtained data were compared with the protective effects of α-tocopherol, which is the natural antioxidant and protector of MXs within the retina. The new strategies employed here to maintain the intact structure of MXs may enhance their protective potential against AMD. PMID:27840316

Nitroxide free radicals protect macular carotenoids against chemical destruction (bleaching) during lipid peroxidation.

PubMed

Zareba, M; Widomska, J; Burke, J M; Subczynski, W K

2016-12-01

Macular xanthophylls (MXs) lutein and zeaxanthin are dietary carotenoids that are selectively concentrated in the human eye retina, where they are thought to protect against age-related macular degeneration (AMD) by multiple mechanisms, including filtration of phototoxic blue light and quenching of singlet oxygen and triplet states of photosensitizers. These physical protective mechanisms require that MXs be in their intact structure. Here, we investigated the protection of the intact structure of zeaxanthin incorporated into model membranes subjected to oxidative modification by water- and/or membrane-soluble small nitroxide free radicals. Model membranes were formed from saturated, monounsaturated, and polyunsaturated phosphatidylcholines (PCs). Oxidative modification involved autoxidation, iron-mediated, and singlet oxygen-mediated lipid peroxidation. The extent of chemical destruction (bleaching) of zeaxanthin was evaluated from its absorption spectra and compared with the extent of lipid peroxidation evaluated using the thiobarbituric acid assay. Nitroxide free radicals with different polarity (membrane/water partition coefficients) were used. The extent of zeaxanthin bleaching increased with membrane unsaturation and correlated with the rate of PC oxidation. Protection of the intact structure of zeaxanthin by membrane-soluble nitroxides was much stronger than that by water-soluble nitroxides. The combination of zeaxanthin and lipid-soluble nitroxides exerted strong synergistic protection against singlet oxygen-induced lipid peroxidation. The synergistic effect may be explained in terms of protection of the intact zeaxanthin structure by effective scavenging of free radicals by nitroxides, therefore allowing zeaxanthin to quench the primary oxidant, singlet oxygen, effectively by the physical protective mechanism. The redox state of nitroxides was monitored using electron paramagnetic resonance spectroscopy. Both nitroxide free radicals and their reduced form, hydroxylamines, were equally effective. Obtained data were compared with the protective effects of α-tocopherol, which is the natural antioxidant and protector of MXs within the retina. The new strategies employed here to maintain the intact structure of MXs may enhance their protective potential against AMD. Copyright © 2016 Elsevier Inc. All rights reserved.

Carrier Mediated Distribution System (CAMDIS): a new approach for the measurement of octanol/water distribution coefficients.

PubMed

Wagner, Bjoern; Fischer, Holger; Kansy, Manfred; Seelig, Anna; Assmus, Frauke

2015-02-20

Here we present a miniaturized assay, referred to as Carrier-Mediated Distribution System (CAMDIS) for fast and reliable measurement of octanol/water distribution coefficients, log D(oct). By introducing a filter support for octanol, phase separation from water is facilitated and the tendency of emulsion formation (emulsification) at the interface is reduced. A guideline for the best practice of CAMDIS is given, describing a strategy to manage drug adsorption at the filter-supported octanol/buffer interface. We validated the assay on a set of 52 structurally diverse drugs with known shake flask log D(oct) values. Excellent agreement with literature data (r(2) = 0.996, standard error of estimate, SEE = 0.111), high reproducibility (standard deviation, SD < 0.1 log D(oct) units), minimal sample consumption (10 μL of 100 μM DMSO stock solution) and a broad analytical range (log D(oct) range = -0.5 to 4.2) make CAMDIS a valuable tool for the high-throughput assessment of log D(oc)t. Copyright © 2014 Elsevier B.V. All rights reserved.

Conserved water mediated recognition and the dynamics of active site Cys 331 and Tyr 411 in hydrated structure of human IMPDH-II.

PubMed

Bairagya, Hridoy R; Mukhopadhyay, Bishnu P; Bera, Asim K

2011-01-01

Inosine monophosphate dehydrogenase (IMPDH) of human is involved in GMP biosynthesis pathway, increased level of IMPDH-II (an isoform of enzyme) activity have found in leukemic and sarcoma cells. Modeling and extensive molecular dynamics simulation (15 ns) studies of IMPDH-II (1B3O PDB structure) have indicated the intricate involvement of four conserved water molecules (W 1, W 2, W 3, and W 4) in the conformational transition or the mobilities of "flap" (residues 400-450) and "loop" (residues 325-342) regions in enzyme. The stabilization of active site residues Asn 303, Gly 324, Ser 329, Cys 331, Asp 364, and Tyr 411 through variable H-bonding coordination from the conserved water molecular center seems interesting in the uninhibited hydrated form of human IMPDH-II structures. This conformational transition or the flexibility of mobile regions, water molecular recognition to active site residues Cys 331 and Tyr 411, and the presence of a hydrophilic cavity approximately 540 Å(3) (enclaved by the loop and flap region) near the C-terminal surface of this enzyme may explore a rational hope toward the water mimic inhibitor or anticancer agent design for human. 2010 John Wiley & Sons, Ltd.

The Arsenite Oxidation Potential of Native Microbial Communities from Arsenic-Rich Freshwaters.

PubMed

Fazi, Stefano; Crognale, Simona; Casentini, Barbara; Amalfitano, Stefano; Lotti, Francesca; Rossetti, Simona

2016-07-01

Microorganisms play an important role in speciation and mobility of arsenic in the environment, by mediating redox transformations of both inorganic and organic species. Since arsenite [As(III)] is more toxic than arsenate [As(V)] to the biota, the microbial driven processes of As(V) reduction and As(III) oxidation may play a prominent role in mediating the environmental impact of arsenic contamination. However, little is known about the ecology and dynamics of As(III)-oxidizing populations within native microbial communities exposed to natural high levels of As. In this study, two techniques for single cell quantification (i.e., flow cytometry, CARD-FISH) were used to analyze the structure of aquatic microbial communities across a gradient of arsenic (As) contamination in different freshwater environments (i.e., groundwaters, surface and thermal waters). Moreover, we followed the structural evolution of these communities and their capacity to oxidize arsenite, when experimentally exposed to high As(III) concentrations in experimental microcosms. Betaproteobacteria and Deltaproteobacteria were the main groups retrieved in groundwaters and surface waters, while Beta and Gammaproteobacteria dominated the bacteria community in thermal waters. At the end of microcosm incubations, the communities were able to oxidize up to 95 % of arsenite, with an increase of Alphaproteobacteria in most of the experimental conditions. Finally, heterotrophic As(III)-oxidizing strains (one Alphaproteobacteria and two Gammaproteobacteria) were isolated from As rich waters. Our findings underlined that native microbial communities from different arsenic-contaminated freshwaters can efficiently perform arsenite oxidation, thus contributing to reduce the overall As toxicity to the aquatic biota.

Privatization by Other Means: Social Power, Tankers and Techno-Assemblages of Water Supply in Amman, Jordan.

NASA Astrophysics Data System (ADS)

Mustafa, D.

2016-12-01

Combined piped and tanker based water supply systems have become a ubiquitous feature of urban waterscapes in the global South. Jordanian water sector, and Amman in particular has been a recipient of considerable international financial and technical assistance over the past decades. The international assistance has coupled with the Jordanian state's own pro-market ideological stance, and its political compulsions to spawn a techno-social assemblage of water supply that represents a hybrid state and commercial water supply system. I present the results of a field study in Amman, Jordan on water tankers and water users to understand the techno-political underpinnings of the hybrid system and its impact on differential access to water. I explore how Actor Network Theory (ANT) based analysis of tankers, suction pumps and piped water system and their materiality may explain differential access to water. But that exploration is inflected by a larger political ecological concern with questions of power and discourses about citizenship and claim making on the state. I find that ANT based focus on water technologies, while ontologically fertile, and epistemologically innovative, is nevertheless politically barren. Much richer political insights are to be gained from structural and post-structurally based investigations of the discursive and material drivers of the techno-social assemblages of water supply. The technologies don't just neutrally impact water access, but seem to almost intentionally favour the powerful over the powerless. Surely the political agency must not reside in inanimate technologies but in the social actors and structures that fashion those technologies, and configure them such to reinforce geographies of power. I call for a renewed focus on social power and how its impact on lived geographies is mediated by technology.

How water manifests the structural regimes in ionic liquids.

PubMed

Singh, Akhil Pratap; Gardas, Ramesh L; Senapati, Sanjib

2017-03-22

Ionic liquids (ILs) are being considered as greener alternatives to the conventional organic solvents. However, highly viscous nature of ILs often limits their applications. Hence studies on IL/water binary mixtures have received tremendous attention. These mixtures exhibit much lower viscosity, but almost similar density, compressibility and other properties as that of the neat ILs, up to certain water content. Hence, determining the IL-water ratio till which the solution behaves like IL and subsequently changes to a state of solute IL dissolved in continuous water phase is of paramount importance. Noting the very different and characteristic behaviours of neat ILs and pure water over a temperature range, herein, we measured the various thermophysical properties of the binary mixtures of tetramethylguanidinium benzoate/water and tetramethylguanidinium salicylate/water with water content varying from 20 wt% to 95 wt% for a temperature range of 298 K to 343 K. The results show that similar to neat ILs, the measured densities and compressibility of these mixtures display a linear change, and viscosity decreases rapidly as temperature is increased for water content up to 50 wt%. At higher water concentrations, the measured density and compressibility exhibit nonlinear behaviour and the decrease in viscosity with increased temperature is minute, mimicking the behaviour of bulk water. MD simulations were carried out to explain the experimental observations. Simulation results show a greater temperature-induced disintegration of IL ion-water interactions in dense systems, explaining the rapid decay of the properties with temperature. The results also exhibit the presence of a neat, IL-like, H-bond mediated expanded structure in concentrated solution versus a collapsed IL structure in dilute solution.

Copper-mediated homogeneous living radical polymerization of acrylamide with waxy potato starch-based macroinitiator.

PubMed

Fan, Yifei; Cao, Huatang; van Mastrigt, Frank; Pei, Yutao; Picchioni, Francesco

2018-07-15

Cu 0 -mediated living radical polymerization (Cu 0 -mediated LRP) was employed in this research for the synthesis of starch-g-polyacrylamide (St-g-PAM). The use of a controlled radical grafting technique is necessary, as compared to the traditional free-radical polymerization methods, in order to obtain a well-defined structure of the final product. This is in turn essential for studying the relationship between such structure and the end-properties. Waxy potato starch-based water-soluble macroinitiator was first synthesized by esterification with 2-bromopropionyl bromide in the mixture of dimethylacetamide and lithium chloride. With the obtained macroinitiator, St-g-PAM was homogeneously synthesized by aqueous Cu 0 -mediated LRP using CuBr/hexamethylated tris(2-aminoethyl)amine (Me 6 Tren) as catalyst. The successful synthesis of the macroinitiator and St-g-PAM was proved by NMR, FT-IR, SEM, XRD and TGA analysis. The molecular weight and polydispersity of PAM chains were analyzed by gel permeation chromatography (GPC) after hydrolyzing the starch backbone. Monomer conversion was monitored by gas chromatography (GC), on the basis of which the kinetics were determined. A preliminarily rheological study was performed on aqueous solutions of the prepared materials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Turning things downside up: Adsorbate induced water flipping on Pt(111)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimmel, Gregory A.; Zubkov, Tykhon; Smith, R. Scott

2014-11-14

We have examined the adsorption of the weakly bound species N2, O2, CO and Kr on the water monolayer on Pt(111) using a combination of molecular beam dosing, infrared reflection absorption spectroscopy (IRAS), and temperature programmed desorption (TPD). In contrast to multilayer crystalline ice, the adsorbate-free water monolayer is characterized by a lack of dangling OH bonds protruding into the vacuum (H-up). Instead, the non-hydrogen-bonded OH groups are oriented downward (H-down) to maximize their interaction with the underlying Pt(111) substrate. Adsorption of Kr and O2 have little effect on the structure and vibrational spectrum of the “ ” water monolayermore » while adsorption of both N2, and CO are effective in “flipping” H-down water molecules into an H-up configuration. This “flipping” occurs readily upon adsorption at temperatures as low as 20 K and the water monolayer transforms back to the H-down, “ ” structure upon adsorbate desorption above 35 K, indicating small energy differences and barriers between the H-down and H-up configurations. The results suggest that converting water in the first layer from H-down to H-up is mediated by the electrostatic interactions between the water and the adsorbates.« less

Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity

DOE PAGES

Kim, Youngchang; Makowska-Grzyska, Magdalena; Gorla, Suresh Kumar; ...

2015-04-21

Inosine 5´-monophosphate dehydrogenase (IMPDH) is a promising target for the treatment of Cryptosporidium infections. Here, the structure of C. parvum IMPDH ( CpIMPDH) in complex with inosine 5´-monophosphate (IMP) and P131, an inhibitor with in vivo anticryptosporidial activity, is reported. P131 contains two aromatic groups, one of which interacts with the hypoxanthine ring of IMP, while the second interacts with the aromatic ring of a tyrosine in the adjacent subunit. In addition, the amine and NO 2 moieties bind in hydrated cavities, forming water-mediated hydrogen bonds to the protein. The design of compounds to replace these water molecules is amore » new strategy for the further optimization of C. parvum inhibitors for both antiparasitic and antibacterial applications.« less

Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Youngchang; Makowska-Grzyska, Magdalena; Gorla, Suresh Kumar

2015-04-21

Inosine 5'-monophosphate dehydrogenase (IMPDH) is a promising target for the treatment ofCryptosporidiuminfections. Here, the structure ofC. parvumIMPDH (CpIMPDH) in complex with inosine 5'-monophosphate (IMP) and P131, an inhibitor within vivoanticryptosporidial activity, is reported. P131 contains two aromatic groups, one of which interacts with the hypoxanthine ring of IMP, while the second interacts with the aromatic ring of a tyrosine in the adjacent subunit. In addition, the amine and NO 2moieties bind in hydrated cavities, forming water-mediated hydrogen bonds to the protein. The design of compounds to replace these water molecules is a new strategy for the further optimization ofC. parvuminhibitorsmore » for both antiparasitic and antibacterial applications.« less

Thiabendazole inhibits ubiquinone reduction activity of mitochondrial respiratory complex II via a water molecule mediated binding feature.

PubMed

Zhou, Qiangjun; Zhai, Yujia; Lou, Jizhong; Liu, Man; Pang, Xiaoyun; Sun, Fei

2011-07-01

The mitochondrial respiratory complex II or succinate: ubiquinone oxidoreductase (SQR) is a key membrane complex in both the tricarboxylic acid cycle and aerobic respiration. Five disinfectant compounds were investigated with their potent inhibition effects on the ubiquinone reduction activity of the porcine mitochondrial SQR by enzymatic assay and crystallography. Crystal structure of the SQR bound with thiabendazole (TBZ) reveals a different inhibitor-binding feature at the ubiquinone binding site where a water molecule plays an important role. The obvious inhibitory effect of TBZ based on the biochemical data (IC(50) ~100 μmol/L) and the significant structure-based binding affinity calculation (~94 μmol/L) draw the suspicion of using TBZ as a good disinfectant compound for nematode infections treatment and fruit storage.

Benzyl Alcohol-Mediated Versatile Method to Fabricate Nonstoichiometric Metal Oxide Nanostructures.

PubMed

Qamar, Mohammad; Adam, Alaaldin; Azad, Abdul-Majeed; Kim, Yong-Wah

2017-11-22

Nanostructured metal oxides with cationic or anionic deficiency find applications in a wide range of technological areas including the energy sector and environment. However, a facile route to prepare such materials in bulk with acceptable reproducibility is still lacking; many synthesis techniques are still only bench-top and cannot be easily scaled-up. Here, we report that the benzyl alcohol (BA)-mediated method is capable of producing a host of nanostructured metal oxides (MO x , where M = Ti, Zn, Ce, Sn, In, Ga, or Fe) with inherent nonstoichiometry. It employs multifunctional BA as a solvent, a reducing agent, and a structure-directing agent. Depending on the oxidation states of metal, elemental or nonstoichiometric oxide forms are obtained. Augmented photoelectrochemical oxidation of water under visible light by some of these nonstoichiometric oxides highlights the versatility of the BA-mediated synthesis protocol.

Nitrogen-mediated effects of elevated CO2 on intra-aggregate soil pore structure.

PubMed

Caplan, Joshua S; Giménez, Daniel; Subroy, Vandana; Heck, Richard J; Prior, Stephen A; Runion, G Brett; Torbert, H Allen

2017-04-01

Soil pore structure has a strong influence on water retention, and is itself influenced by plant and microbial dynamics such as root proliferation and microbial exudation. Although increased nitrogen (N) availability and elevated atmospheric CO 2 concentrations (eCO 2 ) often have interacting effects on root and microbial dynamics, it is unclear whether these biotic effects can translate into altered soil pore structure and water retention. This study was based on a long-term experiment (7 yr at the time of sampling) in which a C 4 pasture grass (Paspalum notatum) was grown on a sandy loam soil while provided factorial additions of N and CO 2 . Through an analysis of soil aggregate fractal properties supported by 3D microtomographic imagery, we found that N fertilization induced an increase in intra-aggregate porosity and a simultaneous shift toward greater accumulation of pore space in larger aggregates. These effects were enhanced by eCO 2 and yielded an increase in water retention at pressure potentials near the wilting point of plants. However, eCO 2 alone induced changes in the opposite direction, with larger aggregates containing less pore space than under control conditions, and water retention decreasing accordingly. Results on biotic factors further suggested that organic matter gains or losses induced the observed structural changes. Based on our results, we postulate that the pore structure of many mineral soils could undergo N-dependent changes as atmospheric CO 2 concentrations rise, having global-scale implications for water balance, carbon storage, and related rhizosphere functions. © 2016 John Wiley & Sons Ltd.

Tracking solvent and protein movement during CO2 release in carbonic anhydrase II crystals

PubMed Central

Kim, Chae Un; Song, HyoJin; Avvaru, Balendu Sankara; Gruner, Sol M.; Park, SangYoun; McKenna, Robert

2016-01-01

Carbonic anhydrases are mostly zinc metalloenzymes that catalyze the reversible hydration/dehydration of CO2/HCO3−. Previously, the X-ray crystal structures of CO2-bound holo (zinc-bound) and apo (zinc-free) human carbonic anhydrase IIs (hCA IIs) were captured at high resolution. Here, we present sequential timeframe structures of holo- [T = 0 s (CO2-bound), 50 s, 3 min, 10 min, 25 min, and 1 h] and apo-hCA IIs [T = 0 s, 50 s, 3 min, and 10 min] during the “slow” release of CO2. Two active site waters, WDW (deep water) and WDW′ (this study), replace the vacated space created on CO2 release, and another water, WI (intermediate water), is seen to translocate to the proton wire position W1. In addition, on the rim of the active site pocket, a water W2′ (this study), in close proximity to residue His64 and W2, gradually exits the active site, whereas His64 concurrently rotates from pointing away (“out”) to pointing toward (“in”) active site rotameric conformation. This study provides for the first time, to our knowledge, structural “snapshots” of hCA II intermediate states during the formation of the His64-mediated proton wire that is induced as CO2 is released. Comparison of the holo- and apo-hCA II structures shows that the solvent network rearrangements require the presence of the zinc ion. PMID:27114542

Formation of vesicles through solvent assisted self-assembly of hydrophobic pentapeptides: encapsulation and pH responsive release of dyes by the vesicles.

PubMed

Kar, Sudeshna; Drew, Michael G B; Pramanik, Animesh

2011-09-01

In the biomimetic design two hydrophobic pentapetides Boc-Ile-Aib-Leu-Phe-Ala-OMe (I) and Boc-Gly-Ile-Aib-Leu-Phe-OMe (II) (Aib: α-aminoisobutyric acid) containing one Aib each are found to undergo solvent assisted self-assembly in methanol/water to form vesicular structures, which can be disrupted by simple addition of acid. The nanovesicles are found to encapsulate dye molecules that can be released by the addition of acid as confirmed by fluorescence microscopy and UV studies. The influence of solvent polarity on the morphology of the materials generated from the peptides has been examined systematically, and shows that fibrillar structures are formed in less polar chloroform/petroleum ether mixture and vesicular structures are formed in more polar methanol/water. Single crystal X-ray diffraction studies reveal that while β-sheet mediated self-assembly leads to the formation of fibrillar structures, the solvated β-sheet structure leads to the formation of vesicular structures. The results demonstrate that even hydrophobic peptides can generate vesicular structures from polar solvent which may be employed in model studies of complex biological phenomena.

Role of water mediated interactions in protein-protein recognition landscapes.

PubMed

Papoian, Garegin A; Ulander, Johan; Wolynes, Peter G

2003-07-30

The energy landscape picture of protein folding and binding is employed to optimize a number of pair potentials for direct and water-mediated interactions in protein complex interfaces. We find that water-mediated interactions greatly complement direct interactions in discriminating against various types of trap interactions that model those present in the cell. We highlight the context dependent nature of knowledge-based binding potentials, as contrasted with the situation for autonomous folding. By performing a Principal Component Analysis (PCA) of the corresponding interaction matrixes, we rationalize the strength of the recognition signal for each combination of the contact type and reference trap states using the differential in the idealized "canonical" amino acid compositions of native and trap layers. The comparison of direct and water-mediated contact potential matrixes emphasizes the importance of partial solvation in stabilizing charged groups in the protein interfaces. Specific water-mediated interresidue interactions are expected to influence significantly the kinetics as well as thermodynamics of protein association.

Household water insecurity, missed schooling, and the mediating role of caregiver depression in rural Uganda.

PubMed

Cooper-Vince, C E; Kakuhikire, B; Vorechovska, D; McDonough, A Q; Perkins, J; Venkataramani, A S; Mushavi, R C; Baguma, C; Ashaba, S; Bangsberg, D R; Tsai, A C

2017-01-01

School attendance rates in sub-Saharan Africa are among the lowest worldwide, placing children at heightened risk for poor educational and economic outcomes. One understudied risk factor for missed schooling is household water insecurity, which is linked to depression among women and may increase children's water-fetching burden at the expense of educational activities, particularly among children of depressed caregivers. In this study conducted in rural Uganda, we assessed the association between household water insecurity and child school participation and the mediating pathways behind these associations. We conducted a population-based, cross-sectional study of female household heads ( N = 257) and their children ages 5-17 ( N = 551) in the rural regions surrounding the town of Mbarara, in southwestern Uganda. We used multivariable linear regressions to estimate the association between water insecurity and missed schooling. We then assessed the extent to which the association was mediated by caregiver depression. Among children, water insecurity had a statistically significant association with the number of missed school days (a standard deviation increase in water insecurity resulted in 0.30 more missed school days in the last week). The estimated association was partially mediated by caregiver depression. When stratified by sex, this mediating pathway remained significant for boys, but not among girls. Water insecurity is a risk factor for missed schooling among children in rural Uganda. Caregiver depression partially mediated this relationship. Also addressing caregiver mental health in water insecure families may more fully address the needs of sub-Saharan African families and promote educational participation among youth.

Significance of hypoburrow nodule formation associated with large biogenic sedimentary structures in open-marine bay siliciclastics of the Upper Eocene Birket Qarun Formation, Wadi El-Hitan, Fayum, Egypt

NASA Astrophysics Data System (ADS)

Abdel-Fattah, Zaki A.; Gingras, Murray K.; Pemberton, S. George

Unusually large biogenic sedimentary structures from the shallow quiescent-marine siliciclastics of the Upper Eocene Birket Qarun Formation in the Fayum area of Egypt display pronounced concretion formation around the trace fossils. The structures are massive, and vary morphologically, forming branched pillars (up to dm-scale), vertical (up to 180 cm height) amphora-like masses, and 3-D box-work "maze". Bioturbation, mainly Thalassinoides attributable to the Glossifungites ichnofacies, mediated and modified the physical and chemical microenvironments influencing early diagenesis; i.e., burrows promote the precipitation of pervasive calcite-dominated cement. The inferred paragenesis, combined with the negative (light) carbon and oxygen stable-isotopic values of the bulk calcite (δ 13C PDB from -0.94 to -4.98‰ and δ 18O PDB from -4.63 to -7.22‰) and bulk dolomite (δ 13C PDB from -2.05 to -8.23‰ and δ 18O PDB from -1.41 to -11.20‰), imply that the pore-water carbon was derived directly from seawater and dissolution of metastable carbonate, which was mediated by bacterial decomposition of organic matter and mixing of meteoric ground water. Thereby, the carbonate cement precipitated mostly under eodiagenetic conditions near the sediment/water interface (<~3 m in depth). The distribution of these structures is confined to parasequence-bounding flooding surfaces (generally expressed as transgressive surfaces of erosion). Notably, sedimentological, ichnological and paragenetic data can be related to stratigraphic evolution such that geochemical and textural evidence is distinctly associated with (1) early cementation of the host sandstone during highstands of relative sea level, (2) the formation of firmgrounds during low relative sea level, (3) the development of a Glossifungites-demarcated discontinuity during initial relative sea-level rise, and (4) continued cementation with rising relative sea level. This was followed by burial diagenesis, evidence for which is derived from petrographic and isotopic data.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoo, Soohaeng; Xantheas, Sotiris S.

Water's function as a universal solvent and its role in mediating several biological functions that are responsible for sustaining life has created tremendous interest in the understanding of its structure at the molecular level.1 Due to the size of the simulation cells and the sampling time needed to compute many macroscopic properties, most of the initial simulations are performed using a classical force field whereas several processes that involve chemistry are subsequently probed with electronic structure based methods. A significant effort has therefore been devoted towards the development of classical force fields for water.2 Clusters of water molecules are usefulmore » in probing the intermolecular interactions at the microscopic level as well as providing information about the subtle energy differences that are associated with different bonding arrangements within a hydrogen bonded network. They moreover render a quantitative picture of the nature and magnitude of the various components of the intermolecular interactions such as exchange, dispersion, induction etc. They can finally serve as a vehicle for the study of the convergence of properties with increasing size.« less

Calcium delivery and storage in plant leaves: exploring the link with water flow.

PubMed

Gilliham, Matthew; Dayod, Maclin; Hocking, Bradleigh J; Xu, Bo; Conn, Simon J; Kaiser, Brent N; Leigh, Roger A; Tyerman, Stephen D

2011-04-01

Calcium (Ca) is a unique macronutrient with diverse but fundamental physiological roles in plant structure and signalling. In the majority of crops the largest proportion of long-distance calcium ion (Ca(2+)) transport through plant tissues has been demonstrated to follow apoplastic pathways, although this paradigm is being increasingly challenged. Similarly, under certain conditions, apoplastic pathways can dominate the proportion of water flow through plants. Therefore, tissue Ca supply is often found to be tightly linked to transpiration. Once Ca is deposited in vacuoles it is rarely redistributed, which results in highly transpiring organs amassing large concentrations of Ca ([Ca]). Meanwhile, the nutritional flow of Ca(2+) must be regulated so it does not interfere with signalling events. However, water flow through plants is itself regulated by Ca(2+), both in the apoplast via effects on cell wall structure and stomatal aperture, and within the symplast via Ca(2+)-mediated gating of aquaporins which regulates flow across membranes. In this review, an integrated model of water and Ca(2+) movement through plants is developed and how this affects [Ca] distribution and water flow within tissues is discussed, with particular emphasis on the role of aquaporins.

Conserved water-mediated recognition and dynamics of NAD+ (carboxamide group) to hIMPDH enzyme: water mimic approach toward the design of isoform-selective inhibitor.

PubMed

Bairagya, Hridoy R; Mishra, Deepak K; Mukhopadhyay, Bishnu P; Sekar, K

2014-01-01

Inosine monophosphate dehydrogenase (IMPDH) enzyme involves in GMP biosynthesis pathway. Type I hIMPDH is expressed at lower levels in all cells, whereas type II is especially observed in acute myelogenous leukemia, chronic myelogenous leukemia cancer cells, and 10 ns simulation of the IMP-NAD(+) complex structures (PDB ID. 1B3O and 1JCN) have revealed the presence of a few conserved hydrophilic centers near carboxamide group of NAD(+). Three conserved water molecules (W1, W, and W1') in di-nucleotide binding pocket of enzyme have played a significant role in the recognition of carboxamide group (of NAD(+)) to D274 and H93 residues. Based on H-bonding interaction of conserved hydrophilic (water molecular) centers within IMP-NAD(+)-enzyme complexes and their recognition to NAD(+), some covalent modification at carboxamide group of di-nucleotide (NAD(+)) has been made by substituting the -CONH2group by -CONHNH2 (carboxyl hydrazide group) using water mimic inhibitor design protocol. The modeled structure of modified ligand may, though, be useful for the development of antileukemic agent or it could be act as better inhibitor for hIMPDH-II.

Ballistic delivery of dyes for structural and functional studies of the nervous system

PubMed Central

Gan, Wen-Biao; Grutzendler, Jaime; Wong, Rachel O.; Lichtman, Jeff W.

2010-01-01

This chapter describes a detail protocol for rapid labeling of cells in a variety of preparations by means of particle-mediated ballistic (gene gun) delivery of fluorescent dyes. This method has been used for rapid labeling of cells with either lipid or water-soluble dyes in a variety of preparations. In particular, carbocyanine lipophilic dyes such as DiI have been used to obtain Golgi-like labeling of neurons and glia in fixed and live cell cultures, brain slices, as well as fixed post-mortem human brain. Water-soluble calcium indicators such as calcium green-1 dextran have been used to image calcium dynamics in living brain slices and retinal explants. This ballistic labeling technique is thus useful for studying the structure and function of neurons and glia in both living and fixed specimens. PMID:20147144

Bulk water freezing dynamics on superhydrophobic surfaces

NASA Astrophysics Data System (ADS)

Chavan, S.; Carpenter, J.; Nallapaneni, M.; Chen, J. Y.; Miljkovic, N.

2017-01-01

In this study, we elucidate the mechanisms governing the heat-transfer mediated, non-thermodynamic limited, freezing delay on non-wetting surfaces for a variety of characteristic length scales, Lc (volume/surface area, 3 mm < Lc < 6 mm) using carefully designed freezing experiments in a temperature-controlled, zero-humidity environment on thin water slabs. To probe the effect of surface wettability, we investigated the total time for room temperature water to completely freeze into ice on superhydrophilic ( θaapp→ 0°), hydrophilic (0° < θa < 90°), hydrophobic (90° < θa < 125°), and superhydrophobic ( θaapp→ 180°) surfaces. Our results show that at macroscopic length scales, heat conduction through the bulk water/ice layer dominates the freezing process when compared to heat conduction through the functional coatings or nanoscale gaps at the superhydrophobic substrate-water/ice interface. In order to verify our findings, and to determine when the surface structure thermal resistance approaches the water/ice resistance, we fabricated and tested the additional substrates coated with commercial superhydrophobic spray coatings, showing a monotonic increase in freezing time with coating thickness. The added thermal resistance of thicker coatings was much larger than that of the nanoscale superhydrophobic features, which reduced the droplet heat transfer and increased the total freezing time. Transient finite element method heat transfer simulations of the water slab freezing process were performed to calculate the overall heat transfer coefficient at the substrate-water/ice interface during freezing, and shown to be in the range of 1-2.5 kW/m2K for these experiments. The results shown here suggest that in order to exploit the heat-transfer mediated freezing delay, thicker superhydrophobic coatings must be deposited on the surface, where the coating resistance is comparable to the bulk water/ice conduction resistance.

Molecular docking and molecular dynamics simulations of fumarate hydratase and its mutant H235N complexed with pyromellitic acid and citrate.

PubMed

Subasri, S; Chaudhary, Santosh Kumar; Sekar, K; Kesherwani, Manish; Velmurugan, D

2017-12-01

Fumarase catalyzes the reversible, stereospecific hydration/dehydration of fumarate to L-malate during the Kreb's cycle. In the crystal structure of the tetrameric fumarase, it was found that some of the active site residues S145, T147, N188 G364 and H235 had water-mediated hydrogen bonding interactions with pyromellitic acid and citrate which help to the protonation state for the conversion of fumarate to malate. When His 235 is mutated with Asn (H235N), water-mediated interactions were lost due to the shifting of active site water molecule by 0.7 Å away. Molecular dynamics (MD) simulations were also carried out by NAMD and analyzed using Assisted Model Building with Energy Refinement (AMBER) program to better understand the conformational stability and other aspects during the binding of pyromellitic acid and citrate with native and mutant FH. The role of hydrogen bonds and hydrophobic interactions was also analyzed. The present study confirms that the H235N mutation has a major effect on the catalytic activity of fumarase which is evident from the biochemical studies.

Structure-reactivity relationship of naphthenic acids in the photocatalytic degradation process.

PubMed

de Oliveira Livera, Diogo; Leshuk, Tim; Peru, Kerry M; Headley, John V; Gu, Frank

2018-06-01

Bitumen extraction in Canada's oil sands generates oil sands process-affected water (OSPW) as a toxic by-product. Naphthenic acids (NAs) contribute to the water's toxicity, and treatment methods may need to be implemented to enable safe discharge. Heterogeneous photocatalysis is a promising advanced oxidation process (AOP) for OSPW remediation, however, its successful implementation requires understanding of the complicated relationship between structure and reactivity of NAs. This work aimed to study the effect of various structural properties of model compounds on the photocatalytic degradation kinetics via high resolution mass spectrometry (HRMS), including diamondoid structures, heteroatomic species, and degree of unsaturation. The rate of photocatalytic treatment increased significantly with greater structural complexity, namely with carbon number, aromaticity and degree of cyclicity, properties that render particular NAs recalcitrant to biodegradation. It is hypothesized that a superoxide radical-mediated pathway explains these observations and offers additional benefits over traditional hydroxyl radical-based AOPs. Detailed structure-reactivity investigations of NAs in photocatalysis have not previously been undertaken, and the results described herein illustrate the potential benefit of combining photocatalysis and biodegradation as a complete OSPW remediation technology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Turning things downside up: Adsorbate induced water flipping on Pt(111)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kimmel, Greg A., E-mail: gregory.kimmel@pnnl.gov, E-mail: bruce.kay@pnnl.gov; Zubkov, Tykhon; Smith, R. Scott

2014-11-14

We have examined the adsorption of the weakly bound species N{sub 2}, O{sub 2}, CO, and Kr on the (√(37)×√(37))R25.3{sup ∘} water monolayer on Pt(111) using a combination of molecular beam dosing, infrared reflection absorption spectroscopy, and temperature programmed desorption. In contrast to multilayer crystalline ice, the adsorbate-free water monolayer is characterized by a lack of dangling OH bonds protruding into the vacuum (H-up). Instead, the non-hydrogen-bonded OH groups are oriented downward (H-down) to maximize their interaction with the underlying Pt(111) substrate. Adsorption of Kr and O{sub 2} have little effect on the structure and vibrational spectrum of the “√(37)”more » water monolayer while adsorption of both N{sub 2}, and CO are effective in “flipping” H-down water molecules into an H-up configuration. This “flipping” occurs readily upon adsorption at temperatures as low as 20 K and the water monolayer transforms back to the H-down, “√(37)” structure upon adsorbate desorption above 35 K, indicating small energy differences and barriers between the H-down and H-up configurations. The results suggest that converting water in the first layer from H-down to H-up is mediated by the electrostatic interactions between the water and the adsorbates.« less

Recovery of aquatic insect-mediated methylmercury flux from ponds following drying disturbance.

PubMed

Chumchal, Matthew M; Drenner, Ray W; Greenhill, Frank M; Kennedy, James H; Courville, Ashlyn E; Gober, Charlie A A; Lossau, Luke O

2017-08-01

Small ponds exist across a permanence gradient, and pond permanence is hypothesized to be a primary determinant of insect community structure and insect-mediated methylmercury (MeHg) flux from ponds to the surrounding terrestrial landscape. The present study describes the first experiment examining the recovery of insect-mediated MeHg flux following a drying disturbance that converted permanent ponds with insectivorous fish to semipermanent ponds without fish. Floating emergence traps were used to collect emergent insects for 10 wk in the spring and summer from 5 ponds with fish (permanent) and 5 ponds that were drained to remove fish, dried, and refilled with water (semipermanent). During the 73-d period after semipermanent ponds were refilled, total MeHg flux from semipermanent ponds was not significantly different than total MeHg flux from permanent ponds, indicating that insect-mediated MeHg flux had rapidly recovered in semipermanent ponds following the drying disturbance. Methylmercury fluxes from dragonflies (Odonata: Anisoptera) and phantom midges (Diptera: Chaoboridae) were significantly greater from newly refilled semipermanent ponds than permanent ponds, but the MeHg fluxes from the other 8 emergent insect taxa did not differ between treatments. The present study demonstrates the impact of drying disturbance and the effect of community structure on the cross-system transport of contaminants from aquatic to terrestrial ecosystems. Environ Toxicol Chem 2017;36:1986-1990. © 2017 SETAC. © 2017 SETAC.

Information processing speed mediates the relationship between white matter and general intelligence in schizophrenia.

PubMed

Alloza, Clara; Cox, Simon R; Duff, Barbara; Semple, Scott I; Bastin, Mark E; Whalley, Heather C; Lawrie, Stephen M

2016-08-30

Several authors have proposed that schizophrenia is the result of impaired connectivity between specific brain regions rather than differences in local brain activity. White matter abnormalities have been suggested as the anatomical substrate for this dysconnectivity hypothesis. Information processing speed may act as a key cognitive resource facilitating higher order cognition by allowing multiple cognitive processes to be simultaneously available. However, there is a lack of established associations between these variables in schizophrenia. We hypothesised that the relationship between white matter and general intelligence would be mediated by processing speed. White matter water diffusion parameters were studied using Tract-based Spatial Statistics and computed within 46 regions-of-interest (ROI). Principal component analysis was conducted on these white matter ROI for fractional anisotropy (FA) and mean diffusivity, and on neurocognitive subtests to extract general factors of white mater structure (gFA, gMD), general intelligence (g) and processing speed (gspeed). There was a positive correlation between g and gFA (r= 0.67, p =0.001) that was partially and significantly mediated by gspeed (56.22% CI: 0.10-0.62). These findings suggest a plausible model of structure-function relations in schizophrenia, whereby white matter structure may provide a neuroanatomical substrate for general intelligence, which is partly supported by speed of information processing. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An insight to conserved water molecular dynamics of catalytic and structural Zn(+2) ions in matrix metalloproteinase 13 of human.

PubMed

Chakrabarti, Bornali; Bairagya, Hridoy R; Mallik, Payel; Mukhopadhyay, Bishnu P; Bera, Asim K

2011-02-01

Matrix Metalloproteinase (MMP)--13 or Collagenase--3 plays a significant role in the formation and remodeling of bone, tumor invasion and causes osteoarthritis. Water molecular dynamic studies of the five (1XUC, 1XUD, 1XUR, 456C, 830C) PDB and solvated structures of MMP-13 in human have been carried out upto 5 ns on assigning the differential charges (+2, +1, +0.5 e) to both the Zinc ions. The MM and MD-studies have revealed the coordination of three water molecules (W(H), W(I) and W(S)) to Zn(c) and one water to Zn(s). The transition of geometry around the Znc from tetrahedral to octahedral via trigonal bipyramidal, and for Zn(s) from tetrahedral to trigonal bipyramidal are seem interesting. Recognition of two zinc ions through water molecular bridging (Zn(c) - W(H) (W(1))...W(2)....W(3)....H(187) Zn(s)) and the stabilization of variable coordination geometries around metal ions may indicate the possible involvement of Zn(c) ...Zn(s) coupled mechanism in the catalytic process. So the hydrophilic topology and stereochemistry of water mediated coupling between Zn-ions may provide some plausible hope towards the design of some bidentate/polydentate bridging ligands or inhibitors for MMP-13.

The role of water molecules in stereoselectivity of glucose/galactose-binding protein

NASA Astrophysics Data System (ADS)

Kim, Minsup; Cho, Art E.

2016-11-01

Using molecular dynamics (MD) simulation methods, we attempted to explain the experimental results on ligand specificity of glucose/galactose-binding protein (GGBP) to β-D-glucose and β-D-galactose. For the simulation, a three-dimensional structure of GGBP was prepared, and homology modeling was performed to generate variant structures of GGBP with mutations at Asp14. Then, docking was carried out to find a reasonable β-D-glucose and β-D-galactose binding conformations with GGBP. Subsequent molecular dynamics simulations of β-D-glucose-GGBP and β-D-galactose-GGBP complexes and estimation of the orientation and stability of water molecules at the binding site revealed how water molecules influence ligand specificity. In our simulation, water molecules mediated interactions of β-D-glucose or β-D-galactose with residue 14 of GGBP. In this mechanism, the Phe16Ala mutant leaves both sugar molecules free to move, and the specific role of water molecules were eliminated, while the wild type, Asp14Asn mutant, and Asp14Glu mutant make hydrogen bond interactions with β-D-glucose more favorable. Our results demonstrate that bound water molecules at the binding site of GGBP are related to localized conformational change, contributing to ligand specificity of GGBP for β-D-glucose over β-D-galactose.

Role of adventitious roots in water relations of tamarack (Larix laricina) seedlings exposed to flooding

PubMed Central

2012-01-01

Background Flooding reduces supply of oxygen to the roots affecting plant water uptake. Some flooding-tolerant tree species including tamarack (Larix laricina (Du Roi) K. Koch) produce adventitious roots in response to flooding. These roots were reported to have higher hydraulic conductivity under flooding conditions compared with non-adventitious roots. In the present study, we examined structural and functional modifications in adventitious roots of tamarack seedlings to explain their flooding tolerance. Results Seedlings were subjected to the flooding treatment for six months, which resulted in an almost complete disintegration of the existing root system and its replacement with adventitious roots. We compared gas exchange parameters and water relations of flooded plants with the plants growing in well-drained soil and examined the root structures and root water transport properties. Although flooded seedlings had lower needle chlorophyll concentrations, their stomatal conductance, net photosynthesis rates and shoot water potentials were similar to non-flooded plants, indicative of flooding tolerance. Flooded adventitious roots had higher activation energy and a higher ratio of apoplastic to cell-to-cell water flow compared with non-flooded control roots as determined with the 1-hydroxypirene 3,6,8-trisulfonic acid apoplastic tracer dye. The adventitious roots in flooded plants also exhibited retarded xylem and endodermal development and accumulated numerous starch grains in the cortex. Microscopic examination of root sections treated with the PIP1 and PIP2 antibodies revealed high immunoreactivity in the cortex of non-flooded roots, as compared with flooded roots. Conclusions Structural modifications of adventitious roots suggest increased contribution of apoplastic bypass to water flow. The reduced dependence of roots on the hypoxia-sensitive aquaporin-mediated water transport is likely among the main mechanisms allowing tamarack seedlings to maintain water balance and gas exchange under flooding conditions. PMID:22738296

Role of adventitious roots in water relations of tamarack (Larix laricina) seedlings exposed to flooding.

PubMed

Calvo-Polanco, Mónica; Señorans, Jorge; Zwiazek, Janusz J

2012-06-27

Flooding reduces supply of oxygen to the roots affecting plant water uptake. Some flooding-tolerant tree species including tamarack (Larix laricina (Du Roi) K. Koch) produce adventitious roots in response to flooding. These roots were reported to have higher hydraulic conductivity under flooding conditions compared with non-adventitious roots. In the present study, we examined structural and functional modifications in adventitious roots of tamarack seedlings to explain their flooding tolerance. Seedlings were subjected to the flooding treatment for six months, which resulted in an almost complete disintegration of the existing root system and its replacement with adventitious roots. We compared gas exchange parameters and water relations of flooded plants with the plants growing in well-drained soil and examined the root structures and root water transport properties. Although flooded seedlings had lower needle chlorophyll concentrations, their stomatal conductance, net photosynthesis rates and shoot water potentials were similar to non-flooded plants, indicative of flooding tolerance. Flooded adventitious roots had higher activation energy and a higher ratio of apoplastic to cell-to-cell water flow compared with non-flooded control roots as determined with the 1-hydroxypirene 3,6,8-trisulfonic acid apoplastic tracer dye. The adventitious roots in flooded plants also exhibited retarded xylem and endodermal development and accumulated numerous starch grains in the cortex. Microscopic examination of root sections treated with the PIP1 and PIP2 antibodies revealed high immunoreactivity in the cortex of non-flooded roots, as compared with flooded roots. Structural modifications of adventitious roots suggest increased contribution of apoplastic bypass to water flow. The reduced dependence of roots on the hypoxia-sensitive aquaporin-mediated water transport is likely among the main mechanisms allowing tamarack seedlings to maintain water balance and gas exchange under flooding conditions.

Structural Determinants of Oligomerization of the Aquaporin-4 Channel.

PubMed

Kitchen, Philip; Conner, Matthew T; Bill, Roslyn M; Conner, Alex C

2016-03-25

The aquaporin (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization, and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3, and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Review: mechanisms for boron deficiency-mediated changes in plant water relations.

PubMed

Wimmer, Monika A; Eichert, Thomas

2013-04-01

Boron (B) is an essential microelement for plants and is constantly needed throughout the plant life due to its function as a structural element of the plant cell wall. B deficiency is a wide-spread problem in agricultural areas world-wide, and management of B nutrition is challenged by sudden occurrences of B deficiency or inconsistent effects of foliar B application. The effects of insufficient B supply on different structures relevant for the plant water status have been heavily researched, but the resulting conclusions are contradictory and no clear picture has so far emerged that fully explains the inconsistencies. B deficiency can affect water uptake by inhibition of root and shoot growth and by upregulation of water channels. Structural damage to xylem vessels can limit water transport to arial plant parts, while water loss can be altered by impaired barrier functions of leaf surfaces and reduced photosynthesis. In consequence of all these effects, transpiration is reduced in B-deficient plants under well-watered conditions. Under drought conditions, the responsiveness of stomata is impaired. Possible consequences of damaged vasculature for plant B nutrition include the reduced effectiveness of foliar B fertilization, especially in species with high B phloem mobility. Changes in leaf surface properties can further reduce B uptake after foliar application. In species with low B phloem mobility, weakened xylem vessels may not be able to supply sufficient B to arial parts under conditions of increased B demand, such as during bud development of trees. Since structural damage to vessels is hardly reversible, these effects could be permanent, even if B deficiency was only transient. Another consequence of reduced water status is the higher susceptibility of B-deficient plants to other abiotic stresses, which also impair water relations, especially drought. Since damage to vasculature can occur before visible symptoms of B deficiency appear in shoots, the importance to develop reliable diagnostic tools for detection of sub-acute B deficiency is highlighted. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Electrochemically modified dissolved organic matter accelerates the combining photodegradation and biodegradation of 17α-ethinylestradiol in natural aquatic environment.

PubMed

He, Huan; Huang, Bin; Fu, Gen; Xiong, Dan; Xu, Zhixiang; Wu, Xinhao; Pan, Xuejun

2018-06-15

The photochemical conversion and microbial transformation of pollutants mediated by dissolved organic matter (DOM), including 17α-ethinylestradiol (EE2), are often accompanied in natural water. However, there are few studies to explore the connection and mechanism between the two processes. This research aims to investigate the mechanism of DOM after electrochemically modification mediated EE2 combining photodegradation and biodegradation in the environment and it want to explain the natural phenomena of DOM after electrochemical advanced treatment entering the water environment mediated EE2 natural degradation. The results showed that combining photodegradation with biodegradation rates of EE2 mediated by DOM and electrochemically modified DOM (E-DOM) were promoted obviously. The efficiency of EE2 biodegradation was shown to be strongly correlated with electron accepting capacity (EAC) of DOM. Electrochemical modification can increase the EAC of DOM leading to EE2 biodegradation accelerated, and it also can form more triplet-state DOM moieties to promote the EE2 photodegradation in irradiation conditions, due to the increasing of quinone-type structures in DOM. Moreover, cell polymeric secretion (CPS) secreted from the microorganism could be stimulated to an excited state by irradiation, and that also accelerated EE2 degradation. Photolysis combined with biochemical degradation yielded less toxic degradation products. This study shows that the emission of DOM in wastewater after electrochemical treatment could accelerate estrogen degradation and play a positive role on the pollutant transformation in the environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Vertical stratification of bacterial communities driven by multiple environmental factors in the waters (0-5000 m) off the Galician coast (NW Iberian margin)

NASA Astrophysics Data System (ADS)

Dobal-Amador, Vladimir; Nieto-Cid, Mar; Guerrero-Feijoo, Elisa; Hernando-Morales, Victor; Teira, Eva; Varela-Rozados, Marta M.

2016-08-01

The processes mediated by microbial planktonic communities occur along the entire water column, yet the microbial activity and composition have been studied mainly in surface waters. This research examined the vertical variation in bacterial abundance, activity and community composition and structure from surface down to 5000 m depth following a longitudinal transect off the Galician coast (NW Iberian margin, from 43°N, 9°W to 43°N, 15°W). Community activity and composition changed with depth. The leucine incorporation rates decreased from the euphotic layer to the bathypelagic waters by three orders of magnitude, whereas prokaryotic abundance decreased only by one order of magnitude. The relative abundance of SAR11 and Alteromonas, determined by catalyzed reported deposition fluorescence in situ hybridization (CARD-FISH), decreased with depth. Meanwhile, the contribution of SAR 202 and SAR324 was significantly higher in the deeper layers (i.e. NEADW, North East Atlantic Deep Water and LDW, Lower Deep Water) than in the euphotic zone. Bacterial community structure, assessed by Automated Ribosomal Intergenic Spacer Analysis (ARISA), was depth-specific. A distance based linear model (DistLM) revealed that the variability found in bacterial community structure was mainly explained by temperature nitrate, phosphate, dissolved organic matter (DOM) fluorescence, prokaryotic abundance, leucine incorporation and to a lesser extent salinity, oxygen, CDOM absorbance and dissolved organic carbon concentration. Our results displayed a bacterial community structure shaped not only by depth-related physicochemical features but also by DOM quality, indicating that different prokaryotic taxa have the potential to metabolize particular DOM sources.

Effects of a behavior change campaign on household drinking water disinfection in the Lake Chad basin using the RANAS approach.

PubMed

Lilje, Jonathan; Mosler, Hans-Joachim

2018-04-01

Worldwide, an estimated 700 million people rely on unimproved drinking water sources; even more consume water that is not safe to drink. Inadequate drinking water quality constitutes a major risk factor for cholera and other diarrheal diseases around the globe, especially for young children in developing countries. Household water treatment and safe storage systems represent an intermediate solution for settings that lack infrastructure supplying safe drinking water. However, the correct and consistent usage of such treatment technologies rely almost exclusively on the consumer's behavior. This study targeted at evaluating effects of a behavior change campaign promoting the uptake of household drinking water chlorination in communities along the Chari and Logone rivers in Chad. The campaign was based on formative research using health psychological theory and targeted several behavioral factors identified as relevant. A total of 220 primary caregivers were interviewed concerning their household water treatment practices and mindset related to water treatment six months after the campaign. The Risks, Attitudes, Norms, Abilities, and Self-regulation (RANAS) model was used to structure the interviews as the RANAS approach had been used for designing the campaign. Results show significantly higher self-reported drinking water chlorination among participants of the intervention. Significant differences from a control group were identified regarding several behavioral factors. Mediation analysis revealed that the intervention positively affected participants' individual risk estimation for diarrheal disease, health knowledge, perceived efforts and benefits of water treatment, social support strategies, knowledge of how to perform chlorination, and perceived ability to do so. The campaign's effect on water treatment was mainly mediated through differences in health knowledge, changes in norms, and self-efficacy convictions. The findings imply that water treatment behavior can be successfully promoted using health psychological theory. However, they also indicate opportunities for improvement in the campaign design and implementation. Copyright © 2017 Elsevier B.V. All rights reserved.

Climate-mediated changes in zooplankton community structure for the eastern Bering Sea

NASA Astrophysics Data System (ADS)

Eisner, Lisa B.; Napp, Jeffrey M.; Mier, Kathryn L.; Pinchuk, Alexei I.; Andrews, Alexander G.

2014-11-01

Zooplankton are critical to energy transfer between higher and lower trophic levels in the eastern Bering Sea ecosystem. Previous studies from the southeastern Bering Sea shelf documented substantial differences in zooplankton taxa in the Middle and Inner Shelf Domains between warm and cold years. Our investigation expands this analysis into the northern Bering Sea and the south Outer Domain, looking at zooplankton community structure during a period of climate-mediated, large-scale change. Elevated air temperatures in the early 2000s resulted in regional warming and low sea-ice extent in the southern shelf whereas the late 2000s were characterized by cold winters, extensive spring sea ice, and a well-developed pool of cold water over the entire Middle Domain. The abundance of large zooplankton taxa such as Calanus spp. (C. marshallae and C. glacialis), and Parasagitta elegans, increased from warm to cold periods, while the abundance of gelatinous zooplankton (Cnidaria) and small taxa decreased. Biomass followed the same trends as abundance, except that the biomass of small taxa in the southeastern Bering Sea remained constant due to changes in abundance of small copepod taxa (increases in Acartia spp. and Pseudocalanus spp. and decreases in Oithona spp.). Statistically significant changes in zooplankton community structure and individual species were greatest in the Middle Domain, but were evident in all shelf domains, and in both the northern and southern portions of the eastern shelf. Changes in community structure did not occur abruptly during the transition from warm to cold, but seemed to begin gradually and build as the influence of the sea ice and cold water temperatures persisted. The change occurred one year earlier in the northern than the southern Middle Shelf. These and previous observations demonstrate that lower trophic levels within the eastern Bering Sea respond to climate-mediated changes on a variety of time scales, including those shorter than the commonly accepted quasi-decadal time periods. This lack of resilience or inertia at the lowest trophic levels affects production at higher trophic levels and must be considered in management strategy evaluations of living marine resources.

Water penetration/accommodation and phase behaviour of the neutral Langmuir monolayer at the air/water interface probed with sum frequency generation vibrational spectroscopy (SFG-VS).

PubMed

Zhang, Zhen; Zheng, De-Sheng; Guo, Yuan; Wang, Hong-Fei

2009-02-14

A strong and broad hydrogen bonded O-H band around 3520 cm(-1) is observed in the insoluble monolayer of the neutral liquid crystal molecules of 4''-n-pentyl-4-p-cyanobiphenyl (5CB) and 4''-n-octyl-4-p-cyanobiphenyl (8CB) throughout the whole surface density range, but not in the 4-pentyl-4'-cyanoterphenyl (5CT) monolayer, at the air/water interface. This novel spectral feature suggests the existence of an oriented water cluster species which has penetrated or accommodated into the Langmuir monolayer of the 8CB and 5CB molecules. This finding provided a molecular level mechanism for the stark difference in the phase behaviour between the CB and CT insoluble Langmuir monolayers at the air/water interface. It also calls for attention to the details of the specific water-surface interaction in mediating the structure and the phase behaviour of the molecular assemblies at the heterogeneous aqueous interfaces.

Spectral and structural studies of dimethylphenyl betaine hydrate

NASA Astrophysics Data System (ADS)

Szafran, M.; Ostrowska, K.; Katrusiak, A.; Dega-Szafran, Z.

2014-07-01

Hydrates of betaines can be divided into four groups depending on the interactions of their water molecules with the carboxylate group. Dimethylphenyl betaine crystallizes as monohydrate (1), in which water molecules mediate in hydrogen bonds between the carboxylate groups. The water molecules are H-bonded only to one oxygen atom of the dimethylphenyl betaine molecules and link them into a chain via two O(1 W)sbnd H⋯O hydrogen bonds of the lengths 2.779(2) and 2.846(2) Å. The structures of monomer (2) and dimer (4) hydrates in vacuum, and the structure of monomer (3) in an aqueous environment have been optimized by the B3LYP/6-311++G(d,p) approach and the geometrical results have been compared with the X-ray diffraction data of 1. The calculated IR frequencies for the optimized structure have been used for the assignments of FTIR bands, the broad absorption band in the range 3415-3230 cm-1 has been assigned to the O(1w)sbnd H⋯O hydrogen bonds. The correlations between the experimental 1H and 13C NMR chemical shifts (δexp) of 1 in D2O and the magnetic isotropic shielding constants (σcalc) calculated by the GIAO/B3LYP/6-311G++(d,p) approach, using the screening solvation model (COSMO), δexp = a + b σcalc, for optimized molecule 3 in water solution are linear and well reproduce the experimental chemical shifts.

Phosphodiester Cleavage in Ribonuclease H Occurs via an Associative Two-Metal-Aided Catalytic Mechanism

PubMed Central

De Vivo, Marco; Dal Peraro, Matteo; Klein, Michael L.

2009-01-01

Ribonuclease H (RNase H) belongs to the nucleotidyl-transferase (NT) superfamily and hydrolyzes the phosphodiester linkages that form the backbone of the RNA strand in RNA·DNA hybrids. This enzyme is implicated in replication initiation and DNA topology restoration and represents a very promising target for anti-HIV drug design. Structural information has been provided by high-resolution crystal structures of the complex RNase H/RNA·DNA from Bacillus halodurans (Bh), which reveals that two metal ions are required for formation of a catalytic active complex. Here, we use classical force field-based and quantum mechanics/molecular mechanics calculations for modeling the nucleotidyl transfer reaction in RNase H, clarifying the role of the metal ions and the nature of the nucleophile (water versus hydroxide ion). During the catalysis, the two metal ions act cooperatively, facilitating nucleophile formation and stabilizing both transition state and leaving group. Importantly, the two Mg2+ metals also support the formation of a meta-stable phosphorane intermediate along the reaction, which resembles the phosphorane intermediate structure obtained only in the debated β-phosphoglucomutase crystal. The nucleophile formation (i.e., water deprotonation) can be achieved in situ, after migration of one proton from the water to the scissile phosphate in the transition state. This proton transfer is actually mediated by solvation water molecules. Due to the highly conserved nature of the enzymatic bimetal motif, these results might also be relevant for structurally similar enzymes belonging to the NT superfamily. PMID:18662000

Can Parenting Practices Explain the Differences in Beverage Intake According to Socio-Economic Status: The Toybox-Study

PubMed Central

Pinket, An-Sofie; De Craemer, Marieke; De Bourdeaudhuij, Ilse; Deforche, Benedicte; Cardon, Greet; Androutsos, Odysseas; Koletzko, Berthold; Moreno, Luis A.; Socha, Piotr; Iotova, Violeta; Manios, Yannis; Van Lippevelde, Wendy

2016-01-01

Previous research indicated that preschoolers of lower socioeconomic status (SES) consume less healthy beverages than high SES preschoolers. The purpose of this study is to investigate the mediating role of parenting practices in the relationship between SES and plain water, soft drink and prepacked fruit juice (FJ) consumption in European preschoolers. Parents/caregivers of 3.5 to 5.5 years old (n = 6776) recruited through kindergartens in six European countries within the ToyBox-study completed questionnaires on socio-demographics, parenting practices and a food frequency questionnaire. Availability of sugared beverages and plain water, permissiveness towards sugared beverages and lack of self-efficacy showed a mediating effect on SES-differences in all three beverages. Rewarding with sugared beverages significantly mediated SES-differences for both plain water and prepacked FJ. Encouragement to drink plain water and awareness significantly mediated SES-differences for, respectively, plain water and prepacked FJ consumption. Avoiding negative modelling did not mediate any associations. Overall, lower SES preschoolers were more likely to be confronted with lower levels of favourable and higher levels of unfavourable parenting practices, which may lead to higher sugared beverage and lower plain water consumption. The current study highlights the importance of parenting practices in explaining the relation between SES and both healthy and unhealthy beverage consumption. PMID:27669290

A mediated modelling approach to promote collaborative learning in Andean rural micro-catchments in Colombia

NASA Astrophysics Data System (ADS)

Gowing, John; Dominguez, Isabel

2013-04-01

In rural catchments of developing countries water-related diseases, due to land use patterns (agriculture and livestock), microbial pollution, inadequate sanitation systems, access to water of poor quality, and lack of institutional support are common problems which disproportionally affect poor and vulnerable people. This research aims at developing a system dynamic model to improve the understanding of the macro and micro factors that influence human health and environmental health in rural micro-catchments in Valle del Cauca, Colombia. In this catchment livelihoods for most people depend on agriculture, particularly coffee. The research uses a mediated modeling approach, in which different stakeholders in modeling sessions, develop a STELLA model that allows them to identify relations between the economic, social and environmental factors and driving forces over the performance of their system. Stakeholders jointly develop the model structure in sessions facilitated by the researcher and the data required is gathered using secondary information from the different relevant institutions and primary information from field surveys that cover socioeconomic and environmental aspects that has not been previously collected by any institution or organization (i.e. household survey, stream water survey, and drinking water survey). Representation and understanding of their system will allow the stakeholders to test the effect of different management strategies in the micro-catchment and their associated socioeconomic, environmental and human health outcomes.

Subunit architecture and functional modular rearrangements of the transcriptional Mediator complex

PubMed Central

Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C.; Conaway, Joan W.; Asturias, Francisco J.

2014-01-01

SUMMARY The multisubunit Mediator comprising ~30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. PMID:24882805

Water as a matrix for life

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Pratt, Lawrence

2006-01-01

"Follow the water" is the canonical strategy in searching for life in the universe. Conventionally, discussion of this topic is focused on how solvent supports organic chemistry sufficiently rich to seed life. Perhaps more importantly, solvent must promote self-organization of organic matter into functional structures capable of responding to environmental changes. This process is based on non-covalent interactions. They are constantly formed and broken in response to internal and external stimuli. This requires that their strength must be properly tuned. If they were too weak, the system would exhibit undesired, uncontrolled response to natural fluctuations of physical and chemical parameters. If they were too strong kinetics of biological processes would be slow and energetics costly. Non-covalent interactions are strongly mediated by the solvent. Specifically, high dielectric solvents for life are needed for solubility of polar species and flexibility of biological structures stabilized by electrostatic interactions. Water exhibits a remarkable trait that it promotes solvophobic interactions between non-polar species, which are responsible for self-organization phenomena such as the formation of cellular boundary structures, and protein folding and aggregation. Unusual temperature dependence of hydrophobic interactions - they often become stronger as temperature increases - is a consequence of the temperature insensitivity of properties of the liquid water. This contributes to the existence of robust life over a wide temperature range. Water is not the only liquid with favorable properties for supporting life. Other pure liquids or their mixtures that have high dielectric constants and simultaneously support some level of self-organization will be discussed.

Renewable bio ionic liquids-water mixtures-mediated selective removal of lignin from rice straw: visualization of changes in composition and cell wall structure.

PubMed

Hou, Xue-Dan; Li, Ning; Zong, Min-Hua

2013-07-01

Pretreatment of rice straw by using renewable cholinium amino acids ionic liquids ([Ch][AA] ILs)-water mixtures and the subsequent enzymatic hydrolysis of the residues were conducted in the present work. Of the eight mixtures composed of ILs and water, most were found to be effective for rice straw pretreatment. After pretreatment with 50% ILs-water mixtures, the enzymatic digestion of the lignocellulosic biomass was enhanced significantly, thus leading to satisfactory sugar yields of >80% for glucose and approximately 50% for xylose. To better understand the ILs pretreatment mechanism, confocal laser scanning microscopy combined with immunolabeling and transmission electron microscopy were used to visualize changes in the contents and distribution of two major components--lignin and xylan. The results coupled with changes in chemical structures (infrared spectra) of the substrates indicated occurrence of extensive delignification, especially in cell corner and compound middle lumen of cell walls, which made polysaccharides more accessible to enzymes. This pretreatment process is promising for large-scale application because of the high sugar yields, easy handling, being environmentally benign and highly tolerant to moisture, and significantly reduced cost and energy consumption. Copyright © 2013 Wiley Periodicals, Inc.

Crystal structure of the Msx-1 homeodomain/DNA complex.

PubMed

Hovde, S; Abate-Shen, C; Geiger, J H

2001-10-09

The Msx-1 homeodomain protein plays a crucial role in craniofacial, limb, and nervous system development. Homeodomain DNA-binding domains are comprised of 60 amino acids that show a high degree of evolutionary conservation. We have determined the structure of the Msx-1 homeodomain complexed to DNA at 2.2 A resolution. The structure has an unusually well-ordered N-terminal arm with a unique trajectory across the minor groove of the DNA. DNA specificity conferred by bases flanking the core TAAT sequence is explained by well ordered water-mediated interactions at Q50. Most interactions seen at the TAAT sequence are typical of the interactions seen in other homeodomain structures. Comparison of the Msx-1-HD structure to all other high resolution HD-DNA complex structures indicate a remarkably well-conserved sphere of hydration between the DNA and protein in these complexes.

Massive shelf dense water flow influences plankton community structure and particle transport over long distance.

PubMed

Bernardi Aubry, Fabrizio; Falcieri, Francesco Marcello; Chiggiato, Jacopo; Boldrin, Alfredo; Luna, Gian Marco; Finotto, Stefania; Camatti, Elisa; Acri, Francesco; Sclavo, Mauro; Carniel, Sandro; Bongiorni, Lucia

2018-03-14

Dense waters (DW) formation in shelf areas and their cascading off the shelf break play a major role in ventilating deep waters, thus potentially affecting ecosystem functioning and biogeochemical cycles. However, whether DW flow across shelves may affect the composition and structure of plankton communities down to the seafloor and the particles transport over long distances has not been fully investigated. Following the 2012 north Adriatic Sea cold outbreak, DW masses were intercepted at ca. 460 km south the area of origin and compared to resident ones in term of plankton biomass partitioning (pico to micro size) and phytoplankton species composition. Results indicated a relatively higher contribution of heterotrophs in DW than in deep resident water masses, probably as result of DW-mediated advection of fresh organic matter available to consumers. DWs showed unusual high abundances of Skeletonema sp., a diatom that bloomed in the north Adriatic during DW formation. The Lagrangian numerical model set up on this diatom confirmed that DW flow could be an important mechanism for plankton/particles export to deep waters. We conclude that the predicted climate-induced variability in DW formation events could have the potential to affect the ecosystem functioning of the deeper part of the Mediterranean basin, even at significant distance from generation sites.

Mercury increases water permeability of a plant aquaporin through a non-cysteine-related mechanism.

PubMed

Frick, Anna; Järvå, Michael; Ekvall, Mikael; Uzdavinys, Povilas; Nyblom, Maria; Törnroth-Horsefield, Susanna

2013-09-15

Water transport across cellular membranes is mediated by a family of membrane proteins known as AQPs (aquaporins). AQPs were first discovered on the basis of their ability to be inhibited by mercurial compounds, an experiment which has followed the AQP field ever since. Although mercury inhibition is most common, many AQPs are mercury insensitive. In plants, regulation of AQPs is important in order to cope with environmental changes. Plant plasma membrane AQPs are known to be gated by phosphorylation, pH and Ca²⁺. We have previously solved the structure of the spinach AQP SoPIP2;1 (Spinacia oleracea plasma membrane intrinsic protein 2;1) in closed and open conformations and proposed a mechanism for how this gating can be achieved. To study the effect of mercury on SoPIP2;1 we solved the structure of the SoPIP2;1-mercury complex and characterized the water transport ability using proteoliposomes. The structure revealed mercury binding to three out of four cysteine residues. In contrast to what is normally seen for AQPs, mercury increased the water transport rate of SoPIP2;1, an effect which could not be attributed to any of the cysteine residues. This indicates that other factors might influence the effect of mercury on SoPIP2;1, one of which could be the properties of the lipid bilayer.

Confronting water in an Israeli-Palestinian peace agreement

NASA Astrophysics Data System (ADS)

Brooks, David; Trottier, Julie

2010-03-01

SummaryTrans-boundary water agreements are usually conceived as allocation agreements. In other words, water is treated as if it were a pie to be divided among the riparian states. The treatment of water as if it were as immobile as land may be useful in the short term, but it is fundamentally flawed as a means to avoid conflict as well as to ensure efficient, equitable, and sustainable management of water over the long term. This article proposes to avoid quantitative allocations within international water agreements, whether they be presented as percentage or fixed allocations or whether or not accompanied by a periodic revision clause. It proposes instead an ongoing joint management structure that allows for continuous conflict resolution concerning water demands and uses in a manner that effectively de-nationalises water uses. As well, it builds on existing, functioning institutions that are already active over a variety of scalar levels. It disaggregates what is usually perceived as a national water demand into its component institutions and re-aggregates them within an international institutional context. Though this approach for building trans-boundary water agreements can prove useful in any geographical situation, this article uses the Israeli-Palestinian conflict as a model. It proposes to respect the existing differences in the institutional management of water between the two entities and to reach four general objectives: economic efficiency, social and political equity, ecological sustainability, and the ability to implement the agreement in practice. The institutional design and proposed mechanisms follow five key principles for shared management: water allocations that are not fixed but variable over time; equality in rights and responsibilities; priority for demand management over supply management; continuous monitoring of water quality and quantity; and mediation among competing uses of fresh water. This institutional structure balances water quantity and water quality issues and economic and environmental goals in a de-securitised fashion. Though specifically applied to water shared by Israelis and Palestinians, the objectives, principles and institutional structure are relevant to any place in the world where trans-boundary water divides rather than unites two or more peoples.

DNA octaplex formation with an I-motif of water-mediated A-quartets: reinterpretation of the crystal structure of d(GCGAAAGC).

PubMed

Sato, Yoshiteru; Mitomi, Kenta; Sunami, Tomoko; Kondo, Jiro; Takénaka, Akio

2006-12-01

The crystal structure of the tetragonal form of d(gcGAAAgc) has been revised and reasonably refined including the disordered residues. The two DNA strands form a base-intercalated duplex, and the four duplexes are assembled according to the crystallographic 222 symmetry to form an octaplex. In the central region, the eight strands are associated by I-motif of double A-quartets. Furthermore, eight hydrated-magnesium cations link the four duplexes to support the octaplex formation. Based on these structural features, a proposal that folding of d(GAAA)n, found in the non-coding region of genomes, into an octaplex can induce slippage during replication to facilitate length polymorphism is presented.

WatAA: Atlas of Protein Hydration. Exploring synergies between data mining and ab initio calculations.

PubMed

Černý, Jiří; Schneider, Bohdan; Biedermannová, Lada

2017-07-14

Water molecules represent an integral part of proteins and a key determinant of protein structure, dynamics and function. WatAA is a newly developed, web-based atlas of amino-acid hydration in proteins. The atlas provides information about the ordered first hydration shell of the most populated amino-acid conformers in proteins. The data presented in the atlas are drawn from two sources: experimental data and ab initio quantum-mechanics calculations. The experimental part is based on a data-mining study of a large set of high-resolution protein crystal structures. The crystal-derived data include 3D maps of water distribution around amino-acids and probability of occurrence of each of the identified hydration sites. The quantum mechanics calculations validate and extend this primary description by optimizing the water position for each hydration site, by providing hydrogen atom positions and by quantifying the interaction energy that stabilizes the water molecule at the particular hydration site position. The calculations show that the majority of experimentally derived hydration sites are positioned near local energy minima for water, and the calculated interaction energies help to assess the preference of water for the individual hydration sites. We propose that the atlas can be used to validate water placement in electron density maps in crystallographic refinement, to locate water molecules mediating protein-ligand interactions in drug design, and to prepare and evaluate molecular dynamics simulations. WatAA: Atlas of Protein Hydration is freely available without login at .

Environmental constraints on the compositional and phylogenetic beta-diversity of tropical forest snake assemblages.

PubMed

Moura, Mario R; Costa, Henrique C; Argôlo, Antônio J S; Jetz, Walter

2017-09-01

The ongoing biodiversity crisis increases the importance and urgency of studies addressing the role of environmental variation on the composition and evolutionary history of species assemblages, but especially the tropics and ectotherms remain understudied. In regions with rainy summers, coexistence of tropical ectothermic species may be determined by the partitioning of the climatic niche, as ectotherms can rely on water availability and thermoregulatory behaviour to buffer constraints along their climatic niche. Conversely, tropical ectotherms facing dry summers would have fewer opportunities to climatic niche partitioning and other processes rather than environmental filtering would mediate species coexistence. We used 218 snake assemblages to quantify the compositional (CBD) and phylogenetic (PBD) beta-diversity of snakes in the Atlantic Forest (AF) hotspot, South America. We identify two AF regions with distinct climatological regimes: dry summers in the northern-AF and rainy summers in the southern-AF. While accounting for the influence of multiscale spatial processes, we disentangle the relative contribution of thermal, water-related and topographic conditions in structuring the CBD and PBD of snake assemblages, and determine the extent in which snake assemblages under distinct climatological regimes are affected by environmental filtering. Thermal conditions best explain CBD and PBD of snakes for the whole AF, whereas water-related factors best explain the structure of snake assemblages within a same climatological regime. CBD and PBD patterns are similarly explained by spatial factors but snake assemblages facing dry summers are more affected by spatial processes operating at fine to intermediate spatial scale, whereas those assemblages in regions with rainy summers have a stronger signature of coarse-scale processes. As expected, environmental filtering plays a stronger role in southern-AF than northern-AF, and the synergism between thermal and water-related conditions is the key cause behind this difference. Differences in climatological regimes within the tropics affect processes mediating species coexistence. The influence of broad-scale gradients (e.g. temperature and precipitation) in structuring tropical ectothermic assemblages is greater in regions with rainy summers where climatic niche partitioning is more likely. Our findings highlight the potential stronger role of biotic interactions and neutral processes in structuring ectothermic assemblages facing changes towards warmer and dryer climates. © 2017 The Authors. Journal of Animal Ecology © 2017 British Ecological Society.

Cu,Zn superoxide dismutase structure from a microbial pathogen establishes a class with a conserved dimer interface.

PubMed

Forest, K T; Langford, P R; Kroll, J S; Getzoff, E D

2000-02-11

Macrophages and neutrophils protect animals from microbial infection in part by issuing a burst of toxic superoxide radicals when challenged. To counteract this onslaught, many Gram-negative bacterial pathogens possess periplasmic Cu,Zn superoxide dismutases (SODs), which act on superoxide to yield molecular oxygen and hydrogen peroxide. We have solved the X-ray crystal structure of the Cu,Zn SOD from Actinobacillus pleuropneumoniae, a major porcine pathogen, by molecular replacement at 1.9 A resolution. The structure reveals that the dimeric bacterial enzymes form a structurally homologous class defined by a water-mediated dimer interface, and share with all Cu,Zn SODs the Greek-key beta-barrel subunit fold with copper and zinc ions located at the base of a deep loop-enclosed active-site channel. Our structure-based sequence alignment of the bacterial enzymes explains the monomeric nature of at least two of these, and suggests that there may be at least one additional structural class for the bacterial SODs. Two metal-mediated crystal contacts yielded our C222(1) crystals, and the geometry of these sites could be engineered into proteins recalcitrant to crystallization in their native form. This work highlights structural differences between eukaryotic and prokaryotic Cu,Zn SODs, as well as similarities and differences among prokaryotic SODs, and lays the groundwork for development of antimicrobial drugs that specifically target periplasmic Cu,Zn SODs of bacterial pathogens. Copyright 12000 Academic Press.

Prediction of the translocon-mediated membrane insertion free energies of protein sequences.

PubMed

Park, Yungki; Helms, Volkhard

2008-05-15

Helical membrane proteins (HMPs) play crucial roles in a variety of cellular processes. Unlike water-soluble proteins, HMPs need not only to fold but also get inserted into the membrane to be fully functional. This process of membrane insertion is mediated by the translocon complex. Thus, it is of great interest to develop computational methods for predicting the translocon-mediated membrane insertion free energies of protein sequences. We have developed Membrane Insertion (MINS), a novel sequence-based computational method for predicting the membrane insertion free energies of protein sequences. A benchmark test gives a correlation coefficient of 0.74 between predicted and observed free energies for 357 known cases, which corresponds to a mean unsigned error of 0.41 kcal/mol. These results are significantly better than those obtained by traditional hydropathy analysis. Moreover, the ability of MINS to reasonably predict membrane insertion free energies of protein sequences allows for effective identification of transmembrane (TM) segments. Subsequently, MINS was applied to predict the membrane insertion free energies of 316 TM segments found in known structures. An in-depth analysis of the predicted free energies reveals a number of interesting findings about the biogenesis and structural stability of HMPs. A web server for MINS is available at http://service.bioinformatik.uni-saarland.de/mins

A proactive role of water molecules in acceptor recognition by protein O-fucosyltransferase 2.

PubMed

Valero-González, Jessika; Leonhard-Melief, Christina; Lira-Navarrete, Erandi; Jiménez-Osés, Gonzalo; Hernández-Ruiz, Cristina; Pallarés, María Carmen; Yruela, Inmaculada; Vasudevan, Deepika; Lostao, Anabel; Corzana, Francisco; Takeuchi, Hideyuki; Haltiwanger, Robert S; Hurtado-Guerrero, Ramon

2016-04-01

Protein O-fucosyltransferase 2 (POFUT2) is an essential enzyme that fucosylates serine and threonine residues of folded thrombospondin type 1 repeats (TSRs). To date, the mechanism by which this enzyme recognizes very dissimilar TSRs has been unclear. By engineering a fusion protein, we report the crystal structure of Caenorhabditis elegans POFUT2 (CePOFUT2) in complex with GDP and human TSR1 that suggests an inverting mechanism for fucose transfer assisted by a catalytic base and shows that nearly half of the TSR1 is embraced by CePOFUT2. A small number of direct interactions and a large network of water molecules maintain the complex. Site-directed mutagenesis demonstrates that POFUT2 fucosylates threonine preferentially over serine and relies on folded TSRs containing the minimal consensus sequence C-X-X-S/T-C. Crystallographic and mutagenesis data, together with atomic-level simulations, uncover a binding mechanism by which POFUT2 promiscuously recognizes the structural fingerprint of poorly homologous TSRs through a dynamic network of water-mediated interactions.

Unusual Water-mediated Antigenic Recognition of the Proinflammatory Cytokine Interleukin-18

DOE Office of Scientific and Technical Information (OSTI.GOV)

Argiriadi, Maria A.; Xiang, Tao; Wu, Chengbin

2009-10-21

The unique cytokine interleukin-18 (IL-18) acts synergistically with IL-12 to regulate T-helper 1 and 2 lymphocytes and, as such, seems to underlie the pathogenesis of various autoimmune and allergic diseases. Several anti-IL-18 agents are in clinical development, including the recombinant human antibody ABT-325, which is entering trials for autoimmune diseases. Given competing cytokine/receptor and cytokine/receptor decoy interactions, understanding the structural basis for recognition is critical for effective development of anti-cytokine therapies. Here we report three crystal structures: the murine antibody 125-2H Fab fragment bound to human IL-18, at 1.5 {angstrom} resolution; the 125-2H Fab (2.3 {angstrom}); and the ABT-325 Fabmore » (1.5 {angstrom}). These structures, along with human/mouse IL-18 chimera binding data, allow us to make three key observations relevant to the biology and antigenic recognition of IL-18 and related cytokines. First, several IL-18 residues shift dramatically (>10 {angstrom}) upon binding 125-2H, compared with unbound IL-18 (Kato, Z., Jee, J., Shikano, H., Mishima, M., Ohki, I., Ohnishi, H., Li, A., Hashimoto, K., Matsukuma, E., Omoya, K., Yamamoto, Y., Yoneda, T., Hara, T., Kondo, N., and Shirakawa, M. (2003) Nat. Struct. Biol. 10, 966-971). IL-18 thus exhibits plasticity that may be common to its interactions with other receptors. Related cytokines may exhibit similar plasticity. Second, ABT-325 and 125-2H differ significantly in combining site character and architecture, thus explaining their ability to bind IL-18 simultaneously at distinct epitopes. These data allow us to define the likely ABT-325 epitope and thereby explain the distinct neutralizing mechanisms of both antibodies. Third, given the high 125-2H potency, 10 well ordered water molecules are trapped upon complex formation in a cavity between two IL-18 loops and all six 125-2H complementarity-determining regions. Thus, counterintuitively, tight and specific antibody binding may in some cases be water-mediated.« less

Control of size and viscoelastic properties of nanofibrillated cellulose from palm tree by varying the TEMPO-mediated oxidation time.

PubMed

Benhamou, Karima; Dufresne, Alain; Magnin, Albert; Mortha, Gérard; Kaddami, Hamid

2014-01-01

The main objective of the present study was to control and optimize the preparation of nanofibrillated cellulose (NFC) from the date palm tree by monitoring the oxidation time (degree of oxidation) of the pristine cellulose and the number of cycles through the homogenizer. The oxidation was monitored by TEMPO (1-oxo-2,2,6,6-tétraméthylpipyridine 1-oxyle) mediated oxidation. Evidence of the successful isolation of NFC was given by FE-SEM observation revealing fibrils with a width in the range 20-30nm, depending of the oxidation time. The evolution of the transparency of the aqueous NFC suspension and carboxylic content according to the degree of oxidation and number of cycles were also analyzed by UV-vis transmittance, Fourier-transform infrared spectroscopy (FT-IR), conductimetry, and X-ray diffraction analysis. A significant NFC length reduction occurred during the TEMPO-mediated oxidation. The rheological properties of NFC suspensions were characterized as function of the oxidation time. Dynamic rheology showed that the aqueous suspension behavior changed from liquid to gel depending on the concentration. The highest concentration studied was 1wt% and the modulus reached 1MPa which was higher than for non-oxidized NFC. An explanation of the gel structure evolution with the oxidation time applied to the NFC (NFC length) was proposed. The gel structure evolves from an entanglement-governed gel structure to an immobilized water molecule-governed one. Copyright © 2013 Elsevier Ltd. All rights reserved.

Long-term impact of hydrological regime on structure and functions of microbial communities in riverine wetland sediments.

PubMed

Foulquier, Arnaud; Volat, Bernadette; Neyra, Marc; Bornette, Gudrun; Montuelle, Bernard

2013-08-01

In a context of global change, alterations in the water cycle may impact the structure and function of terrestrial and aquatic ecosystems. Wetlands are particularly at risk because hydrological regime has a major influence on microbially mediated biogeochemical processes in sediments. While the influence of water availability on wetland biogeochemical processes has been comprehensively studied, the influence of hydrological regime on microbial community structure has been overlooked. We tested for the effect of hydrological regime on the structure and functions of microbial communities by comparing sediments collected at multiple sites in the Ain département (Eastern France). Each site consisted of two plots, one permanently and one seasonally inundated. At the time of sampling, all plots were continuously inundated for more than 6 months but still harboured distinct bacterial communities. This change in community structure was not associated with marked modifications in the rates of microbial activities involved in the C and N cycles. These results suggest that the observed structural change could be related to bacterial taxa responding to the environmental variations associated with different hydrological regimes, but not strongly associated with the biogeochemical processes monitored here. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Plasma membrane aquaporins mediates vesicle stability in broccoli

PubMed Central

Martínez-Ballesta, Maria del Carmen; García-Gomez, Pablo; Yepes-Molina, Lucía; Guarnizo, Angel L.; Teruel, José A.

2018-01-01

The use of in vitro membrane vesicles is attractive because of possible applications in therapies. Here we aimed to compare the stability and functionality of plasma membrane vesicles extracted from control and salt-treated broccoli. The impact of the amount of aquaporins was related to plasma membrane osmotic water permeability and the stability of protein secondary structure. Here, we describe for first time an increase in plant aquaporins acetylation under high salinity. Higher osmotic water permeability in NaCl vesicles has been related to higher acetylation, upregulation of aquaporins, and a more stable environment to thermal denaturation. Based on our findings, we propose that aquaporins play an important role in vesicle stability. PMID:29420651

Multiscale and Multifunctional Emulsions by Host–Guest Interaction-Mediated Self-Assembly

PubMed Central

2018-01-01

Emulsions are widely used in numerous fields. Therefore, there has been increasing interest in the development of new emulsification strategies toward emulsions with advanced functions. Herein we report the formation of diverse emulsions by host–guest interaction-mediated interfacial self-assembly under mild conditions. In this strategy, a hydrophilic diblock copolymer with one block containing β-cyclodextrin (β-CD) can assemble at the oil/water interface when its aqueous solution is mixed with an oil phase of benzyl alcohol (BA), by host–guest interactions between β-CD and BA. This results in significantly reduced interfacial tension and the formation of switchable emulsions with easily tunable droplet sizes. Furthermore, nanoemulsions with excellent stability are successfully prepared simply via vortexing. The self-assembled oil-in-water emulsions also show catastrophic phase inversion, which can generate stable bicontinuous phase and water-in-oil emulsions, thereby further extending phase structures that can be realized by this host–guest self-assembly approach. Moreover, the host–guest nanoemulsions are able to engineer different nanoparticles and microstructures as well as solubilize a diverse array of hydrophobic drugs and dramatically enhance their oral bioavailability. The host–guest self-assembly emulsification is facile, energetically friendly, and fully translatable to industry, therefore representing a conceptually creative approach toward advanced emulsions. PMID:29806006

Acute vascular effects of carbonated warm water lower leg immersion in healthy young adults.

PubMed

Ogoh, Shigehiko; Nagaoka, Ryohei; Mizuno, Takamasa; Kimura, Shohei; Shidahara, Yasuhiro; Ishii, Tomomi; Kudoh, Michinari; Iwamoto, Erika

2016-12-01

Endothelial dysfunction is associated with increased cardiovascular mortality and morbidity; however, this dysfunction may be ameliorated by several therapies. For example, it has been reported that heat-induced increases in blood flow and shear stress enhance endothelium-mediated vasodilator function. Under these backgrounds, we expect that carbon dioxide (CO 2 )-rich water-induced increase in skin blood flow improves endothelium-mediated vasodilation with less heat stress. To test our hypothesis, we measured flow-mediated dilation (FMD) before and after acute immersion of the lower legs and feet in mild warm (38°C) normal or CO 2 -rich tap water (1000 ppm) for 20 min in 12 subjects. Acute immersion of the lower legs and feet in mild warm CO 2 -rich water increased FMD (P < 0.01) despite the lack of change in this parameter upon mild warm normal water immersion. In addition, FMD was positively correlated with change in skin blood flow regardless of conditions (P < 0.01), indicating that an increase in skin blood flow improves endothelial-mediated vasodilator function. Importantly, the temperature of normal tap water must reach approximately 43°C to achieve the same skin blood flow level as that obtained during mild warm CO 2 -rich water immersion (38°C). These findings suggest that CO 2 -rich water-induced large increases in skin blood flow may improve endothelial-mediated vasodilator function while causing less heat stress. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.

PubMed

Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

2014-06-05

The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Isotopic Studies of O-O Bond Formation During Water Oxidation (SISGR)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roth, Justine P.

Isotopic Studies of O-O Bond Formation During Water Oxidation (SISGR) Research during the project period focused primarily on mechanisms of water oxidation by structurally defined transition metal complexes. Competitive oxygen isotope fractionation of water, mediated by oxidized precursors or reduced catalysts together with ceric, Ce(IV), ammonium nitrate in aqueous media, afforded oxygen-18 kinetic isotope effects (O-18 KIEs). Measurement, calculation, and interpretation of O-18 KIEs, described in the accompanying report has important ramifications for the production of electricity and solar hydrogen (as fuel). The catalysis division of BES has acknowledged that understanding mechanisms of transition metal catalyzed water oxidation has majormore » ramifications, potentially leading to transformation of the global economy and natural environment in years to come. Yet, because of program restructuring and decreased availability of funds, it was recommended that the Solar Photochemistry sub-division of BES would be a more appropriate parent program for support of continued research.« less

Bound Water at Protein-Protein Interfaces: Partners, Roles and Hydrophobic Bubbles as a Conserved Motif

PubMed Central

Ahmed, Mostafa H.; Spyrakis, Francesca; Cozzini, Pietro; Tripathi, Parijat K.; Mozzarelli, Andrea; Scarsdale, J. Neel; Safo, Martin A.; Kellogg, Glen E.

2011-01-01

Background There is a great interest in understanding and exploiting protein-protein associations as new routes for treating human disease. However, these associations are difficult to structurally characterize or model although the number of X-ray structures for protein-protein complexes is expanding. One feature of these complexes that has received little attention is the role of water molecules in the interfacial region. Methodology A data set of 4741 water molecules abstracted from 179 high-resolution (≤ 2.30 Å) X-ray crystal structures of protein-protein complexes was analyzed with a suite of modeling tools based on the HINT forcefield and hydrogen-bonding geometry. A metric termed Relevance was used to classify the general roles of the water molecules. Results The water molecules were found to be involved in: a) (bridging) interactions with both proteins (21%), b) favorable interactions with only one protein (53%), and c) no interactions with either protein (26%). This trend is shown to be independent of the crystallographic resolution. Interactions with residue backbones are consistent for all classes and account for 21.5% of all interactions. Interactions with polar residues are significantly more common for the first group and interactions with non-polar residues dominate the last group. Waters interacting with both proteins stabilize on average the proteins' interaction (−0.46 kcal mol−1), but the overall average contribution of a single water to the protein-protein interaction energy is unfavorable (+0.03 kcal mol−1). Analysis of the waters without favorable interactions with either protein suggests that this is a conserved phenomenon: 42% of these waters have SASA ≤ 10 Å2 and are thus largely buried, and 69% of these are within predominantly hydrophobic environments or “hydrophobic bubbles”. Such water molecules may have an important biological purpose in mediating protein-protein interactions. PMID:21961043

Family Structure and Mediators of Adolescent Drug Use

ERIC Educational Resources Information Center

Broman, Clifford L.; Li, Xin; Reckase, Mark

2008-01-01

This study investigates how family structure is associated with adolescent drug use and how parenting, peer use, religiosity, and neighborhood problems may mediate the relationship. The authors use structural equation modeling to examine the relationship between family structure and drug use across race, and examine potential mediators. Using data…

Exfoliation of graphite into graphene in polar solvents mediated by amphiphilic hexa-peri-hexabenzocoronene.

PubMed

Kabe, Ryota; Feng, Xinliang; Adachi, Chihaya; Müllen, Klaus

2014-11-01

A water-soluble surfactant consisting of hexa-peri-hexabenzocoronene (HBC) as hydrophobic aromatic core and hydrophilic carboxy substituents was synthesized. It exhibited a self-assembled nanofiber structure in the solid state. Profiting from the π interactions between the large aromatic core of HBC and graphene, the surfactant mediated the exfoliation of graphite into graphene in polar solvents, which was further stabilized by the bulky hydrophilic carboxylic groups. A graphene dispersion with a concentration as high as 1.1 mg L(-1) containing 2-6 multilayer nanosheets was obtained. The lateral size of the graphene sheets was in the range of 100-500 nm based on atomic force microscope (AFM) and transmission electron microscope (TEM) measurements. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The influence of Critical Zone structure on runoff paths, seasonal water storage, and ecosystem composition

NASA Astrophysics Data System (ADS)

Hahm, W. J.; Dietrich, W. E.; Rempe, D.; Dralle, D.; Dawson, T. E.; Lovill, S.; Bryk, A.

2017-12-01

Understanding how subsurface water storage mediates water availability to ecosystems is crucial for elucidating linkages between water, energy, and carbon cycles from local to global scales. Earth's Critical Zone (the CZ, which extends from the top of the vegetation canopy downward to fresh bedrock) includes fractured and weathered rock layers that store and release water, thereby contributing to ecosystem water supplies, and yet are not typically represented in land-atmosphere models. To investigate CZ structural controls on water storage dynamics, we intensively studied field sites in a Mediterranean climate where winter rains arrive months before peak solar energy availability, resulting in strong summertime ecosystem reliance on stored subsurface water. Intra-hillslope and catchment-wide observations of CZ water storage capacity across a lithologic boundary in the Franciscan Formation of the Northern California Coast Ranges reveal large differences in the thickness of the CZ and water storage capacity that result in a stark contrast in plant community composition and stream behavior. Where the CZ is thick, rock moisture storage supports forest transpiration and slow groundwater release sustains baseflow and salmon populations. Where the CZ is thin, limited water storage is used by an oak savanna ecosystem, and streams run dry in summer due to negligible hillslope drainage. At both sites, wet season precipitation replenishes the dynamic storage deficit generated during the summer dry season, with excess winter rains exiting the watersheds via storm runoff as perched groundwater fracture flow at the thick-CZ site and saturation overland flow at the thin-CZ site. Annual replenishment of subsurface water storage even in severe drought years may lead to ecosystem resilience to climatic perturbations: during the 2011-2015 drought there was not widespread forest die-off in the study area.

Field solar degradation of pesticides and emerging water contaminants mediated by polymer films containing titanium and iron oxide with synergistic heterogeneous photocatalytic activity at neutral pH.

PubMed

Mazille, F; Schoettl, T; Klamerth, N; Malato, S; Pulgarin, C

2010-05-01

Photocatalytic degradation of phenol, nalidixic acid, mixture of pesticides, and another of emerging contaminants in water was mediated by TiO(2) and iron oxide immobilized on functionalized polyvinyl fluoride films (PVF(f)-TiO(2)-Fe oxide) in a compound parabolic collector (CPC) solar photoreactor. During degradation, little iron leaching (<0.2mgL(-1)) was observed. Phenol was efficiently degraded and mineralized at operational pH<5 and nalidixic acid degradation was complete even at pH 7, but mineralization stopped at 35%. Pesticide mixture was slowly degraded (50%) after 150min of irradiation. Degradation of the emergent contaminant mixture was successful for eight compounds and less efficient for six other compounds. The significant reactivity differences between tested compounds were assigned to the differences in structure namely that the presence of complexing or chelating groups enhanced the rates. PVF(f)-TiO(2)-Fe oxide photoactivity gradually increased during 20 days of experiments. X-ray photoelectron spectroscopy (XPS) measurements revealed significant changes on the catalyst surface. These analyses confirm that during photocatalysis mediated by PVF(f)-TiO(2)-Fe oxide, some iron leaching led to enlargement of the TiO(2) surface exposed to light, increasing its synergy with iron oxides and leading to enhanced pollutant degradation.

Functional Implications of Domain Organization Within Prokaryotic Rhomboid Proteases.

PubMed

Panigrahi, Rashmi; Lemieux, M Joanne

2015-01-01

Intramembrane proteases are membrane embedded enzymes that cleave transmembrane substrates. This interesting class of enzyme and its water mediated substrate cleavage mechanism occurring within the hydrophobic lipid bilayer has drawn the attention of researchers. Rhomboids are a family of ubiquitous serine intramembrane proteases. Bacterial forms of rhomboid proteases are mainly composed of six transmembrane helices that are preceded by a soluble N-terminal domain. Several crystal structures of the membrane domain of the E. coli rhomboid protease ecGlpG have been solved. Independently, the ecGlpG N-terminal cytoplasmic domain structure was solved using both NMR and protein crystallography. Despite these structures, we still do not know the structure of the full-length protein, nor do we know the functional role of these domains in the cell. This chapter will review the structural and functional roles of the different domains associated with prokaryotic rhomboid proteases. Lastly, we will address questions remaining in the field.

Factors shaping bacterial phylogenetic and functional diversity in coastal waters of the NW Mediterranean Sea

NASA Astrophysics Data System (ADS)

Boras, Julia A.; Vaqué, Dolors; Maynou, Francesc; Sà, Elisabet L.; Weinbauer, Markus G.; Sala, Maria Montserrat

2015-03-01

To evaluate the main factors shaping bacterioplankton phylogenetic and functional diversity in marine coastal waters, we carried out a two-year study based on a monthly sampling in Blanes Bay (NW Mediterranean). We expected the key factors driving bacterial diversity to be (1) temperature and nutrient concentration, together with chlorophyll a concentration as an indicator of phytoplankton biomass and, hence, a carbon source for bacteria (here called bottom-up factors), and (2) top-down pressure (virus- and protist-mediated mortality of bacteria). Phylogenetic diversity was analyzed by denaturing gradient gel electrophoresis (DGGE) of 16S rRNA. Functional diversity was assessed by using monomeric carbon sources in Biolog EcoPlates and by determining the activity of six extracellular enzymes. Our results indicate that the bacterial phylogenetic and functional diversity in this coastal system is shaped mainly by bottom-up factors. A dendrogram analysis of the DGGE banding patterns revealed three main sample clusters. Two clusters differed significantly in temperature, nitrate and chlorophyll a concentration, and the third was characterized by the highest losses of bacterial production due to viral lysis detected over the whole study period. Protistan grazing had no effect on bacterial functional diversity, since there were no correlations between protist-mediated mortality (PMM) and extracellular enzyme activities, and utilization of only two out of the 31 carbon sources (N-acetyl-D-glucosamine and α-cyclodextrin) was correlated with PMM. In contrast, virus-mediated mortality correlated with changes in the percentage of use of four carbon sources, and also with specific leu-aminopeptidase and β-glucosidase activity. This suggests that viral lysate provides a pool of labile carbon sources, presumably including amino acids and glucose, which may inhibit proteolytic and glucosidic activity. Our results indicate that bottom-up factors play a more important role than top-down factors (i.e. viral lysis and protistan grazing) in shaping bacterial community structure and activity. Furthermore, they suggest that viruses play a more important role than protists in modifying community structure and functional diversity of bacteria in oligotrophic marine coastal waters.

CW EPR parameters reveal cytochrome P450 ligand binding modes.

PubMed

Lockart, Molly M; Rodriguez, Carlo A; Atkins, William M; Bowman, Michael K

2018-06-01

Cytochrome P450 (CYP) monoxygenses utilize heme cofactors to catalyze oxidation reactions. They play a critical role in metabolism of many classes of drugs, are an attractive target for drug development, and mediate several prominent drug interactions. Many substrates and inhibitors alter the spin state of the ferric heme by displacing the heme's axial water ligand in the resting enzyme to yield a five-coordinate iron complex, or they replace the axial water to yield a nitrogen-ligated six-coordinate iron complex, which are traditionally assigned by UV-vis spectroscopy. However, crystal structures and recent pulsed electron paramagnetic resonance (EPR) studies find a few cases where molecules hydrogen bond to the axial water. The water-bridged drug-H 2 O-heme has UV-vis spectra similar to nitrogen-ligated, six-coordinate complexes, but are closer to "reverse type I" complexes described in older liteature. Here, pulsed and continuous wave (CW) EPR demonstrate that water-bridged complexes are remarkably common among a range of nitrogenous drugs or drug fragments that bind to CYP3A4 or CYP2C9. Principal component analysis reveals a distinct clustering of CW EPR spectral parameters for water-bridged complexes. CW EPR reveals heterogeneous mixtures of ligated states, including multiple directly-coordinated complexes and water-bridged complexes. These results suggest that water-bridged complexes are under-represented in CYP structural databases and can have energies similar to other ligation modes. The data indicates that water-bridged binding modes can be identified and distinguished from directly-coordinated binding by CW EPR. Copyright © 2018 Elsevier Inc. All rights reserved.

Condensation on superhydrophobic surfaces: the role of local energy barriers and structure length scale.

PubMed

Enright, Ryan; Miljkovic, Nenad; Al-Obeidi, Ahmed; Thompson, Carl V; Wang, Evelyn N

2012-10-09

Water condensation on surfaces is a ubiquitous phase-change process that plays a crucial role in nature and across a range of industrial applications, including energy production, desalination, and environmental control. Nanotechnology has created opportunities to manipulate this process through the precise control of surface structure and chemistry, thus enabling the biomimicry of natural surfaces, such as the leaves of certain plant species, to realize superhydrophobic condensation. However, this "bottom-up" wetting process is inadequately described using typical global thermodynamic analyses and remains poorly understood. In this work, we elucidate, through imaging experiments on surfaces with structure length scales ranging from 100 nm to 10 μm and wetting physics, how local energy barriers are essential to understand non-equilibrium condensed droplet morphologies and demonstrate that overcoming these barriers via nucleation-mediated droplet-droplet interactions leads to the emergence of wetting states not predicted by scale-invariant global thermodynamic analysis. This mechanistic understanding offers insight into the role of surface-structure length scale, provides a quantitative basis for designing surfaces optimized for condensation in engineered systems, and promises insight into ice formation on surfaces that initiates with the condensation of subcooled water.

Molecular architecture of the human Mediator-RNA polymerase II-TFIIF assembly.

PubMed

Bernecky, Carrie; Grob, Patricia; Ebmeier, Christopher C; Nogales, Eva; Taatjes, Dylan J

2011-03-01

The macromolecular assembly required to initiate transcription of protein-coding genes, known as the Pre-Initiation Complex (PIC), consists of multiple protein complexes and is approximately 3.5 MDa in size. At the heart of this assembly is the Mediator complex, which helps regulate PIC activity and interacts with the RNA polymerase II (pol II) enzyme. The structure of the human Mediator-pol II interface is not well-characterized, whereas attempts to structurally define the Mediator-pol II interaction in yeast have relied on incomplete assemblies of Mediator and/or pol II and have yielded inconsistent interpretations. We have assembled the complete, 1.9 MDa human Mediator-pol II-TFIIF complex from purified components and have characterized its structural organization using cryo-electron microscopy and single-particle reconstruction techniques. The orientation of pol II within this assembly was determined by crystal structure docking and further validated with projection matching experiments, allowing the structural organization of the entire human PIC to be envisioned. Significantly, pol II orientation within the Mediator-pol II-TFIIF assembly can be reconciled with past studies that determined the location of other PIC components relative to pol II itself. Pol II surfaces required for interacting with TFIIB, TFIIE, and promoter DNA (i.e., the pol II cleft) are exposed within the Mediator-pol II-TFIIF structure; RNA exit is unhindered along the RPB4/7 subunits; upstream and downstream DNA is accessible for binding additional factors; and no major structural re-organization is necessary to accommodate the large, multi-subunit TFIIH or TFIID complexes. The data also reveal how pol II binding excludes Mediator-CDK8 subcomplex interactions and provide a structural basis for Mediator-dependent control of PIC assembly and function. Finally, parallel structural analysis of Mediator-pol II complexes lacking TFIIF reveal that TFIIF plays a key role in stabilizing pol II orientation within the assembly.

ATP-induced conformational changes of nucleotide-binding domains in an ABC transporter. Importance of the water-mediated entropic force.

PubMed

Hayashi, Tomohiko; Chiba, Shuntaro; Kaneta, Yusuke; Furuta, Tadaomi; Sakurai, Minoru

2014-11-06

ATP binding cassette (ABC) proteins belong to a superfamily of active transporters. Recent experimental and computational studies have shown that binding of ATP to the nucleotide binding domains (NBDs) of ABC proteins drives the dimerization of NBDs, which, in turn, causes large conformational changes within the transmembrane domains (TMDs). To elucidate the active substrate transport mechanism of ABC proteins, it is first necessary to understand how the NBD dimerization is driven by ATP binding. In this study, we selected MalKs (NBDs of a maltose transporter) as a representative NBD and calculated the free-energy change upon dimerization using molecular mechanics calculations combined with a statistical thermodynamic theory of liquids, as well as a method to calculate the translational, rotational, and vibrational entropy change. This combined method is applied to a large number of snapshot structures obtained from molecular dynamics simulations containing explicit water molecules. The results suggest that the NBD dimerization proceeds with a large gain of water entropy when ATP molecules bind to the NBDs. The energetic gain arising from direct NBD-NBD interactions is canceled by the dehydration penalty and the configurational-entropy loss. ATP hydrolysis induces a loss of the shape complementarity between the NBDs, which leads to the dissociation of the dimer, due to a decrease in the water-entropy gain and an increase in the configurational-entropy loss. This interpretation of the NBD dimerization mechanism in concert with ATP, especially focused on the water-mediated entropy force, is potentially applicable to a wide variety of the ABC transporters.

Hydrophobic fluorine mediated switching of the hydrogen bonding site as well as orientation of water molecules in the aqueous mixture of monofluoroethanol: IR, molecular dynamics and quantum chemical studies.

PubMed

Mondal, Saptarsi; Biswas, Biswajit; Nandy, Tonima; Singh, Prashant Chandra

2017-09-20

The local structures between water-water, alcohol-water and alcohol-alcohol have been investigated for aqueous mixtures of ethanol (ETH) and monofluoroethanol (MFE) by the deconvolution of IR bands in the OH stretching region, molecular dynamics simulation and quantum chemical calculations. It has been found that the addition of a small amount of ETH into the aqueous medium increases the strength of the hydrogen bonds between water molecules. In an aqueous mixture of MFE, the substitution of a single fluorine induces a change in the orientation as well as the hydrogen bonding site of water molecules from the oxygen to the fluorine terminal of MFE. The switching of the hydrogen bonding site of water in the aqueous mixture of MFE results in comparatively strong hydrogen bonds between MFE and water molecules as well as less clustering of water molecules, unlike the case of the aqueous mixture of ETH. These findings about the modification of a hydrogen bond network by the hydrophobic fluorine group probably make fluorinated molecules useful for pharmaceutical as well as biological applications.

Mediator structure and rearrangements required for holoenzyme formation.

PubMed

Tsai, Kuang-Lei; Yu, Xiaodi; Gopalan, Sneha; Chao, Ti-Chun; Zhang, Ying; Florens, Laurence; Washburn, Michael P; Murakami, Kenji; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

2017-04-13

The conserved Mediator co-activator complex has an essential role in the regulation of RNA polymerase II transcription in all eukaryotes. Understanding the structure and interactions of Mediator is crucial for determining how the complex influences transcription initiation and conveys regulatory information to the basal transcription machinery. Here we present a 4.4 Å resolution cryo-electron microscopy map of Schizosaccharomyces pombe Mediator in which conserved Mediator subunits are individually resolved. The essential Med14 subunit works as a central backbone that connects the Mediator head, middle and tail modules. Comparison with a 7.8 Å resolution cryo-electron microscopy map of a Mediator-RNA polymerase II holoenzyme reveals that changes in the structure of Med14 facilitate a large-scale Mediator rearrangement that is essential for holoenzyme formation. Our study suggests that access to different conformations and crosstalk between structural elements are essential for the Mediator regulation mechanism, and could explain the capacity of the complex to integrate multiple regulatory signals.

Assessing Mediation Using Marginal Structural Models in the Presence of Confounding and Moderation

ERIC Educational Resources Information Center

Coffman, Donna L.; Zhong, Wei

2012-01-01

This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW…

Redefining the modular organization of the core Mediator complex.

PubMed

Wang, Xuejuan; Sun, Qianqian; Ding, Zhenrui; Ji, Jinhua; Wang, Jianye; Kong, Xiao; Yang, Jianghong; Cai, Gang

2014-07-01

The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation.

Redefining the modular organization of the core Mediator complex

PubMed Central

Wang, Xuejuan; Sun, Qianqian; Ding, Zhenrui; Ji, Jinhua; Wang, Jianye; Kong, Xiao; Yang, Jianghong; Cai, Gang

2014-01-01

The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation. PMID:24810298

A crystallographic and thermal study of pridinol mesylate and its monohydrated solvate.

PubMed

Gaztañaga, Pablo; Baggio, Ricardo; Vega, Daniel Roberto

2018-06-01

Herein are reported the crystal and molecular structures of the pridinol mesylate salt (C 20 H 25 NO + ·CH 3 O 3 S - ) (I) and its monohydrated solvate form (C 20 H 25 NO + ·CH 3 O 3 S - ·H 2 O) (II). A comparison of both with the already reported structure of pure pridinol [1,1-diphenyl-3-piperidino-1-propanol, C 20 H 25 NO; Tacke et al. (1980). Chem. Ber. 113, 1962-1980] is made. Molecular structures (I) and (II) are alike in bond distances and bond angles, but differ in their spatial conformation, and, more relevant still, in their hydrogen-bonding motifs. This gives rise to quite different packing schemes, in the form of simple dimers in (I) but water-mediated hydrogen-bonded chains in (II). The dehydration behaviour of form (II) is highly dependent on the heating rate, with slow rates leading to a clear endothermic dehydration step, towards anhydrous (I), with subsequent melting of this latter phase. Increased heating rates result in a more unclear behaviour ending in a structural collapse (melting of the hydrated phase), at temperatures significantly lower than the melting point of the anhydrous phase. The eventual relevance of the water link in the structure of (II) is discussed in regard to this behaviour.

Hydrogen Bond Networks and Hydrophobic Effects in the Amyloid β30-35 Chain in Water: A Molecular Dynamics Study.

PubMed

Jong, KwangHyok; Grisanti, Luca; Hassanali, Ali

2017-07-24

We have studied the conformational landscape of the C-terminal fragment of the amyloid protein Aβ 30-35 in water using well-tempered metadynamics simulations and found that it resembles an intrinsically disordered protein. The conformational fluctuations of the protein are facilitated by a collective reorganization of both protein and water hydrogen bond networks, combined with electrostatic interactions between termini as well as hydrophobic interactions of the side chains. The stabilization of hydrophobic interactions in one of the conformers involves a collective collapse of the side chains along with a squeeze-out of water sandwiched between them. The charged N- and C-termini play a critical role in stabilizing different types of protein conformations, including those involving contact-ion salt bridges as well as solvent-mediated interactions of the termini and the amide backbone. We have examined this by probing the distribution of directed water wires forming the hydrogen bond network enveloping the polypeptide. Water wires and their fluctuations form an integral part of structural signature of the protein conformation.

Synthesis of aspartyl-tRNA(Asp) in Escherichia coli--a snapshot of the second step.

PubMed Central

Eiler, S; Dock-Bregeon, A; Moulinier, L; Thierry, J C; Moras, D

1999-01-01

The 2.4 A crystal structure of the Escherichia coli aspartyl-tRNA synthetase (AspRS)-tRNA(Asp)-aspartyl-adenylate complex shows the two substrates poised for the transfer of the aspartic acid moiety from the adenylate to the 3'-hydroxyl of the terminal adenosine of the tRNA. A general molecular mechanism is proposed for the second step of the aspartylation reaction that accounts for the observed conformational changes, notably in the active site pocket. The stabilization of the transition state is mediated essentially by two amino acids: the class II invariant arginine of motif 2 and the eubacterial-specific Gln231, which in eukaryotes and archaea is replaced by a structurally non-homologous serine. Two archetypal RNA-protein modes of interactions are observed: the anticodon stem-loop, including the wobble base Q, binds to the N-terminal beta-barrel domain through direct protein-RNA interactions, while the binding of the acceptor stem involves both direct and water-mediated hydrogen bonds in an original recognition scheme. PMID:10562565

DOE Office of Scientific and Technical Information (OSTI.GOV)

Olsen, Brett N.; Schlesinger, Paul H.; Ory, Daniel S.

Side-chain oxysterols are enzymatically generated oxidation products of cholesterol that serve a central role in mediating cholesterol homeostasis. Recent work has shown that side-chain oxysterols, such as 25-hydroxycholesterol (25-HC), alter membrane structure in very different ways from cholesterol, suggesting a possible mechanism for how these oxysterols regulate cholesterol homeostasis. Here we extend our previous work, using molecular dynamics simulations of 25-HC and cholesterol mixtures in 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) bilayers to examine interactions between 25-HC and cholesterol in the same bilayer. When added to cholesterol-containing membranes, 25-HC causes larger changes in membrane structure than when added to cholesterol-free membranes, demonstrating interactions betweenmore » the two sterols. We also find that the presence of 25-HC changes the position, orientation, and solvent accessibility of cholesterol, shifting it into the water interface and therefore its availability to external acceptors. This is consistent with experimental results showing that oxysterols can trigger cholesterol trafficking from the plasma membrane to the endoplasmic reticulum. These interactions provide a potential mechanism for 25-HC-mediated regulation of cholesterol trafficking and homeostasis through direct modulation of cholesterol availability.« less

Waterborne zoonotic helminthiases.

PubMed

Nithiuthai, Suwannee; Anantaphruti, Malinee T; Waikagul, Jitra; Gajadhar, Alvin

2004-12-09

This review deals with waterborne zoonotic helminths, many of which are opportunistic parasites spreading directly from animals to man or man to animals through water that is either ingested or that contains forms capable of skin penetration. Disease severity ranges from being rapidly fatal to low-grade chronic infections that may be asymptomatic for many years. The most significant zoonotic waterborne helminthic diseases are either snail-mediated, copepod-mediated or transmitted by faecal-contaminated water. Snail-mediated helminthiases described here are caused by digenetic trematodes that undergo complex life cycles involving various species of aquatic snails. These diseases include schistosomiasis, cercarial dermatitis, fascioliasis and fasciolopsiasis. The primary copepod-mediated helminthiases are sparganosis, gnathostomiasis and dracunculiasis, and the major faecal-contaminated water helminthiases are cysticercosis, hydatid disease and larva migrans. Generally, only parasites whose infective stages can be transmitted directly by water are discussed in this article. Although many do not require a water environment in which to complete their life cycle, their infective stages can certainly be distributed and acquired directly through water. Transmission via the external environment is necessary for many helminth parasites, with water and faecal contamination being important considerations. Human behaviour, particularly poor hygiene, is a major factor in the re-emergence, and spread of parasitic infections. Also important in assessing the risk of infection by water transmission are human habits and population density, the prevalence of infection in them and in alternate animal hosts, methods of treating sewage and drinking water, and climate. Disease prevention methods, including disease surveillance, education and improved drinking water treatment are described.

GALLIUM-MEDIATED ALLYLATION OF CARBONYL COMPOUNDS IN WATER. (R828129)

EPA Science Inventory

Ga-mediated allylation of aldehydes or ketones in distilled or tap water generated the corresponding homoallyl alcohols in high yields without the assistance of either acidic media or sonication.

Nitriles as directionally tolerant hydrogen bond acceptors: IR-UV ion depletion spectroscopy of benzenepropanenitrile and its hydrate clusters

NASA Astrophysics Data System (ADS)

Robertson, Patrick A.; Lobo, Isabella A.; Wilson, David J. D.; Robertson, Evan G.

2016-09-01

Benzenepropanenitrile (BPN) and its hydrate clusters are studied by R2PI and IR-UV ion-depletion spectroscopy in the CH/OH stretch regions, aided by theoretical calculations. A single water molecule binds to the terminal nitrile 'lone-pair' of the anti-BPN host, but there is also evidence for a side-type structure with OH donating to the nitrile π-electrons. In the gauche-BPN cluster, water is located at an intermediate angle that facilitates O⋯HC(ortho) interaction. A wide range of attachment angles is possible, as the intrinsic preference for linear hydrogen bonding is mediated by additional CH⋯O interactions that depend on molecular geometry near the nitrile group.

Determination of Chlorinity of Water without the Use of Chromate Indicator

PubMed Central

Hong, Tae-Kee; Kim, Myung-Hoon; Czae, Myung-Zoon

2010-01-01

A new method for determining chlorinity of water was developed in order to improve the old method by alleviating the environmental problems associated with the toxic chromate. The method utilizes a mediator, a weak acid that can form an insoluble salt with the titrant. The mediator triggers a sudden change in pH at an equivalence point in a titration. Thus, the equivalence point can be determined either potentiometrically (using a pH meter) or simply with an acid-base indicator. Three nontoxic mediators (phosphate, EDTA, and sulfite) were tested, and optimal conditions for the sharpest pH changes were sought. A combination of phosphate (a mediator) and phenolphthalein (an indicator) was found to be the most successful. The choices of the initial pH and the concentration of the mediator are critical in this approach. The optimum concentration of the mediator is ca. 1~2 mM, and the optimum value of the initial pH is ca. 9 for phosphate/phenolphthalein system. The method was applied to a sample of sea water, and the results are compared with those from the conventional Mohr-Knudsen method. The new method yielded chlorinity of a sample of sea water of (17.58 ± 0.22) g/kg, which is about 2.5% higher than the value (17.12 ± 0.22) g/kg from the old method. PMID:21461358

Conservation and Divergence of Mediator Structure and Function: Insights from Plants.

PubMed

Dolan, Whitney L; Chapple, Clint

2017-01-01

The Mediator complex is a large, multisubunit, transcription co-regulator that is conserved across eukaryotes. Studies of the Arabidopsis Mediator complex and its subunits have shown that it functions in nearly every aspect of plant development and fitness. In addition to revealing mechanisms of regulation of plant-specific pathways, studies of plant Mediator complexes have the potential to shed light on the conservation and divergence of Mediator structure and function across Kingdoms and plant lineages. The majority of insights into plant Mediator function have come from Arabidopsis because it is the only plant from which Mediator has been purified and from which an array of Mediator mutants have been isolated by forward and reverse genetics. So far, these studies indicate that, despite low sequence similarity between many orthologous subunits, the overall structure and function of Mediator is well conserved between Kingdoms. Several studies have also expanded our knowledge of Mediator to other plant species, opening avenues of investigation into the role of Mediator in plant adaptation and fitness.

Making Democracy Work Better: Mediating Structures, Social Capital, and the Democratic Prospect.

ERIC Educational Resources Information Center

Couto, Richard A.

This book explores relationships among democracy, social capital, and community-based mediating structures, focusing on Appalachia because of the obvious failures of market capitalism there. It suggests that mediating structures protect communities from the savage side of market capitalism and promote the democratic prospect by increasing and…

Amino acid mediated synthesis of silver nanoparticles and preparation of antimicrobial agar/silver nanoparticles composite films.

PubMed

Shankar, Shiv; Rhim, Jong-Whan

2015-10-05

Silver nanoparticles (AgNPs) were synthesized using amino acids (tyrosine and tryptophan) as reducing and capping agents, and they were incorporated into the agar to prepare antimicrobial composite films. The AgNPs solutions exhibited characteristic absorption peak at 420 nm that showed a red shift to ∼434 nm after forming composite with agar. XRD data demonstrated the crystalline structure of AgNPs with dominant (111) facet. Apparent surface color and transmittance of agar films were greatly influenced by the AgNPs. The incorporation of AgNPs into agar did not exhibit any change in chemical structure, thermal stability, moisture content, and water vapor permeability. The water contact angle, tensile strength, and modulus decreased slightly, but elongation at break increased after AgNPs incorporation. The agar/AgNPs nanocomposite films possessed strong antibacterial activity against Listeria monocytogenes and Escherichia coli. The agar/AgNPs film could be applied to the active food packaging by controlling the food-borne pathogens. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Reovirus Sigmal Aspartic Acid Sandwich: A Trimerization Motif Poised for Conformational Change

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schelling,P.; Guglielml, K.; Kirchner, E.

2007-01-01

Reovirus attachment protein {sigma}1 mediates engagement of receptors on the surface of target cells and undergoes dramatic conformational rearrangements during viral disassembly in the endocytic pathway. The {sigma}1 protein is a filamentous, trimeric molecule with a globular {beta}-barrel head domain. An unusual cluster of aspartic acid residues sandwiched between hydrophobic tyrosines is located at the {sigma}1 subunit interface. A 1.75 {angstrom} structure of the {sigma}1 head domain now reveals two water molecules at the subunit interface that are held strictly in position and interact with neighboring residues. Structural and biochemical analyses of mutants affecting the aspartic acid sandwich indicate thatmore » these residues and the corresponding chelated water molecules act as a plug to block the free flow of solvent and stabilize the trimer. This arrangement of residues at the {sigma}1 head trimer interface illustrates a new protein design motif that may confer conformational mobility during cell entry.« less

Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aoyagi-Scharber, Mika, E-mail: maoyagi@bmrn.com; Gardberg, Anna S.; Yip, Bryan K.

2014-08-29

BMN 673, a novel PARP1/2 inhibitor in clinical development with substantial tumor cytotoxicity, forms extensive hydrogen-bonding and π-stacking in the nicotinamide pocket, with its unique disubstituted scaffold extending towards the less conserved edges of the pocket. These interactions might provide structural insight into the ability of BMN 673 to both inhibit catalysis and affect DNA-binding activity. Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2), which are involved in DNA damage response, are targets of anticancer therapeutics. BMN 673 is a novel PARP1/2 inhibitor with substantially increased PARP-mediated tumor cytotoxicity and is now in later-stage clinical development for BRCA-deficient breast cancers.more » In co-crystal structures, BMN 673 is anchored to the nicotinamide-binding pocket via an extensive network of hydrogen-bonding and π-stacking interactions, including those mediated by active-site water molecules. The novel di-branched scaffold of BMN 673 extends the binding interactions towards the outer edges of the pocket, which exhibit the least sequence homology among PARP enzymes. The crystallographic structural analyses reported here therefore not only provide critical insights into the molecular basis for the exceptionally high potency of the clinical development candidate BMN 673, but also new opportunities for increasing inhibitor selectivity.« less

Structure-function characterization and optimization of a plant-derived antibacterial peptide.

PubMed

Suarez, Mougli; Haenni, Marisa; Canarelli, Stéphane; Fisch, Florian; Chodanowski, Pierre; Servis, Catherine; Michielin, Olivier; Freitag, Ruth; Moreillon, Philippe; Mermod, Nicolas

2005-09-01

Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop.

Structure-Function Characterization and Optimization of a Plant-Derived Antibacterial Peptide

PubMed Central

Suarez, Mougli; Haenni, Marisa; Canarelli, Stéphane; Fisch, Florian; Chodanowski, Pierre; Servis, Catherine; Michielin, Olivier; Freitag, Ruth; Moreillon, Philippe; Mermod, Nicolas

2005-01-01

Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop. PMID:16127062

An aspartate and a water molecule mediate efficient acid-base catalysis in a tailored antibody pocket

PubMed Central

Debler, Erik W.; Müller, Roger; Hilvert, Donald; Wilson, Ian A.

2009-01-01

Design of catalysts featuring multiple functional groups is a desirable, yet formidable goal. Antibody 13G5, which accelerates the cleavage of unactivated benzisoxazoles, is one of few artificial enzymes that harness an acid and a base to achieve efficient proton transfer. X-ray structures of the Fab-hapten complexes of wild-type 13G5 and active-site variants now afford detailed insights into its mechanism. The parent antibody preorganizes AspH35 and GluL34 to abstract a proton from substrate and to orient a water molecule for leaving group stabilization, respectively. Remodeling the environment of the hydrogen bond donor with a compensatory network of ordered waters, as seen in the GluL34 to alanine mutant, leads to an impressive 109-fold rate acceleration over the nonenzymatic reaction with acetate, illustrating the utility of buried water molecules in bifunctional catalysis. Generalization of these design principles may aid in creation of catalysts for other important chemical transformations. PMID:19846764

Amphiphilic polypeptides as a bifunctional template in the mineralization of calcium carbonate at the air/water interface.

PubMed

Cao, Heng; Lin, Guoqiang; Yao, Jinrong; Shao, Zhengzhong

2013-05-01

A well-defined amphiphilic polypeptide, poly(glutamic acid)22 -block-poly(alanine)8 (PGlu22 -b-PAla8 ), which plays the roles of both soluble (functional) additive and insoluble (structural) matrix, is employed to mediate the mineralization of CaCO3 at the air/water interface. X-ray diffraction (XRD) and Raman spectroscopy, for example, show that the polymorph of CaCO3 particles obtained is calcite. The observations from SEM and TEM suggest that PGlu22 -b-PAla8 initiates the amorphous precursor phase and heterogeneous nucleation of CaCO3 at the air/water interface, while temporarily stabilizes the gelatinous precursors as a process-directing agent; nevertheless, the initial concentration of Ca(2+) controls the procedure of crystallization and the final morphology of CaCO3 particles. Such "bifunctional" amphiphilic-polypeptide-regulated mineralization at the air/water interface may be applied to the synthesis of many kinds of symmetrical inorganic/organic hybrids. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An aspartate and a water molecule mediate efficient acid-base catalysis in a tailored antibody pocket.

PubMed

Debler, Erik W; Müller, Roger; Hilvert, Donald; Wilson, Ian A

2009-11-03

Design of catalysts featuring multiple functional groups is a desirable, yet formidable goal. Antibody 13G5, which accelerates the cleavage of unactivated benzisoxazoles, is one of few artificial enzymes that harness an acid and a base to achieve efficient proton transfer. X-ray structures of the Fab-hapten complexes of wild-type 13G5 and active-site variants now afford detailed insights into its mechanism. The parent antibody preorganizes Asp(H35) and Glu(L34) to abstract a proton from substrate and to orient a water molecule for leaving group stabilization, respectively. Remodeling the environment of the hydrogen bond donor with a compensatory network of ordered waters, as seen in the Glu(L34) to alanine mutant, leads to an impressive 10(9)-fold rate acceleration over the nonenzymatic reaction with acetate, illustrating the utility of buried water molecules in bifunctional catalysis. Generalization of these design principles may aid in creation of catalysts for other important chemical transformations.

An ABA-mimicking ligand that reduces water loss and promotes drought resistance in plants

PubMed Central

Cao, Minjie; Liu, Xue; Zhang, Yan; Xue, Xiaoqian; Zhou, X Edward; Melcher, Karsten; Gao, Pan; Wang, Fuxing; Zeng, Liang; Zhao, Yang; Zhao, Yang; Deng, Pan; Zhong, Dafang; Zhu, Jian-Kang; Xu, H Eric; Xu, Yong

2013-01-01

Abscisic acid (ABA) is the most important hormone for plants to resist drought and other abiotic stresses. ABA binds directly to the PYR/PYL family of ABA receptors, resulting in inhibition of type 2C phosphatases (PP2C) and activation of downstream ABA signaling. It is envisioned that intervention of ABA signaling by small molecules could help plants to overcome abiotic stresses such as drought, cold and soil salinity. However, chemical instability and rapid catabolism by plant enzymes limit the practical application of ABA itself. Here we report the identification of a small molecule ABA mimic (AM1) that acts as a potent activator of multiple members of the family of ABA receptors. In Arabidopsis, AM1 activates a gene network that is highly similar to that induced by ABA. Treatments with AM1 inhibit seed germination, prevent leaf water loss, and promote drought resistance. We solved the crystal structure of AM1 in complex with the PYL2 ABA receptor and the HAB1 PP2C, which revealed that AM1 mediates a gate-latch-lock interacting network, a structural feature that is conserved in the ABA-bound receptor/PP2C complex. Together, these results demonstrate that a single small molecule ABA mimic can activate multiple ABA receptors and protect plants from water loss and drought stress. Moreover, the AM1 complex crystal structure provides a structural basis for designing the next generation of ABA-mimicking small molecules. PMID:23835477

Farmers' attitudes toward mandatory water-saving policies: A case study in two basins in northwest China.

PubMed

Chang, Genying; Wang, Lu; Meng, Liuyi; Zhang, Wenxia

2016-10-01

China began to implement stringent water-saving policies in 2012. Mandatory water-saving measures implemented in arid inland river basins include the measures of allocating surface water among upper, middle and lower beaches, restricting household agricultural water use, closing wells, reducing farmland and increasing water prices. These measures have negative influences on the agricultural production of farmers. This study aimed to reveal the demographic and psychological correlates of farmers' attitudes toward these policies. The participants included 672 farmers in the Heihe River Basin and the Shule River Basin in northwest China. Structural equation analyses showed that farmers' awareness of the beneficial consequences of restricting household agricultural water and their perception of policy enforcement had significant relationships with their attitudes toward water-saving policies, whereas the effects of the New Ecological Paradigm and collectivism on farmers' attitudes were mediated through their awareness of beneficial consequences and their perception of policy enforcement. Multivariable regression analyses revealed that as a whole, there were no significant correlations between demographic variables and farmers' attitudes. Policy implications include propagandizing these policies among local farmers, strengthening open and fair policy enforcement, and cautiously using water prices as an instrument to control irrigation water. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spectroscopic Manifestation of Vibrationally-Mediated Structure Change in the Isolated Formate Monohydrate

NASA Astrophysics Data System (ADS)

Denton, Joanna K.; Wolke, Conrad T.; Gorlova, Olga; Gerardi, Helen; McCoy, Anne B.; Johnson, Mark

2016-06-01

The breadth of the OH stretching manifold observed in the IR for bulk water is commonly attributed to the thermal population of excited states and the presence of many configurations within the water network. Here, I use carboxylate species as a rigid framework to isolate a single water molecule in the gas phase and cold ion vibrational pre-dissociation spectroscopy to explore excited state contributions to bandwidth. The spectrum of the carboxylate monohydrate exhibits a signature series of peaks in the OH stretching region of this system, providing an archetypal model to study vibrationally adiabatic mode separation. Previous analysis of this behavior accounts for the extensive progression in a Franck-Condon formalism involving displaced vibrationally adiabatic potentials. In this talk I will challenge this prediction by using isotopic substation to systematically change the level structure within these potentials. This picture quantitatively accounts for the diffuse spectrum of this complex at elevated temperature providing a convenient spectroscopic reporter for the temperature of ions in a trap. E. M. Myshakin, K. D. Jordan, E. L. Sibert III, M. A. Johnson J. Chem. Phys. 119, 10138 (2003) W.H. Robertson, et al. J. Phys Chem. 107, 6527 (2003)

Water organization between oppositely charged surfaces: Implications for protein sliding along DNA a)

NASA Astrophysics Data System (ADS)

Marcovitz, Amir; Naftaly, Aviv; Levy, Yaakov

2015-02-01

Water molecules are abundant in protein-DNA interfaces, especially in their nonspecific complexes. In this study, we investigated the organization and energetics of the interfacial water by simplifying the geometries of the proteins and the DNA to represent them as two equally and oppositely charged planar surfaces immersed in water. We found that the potential of mean force for bringing the two parallel surfaces into close proximity comprises energetic barriers whose properties strongly depend on the charge density of the surfaces. We demonstrated how the organization of the water molecules into discretized layers and the corresponding energetic barriers to dehydration can be modulated by the charge density on the surfaces, salt, and the structure of the surfaces. The 1-2 layers of ordered water are tightly bound to the charged surfaces representing the nonspecific protein-DNA complex. This suggests that water might mediate one-dimensional diffusion of proteins along DNA (sliding) by screening attractive electrostatic interactions between the positively charged molecular surface on the protein and the negatively charged DNA backbone and, in doing so, reduce intermolecular friction in a manner that smoothens the energetic landscape for sliding, and facilitates the 1D diffusion of the protein.

A transcriptome-based assessment of the astrocytic dystrophin-associated complex in the developing human brain.

PubMed

Simon, Matthew J; Murchison, Charles; Iliff, Jeffrey J

2018-02-01

Astrocytes play a critical role in regulating the interface between the cerebral vasculature and the central nervous system. Contributing to this is the astrocytic endfoot domain, a specialized structure that ensheathes the entirety of the vasculature and mediates signaling between endothelial cells, pericytes, and neurons. The astrocytic endfoot has been implicated as a critical element of the glymphatic pathway, and changes in protein expression profiles in this cellular domain are linked to Alzheimer's disease pathology. Despite this, basic physiological properties of this structure remain poorly understood including the developmental timing of its formation, and the protein components that localize there to mediate its functions. Here we use human transcriptome data from male and female subjects across several developmental stages and brain regions to characterize the gene expression profile of the dystrophin-associated complex (DAC), a known structural component of the astrocytic endfoot that supports perivascular localization of the astroglial water channel aquaporin-4. Transcriptomic profiling is also used to define genes exhibiting parallel expression profiles to DAC elements, generating a pool of candidate genes that encode gene products that may contribute to the physiological function of the perivascular astrocytic endfoot domain. We found that several genes encoding transporter proteins are transcriptionally associated with DAC genes. © 2017 Wiley Periodicals, Inc.

How Mg2+ ion and water network affect the stability and structure of non-Watson-Crick base pairs in E. coli loop E of 5S rRNA: a molecular dynamics and reference interaction site model (RISM) study.

PubMed

Shanker, Sudhanshu; Bandyopadhyay, Pradipta

2017-08-01

The non-Watson-Crick (non-WC) base pairs of Escherichia coli loop E of 5S rRNA are stabilized by Mg 2+ ions through water-mediated interaction. It is important to know the synergic role of Mg 2+ and the water network surrounding Mg 2+ in stabilizing the non-WC base pairs of RNA. For this purpose, free energy change of the system is calculated using molecular dynamics (MD) simulation as Mg 2+ is pulled from RNA, which causes disturbance of the water network. It was found that Mg 2+ remains hexahydrated unless it is close to or far from RNA. In the pentahydrated form, Mg 2+ interacts directly with RNA. Water network has been identified by two complimentary methods; MD followed by a density-based clustering algorithm and three-dimensional-reference interaction site model. These two methods gave similar results. Identification of water network around Mg 2+ and non-WC base pairs gives a clue to the strong effect of water network on the stability of this RNA. Based on sequence analysis of all Eubacteria 5s rRNA, we propose that hexahydrated Mg 2+ is an integral part of this RNA and geometry of base pairs surrounding it adjust to accommodate the [Formula: see text]. Overall the findings from this work can help in understanding the basis of the complex structure and stability of RNA with non-WC base pairs.

RNAi-mediated downregulation of poplar plasma membrane intrinsic proteins (PIPs) changes plasma membrane proteome composition and affects leaf physiology.

PubMed

Bi, Zhen; Merl-Pham, Juliane; Uehlein, Norbert; Zimmer, Ina; Mühlhans, Stefanie; Aichler, Michaela; Walch, Axel Karl; Kaldenhoff, Ralf; Palme, Klaus; Schnitzler, Jörg-Peter; Block, Katja

2015-10-14

Plasma membrane intrinsic proteins (PIPs) are one subfamily of aquaporins that mediate the transmembrane transport of water. To reveal their function in poplar, we generated transgenic poplar plants in which the translation of PIP genes was downregulated by RNA interference investigated these plants with a comprehensive leaf plasma membrane proteome and physiome analysis. First, inhibition of PIP synthesis strongly altered the leaf plasma membrane protein composition. Strikingly, several signaling components and transporters involved in the regulation of stomatal movement were differentially regulated in transgenic poplars. Furthermore, hormonal crosstalk related to abscisic acid, auxin and brassinosteroids was altered, in addition to cell wall biosynthesis/cutinization, the organization of cellular structures and membrane trafficking. A physiological analysis confirmed the proteomic results. The leaves had wider opened stomata and higher net CO2 assimilation and transpiration rates as well as greater mesophyll conductance for CO2 (gm) and leaf hydraulic conductance (Kleaf). Based on these results, we conclude that PIP proteins not only play essential roles in whole leaf water and CO2 flux but have important roles in the regulation of stomatal movement. Copyright © 2015. Published by Elsevier B.V.

Experimental warming decreases arbuscular mycorrhizal fungal colonization in prairie plants along a Mediterranean climate gradient.

PubMed

Wilson, Hannah; Johnson, Bart R; Bohannan, Brendan; Pfeifer-Meister, Laurel; Mueller, Rebecca; Bridgham, Scott D

2016-01-01

Arbuscular mycorrhizal fungi (AMF) provide numerous services to their plant symbionts. Understanding climate change effects on AMF, and the resulting plant responses, is crucial for predicting ecosystem responses at regional and global scales. We investigated how the effects of climate change on AMF-plant symbioses are mediated by soil water availability, soil nutrient availability, and vegetation dynamics. We used a combination of a greenhouse experiment and a manipulative climate change experiment embedded within a Mediterranean climate gradient in the Pacific Northwest, USA to examine this question. Structural equation modeling (SEM) was used to determine the direct and indirect effects of experimental warming on AMF colonization. Warming directly decreased AMF colonization across plant species and across the climate gradient of the study region. Other positive and negative indirect effects of warming, mediated by soil water availability, soil nutrient availability, and vegetation dynamics, canceled each other out. A warming-induced decrease in AMF colonization would likely have substantial consequences for plant communities and ecosystem function. Moreover, predicted increases in more intense droughts and heavier rains for this region could shift the balance among indirect causal pathways, and either exacerbate or mitigate the negative, direct effect of increased temperature on AMF colonization.

The development of Fe-nodules surrounding biological material mediated by microorganisms

NASA Astrophysics Data System (ADS)

Yoshida, Hidekazu; Yamamoto, Koshi; Murakami, Yuki; Katsuta, Nagayoshi; Hayashi, Toru; Naganuma, Takeshi

2008-09-01

Takashikozo is a phenomenon of Quaternary sediments in Japan. They are cylindrical Fe-oxyhydroxide nodules that form as plaques round plant roots, where Fe is preferentially concentrated to develop a solid wall. Structural features suggest that after the roots have decayed, the central space where the roots were situated acts as a flow path for oxidized water. Analysis of microbial 16S rDNA extracted from the nodules identified iron-oxidizing bacteria encrusted round the roots where they are the likely initiators of nodule formation. Direct microscopic observation revealed an accumulation of Fe-oxyhydroxides that fill the pore spaces and is also likely to be linked with the encrusting microbial colonies. Geological history and nanofossil evidence suggest that these Fe-nodules may have been buried at a depth of up to several tens of meters for at least 105 years in reducing Quaternary sediments. Thus Fe-oxyhydroxide nodules that have formed in a geological environment at the interfaces between water and rock by microbial mediation can persist under reducing conditions. If this is the case, the phenomenon is significant as an analogue of post-closure conditions in radioactive waste repositories, since it could influence nuclide migration.

The tonoplast-localized sucrose transporter in Populus (PtaSUT4) regulates whole-plant water relations, responses to water stress, and photosynthesis.

PubMed

Frost, Christopher J; Nyamdari, Batbayar; Tsai, Chung-Jui; Harding, Scott A

2012-01-01

The Populus sucrose (Suc) transporter 4 (PtaSUT4), like its orthologs in other plant taxa, is tonoplast localized and thought to mediate Suc export from the vacuole into the cytosol. In source leaves of Populus, SUT4 is the predominantly expressed gene family member, with transcript levels several times higher than those of plasma membrane SUTs. A hypothesis is advanced that SUT4-mediated tonoplast sucrose fluxes contribute to the regulation of osmotic gradients between cellular compartments, with the potential to mediate both sink provisioning and drought tolerance in Populus. Here, we describe the effects of PtaSUT4-RNA interference (RNAi) on sucrose levels and raffinose family oligosaccharides (RFO) induction, photosynthesis, and water uptake, retention and loss during acute and chronic drought stresses. Under normal water-replete growing conditions, SUT4-RNAi plants had generally higher shoot water contents than wild-type plants. In response to soil drying during a short-term, acute drought, RNAi plants exhibited reduced rates of water uptake and delayed wilting relative to wild-type plants. SUT4-RNAi plants had larger leaf areas and lower photosynthesis rates than wild-type plants under well-watered, but not under chronic water-limiting conditions. Moreover, the magnitude of shoot water content, height growth, and photosynthesis responses to contrasting soil moisture regimes was greater in RNAi than wild-type plants. The concentrations of stress-responsive RFOs increased in wild-type plants but were unaffected in SUT4-RNAi plants under chronically dry conditions. We discuss a model in which the subcellular compartmentalization of sucrose mediated by PtaSUT4 is regulated in response to both sink demand and plant water status in Populus.

Protective role of glycerol against benzene stress: insights from the Pseudomonas putida proteome.

PubMed

Bhaganna, Prashanth; Bielecka, Agata; Molinari, Gabriella; Hallsworth, John E

2016-05-01

Chemical activities of hydrophobic substances can determine the windows of environmental conditions over which microbial systems function and the metabolic inhibition of microorganisms by benzene and other hydrophobes can, paradoxically, be reduced by compounds that protect against cellular water stress (Bhaganna et al. in Microb Biotechnol 3:701-716, 2010; Cray et al. in Curr Opin Biotechnol 33:228-259, 2015a). We hypothesized that this protective effect operates at the macromolecule structure-function level and is facilitated, in part at least, by genome-mediated adaptations. Based on proteome profiling of the soil bacterium Pseudomonas putida, we present evidence that (1) benzene induces a chaotrope-stress response, whereas (2) cells cultured in media supplemented with benzene plus glycerol were protected against chaotrope stress. Chaotrope-stress response proteins, such as those involved in lipid and compatible-solute metabolism and removal of reactive oxygen species, were increased by up to 15-fold in benzene-stressed cells relative to those of control cultures (no benzene added). By contrast, cells grown in the presence of benzene + glycerol, even though the latter grew more slowly, exhibited only a weak chaotrope-stress response. These findings provide evidence to support the hypothesis that hydrophobic substances induce a chaotropicity-mediated water stress, that cells respond via genome-mediated adaptations, and that glycerol protects the cell's macromolecular systems. We discuss the possibility of using compatible solutes to mitigate hydrocarbon-induced stresses in lignocellulosic biofuel fermentations and for industrial and environmental applications.

Water Mediated Ligand Functional Group Cooperativity: The Contribution of a Methyl Group to Binding Affinity is Enhanced by a COO− Group Through Changes in the Structure and Thermo dynamics of the Hydration Waters of Ligand-Thermolysin Complexes

PubMed Central

Nasief, Nader N; Tan, Hongwei; Kong, Jing; Hangauer, David

2012-01-01

Ligand functional groups can modulate the contributions of one another to the ligand-protein binding thermodynamics, producing either positive or negative cooperativity. Data presented for four thermolysin phosphonamidate inhibitors demonstrate that the differential binding free energy and enthalpy caused by replacement of a H with a Me group, which binds in the well-hydrated S2′ pocket, are more favorable in presence of a ligand carboxylate. The differential entropy is however less favorable. Dissection of these differential thermodynamic parameters, X-ray crystallography, and density-functional theory calculations suggest that these cooperativities are caused by variations in the thermodynamics of the complex hydration shell changes accompanying the H→Me replacement. Specifically, the COO− reduces both the enthalpic penalty and the entropic advantage of displacing water molecules from the S2′ pocket, and causes a subsequent acquisition of a more enthalpically, less entropically, favorable water network. This study contributes to understanding the important role water plays in ligand-protein binding. PMID:22894131

Perovskite nickelates as electric-field sensors in salt water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Zhen; Schwanz, Derek; Narayanan, Badri

Designing materials to function in harsh environments, such as conductive aqueous media, is a problem of broad interest to a range of technologies, including energy, ocean monitoring and biological applications(1-4). The main challenge is to retain the stability and morphology of the material as it interacts dynamically with the surrounding environment. Materials that respond to mild stimuli through collective phase transitions and amplify signals could open up new avenues for sensing. Here we present the discovery of an electric-field-driven, water-mediated reversible phase change in a perovskite-structured nickelate, SmNiO35-7. This prototypical strongly correlated quantum material is stable in salt water, doesmore » not corrode, and allows exchange of protons with the surrounding water at ambient temperature, with the concurrent modification in electrical resistance and optical properties being capable of multi-modal readout. Besides operating both as thermistors and pH sensors, devices made of this material can detect sub-volt electric potentials in salt water. We postulate that such devices could be used in oceanic environments for monitoring electrical signals from various maritime vessels and sea creatures« less

Perovskite nickelates as electric-field sensors in salt water

NASA Astrophysics Data System (ADS)

Zhang, Zhen; Schwanz, Derek; Narayanan, Badri; Kotiuga, Michele; Dura, Joseph A.; Cherukara, Mathew; Zhou, Hua; Freeland, John W.; Li, Jiarui; Sutarto, Ronny; He, Feizhou; Wu, Chongzhao; Zhu, Jiaxin; Sun, Yifei; Ramadoss, Koushik; Nonnenmann, Stephen S.; Yu, Nanfang; Comin, Riccardo; Rabe, Karin M.; Sankaranarayanan, Subramanian K. R. S.; Ramanathan, Shriram

2018-01-01

Designing materials to function in harsh environments, such as conductive aqueous media, is a problem of broad interest to a range of technologies, including energy, ocean monitoring and biological applications. The main challenge is to retain the stability and morphology of the material as it interacts dynamically with the surrounding environment. Materials that respond to mild stimuli through collective phase transitions and amplify signals could open up new avenues for sensing. Here we present the discovery of an electric-field-driven, water-mediated reversible phase change in a perovskite-structured nickelate, SmNiO3. This prototypical strongly correlated quantum material is stable in salt water, does not corrode, and allows exchange of protons with the surrounding water at ambient temperature, with the concurrent modification in electrical resistance and optical properties being capable of multi-modal readout. Besides operating both as thermistors and pH sensors, devices made of this material can detect sub-volt electric potentials in salt water. We postulate that such devices could be used in oceanic environments for monitoring electrical signals from various maritime vessels and sea creatures.

Target specific proteochemometric model development for BACE1 - protein flexibility and structural water are critical in virtual screening.

PubMed

Manoharan, Prabu; Chennoju, Kiranmai; Ghoshal, Nanda

2015-07-01

BACE1 is an attractive target in Alzheimer's disease (AD) treatment. A rational drug design effort for the inhibition of BACE1 is actively pursued by researchers in both academic and pharmaceutical industries. This continued effort led to the steady accumulation of BACE1 crystal structures, co-complexed with different classes of inhibitors. This wealth of information is used in this study to develop target specific proteochemometric models and these models are exploited for predicting the prospective BACE1 inhibitors. The models developed in this study have performed excellently in predicting the computationally generated poses, separately obtained from single and ensemble docking approaches. The simple protein-ligand contact (SPLC) model outperforms other sophisticated high end models, in virtual screening performance, developed during this study. In an attempt to account for BACE1 protein active site flexibility information in predictive models, we included the change in the area of solvent accessible surface and the change in the volume of solvent accessible surface in our models. The ensemble and single receptor docking results obtained from this study indicate that the structural water mediated interactions improve the virtual screening results. Also, these waters are essential for recapitulating bioactive conformation during docking study. The proteochemometric models developed in this study can be used for the prediction of BACE1 inhibitors, during the early stage of AD drug discovery.

Hierarchical organization of eglin c native state dynamics is shaped by competing direct and water-mediated interactions.

PubMed

Materese, Christopher Kroboth; Goldmon, Christa Charisse; Papoian, Garegin A

2008-08-05

The native state dynamics of the small globular serine protease inhibitor eglin c has been studied in a long 336 ns computer simulation in explicit solvent. We have elucidated the energy landscape explored during the course of the simulation by using Principal Component Analysis. We observe several basins in the energy landscape in which the system lingers for extended periods. Through an iterative process we have generated a tree-like hierarchy of states describing the observed dynamics. We observe a range of divergent contact types including salt bridges, hydrogen bonds, hydrophilic interactions, and hydrophobic interactions, pointing to the frustration between competing interactions. Additionally, we find evidence of competing water-mediated interactions. Divergence in water-mediated interactions may be found to supplement existing direct contacts, but they are also found to be independent of such changes. Water-mediated contacts facilitate interactions between residues of like charge as observed in the simulation. Our results provide insight into the complexity of the dynamic native state of a globular protein and directly probe the residual frustration in the native state.

Electronic and structural aspects of p450-mediated drug metabolism.

PubMed

Lewis, David F V; Ito, Yuko; Lake, Brian G

2009-04-01

From a consideration of first principles for enzymes kinetics, we have employed theoretical methods which enable one to analyse the kinetics of cytochrome P450-mediated reactions which have been based on the known physicochemical principles underlying the majority of chemical or enzymatic reactions. A comparison is made between the correlation equations produced from the QSAR analysis of experimental P450 reaction rate data and those obtained from first principles, where there appears to be a generally satisfactory concordance between the two procedures. In this respect, we have developed expressions based on standard reaction kinetics theory which incorporate the Eyring and Marcus relationships. The analysis of P450-catalyzed reaction rates is elaborated to encompass a treatment of metabolic clearance, and satisfactory correlations are obtained with literature values for both intrinsic clearance and whole body clearance in terms of compound lipophilicity derived from log P data, where P is the octanol/water partition coefficient. The importance of ionization potential as a factor in the overall catalytic turnover of P450-mediated reactions is noted, especially in combination with the lipophilicity parameter, log P.

Microwave-assisted synthesis and crystal structure of oxo(diperoxo)(4,4'-di-tert-butyl-2,2'-bipyridine)-molybdenum(VI).

PubMed

Amarante, Tatiana R; Almeida Paz, Filipe A; Gago, Sandra; Gonçalves, Isabel S; Pillinger, Martyn; Rodrigues, Alírio E; Abrantes, Marta

2009-09-16

The oxodiperoxo complex MoO(O2)(2)(tbbpy) (tbbpy = 4,4'-di-tert-butyl-2,2'- bipyridine) was isolated from the reaction of MoO2Cl(2)(tbbpy) in water under microwaveassisted heating at 120 masculineC for 4 h. The structure of the oxodiperoxo complex was determined by single crystal X-ray diffraction. The Mo(VI) centre is seven-coordinated with a geometry which strongly resembles a highly distorted bipyramid. Individual MoO(O2)(2)(tbbpy) complexes are interdigitated along the [010] direction to form a column. The crystal structure is formed by the close packing of the columnar-stacked complexes. Interactions between neighbouring columns are essentially of van der Waals type mediated by the need to effectively fill the available space.

Ionic Liquids Can Selectively Change the Conformational Free-Energy Landscape of Sugar Rings.

PubMed

Jarin, Zack; Pfaendtner, Jim

2014-02-11

We investigated the conformational free energy landscape of glucose solvated in water and in the ionic liquids (ILs) 1-butyl-3-methylimidazolium chloride ([Bmim][Cl]) and 1-butyl-3-methylimidazoulim boron tetrafluoride ([Bmim][BF4]). To quantify equilibrium thermodynamic solvent effects, molecular dynamics simulations in conjunction with enhanced sampling based on the metadynamics framework were used. The results show that the solvent choice induces significant differences in the equilibrium ring structures, which may help further resolve the molecular mechanism governing IL-mediated cellulose dissolution.

Deprotonation states of the two active site water molecules regulate the binding of protein phosphatase 5 with its substrate: A molecular dynamics study.

PubMed

Wang, Lingyun; Yan, Feng

2017-10-01

Protein phosphatase 5 (PP5), mainly localized in human brain, can dephosphorylate tau protein whose high level of phosphorylation is related to Alzheimer's disease. Similar to other protein phosphatases, PP5 has a conserved motif in the catalytic domain that contains two binding sites for manganese (Mn 2+ ) ions. Structural data indicate that two active site water molecules, one bridging the two Mn 2+ ions and the other terminally coordinated with one of the Mn 2+ ions (Mn1), are involved in catalysis. Recently, a density functional theory study revealed that the two water molecules can be both deprotonated to keep a neutral active site for catalysis. The theoretical study gives us an insight into the catalytic mechanism of PP5, but the knowledge of how the deprotonation states of the two water molecules affect the binding of PP5 with its substrate is still lacking. To approach this problem, molecular dynamics simulations were performed to model the four possible deprotonation states. Through structural, dynamical and energetic analyses, the results demonstrate that the deprotonation states of the two water molecules affect the structure of the active site including the distance between the two Mn 2+ ions and their coordination, impact the interaction energy of residues R275, R400 and H304 which directly interact with the substrate phosphoserine, and mediate the dynamics of helix αJ which is involved in regulation of the enzyme's activity. Furthermore, the deprotonation state that is preferable for PP5 binding of its substrate has been identified. These findings could provide new design strategy for PP5 inhibitor. © 2017 The Protein Society.

Solar photolysis versus TiO2-mediated solar photocatalysis: a kinetic study of the degradation of naproxen and diclofenac in various water matrices.

PubMed

Kanakaraju, Devagi; Motti, Cherie A; Glass, Beverley D; Oelgemöller, Michael

2016-09-01

Given that drugs and their degradation products are likely to occur as concoctions in wastewater, the degradation of a mixture of two nonsteroidal anti-inflammatory drugs (NSAIDs), diclofenac (DCF) and naproxen (NPX), was investigated by solar photolysis and titanium dioxide (TiO2)-mediated solar photocatalysis using an immersion-well photoreactor. An equimolar ratio (1:1) of both NSAIDs in distilled water, drinking water, and river water was subjected to solar degradation. Solar photolysis of the DCF and NPX mixture was competitive particularly in drinking water and river water, as both drugs have the ability to undergo photolysis. However, the addition of TiO2 in the mixture significantly enhanced the degradation rate of both APIs compared to solar photolysis alone. Mineralization, as measured by chemical oxygen demand (COD), was incomplete under all conditions investigated. TiO2-mediated solar photocatalytic degradation of DCF and NPX mixtures produced 15 identifiable degradants corresponding to degradation of the individual NSAIDs, while two degradation products with much higher molecular weight than the parent NSAIDs were identified by liquid chromatography mass spectrometry (LC-MS) and Fourier transform-ion cyclotron resonance-mass spectrometry (FT-ICR-MS). This study showed that the solar light intensity and the water matrix appear to be the main factors influencing the overall performance of the solar photolysis and TiO2-mediated solar photocatalysis for degradation of DCF and NPX mixtures.

Surface analysis characterisation of gum binders used in modern watercolour paints

NASA Astrophysics Data System (ADS)

Sano, Naoko; Cumpson, Peter J.

2016-02-01

Conducting this study has demonstrated that not only SEM-EDX but also XPS can be an efficient tool for characterising watercolour paint surfaces. We find that surface effects are mediated by water. Once the powdered components in the watercolour come into contact with water they dramatically transform their chemical structures at the surface and show the presence of pigment components with a random dispersion within the gum layer. Hence the topmost surface of the paint is confirmed as being composed of the gum binder components. This result is difficult to confirm using just one analytical technique (either XPS or SEM-EDX). In addition, peak fitting of C1s XPS spectra suggests that the gum binder in the commercial watercolour paints is probably gum arabic (by comparison with the reference materials). This identification is not conclusive, but the combination techniques of XPS and SEM shows the surface structure with material distribution of the gum binder and the other ingredients of the watercolour paints. Therefore as a unique technique, XPS combined with SEM-EDX may prove a useful method in the study of surface structure for not only watercolour objects but also other art objects; which may in future help in the conservation for art.

Endotoxin-Induced Structural Transformations in Liquid Crystalline Droplets

NASA Astrophysics Data System (ADS)

Lin, I.-Hsin; Miller, Daniel S.; Bertics, Paul J.; Murphy, Christopher J.; de Pablo, Juan J.; Abbott, Nicholas L.

2011-06-01

The ordering of liquid crystals (LCs) is known to be influenced by surfaces and contaminants. Here, we report that picogram per milliliter concentrations of endotoxin in water trigger ordering transitions in micrometer-size LC droplets. The ordering transitions, which occur at surface concentrations of endotoxin that are less than 10-5 Langmuir, are not due to adsorbate-induced changes in the interfacial energy of the LC. The sensitivity of the LC to endotoxin was measured to change by six orders of magnitude with the geometry of the LC (droplet versus slab), supporting the hypothesis that interactions of endotoxin with topological defects in the LC mediate the response of the droplets. The LC ordering transitions depend strongly on glycophospholipid structure and provide new designs for responsive soft matter.

Ethical Leadership, Leader-Member Exchange and Feedback Seeking: A Double-Moderated Mediation Model of Emotional Intelligence and Work-Unit Structure.

PubMed

Qian, Jing; Wang, Bin; Han, Zhuo; Song, Baihe

2017-01-01

This research elucidates the role of ethical leadership in employee feedback seeking by examining how and when ethical leadership may exert a positive influence on feedback seeking. Using matched reports from 64 supervisors and 265 of their immediate employees from a hotel group located in a major city in China, we proposed and tested a moderated mediation model that examines leader-member exchange (LMX) as the mediator and emotional intelligence as well as work-unit structure as double moderators in the relationships between ethical leadership and followers' feedback-seeking behavior from supervisors and coworkers. Our findings indicated that (1) LMX mediated the positive relationship between ethical leadership and feedback seeking from both ethical leaders and coworkers, and (2) emotional intelligence and work-unit structure served as joint moderators on the mediated positive relationship in such a way that the relationship was strongest when the emotional intelligence was high and work-unit structure was more of an organic structure rather than a mechanistic structure.

Computational investigation of fullerene-DNA interactions: Implications of fullerene's size and functionalization on DNA structure and binding energetics.

PubMed

Papavasileiou, Konstantinos D; Avramopoulos, Aggelos; Leonis, Georgios; Papadopoulos, Manthos G

2017-06-01

DNA is the building block of life, as it carries the biological information controlling development, function and reproduction of all organisms. However, its central role in storing and transferring genetic information can be severely hindered by molecules with structure altering abilities. Fullerenes are nanoparticles that find a broad spectrum of uses, but their toxicological effects on living organisms upon exposure remain unclear. The present study examines the interactions of a diverse array of fullerenes with DNA, by means of Molecular Dynamics and MM-PBSA methodologies, with special focus on structural deformations that may hint toxicity implications. Our results show that pristine and hydroxylated fullerenes have no unwinding effects upon DNA structure, with the latter displaying binding preference to the DNA major groove, achieved by both direct formation of hydrogen bonds and water molecule mediation. Fluorinated derivatives are capable of penetrating DNA structure, forming intercalative complexes with high binding affinities. Copyright © 2017 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

deLorimier, Elaine; Coonrod, Leslie A.; Copperman, Jeremy

In this study, CUG repeat expansions in the 3' UTR of dystrophia myotonica protein kinase ( DMPK) cause myotonic dystrophy type 1 (DM1). As RNA, these repeats elicit toxicity by sequestering splicing proteins, such as MBNL1, into protein–RNA aggregates. Structural studies demonstrate that CUG repeats can form A-form helices, suggesting that repeat secondary structure could be important in pathogenicity. To evaluate this hypothesis, we utilized structure-stabilizing RNA modifications pseudouridine (Ψ) and 2'-O-methylation to determine if stabilization of CUG helical conformations affected toxicity. CUG repeats modified with Ψ or 2'-O-methyl groups exhibited enhanced structural stability and reduced affinity for MBNL1. Molecularmore » dynamics and X-ray crystallography suggest a potential water-bridging mechanism for Ψ-mediated CUG repeat stabilization. Ψ modification of CUG repeats rescued mis-splicing in a DM1 cell model and prevented CUG repeat toxicity in zebrafish embryos. This study indicates that the structure of toxic RNAs has a significant role in controlling the onset of neuromuscular diseases.« less

Crystal Structure of the Potassium Importing KdpFABC Membrane Complex

PubMed Central

Huang, Ching-Shin; Pedersen, Bjørn Panyella; Stokes, David Lloyd

2017-01-01

Cellular potassium import systems play a fundamental role in osmoregulation, pH homeostasis and membrane potential in all domains of life. In bacteria, the kdp operon encodes a four subunit potassium pump that maintains intracellular homeostasis as well as cell shape and turgor under conditions where potassium is limiting1. This membrane complex, called KdpFABC, has one channel-like subunit (KdpA) belonging to the Superfamily of Potassium Transporters and another pump-like subunit (KdpB) belonging to the Superfamily of P-type ATPases. Although there is considerable structural and functional information about members from both superfamilies, the mechanism by which uphill potassium transport through KdpA is coupled with ATP hydrolysis by KdpB remains poorly understood. Here we report the 2.9 Å X-ray structure of the complete Escherichia coli KdpFABC complex with a potassium ion within the selectivity filter of KdpA as well as a water molecule at a canonical cation site in the transmembrane domain of KdpB. The structure also reveals two structural elements that appear to mediate the coupling between these two subunits. Specifically, a protein-embedded tunnel runs between these potassium and water sites and a helix controlling the cytoplasmic gate of KdpA is linked to the phosphorylation domain of KdpB. Based on these observations, we propose an unprecedented mechanism that repurposes protein channel architecture for active transport across biomembranes. PMID:28636601

Structure and functions of water-membrane interfaces and their role in proto-biological evolution

NASA Technical Reports Server (NTRS)

Pohorille, A.; Wilson, M.; Macelroy, R. D.

1991-01-01

Among the most important developments in proto-biological evolution was the emergence of membrane-like structures. These are formed by spontaneous association of relatively simple amphiphilic molecules that would have been readily available in the primordial environment. The resulting interfacial regions between water and nonpolar interior of the membrane have several properties which made them uniquely suitable for promoting subsequent evolution. They can (1) selectively attract organic material and mediate its transport, (2) serve as simple catalysts for chemical reactions, and (3) promote the formation of trans-membrane electrical and chemical gradients which could provide energy sources for proto-cells. Understanding the structure of interfaces, their interactions with organic molecules and molecular mechanisms of their functions is an essential step to understanding proto-biological evolution. In our computer simulation studies, we showed that the structure of water at interfaces with nonpolar media is significantly different from that in the bulk. In particular, the average surface dipole density points from the vapor to the liquid. As a result, negative ions can approach the interface more easily than positive ions. Amphiphilic molecules composed of hydrocarbon conjugated rings and polar substituents (e.g., phenol) assume at the interface rigid orientations in which polar groups are buried in water while hydrocarbon parts are located in the nonpolar environment. These orientational differences are of special interest in connection with the ability of some of these molecules to efficiently absorb photons. Flexible molecules with polar substituents often adopt at interfaces conformations different from those in the bulk aquaeous solution and in the gas phase. As a result, in many instances both specificity and kinetics of chemical reactions in which these molecules can participate is modified by the presence of surfaces. Of special interest is the mechanism by which polar molecules are transferred across interface between water and a nonpolar medium. Our recent study showed that simple ionophores bind ions by the same mechanisms as ion channels and carriers from modern cells.

Amphiphilic Polysaccharide Block Copolymers for pH-Responsive Micellar Nanoparticles.

PubMed

Breitenbach, Benjamin B; Schmid, Ira; Wich, Peter R

2017-09-11

A full polysaccharide amphiphilic block copolymer was prepared from end group-functionalized dextrans using copper-mediated azide-alkyne click chemistry. Sufficient modification of the reducing end in both blocks was achieved by microwave-enhanced reductive amination in a borate-buffer/methanol solvent system. The combination of a hydrophilic dextran block with a hydrophobic acetalated dextran block results in an amphiphilic structure that turns water-soluble upon acid treatment. The material has a low critical micelle concentration and self-assembles in water to spherical micellar nanoparticles. The formed nanoparticles have a narrow size distribution below 70 nm in diameter and disassemble in slightly acidic conditions. The amphiphilic polysaccharide system shows low toxicity and can stabilize the hydrophobic model drug curcumin in aqueous solutions over extended time periods.

Algae-mediated removal of selected pharmaceutical and personal care products (PPCPs) from Lake Mead water.

PubMed

Bai, Xuelian; Acharya, Kumud

2017-03-01

The persistence and fate of pharmaceutical and personal care products (PPCPs) in the Lake Mead ecosystem are particularly important considering the potential ecological risks and human health impacts. This study evaluated the removal of five common PPCPs (i.e., trimethoprim, sulfamethoxazole, carbamazepine, ciprofloxacin, and triclosan) from Lake Mead water mediated by the green alga Nannochloris sp. The results from the incubation studies showed that trimethoprim and carbamazepine were highly resistant to uptake in the algal cultural medium and were measured at approximately 90%-100% of the applied dose after 14days of incubation. Sulfamethoxazole was found relatively persistent, with >60% of the applied dose remaining in the water after 14days, and its removal was mainly caused by algae-mediated photolysis. However, ciprofloxacin and triclosan dissipated significantly and nearly 100% of the compounds were removed from the water after 7days of incubation under 24h of light. Ciprofloxacin and triclosan were highly susceptible to light, and their estimated half-lives were 12.7hours for ciprofloxacin and 31.2hours for triclosan. Algae-mediated sorption contributed to 11% of the removal of trimethoprim and sulfamethoxazole, 13% of the removal of carbamazepine, and 27% of the removal of triclosan from the lake water. This research showed that 1) trimethoprim, sulfamethoxazole, and carbamazepine are quite persistent in aquatic environments and may potentially affect human health via drinking water intake; 2) photolysis is the dominant pathway to remove ciprofloxacin from aquatic ecosystems, which indicates that ciprofloxacin may have lower ecological risks compared with other PPCPs; and 3) triclosan can undergo photolysis as well as algae-mediated uptake and it may potentially affect the food web because of its high toxicity to aquatic species. Copyright © 2017 Elsevier B.V. All rights reserved.

Suspected immune-mediated neutropenia and corticosteroid responsive pancytopenia in a Portuguese water dog.

PubMed

Denstedt, Ellen B

2017-01-01

An 8-year-old spayed Portuguese water dog was presented with dysuria, lethargy, and anorexia. A profound neutropenia and pancytopenia were identified. Bone marrow aspirates revealed neutrophilic hyperplasia, a significant left shift, and toxic changes, suggesting immune-mediated destruction as a likely underlying mechanism. Immunosuppressive therapy was instituted and clinical signs improved.

Unprecedented H-atom transfer from water to ketyl radicals mediated by Cp(2)TiCl.

PubMed

Paradas, Miguel; Campaña, Araceli G; Marcos, Maria Luisa; Justicia, Jose; Haidour, Ali; Robles, Rafael; Cárdenas, Diego J; Oltra, J Enrique; Cuerva, Juan M

2010-10-07

The H-atom transfer (HAT) from water to ketyl radicals, mediated by titanocene(iii) aqua-complexes, can explain the Ti(III)-promoted reduction of ketones in aqueous medium better than the conventional House mechanism. Moreover, we also report novel evidences supporting the existence of these titanocene(iii) aqua-complexes.

NIMROD: The Near and InterMediate Range Order Diffractometer of the ISIS second target station.

PubMed

Bowron, D T; Soper, A K; Jones, K; Ansell, S; Birch, S; Norris, J; Perrott, L; Riedel, D; Rhodes, N J; Wakefield, S R; Botti, A; Ricci, M-A; Grazzi, F; Zoppi, M

2010-03-01

NIMROD is the Near and InterMediate Range Order Diffractometer of the ISIS second target station. Its design is optimized for structural studies of disordered materials and liquids on a continuous length scale that extends from the atomic, upward of 30 nm, while maintaining subatomic distance resolution. This capability is achieved by matching a low and wider angle array of high efficiency neutron scintillation detectors to the broad band-pass radiation delivered by a hybrid liquid water and liquid hydrogen neutron moderator assembly. The capabilities of the instrument bridge the gap between conventional small angle neutron scattering and wide angle diffraction through the use of a common calibration procedure for the entire length scale. This allows the instrument to obtain information on nanoscale systems and processes that are quantitatively linked to the local atomic and molecular order of the materials under investigation.

Chlorine stress mediates microbial surface attachment in drinking water systems.

PubMed

Liu, Li; Le, Yang; Jin, Juliang; Zhou, Yuliang; Chen, Guowei

2015-03-01

Microbial attachment to drinking water pipe surfaces facilitates pathogen survival and deteriorates disinfection performance, directly threatening the safety of drinking water. Notwithstanding that the formation of biofilm has been studied for decades, the underlying mechanisms for the origins of microbial surface attachment in biofilm development in drinking water pipelines remain largely elusive. We combined experimental and mathematical methods to investigate the role of environmental stress-mediated cell motility on microbial surface attachment in chlorination-stressed drinking water distribution systems. Results show that at low levels of disinfectant (0.0-1.0 mg/L), the presence of chlorine promotes initiation of microbial surface attachment, while higher amounts of disinfectant (>1.0 mg/L) inhibit microbial attachment. The proposed mathematical model further demonstrates that chlorination stress (0.0-5.0 mg/L)-mediated microbial cell motility regulates the frequency of cell-wall collision and thereby controls initial microbial surface attachment. The results reveal that transport processes and decay patterns of chlorine in drinking water pipelines regulate microbial cell motility and, thus, control initial surface cell attachment. It provides a mechanistic understanding of microbial attachment shaped by environmental disinfection stress and leads to new insights into microbial safety protocols in water distribution systems.

Social Position Influencing the Water Perception Gap Between Local Leaders and Constituents in a Socio-Hydrological System

NASA Astrophysics Data System (ADS)

Haeffner, Melissa; Jackson-Smith, Douglas; Flint, Courtney G.

2018-02-01

How well city leaders represent their constituents and meet their needs are key concerns in transitioning to local sustainable water governance. To date, however, there is little research documenting the influence of social position between elected leaders who make policy, career staff water managers who design and operate systems and implement policies, and the members of the public whose individual water use behaviors are important drivers of water sustainability outcomes. In this study, we ask: "How does social position explain variation in water perceptions and concerns between different actors in a socio-hydrological system?" Using a mixed method approach with survey and interview data, we explore the ways that positioning within the governance system, geographic context, and citizen engagement in local government mediate perceptions of the urban water system. Regardless of local biophysical water supply conditions, residents showed most concern about future water shortages and high water costs, while their leaders were consistently most concerned about deteriorating local water infrastructure. Further, constituents who received water-related information directly from public utility mailings or served on community committees and boards had perceptions that were more aligned with leaders' concerns. The importance of social structure over natural and built environments in shaping water issue perceptions underscores the value of social analysis in socio-hydrology studies. Further, practitioners looking to increase consensus for a transition to sustainable water governance might work to develop institutional mechanisms to increase opportunities for water user involvement in local water system governance.

Human land uses enhance sediment denitrification and N2O production in Yangtze lakes primarily by influencing lake water quality

NASA Astrophysics Data System (ADS)

Liu, W.; Yao, L.; Wang, Z.; Xiong, Z.; Liu, G.

2015-10-01

Sediment denitrification in lakes alleviates the effects of eutrophication through the removal of nitrogen to the atmosphere as N2O and N2. However, N2O contributes notably to the greenhouse effect and global warming. Human land uses (e.g. agricultural and urban areas) strongly affect lake water quality and sediment characteristics, which, in turn, may regulate lake sediment denitrification and N2O production. In this study, we investigated sediment denitrification and N2O production and their relationships to within-lake variables and watershed land uses in 20 lakes from the Yangtze River basin in China. The results indicated that both lake water quality and sediment characteristics were significantly influenced by watershed land uses. N2O production rates increased with increasing background denitrification rates. Background denitrification and N2O production rates were positively related to water nitrogen concentrations but were not significantly correlated with sediment characteristics and plant community structure. A significant positive relationship was observed between background denitrification rate and percentage of human-dominated land uses (HDL) in watersheds. Structural equation modelling revealed that the indirect effects of HDL on sediment denitrification and N2O production in Yangtze lakes were mediated primarily through lake water quality. Our findings also suggest that although sediments in Yangtze lakes can remove large quantities of nitrogen through denitrification, they may also be an important source of N2O, especially in lakes with high nitrogen content.

Functional mapping and implications of substrate specificity of the yeast high-affinity leucine permease Bap2.

PubMed

Usami, Yuki; Uemura, Satsohi; Mochizuki, Takahiro; Morita, Asami; Shishido, Fumi; Inokuchi, Jin-ichi; Abe, Fumiyoshi

2014-07-01

Leucine is a major amino acid in nutrients and proteins and is also an important precursor of higher alcohols during brewing. In Saccharomyces cerevisiae, leucine uptake is mediated by multiple amino acid permeases, including the high-affinity leucine permease Bap2. Although BAP2 transcription has been extensively analyzed, the mechanisms by which a substrate is recognized and moves through the permease remain unknown. Recently, we determined 15 amino acid residues required for Tat2-mediated tryptophan import. Here we introduced homologous mutations into Bap2 amino acid residues and showed that 7 residues played a role in leucine import. Residues I109/G110/T111 and E305 were located within the putative α-helix break in TMD1 and TMD6, respectively, according to the structurally homologous Escherichia coli arginine/agmatine antiporter AdiC. Upon leucine binding, these α-helix breaks were assumed to mediate a conformational transition in Bap2 from an outward-open to a substrate-binding occluded state. Residues Y336 (TMD7) and Y181 (TMD3) were located near I109 and E305, respectively. Bap2-mediated leucine import was inhibited by some amino acids according to the following order of severity: phenylalanine, leucine>isoleucine>methionine, tyrosine>valine>tryptophan; histidine and asparagine had no effect. Moreover, this order of severity clearly coincided with the logP values (octanol-water partition coefficients) of all amino acids except tryptophan. This result suggests that the substrate partition efficiency to the buried Bap2 binding pocket is the primary determinant of substrate specificity rather than structural amino acid side chain recognition. Copyright © 2014 Elsevier B.V. All rights reserved.

Research in Physical Chemistry and Chemical Education: Part A--Water Mediated Chemistry of Oxidized Atmospheric Compounds Part B--The Development of Surveying Tools to Determine How Effective Laboratory Experiments Contribute to Student Conceptual Understanding

ERIC Educational Resources Information Center

Maron, Marta Katarzyna

2011-01-01

This dissertation is a combination of two research areas, experimental physical chemistry, Chapters I to V, and chemical education, Chapters VI to VII. Chapters I to V describe research on the water-mediated chemistry of oxidized atmospheric molecules and the impact that water has on the spectra of these environmental systems. The role of water…

Insights into water-mediated ion clustering in aqueous CaSO4 solutions: pre-nucleation cluster characteristics studied by ab initio calculations and molecular dynamics simulations.

PubMed

Li, Hui-Ji; Yan, Dan; Cai, Hou-Qin; Yi, Hai-Bo; Min, Xiao-Bo; Xia, Fei-Fei

2017-05-10

The molecular structure of growth units building crystals is a fundamental issue in the crystallization processes from aqueous solutions. In this work, a systematic investigation of pre-nucleation clusters and their hydration characteristics in aqueous CaSO 4 solutions was performed using ab initio calculations and molecular dynamics (MD) simulations. The results of ab initio calculations and MD simulations indicate that the dominant species in aqueous CaSO 4 solutions are monodentate ion-associated structures. Compared with charged ion clusters, neutral clusters are more likely to be present in an aqueous CaSO 4 solution. Neutral (CaSO 4 ) m clusters are probably the growth units involved in the pre-nucleation or crystallization processes. Meanwhile, hydration behavior around ion associated species in aqueous CaSO 4 solutions plays an important role in related phase/polymorphism selections. Upon ion clustering, the residence of some water molecules around Ca 2+ in ion-associated species is weakened while that of some bridging waters is enhanced due to dual interaction by Ca 2+ and SO 4 2- . Some phase/polymorphism selections can be achieved in aqueous CaSO 4 solutions by controlling the hydration around pre-nucleation clusters. Moreover, the association trend between calcium and sulfate is found to be relatively strong, which hints at the low solubility of calcium sulfate in water.

Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution

NASA Astrophysics Data System (ADS)

Shen, Yu-Sheng; Lung, Shih-Chun Candice

2017-02-01

Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, primary and secondary air pollutants separately using partial least squares model with data from Taiwan. The measurable characteristics of green structure include the largest patch percentage, landscape proportion, aggregation, patch distance, and fragmentation. The results showed that mortality of pneumonia and chronic lower respiratory diseases could be reduced by minimizing fragmentation and increasing the largest patch percentage of green structure, and the mediation effects are mostly through reducing air pollutants rather than temperature. Moreover, a high proportion of but fragmented green spaces would increase secondary air pollutants and enhance health risks; demonstrating the deficiency of traditional greening policy with primary focus on coverage ratio. This is the first research focusing on mediation effects of green structure characteristics on respiratory mortality, revealing that appropriate green structure planning can be a useful complementary strategy in environmental health management.

Mediation pathways and effects of green structures on respiratory mortality via reducing air pollution.

PubMed

Shen, Yu-Sheng; Lung, Shih-Chun Candice

2017-02-23

Previous studies have shown both health and environmental benefits of green spaces, especially in moderating temperature and reducing air pollution. However, the characteristics of green structures have been overlooked in previous investigations. In addition, the mediation effects of green structures on respiratory mortality have not been assessed. This study explores the potential mediation pathways and effects of green structure characteristics on respiratory mortality through temperature, primary and secondary air pollutants separately using partial least squares model with data from Taiwan. The measurable characteristics of green structure include the largest patch percentage, landscape proportion, aggregation, patch distance, and fragmentation. The results showed that mortality of pneumonia and chronic lower respiratory diseases could be reduced by minimizing fragmentation and increasing the largest patch percentage of green structure, and the mediation effects are mostly through reducing air pollutants rather than temperature. Moreover, a high proportion of but fragmented green spaces would increase secondary air pollutants and enhance health risks; demonstrating the deficiency of traditional greening policy with primary focus on coverage ratio. This is the first research focusing on mediation effects of green structure characteristics on respiratory mortality, revealing that appropriate green structure planning can be a useful complementary strategy in environmental health management.

Relationship between mediation analysis and the structured life course approach

PubMed Central

Howe, Laura D; Smith, Andrew D; Macdonald-Wallis, Corrie; Anderson, Emma L; Galobardes, Bruna; Lawlor, Debbie A; Ben-Shlomo, Yoav; Hardy, Rebecca; Cooper, Rachel; Tilling, Kate; Fraser, Abigail

2016-01-01

Abstract Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome). PMID:27681097

Electrolytes in a nanometer slab-confinement: Ion-specific structure and solvation forces

NASA Astrophysics Data System (ADS)

Kalcher, Immanuel; Schulz, Julius C. F.; Dzubiella, Joachim

2010-10-01

We study the liquid structure and solvation forces of dense monovalent electrolytes (LiCl, NaCl, CsCl, and NaI) in a nanometer slab-confinement by explicit-water molecular dynamics (MD) simulations, implicit-water Monte Carlo (MC) simulations, and modified Poisson-Boltzmann (PB) theories. In order to consistently coarse-grain and to account for specific hydration effects in the implicit methods, realistic ion-ion and ion-surface pair potentials have been derived from infinite-dilution MD simulations. The electrolyte structure calculated from MC simulations is in good agreement with the corresponding MD simulations, thereby validating the coarse-graining approach. The agreement improves if a realistic, MD-derived dielectric constant is employed, which partially corrects for (water-mediated) many-body effects. Further analysis of the ionic structure and solvation pressure demonstrates that nonlocal extensions to PB (NPB) perform well for a wide parameter range when compared to MC simulations, whereas all local extensions mostly fail. A Barker-Henderson mapping of the ions onto a charged, asymmetric, and nonadditive binary hard-sphere mixture shows that the strength of structural correlations is strongly related to the magnitude and sign of the salt-specific nonadditivity. Furthermore, a grand canonical NPB analysis shows that the Donnan effect is dominated by steric correlations, whereas solvation forces and overcharging effects are mainly governed by ion-surface interactions. However, steric corrections to solvation forces are strongly repulsive for high concentrations and low surface charges, while overcharging can also be triggered by steric interactions in strongly correlated systems. Generally, we find that ion-surface and ion-ion correlations are strongly coupled and that coarse-grained methods should include both, the latter nonlocally and nonadditive (as given by our specific ionic diameters), when studying electrolytes in highly inhomogeneous situations.

Optimal water depth management on river-fed National Wildlife Refuges in a changing climate

USGS Publications Warehouse

Nicol, Samuel; Griffith, Brad; Austin, Jane; Hunter, Christine M.

2014-01-01

The prairie pothole region (PPR) in the north-central United States and south-central Canada constitutes the most important waterfowl breeding area in North America. Projected long-term changes in precipitation and temperature may alter the drivers of waterfowl abundance: wetland availability and emergent vegetation cover. Previous studies have focused on isolated wetland dynamics, but the implications of changing precipitation on managed, river-fed wetlands have not been addressed. Using a structured decision making (SDM) approach, we derived optimal water management actions for 20 years at four river-fed National Wildlife Refuges (NWRs) in North and South Dakota under contrasting increasing/decreasing (+/−0.4 %/year) inflow scenarios derived from empirical trends. Refuge pool depth is manipulated by control structures. Optimal management involves setting control structure heights that have the highest probability of providing a desired mix of waterfowl habitat, given refuge capacities and inflows. We found optimal seasonal control structure heights for each refuge were essentially the same under increasing and decreasing inflow trends of 0.4 %/year over the next 20 years. Results suggest managed pools in the NWRs receive large inflows relative to their capacities. Hence, water availability does not constrain management; pool bathymetry and management tactics can be greater constraints on attaining management objectives than climate-mediated inflow. We present time-dependent optimal seasonal control structure heights for each refuge, which are resilient to the non-stationary precipitation scenarios we examined. Managers can use this information to provide a desired mixture of wildlife habitats, and to re-assess management objectives in reserves where pool bathymetry prevents attaining the currently stated objectives.

The T-TEL Method for Assessing Water, Sediment, and Chemical Connectivity

NASA Astrophysics Data System (ADS)

Ali, Genevieve; Oswald, Claire; Spence, Christopher; Wellen, Christopher

2018-02-01

The concept of connectivity has been the subject of a great deal of recent research and provided new insights and breakthroughs on runoff generation processes and watershed biogeochemistry. However, a consensus definition and cohesive mathematical framework that would permit the consistent quantification of hydrologic connectivity, the examination of the interrelationships between water and material (e.g., sediment and chemicals) connectivity, or rigorous study intercomparison, have not been presented by the water resource community. Building on previous conceptualizations and site-specific or process-specific metrics, this paper aimed to review the current state of science on hydrologic connectivity and its role in water-mediated connectivity of material such as solutes and sediment before introducing a conceptual and a mathematical connectivity assessment framework. These frameworks rely on the quantification of Time scales, Thresholds, Excesses and Losses related to water and water-mediated material transport dynamics and are referred to as the T-TEL method. Through a small case study, we show how the T-TEL method allows a wide range of properties to be quantified, namely the occurrence, frequency, duration, magnitude, and spatial extent of water and water-mediated material connectivity. We also propose a research agenda to refine the T-TEL method and ensure its usefulness for facilitating the research and management of connectivity in pristine and human-impacted landscapes.

Allosteric modulation of Ras positions Q61 for a direct role in catalysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buhrman, Greg; Holzapfel, Genevieve; Fetics, Susan

2010-11-03

Ras and its effector Raf are key mediators of the Ras/Raf/MEK/ERK signal transduction pathway. Mutants of residue Q61 impair the GTPase activity of Ras and are found prominently in human cancers. Yet the mechanism through which Q61 contributes to catalysis has been elusive. It is thought to position the catalytic water molecule for nucleophilic attack on the {gamma}-phosphate of GTP. However, we previously solved the structure of Ras from crystals with symmetry of the space group R32 in which switch II is disordered and found that the catalytic water molecule is present. Here we present a structure of wild-type Rasmore » with calcium acetate from the crystallization mother liquor bound at a site remote from the active site and likely near the membrane. This results in a shift in helix 3/loop 7 and a network of H-bonding interactions that propagates across the molecule, culminating in the ordering of switch II and placement of Q61 in the active site in a previously unobserved conformation. This structure suggests a direct catalytic role for Q61 where it interacts with a water molecule that bridges one of the {gamma}-phosphate oxygen atoms to the hydroxyl group of Y32 to stabilize the transition state of the hydrolysis reaction. We propose that Raf together with the binding of Ca{sup 2+} and a negatively charged group mimicked in our structure by the acetate molecule induces the ordering of switch I and switch II to complete the active site of Ras.« less

Gas/solid carbon branching ratios in surface-mediated reactions and the incorporation of carbonaceous material into planetesimals

PubMed Central

Nuth, Joseph A.; Johnson, Natasha M.; Ferguson, Frank T.; Carayon, Alicia

2018-01-01

We report the ratio of the initial carbon available as CO that forms gas-phase compounds compared to the fraction that deposits as a carbonaceous solid (the gas/solid branching ratio) as a function of time and temperature for iron, magnetite, and amorphous iron silicate smoke catalysts during surface-mediated reactions in an excess of hydrogen and in the presence of N2. This fraction varies from more than 99% for an amorphous iron silicate smoke at 673 K to less than 40% for a magnetite catalyst at 873 K. The CO not converted into solids primarily forms methane, ethane, water, and CO2, as well as a very wide range of organic molecules at very low concentration. Carbon deposits do not form continuous coatings on the catalytic surfaces, but instead form extremely high surface area per unit volume “filamentous” structures. While these structures will likely form more slowly but over much longer times in protostellar nebulae than in our experiments due to the much lower partial pressure of CO, such fluffy coatings on the surfaces of chondrules or calcium aluminum inclusions could promote grain–grain sticking during low-velocity collisions. PMID:29563766

Gas/Solid Carbon Branching Ratios in Surface Mediated Reactions and the Incorporation of Carbonaceous Material into Planetesimals

NASA Technical Reports Server (NTRS)

Nuth, Joseph A.; Johnson, Natasha M.; Ferguson, Frank T.; Carayon, Alicia

2016-01-01

We report the ratio of the initial carbon available as CO that forms gas-phase compounds compared to the fraction that deposits as a carbonaceous solid (the gas solid branching ratio) as a function of time and temperature for iron, magnetite, and amorphous iron silicate smoke catalysts during surface-mediated reactions in an excess of hydrogen and in the presence of N2. This fraction varies from more than 99 for an amorphous iron silicate smoke at 673 K to less than 40% for a magnetite catalyst at 873 K. The CO not converted into solids primarily forms methane, ethane, water, and CO2, as well as a very wide range of organic molecules at very low concentration. Carbon deposits do not form continuous coatings on the catalytic surfaces, but instead form extremely high surface area per unit volume filamentous structures. While these structures will likely form more slowly but over much longer times in protostellar nebulae than in our experiments due to the much lower partial pressure of CO, such fluffy coatings on the surfaces of chondrules or calcium aluminum inclusions could promote grain-grain sticking during low-velocity collisions.

CU(I)BR MEDIATED COUPLING OF ALKYNES WITH N-ACYLIMINE AND N-ACYLIMINIUM IONS IN WATER. (R828129)

EPA Science Inventory

A coupling of alkynes with N-acylimines and N-acyliminium ions mediated by Cu(I) was developed in water to generate propargyl amide derivatives.

Effects of management on aquatic tree-hole communities in temperate forests are mediated by detritus amount and water chemistry.

PubMed

Gossner, Martin M; Lade, Peggy; Rohland, Anja; Sichardt, Nora; Kahl, Tiemo; Bauhus, Jürgen; Weisser, Wolfgang W; Petermann, Jana S

2016-01-01

Arthropod communities in water-filled tree holes may be sensitive to impacts of forest management, for example via changes in environmental conditions such as resource input. We hypothesized that increasing forest management intensity (ForMI) negatively affects arthropod abundance and richness and shifts community composition and trophic structure of tree hole communities. We predicted that this shift is caused by reduced habitat and resource availability at the forest stand scale as well as reduced tree hole size, detritus amount and changed water chemistry at the tree holes scale. We mapped 910 water-filled tree holes in two regions in Germany and studied 199 tree hole inhabiting arthropod communities. We found that increasing ForMI indeed significantly reduced arthropod abundance and richness in water-filled tree holes. The most important indirect effects of management intensity on tree hole community structure were the reduced amounts of detritus for the tree hole inhabiting organisms and changed water chemistry at the tree hole scale, both of which seem to act as a habitat filter. Although habitat availability at the forest stand scale decreased with increasing management intensity, this unexpectedly increased local arthropod abundance in individual tree holes. However, regional species richness in tree holes significantly decreased with increasing management intensity, most likely due to decreased habitat diversity. We did not find that the management-driven increase in plant diversity at the forest stand scale affected communities of individual tree holes, for example via resource availability for adults. Our results suggest that management of temperate forests has to target a number of factors at different scales to conserve diverse arthropod communities in water-filled tree holes. © 2015 The Authors. Journal of Animal Ecology © 2015 British Ecological Society.

New insight into the architecture of oxy-anion pocket in unliganded conformation of GAT domains: A MD-simulation study.

PubMed

Bairagya, Hridoy R; Bansal, Manju

2016-03-01

Human Guanine Monophosphate Synthetase (hGMPS) converts XMP to GMP, and acts as a bifunctional enzyme with N-terminal "glutaminase" (GAT) and C-terminal "synthetase" domain. The enzyme is identified as a potential target for anti-cancer and immunosuppressive therapies. GAT domain of enzyme plays central role in metabolism, and contains conserved catalytic residues Cys104, His190, and Glu192. MD simulation studies on GAT domain suggest that position of oxyanion in unliganded conformation is occupied by one conserved water molecule (W1), which also stabilizes that pocket. This position is occupied by a negatively charged atom of the substrate or ligand in ligand bound crystal structures. In fact, MD simulation study of Ser75 to Val indicates that W1 conserved water molecule is stabilized by Ser75, while Thr152, and His190 also act as anchor residues to maintain appropriate architecture of oxyanion pocket through water mediated H-bond interactions. Possibly, four conserved water molecules stabilize oxyanion hole in unliganded state, but they vacate these positions when the enzyme (hGMPS)-substrate complex is formed. Thus this study not only reveals functionally important role of conserved water molecules in GAT domain, but also highlights essential role of other non-catalytic residues such as Ser75 and Thr152 in this enzymatic domain. The results from this computational study could be of interest to experimental community and provide a testable hypothesis for experimental validation. Conserved sites of water molecules near and at oxyanion hole highlight structural importance of water molecules and suggest a rethink of the conventional definition of chemical geometry of inhibitor binding site. © 2016 Wiley Periodicals, Inc.

Marine Chemical Ecology: Chemical Signals and Cues Structure Marine Populations, Communities, and Ecosystems

PubMed Central

Hay, Mark E.

2012-01-01

Chemical cues constitute much of the language of life in the sea. Our understanding of biotic interactions and their effects on marine ecosystems will advance more rapidly if this language is studied and understood. Here, I review how chemical cues regulate critical aspects of the behavior of marine organisms from bacteria to phytoplankton to benthic invertebrates and water column fishes. These chemically mediated interactions strongly affect population structure, community organization, and ecosystem function. Chemical cues determine foraging strategies, feeding choices, commensal associations, selection of mates and habitats, competitive interactions, and transfer of energy and nutrients within and among ecosystems. In numerous cases, the indirect effects of chemical signals on behavior have as much or more effect on community structure and function as the direct effects of consumers and pathogens. Chemical cues are critical for understanding marine systems, but their omnipresence and impact are inadequately recognized. PMID:21141035

Crystal structure of Bacillus subtilis YabJ, a purine regulatory protein and member of the highly conserved YjgF family

PubMed Central

Sinha, Sangita; Rappu, Pekka; Lange, S. C.; Mäntsälä, Pekka; Zalkin, Howard; Smith, Janet L.

1999-01-01

The yabJ gene in Bacillus subtilis is required for adenine-mediated repression of purine biosynthetic genes in vivo and codes for an acid-soluble, 14-kDa protein. The molecular mechanism of YabJ is unknown. YabJ is a member of a large, widely distributed family of proteins of unknown biochemical function. The 1.7-Å crystal structure of YabJ reveals a trimeric organization with extensive buried hydrophobic surface and an internal water-filled cavity. The most important finding in the structure is a deep, narrow cleft between subunits lined with nine side chains that are invariant among the 25 most similar homologs. This conserved site is proposed to be a binding or catalytic site for a ligand or substrate that is common to YabJ and other members of the YER057c/YjgF/UK114 family of proteins. PMID:10557275

Bioinspired, cysteamine-catalyzed co-silicification of (1H, 1H, 2H, 2HPerfluorooctyl) triethoxysilane and tetraethyl orthosilicate: formation of superhydrophobic surfaces.

PubMed

Park, Ji Hun; Kim, Ji Yup; Cho, Woo Kyung; Choi, Insung S

2014-03-01

Bioinspired silicification attracts a great deal of interest because of its physiologically relevant, mild conditions for hydrolysis and condensation of silica precursors, which makes the bioinspired approach superior to the conventional sol–gel process, particularly when dealing with biological entities. However, the morphological control of silica structures with incorporation of functional groups in the bioinspired silicilication has been unexplored. In this work, we co-silicificated (1H, 1H, 2H, 2H-perfluorooctyl)triethoxysilane and tetraethyl orthosilicate to investigate the morphological evolution of fluorinated silica structures in the cetyltrimethylammonium bromide-mediated, cysteamine-catalyzed silicification. The generated micrometer-long wormlike and spherical silica structures display superhydrophobicity after film formation. Interestingly, the measurement of dynamic water contact angles shows that the morphological difference leads to a different wetting state, either the self-cleaning or the pinning state of the superhydrophobic surface.

Ethical Leadership, Leader-Member Exchange and Feedback Seeking: A Double-Moderated Mediation Model of Emotional Intelligence and Work-Unit Structure

PubMed Central

Qian, Jing; Wang, Bin; Han, Zhuo; Song, Baihe

2017-01-01

This research elucidates the role of ethical leadership in employee feedback seeking by examining how and when ethical leadership may exert a positive influence on feedback seeking. Using matched reports from 64 supervisors and 265 of their immediate employees from a hotel group located in a major city in China, we proposed and tested a moderated mediation model that examines leader-member exchange (LMX) as the mediator and emotional intelligence as well as work-unit structure as double moderators in the relationships between ethical leadership and followers’ feedback-seeking behavior from supervisors and coworkers. Our findings indicated that (1) LMX mediated the positive relationship between ethical leadership and feedback seeking from both ethical leaders and coworkers, and (2) emotional intelligence and work-unit structure served as joint moderators on the mediated positive relationship in such a way that the relationship was strongest when the emotional intelligence was high and work-unit structure was more of an organic structure rather than a mechanistic structure. PMID:28744251

Why do proteins aggregate? “Intrinsically insoluble proteins” and “dark mediators” revealed by studies on “insoluble proteins” solubilized in pure water

PubMed Central

Song, Jianxing

2013-01-01

In 2008, I reviewed and proposed a model for our discovery in 2005 that unrefoldable and insoluble proteins could in fact be solubilized in unsalted water. Since then, this discovery has offered us and other groups a powerful tool to characterize insoluble proteins, and we have further addressed several fundamental and disease-relevant issues associated with this discovery. Here I review these results, which are conceptualized into several novel scenarios. 1) Unlike 'misfolded proteins', which still retain the capacity to fold into well-defined structures but are misled to 'off-pathway' aggregation, unrefoldable and insoluble proteins completely lack this ability and will unavoidably aggregate in vivo with ~150 mM ions, thus designated as 'intrinsically insoluble proteins (IIPs)' here. IIPs may largely account for the 'wastefully synthesized' DRiPs identified in human cells. 2) The fact that IIPs including membrane proteins are all soluble in unsalted water, but get aggregated upon being exposed to ions, logically suggests that ions existing in the background play a central role in mediating protein aggregation, thus acting as 'dark mediators'. Our study with 14 salts confirms that IIPs lack the capacity to fold into any well-defined structures. We uncover that salts modulate protein dynamics and anions bind proteins with high selectivity and affinity, which is surprisingly masked by pre-existing ions. Accordingly, I modified my previous model. 3) Insoluble proteins interact with lipids to different degrees. Remarkably, an ALS-causing P56S mutation transforms the β-sandwich MSP domain into a helical integral membrane protein. Consequently, the number of membrane-interacting proteins might be much larger than currently recognized. To attack biological membranes may represent a common mechanism by which aggregated proteins initiate human diseases. 4) Our discovery also implies a solution to the 'chicken-and-egg paradox' for the origin of primitive membranes embedded with integral membrane proteins, if proteins originally emerged in unsalted prebiotic media. PMID:24555050

Differential Deformability of the DNA Minor Groove and Altered BI/BII Backbone Conformational Equilibrium by the Monovalent Ions Li+, Na+, K+ and Rb+ via Water-Mediated Hydrogen Bonding

PubMed Central

Savelyev, Alexey; MacKerell, Alexander D.

2015-01-01

Recently, we reported the differential impact of the monovalent cations Li+, Na+, K+ and Rb+ on DNA conformational properties. These were identified from variations in the calculated solution-state X-ray DNA spectra as a function of the ion type in the solvation buffer in MD simulations using our recently developed polarizable force field based on the classical Drude oscillator. Changes in the DNA structure were found to mainly involve variations in the minor groove width. Because minor groove dimensions vary significantly in protein-DNA complexes and have been shown to play a critical role in both specific and nonspecific DNA readout, understanding the origins of the observed differential DNA modulation by the first-group monovalent ions is of great biological importance. In the present study we show that the primary microscopic mechanism for the phenomenon is the formation of the water-mediated hydrogen bonds between solvated cations located inside the minor groove and simultaneously to two DNA strands, a process whose intensity and impact on DNA structure depends on both the type of the ion and DNA sequence. Additionally, it is shown that formation of such ion-DNA hydrogen bond complexes appreciably modulates the conformation of the backbone by increasing the population of the BII substate. Notably, the differential impact of the ions on DNA conformational behavior is only predicted by the Drude polarizable model for DNA, with virtually no effect observed from MD simulations utilizing the additive CHARMM36 model. Analysis of dipole moments of the water shows the Drude SWM4 model to possess high sensitivity to changes in the local environment, which indicates the important role of electronic polarization in the salt-dependent conformational properties. This also suggests that inclusion of polarization effects is required to model even relatively simple biological systems such as DNA in various ionic solutions. PMID:26575937

Dissociation of the trimeric gp41 ectodomain at the lipid-water interface suggests an active role in HIV-1 Env-mediated membrane fusion.

PubMed

Roche, Julien; Louis, John M; Grishaev, Alexander; Ying, Jinfa; Bax, Adriaan

2014-03-04

The envelope glycoprotein gp41 mediates the process of membrane fusion that enables entry of the HIV-1 virus into the host cell. The actual fusion process involves a switch from a homotrimeric prehairpin intermediate conformation, consisting of parallel coiled-coil helices, to a postfusion state where the ectodomains are arranged as a trimer of helical hairpins, adopting a six-helix bundle (6HB) state. Here, we show by solution NMR spectroscopy that a water-soluble 6HB gp41 ectodomain binds to zwitterionic detergents that contain phosphocholine or phosphatidylcholine head groups and phospholipid vesicles that mimic T-cell membrane composition. Binding results in the dissociation of the 6HB and the formation of a monomeric state, where its two α-helices, N-terminal heptad repeat (NHR) and C-terminal heptad repeat (CHR), become embedded in the lipid-water interface of the virus and host cell. The atomic structure of the gp41 ectodomain monomer, based on NOE distance restraints and residual dipolar couplings, shows that the NHR and CHR helices remain mostly intact, but they completely lose interhelical contacts. The high affinity of the ectodomain helices for phospholipid surfaces suggests that unzippering of the prehairpin intermediate leads to a state where the NHR and CHR helices become embedded in the host cell and viral membranes, respectively, thereby providing a physical force for bringing these membranes into close juxtaposition before actual fusion.

The Influence of Environmental Hazard Maps on Risk Beliefs, Emotion, and Health-related Behavioral Intentions

PubMed Central

Severtson, Dolores

2013-01-01

To test a theoretical explanation of how attributes of mapped environmental health hazards influence health-related behavioral intentions and how beliefs and emotion mediate the influences of attributes, 24 maps were developed that varied by four attributes of a residential drinking water hazard: level, proximity, prevalence, and density. In a factorial design, student participants (N=446) answered questions for a subset of maps. Hazard level and proximity had the largest influences on intentions to test water and mitigate exposure. Belief in the problem’s seriousness mediated attributes’ influence on intention to test drinking water, and perceived susceptibility mediated the influence of attributes on intention to mitigate risk. Maps with carefully illustrated attributes of hazards may promote appropriate health-related risk beliefs, intentions, and behavior. PMID:23533022

Modifications to toxic CUG RNAs induce structural stability, rescue mis-splicing in a myotonic dystrophy cell model and reduce toxicity in a myotonic dystrophy zebrafish model

DOE PAGES

deLorimier, Elaine; Coonrod, Leslie A.; Copperman, Jeremy; ...

2014-10-10

In this study, CUG repeat expansions in the 3' UTR of dystrophia myotonica protein kinase ( DMPK) cause myotonic dystrophy type 1 (DM1). As RNA, these repeats elicit toxicity by sequestering splicing proteins, such as MBNL1, into protein–RNA aggregates. Structural studies demonstrate that CUG repeats can form A-form helices, suggesting that repeat secondary structure could be important in pathogenicity. To evaluate this hypothesis, we utilized structure-stabilizing RNA modifications pseudouridine (Ψ) and 2'-O-methylation to determine if stabilization of CUG helical conformations affected toxicity. CUG repeats modified with Ψ or 2'-O-methyl groups exhibited enhanced structural stability and reduced affinity for MBNL1. Molecularmore » dynamics and X-ray crystallography suggest a potential water-bridging mechanism for Ψ-mediated CUG repeat stabilization. Ψ modification of CUG repeats rescued mis-splicing in a DM1 cell model and prevented CUG repeat toxicity in zebrafish embryos. This study indicates that the structure of toxic RNAs has a significant role in controlling the onset of neuromuscular diseases.« less

25 CFR 161.603 - Can mediation be used in the event of a permit violation or dispute?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Can mediation be used in the event of a permit violation... AND WATER NAVAJO PARTITIONED LANDS GRAZING PERMITS Permit Violations § 161.603 Can mediation be used... to be resolved with the District Grazing Committee through mediation. (a) The District Grazing...

A structural and mechanistic study of π-clamp-mediated cysteine perfluoroarylation.

PubMed

Dai, Peng; Williams, Jonathan K; Zhang, Chi; Welborn, Matthew; Shepherd, James J; Zhu, Tianyu; Van Voorhis, Troy; Hong, Mei; Pentelute, Bradley L

2017-08-11

Natural enzymes use local environments to tune the reactivity of amino acid side chains. In searching for small peptides with similar properties, we discovered a four-residue π-clamp motif (Phe-Cys-Pro-Phe) for regio- and chemoselective arylation of cysteine in ribosomally produced proteins. Here we report mutational, computational, and structural findings directed toward elucidating the molecular factors that drive π-clamp-mediated arylation. We show the significance of a trans conformation prolyl amide bond for the π-clamp reactivity. The π-clamp cysteine arylation reaction enthalpy of activation (ΔH ‡ ) is significantly lower than a non-π-clamp cysteine. Solid-state NMR chemical shifts indicate the prolyl amide bond in the π-clamp motif adopts a 1:1 ratio of the cis and trans conformation, while in the reaction product Pro3 was exclusively in trans. In two structural models of the perfluoroarylated product, distinct interactions at 4.7 Å between Phe1 side chain and perfluoroaryl electrophile moiety are observed. Further, solution 19 F NMR and isothermal titration calorimetry measurements suggest interactions between hydrophobic side chains in a π-clamp mutant and the perfluoroaryl probe. These studies led us to design a π-clamp mutant with an 85-fold rate enhancement. These findings will guide us toward the discovery of small reactive peptides to facilitate abiotic chemistry in water.

The molecular basis for water taste in Drosophila

PubMed Central

Cameron, Peter; Hiroi, Makoto; Ngai, John; Scott, Kristin

2010-01-01

The detection of water and the regulation of water intake are essential for animals to maintain proper osmotic homeostasis1. Drosophila and other insects have gustatory sensory neurons that mediate the recognition of external water sources2-4, but little is known about the underlying molecular mechanism for water taste detection. Here, we identify a member of the Degenerin/Epithelial Sodium Channel family5, ppk28, as an osmosensitive ion channel that mediates the cellular and behavioral response to water. We use molecular, cellular, calcium imaging and electrophysiological approaches to show that ppk28 is expressed in water-sensing neurons and loss of ppk28 abolishes water sensitivity. Moreover, ectopic expression of ppk28 confers water sensitivity to bitter-sensing gustatory neurons in the fly and sensitivity to hypo-osmotic solutions when expressed in heterologous cells. These studies link an osmosensitive ion channel to water taste detection and drinking behavior, providing the framework for examining the molecular basis for water detection in other animals. PMID:20364123

The polar warhead of a TRIM24 bromodomain inhibitor rearranges a water-mediated interaction network.

PubMed

Liu, Jiuyang; Li, Fudong; Bao, Hongyu; Jiang, Yiyang; Zhang, Shuya; Ma, Rongsheng; Gao, Jia; Wu, Jihui; Ruan, Ke

2017-04-01

Tripartite motif-containing protein 24 (TRIM24) is closely correlated with multiple cancers, and a recent study demonstrated that the bromodomain of TRIM24 is essential for the proliferation of lethal castration-resistant prostate cancer. Here, we identify three new inhibitors of the TRIM24 bromodomain using NMR fragment-based screening. The crystal structures of two new inhibitors in complex with the TRIM24 bromodomain reveal that the water-bridged interaction network is conserved in the same fashion as those for known benzoimidazolone inhibitors. Interestingly, the polar substitution on the warhead of one new inhibitor pulls the whole ligand approximately 2 Å into the inner side pocket of the TRIM24 bromodomain, and thus exhibits a binding mode significantly different from other known bromodomain ligands. This mode provides a useful handle for further hit-to-lead evolution toward novel inhibitors of the TRIM24 bromodomain. Structural data are available in the PDB under the accession numbers 5H1T, 5H1U, and 5H1V. © 2017 Federation of European Biochemical Societies.

Solvent-coordinate free-energy landscape view of water-mediated ion-pair dissociation

NASA Astrophysics Data System (ADS)

Yonetani, Yoshiteru

2017-12-01

Water-mediated ion-pair dissociation is studied by molecular dynamics simulations of NaCl in water. Multidimensional free-energy analysis clarifies the relation between two essential solvent coordinates: the water coordination number and water-bridge formation. These two are related in a complex way. Both are necessary to describe ion-pair dissociation. The mechanism constructed with both solvent variables clearly shows the individual roles. The water coordination number is critical for starting ion-pair dissociation. Water-bridge formation is also important because it increases the likelihood of ion-pair dissociation by reducing the dissociation free-energy barrier. Additional Ca-Cl and NH4-Cl calculations show that these conclusions are unaffected by changes in the ion charge and shape. The present results will contribute to future explorations of many other molecular events such as surface water exchange and protein-ligand dissociation because the same mechanism is involved in such events.

Rapid aquaporin translocation regulates cellular water flow: mechanism of hypotonicity-induced subcellular localization of aquaporin 1 water channel.

PubMed

Conner, Matthew T; Conner, Alex C; Bland, Charlotte E; Taylor, Luke H J; Brown, James E P; Parri, H Rheinallt; Bill, Roslyn M

2012-03-30

The control of cellular water flow is mediated by the aquaporin (AQP) family of membrane proteins. The structural features of the family and the mechanism of selective water passage through the AQP pore are established, but there remains a gap in our knowledge of how water transport is regulated. Two broad possibilities exist. One is controlling the passage of water through the AQP pore, but this only has been observed as a phenomenon in some plant and microbial AQPs. An alternative is controlling the number of AQPs in the cell membrane. Here, we describe a novel pathway in mammalian cells whereby a hypotonic stimulus directly induces intracellular calcium elevations through transient receptor potential channels, which trigger AQP1 translocation. This translocation, which has a direct role in cell volume regulation, occurs within 30 s and is dependent on calmodulin activation and phosphorylation of AQP1 at two threonine residues by protein kinase C. This direct mechanism provides a rationale for the changes in water transport that are required in response to constantly changing local cellular water availability. Moreover, because calcium is a pluripotent and ubiquitous second messenger in biological systems, the discovery of its role in the regulation of AQP translocation has ramifications for diverse physiological and pathophysiological processes, as well as providing an explanation for the rapid regulation of water flow that is necessary for cell homeostasis.

Water-soluble polymers bearing phosphorylcholine group and other zwitterionic groups for carrying DNA derivatives.

PubMed

Lin, Xiaojie; Ishihara, Kazuhiko

2014-01-01

Water-soluble polymers with equal positive and negative charges in the same monomer unit, such as the phosphorylcholine group and other zwitterionic groups, exhibit promising potential in gene delivery with appreciable transfection efficiency, compared with the traditional poly(ethylene glycol)-based polycation-gene complexes. These zwitterionic polymers with various architectural structures and properties have been synthesized by various polymerization methods, such as conventional radical polymerization, atom-transfer radical-polymerization, reversible addition-fragmentation chain-transfer polymerization, and nitroxide-mediated radical polymerization. These techniques have been used to efficiently facilitate gene therapy by fabrication of non-viral vectors with high cytocompatibility, large gene-carrying capacity, effective cell-membrane permeability, and in vivo gene-loading/releasing functionality. Zwitterionic polymer-based gene delivery vectors systems can be categorized into soluble-polymer/gene mixing, molecular self-assembly, and polymer-gene conjugation systems. This review describes the preparation and characterization of various zwitterionic polymer-based gene delivery vectors, specifically water-soluble phospholipid polymers for carrying gene derivatives.

Structure and Function of Thermostable Direct Hemolysin (TDH) from Vibrio Parahaemolyticus

NASA Astrophysics Data System (ADS)

Hashimoto, Hiroshi; Yamane, Tsutomu; Ikeguchi, Mitsunori; Nakahira, Kumiko; Yanagihara, Itaru

Thermostable direct hemolysin (TDH) is a major virulence factor of Vibrio parahaemolyticus that causes pandemic food-borne enterocolitis mediated by seafood. TDH exists as a tetramer in solution, and it possesses extreme hemolytic activity. Here, we present the crystal structure of the TDH tetramer at 1.5 Å resolution. The TDH tetramer forms a central pore with dimensions of 23 Å in diameter and ∼50 Å in depth. π-cation interactions between protomers comprising the tetramer were indispensable for hemolytic activity of TDH. The N-terminal region was intrinsically disordered outside the pore. Molecular dynamics (MD) simulations suggested that water molecules permeate freely through the central and side channel pores. These findings imply a novel membrane attachment mechanism by a soluble tetrameric pore-forming toxin.

Development of a Ground Water Data Portal for Interoperable Data Exchange within the U.S. National Ground Water Monitoring Network and Beyond

NASA Astrophysics Data System (ADS)

Booth, N. L.; Brodaric, B.; Lucido, J. M.; Kuo, I.; Boisvert, E.; Cunningham, W. L.

2011-12-01

The need for a national groundwater monitoring network within the United States is profound and has been recognized by organizations outside government as a major data gap for managing ground-water resources. Our country's communities, industries, agriculture, energy production and critical ecosystems rely on water being available in adequate quantity and suitable quality. To meet this need the Subcommittee on Ground Water, established by the Federal Advisory Committee on Water Information, created a National Ground Water Monitoring Network (NGWMN) envisioned as a voluntary, integrated system of data collection, management and reporting that will provide the data needed to address present and future ground-water management questions raised by Congress, Federal, State and Tribal agencies and the public. The NGWMN Data Portal is the means by which policy makers, academics and the public will be able to access ground water data through one seamless web-based application from disparate data sources. Data systems in the United States exist at many organizational and geographic levels and differing vocabulary and data structures have prevented data sharing and reuse. The data portal will facilitate the retrieval of and access to groundwater data on an as-needed basis from multiple, dispersed data repositories allowing the data to continue to be housed and managed by the data provider while being accessible for the purposes of the national monitoring network. This work leverages Open Geospatial Consortium (OGC) data exchange standards and information models. To advance these standards for supporting the exchange of ground water information, an OGC Interoperability Experiment was organized among international participants from government, academia and the private sector. The experiment focused on ground water data exchange across the U.S. / Canadian border. WaterML2.0, an evolving international standard for water observations, encodes ground water levels and is exchanged using the OGC Sensor Observation Service (SOS) standard. Ground Water Markup Language (GWML) encodes well log, lithology and construction information and is exchanged using the OGC Web Feature Service (WFS) standard. Within the NGWMN Data Portal, data exchange between distributed data provider repositories is achieved through the use of these web services and a central mediation hub, which performs both format (syntactic) and nomenclature (semantic) mediation, conforming heterogeneous inputs into common standards-based outputs. Through these common standards, interoperability between the U.S. NGWMN and Canada's Groundwater Information Network (GIN) is achieved, advancing a ground water virtual observatory across North America.

Do biomass fuel use and consumption of unsafe water mediate educational inequalities in stillbirth risk? An analysis of the 2007 Ghana Maternal Health Survey

PubMed Central

Näyhä, Simo; Jaakkola, Jouni J K

2017-01-01

Background Numerous studies have explored the association between educational inequalities and stillbirth but most have failed to elaborate how low educational attainment leads to an increased risk of stillbirth. We hypothesised that use of biomass fuels and consumption of unsafe water related to low educational attainment could explain the stillbirth burden in Ghana attributable to socioeconomic disadvantage. Methods Data from the 2007 Ghana Maternal Health Survey, a nationally representative population-based survey were analysed for this study. Of the10 370 women aged 15–49 years interviewed via structured questionnaires for the survey, 7183 primiparous and multiparous women qualified for inclusion in the present study. Results In a logistic regression analysis that adjusted for age, area of residence, marital status and ethnicity of women, lower maternal primary education was associated with a 62% (OR=1.62; 95% CI 1.04 to 2.52) increased lifetime risk of stillbirth. Biomass fuel use and consumption of unsafe water mediated 18% and 8% of the observed effects, respectively. Jointly these two exposures explained 24% of the observed effects. The generalised additive modelling revealed a very flat inverted spoon-shaped smoothed curve which peaked at low levels of schooling (2–3 years) and confirms the findings from the logistic regression analysis. Conclusions Our results show that biomass fuel use and unsafe water consumption could be important pathways through which low maternal educational attainment leads to stillbirths in Ghana and similar developing countries. Addressing educational inequalities in developing countries is thus essential for ensuring household choices that curtail environmental exposures and help improve pregnancy outcomes. PMID:28174221

Energy and charge transfer in ionized argon coated water clusters.

PubMed

Kočišek, J; Lengyel, J; Fárník, M; Slavíček, P

2013-12-07

We investigate the electron ionization of clusters generated in mixed Ar-water expansions. The electron energy dependent ion yields reveal the neutral cluster composition and structure: water clusters fully covered with the Ar solvation shell are formed under certain expansion conditions. The argon atoms shield the embedded (H2O)n clusters resulting in the ionization threshold above ≈15 eV for all fragments. The argon atoms also mediate more complex reactions in the clusters: e.g., the charge transfer between Ar(+) and water occurs above the threshold; at higher electron energies above ~28 eV, an excitonic transfer process between Ar(+)* and water opens leading to new products Ar(n)H(+) and (H2O)(n)H(+). On the other hand, the excitonic transfer from the neutral Ar* state at lower energies is not observed although this resonant process was demonstrated previously in a photoionization experiment. Doubly charged fragments (H2O)(n)H2(2+) and (H2O)(n)(2+) ions are observed and Intermolecular Coulomb decay (ICD) processes are invoked to explain their thresholds. The Coulomb explosion of the doubly charged cluster formed within the ICD process is prevented by the stabilization effect of the argon solvent.

Structural and electronic snapshots during the transition from a Cu(II) to Cu(I) metal center of a lytic polysaccharide monooxygenase by X-ray photoreduction.

PubMed

Gudmundsson, Mikael; Kim, Seonah; Wu, Miao; Ishida, Takuya; Momeni, Majid Hadadd; Vaaje-Kolstad, Gustav; Lundberg, Daniel; Royant, Antoine; Ståhlberg, Jerry; Eijsink, Vincent G H; Beckham, Gregg T; Sandgren, Mats

2014-07-04

Lytic polysaccharide monooxygenases (LPMOs) are a recently discovered class of enzymes that employ a copper-mediated, oxidative mechanism to cleave glycosidic bonds. The LPMO catalytic mechanism likely requires that molecular oxygen first binds to Cu(I), but the oxidation state in many reported LPMO structures is ambiguous, and the changes in the LPMO active site required to accommodate both oxidation states of copper have not been fully elucidated. Here, a diffraction data collection strategy minimizing the deposited x-ray dose was used to solve the crystal structure of a chitin-specific LPMO from Enterococcus faecalis (EfaCBM33A) in the Cu(II)-bound form. Subsequently, the crystalline protein was photoreduced in the x-ray beam, which revealed structural changes associated with the conversion from the initial Cu(II)-oxidized form with two coordinated water molecules, which adopts a trigonal bipyramidal geometry, to a reduced Cu(I) form in a T-shaped geometry with no coordinated water molecules. A comprehensive survey of Cu(II) and Cu(I) structures in the Cambridge Structural Database unambiguously shows that the geometries observed in the least and most reduced structures reflect binding of Cu(II) and Cu(I), respectively. Quantum mechanical calculations of the oxidized and reduced active sites reveal little change in the electronic structure of the active site measured by the active site partial charges. Together with a previous theoretical investigation of a fungal LPMO, this suggests significant functional plasticity in LPMO active sites. Overall, this study provides molecular snapshots along the reduction process to activate the LPMO catalytic machinery and provides a general method for solving LPMO structures in both copper oxidation states. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical and Photochemical Water Oxidation Mediated by an Efficient Single-Site Ruthenium Catalyst.

PubMed

Abdel-Magied, Ahmed F; Shatskiy, Andrey; Liao, Rong-Zhen; Laine, Tanja M; Arafa, Wael A A; Siegbahn, Per E M; Kärkäs, Markus D; Åkermark, Björn; Johnston, Eric V

2016-12-20

Water oxidation is a fundamental step in artificial photosynthesis for solar fuels production. In this study, we report a single-site Ru-based water oxidation catalyst, housing a dicarboxylate-benzimidazole ligand, that mediates both chemical and light-driven oxidation of water efficiently under neutral conditions. The importance of the incorporation of the negatively charged ligand framework is manifested in the low redox potentials of the developed complex, which allows water oxidation to be driven by the mild one-electron oxidant [Ru(bpy) 3 ] 3+ (bpy=2,2'-bipyridine). Furthermore, combined experimental and DFT studies provide insight into the mechanistic details of the catalytic cycle. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Nanomolar detection of hypochlorite by a rhodamine-based chiral hydrazide in absolute aqueous media: application in tap water analysis with live-cell imaging.

PubMed

Goswami, Shyamaprosad; Das, Avijit Kumar; Manna, Abhishek; Maity, Anup Kumar; Saha, Partha; Quah, Ching Kheng; Fun, Hoong-Kun; Abdel-Aziz, Hatem A

2014-07-01

By employing the oxidation property of hypochlorite (OCl(-)), a novel rhodamine-based hydrazide of the chiral acid ((S)-(-)-2-pyrrolidone-5-carboxylic acid) (RHHP) was designed and synthesized for detection of OCl(-) absolutely in aqueous medium at nanomolar level. The structure of the chiral sensor was also proved by the X-ray crystallography. The bioactivity and the application of the probe for detection of OCl(-) in natural water system have been demonstrated. A plausible mechanism for oxidation of the sensor followed by hydrolysis is also proposed. The sensibility of the receptor toward OCl(-) was studied in absolute aqueous media, and the detection limit of hypochlorite-mediated oxidation to the receptor in nanomolar level makes this platform (RHHP) an ultrasensitive and unique system for OCl(-) oxidation.

Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging

PubMed Central

Oza, Goldie; Ravichandran, M.; Merupo, Victor-Ishrayelu; Shinde, Sachin; Mewada, Ashmi; Ramirez, Jose Tapia; Velumani, S.; Sharon, Madhuri; Sharon, Maheshwar

2016-01-01

A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent. PMID:26905737

Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging

NASA Astrophysics Data System (ADS)

Oza, Goldie; Ravichandran, M.; Merupo, Victor-Ishrayelu; Shinde, Sachin; Mewada, Ashmi; Ramirez, Jose Tapia; Velumani, S.; Sharon, Madhuri; Sharon, Maheshwar

2016-02-01

A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent.

Relationship between mediation analysis and the structured life course approach.

PubMed

Howe, Laura D; Smith, Andrew D; Macdonald-Wallis, Corrie; Anderson, Emma L; Galobardes, Bruna; Lawlor, Debbie A; Ben-Shlomo, Yoav; Hardy, Rebecca; Cooper, Rachel; Tilling, Kate; Fraser, Abigail

2016-08-01

Many questions in life course epidemiology involve mediation and/or interaction because of the long latency period between exposures and outcomes. In this paper, we explore how mediation analysis (based on counterfactual theory and implemented using conventional regression approaches) links with a structured approach to selecting life course hypotheses. Using theory and simulated data, we show how the alternative life course hypotheses assessed in the structured life course approach correspond to different combinations of mediation and interaction parameters. For example, an early life critical period model corresponds to a direct effect of the early life exposure, but no indirect effect via the mediator and no interaction between the early life exposure and the mediator. We also compare these methods using an illustrative real-data example using data on parental occupational social class (early life exposure), own adult occupational social class (mediator) and physical capability (outcome). © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association.

Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water.

PubMed

Frawley, Rachel P; Smith, Matthew J; White, Kimber L; Elmore, Susan A; Herbert, Ron; Moore, Rebecca; Staska, Lauren M; Behl, Mamta; Hooth, Michelle J; Kissling, Grace E; Germolec, Dori R

2016-09-01

Tungsten is a naturally occurring, high-tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0-2000 mg STD/L in their drinking water for 28 d, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3(+) T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely affect cell-mediated immunity.

Immunotoxic Effects of Sodium Tungstate Dihydrate on Female B6C3F1/N Mice When Administered in Drinking Water

PubMed Central

Frawley, Rachel P.; Smith, Matthew J.; White, Kimber L; Elmore, Susan; Herbert, Ron; Moore, Rebecca; Staska, Lauren M.; Behl, Mamta; Hooth, Michelle J.; Kissling, Grace E.; Germolec, Dori R.

2018-01-01

Tungsten is a naturally occurring, high tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0–2000 mg STD/L in their drinking water for 28 days, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3+ T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely effect cell-mediated immunity. PMID:27223060

Neutral vs zwitterionic glycine forms at the water/silica interface: structure, energies, and vibrational features from B3LYP periodic simulations.

PubMed

Rimola, Albert; Civalleri, Bartolomeo; Ugliengo, Piero

2008-12-16

B3LYP periodic calculations with a triple-xi-polarized Gaussian basis set have been used to study adsorption of glycine on a hydroxylated silica surface (2.2 OH/nm2) model derived from the (001) surface of edingtonite. The simulation envisages glycine adsorbed either as a gas-phase molecule or when microsolvated by up to five H20 molecules. Both neutral and zwitterionic forms of glycine have been considered and their structural, energetic, and spectroscopic vibrational features compared internally and with experiments. As a gas phase glycine sticks in its neutral form at the silica surface, the zwitterion being highly unstable and with transition-state character. When glycine is microsolvated at the silica interface, two H20 molecules render the zwitterion population comparable to that of the neutral form whereas with four H2O molecules the neutral glycine population is wiped out in favor of the zwitterion. With four H20 molecules the most stable structure shows no direct contact between glycine and the silica surface, H20 acting as a mediator via H-bond interactions. The B3LYP energies and structural data were also supported by comparing the scaled harmonic vibrational features with literature FTIR data of glycine adsorbed on an amorphous silica surface either from the gas phase or in water solution.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Ching-Shin; Pedersen, Bjørn Panyella; Stokes, David L.

Cellular potassium import systems play a fundamental role in osmoregulation, pH homeostasis and membrane potential in all domains of life. In bacteria, the kdp operon encodes a four-subunit potassium pump that maintains intracellular homeostasis, cell shape and turgor under conditions in which potassium is limiting1. This membrane complex, called KdpFABC, has one channel-like subunit (KdpA) belonging to the superfamily of potassium transporters and another pump-like subunit (KdpB) belonging to the superfamily of P-type ATPases. Although there is considerable structural and functional information about members of both superfamilies, the mechanism by which uphill potassium transport through KdpA is coupled with ATPmore » hydrolysis by KdpB remains poorly understood. Here we report the 2.9 Å X-ray structure of the complete Escherichia coli KdpFABC complex with a potassium ion within the selectivity filter of KdpA and a water molecule at a canonical cation site in the transmembrane domain of KdpB. The structure also reveals two structural elements that appear to mediate the coupling between these two subunits. Specifically, a protein-embedded tunnel runs between these potassium and water sites and a helix controlling the cytoplasmic gate of KdpA is linked to the phosphorylation domain of KdpB. On the basis of these observations, we propose a mechanism that repurposes protein channel architecture for active transport across biomembranes.« less

Trace Water as Prominent Factor to Induce Peptide Self-Assembly: Dynamic Evolution and Governing Interactions in Ionic Liquids.

PubMed

Wang, Juan; Yuan, Chengqian; Han, Yuchun; Wang, Yilin; Liu, Xiaomin; Zhang, Suojiang; Yan, Xuehai

2017-11-01

The interaction between water and biomolecules including peptides is of critical importance for forming high-level architectures and triggering life's functions. However, the bulk aqueous environment has limitations in detecting the kinetics and mechanisms of peptide self-assembly, especially relating to interactions of trace water. With ionic liquids (ILs) as a nonconventional medium, herein, it is discovered that trace amounts of water play a decisive role in triggering self-assembly of a biologically derived dipeptide. ILs provide a suitable nonaqueous environment, enabling us to mediate water content and follow the dynamic evolution of peptide self-assembly. The trace water is found to be involved in the assembly process of dipeptide, especially leading to the formation of stable noncovalent dipeptide oligomers in the early stage of nucleation, as evident by both experimental studies and theoretical simulations. The thermodynamics of the growth process is mainly governed by a synergistic effect of hydrophobic interaction and hydrogen bonds. Each step of assembly presents a different trend in thermodynamic energy. The dynamic evolution of assembly process can be efficiently mediated by changing trace water content. The decisive role of trace water in triggering and mediating self-assembly of biomolecules provides a new perspective in understanding supramolecular chemistry and molecular self-organization in biology. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Is it the shape of the cavity, or the shape of the water in the cavity?

NASA Astrophysics Data System (ADS)

Snyder, Phillip W.; Lockett, Matthew R.; Moustakas, Demetri T.; Whitesides, George M.

2014-04-01

Historical interpretations of the thermodynamics characterizing biomolecular recognition have marginalized the role of water. An important (even, perhaps, dominant) contribution to molecular recognition in water comes from the "hydrophobic effect," in which non-polar portions of a ligand interact preferentially with non-polar regions of a protein. Water surrounds the ligand, and water fills the binding pocket of the protein: when the protein-ligand complex forms, and hydrophobic surfaces of the binding pocket and the ligand approach one another, the molecules (and hydrogen-bonded networks of molecules) of water associated with both surfaces rearrange and, in part, entirely escape into the bulk solution. It is now clear that neither of the two most commonly cited rationalizations for the hydrophobic effect-an entropy-dominated hydrophobic effect, in which ordered waters at the surface of the ligand, and water at the surface of the protein, are released to the bulk upon binding, and a "lock-and-key" model, in which the surface of a ligand interacts directly with a surface of a protein having a complementary shape-can account for water-mediated interactions between the ligand and the protein, and neither is sufficient to account for the experimental observation of both entropy- andenthalpy-dominated hydrophobic effects. What is now clear is that there is no single hydrophobic effect, with a universally applicable, common, thermodynamic description: different processes (i.e., partitioning between phases of different hydrophobicity, aggregation in water, and binding) with different thermodynamics, depend on the molecular-level details of the structures of the molecules involved, and of the aggregates that form. A "water-centric" description of the hydrophobic effect in biomolecular recognition focuses on the structures of water surrounding the ligand, and of water filling the binding pocket of the protein, both before and after binding. This view attributes the hydrophobic effect to changes in the free energy of the networks of hydrogen bonds that are formed, broken, or re-arranged when two hydrophobic surfaces approach (but do not necessarily contact) one another. The details of the molecular topography (and the polar character) of the mole- cular surfaces play an important role in determining the structure of these networks of hydrogen-bonded waters, and in the thermodynamic description of the hydrophobic effect(s). Theorists have led the formulation of this "water-centric view", although experiments are now supplying support for it. It poses complex problems for would-be "designers" of protein-ligand interactions, and for so-called "rational drug design".

Testing Mediation Using Multiple Regression and Structural Equation Modeling Analyses in Secondary Data

ERIC Educational Resources Information Center

Li, Spencer D.

2011-01-01

Mediation analysis in child and adolescent development research is possible using large secondary data sets. This article provides an overview of two statistical methods commonly used to test mediated effects in secondary analysis: multiple regression and structural equation modeling (SEM). Two empirical studies are presented to illustrate the…

Evaluation of side-effects of glyphosate mediated control of giant reed (Arundo donax) on the structure and function of a nearby Mediterranean river ecosystem.

PubMed

Puértolas, Laura; Damásio, Joana; Barata, Carlos; Soares, Amadeu M V M; Prat, Narcís

2010-08-01

The aim of this study was to evaluate the effect of the application of the herbicide Herbolex (Aragonesas Agro, S.A., Madrid, Spain) to control giant reed (Arundo donax), which has glyphosate as active ingredient, on the structure and function of a nearby river ecosystem. Specifically, we assessed glyphosate environmental fate in the surrounding water and its effects on transplanted Daphnia magna, field collected caddisfly (Hydropsyche exocellata) and on benthic macroinvertebrate structure assemblages. Investigations were conducted in the industrialized and urbanized Mediterranean river Llobregat (NE Spain) before and after a terrestrial spray of glyphosate. Four locations were selected to include an upstream site and three affected ones. Measured glyphosate levels in river water following herbicide application were quite high (20-60 microg/l) with peak values of 137 microg/l after three days. After 12 days of its application, leaching of glyphosate from sprayed riverbanks was quite high in pore water (20-85 microg/l) but not in the river. Closely linked with the measured poor habitat and water physico-chemical conditions, macroinvertebrate communities were dominated by taxa tolerant to pollution and herbicide application did not affect the abundance or number of taxa in any location. Nevertheless, significant specific toxic effects on transplanted D. magna and field collected H. exocellata were observed. Effects included D. magna feeding inhibition and oxidative stress related responses such as increased antioxidant enzyme activities related with the metabolism of glutathione and increased levels of lipid peroxidation. These results emphasize the importance of combined chemical, ecological and specific biological responses to identify ecological effects of pesticides in the field. Copyright 2010 Elsevier Inc. All rights reserved.

The influence of environmental hazard maps on risk beliefs, emotion, and health-related behavioral intentions.

PubMed

Severtson, Dolores J

2013-08-01

To test a theoretical explanation of how attributes of mapped environmental health hazards influence health-related behavioral intentions and how beliefs and emotion mediate the influences of attributes, 24 maps were developed that varied by four attributes of a residential drinking water hazard: level, proximity, prevalence, and density. In a factorial design, student participants (N = 446) answered questions about a subset of maps. Hazard level and proximity had the largest influences on intentions to test water and mitigate exposure. Belief in the problem's seriousness mediated attributes' influence on intention to test drinking water, and perceived susceptibility mediated the influence of attributes on intention to mitigate risk. Maps with carefully illustrated attributes of hazards may promote appropriate health-related risk beliefs, intentions, and behavior. Copyright © 2013 Wiley Periodicals, Inc.

Core Mediator structure at 3.4 Å extends model of transcription initiation complex.

PubMed

Nozawa, Kayo; Schneider, Thomas R; Cramer, Patrick

2017-05-11

Mediator is a multiprotein co-activator that binds the transcription pre-initiation complex (PIC) and regulates RNA polymerase (Pol) II. The Mediator head and middle modules form the essential core Mediator (cMed), whereas the tail and kinase modules play regulatory roles. The architecture of Mediator and its position on the PIC are known, but atomic details are limited to Mediator subcomplexes. Here we report the crystal structure of the 15-subunit cMed from Schizosaccharomyces pombe at 3.4 Å resolution. The structure shows an unaltered head module, and reveals the intricate middle module, which we show is globally required for transcription. Sites of known Mediator mutations cluster at the interface between the head and middle modules, and in terminal regions of the head subunits Med6 (ref. 16) and Med17 (ref. 17) that tether the middle module. The structure led to a model for Saccharomyces cerevisiae cMed that could be combined with the 3.6 Å cryo-electron microscopy structure of the core PIC (cPIC). The resulting atomic model of the cPIC-cMed complex informs on interactions of the submodules forming the middle module, called beam, knob, plank, connector, and hook. The hook is flexibly linked to Mediator by a conserved hinge and contacts the transcription initiation factor IIH (TFIIH) kinase that phosphorylates the carboxy (C)-terminal domain (CTD) of Pol II and was recently positioned on the PIC. The hook also contains residues that crosslink to the CTD and reside in a previously described cradle. These results provide a framework for understanding Mediator function, including its role in stimulating CTD phosphorylation by TFIIH.

Structures of Prostacyclin Synthase and Its Complexes with Substrate Analog and Inhibitor Reveal a Ligand-specific Heme Conformation Change*s

PubMed Central

Li, Yi-Ching; Chiang, Chia-Wang; Yeh, Hui-Chun; Hsu, Pei-Yung; Whitby, Frank G.; Wang, Lee-Ho; Chan, Nei-Li

2008-01-01

Prostacyclin synthase (PGIS) is a cytochrome P450 (P450) enzyme that catalyzes production of prostacyclin from prostaglandin H2. PGIS is unusual in that it catalyzes an isomerization rather than a monooxygenation, which is typical of P450 enzymes. To understand the structural basis for prostacyclin biosynthesis in greater detail, we have determined the crystal structures of ligand-free, inhibitor (minoxidil)-bound and substrate analog U51605-bound PGIS. These structures demonstrate a stereo-specific substrate binding and suggest features of the enzyme that facilitate isomerization. Unlike most microsomal P450s, where large substrate-induced conformational changes take place at the distal side of the heme, conformational changes in PGIS are observed at the proximal side and in the heme itself. The conserved and extensive heme propionate-protein interactions seen in all other P450s, which are largely absent in the ligand-free PGIS, are recovered upon U51605 binding accompanied by water exclusion from the active site. In contrast, when minoxidil binds, the propionate-protein interactions are not recovered and water molecules are largely retained. These findings suggest that PGIS represents a divergent evolution of the P450 family, in which a heme barrier has evolved to ensure strict binding specificity for prostaglandin H2, leading to a radical-mediated isomerization with high product fidelity. The U51605-bound structure also provides a view of the substrate entrance and product exit channels. PMID:18032380

Mediating and/or moderating roles of psychological empowerment.

PubMed

Meng, Lina; Jin, Yi; Guo, Jiajia

2016-05-01

The purpose of this study was to explore the mediating and/or moderating effects of psychological empowerment in the relationship between structural empowerment and burnout among nurses in China. Burnout is prevalent among nurses. Previous studies have found that empowering organizational structures contribute to reduce nurses' burnout. However, little is known about the mediating or moderating role of psychological empowerment in the relationship between structural empowerment and burnout among nurses in China. A cross-sectional design was conducted. A total of 244 nurses participated in this study. The data were collected in March 2013. Multiple regressions were used to test the hypothesized models. Psychological empowerment was found to be a significant mediator of the relationship between structural empowerment and burnout (standardized β=-0.553, Sobel test: z=7.79, p<0.001). The moderating effect of psychological empowerment in that relationship was not verified. Both structural and psychological empowerment negatively correlated with burnout. The psychological empowerment had a mediating effect on burnout. It is important for nurse managers to develop strategies to ensure that empowering structures are in place and to facilitate nurses' perception of psychological empowerment. Copyright © 2015 Elsevier Inc. All rights reserved.

Propelling a water drop with the vapor-mediated Marangoni effect

NASA Astrophysics Data System (ADS)

Kim, Seungho; Kim, Ho-Young

2013-11-01

We show that a water drop on solid surfaces can be propelled just by placing a volatile alcohol drop nearby. It is found to be because the water-air interface near the alcohol drop mixes with alcohol vapor, thereby locally lowering the surface tension. The surface-tension-gradient induces the motion of the water drop, enabling the trajectory control of water drops through the motion of remote alcohol drops. This vapor-mediated Marangoni effect also gives rise to other interesting interfacial flow phenomena, such as nucleation of holes on a water film and ballooning of a water drop hanging from a syringe needle with the approach of an alcohol drop. We visualize such interfacial dynamics with a high-speed camera and rationalize their salient features by scaling analysis. This work was supported by the National Research Foundation of Korea (grant no. 2012-008023).

Variation in short-term and long-term responses of photosynthesis and isoprenoid-mediated photoprotection to soil water availability in four Douglas-fir provenances

PubMed Central

Junker, Laura Verena; Kleiber, Anita; Jansen, Kirstin; Wildhagen, Henning; Hess, Moritz; Kayler, Zachary; Kammerer, Bernd; Schnitzler, Jörg-Peter; Kreuzwieser, Jürgen; Gessler, Arthur; Ensminger, Ingo

2017-01-01

For long-lived forest tree species, the understanding of intraspecific variation among populations and their response to water availability can reveal their ability to cope with and adapt to climate change. Dissipation of excess excitation energy, mediated by photoprotective isoprenoids, is an important defense mechanism against drought and high light when photosynthesis is hampered. We used 50-year-old Douglas-fir trees of four provenances at two common garden experiments to characterize provenance-specific variation in photosynthesis and photoprotective mechanisms mediated by essential and non-essential isoprenoids in response to soil water availability and solar radiation. All provenances revealed uniform photoprotective responses to high solar radiation, including increased de-epoxidation of photoprotective xanthophyll cycle pigments and enhanced emission of volatile monoterpenes. In contrast, we observed differences between provenances in response to drought, where provenances sustaining higher CO2 assimilation rates also revealed increased water-use efficiency, carotenoid-chlorophyll ratios, pools of xanthophyll cycle pigments, β-carotene and stored monoterpenes. Our results demonstrate that local adaptation to contrasting habitats affected chlorophyll-carotenoid ratios, pool sizes of photoprotective xanthophylls, β-carotene, and stored volatile isoprenoids. We conclude that intraspecific variation in isoprenoid-mediated photoprotective mechanisms contributes to the adaptive potential of Douglas-fir provenances to climate change. PMID:28071755

Insect Responses to Linearly Polarized Reflections: Orphan Behaviors Without Neural Circuits.

PubMed

Heinloth, Tanja; Uhlhorn, Juliane; Wernet, Mathias F

2018-01-01

The e-vector orientation of linearly polarized light represents an important visual stimulus for many insects. Especially the detection of polarized skylight by many navigating insect species is known to improve their orientation skills. While great progress has been made towards describing both the anatomy and function of neural circuit elements mediating behaviors related to navigation, relatively little is known about how insects perceive non-celestial polarized light stimuli, like reflections off water, leaves, or shiny body surfaces. Work on different species suggests that these behaviors are not mediated by the "Dorsal Rim Area" (DRA), a specialized region in the dorsal periphery of the adult compound eye, where ommatidia contain highly polarization-sensitive photoreceptor cells whose receptive fields point towards the sky. So far, only few cases of polarization-sensitive photoreceptors have been described in the ventral periphery of the insect retina. Furthermore, both the structure and function of those neural circuits connecting to these photoreceptor inputs remain largely uncharacterized. Here we review the known data on non-celestial polarization vision from different insect species (dragonflies, butterflies, beetles, bugs and flies) and present three well-characterized examples for functionally specialized non-DRA detectors from different insects that seem perfectly suited for mediating such behaviors. Finally, using recent advances from circuit dissection in Drosophila melanogaster , we discuss what types of potential candidate neurons could be involved in forming the underlying neural circuitry mediating non-celestial polarization vision.

Urea-mediated protein denaturation: a consensus view.

PubMed

Das, Atanu; Mukhopadhyay, Chaitali

2009-09-24

We have performed all-atom molecular dynamics simulations of three structurally similar small globular proteins in 8 M urea and compared the results with pure aqueous simulations. Protein denaturation is preceded by an initial loss of water from the first solvation shell and consequent in-flow of urea toward the protein. Urea reaches the first solvation shell of the protein mainly due to electrostatic interaction with a considerable contribution coming from the dispersion interaction. Urea shifts the equilibrium from the native to denatured ensemble by making the protein-protein contact less stable than protein-urea contact, which is just the reverse of the condition in pure water, where protein-protein contact is more stable than protein-water contact. We have also seen that water follows urea and reaches the protein interior at later stages of denaturation, while urea preferentially and efficiently solvates different parts of the protein. Solvation of the protein backbone via hydrogen bonding, favorable electrostatic interaction with hydrophilic residues, and dispersion interaction with hydrophobic residues are the key steps through which urea intrudes the core of the protein and denatures it. Why urea is preferred over water for binding to the protein backbone and how urea orients itself toward the protein backbone have been identified comprehensively. All the key components of intermolecular forces are found to play a significant part in urea-induced protein denaturation and also toward the stability of the denatured state ensemble. Changes in water network/structure and dynamical properties and higher degree of solvation of the hydrophobic residues validate the presence of "indirect mechanism" along with the "direct mechanism" and reinforce the effect of urea on protein.

Microbialites and global environmental change across the Permian-Triassic boundary: a synthesis.

PubMed

Kershaw, S; Crasquin, S; Li, Y; Collin, P-Y; Forel, M-B; Mu, X; Baud, A; Wang, Y; Xie, S; Maurer, F; Guo, L

2012-01-01

Permian-Triassic boundary microbialites (PTBMs) are thin (0.05-15 m) carbonates formed after the end-Permian mass extinction. They comprise Renalcis-group calcimicrobes, microbially mediated micrite, presumed inorganic micrite, calcite cement (some may be microbially influenced) and shelly faunas. PTBMs are abundant in low-latitude shallow-marine carbonate shelves in central Tethyan continents but are rare in higher latitudes, likely inhibited by clastic supply on Pangaea margins. PTBMs occupied broadly similar environments to Late Permian reefs in Tethys, but extended into deeper waters. Late Permian reefs are also rich in microbes (and cements), so post-extinction seawater carbonate saturation was likely similar to the Late Permian. However, PTBMs lack widespread abundant inorganic carbonate cement fans, so a previous interpretation that anoxic bicarbonate-rich water upwelled to rapidly increase carbonate saturation of shallow seawater, post-extinction, is problematic. Preliminary pyrite framboid evidence shows anoxia in PTBM facies, but interbedded shelly faunas indicate oxygenated water, perhaps there was short-term pulsing of normally saturated anoxic water from the oxygen-minimum zone to surface waters. In Tethys, PTBMs show geographic variations: (i) in south China, PTBMs are mostly thrombolites in open shelf settings, largely recrystallised, with remnant structure of Renalcis-group calcimicrobes; (ii) in south Turkey, in shallow waters, stromatolites and thrombolites, lacking calcimicrobes, are interbedded, likely depth-controlled; and (iii) in the Middle East, especially Iran, stromatolites and thrombolites (calcimicrobes uncommon) occur in different sites on open shelves, where controls are unclear. Thus, PTBMs were under more complex control than previously portrayed, with local facies control playing a significant role in their structure and composition. © 2011 Blackwell Publishing Ltd.

Neural control of renal function: role of renal alpha adrenoceptors.

PubMed

DiBona, G F

1985-01-01

Adrenoceptors of various subtypes mediate the renal functional responses to alterations in efferent renal sympathetic nerve activity, the neural component, and renal arterial plasma catecholamine concentrations, the humoral component, of the sympathoadrenergic nervous system. Under normal physiologic as well as hypertensive conditions, the influence of the renal sympathetic nerves predominates over that of circulating plasma catecholamines. In most mammalian species, increases in efferent renal sympathetic nerve activity elicit renal vasoconstrictor responses mediated predominantly by renal vascular alpha-1 adrenoceptors, increases in renin release mediated largely by renal juxtaglomerular granular cell beta-1 adrenoceptors with involvement of renal vascular alpha-1 adrenoceptors only when renal vasoconstriction occurs, and direct increases in renal tubular sodium and water reabsorption mediated predominantly by renal tubular alpha-1 adrenoceptors. In most mammalian species, alpha-2 adrenoceptors do not play a significant role in the renal vascular or renin release responses to renal sympathoadrenergic stimulation. Although renal tubular alpha-2 adrenoceptors do not mediate the increases in renal tubular sodium and water reabsorption produced by increases in efferent renal sympathetic nerve activity, they may be involved through their inhibitory effect on adenylate cyclase in modulating the response to other hormonal agents that influence renal tubular sodium and water reabsorption via stimulation of adenylate cyclase.

Extending RosettaDock with water, sugar, and pH for prediction of complex structures and affinities for CAPRI rounds 20-27.

PubMed

Kilambi, Krishna Praneeth; Pacella, Michael S; Xu, Jianqing; Labonte, Jason W; Porter, Justin R; Muthu, Pravin; Drew, Kevin; Kuroda, Daisuke; Schueler-Furman, Ora; Bonneau, Richard; Gray, Jeffrey J

2013-12-01

Rounds 20-27 of the Critical Assessment of PRotein Interactions (CAPRI) provided a testing platform for computational methods designed to address a wide range of challenges. The diverse targets drove the creation of and new combinations of computational tools. In this study, RosettaDock and other novel Rosetta protocols were used to successfully predict four of the 10 blind targets. For example, for DNase domain of Colicin E2-Im2 immunity protein, RosettaDock and RosettaLigand were used to predict the positions of water molecules at the interface, recovering 46% of the native water-mediated contacts. For α-repeat Rep4-Rep2 and g-type lysozyme-PliG inhibitor complexes, homology models were built and standard and pH-sensitive docking algorithms were used to generate structures with interface RMSD values of 3.3 Å and 2.0 Å, respectively. A novel flexible sugar-protein docking protocol was also developed and used for structure prediction of the BT4661-heparin-like saccharide complex, recovering 71% of the native contacts. Challenges remain in the generation of accurate homology models for protein mutants and sampling during global docking. On proteins designed to bind influenza hemagglutinin, only about half of the mutations were identified that affect binding (T55: 54%; T56: 48%). The prediction of the structure of the xylanase complex involving homology modeling and multidomain docking pushed the limits of global conformational sampling and did not result in any successful prediction. The diversity of problems at hand requires computational algorithms to be versatile; the recent additions to the Rosetta suite expand the capabilities to encompass more biologically realistic docking problems. Copyright © 2013 Wiley Periodicals, Inc.

An ab initio molecular orbital study of the mechanism for the gas-phase water-mediated decomposition and the formation of hydrates of peroxyacetyl nitrate (PAN).

PubMed

Li, Yumin; Francisco, Joseph S

2005-08-31

There is uncertainty in the mechanism for the hydrolysis of peroxyacetyl nitrate (PAN), and experimental attempts to detect products of the direct reaction have been unsuccessful. Ab initio calculations are used to examine the energetics of water-mediated decomposition of gas-phase PAN into acetic acid and peroxynitric acid. On the basis of ab initio calculations, an alternative reaction mechanism for the decomposition of PAN is proposed. The calculations indicate that the barrier for one water addition to PAN is large. However, including additional water molecules reveals a substantially lower energy route. The calculations suggest that the formation of PAN hydrate complexes are energetically favorable and stable. Additional waters are increasingly efficient at stabilizing hydrated PAN.

Enhanced solar evaporation of water from porous media, through capillary mediated forces and surface treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canbazoglu, F. M.; Fan, B.; Kargar, A.

2016-08-15

The relative influence of the capillary, Marangoni, and hydrophobic forces in mediating the evaporation of water from carbon foam based porous media, in response to incident solar radiation, are investigated. It is indicated that inducing hydrophilic interactions on the surface, through nitric acid treatment of the foams, has a similar effect to reduced pore diameter and the ensuing capillary forces. The efficiency of water evaporation may be parameterized through the Capillary number (Ca), with a lower Ca being preferred. The proposed study is of much relevance to efficient solar energy utilization.

Ebullition, Plant-Mediated Transport, and Subsurface Horizontal Water Flow Dominate Methane Transport in an Arctic Sphagnum Bog

NASA Astrophysics Data System (ADS)

Wehr, R. A.; McCalley, C. K.; Logan, T. A.; Chanton, J.; Crill, P. M.; Rich, V. I.; Saleska, S. R.

2017-12-01

Emission of the greenhouse gas methane from wetlands is of prime concern in the prediction of climate change - especially emission associated with thawing permafrost, which may drive a positive feedback loop of emission and warming. In addition to the biochemistry of methane production and consumption, wetland methane emission depends critically on the transport mechanisms by which methane moves through and out of the ecosystem. We therefore developed a model of methane biochemistry and transport for a sphagnum bog representing an intermediate permafrost thaw stage in Stordalen Mire, Sweden. In order to simultaneously reproduce measured profiles of both the concentrations and isotopic compositions of both methane and carbon dioxide in the peat pore water (Fig. 1) - as well as the surface methane emission - it was necessary for the model to include ebullition, plant-mediated transport via aerenchyma, and subsurface horizontal water flow. Diffusion of gas through the pore water was relatively unimportant. As a result, 90% of the produced methane escaped the wetland rather than being consumed by methanotrophic organisms in the near-surface pore water. Our model provides a comprehensive picture of methane emission from this bog site by quantifying the vertical profiles of: acetoclastic methanogenesis, hydrogenotrophic methanogenesis, methane oxidation, aerobic respiration, ebullition, plant-mediated transport, subsurface horizontal water flow, and diffusion.

Organic extract contaminants from drinking water activate Nrf2-mediated antioxidant response in a human cell line.

PubMed

Wang, Shu; Zhang, Hao; Zheng, Weiwei; Wang, Xia; Andersen, Melvin E; Pi, Jingbo; He, Gengsheng; Qu, Weidong

2013-05-07

Traditional risk assessment methods face challenges in estimating risks from drinking waters that contain low-levels of large numbers of contaminants. Here, we evaluate the toxicity of organic contaminant (OC) extracts from drinking water by examining activation of nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant response. In HepG2 cells, the Nrf2-mediated antioxidant response-measured as Nrf2 protein accumulation, expression of antioxidant response element (ARE)-regulated genes and ARE-luciferase reporter gene assays were activated by OC extracts from drinking water sources that detected 25 compounds in 9 classification groups. Individual OCs induced oxidative stress at concentrations much higher than their environmental levels; however, mixtures of contaminants induced oxidative stress response at only 8 times the environmental levels. Additionally, a synthetic OC mixture prepared based on the contamination profiling of drinking water induced ARE activity to the same extent as the real-world mixture, reinforcing our conclusion that these mixture exposures produce responses relevant for human exposure situations. Our study tested the possibility of assessing toxicity of OCs of drinking water using a specific ARE-pathway measurement. This approach should be broadly useful in assisting risk assessment of mixed environmental exposure.

Mediation analysis with time varying exposures and mediators

PubMed Central

VanderWeele, Tyler J.; Tchetgen Tchetgen, Eric J.

2016-01-01

Summary In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the “mediational g-formula.” When there is no mediation, the mediational g-formula reduces to Robins’ regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl’s mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators. PMID:28824285

Mediation analysis with time varying exposures and mediators.

PubMed

VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

2017-06-01

In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

Employing a Structured Interface to Advance Primary Students' Communicative Competence in a Text-Based Computer Mediated Environment

ERIC Educational Resources Information Center

Chiu, Chiung-Hui; Wu, Chiu-Yi; Hsieh, Sheng-Jieh; Cheng, Hsiao-Wei; Huang, Chung-Kai

2013-01-01

This study investigated whether a structured communication interface fosters primary students' communicative competence in a synchronous typewritten computer-mediated collaborative learning environment. The structured interface provided a set of predetermined utterance patterns for elementary students to use or imitate to develop communicative…

Symbolic Instruments and the Internet Mediation of Knowledge and Expertise

ERIC Educational Resources Information Center

Johnson, Nicola F.

2014-01-01

In this chapter, I demonstrate how Bourdieu's (1991) notion of symbolic instruments, that is structured and structuring structures, can be applied to the Internet to demonstrate the mediation and construction of knowledge and validation of expertise. This qualitative pilot study explored the online language and interrelationship between expertise,…

Regulatory Focus as a Mediator of the Influence of Initiating Structure and Servant Leadership on Employee Behavior

ERIC Educational Resources Information Center

Neubert, Mitchell J.; Kacmar, K. Michele; Carlson, Dawn S.; Chonko, Lawrence B.; Roberts, James A.

2008-01-01

In this research, the authors test a model in which the regulatory focus of employees at work mediates the influence of leadership on employee behavior. In a nationally representative sample of 250 workers who responded over 2 time periods, prevention focus mediated the relationship of initiating structure to in-role performance and deviant…

Docking glycosaminoglycans to proteins: analysis of solvent inclusion

NASA Astrophysics Data System (ADS)

Samsonov, Sergey A.; Teyra, Joan; Pisabarro, M. Teresa

2011-05-01

Glycosaminoglycans (GAGs) are anionic polysaccharides, which participate in key processes in the extracellular matrix by interactions with protein targets. Due to their charged nature, accurate consideration of electrostatic and water-mediated interactions is indispensable for understanding GAGs binding properties. However, solvent is often overlooked in molecular recognition studies. Here we analyze the abundance of solvent in GAG-protein interfaces and investigate the challenges of adding explicit solvent in GAG-protein docking experiments. We observe PDB GAG-protein interfaces being significantly more hydrated than protein-protein interfaces. Furthermore, by applying molecular dynamics approaches we estimate that about half of GAG-protein interactions are water-mediated. With a dataset of eleven GAG-protein complexes we analyze how solvent inclusion affects Autodock 3, eHiTs, MOE and FlexX docking. We develop an approach to de novo place explicit solvent into the binding site prior to docking, which uses the GRID program to predict positions of waters and to locate possible areas of solvent displacement upon ligand binding. To investigate how solvent placement affects docking performance, we compare these results with those obtained by taking into account information about the solvent position in the crystal structure. In general, we observe that inclusion of solvent improves the results obtained with these methods. Our data show that Autodock 3 performs best, though it experiences difficulties to quantitatively reproduce experimental data on specificity of heparin/heparan sulfate disaccharides binding to IL-8. Our work highlights the current challenges of introducing solvent in protein-GAGs recognition studies, which is crucial for exploiting the full potential of these molecules for rational engineering.

A Quantitative Description of Suicide Inhibition of Dichloroacetic Acid in Rats and Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keys, Deborah A.; Schultz, Irv R.; Mahle, Deirdre A.

Dichloroacetic acid (DCA), a minor metabolite of trichloroethylene (TCE) and water disinfection byproduct, remains an important risk assessment issue because of its carcinogenic potency. DCA has been shown to inhibit its own metabolism by irreversibly inactivating glutathione transferase zeta (GSTzeta). To better predict internal dosimetry of DCA, a physiologically based pharmacokinetic (PBPK) model of DCA was developed. Suicide inhibition was described dynamically by varying the rate of maximal GSTzeta mediated metabolism of DCA (Vmax) over time. Resynthesis (zero-order) and degradation (first-order) of metabolic activity were described. Published iv pharmacokinetic studies in native rats were used to estimate an initial Vmaxmore » value, with Km set to an in vitro determined value. Degradation and resynthesis rates were set to estimated values from a published immunoreactive GSTzeta protein time course. The first-order inhibition rate, kd, was estimated to this same time course. A secondary, linear non-GSTzeta-mediated metabolic pathway is proposed to fit DCA time courses following treatment with DCA in drinking water. The PBPK model predictions were validated by comparing predicted DCA concentrations to measured concentrations in published studies of rats pretreated with DCA following iv exposure to 0.05 to 20 mg/kg DCA. The same model structure was parameterized to simulate DCA time courses following iv exposure in native and pretreated mice. Blood and liver concentrations during and postexposure to DCA in drinking water were predicted. Comparisons of PBPK model predicted to measured values were favorable, lending support for the further development of this model for application to DCA or TCE human health risk assessment.« less

Photodynamic therapy with fullerenes in vivo: reality or a dream?

PubMed

Sharma, Sulbha K; Chiang, Long Y; Hamblin, Michael R

2011-12-01

Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light that is absorbed by the chromophore to produce long-lived triplet states that can carry out photochemistry in the presence of oxygen to kill cells. The closed carbon-cage structure found in fullerenes can act as a photosensitizer, especially when functionalized to impart water solubility. Although there are reports of the use of fullerenes to carry out light-mediated destruction of viruses, microorganisms and cancer cells in vitro, the use of fullerenes to mediate PDT of diseases such as cancer and infections in animal models is less well developed. It has recently been shown that fullerene PDT can be used to save the life of mice with wounds infected with pathogenic Gram-negative bacteria. Fullerene PDT has also been used to treat mouse models of various cancers including disseminated metastatic cancer in the peritoneal cavity. In vivo PDT with fullerenes represents a new application in nanomedicine.

Simulating 2,368 temperate lakes reveals weak coherence in stratification phenology

USGS Publications Warehouse

Read, Jordan S.; Winslow, Luke A.; Hansen, Gretchen J. A.; Van Den Hoek, Jamon; Hanson, Paul C.; Bruce, Louise C; Markfort, Corey D.

2014-01-01

Changes in water temperatures resulting from climate warming can alter the structure and function of aquatic ecosystems. Lake-specific physical characteristics may play a role in mediating individual lake responses to climate. Past mechanistic studies of lake-climate interactions have simulated generic lake classes at large spatial scales or performed detailed analyses of small numbers of real lakes. Understanding the diversity of lake responses to climate change across landscapes requires a hybrid approach that couples site-specific lake characteristics with broad-scale environmental drivers. This study provides a substantial advancement in lake ecosystem modeling by combining open-source tools with freely available continental-scale data to mechanistically model daily temperatures for 2,368 Wisconsin lakes over three decades (1979-2011). The model accurately predicted observed surface layer temperatures (RMSE: 1.74°C) and the presence/absence of stratification (81.1% agreement). Among-lake coherence was strong for surface temperatures and weak for the timing of stratification, suggesting individual lake characteristics mediate some - but not all - ecologically relevant lake responses to climate.

Branch length mediates flower production and inflorescence architecture of Fouquieria splendens (ocotillo)

USGS Publications Warehouse

Bowers, Janice E.

2006-01-01

The capacity of individual branches to store water and fix carbon can have profound effects on inflorescence size and architecture, thus on floral display, pollination, and fecundity. Mixed regression was used to investigate the relation between branch length, a proxy for plant resources, and floral display of Fouquieria splendens (ocotillo), a woody, candelabraform shrub of wide distribution in arid North America. Long branches produced three times as many flowers as short branches, regardless of overall plant size. Long branches also had more complex panicles with more cymes and cyme types than short branches; thus, branch length also influenced inflorescence architecture. Within panicles, increasing the number of cymes by one unit added about two flowers, whereas increasing the number of cyme types by one unit added about 21 flowers. Because flower production is mediated by branch length, and because most plants have branches of various lengths, the floral display of individual plants necessarily encompasses a wide range of inflorescence size and structure. ?? Springer 2006.

Synthesis and characterization of boric acid mediated metal-organic frameworks based on trimesic acid and terephthalic acid

NASA Astrophysics Data System (ADS)

Ozer, Demet; Köse, Dursun A.; Şahin, Onur; Oztas, Nursen Altuntas

2017-08-01

The new metal-organic framework materials based on boric acid reported herein. Sodium and boron containing metal-organic frameworks were synthesized by one-pot self-assembly reaction in the presence of trimesic acid and terephthalic acid in water/ethanol solution. Boric acid is a relatively cheap boron source and boric acid mediated metal-organic framework prepared mild conditions compared to the other boron source based metal-organic framework. The synthesized compounds were characterized by FT-IR, p-XRD, TGA/DTA, elemental analysis, 13C-MAS NMR, 11B-NMR and single crystal measurements. The molecular formulas of compounds were estimated as C18H33B2Na5O28 and C8H24B2Na2O17 according to the structural analysis. The obtained complexes were thermally stable. Surface properties of inorganic polymer complexes were investigated by BET analyses and hydrogen storage properties of compound were also calculated.

Hydration of protein–RNA recognition sites

PubMed Central

Barik, Amita; Bahadur, Ranjit Prasad

2014-01-01

We investigate the role of water molecules in 89 protein–RNA complexes taken from the Protein Data Bank. Those with tRNA and single-stranded RNA are less hydrated than with duplex or ribosomal proteins. Protein–RNA interfaces are hydrated less than protein–DNA interfaces, but more than protein–protein interfaces. Majority of the waters at protein–RNA interfaces makes multiple H-bonds; however, a fraction do not make any. Those making H-bonds have preferences for the polar groups of RNA than its partner protein. The spatial distribution of waters makes interfaces with ribosomal proteins and single-stranded RNA relatively ‘dry’ than interfaces with tRNA and duplex RNA. In contrast to protein–DNA interfaces, mainly due to the presence of the 2′OH, the ribose in protein–RNA interfaces is hydrated more than the phosphate or the bases. The minor groove in protein–RNA interfaces is hydrated more than the major groove, while in protein–DNA interfaces it is reverse. The strands make the highest number of water-mediated H-bonds per unit interface area followed by the helices and the non-regular structures. The preserved waters at protein–RNA interfaces make higher number of H-bonds than the other waters. Preserved waters contribute toward the affinity in protein–RNA recognition and should be carefully treated while engineering protein–RNA interfaces. PMID:25114050

Performance improvement of IPMC flow sensors with a biologically-inspired cupula structure

NASA Astrophysics Data System (ADS)

Lei, Hong; Sharif, Montassar Aidi; Paley, Derek A.; McHenry, Matthew J.; Tan, Xiaobo

2016-04-01

Ionic polymer-metal composites (IPMCs) have inherent underwater sensing and actuation properties. They can be used as sensors to collect flow information. Inspired by the hair-cell mediated receptor in the lateral line system of fish, the impact of a flexible, cupula-like structure on the performance of IPMC flow sensors is experimentally explored. The fabrication method to create a silicone-capped IPMC sensor is reported. Experiments are conducted to compare the sensing performance of the IPMC flow sensor before and after the PDMS coating under the periodic flow stimulus generated by a dipole source in still water and the laminar flow stimulus generated in a flow tank. Experimental results show that the performance of IPMC flow sensors is significantly improved under the stimulus of both periodic flow and laminar flow by the proposed silicone-capping.

Chemical cues from fish heighten visual sensitivity in larval crabs through changes in photoreceptor structure and function.

PubMed

Charpentier, Corie L; Cohen, Jonathan H

2015-11-01

Several predator avoidance strategies in zooplankton rely on the use of light to control vertical position in the water column. Although light is the primary cue for such photobehavior, predator chemical cues or kairomones increase swimming responses to light. We currently lack a mechanistic understanding for how zooplankton integrate visual and chemical cues to mediate phenotypic plasticity in defensive photobehavior. In marine systems, kairomones are thought to be amino sugar degradation products of fish body mucus. Here, we demonstrate that increasing concentrations of fish kairomones heightened sensitivity of light-mediated swimming behavior for two larval crab species (Rhithropanopeus harrisii and Hemigrapsus sanguineus). Consistent with these behavioral results, we report increased visual sensitivity at the retinal level in larval crab eyes directly following acute (1-3 h) kairomone exposure, as evidenced electrophysiologically from V-log I curves and morphologically from wider, shorter rhabdoms. The observed increases in visual sensitivity do not correspond with a decline in temporal resolution, because latency in electrophysiological responses actually increased after kairomone exposure. Collectively, these data suggest that phenotypic plasticity in larval crab photobehavior is achieved, at least in part, through rapid changes in photoreceptor structure and function. © 2015. Published by The Company of Biologists Ltd.

Bile Salt Mediated Growth of Reverse Wormlike Micelles in Nonpolar Liquids

NASA Astrophysics Data System (ADS)

Tung, Shih-Huang; Huang, Yi-En; Raghavan, Srinivasa

2006-03-01

We report the growth of reverse wormlike micelles induced by the addition of a bile salt in trace amounts to solutions of the phospholipid, lecithin in nonpolar organic solvents. Previous recipes for reverse wormlike micelles have usually required the addition of water to induce reverse micellar growth; here, we show that bile salts, due to their unique ``facially amphiphilic'' structure, can play a role analogous to water and promote the longitudinal aggregation of lecithin molecules into reverse micellar chains. The formation of transient entangled networks of these reverse micelles transforms low-viscosity lecithin organosols into strongly viscoelastic fluids. The zero-shear viscosity increases by more than five orders of magnitude, and it is the molar ratio of bile salt to lecithin that controls this viscosity enhancement. The growth of reverse wormlike micelles is also confirmed by small-angle neutron scattering (SANS) experiments on these fluids.

Water-Network Mediated, Electron Induced Proton Transfer in Anionic [C5H5N\\cdot(H2O)n]- Clusters: Size Dependent Formation of the Pyridinium Radical for n ≥ 3

NASA Astrophysics Data System (ADS)

DeBlase, Andrew F.; Weddle, Gary H.; Archer, Kaye A.; Jordan, Kenneth D.; Johnson, Mark

2015-06-01

As an isolated species, the radical anion of pyridine (Py-) exists as an unstable transient negative ion, while in aqueous environments it is known to undergo rapid protonation to form the neutral pyridinium radical [PyH(0)] along with hydroxide. Furthermore, the negative adiabatic electron affinity (AEA) of Py- can become diminished by the solvation energy associated with cluster formation. In this work, we focus on the hydrates [Py\\cdot(H2O)n]- with n = 3-5 and elucidate the structures of these water clusters using a combination of vibrational predissociation and photoelectron spectroscopies. We show that H-trasfer to form PyH(0) occurs in these clusters by the infrared signature of the nascent hydroxide ion and by the sharp bending vibrations of aromatic ring CH bending.

Design and Development of Mixed-Metal Oxide Photocatalysts: the Band Engineering Approach

NASA Astrophysics Data System (ADS)

Boltersdorf, Jonathan Andrew

The design and development of mixed-metal oxides incorporating Ag(I), Pb(II), Sn(II), and Bi(III), i.e., with filled d10 or d10s2 electron configurations, have yielded new approaches to tune optical and photocatalytic properties for solar energy conversion. My research efforts in the area of solid-state photochemistry have focused on utilizing flux-mediated ion-exchange methods in conjunction with the band engineering approach to synthesize new materials for solar energy driven total water splitting. Layered perovskite phases and the polysomatic family of tantalate/niobate structures, with the general formula Am+ ( n+1)/mB(3 n+1)O(8n +3) (A = Na, Ag; B = Ta, Nb), have received increasing attention owing to their synthetic flexibility, tunable optical band gaps, and photocatalytic activities for total water splitting. Structures in the family of A m+ (n+1)/ mB(3n +1)O(8n+3) structures are based on the stacking of pentagonal bipyramidal layers, where n defines the average thickness (1 ≤ n ≤ 2) of the BO7 layers that alternate with isolated BO6 octahedra surrounded by A-site cations. Synthetic limitations in the discovery of new phases within the layered perovskites and the Am + (n+1)/mB(3 n+1)O(8n +3) structural families can be addressed with the aid of a metal-salt solvent, known as the molten-salt flux method. The flux synthetic route requires the use of an inorganic salt heated above its melting temperature in order to serve as a solvent system for crystallization. Molten fluxes allow for synthetic modification of particle characteristics and can enable the low temperature stabilization of new compositions and phases with limited stability using ion-exchange reactions (e.g., PbTa4O11, AgLaNb 2O7). Solid-state and flux-mediated exchange methods were utilized in order to synthetically explore and investigate the layered perovskites ALaNb2O7, AA2Nb3O 10, A'2La2Ti3O10 (A' = Rb, Ag; A = Ca, Sr), the Am+ (n+1)/mB 3n+1O(8 n+3) structural family (Am + = Na(I), Ag(I), Pb(II), Sn(II), Bi(III); B = Ta, Nb), Pb3Ta 4O13, PbTa2O6, Bi7Ta 3O18, and Sn2TiO4. The impact of the dimensionality of the structural features on the photocatalytic activities of the metal-oxides will be examined. A comparison of the influence of Ag(I), Pb(II), Sn(II), and Bi(III) cations in combination with Ti(IV), Nb(V), and Ta(V) cations on the optical properties and photocatalytic rates of the mixed-metal oxides will be presented. The results of these investigations have led to new insights into synthetic strategies for the development of new metal-oxide photocatalysts, which have aided in understanding the effects of transition and post-transition metals, structural features, and flux-mediated synthesis methods on the optical and photocatalytic properties of metal oxides for solar fuel production.

[Analysis of heavy-metal-mediated disease and development of a novel remediation system based on fieldwork and experimental research].

PubMed

Yajima, Ichiro; Zou, Cunchao; Li, Xiang; Nakano, Chizuru; Omata, Yasuhiro; Kumasaka, Mayuko Y

2015-01-01

Heavy-metal pollution occurs in various environments, including water, air and soil, and has serious effects on human health. Since heavy-metal pollution in drinking water causes various diseases including skin cancer, it has become a global problem worldwide. However, there is limited information on the mechanism of development of heavy-metal-mediated disease. We performed both fieldwork and experimental studies to elucidate the levels of heavy-metal pollution and mechanisms of development of heavy-metal-related disease and to develop a novel remediation system. Our fieldwork in Bangladesh, Vietnam and Malaysia demonstrated that drinking well water in these countries was polluted with high concentrations of several heavy metals including arsenic, barium, iron and manganese. Our experimental studies based on the data from our fieldwork demonstrated that these heavy metals caused skin cancer and hearing loss. Further experimental studies resulted in the development of a novel remediation system with which toxic heavy metals were absorbed from polluted drinking water. Implementation of both fieldwork and experimental studies is important for prediction, prevention and therapy of heavy-metal-mediated diseases.

Water-Mediated Proton Hopping on an Iron Oxide Surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Merte, L. R.; Peng, Guowen; Bechstein, Ralf

2012-05-18

The diffusion of hydrogen atoms across solid oxide surfaces is often assumed to be accelerated by the presence of water molecules. Here we present a high-resolution, high-speed scanning tunneling microscopy (STM) study of the diffusion of H atoms on an FeO thin film. STM movies directly reveal a water-mediated hydrogen diffusion mechanism on the oxide surface at temperatures between 100 and 300 kelvin. Density functional theory calculations and isotope-exchange experiments confirm the STM observations, and a proton-transfer mechanism that proceeds via an H3O+-like transition state is revealed. This mechanism differs from that observed previously for rutile TiO2(110), where water dissociationmore » is a key step in proton diffusion.« less

Microelectrode-based technology for the detection of low levels of bacteria

NASA Technical Reports Server (NTRS)

Rogers, Tom D.; Hitchens, G. D.; Mishra, S. K.; Pierson, D. L.

1992-01-01

A microelectrode-based electrochemical detection method was used for quantitation of bacteria in water samples. The redox mediator, benzoquinone, was used to accept electrons from the bacterial metabolic pathway to create a flow of electrons by reducing the mediator. Electrochemical monitoring electrodes detected the reduced mediator as it diffused out of the cells and produced a small electrical current. By using a combination of microelectrodes and monitoring instrumentation, the cumulative current generated by a particular bacterial population could be monitored. Using commercially available components, an electrochemical detection system was assembled and tested to evaluate its potential as an emerging technology for rapid detection and quantitation of bacteria in water samples.

Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells.

PubMed

Yajima, Ichiro; Uemura, Noriyuki; Nizam, Saika; Khalequzzaman, Md; Thang, Nguyen D; Kumasaka, Mayuko Y; Akhand, Anwarul A; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

2012-06-01

Our fieldwork showed more than 1 μM (145.1 μg/L) barium in about 3 μM (210.7 μg/L) arsenic-polluted drinking well water (n = 72) in cancer-prone areas in Bangladesh, while the mean concentrations of nine other elements in the water were less than 3 μg/L. The types of cancer include squamous cell carcinomas (SCC). We hypothesized that barium modulates arsenic-mediated biological effects, and we examined the effect of barium (1 μM) on arsenic (3 μM)-mediated apoptotic cell death of human HSC-5 and A431 SCC cells in vitro. Arsenic promoted SCC apoptosis with increased reactive oxygen species (ROS) production and JNK1/2 and caspase-3 activation (apoptotic pathway). In contrast, arsenic also inhibited SCC apoptosis with increased NF-κB activity and X-linked inhibitor of apoptosis protein (XIAP) expression level and decreased JNK activity (antiapoptotic pathway). These results suggest that arsenic bidirectionally promotes apoptotic and antiapoptotic pathways in SCC cells. Interestingly, barium in the presence of arsenic increased NF-κB activity and XIAP expression and decreased JNK activity without affecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer effect of arsenic is mainly dependent on cancer apoptosis, barium-mediated inhibition of arsenic-induced apoptosis may promote progression of SCC in patients in Bangladesh who keep drinking barium and arsenic-polluted water after the development of cancer. Thus, we newly showed that barium in the presence of arsenic might inhibit arsenic-mediated cancer apoptosis with the modulation of the balance between arsenic-mediated promotive and suppressive apoptotic pathways.

Relative lipophilicities and structural-pharmacological considerations of various angiotensin-converting enzyme (ACE) inhibitors.

PubMed

Ranadive, S A; Chen, A X; Serajuddin, A T

1992-11-01

Lipophilicities of seven structurally diverse angiotensin-converting enzyme (ACE) inhibitors, viz., captopril, zofenoprilat, enalaprilat, ramiprilat, lisinopril, fosinoprilat, and ceronapril (SQ29852), were compared by determining their octanol-water distribution coefficients (D) under physiological pH conditions. The distribution co-efficients of zofenopril, enalapril, ramipril and fosinopril, which are the prodrug forms of zofenoprilat, enalaprilat, ramiprilat, and fosinoprilat, respectively, were also determined. Attempts were made to correlate lipophilicities with the reported data for oral absorption, protein binding, ACE inhibitory activity, propensity for biliary excretion, and penetration across the blood-brain barrier for these therapeutic entities. Better absorption of prodrugs compared to their respective active forms is in agreement with their greater lipophilicities. Captopril, lisinopril, and ceronapril are orally well absorbed despite their low lipophilicities, suggesting involvement of other factors such as a carrier-mediated transport process. Of all the compounds studied, the two most lipophilic ACE inhibitors, fosinoprilat and zofenoprilat, exhibit a rank-order correlation with respect to biliary excretion. This may explain the dual routes of elimination (renal and hepatic) observed with fosinoprilat in humans. The more lipophilic compounds also exhibit higher protein binding. Both the lipophilicity and a carrier-mediated process may be involved in penetration of some of these drugs into brain. For structurally similar compounds, in vitro ACE inhibitory activity increased with the increase in lipophilicity. However, no clear correlation between lipophilicity and ACE inhibitory activity emerged when different types of inhibitors are compared, possibly because their interactions with enzymes are primarily ionic in nature.

The Antimicrobial Properties of Silver Nanoparticles in Bacillus subtilis Are Mediated by Released Ag+ Ions

PubMed Central

Hsueh, Yi-Huang; Lin, Kuen-Song; Ke, Wan-Ju; Hsieh, Chien-Te; Chiang, Chao-Lung; Tzou, Dong-Ying; Liu, Shih-Tung

2015-01-01

The superior antimicrobial properties of silver nanoparticles (Ag NPs) are well-documented, but the exact mechanisms underlying Ag-NP microbial toxicity remain the subject of intense debate. Here, we show that Ag-NP concentrations as low as 10 ppm exert significant toxicity against Bacillus subtilis, a beneficial bacterium ubiquitous in the soil. Growth arrest and chromosomal DNA degradation were observed, and flow cytometric quantification of propidium iodide (PI) staining also revealed that Ag-NP concentrations of 25 ppm and above increased membrane permeability. RedoxSensor content analysis and Phag-GFP expression analysis further indicated that reductase activity and cytosolic protein expression decreased in B. subtilis cells treated with 10–50 ppm of Ag NPs. We conducted X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analyses to directly clarify the valence and fine structure of Ag atoms in B. subtilis cells placed in contact with Ag NPs. The results confirmed the Ag species in Ag NP-treated B. subtilis cells as Ag2O, indicating that Ag-NP toxicity is likely mediated by released Ag+ ions from Ag NPs, which penetrate bacterial cells and are subsequently oxidized intracellularly to Ag2O. These findings provide conclusive evidence for the role of Ag+ ions in Ag-NP microbial toxicity, and suggest that the impact of inappropriately disposed Ag NPs to soil and water ecosystems may warrant further investigation. PMID:26669836

Biological forcing controls the chemistry of reef-building coral skeleton

NASA Astrophysics Data System (ADS)

Meibom, Anders; Mostefaoui, Smail; Cuif, Jean-Pierre; Dauphin, Yannicke; Houlbreque, Fanny; Dunbar, Robert; Constantz, Brent

2007-01-01

We present analyses of major elements C and Ca and trace elements N, S, Mg and Sr in a Porites sp. exoskeleton with a spatial resolution better than ˜150 nm. Trace element variations are evaluated directly against the ultra-structure of the skeleton and are ascribed to dynamic biological forcing. Individual growth layers in the bulk fibrous aragonite skeleton form on sub-daily timescales. Magnesium concentration variations are dramatically correlated with the growth layers, but are uncorrelated with Sr concentration variations. Observed (sub)seasonal relationships between water temperature and skeletal trace-element chemistry are secondary, mediated by sensitive biological processes to which classical thermodynamic formalism does not apply.

Structure of a Complete Mediator-RNA Polymerase II Pre-Initiation Complex.

PubMed

Robinson, Philip J; Trnka, Michael J; Bushnell, David A; Davis, Ralph E; Mattei, Pierre-Jean; Burlingame, Alma L; Kornberg, Roger D

2016-09-08

A complete, 52-protein, 2.5 million dalton, Mediator-RNA polymerase II pre-initiation complex (Med-PIC) was assembled and analyzed by cryo-electron microscopy and by chemical cross-linking and mass spectrometry. The resulting complete Med-PIC structure reveals two components of functional significance, absent from previous structures, a protein kinase complex and the Mediator-activator interaction region. It thereby shows how the kinase and its target, the C-terminal domain of the polymerase, control Med-PIC interaction and transcription. Copyright © 2016 Elsevier Inc. All rights reserved.

Variation in short-term and long-term responses of photosynthesis and isoprenoid-mediated photoprotection to soil water availability in four Douglas-fir provenances

DOE PAGES

Junker, Laura Verena; Kleiber, Anita; Jansen, Kirstin; ...

2017-01-10

For long-lived forest tree species, the understanding of intraspecific variation among populations and their response to water availability can reveal their ability to cope with and adapt to climate change. Dissipation of excess excitation energy, mediated by photoprotective isoprenoids, is an important defense mechanism against drought and high light when photosynthesis is hampered. We used 50-year-old Douglas-fir trees of four provenances at two common garden experiments to characterize provenance-specific variation in photosynthesis and photoprotective mechanisms mediated by essential and non-essential isoprenoids in response to soil water availability and solar radiation. All provenances revealed uniform photoprotective responses to high solar radiation,more » including increased de-epoxidation of photoprotective xanthophyll cycle pigments and enhanced emission of volatile monoterpenes. In contrast, we observed differences between provenances in response to drought, where provenances sustaining higher CO2 assimilation rates also revealed increased water-use efficiency, carotenoid-chlorophyll ratios, pools of xanthophyll cycle pigments, β-carotene and stored monoterpenes. Our results demonstrate that local adaptation to contrasting habitats affected chlorophyll-carotenoid ratios, pool sizes of photoprotective xanthophylls, β-carotene, and stored volatile isoprenoids. We conclude that intraspecific variation in isoprenoid-mediated photoprotective mechanisms contributes to the adaptive potential of Douglas-fir provenances to climate change.« less

Variation in short-term and long-term responses of photosynthesis and isoprenoid-mediated photoprotection to soil water availability in four Douglas-fir provenances

DOE Office of Scientific and Technical Information (OSTI.GOV)

Junker, Laura Verena; Kleiber, Anita; Jansen, Kirstin

For long-lived forest tree species, the understanding of intraspecific variation among populations and their response to water availability can reveal their ability to cope with and adapt to climate change. Dissipation of excess excitation energy, mediated by photoprotective isoprenoids, is an important defense mechanism against drought and high light when photosynthesis is hampered. We used 50-year-old Douglas-fir trees of four provenances at two common garden experiments to characterize provenance-specific variation in photosynthesis and photoprotective mechanisms mediated by essential and non-essential isoprenoids in response to soil water availability and solar radiation. All provenances revealed uniform photoprotective responses to high solar radiation,more » including increased de-epoxidation of photoprotective xanthophyll cycle pigments and enhanced emission of volatile monoterpenes. In contrast, we observed differences between provenances in response to drought, where provenances sustaining higher CO2 assimilation rates also revealed increased water-use efficiency, carotenoid-chlorophyll ratios, pools of xanthophyll cycle pigments, β-carotene and stored monoterpenes. Our results demonstrate that local adaptation to contrasting habitats affected chlorophyll-carotenoid ratios, pool sizes of photoprotective xanthophylls, β-carotene, and stored volatile isoprenoids. We conclude that intraspecific variation in isoprenoid-mediated photoprotective mechanisms contributes to the adaptive potential of Douglas-fir provenances to climate change.« less

Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOSmore » and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced vascular dysfunction. • Arsenic reduced ACh-induced aortic relaxation but didn’t alter response to SNP and PE. • Arsenic affected aortic NO signalling and production of inflammatory mediators. • Arsenic produced vasculopathic lesions in aorta. • Atorvastatin restored arsenic-induced functional, biochemical and structural changes.« less

Depressive symptoms, lifestyle structure, and ART adherence among HIV-infected individuals: a longitudinal mediation analysis.

PubMed

Magidson, Jessica F; Blashill, Aaron J; Safren, Steven A; Wagner, Glenn J

2015-01-01

Despite the well-documented relationship between depression and antiretroviral therapy (ART) nonadherence, few studies have identified explanatory pathways through which depression affects adherence. The current study tested lifestyle structure-the degree of organization and routinization of daily activities-as a mediator of this relationship, given previous evidence of lifestyle structure being associated with both depression and ART nonadherence. HIV-infected individuals starting or re-starting ART in the California Collaborative Treatment Group 578 study (n = 199) were assessed over 48 weeks. Adherence was measured using electronic monitoring caps to determine dose timing and doses taken, and viral load was assessed. The mediating role of lifestyle structure was tested using generalized linear mixed-effects modeling and bootstrapping. Lifestyle significantly mediated the relationship between depression and both measures of ART adherence behavior. Interventions that minimize disruptions to lifestyle structure and link adherence to daily activities may be useful for individuals with depression and ART nonadherence.

Facile preparation of raisin-bread sandwich-structured magnetic graphene/mesoporous silica composites with C18-modified pore-walls for efficient enrichment of phthalates in environmental water.

PubMed

Huang, Danni; Wang, Xianying; Deng, Chunhui; Song, Guoxin; Cheng, Hefa; Zhang, Xiangmin

2014-01-17

In this study, novel raisin-bread sandwich-structured magnetic graphene/mesoporous silica composites with C18-modified interior pore-walls (mag-graphene@mSiO2-C18) were synthesized by coating mesoporous silica layers onto each side of magnetic graphene through a surfactant-mediated co-condensation sol-gel process. The prepared functionalized nanocomposites possessed marvelous properties of extended plate-like morphology, fine water dispersibility, high magnetic response, large surface area (315.4cm(2)g(-1)), uniform pore size (3.3nm) and C18-modified interior pore-walls. Several kinds of phthalates were selected as model analytes to systematically evaluate the performance of adsorbents in extracting hydrophobic molecules followed by gas chromatography-mass spectrometry analyses. Various extraction parameters, including pH value of sample solution, amounts of adsorbents, adsorption time, species and volume of eluting solvent, and desorption time were optimized. The anti-interference ability to macromolecular proteins was also investigated. Method validations such as linearity, recovery, reproducibility, and limit of detection were also studied. Finally, mag-graphene@mSiO2-C18 composites were successfully applied to analyzing phthalates in environmental water samples. The results indicated that this novel approach offered an attractive alternative for rapid, convenient, efficient and selective magnetic solid-phase extraction for targeted hydrophobic compounds. Copyright © 2013 Elsevier B.V. All rights reserved.

Community Structural Instability, Anomie, Imitation and Adolescent Suicidal Behavior

ERIC Educational Resources Information Center

Thorlindsson, Thorolfur; Bernburg, Jon Gunnar

2009-01-01

The current study examines the contextual effects of community structural characteristics, as well as the mediating role of key social mechanisms, on youth suicidal behavior in Iceland. We argue that the contextual influence of community structural instability on youth suicidal behavior should be mediated by weak attachment to social norms and…

Structural, spectroscopic and DFT study of 4-methoxybenzohydrazide Schiff bases. A new series of polyfunctional ligands.

PubMed

Ferraresi-Curotto, Verónica; Echeverría, Gustavo A; Piro, Oscar E; Pis-Diez, Reinaldo; González-Baró, Ana C

2015-02-25

Five Schiff bases obtained from condensation of 4-methoxybenzohydrazide with related aldehydes, namely o-vanillin, vanillin, 5-bromovanillin, 5-chlorosalicylaldehyde and 5-bromosalicylaldehyde were prepared. A detailed structural and spectroscopic study is reported. The crystal structures of four members of the family were determined and compared with one another. The hydrazones obtained from 5-chlorosalicylaldehyde and 5-bromosalicylaldehyde resulted to be isomorphic to each other. The solid-state structures are stabilized by intra-molecular O-H⋯N interactions in salicylaldehyde derivatives between the O-H moiety from the aldehyde and the hydrazone nitrogen atom. All crystals are further stabilized by inter-molecular H-bonds mediated by the crystallization water molecule. A comparative analysis between experimental and theoretical results is presented. The conformational space was searched and geometries were optimized both in gas phase and including solvent effects. The structure is predicted for the compound for which the crystal structure was not determined. Infrared and electronic spectra were measured and assigned with the help of data obtained from computational methods based on the Density Functional Theory. Copyright © 2014 Elsevier B.V. All rights reserved.

Students' Conceptions of Water Transport

ERIC Educational Resources Information Center

Rundgren, Carl-Johan; Rundgren, Shu-Nu Chang; Schonborn, Konrad J.

2010-01-01

Understanding diffusion of water into and out of the cell through osmosis is fundamental to the learning and teaching of biology. Although this process is thought of as occurring directly across the lipid bilayer, the majority of water transport is actually mediated by specialised transmembrane water-channels called aquaporins. This study…

Blinded by the light? Nearshore energy pathway coupling and relative predator biomass increase with reduced water transparency across lakes.

PubMed

Tunney, Tyler D; McCann, Kevin S; Jarvis, Lauren; Lester, Nigel P; Shuter, Brian J

2018-04-01

Habitat coupling is a concept that refers to consumer integration of resources derived from different habitats. This coupling unites fundamental food web pathways (e.g., cross-habitat trophic linkages) that mediate key ecological processes such as biomass flows, nutrient cycling, and stability. We consider the influence of water transparency, an important environmental driver in aquatic ecosystems, on habitat coupling by a light-sensitive predator, walleye (Sander vitreus), and its prey in 33 Canadian lakes. Our large-scale, across-lake study shows that the contribution of nearshore carbon (δ 13 C) relative to offshore carbon (δ 13 C) to walleye is higher in less transparent lakes. To a lesser degree, the contribution of nearshore carbon increased with a greater proportion of prey in nearshore compared to offshore habitats. Interestingly, water transparency and habitat coupling predict among-lake variation in walleye relative biomass. These findings support the idea that predator responses to changing conditions (e.g., water transparency) can fundamentally alter carbon pathways, and predator biomass, in aquatic ecosystems. Identifying environmental factors that influence habitat coupling is an important step toward understanding spatial food web structure in a changing world.

Industrial water pollution, water environment treatment, and health risks in China.

PubMed

Wang, Qing; Yang, Zhiming

2016-11-01

The negative health effects of water pollution remain a major source of morbidity and mortality in China. The Chinese government is making great efforts to strengthen water environment treatment; however, no studies have evaluated the effects of water treatment on human health by water pollution in China. This study evaluated the association between water pollution and health outcomes, and determined the extent to which environmental regulations on water pollution may lead to health benefits. Data were extracted from the 2011 and 2013 China Health and Retirement Longitudinal Study (CHARLS). Random effects model and random effects Logit model were applied to study the relationship between health and water pollution, while a Mediator model was used to estimate the effects of environmental water treatment on health outcomes by the intensity of water pollution. Unsurprisingly, water pollution was negatively associated with health outcomes, and the common pollutants in industrial wastewater had differential impacts on health outcomes. The effects were stronger for low-income respondents. Water environment treatment led to improved health outcomes among Chinese people. Reduced water pollution mediated the associations between water environment treatment and health outcomes. The results of this study offer compelling evidence to support treatment of water pollution in China. Copyright © 2016 Elsevier Ltd. All rights reserved.

Highly efficient water-mediated approach to access benzazoles: metal catalyst and base-free synthesis of 2-substituted benzimidazoles, benzoxazoles, and benzothiazoles.

PubMed

Bala, Manju; Verma, Praveen Kumar; Sharma, Deepika; Kumar, Neeraj; Singh, Bikram

2015-05-01

An efficient water-catalyzed method has been developed for the synthesis of 2-substituted benzimidazoles, benzoxazoles, and benzothiazoles in one step. The present method excludes the usage of toxic metal catalysts and bases to produce benzazoles in good to excellent yields. An efficient and versatile water-mediated method has been established for the synthesis of various 2-arylbenzazoles. The present protocol excludes the usage of any catalyst and additive provided excellent selectivities and yields with high functional group tolerance for the synthesis of 2-arylated benzimidazoles, benzoxazoles, and benzothiazoles. Benzazolones were also synthesized using similar reaction protocol.

Arbuscular mycorrhizal mediation of biomass-density relationship of Medicago sativa L. under two water conditions in a field experiment.

PubMed

Zhang, Qian; Xu, Liming; Tang, Jianjun; Bai, Minge; Chen, Xin

2011-05-01

The biomass-density relationship (whereby the biomass of individual plants decreases as plant density increases) has generally been explained by competition for resources. Arbuscular mycorrhizal fungi (AMF) are able to affect plant interactions by mediating resource utilization, but whether this AMF-mediated interaction will change the biomass-density relationship is unclear. We conducted an experiment to test the hypothesis that AMF will shift the biomass-density relationship by affecting intraspecific competition. Four population densities (10, 100, 1,000, or 10,000 seedlings per square meter) of Medicago sativa L. were planted in field plots. Water application (1,435 or 327.7 mm/year) simulated precipitation in wet areas (sufficient water) and arid areas (insufficient water). The fungicide benomyl was applied to suppress AMF in some plots ("low-AMF" treatment) and not in others ("high-AMF" treatment). The effect of the AMF treatment on the biomass-density relationship depended on water conditions. High AMF enhanced the decrease of individual biomass with increasing density (the biomass-density line had a steeper slope) when water was sufficient but not when water was insufficient. AMF treatment did not affect plant survival rate or population size but did affect absolute competition intensity (ACI). When water was sufficient, ACI was significantly higher in the high-AMF treatment than in the low-AMF treatment, but ACI was unaffected by AMF treatment when water was insufficient. Our results suggest that AMF status did not impact survival rate and population size but did shift the biomass-density relationship via effects on intraspecific competition. This effect of AMF on the biomass-density relationship depended on the availability of water.

A Waterborne Pursuit-Deterrent Signal Deployed by a Sea Urchin.

PubMed

Sheppard-Brennand, Hannah; Poore, Alistair G B; Dworjanyn, Symon A

2017-06-01

Selection by consumers has led to the evolution of a vast array of defenses in animals and plants. These defenses include physical structures, behaviors, and chemical signals that mediate interactions with predators. Some of the strangest defensive structures in nature are the globiferous pedicellariae of the echinoderms. These are small venomous appendages with jaws and teeth that cover the test of many sea urchins and sea stars. In this study, we report a unique use of these defensive structures by the collector sea urchin Tripneustes gratilla. In both the laboratory and the field, globiferous pedicellariae were unpalatable to fish consumers. When subject to simulated predator attack, sea urchins released a cloud of pedicellaria heads into the water column. Flume experiments established the presence of a waterborne cue associated with this release of pedicellariae that is deterrent to predatory fish. These novel results add to our understanding of how the ecosystem-shaping sea urchin T. gratilla is able to reach high densities in many reef habitats, with subsequent impacts on algal cover.

Investigation of organic solvents assisted nano magnesium oxide nanoparticles and their structural, morphological, optical and antimicrobial performance

NASA Astrophysics Data System (ADS)

Deepa, B.; Rajendran, V.

2018-01-01

Investigation on the structural, morphological, optical studies and antimicrobial performance of organic solvent assisted magnesium oxide (MgO) nanoparticles. Nanoparticles are in 16-18 nm of grain size prepared by sol-gel method. The XRD studies shows as synthesized products are in cubic phase with periclase structurer. The well disperesd spherical morphology were obtained in SEM and TEM. The organic solvent methanol had profound effects on the size of the nano particles. The optical absorption edge energy was present in UV region and the corresponding band gap energy values are 4.5 and 4.9 eV for water with ethanol and methanol mediated MgO sample respectively. The PL emission spectrum has a emission peak at 340 and 353 nm which is due to surface defects. The obtained MgO nanoparticles showed superior antimicrobial activities for the gram positive, gram negative and fungus strains using the ELISA reader at 450 nm.

Crystal structure of 4-hydroxybutyryl-CoA dehydratase: radical catalysis involving a [4Fe-4S] cluster and flavin.

PubMed

Martins, Berta M; Dobbek, Holger; Cinkaya, Irfan; Buckel, Wolfgang; Messerschmidt, Albrecht

2004-11-02

Dehydratases catalyze the breakage of a carbon-oxygen bond leading to unsaturated products via the elimination of water. The 1.6-A resolution crystal structure of 4-hydroxybutyryl-CoA dehydratase from the gamma-aminobutyrate-fermenting Clostridium aminobutyricum represents a new class of dehydratases with an unprecedented active site architecture. A [4Fe-4S](2+) cluster, coordinated by three cysteine and one histidine residues, is located 7 A from the Re-side of a flavin adenine dinucleotide (FAD) moiety. The structure provides insight into the function of these ubiquitous prosthetic groups in the chemically nonfacile, radical-mediated dehydration of 4-hydroxybutyryl-CoA. The substrate can be bound between the [4Fe-4S](2+) cluster and the FAD with both cofactors contributing to its radical activation and catalytic conversion. Our results raise interesting questions regarding the mechanism of acyl-CoA dehydrogenases, which are involved in fatty acid oxidation, and address the divergent evolution of the ancestral common gene.

Structural and Functional Analysis of Phytotoxin Toxoflavin-Degrading Enzyme

PubMed Central

Kim, Myung-Il; Ma, Jun; Nagamatsu, Tomohisa; Goo, Eunhye; Kim, Hongsup; Hwang, Ingyu; Han, Jaehong; Rhee, Sangkee

2011-01-01

Pathogenic bacteria synthesize and secrete toxic low molecular weight compounds as virulence factors. These microbial toxins play essential roles in the pathogenicity of bacteria in various hosts, and are emerging as targets for antivirulence strategies. Toxoflavin, a phytotoxin produced by Burkholderia glumae BGR1, has been known to be the key factor in rice grain rot and wilt in many field crops. Recently, toxoflavin-degrading enzyme (TxDE) was identified from Paenibacillus polymyxa JH2, thereby providing a possible antivirulence strategy for toxoflavin-mediated plant diseases. Here, we report the crystal structure of TxDE in the substrate-free form and in complex with toxoflavin, along with the results of a functional analysis. The overall structure of TxDE is similar to those of the vicinal oxygen chelate superfamily of metalloenzymes, despite the lack of apparent sequence identity. The active site is located at the end of the hydrophobic channel, 9 Å in length, and contains a Mn(II) ion interacting with one histidine residue, two glutamate residues, and three water molecules in an octahedral coordination. In the complex, toxoflavin binds in the hydrophobic active site, specifically the Mn(II)-coordination shell by replacing a ligating water molecule. A functional analysis indicated that TxDE catalyzes the degradation of toxoflavin in a manner dependent on oxygen, Mn(II), and the reducing agent dithiothreitol. These results provide the structural features of TxDE and the early events in catalysis. PMID:21799856

High-resolution crystal structure of HA33 of botulinum neurotoxin type B progenitor toxin complex.

PubMed

Lee, Kwangkook; Lam, Kwok-Ho; Kruel, Anna Magdalena; Perry, Kay; Rummel, Andreas; Jin, Rongsheng

2014-04-04

Botulinum neurotoxins (BoNTs) are produced as progenitor toxin complexes (PTCs) by Clostridium botulinum. The PTCs are composed of BoNT and non-toxic neurotoxin-associated proteins (NAPs), which serve to protect and deliver BoNT through the gastrointestinal tract in food borne botulism. HA33 is a key NAP component that specifically recognizes host carbohydrates and helps enrich PTC on the intestinal lumen preceding its transport across the epithelial barriers. Here, we report the crystal structure of HA33 of type B PTC (HA33/B) in complex with lactose at 1.46Å resolution. The structural comparisons among HA33 of serotypes A-D reveal two different HA33-glycan interaction modes. The glycan-binding pockets on HA33/A and B are more suitable to recognize galactose-containing glycans in comparison to the equivalent sites on HA33/C and D. On the contrary, HA33/C and D could potentially recognize Neu5Ac as an independent receptor, whereas HA33/A and B do not. These findings indicate that the different oral toxicity and host susceptibility observed among different BoNT serotypes could be partly determined by the serotype-specific interaction between HA33 and host carbohydrate receptors. Furthermore, we have identified a key structural water molecule that mediates the HA33/B-lactose interactions. It provides the structural basis for development of new receptor-mimicking compounds, which have enhanced binding affinity with HA33 through their water-displacing moiety. Copyright © 2014 Elsevier Inc. All rights reserved.

Crystal structures of 5-amino-N-phenyl-3H-1,2,4-di-thia-zol-3-iminium chloride and 5-amino-N-(4-chloro-phen-yl)-3H-1,2,4-di-thia-zol-3-iminium chloride monohydrate.

PubMed

Yeo, Chien Ing; Tan, Yee Seng; Tiekink, Edward R T

2015-10-01

The crystal and mol-ecular structures of the title salt, C8H8N3S2 (+)·Cl(-), (I), and salt hydrate, C8H7ClN3S2 (+)·Cl(-)·H2O, (II), are described. The heterocyclic ring in (I) is statistically planar and forms a dihedral angle of 9.05 (12)° with the pendant phenyl ring. The comparable angle in (II) is 15.60 (12)°, indicating a greater twist in this cation. An evaluation of the bond lengths in the H2N-C-N-C-N sequence of each cation indicates significant delocalization of π-electron density over these atoms. The common feature of the crystal packing in (I) and (II) is the formation of charge-assisted amino-N-H⋯Cl(-) hydrogen bonds, leading to helical chains in (I) and zigzag chains in (II). In (I), these are linked by chains mediated by charge-assisted iminium-N(+)-H⋯Cl(-) hydrogen bonds into a three-dimensional architecture. In (II), the chains are linked into a layer by charge-assisted water-O-H⋯Cl(-) and water-O-H⋯O(water) hydrogen bonds with charge-assisted iminium-N(+)-H⋯O(water) hydrogen bonds providing the connections between the layers to generate the three-dimensional packing. In (II), the chloride anion and water mol-ecules are resolved into two proximate sites with the major component being present with a site occupancy factor of 0.9327 (18).

Causal Models for Mediation Analysis: An Introduction to Structural Mean Models.

PubMed

Zheng, Cheng; Atkins, David C; Zhou, Xiao-Hua; Rhew, Isaac C

2015-01-01

Mediation analyses are critical to understanding why behavioral interventions work. To yield a causal interpretation, common mediation approaches must make an assumption of "sequential ignorability." The current article describes an alternative approach to causal mediation called structural mean models (SMMs). A specific SMM called a rank-preserving model (RPM) is introduced in the context of an applied example. Particular attention is given to the assumptions of both approaches to mediation. Applying both mediation approaches to the college student drinking data yield notable differences in the magnitude of effects. Simulated examples reveal instances in which the traditional approach can yield strongly biased results, whereas the RPM approach remains unbiased in these cases. At the same time, the RPM approach has its own assumptions that must be met for correct inference, such as the existence of a covariate that strongly moderates the effect of the intervention on the mediator and no unmeasured confounders that also serve as a moderator of the effect of the intervention or the mediator on the outcome. The RPM approach to mediation offers an alternative way to perform mediation analysis when there may be unmeasured confounders.

Catalytic transformation of persistent contaminants using a new composite material based on nanosized zero-valent iron.

PubMed

Dror, Ishai; Jacov, Osnat Merom; Cortis, Andrea; Berkowitz, Brian

2012-07-25

A new composite material based on deposition of nanosized zerovalent iron (nZVI) particles and cyanocobalamine (vitamin B12) on a diatomite matrix is presented, for catalytic transformation of organic contaminants in water. Cyanocobalamine is known to be an effective electron mediator, having strong synergistic effects with nZVI for reductive dehalogenation reactions. This composite material also improves the reducing capacity of nZVI by preventing agglomeration of iron nanoparticles, thus increasing their active surface area. The porous structure of the diatomite matrix allows high hydraulic conductivity, which favors channeling of contaminated water to the reactive surface of the composite material resulting in faster rates of remediation. The composite material rapidly degrades or transforms completely a large spectrum of water contaminants, including halogenated solvents like TCE, PCE, and cis-DCE, pesticides like alachlor, atrazine and bromacyl, and common ions like nitrate, within minutes to hours. A field experiment where contaminated groundwater containing a mixture of industrial and agricultural persistent pollutants was conducted together with a set of laboratory experiments using individual contaminant solutions to analyze chemical transformations under controlled conditions.

Exogenous nitric oxide improves sugarcane growth and photosynthesis under water deficit.

PubMed

Silveira, Neidiquele M; Frungillo, Lucas; Marcos, Fernanda C C; Pelegrino, Milena T; Miranda, Marcela T; Seabra, Amedea B; Salgado, Ione; Machado, Eduardo C; Ribeiro, Rafael V

2016-07-01

Nitric oxide (NO)-mediated redox signaling plays a role in alleviating the negative impact of water stress in sugarcane plants by improving root growth and photosynthesis. Drought is an environmental limitation affecting sugarcane growth and yield. The redox-active molecule nitric oxide (NO) is known to modulate plant responses to stressful conditions. NO may react with glutathione (GSH) to form S-nitrosoglutathione (GSNO), which is considered the main reservoir of NO in cells. Here, we investigate the role of NO in alleviating the effects of water deficit on growth and photosynthesis of sugarcane plants. Well-hydrated plants were compared to plants under drought and sprayed with mock (water) or GSNO at concentrations ranging from 10 to 1000 μM. Leaf GSNO sprayed plants showed significant improvement of relative water content and leaf and root dry matter under drought compared to mock-sprayed plants. Additionally, plants sprayed with GSNO (≥ 100 μM) showed higher leaf gas exchange and photochemical activity as compared to mock-sprayed plants under water deficit and after rehydration. Surprisingly, a raise in the total S-nitrosothiols content was observed in leaves sprayed with GSH or GSNO, suggesting a long-term role of NO-mediated responses to water deficit. Experiments with leaf discs fumigated with NO gas also suggested a role of NO in drought tolerance of sugarcane plants. Overall, our data indicate that the NO-mediated redox signaling plays a role in alleviating the negative effects of water stress in sugarcane plants by protecting the photosynthetic apparatus and improving shoot and root growth.

Insect Responses to Linearly Polarized Reflections: Orphan Behaviors Without Neural Circuits

PubMed Central

Heinloth, Tanja; Uhlhorn, Juliane; Wernet, Mathias F.

2018-01-01

The e-vector orientation of linearly polarized light represents an important visual stimulus for many insects. Especially the detection of polarized skylight by many navigating insect species is known to improve their orientation skills. While great progress has been made towards describing both the anatomy and function of neural circuit elements mediating behaviors related to navigation, relatively little is known about how insects perceive non-celestial polarized light stimuli, like reflections off water, leaves, or shiny body surfaces. Work on different species suggests that these behaviors are not mediated by the “Dorsal Rim Area” (DRA), a specialized region in the dorsal periphery of the adult compound eye, where ommatidia contain highly polarization-sensitive photoreceptor cells whose receptive fields point towards the sky. So far, only few cases of polarization-sensitive photoreceptors have been described in the ventral periphery of the insect retina. Furthermore, both the structure and function of those neural circuits connecting to these photoreceptor inputs remain largely uncharacterized. Here we review the known data on non-celestial polarization vision from different insect species (dragonflies, butterflies, beetles, bugs and flies) and present three well-characterized examples for functionally specialized non-DRA detectors from different insects that seem perfectly suited for mediating such behaviors. Finally, using recent advances from circuit dissection in Drosophila melanogaster, we discuss what types of potential candidate neurons could be involved in forming the underlying neural circuitry mediating non-celestial polarization vision. PMID:29615868

Uncovering the Key Role of the Fermi Level of the Electron Mediator in a Z-Scheme Photocatalyst by Detecting the Charge Transfer Process of WO3-metal-gC3N4 (Metal = Cu, Ag, Au).

PubMed

Li, Houfen; Yu, Hongtao; Quan, Xie; Chen, Shuo; Zhang, Yaobin

2016-01-27

Z-scheme photocatalytic system shows superiority in degradation of refractory pollutants and water splitting due to the high redox capacities caused by its unique charge transfer behaviors. As a key component of Z-scheme system, the electron mediator plays an important role in charge carrier migration. According to the energy band theory, we believe the interfacial energy band bendings facilitate the electron transfer via Z-scheme mechanism when the Fermi level of electron mediator is between the Fermi levels of Photosystem II (PS II) and Photosystem I (PS I), whereas charge transfer is inhibited in other cases as energy band barriers would form at the semiconductor-metal interfaces. Here, this inference was verified by the increased hydroxyl radical generation and improved photocurrent on WO3-Cu-gC3N4 (with the desired Fermi level structure), which were not observed on either WO3-Ag-gC3N4 or WO3-Au-gC3N4. Finally, photocatalytic degradation rate of 4-nonylphenol on WO3-Cu-gC3N4 was proved to be as high as 11.6 times than that of WO3-gC3N4, further demonstrating the necessity of a suitable electron mediator in Z-scheme system. This study provides scientific basis for rational construction of Z-scheme photocatalytic system.

Building Collaborative Structures for Teachers' Autonomy and Self-Efficacy: The Mediating Role of Participative Management and Learning Culture

ERIC Educational Resources Information Center

Lu, Jiafang; Jiang, Xinhui; Yu, Huen; Li, Dongyu

2015-01-01

This study focused on the collaborative structure-building behavior of school principals and examined how such behavior affects teacher empowerment. More important, it tested the mediating effects of participative management and learning culture. By collecting nested data from 104 schools in Hong Kong and adopting multilevel structural equation…

Statistical modeling implicates neuroanatomical circuit mediating stress relief by ‘comfort’ food

PubMed Central

Ulrich-Lai, Yvonne M.; Christiansen, Anne M.; Wang, Xia; Song, Seongho; Herman, James P.

2015-01-01

A history of eating highly-palatable foods reduces physiological and emotional responses to stress. For instance, we have previously shown that limited sucrose intake (4 ml of 30% sucrose twice daily for 14 days) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. However, the neural mechanisms underlying stress relief by such ‘comfort’ foods are unclear, and could reveal an endogenous brain pathway for stress mitigation. As such, the present work assessed the expression of several proteins related to neuronal activation and/or plasticity in multiple stress- and reward-regulatory brain regions of rats after limited sucrose (vs. water control) intake. These data were then subjected to a series of statistical analyses, including Bayesian modeling, to identify the most likely neurocircuit mediating stress relief by sucrose. The analyses suggest that sucrose reduces HPA activation by dampening an excitatory basolateral amygdala - medial amygdala circuit, while also potentiating an inhibitory bed nucleus of the stria terminalis principle subdivision-mediated circuit, resulting in reduced HPA activation after stress. Collectively, the results support the hypothesis that sucrose limits stress responses via plastic changes to the structure and function of stress-regulatory neural circuits. The work also illustrates that advanced statistical methods are useful approaches to identify potentially novel and important underlying relationships in biological data sets. PMID:26246177

Statistical modeling implicates neuroanatomical circuit mediating stress relief by 'comfort' food.

PubMed

Ulrich-Lai, Yvonne M; Christiansen, Anne M; Wang, Xia; Song, Seongho; Herman, James P

2016-07-01

A history of eating highly palatable foods reduces physiological and emotional responses to stress. For instance, we have previously shown that limited sucrose intake (4 ml of 30 % sucrose twice daily for 14 days) reduces hypothalamic-pituitary-adrenocortical (HPA) axis responses to stress. However, the neural mechanisms underlying stress relief by such 'comfort' foods are unclear, and could reveal an endogenous brain pathway for stress mitigation. As such, the present work assessed the expression of several proteins related to neuronal activation and/or plasticity in multiple stress- and reward-regulatory brain regions of rats after limited sucrose (vs. water control) intake. These data were then subjected to a series of statistical analyses, including Bayesian modeling, to identify the most likely neurocircuit mediating stress relief by sucrose. The analyses suggest that sucrose reduces HPA activation by dampening an excitatory basolateral amygdala-medial amygdala circuit, while also potentiating an inhibitory bed nucleus of the stria terminalis principle subdivision-mediated circuit, resulting in reduced HPA activation after stress. Collectively, the results support the hypothesis that sucrose limits stress responses via plastic changes to the structure and function of stress-regulatory neural circuits. The work also illustrates that advanced statistical methods are useful approaches to identify potentially novel and important underlying relationships in biological datasets.

Mechanistic Insight into Caffeine-Oxalic Cocrystal Dissociation in Formulations: Role of Excipients.

PubMed

Duggirala, Naga Kiran; Vyas, Amber; Krzyzaniak, Joseph F; Arora, Kapildev K; Suryanarayanan, Raj

2017-11-06

Caffeine-oxalic acid cocrystal, widely reported to be stable under high humidity, dissociated in the presence of numerous pharmaceutical excipients. In cocrystal-excipient binary systems, the water mediated dissociation reaction occurred under pharmaceutically relevant storage conditions. Powder X-ray diffractometry was used to identify the dissociated products obtained as a consequence of coformer-excipient interaction. The proposed cocrystal dissociation mechanism involved water sorption, dissolution of cocrystal and excipient in the sorbed water, proton transfer from oxalic acid to the excipient, and formation of metal salts and caffeine hydrate. In compressed tablets with magnesium stearate, the cocrystal dissociation was readily discerned from the appearance of peaks attributable to caffeine hydrate and stearic acid. Neutral excipients provide an avenue to circumvent the risk of water mediated cocrystal dissociation.

Water-Mediated Photochemical Treatments for Low-Temperature Passivation of Metal-Oxide Thin-Film Transistors.

PubMed

Heo, Jae Sang; Jo, Jeong-Wan; Kang, Jingu; Jeong, Chan-Yong; Jeong, Hu Young; Kim, Sung Kyu; Kim, Kwanpyo; Kwon, Hyuck-In; Kim, Jaekyun; Kim, Yong-Hoon; Kim, Myung-Gil; Park, Sung Kyu

2016-04-27

The low-temperature electrical passivation of an amorphous oxide semiconductor (AOS) thin-film transistor (TFT) is achieved by a deep ultraviolet (DUV) light irradiation-water treatment-DUV irradiation (DWD) method. The water treatment of the first DUV-annealed amorphous indium-gallium-zinc-oxide (a-IGZO) thin film is likely to induce the preferred adsorption of water molecules at the oxygen vacancies and leads to subsequent hydroxide formation in the bulk a-IGZO films. Although the water treatment initially degraded the electrical performance of the a-IGZO TFTs, the second DUV irradiation on the water-treated devices may enable a more complete metal-oxygen-metal lattice formation while maintaining low oxygen vacancies in the oxide films. Overall, the stable and dense metal-oxygen-metal (M-O-M) network formation could be easily achieved at low temperatures (below 150 °C). The successful passivation of structural imperfections in the a-IGZO TFTs, such as hydroxyl group (OH-) and oxygen vacancies, mainly results in the enhanced electrical performances of the DWD-processed a-IGZO TFTs (on/off current ratio of 8.65 × 10(9), subthreshold slope of 0.16 V/decade, an average mobility of >6.94 cm(2) V(-1) s(-1), and a bias stability of ΔVTH < 2.5 V), which show more than a 30% improvement over the simple DUV-treated a-IGZO TFTs.

Triangulating the Sociohydrology of Water Supply, Quality and Forests in the Triangle

NASA Astrophysics Data System (ADS)

Band, L. E.

2016-12-01

The North Carolina Research Triangle is among the most rapidly growing metropolitan areas in the United States, with decentralized governance split among several different municipalities, counties and water utilities. Historically smaller populations, plentiful rainfall, and riparian rights based water law provided both a sense of security for water resources and influenced the development of separate infrastructure systems across the region. The growth of water demand with rising populations with typical suburban sprawl, the development of multi-use reservoirs immediately downstream of urban areas, and increased hydroclimate variability have raised the potential for periodic water scarcity coupled with increasing eutrophication of water supplies. We discuss the interactions and tradeoffs between management of emerging water scarcity, quality and forest biodiversity in the Triangle as a model for the US Southeast. Institutional stakeholders include water supply and stormwater utilities, environmental NGOs, federal, state, county and municipal governments, developers and home owner associations. We emphasize principles of ecohydrologic resilience learned in heavily instrumented research watersheds, adapted to rapidly developing urban systems, and including socioeconomic and policy dynamics. Significant 20th century reforestation of central North Carolina landscapes have altered regional water balances, while providing both flood and water quality mitigation. The regrowth forest is dynamic and heterogeneous in water use based on age class and species distribution, with substantial plantation and natural regeneration. Forecasts of land use and forest structural and compositional change are based on scenario socioeconomic development, climate change and forecast wood product markets. Urban forest and green infrastructure has the potential to mediate the trade-offs and synergies of these goals, but is in a very nascent state. Computational tools to assess policy alternatives impacts on water quality, quantity and forest biodiversity are developed to serve information to multiple stakeholders, and communicate and visualize outcomes.

Metabolite profiles of Stachybotrys isolates from water-damaged buildings and their induction of inflammatory mediators and cytotoxicity in macrophages.

PubMed

Nielsen, Kristian Fog; Huttunen, Kati; Hyvärinen, Anne; Andersen, Birgitte; Jarvis, Bruce B; Hirvonen, Maija-Riitta

2002-01-01

The metabolite profiles of 20 Stachybotrys spp. isolates from Finnish water-damaged buildings were compared with their biological activities. Effects of purified compounds on cytotoxicity and production of inflammatory mediators such as nitric oxide, IL-6 and TNFalpha in murine RAW264.7 macrophage cells were studied. The 11 isolates belonging to the satratoxin-producing chemotype were highly cytotoxic to the macrophages. The isolates inducing inflammatory mediators all belonged to the atranone-producing chemotype, but pure atranones B, and D did not elicit a response in the bioassay. Altogether, cytotoxicity of Stachybotrys sp. isolates appear to be related to satratoxin production whereas the specific component inducing inflammatory responses in atranone-producing isolates remains obscure.

Simulating Protein Mediated Hydrolysis of ATP and Other Nucleoside Triphosphates by Combining QM/MM Molecular Dynamics with Advances in Metadynamics

PubMed Central

2017-01-01

The protein mediated hydrolysis of nucleoside triphosphates such as ATP or GTP is one of the most important and challenging biochemical reactions in nature. The chemical environment (water structure, catalytic metal, and amino acid residues) adjacent to the hydrolysis site contains hundreds of atoms, usually greatly limiting the amount of the free energy sampling that one can achieve from computationally demanding electronic structure calculations such as QM/MM simulations. Therefore, the combination of QM/MM molecular dynamics with the recently developed transition-tempered metadynamics (TTMetaD), an enhanced sampling method that can provide a high-quality free energy estimate at an early stage in a simulation, is an ideal approach to address the biomolecular nucleoside triphosphate hydrolysis problem. In this work the ATP hydrolysis process in monomeric and filamentous actin is studied as an example application of the combined methodology. The performance of TTMetaD in these demanding QM/MM simulations is compared with that of the more conventional well-tempered metadynamics (WTMetaD). Our results show that TTMetaD exhibits much better exploration of the hydrolysis reaction free energy surface in two key collective variables (CVs) during the early stages of the QM/MM simulation than does WTMetaD. The TTMetaD simulations also reveal that a key third degree of freedom, the O–H bond-breaking and proton transfer from the lytic water, must be biased for TTMetaD to converge fully. To perturb the NTP hydrolysis dynamics to the least extent and to properly focus the MetaD free energy sampling, we also adopt here the recently developed metabasin metadynamics (MBMetaD) to construct a self-limiting bias potential that only applies to the lytic water after its nucleophilic attack of the phosphate of ATP. With these new, state-of-the-art enhanced sampling metadynamics techniques, we present an effective and accurate computational strategy for combining QM/MM molecular dynamics simulation with free energy sampling methodology, including a means to analyze the convergence of the calculations through robust numerical criteria. PMID:28345907

Simulating Protein Mediated Hydrolysis of ATP and Other Nucleoside Triphosphates by Combining QM/MM Molecular Dynamics with Advances in Metadynamics.

PubMed

Sun, Rui; Sode, Olaseni; Dama, James F; Voth, Gregory A

2017-05-09

The protein mediated hydrolysis of nucleoside triphosphates such as ATP or GTP is one of the most important and challenging biochemical reactions in nature. The chemical environment (water structure, catalytic metal, and amino acid residues) adjacent to the hydrolysis site contains hundreds of atoms, usually greatly limiting the amount of the free energy sampling that one can achieve from computationally demanding electronic structure calculations such as QM/MM simulations. Therefore, the combination of QM/MM molecular dynamics with the recently developed transition-tempered metadynamics (TTMetaD), an enhanced sampling method that can provide a high-quality free energy estimate at an early stage in a simulation, is an ideal approach to address the biomolecular nucleoside triphosphate hydrolysis problem. In this work the ATP hydrolysis process in monomeric and filamentous actin is studied as an example application of the combined methodology. The performance of TTMetaD in these demanding QM/MM simulations is compared with that of the more conventional well-tempered metadynamics (WTMetaD). Our results show that TTMetaD exhibits much better exploration of the hydrolysis reaction free energy surface in two key collective variables (CVs) during the early stages of the QM/MM simulation than does WTMetaD. The TTMetaD simulations also reveal that a key third degree of freedom, the O-H bond-breaking and proton transfer from the lytic water, must be biased for TTMetaD to converge fully. To perturb the NTP hydrolysis dynamics to the least extent and to properly focus the MetaD free energy sampling, we also adopt here the recently developed metabasin metadynamics (MBMetaD) to construct a self-limiting bias potential that only applies to the lytic water after its nucleophilic attack of the phosphate of ATP. With these new, state-of-the-art enhanced sampling metadynamics techniques, we present an effective and accurate computational strategy for combining QM/MM molecular dynamics simulation with free energy sampling methodology, including a means to analyze the convergence of the calculations through robust numerical criteria.

RPA-mediated unfolding of systematically varying G-quadruplex structures.

PubMed

Ray, Sujay; Qureshi, Mohammad H; Malcolm, Dominic W; Budhathoki, Jagat B; Celik, Uğur; Balci, Hamza

2013-05-21

G-quadruplex (GQ) is a noncanonical nucleic acid structure that is formed by guanine rich sequences. Unless it is destabilized by proteins such as replication protein A (RPA), GQ could interfere with DNA metabolic functions, such as replication or repair. We studied RPA-mediated GQ unfolding using single-molecule FRET on two groups of GQ structures that have different loop lengths and different numbers of G-tetrad layers. We observed a linear increase in the steady-state stability of the GQ against RPA-mediated unfolding with increasing number of layers or decreasing loop length. The stability demonstrated by different GQ structures varied by at least three orders of magnitude. Those with shorter loops (less than three nucleotides long) or a greater number of layers (more than three layers) maintained a significant folded population even at physiological RPA concentration (≈1 μM), raising the possibility of physiological viability of such GQ structures. Finally, we measured the transition time between the start and end of the RPA-mediated GQ unfolding process to be 0.35 ± 0.10 s for all GQ constructs we studied, despite significant differences in their steady-state stabilities. We propose a two-step RPA-mediated GQ unfolding mechanism that is consistent with our observations. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

RPA-Mediated Unfolding of Systematically Varying G-Quadruplex Structures

PubMed Central

Ray, Sujay; Qureshi, Mohammad H.; Malcolm, Dominic W.; Budhathoki, Jagat B.; Çelik, Uğur; Balci, Hamza

2013-01-01

G-quadruplex (GQ) is a noncanonical nucleic acid structure that is formed by guanine rich sequences. Unless it is destabilized by proteins such as replication protein A (RPA), GQ could interfere with DNA metabolic functions, such as replication or repair. We studied RPA-mediated GQ unfolding using single-molecule FRET on two groups of GQ structures that have different loop lengths and different numbers of G-tetrad layers. We observed a linear increase in the steady-state stability of the GQ against RPA-mediated unfolding with increasing number of layers or decreasing loop length. The stability demonstrated by different GQ structures varied by at least three orders of magnitude. Those with shorter loops (less than three nucleotides long) or a greater number of layers (more than three layers) maintained a significant folded population even at physiological RPA concentration (≈1 μM), raising the possibility of physiological viability of such GQ structures. Finally, we measured the transition time between the start and end of the RPA-mediated GQ unfolding process to be 0.35 ± 0.10 s for all GQ constructs we studied, despite significant differences in their steady-state stabilities. We propose a two-step RPA-mediated GQ unfolding mechanism that is consistent with our observations. PMID:23708363

Structure of the myotonic dystrophy type 2 RNA and designed small molecules that reduce toxicity.

PubMed

Childs-Disney, Jessica L; Yildirim, Ilyas; Park, HaJeung; Lohman, Jeremy R; Guan, Lirui; Tran, Tuan; Sarkar, Partha; Schatz, George C; Disney, Matthew D

2014-02-21

Myotonic dystrophy type 2 (DM2) is an incurable neuromuscular disorder caused by a r(CCUG) expansion (r(CCUG)(exp)) that folds into an extended hairpin with periodically repeating 2×2 nucleotide internal loops (5'CCUG/3'GUCC). We designed multivalent compounds that improve DM2-associated defects using information about RNA-small molecule interactions. We also report the first crystal structure of r(CCUG) repeats refined to 2.35 Å. Structural analysis of the three 5'CCUG/3'GUCC repeat internal loops (L) reveals that the CU pairs in L1 are each stabilized by one hydrogen bond and a water-mediated hydrogen bond, while CU pairs in L2 and L3 are stabilized by two hydrogen bonds. Molecular dynamics (MD) simulations reveal that the CU pairs are dynamic and stabilized by Na(+) and water molecules. MD simulations of the binding of the small molecule to r(CCUG) repeats reveal that the lowest free energy binding mode occurs via the major groove, in which one C residue is unstacked and the cross-strand nucleotides are displaced. Moreover, we modeled the binding of our dimeric compound to two 5'CCUG/3'GUCC motifs, which shows that the scaffold on which the RNA-binding modules are displayed provides an optimal distance to span two adjacent loops.

Structure of the Myotonic Dystrophy Type 2 RNA and Designed Small Molecules That Reduce Toxicity

PubMed Central

Park, HaJeung; Lohman, Jeremy R.; Guan, Lirui; Tran, Tuan; Sarkar, Partha; Schatz, George C.; Disney, Matthew D.

2014-01-01

Myotonic dystrophy type 2 (DM2) is an untreatable neuromuscular disorder caused by a r(CCUG) expansion (r(CCUG)exp) that folds into an extended hairpin with periodically repeating 2×2 nucleotide internal loops (5’CCUG/3’GUCC). We designed multivalent compounds that improve DM2-associated defects using information about RNA-small molecule interactions. We also report the first crystal structure of r(CCUG)exp refined to 2.35 Å. Structural analysis of the three 5’CCUG/3’GUCC repeat internal loops (L) reveals that the CU pairs in L1 are each stabilized by one hydrogen bond and a water-mediated hydrogen bond while CU pairs in L2 and L3 are stabilized by two hydrogen bonds. Molecular dynamics (MD) simulations reveal that the CU pairs are dynamic and stabilized by Na+ and water molecules. MD simulations of the binding of the small molecule to r(CCUG) repeats reveal that the lowest free energy binding mode occurs via the major groove, in which one C residue is unstacked and the cross-strand nucleotides are displaced. Moreover, we modeled the binding of our dimeric compound to two 5’CCUG/3’GUCC motifs, which shows that the scaffold on which the RNA-binding modules are displayed provides an optimal distance to span two adjacent loops. PMID:24341895

Multiscale regression modeling in mouse supraspinatus tendons reveals that dynamic processes act as mediators in structure-function relationships.

PubMed

Connizzo, Brianne K; Adams, Sheila M; Adams, Thomas H; Jawad, Abbas F; Birk, David E; Soslowsky, Louis J

2016-06-14

Recent advances in technology have allowed for the measurement of dynamic processes (re-alignment, crimp, deformation, sliding), but only a limited number of studies have investigated their relationship with mechanical properties. The overall objective of this study was to investigate the role of composition, structure, and the dynamic response to load in predicting tendon mechanical properties in a multi-level fashion mimicking native hierarchical collagen structure. Multiple linear regression models were investigated to determine the relationships between composition/structure, dynamic processes, and mechanical properties. Mediation was then used to determine if dynamic processes mediated structure-function relationships. Dynamic processes were strong predictors of mechanical properties. These predictions were location-dependent, with the insertion site utilizing all four dynamic responses and the midsubstance responding primarily with fibril deformation and sliding. In addition, dynamic processes were moderately predicted by composition and structure in a regionally-dependent manner. Finally, dynamic processes were partial mediators of the relationship between composition/structure and mechanical function, and results suggested that mediation is likely shared between multiple dynamic processes. In conclusion, the mechanical properties at the midsubstance of the tendon are controlled primarily by fibril structure and this region responds to load via fibril deformation and sliding. Conversely, the mechanical function at the insertion site is controlled by many other important parameters and the region responds to load via all four dynamic mechanisms. Overall, this study presents a strong foundation on which to design future experimental and modeling efforts in order to fully understand the complex structure-function relationships present in tendon. Copyright © 2016 Elsevier Ltd. All rights reserved.

INDIUM AND ZINC MEDIATED ONE-ATOM CARBOCYCLE ENLARGEMENT IN WATER. (R822668)

EPA Science Inventory

Abstract

Six-, seven-, eight-membered rings are enlarged by one carbon-atom into seven-, eight- and nine-membered ring derivatives respectively, via indium or zinc mediated reactions in aqueous medium.

Effect of urea and alkylureas on the stability and structural fluctuation of the M80-containing Ω-loop of horse cytochrome c.

PubMed

Kumar, Sandeep; Sharma, Deepak; Kumar, Rajesh

2014-03-01

The effect of denaturants on the structural fluctuation of M80-containing Ω-loop of ferrocytochrome c was determined by measuring the rate coefficient of CO-association with ferrocytochrome c under varying concentrations of urea and alkylureas (methylurea (MU), N,N'-dimethylurea (DMU), ethylurea (EU), tetramethylurea (TMU)) at pH7.0, 25°C. As denaturant concentration is increased within the subdenaturing limit, the CO-association reaction is decelerated indicating that subdenaturing concentrations of denaturant reduce the structural fluctuation of the Ω-loop. Structural fluctuation of the Ω-loop is reduced more for urea and least for TMU. Intermolecular docking between horse cytochrome c and denaturant molecule (urea, MU, DMU, EU and TMU) reveals that polyfunctional interactions between the denaturant and different groups of Ω-loop and other part of protein decrease with an increase of alkyl group on urea molecule, which suggests that the decrease in the extent of restricted dynamics of Ω-loop with a corresponding increase of alkyl groups on urea molecule is due to the decrease of denaturant-mediated cross-linking interactions. These denaturant-mediated interactions are expected to reduce the conformational entropy of protein. Analysis of rate-temperature data shows a progressive decrease in conformational entropy of protein in the native to subdenaturing region. Thermodynamic analysis of denaturant (urea, MU, DMU, EU, TMU) effects on the thermal unfolding of ferrocytochrome c reveals that (i) thermodynamic stability of protein decreases with increasing concentration of denaturant or hydrophobicity of urea derivatives, (ii) water activity plays an important role in stabilization of ferrocytochrome c, and (iii) destabilization of ferrocytochrome c by denaturant occurs through the disturbance of hydrophobic interactions and hydrogen-bonding. Copyright © 2014 Elsevier B.V. All rights reserved.

Solvent-dependent oxidations of 5- and 6-azaindoles to trioxopyrrolopyridines and functionalised azaindoles.

PubMed

Mahiout, Zahia; Lomberget, Thierry; Goncalves, Sylvie; Barret, Roland

2008-04-21

A regioselective synthesis of 4,7-dimethoxy 5- and 6-azaindoles 2 has been achieved, based on the appropriate choice of ortho-directing or ortho-repulsing groups in the formylation of a pyridine ring. Studies on the regioselectivity of the formylation step and on the preparation of azidoacrylate intermediates 4 are described in this paper. The reactivity of the 5- and 6-azaindole structures towards BBr3-mediated selective monodemethylation and oxidative demethylation reactions were also investigated. The regioselectivity of the deprotection was confirmed using a chemical approach. Oxidation reactions were then carried out on either dimethoxy- or hydroxymethoxyazaindoles, in different solvents, using [bis(trifluoroacetoxy)iodo]benzene. In acetonitrile-water, trioxopyrrolopyridines 12 were obtained, whereas the formation of functionalised azaindoles 17 was observed in acetonitrile-methanol. The tautomeric structure of the trioxopyrrolopyridines was proved by X-ray diffraction analysis.

Structure and Functional Characterization of Vibrio parahaemolyticus Thermostable Direct Hemolysin*

PubMed Central

Yanagihara, Itaru; Nakahira, Kumiko; Yamane, Tsutomu; Kaieda, Shuji; Mayanagi, Kouta; Hamada, Daizo; Fukui, Takashi; Ohnishi, Kiyouhisa; Kajiyama, Shin'ichiro; Shimizu, Toshiyuki; Sato, Mamoru; Ikegami, Takahisa; Ikeguchi, Mitsunori; Honda, Takeshi; Hashimoto, Hiroshi

2010-01-01

Thermostable direct hemolysin (TDH) is a major virulence factor of Vibrio parahaemolyticus that causes pandemic foodborne enterocolitis mediated by seafood. TDH exists as a tetramer in solution, and it possesses extreme hemolytic activity. Here, we present the crystal structure of the TDH tetramer at 1.5 Å resolution. The TDH tetramer forms a central pore with dimensions of 23 Å in diameter and ∼50 Å in depth. π-Cation interactions between protomers comprising the tetramer were indispensable for hemolytic activity of TDH. The N-terminal region was intrinsically disordered outside of the pore. Molecular dynamic simulations suggested that water molecules permeate freely through the central and side channel pores. Electron micrographs showed that tetrameric TDH attached to liposomes, and some of the tetramer associated with liposome via one protomer. These findings imply a novel membrane attachment mechanism by a soluble tetrameric pore-forming toxin. PMID:20335168

Molecular Characteristics and Biological Functions of Surface-Active and Surfactant Proteins.

PubMed

Sunde, Margaret; Pham, Chi L L; Kwan, Ann H

2017-06-20

Many critical biological processes take place at hydrophobic:hydrophilic interfaces, and a wide range of organisms produce surface-active proteins and peptides that reduce surface and interfacial tension and mediate growth and development at these boundaries. Microorganisms produce both small lipid-associated peptides and amphipathic proteins that allow growth across water:air boundaries, attachment to surfaces, predation, and improved bioavailability of hydrophobic substrates. Higher-order organisms produce surface-active proteins with a wide variety of functions, including the provision of protective foam environments for vulnerable reproductive stages, evaporative cooling, and gas exchange across airway membranes. In general, the biological functions supported by these diverse polypeptides require them to have an amphipathic nature, and this is achieved by a diverse range of molecular structures, with some proteins undergoing significant conformational change or intermolecular association to generate the structures that are surface active.

Salt water and skin interactions: new lines of evidence

NASA Astrophysics Data System (ADS)

Carbajo, Jose Manuel; Maraver, Francisco

2018-04-01

In Health Resort Medicine, both balneotherapy and thalassotherapy, salt waters and their peloids, or mud products are mainly used to treat rheumatic and skin disorders. These therapeutic agents act jointly via numerous mechanical, thermal, and chemical mechanisms. In this review, we examine a new mechanism of action specific to saline waters. When topically administered, this water rich in sodium and chloride penetrates the skin where it is able to modify cellular osmotic pressure and stimulate nerve receptors in the skin via cell membrane ion channels known as "Piezo" proteins. We describe several models of cutaneous adsorption/desorption and penetration of dissolved ions in mineral waters through the skin (osmosis and cell volume mechanisms in keratinocytes) and examine the role of these resources in stimulating cutaneous nerve receptors. The actions of salt mineral waters are mediated by a mechanism conditioned by the concentration and quality of their salts involving cellular osmosis-mediated activation/inhibition of cell apoptotic or necrotic processes. In turn, this osmotic mechanism modulates the recently described mechanosensitive piezoelectric channels.

Water Splitting via Decoupled Photocatalytic Water Oxidation and Electrochemical Proton Reduction Mediated by Electron-Coupled-Proton Buffer.

PubMed

Li, Fei; Yu, Fengshou; Du, Jian; Wang, Yong; Zhu, Yong; Li, Xiaona; Sun, Licheng

2017-10-18

Water splitting mediated by electron-coupled-proton buffer (ECPB) provides an efficient way to avoid gas mixing by separating oxygen evolution from hydrogen evolution in space and time. Though electrochemical and photoelectrochemcial water oxidation have been incorporated in such a two-step water splitting system, alternative ways to reduce the cost and energy input for decoupling two half-reactions are desired. Herein, we show the feasibility of photocatalytic oxygen evolution in a powder system with BiVO 4 as a photocatalyst and polyoxometalate H 3 PMo 12 O 40 as an electron and proton acceptor. The resulting reaction mixture was allowed to be directly used for the subsequent hydrogen evolution with the reduced H 3 PMo 12 O 40 as electron and proton donors. Our system exhibits excellent stability in repeated oxygen and hydrogen evolution, which brings considerable convenience to decoupled water splitting. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Measurement Structure, Stability and Mediating Effects of Achievement Goals in Math with Middle-School Student Data

ERIC Educational Resources Information Center

Chiang, Yu-Tzu; Lin, Sunny S. J.

2014-01-01

This study examined the measurement structure, cross-year stability of achievement goals, and mediating effects of achievement goals between self-efficacy and math grades in a national sample of Taiwan middle school students. The measurement model with factorial structure showed good fit to the data. In the panel data (N?=?343), four achievement…

Mediational and Deviance Theories of Late High School Failure: Process Roles of Structural Strains, Academic Competence, and General versus Specific Problem Behavior

ERIC Educational Resources Information Center

Newcomb, Michael D.; Abbott, Robert D.; Catalano, Richard F.; Hawkins, J. David; Battin-Pearson, Sara; Hill, Karl

2002-01-01

Understanding and preventing high school failure is a national priority. Structural strain and general deviance theories attempt to explain late high school failure. The authors tested the hypotheses that general (vs. specific) deviance and academic competence mediate the relationships between structural strain factors (gender, ethnicity, and…

Phytoremediation of trichloroethene (TCE) using cottonwood trees

USGS Publications Warehouse

Jones, S.A.; Lee, R.W.; Kuniansky, E.L.; Leeson, Andrea; Alleman, Bruce C.

1999-01-01

Phytoremediation uses the natural ability of plants to degrade contaminants in ground water. A field demonstration designed to remediate aerobic shallow ground water that contains trichloroethene began in April 1996 with the planting of cottonwood trees over an approximately 0.2-hectare area at the Naval Air Station, Fort Worth, Tx. Ground water was sampled in July 1997, November 1997, February 1998, and June 1998. Analyses from samples indicate that tree roots have the potential to create anaerobic conditions in the ground water that will facilitate degradation of trichloroethene by microbially mediated reductive dichlorination. Dissolved oxygen concentrations, which varied across the site, were smallest near a mature cottonwood tree (about-20 years old) 60 meters southwest of the cottonwood plantings. Reduction of dissolved oxygen is the primary microbially mediated reaction occurring in the ground water beneath the planted trees, whereas near the mature cottonwood tree, data indicate that methanogenesis is the most probable reaction occurring. Reductive dichlorination either is not occurring or is not a primary process away from the mature tree. On the basis of isotopic analyses of carbon-13 at locations away from the mature tree, trichloroethene concentration is controlled by volatilization.Phytoremediation uses the natural ability of plants to degrade contaminants in ground water. A field demonstration designed to remediate aerobic shallow ground water that contains trichloroethene began in April 1996 with the planting of cottonwood trees over an approximately 0.2-hectare area at the Naval Air Station, Fort Worth, Tx. Ground water was sampled in July 1997, November 1997, February 1998, and June 1998. Analyses from samples indicate that tree roots have the potential to create anaerobic conditions in the ground water that will facilitate degradation of trichloroethene by microbially mediated reductive dichlorination. Dissolved oxygen concentrations, which varied across the site, were smallest near a mature cottonwood tree (about-20 years old) 60 meters southwest of the cottonwood plantings. Reduction of dissolved oxygen is the primary microbially mediated reaction occurring in the ground water beneath the planted trees, whereas near the mature cottonwood tree, data indicate that methanogenesis is the most probable reaction occurring. Reductive dichlorination either is not occurring or is not a primary process away from the mature tree. On the basis of isotopic analyses of carbon-13 at locations away from the mature tree, trichloroethene concentration is controlled by volatilization.

Is Water a Universal Solvent for Life?

NASA Technical Reports Server (NTRS)

Pohorill, Andrew

2012-01-01

There are strong reasons to believe that the laws, principles and constraints of physics and chemistry are universal. It is much less clear how this universality translates into our understanding of the origins of life. Conventionally, discussions of this topic focus on chemistry that must be sufficiently rich to seed life. Although this is clearly a prerequisite for the emergence of living systems, I propose to focus instead on self-organization of matter into functional structures capable of reproduction, evolution and responding to environmental changes. In biology, most essential functions are largely mediated by noncovalent interactions (interactions that do not involve making or breaking chemical bonds). Forming chemical bonds is only a small part of what living systems do. There are specific implications of this point of view for universality. I will concentrate on one of these implications. Strength of non-covalent interactions must be properly tuned. If they were too weak, the system would exhibit undesired, uncontrolled response to natural fluctuations of physical and chemical parameters. If they were too strong kinetics of biological processes would be slow and energetics costly. This balance, however, is not a natural property of complex chemical systems. Instead, it has to be achieved with the aid of an appropriate solvent for life. In particular, potential solvents for life must be characterized by a high dielectric constant to ensure solubility of polar species and sufficient flexibility of biological structures stabilized by electrostatic interactions. Among these solvents, water exhibits a remarkable trait that it also promotes solvophobic (hydrophobic) interactions between non-polar species, typically manifested by a tendency of these species to aggregate and minimize their contacts with the aqueous solvent. Hydrophobic interactions are responsible, at least in part, for many self-organization phenomena in biological systems, such as the formation of cellular boundary structures or protein folding. Strengths of electrostatic and hydrophobic interactions are similar and can be balanced over a wide range of temperatures, which considerably increases the repertoire of interactions that can be used to modulate biological functions. Some properties of water, e.g. its chemical activity against polymerization reactions, are considered as unfavorable to life. In actuality, this might be a favorable trait because life requires a balance between constructive and destructive processes. For example, molecules synthesized in response to specific conditions must be degraded once these conditions change. Otherwise regulation of biological processes would be virtually impossible. Water might not be the only liquid with favorable properties for supporting life. It has been proposed that formamide, which might be present elsewhere in the universe in sufficient quantities to warrant interest, could be a potential alternative to water for the origin of life. However, this will remain highly hypothetical until it is demonstrated in further studies on its physical, chemical and biological properties it is capable of mediating self-organization of matter and providing proper balance between different types of non-covalent interactions.

Radical O-O coupling reaction in diferrate-mediated water oxidation studied using multireference wave function theory.

PubMed

Kurashige, Yuki; Saitow, Masaaki; Chalupský, Jakub; Yanai, Takeshi

2014-06-28

The O-O (oxygen-oxygen) bond formation is widely recognized as a key step of the catalytic reaction of dioxygen evolution from water. Recently, the water oxidation catalyzed by potassium ferrate (K2FeO4) was investigated on the basis of experimental kinetic isotope effect analysis assisted by density functional calculations, revealing the intramolecular oxo-coupling mechanism within a di-iron(vi) intermediate, or diferrate [Sarma et al., J. Am. Chem. Soc., 2012, 134, 15371]. Here, we report a detailed examination of this diferrate-mediated O-O bond formation using scalable multireference electronic structure theory. High-dimensional correlated many-electron wave functions beyond the one-electron picture were computed using the ab initio density matrix renormalization group (DMRG) method along the O-O bond formation pathway. The necessity of using large active space arises from the description of complex electronic interactions and varying redox states both associated with two-center antiferromagnetic multivalent iron-oxo coupling. Dynamic correlation effects on top of the active space DMRG wave functions were additively accounted for by complete active space second-order perturbation (CASPT2) and multireference configuration interaction (MRCI) based methods, which were recently introduced by our group. These multireference methods were capable of handling the double shell effects in the extended active space treatment. The calculations with an active space of 36 electrons in 32 orbitals, which is far over conventional limitation, provide a quantitatively reliable prediction of potential energy profiles and confirmed the viability of the direct oxo coupling. The bonding nature of Fe-O and dual bonding character of O-O are discussed using natural orbitals.

THE NEAR-EQUILIBRIUM OF MICROBIALLY MEDIATED REDOX COUPLES IN REDUCING GROUNDWATER ENVIRONMENTS

EPA Science Inventory

Redox couples are commonly held to be in disequilibrium among each other in most natural waters. To evaluate this view for microbially mediated, reducing, groundwater environments, monitoring data were examined for several couples under conditions ranging from nitrate-detectable...

25 CFR 161.603 - Can mediation be used in the event of a permit violation or dispute?

Code of Federal Regulations, 2012 CFR

2012-04-01

... AND WATER NAVAJO PARTITIONED LANDS GRAZING PERMITS Permit Violations § 161.603 Can mediation be used... question of law. BIA will defer to any ongoing proceedings, as appropriate, in deciding whether to exercise...

25 CFR 161.603 - Can mediation be used in the event of a permit violation or dispute?

Code of Federal Regulations, 2013 CFR

2013-04-01

... AND WATER NAVAJO PARTITIONED LANDS GRAZING PERMITS Permit Violations § 161.603 Can mediation be used... question of law. BIA will defer to any ongoing proceedings, as appropriate, in deciding whether to exercise...

25 CFR 161.603 - Can mediation be used in the event of a permit violation or dispute?

Code of Federal Regulations, 2014 CFR

2014-04-01

... AND WATER NAVAJO PARTITIONED LANDS GRAZING PERMITS Permit Violations § 161.603 Can mediation be used... question of law. BIA will defer to any ongoing proceedings, as appropriate, in deciding whether to exercise...

25 CFR 161.603 - Can mediation be used in the event of a permit violation or dispute?

Code of Federal Regulations, 2011 CFR

2011-04-01

... AND WATER NAVAJO PARTITIONED LANDS GRAZING PERMITS Permit Violations § 161.603 Can mediation be used... question of law. BIA will defer to any ongoing proceedings, as appropriate, in deciding whether to exercise...

Intuitive, but not simple: including explicit water molecules in protein-protein docking simulations improves model quality.

PubMed

Parikh, Hardik I; Kellogg, Glen E

2014-06-01

Characterizing the nature of interaction between proteins that have not been experimentally cocrystallized requires a computational docking approach that can successfully predict the spatial conformation adopted in the complex. In this work, the Hydropathic INTeractions (HINT) force field model was used for scoring docked models in a data set of 30 high-resolution crystallographically characterized "dry" protein-protein complexes and was shown to reliably identify native-like models. However, most current protein-protein docking algorithms fail to explicitly account for water molecules involved in bridging interactions that mediate and stabilize the association of the protein partners, so we used HINT to illuminate the physical and chemical properties of bridging waters and account for their energetic stabilizing contributions. The HINT water Relevance metric identified the "truly" bridging waters at the 30 protein-protein interfaces and we utilized them in "solvated" docking by manually inserting them into the input files for the rigid body ZDOCK program. By accounting for these interfacial waters, a statistically significant improvement of ∼24% in the average hit-count within the top-10 predictions the protein-protein dataset was seen, compared to standard "dry" docking. The results also show scoring improvement, with medium and high accuracy models ranking much better than incorrect ones. These improvements can be attributed to the physical presence of water molecules that alter surface properties and better represent native shape and hydropathic complementarity between interacting partners, with concomitantly more accurate native-like structure predictions. © 2013 Wiley Periodicals, Inc.

Chronic Arsenic Exposure in Nanomolar Concentrations Compromises Wound Response and Intercellular Signaling in Airway Epithelial Cells

PubMed Central

Boitano, Scott

2013-01-01

Paracrine ATP signaling in the lung epithelium participates in a variety of innate immune functions, including mucociliary clearance, bactericide production, and as an initiating signal in wound repair. We evaluated the effects of chronic low-dose arsenic relevant to U.S. drinking water standards (i.e., 10 ppb [130nM]) on airway epithelial cells. Immortalized human bronchial epithelial cells (16HBE14o-) were exposed to 0, 130, or 330nM arsenic (as Na-arsenite) for 4–5 weeks and examined for wound repair efficiency and ATP-mediated Ca2+ signaling. We found that chronic arsenic exposure at these low doses slows wound repair and reduces ATP-mediated Ca2+ signaling. We further show that arsenic compromises ATP-mediated Ca2+ signaling by altering both Ca2+ release from intracellular stores (via metabotropic P2Y receptors) and Ca2+ influx mechanisms (via ionotropic P2X receptors). To better model the effects of arsenic on ATP-mediated Ca2+ signaling under conditions of natural exposure, we cultured tracheal epithelial cells obtained from mice exposed to control or 50 ppb Na-arsenite supplemented drinking water for 4 weeks. Tracheal epithelial cells from arsenic-exposed mice displayed reduced ATP-mediated Ca2+ signaling dynamics similar to our in vitro chronic exposure. Our findings demonstrate that chronic arsenic exposure at levels that are commonly found in drinking water (i.e., 10–50 ppb) alters cellular mechanisms critical to airway innate immunity. PMID:23204110

Effect of variable water intake as mediated by dietary potassium carbonate supplementation on rumen dynamics in lactating dairy cows

USDA-ARS?s Scientific Manuscript database

Water is a critical nutrient for dairy cows, with intake varying with environment, production, and diet. However, little work has evaluated the effects of water intake on rumen parameters. Using dietary potassium carbonate (Kcarb) as a K supplement to increase water intake, the objective of this stu...

A spatial evaluation of global wildfire-water risks to human and natural systems

Treesearch

Francois-Nicolas Robinne; Kevin D. Bladon; Carol Miller; Marc-Andre Parisien; Jerome Mathieu; Mike D. Flannigan

2017-01-01

The large mediatic coverage of recent massive wildfires across the world has emphasized the vulnerability of freshwater resources. The extensive hydrogeomorphic effects from a wildfire can impair the ability of watersheds to provide safe drinking water to downstream communities and high-quality water to maintain riverine ecosystem health. Safeguarding water use for...

Sample Size Limits for Estimating Upper Level Mediation Models Using Multilevel SEM

ERIC Educational Resources Information Center

Li, Xin; Beretvas, S. Natasha

2013-01-01

This simulation study investigated use of the multilevel structural equation model (MLSEM) for handling measurement error in both mediator and outcome variables ("M" and "Y") in an upper level multilevel mediation model. Mediation and outcome variable indicators were generated with measurement error. Parameter and standard…

Do biomass fuel use and consumption of unsafe water mediate educational inequalities in stillbirth risk? An analysis of the 2007 Ghana Maternal Health Survey.

PubMed

Amegah, A Kofi; Näyhä, Simo; Jaakkola, Jouni J K

2017-02-07

Numerous studies have explored the association between educational inequalities and stillbirth but most have failed to elaborate how low educational attainment leads to an increased risk of stillbirth. We hypothesised that use of biomass fuels and consumption of unsafe water related to low educational attainment could explain the stillbirth burden in Ghana attributable to socioeconomic disadvantage. Data from the 2007 Ghana Maternal Health Survey, a nationally representative population-based survey were analysed for this study. Of the10 370 women aged 15-49 years interviewed via structured questionnaires for the survey, 7183 primiparous and multiparous women qualified for inclusion in the present study. In a logistic regression analysis that adjusted for age, area of residence, marital status and ethnicity of women, lower maternal primary education was associated with a 62% (OR=1.62; 95% CI 1.04 to 2.52) increased lifetime risk of stillbirth. Biomass fuel use and consumption of unsafe water mediated 18% and 8% of the observed effects, respectively. Jointly these two exposures explained 24% of the observed effects. The generalised additive modelling revealed a very flat inverted spoon-shaped smoothed curve which peaked at low levels of schooling (2-3 years) and confirms the findings from the logistic regression analysis. Our results show that biomass fuel use and unsafe water consumption could be important pathways through which low maternal educational attainment leads to stillbirths in Ghana and similar developing countries. Addressing educational inequalities in developing countries is thus essential for ensuring household choices that curtail environmental exposures and help improve pregnancy outcomes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Med5(Nut1) and Med17(Srb4) Are Direct Targets of Mediator Histone H4 Tail Interactions

PubMed Central

Liu, Zhongle; Myers, Lawrence C.

2012-01-01

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. In addition to its canonical role in transcriptional activation, recent studies have demonstrated that S. cerevisiae Mediator can interact directly with nucleosomes, and their histone tails. Mutations in Mediator subunits have shown that Mediator and certain chromatin structures mutually impact each other structurally and functionally in vivo. We have taken a UV photo cross-linking approach to further delineate the molecular basis of Mediator chromatin interactions and help determine whether the impact of certain Mediator mutants on chromatin is direct. Specifically, by using histone tail peptides substituted with an amino acid analog that is a UV activatible crosslinker, we have identified specific subunits within Mediator that participate in histone tail interactions. Using Mediator purified from mutant yeast strains we have evaluated the impact of these subunits on histone tail binding. This analysis has identified the Med5 subunit of Mediator as a target for histone tail interactions and suggests that the previously observed effect of med5 mutations on telomeric heterochromatin and silencing is direct. PMID:22693636

Causal mediation analysis with a latent mediator.

PubMed

Albert, Jeffrey M; Geng, Cuiyu; Nelson, Suchitra

2016-05-01

Health researchers are often interested in assessing the direct effect of a treatment or exposure on an outcome variable, as well as its indirect (or mediation) effect through an intermediate variable (or mediator). For an outcome following a nonlinear model, the mediation formula may be used to estimate causally interpretable mediation effects. This method, like others, assumes that the mediator is observed. However, as is common in structural equations modeling, we may wish to consider a latent (unobserved) mediator. We follow a potential outcomes framework and assume a generalized structural equations model (GSEM). We provide maximum-likelihood estimation of GSEM parameters using an approximate Monte Carlo EM algorithm, coupled with a mediation formula approach to estimate natural direct and indirect effects. The method relies on an untestable sequential ignorability assumption; we assess robustness to this assumption by adapting a recently proposed method for sensitivity analysis. Simulation studies show good properties of the proposed estimators in plausible scenarios. Our method is applied to a study of the effect of mother education on occurrence of adolescent dental caries, in which we examine possible mediation through latent oral health behavior. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure of the OsSERK2 leucine-rich repeat extracellular domain.

PubMed

McAndrew, Ryan; Pruitt, Rory N; Kamita, Shizuo G; Pereira, Jose Henrique; Majumdar, Dipali; Hammock, Bruce D; Adams, Paul D; Ronald, Pamela C

2014-11-01

Somatic embryogenesis receptor kinases (SERKs) are leucine-rich repeat (LRR)-containing integral membrane receptors that are involved in the regulation of development and immune responses in plants. It has recently been shown that rice SERK2 (OsSERK2) is essential for XA21-mediated resistance to the pathogen Xanthomonas oryzae pv. oryzae. OsSERK2 is also required for the BRI1-mediated, FLS2-mediated and EFR-mediated responses to brassinosteroids, flagellin and elongation factor Tu (EF-Tu), respectively. Here, crystal structures of the LRR domains of OsSERK2 and a D128N OsSERK2 mutant, expressed as hagfish variable lymphocyte receptor (VLR) fusions, are reported. These structures suggest that the aspartate mutation does not generate any significant conformational change in the protein, but instead leads to an altered interaction with partner receptors.

Regulatory focus as a mediator of the influence of initiating structure and servant leadership on employee behavior.

PubMed

Neubert, Mitchell J; Kacmar, K Michele; Carlson, Dawn S; Chonko, Lawrence B; Roberts, James A

2008-11-01

In this research, the authors test a model in which the regulatory focus of employees at work mediates the influence of leadership on employee behavior. In a nationally representative sample of 250 workers who responded over 2 time periods, prevention focus mediated the relationship of initiating structure to in-role performance and deviant behavior, whereas promotion focus mediated the relationship of servant leadership to helping and creative behavior. The results indicate that even though initiating structure and servant leadership share some variance in explaining other variables, each leadership style incrementally predicts disparate outcomes after controlling for the other style and dispositional tendencies. A new regulatory focus scale, the Work Regulatory Focus (WRF) Scale, also was developed and initially validated for this study. Implications for the results and the WRF Scale are discussed.

Mediator- and co-catalyst-free direct Z-scheme composites of Bi2WO6-Cu3P for solar-water splitting.

PubMed

Rauf, Ali; Ma, Ming; Kim, Sungsoon; Sher Shah, Md Selim Arif; Chung, Chan-Hwa; Park, Jong Hyeok; Yoo, Pil J

2018-02-08

Exploring new single, active photocatalysts for solar-water splitting is highly desirable to expedite current research on solar-chemical energy conversion. In particular, Z-scheme-based composites (ZBCs) have attracted extensive attention due to their unique charge transfer pathway, broader redox range, and stronger redox power compared to conventional heterostructures. In the present report, we have for the first time explored Cu 3 P, a new, single photocatalyst for solar-water splitting applications. Moreover, a novel ZBC system composed of Bi 2 WO 6 -Cu 3 P was designed employing a simple method of ball-milling complexation. The synthesized materials were examined and further investigated through various microscopic, spectroscopic, and surface area characterization methods, which have confirmed the successful hybridization between Bi 2 WO 6 and Cu 3 P and the formation of a ZBC system that shows the ideal position of energy levels for solar-water splitting. Notably, the ZBC composed of Bi 2 WO 6 -Cu 3 P is a mediator- and co-catalyst-free photocatalyst system. The improved photocatalytic efficiency obtained with this system compared to other ZBC systems assisted by mediators and co-catalysts establishes the critical importance of interfacial solid-solid contact and the well-balanced position of energy levels for solar-water splitting. The promising solar-water splitting under optimum composition conditions highlighted the relationship between effective charge separation and composition.

Effects of low-dose light-emitting-diode therapy in combination with water bath for atopic dermatitis in NC/Nga mice.

PubMed

Kim, Chang-Hyun; Cheong, Kyung Ah; Lim, Won Suk; Park, Hyung-Moo; Lee, Ai-Young

2016-01-01

Light-emitting diode (LED) phototherapy and water bath therapy have beneficial effect on atopic dermatitis (AD)-like skin disease. However, not all current treatments work well and alternative therapies are need. The contribution of combination therapy with low-dose 850 nm LED and water bath was investigated on dermatophagoides farina (Df)-induced dermatitis in NC/Nga mice. Low-dose LED (10, 15, and 20 J/cm(2) ) irradiation, water bath (36 ± 1°C) were administered separately and together to the Df-induced NC/Nga mice in acrylic jar once a day for 2 weeks. Combined therapy with low-dose LED therapy and water bath therapy significantly ameliorated the development of AD-like skin lesions. These effects were correlated with the suppression of total IgE, NO, histamine, and Th2-mediated immune responses. Furthermore, combination therapy significantly reduced the infiltration of inflammatory cells and the induction of thymic stromal lymphopoietin (TSLP) in the skin lesions. The beneficial therapeutic effects of this combination therapy might regulate by the inhibition of various immunological responses including Th2-mediated immune responses, inflammatory mediators such as IgE, histamine, and NO, as well as inflammatory cells. The combination therapy of LED and water bath might be used as an efficacious, safe, and steroid-free alternative therapeutic strategy for the treatment of AD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Drinking sucrose enhances quinpirole-induced yawning in rats

PubMed Central

Baladi, Michelle G; Newman, Amy H; Thomas, Yvonne M; France, Charles P

2011-01-01

Food and drugs can activate brain dopamine systems and sensitivity to the effects of drugs acting on those systems is influenced by amount and content of food consumed. This study examined the effects of drinking sucrose on behavioral effects of the directly-acting dopamine receptor agonist quinpirole. Male Sprague-Dawley rats (n=6/group) had free access to water or 10% sucrose and quinpirole dose-response curves (yawning and hypothermia) were generated weekly for 8 weeks. Subsequently, all rats drank water for 8 weeks with quinpirole dose-response curves determined on weeks 9, 10, and 16. In rats drinking sucrose, the ascending (D3 receptor-mediated), but not descending (D2 receptor-mediated), limb of the yawning dose-response curve shifted leftward. The D3 receptor-selective antagonist PG01037 shifted the ascending limb of the dose-response curve to the right in all rats. When rats that previously drank sucrose drank water, their sensitivity to quinpirole did not return to normal. Quinpirole-induced hypothermia was not different between groups. These data show that drinking sucrose increases sensitivity to a dopamine D3, but not D2, receptor-mediated effect and that this change is long lasting. Dopamine receptors mediate the effects of many drugs and the actions of those drugs are likely impacted by dietary factors. PMID:21979833

Drinking sucrose enhances quinpirole-induced yawning in rats.

PubMed

Baladi, Michelle G; Newman, Amy H; Thomas, Yvonne M; France, Charles P

2011-12-01

Food and drugs can activate brain dopamine systems and sensitivity to the effects of drugs acting on those systems is influenced by amount and content of food consumed. This study examined the effects of drinking sucrose on behavioral effects of the direct-acting dopamine receptor agonist quinpirole. Male Sprague-Dawley rats (n=6/group) had free access to water or 10% sucrose and quinpirole dose-response curves (yawning and hypothermia) were generated weekly for 8 weeks. Subsequently, all rats drank water for 8 weeks with quinpirole dose-response curves determined on weeks 9, 10, and 16. In rats drinking sucrose, the ascending (D3 receptor-mediated), but not descending (D2 receptor-mediated), limb of the yawning dose-response curve shifted leftward. The D3 receptor-selective antagonist PG01037 shifted the ascending limb of the dose-response curve to the right in all rats. When rats that previously drank sucrose drank water, their sensitivity to quinpirole did not return to normal. Quinpirole-induced hypothermia was not different between groups. These data show that drinking sucrose increases sensitivity to a dopamine D3, but not D2, receptor-mediated effect and that this change is long lasting. Dopamine receptors mediate the effects of many drugs and the actions of those drugs are likely impacted by dietary factors.

High-Potential Electrocatalytic O2 Reduction with Nitroxyl/NOx Mediators: Implications for Fuel Cells and Aerobic Oxidation Catalysis

PubMed Central

2015-01-01

Efficient reduction of O2 to water is a central challenge in energy conversion and many aerobic oxidation reactions. Here, we show that the electrochemical oxygen reduction reaction (ORR) can be achieved at high potentials by using soluble organic nitroxyl and nitrogen oxide (NOx) mediators. When used alone, neither organic nitroxyls, such as 2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl (TEMPO), nor NOx species, such as sodium nitrite, are effective ORR mediators. The combination of nitroxyl/NOx species, however, mediates sustained O2 reduction with overpotentials as low as 300 mV in acetonitrile containing trifluoroacetic acid. Mechanistic analysis of the coupled redox reactions supports a process in which the nitrogen oxide catalyst drives aerobic oxidation of a nitroxyl mediator to an oxoammonium species, which then is reduced back to the nitroxyl at the cathode. The electrolysis potential is dictated by the oxoammonium/nitroxyl reduction potential. The overpotentials accessible with this ORR system are significantly lower than widely studied molecular metal-macrocycle ORR catalysts and benefit from the mechanism-based specificity for four-electron reduction of oxygen to water mediated by NOx species, together with kinetically efficient reduction of oxidized NOx species by TEMPO and other organic nitroxyls. PMID:27162977

Structure of Ceramide-1-Phosphate at the Air-Water Solution Interface in the Absence and Presence of Ca2+

PubMed Central

Kooijman, Edgar E.; Vaknin, David; Bu, Wei; Joshi, Leela; Kang, Shin-Woong; Gericke, Arne; Mann, Elizabeth K.; Kumar, Satyendra

2009-01-01

Ceramide-1-phosphate, the phosphorylated form of ceramide, gained attention recently due to its diverse intracellular roles, in particular in inflammation mediated by cPLA2α. However, surprisingly little is known about the physical chemical properties of this lipid and its potential impact on physiological function. For example, the presence of Ca2+ is indispensable for the interaction of Cer-1-P with the C2 domain of cPLA2α. We report on the structure and morphology of Cer-1-P in monomolecular layers at the air/water solution interface in the absence and presence of Ca2+ using diverse biophysical techniques, including synchrotron x-ray reflectivity and grazing angle diffraction, to gain insight into the role and function of Cer-1-P in biomembranes. We show that relatively small changes in pH and the presence of monovalent cations dramatically affect the behavior of Cer-1-P. On pure water Cer-1-P forms a solid monolayer despite the negative charge of the phosphomonoester headgroup. In contrast, pH 7.2 buffer yields a considerably less solid-like monolayer, indicating that charge-charge repulsion becomes important at higher pH. Calcium was found to bind strongly to the headgroup of Cer-1-P even in the presence of a 100-fold larger Na+ concentration. Analysis of the x-ray reflectivity data allowed us to estimate how much Ca2+ is bound to the headgroup, ∼0.5 Ca2+ and ∼1.0 Ca2+ ions per Cer-1-P molecule for the water and buffer subphase respectively. These results can be qualitatively understood based on the molecular structure of Cer-1-P and the electrostatic/hydrogen-bond interactions of its phosphomonoester headgroup. Biological implications of our results are also discussed. PMID:19289047

The Asian tiger mosquito, Aedes (Stegomyia) albopictus (Skuse), a vector of dengue, chikungunya and zika viruses, reaches Portugal (Diptera: Culicidae).

PubMed

Marabuto, Eduardo; Rebelo, Maria Teresa

2018-04-20

The Asian tiger mosquito, Aedes (Stegomyia) albopictus (Skuse), is a tropical species originally from south-eastern Asia (Hawley, 1988). It has experienced a rampant human-mediated range expansion since the 1970s to now occupy almost the whole of the tropical and subtropical areas of the world. As an eclectic haematophagous species, it attacks humans and is able to use a number of man-made and natural structures where stagnant water is present (Estrada-Franco Craig, 1995). Eggs are able to survive for extended periods of time in complete dryness and diapause over unsuitable cold season, making it an especially resilient species (Hawley, 1988).

A Microscopic Interpretation of Pump-Probe Vibrational Spectroscopy Using Ab Initio Molecular Dynamics.

PubMed

Lesnicki, Dominika; Sulpizi, Marialore

2018-06-13

What happens when extra vibrational energy is added to water? Using nonequilibrium molecular dynamics simulations, also including the full electronic structure, and novel descriptors, based on projected vibrational density of states, we are able to follow the flow of excess vibrational energy from the excited stretching and bending modes. We find that the energy relaxation, mostly mediated by a stretching-stretching coupling in the first solvation shell, is highly heterogeneous and strongly depends on the local environment, where a strong hydrogen bond network can transport energy with a time scale of 200 fs, whereas a weaker network can slow down the transport by a factor 2-3.

Shifts in water availability mediate plant-pollinator interactions.

PubMed

Gallagher, M Kate; Campbell, Diane R

2017-07-01

Altered precipitation patterns associated with anthropogenic climate change are expected to have many effects on plants and insect pollinators, but it is unknown if effects on pollination are mediated by changes in water availability. We tested the hypothesis that impacts of climate on plant-pollinator interactions operate through changes in water availability, and specifically that such effects occur through alteration of floral attractants. We manipulated water availability in two naturally occurring Mertensia ciliata (Boraginaceae) populations using water addition, water reduction and control plots and measured effects on vegetative and floral traits, pollinator visitation and seed set. While most floral trait values, including corolla size and nectar, increased linearly with increasing water availability, in this bumblebee-pollinated species, pollinator visitation peaked at intermediate water levels. Visitation also peaked at an intermediate corolla length, while its relationship to corolla width varied across sites. Seed set, however, increased linearly with water. These results demonstrate the potential for changes in water availability to impact plant-pollinator interactions through pollinator responses to differences in floral attractants, and that the effects of water on pollinator visitation can be nonlinear. Plant responses to changes in resource availability may be an important mechanism by which climate change will affect species interactions. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Detection of different β-lactamases encoding genes, including blaNDM, and plasmid-mediated quinolone resistance genes in different water sources from Brazil.

PubMed

Sanchez, Danilo Garcia; de Melo, Fernanda Maciel; Savazzi, Eduardo Angelino; Stehling, Eliana Guedes

2018-06-16

Bacterial resistance occurs by spontaneous mutations or horizontal gene transfer mediated by mobile genetic elements, which represents a great concern. Resistance to β-lactam antibiotics is mainly due to the production of β-lactamases, and an important mechanism of fluoroquinolone resistance is the acquisition plasmid determinants. The aim of this study was to verify the presence of β-lactamase-encoding genes and plasmid-mediated quinolone resistance genes in different water samples obtained from São Paulo state, Brazil. A high level of these resistance genes was detected, being the bla SHV , bla GES , and qnr the most prevalent. Besides that, the bla NDM gene, which codify an important and hazardous metallo-β-lactamase, was detected.

Persistent Neuroinflammatory Effects of Serial Exposure to Stress and Methamphetamine on the Blood-Brain Barrier

PubMed Central

Northrop, Nicole A.

2013-01-01

Studies of methamphetamine (Meth)-induced neurotoxicity have traditionally focused on monoaminergic terminal damage while more recent studies have found that stress exacerbates these damaging effects of Meth. Similarities that exist between the mechanisms that cause monoaminergic terminal damage in response to stress and Meth and those capable of producing a disruption of the blood-brain barrier (BBB) suggest that the well-known high comorbidity of stress and Meth could produce long-lasting structural and functional BBB disruption. The current studies examined the role of neuroinflammation in mediating the effects of exposure to chronic stress and/or Meth on BBB structure and function. Rats were pre-exposed to chronic unpredictable stress (CUS) and/or challenged with Meth. Twenty-four hours after the treatment of Meth in rats pre-exposed to CUS, occludin and claudin-5 immunoreactivity were decreased while truncation of β-dystroglycan, as well as FITC-dextran and water extravasation was increased. All changes other than β-dystroglycan and edema persisted 7 days later, occurred with increases in GFAP and COX-2, and were blocked by ketoprofen after Meth treatment. In addition, persistent increases in FITC-dextran extravasation were prevented by treatment with an EP1 receptor antagonist after Meth exposure. The results indicate that CUS and Meth synergize to produce long-lasting structural and functional BBB disruptions that are mediated by cyclooxygenase and protracted increases in inflammation. These results suggest that stress and Meth can synergize to produce a long-lasting vulnerability of the brain to subsequent environmental insults resulting from the persistent breach of the BBB. PMID:22833424

Abscisic Acid Regulation of Root Hydraulic Conductivity and Aquaporin Gene Expression Is Crucial to the Plant Shoot Growth Enhancement Caused by Rhizosphere Humic Acids.

PubMed

Olaetxea, Maite; Mora, Verónica; Bacaicoa, Eva; Garnica, María; Fuentes, Marta; Casanova, Esther; Zamarreño, Angel M; Iriarte, Juan C; Etayo, David; Ederra, Iñigo; Gonzalo, Ramón; Baigorri, Roberto; García-Mina, Jose M

2015-12-01

The physiological and metabolic mechanisms behind the humic acid-mediated plant growth enhancement are discussed in detail. Experiments using cucumber (Cucumis sativus) plants show that the shoot growth enhancement caused by a structurally well-characterized humic acid with sedimentary origin is functionally associated with significant increases in abscisic acid (ABA) root concentration and root hydraulic conductivity. Complementary experiments involving a blocking agent of cell wall pores and water root transport (polyethylenglycol) show that increases in root hydraulic conductivity are essential in the shoot growth-promoting action of the model humic acid. Further experiments involving an inhibitor of ABA biosynthesis in root and shoot (fluridone) show that the humic acid-mediated enhancement of both root hydraulic conductivity and shoot growth depended on ABA signaling pathways. These experiments also show that a significant increase in the gene expression of the main root plasma membrane aquaporins is associated with the increase of root hydraulic conductivity caused by the model humic acid. Finally, experimental data suggest that all of these actions of model humic acid on root functionality, which are linked to its beneficial action on plant shoot growth, are likely related to the conformational structure of humic acid in solution and its interaction with the cell wall at the root surface. © 2015 American Society of Plant Biologists. All Rights Reserved.

Aquaporin8 regulates cellular development and reactive oxygen species production, a critical component of virulence in Botrytis cinerea.

PubMed

An, Bang; Li, Boqiang; Li, Hua; Zhang, Zhanquan; Qin, Guozheng; Tian, Shiping

2016-03-01

Aquaporins (AQPs) are ubiquitous in nearly all organisms, mediating selective and rapid flux of water across biological membranes. The role of AQPs in phytopathogenic fungi is poorly understood. Orthologs of AQP genes in Botrytis cinerea were identified and knocked out. The effects of AQPs on hyphal growth and conidiation, formation of infection structures and virulence on plant hosts were examined. The role of AQP8 in reactive oxygen species (ROS) production, distribution and transport were further determined. Among eight AQPs, only AQP8 was essential for the ability of B. cinerea to infect plants. AQP8 was demonstrated to be an intrinsic plasma membrane protein, which may function as a channel and mediate hydrogen peroxide uptake. Deletion of AQP8 in B. cinerea completely inhibited the development of conidia and infection structures, and significantly affected noxR expression. Further observations revealed that both AQP8 and noxR impacted ROS distribution in the hyphal tips of B. cinerea. Moreover, AQP8 affected the expression of a mitochondrial protein, NQO1. A knockout mutant of NQO1 was observed to display reduced virulence. These data lead to a better understanding of the important role of AQP8 in the development and pathogenesis of plant pathogens. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Environmental change mediates mate choice for an extended phenotype, but not for mate quality.

PubMed

Head, Megan L; Fox, Rebecca J; Barber, Iain

2017-01-01

Sexual cues, including extended phenotypes, are expected to be reliable indicators of male genetic quality and/or provide information on parental quality. However, the reliability of these cues may be dependent on stability of the environment, with heterogeneity affecting how selection acts on such traits. Here, we test how environmental change mediates mate choice for multiple sexual traits, including an extended phenotype--the structure of male-built nests - in stickleback fish. First, we manipulated the dissolved oxygen (DO) content of water to create high or low DO environments in which male fish built nests. Then we recorded the mate choice of females encountering these males (and their nests), under either the same or reversed DO conditions. Males in high DO environments built more compact nests than those in low DO conditions and males adjusted their nest structure in response to changing conditions. Female mate choice for extended phenotype (male nests) was environmentally dependent (females chose more compact nests in high DO conditions), while female choice for male phenotype was not (females chose large, vigorous males regardless of DO level). Examining mate choice in this dynamic context suggests that females evaluate the reliability of multiple sexual cues, taking into account environmental heterogeneity. © 2016 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Abscisic Acid Regulation of Root Hydraulic Conductivity and Aquaporin Gene Expression Is Crucial to the Plant Shoot Growth Enhancement Caused by Rhizosphere Humic Acids1

PubMed Central

Bacaicoa, Eva; Garnica, María; Fuentes, Marta; Casanova, Esther; Etayo, David; Ederra, Iñigo; Gonzalo, Ramón

2015-01-01

The physiological and metabolic mechanisms behind the humic acid-mediated plant growth enhancement are discussed in detail. Experiments using cucumber (Cucumis sativus) plants show that the shoot growth enhancement caused by a structurally well-characterized humic acid with sedimentary origin is functionally associated with significant increases in abscisic acid (ABA) root concentration and root hydraulic conductivity. Complementary experiments involving a blocking agent of cell wall pores and water root transport (polyethylenglycol) show that increases in root hydraulic conductivity are essential in the shoot growth-promoting action of the model humic acid. Further experiments involving an inhibitor of ABA biosynthesis in root and shoot (fluridone) show that the humic acid-mediated enhancement of both root hydraulic conductivity and shoot growth depended on ABA signaling pathways. These experiments also show that a significant increase in the gene expression of the main root plasma membrane aquaporins is associated with the increase of root hydraulic conductivity caused by the model humic acid. Finally, experimental data suggest that all of these actions of model humic acid on root functionality, which are linked to its beneficial action on plant shoot growth, are likely related to the conformational structure of humic acid in solution and its interaction with the cell wall at the root surface. PMID:26450705

Vesicle-mediated growth of tubular branches and centimeter-long microtubes from a single molecule.

PubMed

Abbas, Abdennour; Brimer, Andrew; Tian, Limei; d'Avignon, D André; Hameed, Abdulrahman Shahul; Vittal, Jagadese J; Singamaneni, Srikanth

2013-08-12

The mechanism by which small molecules assemble into microscale tubular structures in aqueous solution remains poorly understood, particularly when the initial building blocks are non-amphiphilic molecules and no surfactant is used. It is here shown how a subnanometric molecule, namely p-aminothiophenol (p-ATP), prepared in normal water with a small amount of ethanol, spontaneously assembles into a new class of nanovesicle. Due to Brownian motion, these nanostructures rapidly grow into micrometric vesicles and start budding to yield macroscale tubular branches with a remarkable growth rate of ∼20 μm s⁻¹. A real-time visualization by optical microscopy reveals that tubular growth proceeds by vesicle walk and fusion on the apex (growth cone) and sides of the branches and ultimately leads to the generation of centimeter-long microtubes. This unprecedented growth mechanism is triggered by a pH-activated proton switch and maintained by hydrogen bonding. The vesicle fusion-mediated synthesis suggests that functional microtubes with biological properties can be efficiently prepared with a mixture of appropriate diaminophenyl blocks and the desired macromolecule. The reversibility, timescale, and very high yield (90%) of this synthetic approach make it a valuable model for the investigation of hierarchical and structural transition between organized assemblies with different size scales and morphologies. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plant Clonal Integration Mediates the Horizontal Redistribution of Soil Resources, Benefiting Neighboring Plants.

PubMed

Ye, Xue-Hua; Zhang, Ya-Lin; Liu, Zhi-Lan; Gao, Shu-Qin; Song, Yao-Bin; Liu, Feng-Hong; Dong, Ming

2016-01-01

Resources such as water taken up by plants can be released into soils through hydraulic redistribution and can also be translocated by clonal integration within a plant clonal network. We hypothesized that the resources from one (donor) microsite could be translocated within a clonal network, released into different (recipient) microsites and subsequently used by neighbor plants in the recipient microsite. To test these hypotheses, we conducted two experiments in which connected and disconnected ramet pairs of Potentilla anserina were grown under both homogeneous and heterogeneous water regimes, with seedlings of Artemisia ordosica as neighbors. The isotopes [(15)N] and deuterium were used to trace the translocation of nitrogen and water, respectively, within the clonal network. The water and nitrogen taken up by P. anserina ramets in the donor microsite were translocated into the connected ramets in the recipient microsites. Most notably, portions of the translocated water and nitrogen were released into the recipient microsite and were used by the neighboring A. ordosica, which increased growth of the neighboring A. ordosica significantly. Therefore, our hypotheses were supported, and plant clonal integration mediated the horizontal hydraulic redistribution of resources, thus benefiting neighboring plants. Such a plant clonal integration-mediated resource redistribution in horizontal space may have substantial effects on the interspecific relations and composition of the community and consequently on ecosystem processes.

Dominant forest tree mycorrhizal type mediates understory plant invasions

Treesearch

Insu Jo; Kevin M. Potter; Grant M. Domke; Songlin Fei

2017-01-01

Forest mycorrhizal type mediates nutrient dynamics, which in turn can influence forest community structure and processes. Using forest inventory data, we explored how dominant forest tree mycorrhizal type affects understory plant invasions with consideration of forest structure and soil properties. We found that arbuscular mycorrhizal (AM) dominant forests, which are...

Class Inclusion and Role-Taking: Structural Mediation.

ERIC Educational Resources Information Center

Gash, Hugh

The mediational linkage between class inclusion and role-taking skills was investigated by studying the effects of a successive perspective-taking training technique on the consolidation of class inclusion structures. Sixty preoperational Irish boys were given two pretest measures of class inclusion and two of role-taking. They were then grouped…

Effects of climate change on hydrology, water resources, and soil [Chapter 4

Treesearch

Mark J. Muir; Charles H. Luce; Joseph T. Gurrieri; Marek Matyjasik; Jeffrey L. Bruggink; Stacey L. Weems; James C. Hurja; David B. Marr; Sarah D. Leahy

2018-01-01

Water is critical to life, and many of the effects of climate change on ecosystems are mediated through altered hydrology. Snow accumulation and melt are consistently cited as the most important changes to water in the western United States (Barnett et al. 2005; Service 2004), affecting when water will be available for forests, fish, and people. Changes in summer...

Effect of 4-hydroxy-2-nonenal on myoglobin-mediated lipid oxidation when varying histidine content and hemin affinity.

PubMed

Grunwald, Eric W; Tatiyaborworntham, Nantawat; Faustman, Cameron; Richards, Mark P

2017-07-15

The compound 4-hydroxy-2-nonenal (HNE) dissolved in water was examined to remove potential effects of using ethanol to solubilize the aldehyde such as altering protein structure or redox properties of myoglobin (Mb). HNE became covalently bound to sperm whale Mb at up to five sites based on ESI-MS analysis. Adducted Mb promoted lipid oxidation in washed muscle more effectively than non-adducted Mb. Alkylation of P88H/Q152HMb with HNE accelerated metMb formation and subsequent lipid oxidation. P88H/Q152HMb exposed to HNE enhanced lipid oxidation compared to wild-type Mb exposed to HNE. Results using H97A Mb suggested that the combination of HNE and low hemin affinity facilitated rapid decomposition of preformed lipid hydroperoxides to secondary lipid oxidation products. HNE and HHE (4-hydroxy-2-hexenal) facilitated Mb-mediated lipid oxidation similarly. The potential mechanisms by which Mb binding of α,β-unsaturated aldehydes affect Mb oxidation and the onset of lipid oxidation are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Plant-plant competition outcomes are modulated by plant effects on the soil bacterial community.

PubMed

Hortal, S; Lozano, Y M; Bastida, F; Armas, C; Moreno, J L; Garcia, C; Pugnaire, F I

2017-12-19

Competition is a key process that determines plant community structure and dynamics, often mediated by nutrients and water availability. However, the role of soil microorganisms on plant competition, and the links between above- and belowground processes, are not well understood. Here we show that the effects of interspecific plant competition on plant performance are mediated by feedbacks between plants and soil bacterial communities. Each plant species selects a singular community of soil microorganisms in its rhizosphere with a specific species composition, abundance and activity. When two plant species interact, the resulting soil bacterial community matches that of the most competitive plant species, suggesting strong competitive interactions between soil bacterial communities as well. We propose a novel mechanism by which changes in belowground bacterial communities promoted by the most competitive plant species influence plant performance and competition outcome. These findings emphasise the strong links between plant and soil communities, paving the way to a better understanding of plant community dynamics and the effects of soil bacterial communities on ecosystem functioning and services.

Structure and Properties of Polysaccharide Based BioPolymer Gels

NASA Astrophysics Data System (ADS)

Prud'Homme, Robert K.

2000-03-01

Nature uses the pyranose ring as the basic building unit for a wideclass of biopolymers. Because of their biological origin these biopolymers naturally find application as food additives, rheology modifiers. These polymers range from being rigid skeletal material, such as cellulose that resist dissolution in water, to water soluble polymers, such as guar or carrageenan. The flexibility of the basic pyranose ring structure to provide materials with such a wide range of properties comes from the specific interactions that can be engineered by nature into the structure. We will present several examples of specific interactions for these systems: hydrogen bonding, hydrophobic interactions, and specific ion interactions. The relationship between molecular interations and rheology will be emphasized. Hydrogen bonding mediated by steric interference is used to control of solubility of starch and the rheology of guar gels. A more interesting example is the hydrogen bonding induced by chemical modification in konjac glucomannan that results in a gel that melts upon cooling. Hydrogen bonding interactions in xanthan lead to gel formation at very low polymer concentrations which is a result of the fine tuning of the polymer persistence length and total contour length. Given the function of xanthan in nature its molecular architecture has been optimized. Hydrophobic interactions in methylcellulose show a reverse temperature dependence arising from solution entropy. Carrageenan gelation upon the addition of specific cations will be addressed to show the interplay of polymer secondary structure on chemical reactivity. And finally the cis-hydroxyls on galactomannans permit crosslinking by a variety of metal ions some of which lead to "living gels" and some of which lead to permanently crosslinked networks.

Aqua mediated synthesis of bio-active compounds.

PubMed

Panda, Siva S

2013-05-01

Recently the aqueous medium has attracted the interest of organic chemists, and many. Moreover, in the past 20 years, the drug-discovery process has undergone extraordinary changes, and high-throughput biological screening of potential drug candidates has led to an ever-increasing demand for novel drug-like compounds. Noteworthy advantages were observed during the course of study on aqua mediated synthesis of compounds of medicinal importance. The established advantages of water as a solvent for reactions are, water is the most abundant and available resource on the planet and many biochemical processes occur in aqueous medium. This review will focus on describing new developments in the application of water in medicinal chemistry for the synthesis of bio-active compounds possessing various biological properties.

Gas-phase water-mediated equilibrium between methylglyoxal and its geminal diol

PubMed Central

Axson, Jessica L.; Takahashi, Kaito; De Haan, David O.; Vaida, Veronica

2010-01-01

In aqueous solution, aldehydes, and to a lesser extent ketones, hydrate to form geminal diols. We investigate the hydration of methylglyoxal (MG) in the gas phase, a process not previously considered to occur in water-restricted environments. In this study, we spectroscopically identified methylglyoxal diol (MGD) and obtained the gas-phase partial pressures of MG and MGD. These results, in conjunction with the relative humidity, were used to obtain the equilibrium constant, KP, for the water-mediated hydration of MG in the gas phase. The Gibbs free energy for this process, ΔG°, obtained as a result, suggests a larger than expected gas-phase diol concentration. This may have significant implications for understanding the role of organics in atmospheric chemistry. PMID:20142510

Assessing mediation using marginal structural models in the presence of confounding and moderation

PubMed Central

Coffman, Donna L.; Zhong, Wei

2012-01-01

This paper presents marginal structural models (MSMs) with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of non-randomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PMID:22905648

Assessing mediation using marginal structural models in the presence of confounding and moderation.

PubMed

Coffman, Donna L; Zhong, Wei

2012-12-01

This article presents marginal structural models with inverse propensity weighting (IPW) for assessing mediation. Generally, individuals are not randomly assigned to levels of the mediator. Therefore, confounders of the mediator and outcome may exist that limit causal inferences, a goal of mediation analysis. Either regression adjustment or IPW can be used to take confounding into account, but IPW has several advantages. Regression adjustment of even one confounder of the mediator and outcome that has been influenced by treatment results in biased estimates of the direct effect (i.e., the effect of treatment on the outcome that does not go through the mediator). One advantage of IPW is that it can properly adjust for this type of confounding, assuming there are no unmeasured confounders. Further, we illustrate that IPW estimation provides unbiased estimates of all effects when there is a baseline moderator variable that interacts with the treatment, when there is a baseline moderator variable that interacts with the mediator, and when the treatment interacts with the mediator. IPW estimation also provides unbiased estimates of all effects in the presence of nonrandomized treatments. In addition, for testing mediation we propose a test of the null hypothesis of no mediation. Finally, we illustrate this approach with an empirical data set in which the mediator is continuous, as is often the case in psychological research. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Light-scattering studies of protein solutions: role of hydration in weak protein-protein interactions.

PubMed

Paliwal, A; Asthagiri, D; Abras, D; Lenhoff, A M; Paulaitis, M E

2005-09-01

We model the hydration contribution to short-range electrostatic/dispersion protein interactions embodied in the osmotic second virial coefficient, B(2), by adopting a quasi-chemical description in which water molecules associated with the protein are identified through explicit molecular dynamics simulations. These water molecules reduce the surface complementarity of highly favorable short-range interactions, and therefore can play an important role in mediating protein-protein interactions. Here we examine this quasi-chemical view of hydration by predicting the interaction part of B(2) and comparing our results with those derived from light-scattering measurements of B(2) for staphylococcal nuclease, lysozyme, and chymotrypsinogen at 25 degrees C as a function of solution pH and ionic strength. We find that short-range protein interactions are influenced by water molecules strongly associated with a relatively small fraction of the protein surface. However, the effect of these strongly associated water molecules on the surface complementarity of short-range protein interactions is significant, and must be taken into account for an accurate description of B(2). We also observe remarkably similar hydration behavior for these proteins despite substantial differences in their three-dimensional structures and spatial charge distributions, suggesting a general characterization of protein hydration.

Calculation of Relative Binding Free Energy in the Water-Filled Active Site of Oligopeptide-Binding Protein A.

PubMed

Maurer, Manuela; de Beer, Stephanie B A; Oostenbrink, Chris

2016-04-15

The periplasmic oligopeptide binding protein A (OppA) represents a well-known example of water-mediated protein-ligand interactions. Here, we perform free-energy calculations for three different ligands binding to OppA, using a thermodynamic integration approach. The tripeptide ligands share a high structural similarity (all have the sequence KXK), but their experimentally-determined binding free energies differ remarkably. Thermodynamic cycles were constructed for the ligands, and simulations conducted in the bound and (freely solvated) unbound states. In the unbound state, it was observed that the difference in conformational freedom between alanine and glycine leads to a surprisingly slow convergence, despite their chemical similarity. This could be overcome by increasing the softness parameter during alchemical transformations. Discrepancies remained in the bound state however, when comparing independent simulations of the three ligands. These difficulties could be traced to a slow relaxation of the water network within the active site. Fluctuations in the number of water molecules residing in the binding cavity occur mostly on a timescale larger than the simulation time along the alchemical path. After extensive simulations, relative binding free energies that were converged to within thermal noise could be obtained, which agree well with available experimental data.

Calculation of Relative Binding Free Energy in the Water-Filled Active Site of Oligopeptide-Binding Protein A

PubMed Central

Maurer, Manuela; de Beer, Stephanie B. A.; Oostenbrink, Chris

2018-01-01

The periplasmic oligopeptide binding protein A (OppA) represents a well-known example of water-mediated protein-ligand interactions. Here, we perform free-energy calculations for three different ligands binding to OppA, using a thermodynamic integration approach. The tripeptide ligands share a high structural similarity (all have the sequence KXK), but their experimentally-determined binding free energies differ remarkably. Thermodynamic cycles were constructed for the ligands, and simulations conducted in the bound and (freely solvated) unbound states. In the unbound state, it was observed that the difference in conformational freedom between alanine and glycine leads to a surprisingly slow convergence, despite their chemical similarity. This could be overcome by increasing the softness parameter during alchemical transformations. Discrepancies remained in the bound state however, when comparing independent simulations of the three ligands. These difficulties could be traced to a slow relaxation of the water network within the active site. Fluctuations in the number of water molecules residing in the binding cavity occur mostly on a timescale larger than the simulation time along the alchemical path. After extensive simulations, relative binding free energies that were converged to within thermal noise could be obtained, which agree well with available experimental data. PMID:27092480

Fate of internal waves on a shallow shelf

NASA Astrophysics Data System (ADS)

Davis, Kristen; Arthur, Robert; Reid, Emma; Decarlo, Thomas; Cohen, Anne

2017-11-01

Internal waves strongly influence the physical and chemical environment of coastal ecosystems worldwide. We report novel observations from a distributed temperature sensing (DTS) system that tracked the transformation of internal waves from the shelf break to the surf zone over a shelf-slope region of a coral atoll in the South China Sea. The spatially-continuous view of the near-bottom temperature field provided by the DTS offers a perspective of physical processes previously available only in laboratory settings or numerical models. These processes include internal wave reflection off a natural slope, shoreward transport of dense fluid within trapped cores, internal ``tide pools'' (dense water left behind after the retreat of an internal wave), and internal run-down (near-bottom, offshore-directed jets of water preceding a breaking internal wave). Analysis shows that the fate of internal waves on this shelf - whether they are transmitted into shallow waters or reflected back offshore - is mediated by local water column density and shear structure, with important implications for nearshore distributions of energy, heat, and nutrients. We acknowledge the US Army Research Laboratory DoD Supercomputing Resource Center for computer time on Excalibur, which was used for the numerical simulations in this work. Funding for field work supported by Academia Sinica and for K.D. and E.R. from NSF.

Histone modifications influence mediator interactions with chromatin

PubMed Central

Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

2011-01-01

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760

Structures of rat cytosolic PEPCK: insight into the mechanism of phosphorylation and decarboxylation of oxaloacetic acid.

PubMed

Sullivan, Sarah M; Holyoak, Todd

2007-09-04

The structures of the rat cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK) reported in the PEPCK-Mn2+, -Mn2+-oxaloacetic acid (OAA), -Mn2+-OAA-Mn2+-guanosine-5'-diphosphate (GDP), and -Mn2+-Mn2+-guanosine-5'-tri-phosphate (GTP) complexes provide insight into the mechanism of phosphoryl transfer and decarboxylation mediated by this enzyme. OAA is observed to bind in a number of different orientations coordinating directly to the active site metal. The Mn2+-OAA and Mn2+-OAA-Mn2+GDP structures illustrate inner-sphere coordination of OAA to the manganese ion through the displacement of two of the three water molecules coordinated to the metal in the holo-enzyme by the C3 and C4 carbonyl oxygens. In the PEPCK-Mn2+-OAA complex, an alternate bound conformation of OAA is present. In this conformation, in addition to the previous interactions, the C1 carboxylate is directly coordinated to the active site Mn2+, displacing all of the waters coordinated to the metal in the holo-enzyme. In the PEPCK-Mn2+-GTP structure, the same water molecule displaced by the C1 carboxylate of OAA is displaced by one of the gamma-phosphate oxygens of the triphosphate nucleotide. The structures are consistent with a mechanism of direct in-line phosphoryl transfer, supported by the observed stereochemistry of the reaction. In the catalytically competent binding mode, the C1 carboxylate of OAA is sandwiched between R87 and R405 in an environment that would serve to facilitate decarboxylation. In the reverse reaction, these two arginines would form the CO2 binding site. Comparison of the Mn2+-OAA-Mn2+GDP and Mn2+-Mn2+GTP structures illustrates a marked difference in the bound conformations of the nucleotide substrates in which the GTP nucleotide is bound in a high-energy state resulting from the eclipsing of all three of the phosphoryl groups along the triphosphate chain. This contrasts a previously determined structure of PEPCK in complex with a triphosphate nucleotide analogue in which the analogue mirrors the conformation of GDP as opposed to GTP. Last, the structures illustrate a correlation between conformational changes in the P-loop, the nucleotide binding site, and the active site lid that are important for catalysis.

Degradation of sulfadimethoxine catalyzed by laccase with soybean meal extract as natural mediator: Mechanism and reaction pathway.

PubMed

Liang, Shangtao; Luo, Qi; Huang, Qingguo

2017-08-01

Natural laccase-mediator systems have been well recognized as an eco-friendly and energy-saving approach in environmental remediation, whose further application is however limited by the high cost of natural mediators and relatively long treatment time span. This study evaluated the water extract of soybean meal, a low-cost compound system, in mediating the laccase catalyzed degradation of a model contaminant of emerging concern, sulfadimethoxine (SDM), and demonstrated it as a promising alternative mediator for soil and water remediation. Removal of 73.3% and 65.6% was achieved in 9 h using soybean meal extract (SBE) as the mediating system for laccase-catalyzed degradation of sulfadimethoxine at the concentration of 1 ppm and 10 ppm, respectively. Further degradation of sulfadimethoxine was observed with multiple SBE additions. Using SBE as mediator increased the 9-h removal of SDM at 1 ppm initial concentration by 52.9%, 49.4%, and 36.3% in comparison to the system mediated by 1-Hydroxybenzotriazole (HBT), p-Coumaric acid (COU) and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonate) (ABTS), respectively. With the detection of stable coupling products formed with radical scavenger (5,5-Dimethyl-1-pyrroline N-oxide, DMPO), three phenolic compounds (vanillin, apocynin, and daidzein) in SBE were confirmed to serve as mediators for Trametes versicolor laccase. Reaction pathways were proposed based on the results of High Resolution Mass Spectrometry. SO 2 excursion happened during SDM transformation, leading to elimination of antimicrobial activity. Therefore, as a natural, phenol rich, and affordable compound system, the future application of SBE in wastewater and soil remediation is worth exploring. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aquaporins in Clinical Medicine

PubMed Central

Verkman, A.S.

2012-01-01

The aquaporins are a family of membrane water channels, some of which also transport glycerol. They are involved in a wide range of physiological functions (including water/salt homeostasis, exocrine fluid secretion, and epidermal hydration) and human diseases (including glaucoma, cancer, epilepsy, and obesity). At the cellular level, aquaporin-mediated osmotic water transport across cell plasma membranes facilitates transepithelial fluid transport, cell migration, and neuroexcitation; aquaporin-mediated glycerol transport regulates cell proliferation, adipocyte metabolism, and epidermal water retention. Genetic diseases caused by loss-of-function mutations in aquaporins include nephrogenic diabetes insipidus and congenital cataracts. The neuroinflammatory demyelinating disease neuromyelitis optica is marked by pathogenic autoantibodies against astrocyte water channel aquaporin-4. There remain broad opportunities for the development of aquaporin-based diagnostics and therapeutics. Disease-relevant aquaporin polymorphisms are beginning to be explored. There is great promise in the development of small-molecule aquaporin modulators for therapy of some types of refractory edema, brain swelling, neuroinflammation, glaucoma, epilepsy, cancer, pain, and obesity. PMID:22248325

Infrared photodissociation spectroscopy of H(+)(H2O)6·M(m) (M = Ne, Ar, Kr, Xe, H2, N2, and CH4): messenger-dependent balance between H3O(+) and H5O2(+) core isomers.

PubMed

Mizuse, Kenta; Fujii, Asuka

2011-04-21

Although messenger mediated spectroscopy is a widely-used technique to study gas phase ionic species, effects of messengers themselves are not necessarily clear. In this study, we report infrared photodissociation spectroscopy of H(+)(H(2)O)(6)·M(m) (M = Ne, Ar, Kr, Xe, H(2), N(2), and CH(4)) in the OH stretch region to investigate messenger(M)-dependent cluster structures of the H(+)(H(2)O)(6) moiety. The H(+)(H(2)O)(6), the protonated water hexamer, is the smallest system in which both the H(3)O(+) (Eigen) and H(5)O(2)(+) (Zundel) hydrated proton motifs coexist. All the spectra show narrower band widths reflecting reduced internal energy (lower vibrational temperature) in comparison with bare H(+)(H(2)O)(6). The Xe-, CH(4)-, and N(2)-mediated spectra show additional band features due to the relatively strong perturbation of the messenger. The observed band patterns in the Ar-, Kr-, Xe-, N(2)-, and CH(4)-mediated spectra are attributed mainly to the "Zundel" type isomer, which is more stable. On the other hand, the Ne- and H(2)-mediated spectra are accounted for by a mixture of the "Eigen" and "Zundel" types, like that of bare H(+)(H(2)O)(6). These results suggest that a messenger sometimes imposes unexpected isomer-selectivity even though it has been thought to be inert. Plausible origins of the isomer-selectivity are also discussed.

DOMMINO 2.0: integrating structurally resolved protein-, RNA-, and DNA-mediated macromolecular interactions

PubMed Central

Kuang, Xingyan; Dhroso, Andi; Han, Jing Ginger; Shyu, Chi-Ren; Korkin, Dmitry

2016-01-01

Macromolecular interactions are formed between proteins, DNA and RNA molecules. Being a principle building block in macromolecular assemblies and pathways, the interactions underlie most of cellular functions. Malfunctioning of macromolecular interactions is also linked to a number of diseases. Structural knowledge of the macromolecular interaction allows one to understand the interaction’s mechanism, determine its functional implications and characterize the effects of genetic variations, such as single nucleotide polymorphisms, on the interaction. Unfortunately, until now the interactions mediated by different types of macromolecules, e.g. protein–protein interactions or protein–DNA interactions, are collected into individual and unrelated structural databases. This presents a significant obstacle in the analysis of macromolecular interactions. For instance, the homogeneous structural interaction databases prevent scientists from studying structural interactions of different types but occurring in the same macromolecular complex. Here, we introduce DOMMINO 2.0, a structural Database Of Macro-Molecular INteractiOns. Compared to DOMMINO 1.0, a comprehensive database on protein-protein interactions, DOMMINO 2.0 includes the interactions between all three basic types of macromolecules extracted from PDB files. DOMMINO 2.0 is automatically updated on a weekly basis. It currently includes ∼1 040 000 interactions between two polypeptide subunits (e.g. domains, peptides, termini and interdomain linkers), ∼43 000 RNA-mediated interactions, and ∼12 000 DNA-mediated interactions. All protein structures in the database are annotated using SCOP and SUPERFAMILY family annotation. As a result, protein-mediated interactions involving protein domains, interdomain linkers, C- and N- termini, and peptides are identified. Our database provides an intuitive web interface, allowing one to investigate interactions at three different resolution levels: whole subunit network, binary interaction and interaction interface. Database URL: http://dommino.org PMID:26827237

Analysis and assessment of microbial biofilm-mediated concrete deterioration.

DOT National Transportation Integrated Search

2008-10-01

Inspections of bridge substructures in Texas identified surface deterioration of reinforced concrete columns on : bridges continuously exposed water. Initial hypothesis were that the surface deterioration was a result of the : acidity of the water in...

Catalytic transformation of persistent contaminants using a new composite material based on nanosized zero-valent metal - field experiment results

NASA Astrophysics Data System (ADS)

Dror, I.; Merom Jacov, O.; Berkowitz, B.

2010-12-01

A new composite material based on deposition of nanosized zero valent iron (ZVI) particles and cyanocobalamine (vitamin B12) on a diatomite matrix is presented. Cyanocobalamine is known to be an effective electron mediator, having strong synergistic effects with ZVI for reductive dehalogenation reactions. This composite material also improves the reducing capacity of nanosized ZVI by preventing agglomeration of iron particles, thus increasing their active surface area. The porous structure of the diatomite matrix allows high hydraulic conductivity, which favors channeling of contaminated water to the reactive surface of the composite material and in turn faster rates of remediation. The ability of the material to degrade or transform rapidly and completely a large spectrum of water pollutants will be demonstrated, based on results from two field site experiments where polluted groundwater containing a mixture of industrial and agricultural persistent pollutants was treated. In addition a set of laboratory experiments using individual contaminant solutions to analyze chemical transformations under controlled conditions will be presented.

Ameliorating effect of new constituents from the hooks of Uncaria rhynchophylla on scopolamine-induced memory impairment.

PubMed

Shin, Suk-Chul; Lee, Dong-Ung

2013-07-01

To study the chemical constituents and their anti-amnesic effect from the hooks of Uncaria rhynchophylla. The isolation of compounds was performed by chromatographic techniques and their structures were identified on the basis of spectral analysis. Their ameliorating effects on scopolamine-induced memory impairment in vivo using a Morris water-maze task and passive avoidance task system were evaluated. Activity-guided fractionation of the total extracts resulted in the isolation of four constituents, trans-anethole (1), p-anisaldehyde (2), estragole (3), and 3-oxo-olean-12-en-28-oic acid (4), which were found for the first time from this plant. Compound 1 exhibited a better memory enhancing effect than tacrine, a positive agent, at the same dose in the passive avoidance test and a similar property in the water-maze test, and its action may be mediated, in part, by the acetylcholine enhancing cholinergic nervous system. Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Water-Soluble Phosphinothiols for Traceless Staudinger Ligation and Integration with Expressed Protein Ligation

PubMed Central

Tam, Annie; Soellner, Matthew B.; Raines, Ronald T.

2010-01-01

The traceless Staudinger ligation is an effective means to synthesize an amide bond between two groups of otherwise orthogonal reactivity: a phosphinothioester and an azide. An important application of the Staudinger ligation is in the ligation of peptides at a variety of residues. Here, we demonstrate that the traceless Staudinger ligation can be achieved in water with a water-soluble reagent. Those reagents that provide a high yield of amide product discourage protonation of the nitrogen in the key iminophosphorane intermediate. The most efficacious reagent, bis(p-dimethylaminoethylphenyl)phosphinomethanethiol, mediates the rapid ligation of equimolar substrates in water. This reagent is also able to perform a transthioesterification reaction with the thioester intermediate formed during intein-mediated protein splicing. Hence, the traceless Staudinger ligation can be integrated with expressed protein ligation, extending the reach of modern protein chemistry. PMID:17713909

Parahippocampal Cortex Mediates the Relationship between Lutein and Crystallized Intelligence in Healthy, Older Adults

PubMed Central

Zamroziewicz, Marta K.; Paul, Erick J.; Zwilling, Chris E.; Johnson, Elizabeth J.; Kuchan, Matthew J.; Cohen, Neal J.; Barbey, Aron K.

2016-01-01

Introduction: Although, diet has a substantial influence on the aging brain, the relationship between dietary nutrients and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between a carotenoid important for brain health across the lifespan, lutein, and crystallized intelligence in cognitively intact older adults. We hypothesized that higher serum levels of lutein are associated with better performance on a task of crystallized intelligence, and that this relationship is mediated by gray matter structure of regions within the temporal cortex. This investigation aims to contribute to a growing line of evidence, which suggests that particular nutrients may slow or prevent aspects of cognitive decline by targeting specific features of brain aging. Methods: We examined 76 cognitively intact adults between the ages of 65 and 75 to investigate the relationship between serum lutein, tests of crystallized intelligence (measured by the Wechsler Abbreviated Scale of Intelligence), and gray matter volume of regions within the temporal cortex. A three-step mediation analysis was implemented using multivariate linear regressions to control for age, sex, education, income, depression status, and body mass index. Results: The mediation analysis revealed that gray matter thickness of one region within the temporal cortex, the right parahippocampal cortex (Brodmann's Area 34), partially mediates the relationship between serum lutein and crystallized intelligence. Conclusion: These results suggest that the parahippocampal cortex acts as a mediator of the relationship between serum lutein and crystallized intelligence in cognitively intact older adults. Prior findings substantiate the individual relationships reported within the mediation, specifically the links between (i) serum lutein and temporal cortex structure, (ii) serum lutein and crystallized intelligence, and (iii) parahippocampal cortex structure and crystallized intelligence. This report demonstrates a novel structural mediation between lutein status and crystallized intelligence, and therefore provides further evidence that specific nutrients may slow or prevent features of cognitive decline by hindering particular aspects of brain aging. Future work should examine the potential mechanisms underlying this mediation, including the antioxidant, anti-inflammatory, and membrane modulating properties of lutein. PMID:27999541

Glutamate-mediated excitotoxicity in schizophrenia: A review

PubMed Central

Plitman, Eric; Nakajima, Shinichiro; de la Fuente-Sandoval, Camilo; Gerretsen, Philip; Chakravarty, M. Mallar; Kobylianskii, Jane; Chung, Jun Ku; Caravaggio, Fernando; Iwata, Yusuke; Remington, Gary; Graff-Guerrero, Ariel

2015-01-01

Findings from neuroimaging studies in patients with schizophrenia suggest widespread structural changes although the mechanisms through which these changes occur are currently unknown. Glutamatergic activity appears to be increased in the early phases of schizophrenia and may contribute to these structural alterations through an excitotoxic effect. The primary aim of this review was to describe the possible role of glutamate-mediated excitotoxicity in explaining the presence of neuroanatomical changes within schizophrenia. A Medline® literature search was conducted, identifying English language studies on the topic of glutamate-mediated excitotoxicity in schizophrenia, using the terms “schizophreni*” and “glutam*” and ((“MRS” or “MRI” or “magnetic resonance”) or (“computed tomography” or “CT”)). Studies concomitantly investigating glutamatergic activity and brain structure in patients with schizophrenia were included. Results are discussed in the context of findings from preclinical studies. Seven studies were identified that met the inclusion criteria. These studies provide inconclusive support for the role of glutamate-mediated excitotoxicity in the occurrence of structural changes within schizophrenia, with the caveat that there is a paucity of human studies investigating this topic. Preclinical data suggest that an excitotoxic effect may occur as a result of a paradoxical increase in glutamatergic activity following N-methyl-D-aspartate receptor hypofunction. Based on animal literature, glutamate-mediated excitotoxicity may account for certain structural changes present in schizophrenia, but additional human studies are required to substantiate these findings. Future studies should adopt a longitudinal design and employ magnetic resonance imaging techniques to investigate whether an association between glutamatergic activity and structural changes exists in patients with schizophrenia. PMID:25159198

Structures of transcription pre-initiation complex with TFIIH and Mediator.

PubMed

Schilbach, S; Hantsche, M; Tegunov, D; Dienemann, C; Wigge, C; Urlaub, H; Cramer, P

2017-11-09

For the initiation of transcription, RNA polymerase II (Pol II) assembles with general transcription factors on promoter DNA to form the pre-initiation complex (PIC). Here we report cryo-electron microscopy structures of the Saccharomyces cerevisiae PIC and PIC-core Mediator complex at nominal resolutions of 4.7 Å and 5.8 Å, respectively. The structures reveal transcription factor IIH (TFIIH), and suggest how the core and kinase TFIIH modules function in the opening of promoter DNA and the phosphorylation of Pol II, respectively. The TFIIH core subunit Ssl2 (a homologue of human XPB) is positioned on downstream DNA by the 'E-bridge' helix in TFIIE, consistent with TFIIE-stimulated DNA opening. The TFIIH kinase module subunit Tfb3 (MAT1 in human) anchors the kinase Kin28 (CDK7), which is mobile in the PIC but preferentially located between the Mediator hook and shoulder in the PIC-core Mediator complex. Open spaces between the Mediator head and middle modules may allow access of the kinase to its substrate, the C-terminal domain of Pol II.

Bottom-up view of water network-mediated CO2 reduction using cryogenic cluster ion spectroscopy and direct dynamics simulations.

PubMed

Breen, Kristin J; DeBlase, Andrew F; Guasco, Timothy L; Voora, Vamsee K; Jordan, Kenneth D; Nagata, Takashi; Johnson, Mark A

2012-01-26

The transition states of a chemical reaction in solution are generally accessed through exchange of thermal energy between the solvent and the reactants. As such, an ensemble of reacting systems approaches the transition state configuration of reactant and surrounding solvent in an incoherent manner that does not lend itself to direct experimental observation. Here we describe how gas-phase cluster chemistry can provide a detailed picture of the microscopic mechanics at play when a network of six water molecules mediates the trapping of a highly reactive "hydrated electron" onto a neutral CO(2) molecule to form a radical anion. The exothermic reaction is triggered from a metastable intermediate by selective excitation of either the reactant CO(2) or the water network, which is evidenced by the evaporative decomposition of the product cluster. Ab initio molecular dynamics simulations of energized CO(2)·(H(2)O)(6)(-) clusters are used to elucidate the nature of the network deformations that mediate intracluster electron capture, thus revealing the detailed solvent fluctuations implicit in the Marcus theory for electron-transfer kinetics in solution.

FISH-MEDIATED NUTRIENT AND ENERGY EXCHANGE BETWEEN A LAKE SUPERIOR COASTAL WETLAND AND ITS ADJACENT BAY

EPA Science Inventory

Little has been done to quantify fluxes of organisms, nutrients, and energy between freshwater coastal habitats and adjacent offshore waters or to evaluate the ecological implications of these exchanges on a whole-lake basis. To test the hypothesis that fish-mediated transport m...

COLBALT-MEDIATED ACTIVATION OF PEROXYMONOSULFATE AND SULFATE RADICAL ATTACK ON PHENOLIC COMPOUNDS, IMPLICATIONS OF CHLORIDE IONS

EPA Science Inventory

This study reports on the sulfate radical pathway of room temperature degradation of two phenolic compounds in water. The radicals were produced by the cobalt-mediated decomposition of peroxymonosulfate (Oxone) in an aqueous homogeneous system. The major intermediates formed from...

Physical driving force of actomyosin motility based on the hydration effect.

PubMed

Suzuki, Makoto; Mogami, George; Ohsugi, Hideyuki; Watanabe, Takahiro; Matubayasi, Nobuyuki

2017-12-01

We propose a driving force hypothesis based on previous thermodynamics, kinetics and structural data as well as additional experiments and calculations presented here on water-related phenomena in the actomyosin systems. Although Szent-Györgyi pointed out the importance of water in muscle contraction in 1951, few studies have focused on the water science of muscle because of the difficulty of analyzing hydration properties of the muscle proteins, actin, and myosin. The thermodynamics and energetics of muscle contraction are linked to the water-mediated regulation of protein-ligand and protein-protein interactions along with structural changes in protein molecules. In this study, we assume the following two points: (1) the periodic electric field distribution along an actin filament (F-actin) is unidirectionally modified upon binding of myosin subfragment 1 (M or myosin S1) with ADP and inorganic phosphate Pi (M.ADP.Pi complex) and (2) the solvation free energy of myosin S1 depends on the external electric field strength and the solvation free energy of myosin S1 in close proximity to F-actin can become the potential force to drive myosin S1 along F-actin. The first assumption is supported by integration of experimental reports. The second assumption is supported by model calculations utilizing molecular dynamics (MD) simulation to determine solvation free energies of a small organic molecule and two small proteins. MD simulations utilize the energy representation method (ER) and the roughly proportional relationship between the solvation free energy and the solvent-accessible surface area (SASA) of the protein. The estimated driving force acting on myosin S1 is as high as several piconewtons (pN), which is consistent with the experimentally observed force. © 2017 Wiley Periodicals, Inc.

Structure, function and translational relevance of aquaporin dual water and ion channels.

PubMed

Yool, Andrea J; Campbell, Ewan M

2012-01-01

Aquaporins have been assumed to be selective for water alone, and aquaglyceroporins are accepted as carrying water and small uncharged solutes including glycerol. This review presents an expanded view of aquaporins as channels with more complex mechanisms of regulation and diverse repertoires of substrate permeabilities than were originally appreciated in the early establishment of the field. The role of aquaporins as dual water and gated ion channels is likely to have physiological and potentially translational relevance, and can be evaluated with newly developed molecular and pharmacological tools. Ion channel activity has been shown for Aquaporins -0, -1, and -6, Drosphila Big Brain, and plant Nodulin-26. Although the concept of ion channel function in aquaporins remains controversial, research advances are beginning to define not only the ion channel function but also the detailed molecular mechanisms that govern and mediate the multifunctional capabilities. With regard to physiological relevance, the adaptive benefit of expression of ion channel activity in aquaporins, implied by amino acid sequence conservation of the ion channel gating domains, suggests they provide more than water or glycerol and solute transport. Dual ion and water channels are of interest for understanding the modulation of transmembrane fluid gradients, volume regulation, and possible signal transduction in tissues expressing classes of aquaporins that have the dual function capability. Other aquaporin classes might be found in future work to have ion channel activities, pending identification of the possible signaling pathways that could govern activation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Overview of the National Energy-Water System (NEWS) Assessment Framework Study

NASA Astrophysics Data System (ADS)

Vorosmarty, C. J.; Miara, A.; Rosenzweig, B.; Corsi, F.; Piasecki, M.; Celicourt, P.; Fekete, B. M.; Macknick, J.; Melillo, J. M.; Newmark, R. L.; Tidwell, V. C.; Suh, S.; Prousevitch, A.

2015-12-01

In practical terms, strategic planning for the nation's economic, social and environmental future increasingly centers on issues relating to fresh water. U.S. energy security is highly dependent on electricity generated by the nation's fleet of thermoelectric power stations, which today contribute 90% to total electricity production. This presentation summarizes the overall structure and recent progress on a study devoted to climate adaptation and the reliability of power sector infrastructure and operations, when viewed through the lens of strategic water issues. The focus is on electric power infrastructure, i.e., the types, spatial distributions and levels of investment in technologies that deliver or could deliver electricity to the U.S. economy. The work is guided by a central hypothesis, that today's portfolio of electric power sector infrastructure is unsustainable in the context of satisfying its water needs under anticipated climate change and rising electricity demands. Insofar as water-mediated feedbacks reverberate throughout the national economy, we include macro-economic perspectives as well. The work is organized around the technical development of the NEWS framework which is then used to evaluate, in the context of anticipated climate, economic change and regulatory context: the performance of the nation's electricity sector, the feasibility of alternative pathways to improve climate adaptation, and impacts of energy technology. Scenarios are co-designed with a stakeholder community, and investment tradeoffs are considered with respect to the productivity of the economy, water availability and aquatic ecosystem condition.

The Role of Water in Mediating Interfacial Adhesion and Shear Strength in Graphene Oxide.

PubMed

Soler-Crespo, Rafael A; Gao, Wei; Mao, Lily; Nguyen, Hoang T; Roenbeck, Michael R; Paci, Jeffrey T; Huang, Jiaxing; Nguyen, SonBinh T; Espinosa, Horacio D

2018-06-12

Graphene oxide (GO), whose highly tunable surface chemistry enables the formation of strong interfacial hydrogen-bond networks, has garnered increasing interest in the design of devices that operate in the presence of water. For instance, previous studies have suggested that controlling GO's surface chemistry leads to enhancements in interfacial shear strength, allowing engineers to manage deformation pathways and control failure mechanisms. However, these previous reports have not explored the role of ambient humidity and only offer extensive chemical modifications to GO's surface as the main pathway to control GO's interfacial properties. Herein, through atomic force microscopy experiments on GO-GO interfaces, the adhesion energy and interfacial shear strength of GO were measured as a function of ambient humidity. Experimental evidence shows that adhesion energy and interfacial shear strength can be improved by a factor of 2-3 when GO is exposed to moderate (∼30% water weight) water content. Furthermore, complementary molecular dynamics simulations uncovered the mechanisms by which these nanomaterial interfaces achieve their properties. They reveal that the strengthening mechanism arises from the formation of strongly interacting hydrogen-bond networks, driven by the chemistry of the GO basal plane and intercalated water molecules between two GO surfaces. In summary, the methodology and findings here reported provide pathways to simultaneously optimize GO's interfacial and in-plane mechanical properties, by tailoring the chemistry of GO and accounting for water content, in engineering applications such as sensors, filtration membranes, wearable electronics, and structural materials.

Insights into the binding of GABA to the insect RDL receptor from atomistic simulations: a comparison of models

NASA Astrophysics Data System (ADS)

Comitani, Federico; Cohen, Netta; Ashby, Jamie; Botten, Dominic; Lummis, Sarah C. R.; Molteni, Carla

2014-01-01

The resistance to dieldrin (RDL) receptor is an insect pentameric ligand-gated ion channel (pLGIC). It is activated by the neurotransmitter γ-aminobutyric acid (GABA) binding to its extracellular domain; hence elucidating the atomistic details of this interaction is important for understanding how the RDL receptor functions. As no high resolution structures are currently available, we built homology models of the extracellular domain of the RDL receptor using different templates, including the widely used acetylcholine binding protein and two pLGICs, the Erwinia Chrysanthemi ligand-gated ion channel (ELIC) and the more recently resolved GluCl. We then docked GABA into the selected three dimensional structures, which we used as starting points for classical molecular dynamics simulations. This allowed us to analyze in detail the behavior of GABA in the binding sites, including the hydrogen bond and cation-π interaction networks it formed, the conformers it visited and the possible role of water molecules in mediating the interactions; we also estimated the binding free energies. The models were all stable and showed common features, including interactions consistent with experimental data and similar to other pLGICs; differences could be attributed to the quality of the models, which increases with increasing sequence identity, and the use of a pLGIC template. We supplemented the molecular dynamics information with metadynamics, a rare event method, by exploring the free energy landscape of GABA binding to the RDL receptor. Overall, we show that the GluCl template provided the best models. GABA forming direct salt-bridges with Arg211 and Glu204, and cation-π interactions with an aromatic cage including Tyr109, Phe206 and Tyr254, represents a favorable binding arrangement, and the interaction with Glu204 can also be mediated by a water molecule.

Effect of artificial electric fields on plants grown under microgravity conditions

NASA Astrophysics Data System (ADS)

Nechitailo, G.; Gordeev, A.

2001-01-01

Ionic and structural hetorogeneity of cells, tissues, and organs of plants are associated with a spectrum of electric characteristics such as bioelectric potentials, electrical conductance, and bioelectric permeability. An important determinant for the plant function is electric properties of the cell membranes and organelles which maintain energy and substance exchange with the environment. Enzymes and other biologically active substances have a powerful charge at the molecular level. Finally, all molecules, including those of water, represent dipoles, and this determines their reactive capacity. A major determinant is the bioelectric polarity of a plant is genetically predetermined and cannot be modified. It is an intrinsic structural feature of the organism whose evolution advent was mediated by gravity. An illustrative presentation of polarity is the downward growth of the roots and upward growth of stems in the Earth's gravitation field. However, gravity is a critical, but not the sole determinant of the plant organism polarization. Potent polarizing effects are exerted by light, the electromagnetic field, moisture, and other factors. It is known that plant cultivation in an upturned position is associated with impairment of water and nutrient uptake, resulting in dyscoordination of physiological processes, growth and developmental retardation. These abnormalities were characteristic when early attempts were made to grow plants in weightlessness conditions.

Study of base pair mutations in proline-rich homeodomain (PRH)-DNA complexes using molecular dynamics.

PubMed

Jalili, Seifollah; Karami, Leila; Schofield, Jeremy

2013-06-01

Proline-rich homeodomain (PRH) is a regulatory protein controlling transcription and gene expression processes by binding to the specific sequence of DNA, especially to the sequence 5'-TAATNN-3'. The impact of base pair mutations on the binding between the PRH protein and DNA is investigated using molecular dynamics and free energy simulations to identify DNA sequences that form stable complexes with PRH. Three 20-ns molecular dynamics simulations (PRH-TAATTG, PRH-TAATTA and PRH-TAATGG complexes) in explicit solvent water were performed to investigate three complexes structurally. Structural analysis shows that the native TAATTG sequence forms a complex that is more stable than complexes with base pair mutations. It is also observed that upon mutation, the number and occupancy of the direct and water-mediated hydrogen bonds decrease. Free energy calculations performed with the thermodynamic integration method predict relative binding free energies of 0.64 and 2 kcal/mol for GC to AT and TA to GC mutations, respectively, suggesting that among the three DNA sequences, the PRH-TAATTG complex is more stable than the two mutated complexes. In addition, it is demonstrated that the stability of the PRH-TAATTA complex is greater than that of the PRH-TAATGG complex.

Water-mediated solid-state transformation of a polymorphic drug during aqueous-based drug-layer coating of pellets.

PubMed

Lust, Andres; Lakio, Satu; Vintsevits, Julia; Kozlova, Jekaterina; Veski, Peep; Heinämäki, Jyrki; Kogermann, Karin

2013-11-01

During aqueous drug-layer coating, drug substance(s) are exposed to water and elevated temperatures which can lead to water-mediated process induced transformations (PITs). The effects of aqueous drug-layer coating of pellets (Cellets(®)) on the anhydrous piroxicam, PRX, were investigated in the miniaturized coating equipment and with free films. Hydroxypropyl methylcellulose (HPMC) was used as a carrier coating polymer. Free films were prepared by using an in-house small-scale rotating plate system equipped with an atomization air nozzle. Raman spectroscopy, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to characterize the solid-state properties and surface morphology of the pellets and free films. The results showed that anhydrous PRX form I (AH) and monohydrate (MH) were stable during drug-layer coating, but amorphous PRX in solid dispersion (SD) crystallized as MH already after 10 min of coating. Furthermore, the increase in a dissolution rate was achieved from the drug-layer coated inert pellets compared to powder forms. In conclusion, water-mediated solid-state PITs of amorphous PRX is evident during aqueous-based drug-layer coating of pellets, and solid-state change can be verified using Raman spectroscopy. Copyright © 2013 Elsevier B.V. All rights reserved.

Surviving a Dry Future: Abscisic Acid (ABA)-Mediated Plant Mechanisms for Conserving Water under Low Humidity

PubMed Central

McAdam, Scott A. M.

2017-01-01

Angiosperms are able to respond rapidly to the first sign of dry conditions, a decrease in air humidity, more accurately described as an increase in the vapor pressure deficit between the leaf and the atmosphere (VPD), by abscisic acid (ABA)-mediated stomatal closure. The genes underlying this response offer valuable candidates for targeted selection of crop varieties with improved drought tolerance, a critical goal for current plant breeding programs, to maximize crop production in drier and increasingly marginalized environments, and meet the demands of a growing population in the face of a changing climate. Here, we review current understanding of the genetic mechanisms underpinning ABA-mediated stomatal closure, a key means for conserving water under dry conditions, examine how these mechanisms evolved, and discuss what remains to be investigated. PMID:29113039

The Effect of Religious Involvement on Life Satisfaction among Korean Christians: Focused on the Mediating Effect of Spiritual Well-Being and Self-Esteem.

PubMed

Yoo, Jieun

2017-12-01

The present study examined the relationship between two categories of religious involvement, namely religious belief and religious behavior, and life satisfaction among Korean Christians (N = 278) with spiritual well-being and self-esteem as potential mediators in this relationship by using structural equation modeling (SEM). The results supported the full mediated structural model and indicated that religious belief had a significant indirect effect on life satisfaction through the mediators, spiritual well-being and self-esteem. Religious behavior did not have an indirect or direct effect on life satisfaction among Korean Christians. The significance, implications, and limitations of the study were discussed.

Smoking mediates the effect of conscientiousness on mortality: The Veterans Affairs Normative Aging Study

PubMed Central

Turiano, Nicholas A.; Hill, Patrick L.; Roberts, Brent W.; Spiro, Avron; Mroczek, Daniel K.

2013-01-01

This study examined the relationship between conscientiousness and mortality over 18 years and whether smoking behavior mediated this relationship. We utilized data from the Veterans Affairs Normative Aging Study on 1349 men who completed the Goldberg (1992) adjectival markers of the Big Five. Over the 18-year follow-up, 547 (41%) participants died. Through proportional hazards modeling in a structural equation modeling framework, we found that higher levels of conscientiousness significantly predicted longer life, and that this effect was mediated by current smoking status at baseline. Methodologically, we also demonstrate the effectiveness of using a structural equation modeling framework to evaluate mediation when using a censored outcome such as mortality. PMID:23504043

Dominant forest tree mycorrhizal type mediates understory plant invasions

Treesearch

Insu Jo; Kevin M. Potter; Grant M. Domke; Songlin Fei

2018-01-01

Forest mycorrhizal type mediates nutrient dynamics, which in turn can influence forest community structure and processes. Using forest inventory data, we explored how dominant forest tree myc- orrhizal type affects understory plant invasions with consideration of forest structure and soil properties. We found that arbuscular mycorrhizal (AM) dominant forests, which are...

Parent-Child Relations and Peer Associations as Mediators of the Family Structure--Substance Use Relationship

ERIC Educational Resources Information Center

Crawford, Lizabeth A.; Novak, Katherine B.

2008-01-01

Using data from the National Education Longitudinal Survey of 1988, the authors assess the extent to which adolescents' levels of parental attachment and opportunities for participating in delinquent activities mediate the family structure--substance use relationship. A series of hierarchical regressions supported the hypotheses that high levels…

Structural effects of Cu(II)-coordination in the octapeptide region of the human prion protein.

PubMed

Riihimäki, Eva-Stina; Martínez, José Manuel; Kloo, Lars

2008-05-14

The copper-binding ability of the prion protein is thought to be central to its function. The structural effects of copper coordination in the octapeptide region of the human prion protein have been investigated by molecular dynamics simulations. Simulations were performed with the apo state, in order to investigate the behavior of the region without copper ions, as well as with the octapeptide region in the presence of copper ions. While the structure of the apo state is greatly influenced by the interaction between the rings in the histidine, tryptophan and proline residues, the region shows evidence of highly ordered coordination sites in the presence of copper ions. The position of the tryptophan indole ring is stabilized by cation-pi interactions. Two stable orientations of the indole ring with respect to the equatorial coordination plane of copper were observed, which showed that the indole ring can reside on both sides of the coordination plane. The interaction with the indole ring was found to occur without a mediating axial water molecule.

The Mediator complex and transcription regulation

PubMed Central

Poss, Zachary C.; Ebmeier, Christopher C.

2013-01-01

The Mediator complex is a multi-subunit assembly that appears to be required for regulating expression of most RNA polymerase II (pol II) transcripts, which include protein-coding and most non-coding RNA genes. Mediator and pol II function within the pre-initiation complex (PIC), which consists of Mediator, pol II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in size. Mediator serves as a central scaffold within the PIC and helps regulate pol II activity in ways that remain poorly understood. Mediator is also generally targeted by sequence-specific, DNA-binding transcription factors (TFs) that work to control gene expression programs in response to developmental or environmental cues. At a basic level, Mediator functions by relaying signals from TFs directly to the pol II enzyme, thereby facilitating TF-dependent regulation of gene expression. Thus, Mediator is essential for converting biological inputs (communicated by TFs) to physiological responses (via changes in gene expression). In this review, we summarize an expansive body of research on the Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on the basics that underlie Mediator function, such as its structure and subunit composition, and describe its broad regulatory influence on gene expression, ranging from chromatin architecture to transcription initiation and elongation, to mRNA processing. We also describe factors that influence Mediator structure and activity, including TFs, non-coding RNAs and the CDK8 module. PMID:24088064

Hydrology Affects Environmental and Spatial Structuring of Microalgal Metacommunities in Tropical Pacific Coast Wetlands.

PubMed

Rojo, Carmen; Mesquita-Joanes, Francesc; Monrós, Juan S; Armengol, Javier; Sasa, Mahmood; Bonilla, Fabián; Rueda, Ricardo; Benavent-Corai, José; Piculo, Rubén; Segura, M Matilde

2016-01-01

The alternating climate between wet and dry periods has important effects on the hydrology and therefore on niche-based processes of water bodies in tropical areas. Additionally, assemblages of microorganism can show spatial patterns, in the form of a distance decay relationship due to their size or life form. We aimed to test spatial and environmental effects, modulated by a seasonal flooding climatic pattern, on the distribution of microalgae in 30 wetlands of a tropical dry forest region: the Pacific coast of Costa Rica and Nicaragua. Three surveys were conducted corresponding to the beginning, the highest peak, and the end of the hydrological year during the wet season, and species abundance and composition of planktonic and benthic microalgae was determined. Variation partitioning analysis (as explained by spatial distance or environmental factors) was applied to each seasonal dataset by means of partial redundancy analysis. Our results show that microalgal assemblages were structured by spatial and environmental factors depending on the hydrological period of the year. At the onset of hydroperiod and during flooding, neutral effects dominated community dynamics, but niche-based local effects resulted in more structured algal communities at the final periods of desiccating water bodies. Results suggest that climate-mediated effects on hydrology can influence the relative role of spatial and environmental factors on metacommunities of microalgae. Such variability needs to be accounted in order to describe accurately community dynamics in tropical coastal wetlands.

Hydrology Affects Environmental and Spatial Structuring of Microalgal Metacommunities in Tropical Pacific Coast Wetlands

PubMed Central

Rojo, Carmen; Mesquita-Joanes, Francesc; Monrós, Juan S.; Armengol, Javier; Sasa, Mahmood; Bonilla, Fabián; Rueda, Ricardo; Benavent-Corai, José; Piculo, Rubén; Segura, M. Matilde

2016-01-01

The alternating climate between wet and dry periods has important effects on the hydrology and therefore on niche-based processes of water bodies in tropical areas. Additionally, assemblages of microorganism can show spatial patterns, in the form of a distance decay relationship due to their size or life form. We aimed to test spatial and environmental effects, modulated by a seasonal flooding climatic pattern, on the distribution of microalgae in 30 wetlands of a tropical dry forest region: the Pacific coast of Costa Rica and Nicaragua. Three surveys were conducted corresponding to the beginning, the highest peak, and the end of the hydrological year during the wet season, and species abundance and composition of planktonic and benthic microalgae was determined. Variation partitioning analysis (as explained by spatial distance or environmental factors) was applied to each seasonal dataset by means of partial redundancy analysis. Our results show that microalgal assemblages were structured by spatial and environmental factors depending on the hydrological period of the year. At the onset of hydroperiod and during flooding, neutral effects dominated community dynamics, but niche-based local effects resulted in more structured algal communities at the final periods of desiccating water bodies. Results suggest that climate-mediated effects on hydrology can influence the relative role of spatial and environmental factors on metacommunities of microalgae. Such variability needs to be accounted in order to describe accurately community dynamics in tropical coastal wetlands. PMID:26900916

Molecular dynamics simulation of sodium dodecylsulfate (SDS) bilayers.

PubMed

Zhang, Hongshu; Yuan, Shiling; Sun, Jichao; Liu, Jianqiang; Li, Haiping; Du, Na; Hou, Wanguo

2017-11-15

Sodium dodecylsulfate (SDS) - a simple single tailed surfactant (STS) can form stable vesicles from its micellar solution without any additives under the mediation of solid surfaces. To further understand the mechanism of this transition on the molecular level, molecular dynamics simulations are performed to study segments of SDS bilayers (as part of vesicles) in the bulk solution systematically, at the moment that the lower leaflet of bilayers already detached from solid surfaces. The SDS membrane would rather keep their bilayers structure than return to micelles when the initial interdigitated degree (δ i ) between alkyl chains is more than 8.0±1.4%. And the interdigitated degree is always approaching to 31.7±2.0% while the equilibrium is reached. The aggregates behave as curved bilayers, planar bilayers, perforated bilayers, and micelles with the increase of the lower leaflet cross-sectional area. Besides, the structures of salt bridge and water bridge structures are formed between DS - and Na + ions or water molecules, which contribute to the stability of SDS bilayers. The distribution difference of the salt bridges along the direction of S-O axis between the two leaflets leads to the asymmetry of the bilayers, which plays supplementary role to the formation of bilayers curvature. We expect that this work help to shed light on the understanding of interface phenomena and the mechanism of simple single-tailed surfactant vesicle self-assembly on the molecular level. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular dynamics simulation study of the structure of poly(ethylene oxide) brushes on nonpolar surfaces in aqueous solution.

PubMed

Bedrov, Dmitry; Smith, Grant D

2006-07-04

The structure of poly(ethylene oxide) (PEO, M(w) = 526) brushes of various grafting density (sigma) on nonpolar graphite and hydrophobic (oily) surfaces in aqueous solution has been studied using atomistic molecular dynamics simulations. Additionally, the influence of PEO-surface interactions on the brush structure was investigated by systematically reducing the strength of the (dispersion) attraction between PEO and the surfaces. PEO chains were found to adsorb strongly to the graphite surface due primarily to the relative strength of dispersion interactions between PEO and the atomically dense graphite compared to those between water and graphite. For the oily surface, PEO-surface and water-surface dispersion interactions are much weaker, greatly reducing the energetic driving force for PEO adsorption. This reduction is mediated to some extent by a hydrophobic driving force for PEO adsorption on the oily surface. Reduction in the strength of PEO-surface attraction results in reduced adsorption of PEO for both surfaces, with the effect being much greater for the graphite surface where the strong PEO-surface dispersion interactions dominate. At high grafting density (sigma approximately 1/R(g)(2)), the PEO density profiles exhibited classical brush behavior and were largely independent of the strength of the PEO-surface interaction. With decreasing grafting density (sigma < 1/R(g)(2)), coverage of the surface by PEO requires an increasingly large fraction of PEO segments resulting in a strong dependence of the PEO density profile on the nature of the PEO-surface interaction.

Interactions of the Human Calcitonin Fragment 9–32 with Phospholipids: A Monolayer Study

PubMed Central

Wagner, Kerstin; Van Mau, Nicole; Boichot, Sylvie; Kajava, Andrey V.; Krauss, Ulrike; Le Grimellec, Christian; Beck-Sickinger, Annette; Heitz, Frédéric

2004-01-01

Human calcitonin and its C-terminal fragment 9–32 (hCT(9–32)) administered in a spray translocate into respiratory nasal epithelium with an effect similar to intravenous injection. hCT(9–32) is an efficient carrier to transfer the green fluorescent protein into excised bovine nasal mucosa. To understand the translocation of hCT(9–32) across plasma membranes, we investigated its interactions with phospholipids and its interfacial structure using model lipid monolayers. A combination of physicochemical methods was applied including surface tension measurements on adsorbed and spread monolayers at the air-water interface, Fourier transform infrared, circular dichroism, and atomic force microscopy on Langmuir-Blodgett monolayers. The results disclose that hCT(9–32) preferentially interacts with negatively charged phospholipids and does not insert spontaneously into lipid monolayers. This supports a nonreceptor-mediated endocytic internalization pathway as previously suggested. Structural studies revealed a random coil conformation of hCT(9–32) in solution, transforming to α-helices when the peptide is localized at lipid-free or lipid-containing air-water interfaces. Atomic force microscopy studies of monolayers of the peptide alone or mixed with dioleoylphosphatidylcholine revealed that hCT(9–32) forms filaments rolled into spirals. In contrast, when interacting with dioleoylphosphatidylglycerol, hCT(9–32) does not adopt filamentous structures. A molecular model and packing is proposed for the spiral-forming hCT(9–32). PMID:15240473

Structure of Energetic Particle Mediated Shocks Revisited

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mostafavi, P.; Zank, G. P.; Webb, G. M.

2017-05-20

The structure of collisionless shock waves is often modified by the presence of energetic particles that are not equilibrated with the thermal plasma (such as pickup ions [PUIs] and solar energetic particles [SEPs]). This is relevant to the inner and outer heliosphere and the Very Local Interstellar Medium (VLISM), where observations of shock waves (e.g., in the inner heliosphere) show that both the magnetic field and thermal gas pressure are less than the energetic particle component pressures. Voyager 2 observations revealed that the heliospheric termination shock (HTS) is very broad and mediated by energetic particles. PUIs and SEPs contribute bothmore » a collisionless heat flux and a higher-order viscosity. We show that the incorporation of both effects can completely determine the structure of collisionless shocks mediated by energetic ions. Since the reduced form of the PUI-mediated plasma model is structurally identical to the classical cosmic ray two-fluid model, we note that the presence of viscosity, at least formally, eliminates the need for a gas sub-shock in the classical two-fluid model, including in that regime where three are possible. By considering parameters upstream of the HTS, we show that the thermal gas remains relatively cold and the shock is mediated by PUIs. We determine the structure of the weak interstellar shock observed by Voyager 1 . We consider the inclusion of the thermal heat flux and viscosity to address the most general form of an energetic particle-thermal plasma two-fluid model.« less

WORKSHOP ON MONITORING OXIDATION-REDUCTION PROCESSES FOR GROUND-WATER RESTORATION

EPA Science Inventory

Redox conditions are among the most important parameters for controlling contaminant transport and fate in ground-water systems. Oxidation-reduction (redox) reactions mediate the chemical behavior of both inorganic and organic chemical constituents by affecting solubility, rea...

Staphylococcus aureus Strain Newman Photoinactivation and Cellular Response to Sunlight Exposure.

PubMed

McClary, Jill S; Sassoubre, Lauren M; Boehm, Alexandria B

2017-09-01

Sunlight influences microbial water quality of surface waters. Previous studies have investigated photoinactivation mechanisms and cellular photostress responses of fecal indicator bacteria (FIB), including Escherichia coli and enterococci, but further work is needed to characterize photostress responses of bacterial pathogens. Here we investigate the photoinactivation of Staphylococcus aureus (strain Newman), a pigmented, waterborne pathogen of emerging concern. We measured photodecay using standard culture-based assays and cellular membrane integrity and investigated photostress response by measuring the relative number of mRNA transcripts of select oxidative stress, DNA repair, and metabolism genes. Photoinactivation experiments were performed in both oxic and anoxic systems to further investigate the role of oxygen-mediated and non-oxygen-mediated photoinactivation mechanisms. S. aureus lost culturability much faster in oxic systems than in anoxic systems, indicating an important role for oxygen in photodecay mechanisms. S. aureus cell membranes were damaged by sunlight exposure in anoxic systems but not in oxic systems, as measured by cell membrane permeability to propidium iodide. After sunlight exposure, S. aureus increased expression of a gene coding for methionine sulfoxide reductase after 12 h of sunlight exposure in the oxic system and after 6 h of sunlight exposure in the anoxic system, suggesting that methionine sulfoxide reductase is an important enzyme for defense against both oxygen-dependent and oxygen-independent photostresses. This research highlights the importance of oxygen in bacterial photoinactivation in environmentally relevant systems and the complexity of the bacterial photostress response with respect to cell structure and transcriptional regulation. IMPORTANCE Staphylococcus aureus is a pathogenic bacterium that causes gastrointestinal, respiratory, and skin infections. In severe cases, S. aureus infection can lead to life-threatening diseases, including pneumonia and sepsis. Cases of community-acquired S. aureus infection have been increasing in recent years, pointing to the importance of considering S. aureus transmission pathways outside the hospital environment. Associations have been observed between recreational water contact and staphylococcal skin infections, suggesting that recreational waters may be an important environmental transmission pathway for S. aureus However, prediction of human health risk in recreational waters is hindered by incomplete knowledge of pathogen sources, fate, and transport in this environment. This study is an in-depth investigation of the inactivation of a representative strain of S. aureus by sunlight exposure, one of the most important factors controlling the fate of microbial contaminants in clear waters, which will improve our ability to predict water quality changes and human health risk in recreational waters. Copyright © 2017 American Society for Microbiology.

Temporal modelling of ballast water discharge and ship-mediated invasion risk to Australia

PubMed Central

Cope, Robert C.; Prowse, Thomas A. A.; Ross, Joshua V.; Wittmann, Talia A.; Cassey, Phillip

2015-01-01

Biological invasions have the potential to cause extensive ecological and economic damage. Maritime trade facilitates biological invasions by transferring species in ballast water, and on ships' hulls. With volumes of maritime trade increasing globally, efforts to prevent these biological invasions are of significant importance. Both the International Maritime Organization and the Australian government have developed policy seeking to reduce the risk of these invasions. In this study, we constructed models for the transfer of ballast water into Australian waters, based on historic ballast survey data. We used these models to hindcast ballast water discharge over all vessels that arrived in Australian waters between 1999 and 2012. We used models for propagule survival to compare the risk of ballast-mediated propagule transport between ecoregions. We found that total annual ballast discharge volume into Australia more than doubled over the study period, with the vast majority of ballast water discharge and propagule pressure associated with bulk carrier traffic. As such, the ecoregions suffering the greatest risk are those associated with the export of mining commodities. As global marine trade continues to increase, effective monitoring and biosecurity policy will remain necessary to combat the risk of future marine invasion events. PMID:26064643

[Mediator processes in the brain structures in the late periods after external and combined exposure to ionizing radiation].

PubMed

Taĭts, M Iu; Dudina, T V; Kandybo, T S; Elkina, A I

1990-01-01

In experiments with mature Wistar male rats it was shown that X-radiation of 12.9 mCi/kg and the combined effect of X-rays and 131I of 6.5 mCi/kg changed the rate of mediator processes in the structures responsible for the hypothalamic function regulation. At remote times (6 months) following irradiation differences were observed in the discoordination of mediator interrelations associated with the peculiarities of the indirect effect of external and combined irradiation implemented via endocrine mechanism system.

Chlorogenic Acid Activates CFTR-Mediated Cl- Secretion in Mice and Humans: Therapeutic Implications for Chronic Rhinosinusitis

PubMed Central

Illing, Elisa; Cho, Do-Yeon; Zhang, Shaoyan; Skinner, Daniel F.; Dunlap, Quinn A.; Sorscher, Eric J.; Woodworth, Bradford A.

2016-01-01

Objectives Salubrious effects of the green coffee bean are purportedly secondary to high concentrations of chlorogenic acid. Chlorogenic acid has a molecular structure similar to bioflavonoids that activate transepithelial Cl- transport in sinonasal epithelia. In contrast to flavonoids, the drug is freely soluble in water. The objective of this study is to evaluate the Cl- secretory capability of chlorogenic acid and its potential as a therapeutic activator of mucus clearance in sinus disease. Study Design Basic research Setting Laboratory Subjects and Methods Chlorogenic acid was tested on primary murine nasal septal epithelial(MNSE)[CFTR+/+ and transgenic CFTR-/-] and human sinonasal epithelial(HSNE)[CFTR+/+ and F508del/F508del] cultures under pharmacologic conditions in Ussing chambers to evaluate effects on transepithelial Cl- transport. Cellular cAMP, phosphorylation of the CFTR regulatory domain(R-D), and CFTR mRNA transcription were also measured. Results Chlorogenic acid stimulated transepithelial Cl- secretion [(change in short-circuit current(ΔISC=μA/cm2)] in MNSE(13.1+/-0.9 vs. 0.1+/-0.1, p<0.05) and HSNE(34.3+/-0.9 vs. 0.0+/-0.1, p<0.05). The drug had a long duration until peak effect at 15-30 minutes after application. Significant inhibition with INH-172, as well as absent stimulation in cultures lacking functional CFTR, suggests effects are dependent on CFTR-mediated pathways. However, the absence of elevated cellular cAMP and phosphorylation the CFTR R-D indicates chlorogenic acid does not work through a PKA-dependent mechanism. Conclusion Chlorogenic acid is a water soluble agent that promotes CFTR-mediated Cl- transport in mouse and human sinonasal epithelium. Translating activators of mucociliary transport to clinical use provides a new therapeutic approach to sinus disease. Further in vivo evaluation is planned. PMID:26019132

Chlorogenic Acid Activates CFTR-Mediated Cl- Secretion in Mice and Humans: Therapeutic Implications for Chronic Rhinosinusitis.

PubMed

Illing, Elisa A; Cho, Do-Yeon; Zhang, Shaoyan; Skinner, Daniel F; Dunlap, Quinn A; Sorscher, Eric J; Woodworth, Bradford A

2015-08-01

Salubrious effects of the green coffee bean are purportedly secondary to high concentrations of chlorogenic acid. Chlorogenic acid has a molecular structure similar to bioflavonoids that activate transepithelial Cl(-) transport in sinonasal epithelia. In contrast to flavonoids, the drug is freely soluble in water. The objective of this study is to evaluate the Cl(-) secretory capability of chlorogenic acid and its potential as a therapeutic activator of mucus clearance in sinus disease. Basic research. Laboratory. Chlorogenic acid was tested on primary murine nasal septal epithelial (MNSE) (CFTR(+/+) and transgenic CFTR(-/-)) and human sinonasal epithelial (HSNE) (CFTR(+/+) and F508del/F508del) cultures under pharmacologic conditions in Ussing chambers to evaluate effects on transepithelial Cl(-) transport. Cellular cyclic adenosine monophosphate (cAMP), phosphorylation of the CFTR regulatory domain (R-D), and CFTR mRNA transcription were also measured. Chlorogenic acid stimulated transepithelial Cl(-) secretion (change in short-circuit current [ΔISC = µA/cm(2)]) in MNSE (13.1 ± 0.9 vs 0.1 ± 0.1; P < .05) and HSNE (34.3 ± 0.9 vs 0.0 ± 0.1; P < .05). The drug had a long duration until peak effect at 15 to 30 minutes after application. Significant inhibition with INH-172 as well as absent stimulation in cultures lacking functional CFTR suggest effects are dependent on CFTR-mediated pathways. However, the absence of elevated cellular cAMP and phosphorylation the CFTR R-D indicates chlorogenic acid does not work through a PKA-dependent mechanism. Chlorogenic acid is a water-soluble agent that promotes CFTR-mediated Cl(-) transport in mouse and human sinonasal epithelium. Translating activators of mucociliary transport to clinical use provides a new therapeutic approach to sinus disease. Further in vivo evaluation is planned. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Soil Nematode Responses to Increases in Nitrogen Deposition and Precipitation in a Temperate Forest

PubMed Central

Sun, Xiaoming; Zhang, Xiaoke; Zhang, Shixiu; Dai, Guanhua; Han, Shijie; Liang, Wenju

2013-01-01

The environmental changes arising from nitrogen (N) deposition and precipitation influence soil ecological processes in forest ecosystems. However, the corresponding effects of environmental changes on soil biota are poorly known. Soil nematodes are the important bioindicator of soil environmental change, and their responses play a key role in the feedbacks of terrestrial ecosystems to climate change. Therefore, to explore the responsive mechanisms of soil biota to N deposition and precipitation, soil nematode communities were studied after 3 years of environmental changes by water and/or N addition in a temperate forest of Changbai Mountain, Northeast China. The results showed that water combined with N addition treatment decreased the total nematode abundance in the organic horizon (O), while the opposite trend was found in the mineral horizon (A). Significant reductions in the abundances of fungivores, plant-parasites and omnivores-predators were also found in the water combined with N addition treatment. The significant effect of water interacted with N on the total nematode abundance and trophic groups indicated that the impacts of N on soil nematode communities were mediated by water availability. The synergistic effect of precipitation and N deposition on soil nematode communities was stronger than each effect alone. Structural equation modeling suggested water and N additions had direct effects on soil nematode communities. The feedback of soil nematodes to water and nitrogen addition was highly sensitive and our results indicate that minimal variations in soil properties such as those caused by climate changes can lead to severe changes in soil nematode communities. PMID:24324794

Transparent Exopolymer Particles (TEP) in the NE Aegean Sea frontal area: Seasonal dynamics under the influence of Black Sea water

NASA Astrophysics Data System (ADS)

Parinos, C.; Gogou, A.; Krasakopoulou, E.; Lagaria, A.; Giannakourou, A.; Karageorgis, A. P.; Psarra, S.

2017-10-01

The abundance of Transparent Exopolymer Particles (TEP) was determined on a seasonal basis (autumn, spring and summer) along a north-south transect in the NE Aegean Sea and the vicinity of the Dardanelles Straits. Their distribution patterns were studied in respect to hydrographic conditions and water mass characteristics in the area, as well as particulate organic carbon (POC) concentrations, changes in standing stocks of chlorophyll-α and bacterial production. TEP concentrations ranged from 15.4 to 188 μg GX eq L-1. Their spatial distribution patterns within the euphotic zone displayed significant seasonal variability, which appears to closely reflect the temporal variation of the water column structure, resulting from the encounter and interplay of the Black Sea and Levantine Water masses, and the associated biogeochemical processes. Minimum TEP concentrations during autumn could be likely attributed to a minor quantity of TEP and/or its dissolved precursors exuded by phytoplankton and their enhanced degradation due to their long residence time in the water column. During spring, high TEP production was mediated by actively growing phytoplankton, while during summer a positive link to the intense stratification of the water column and the enhanced bacterial growth within the Black Sea Water layer was observed. The results reported in this study highlight the fact that TEP carbon represents a significant fraction of the POC pool. Moreover, TEP production is critical in promoting particle coagulation rates, playing an important role in carbon cycling/transportation out of the euphotic zone.

Contribution to the Chemistry of Plasma-Activated Water

NASA Astrophysics Data System (ADS)

Julák, J.; Hujacová, A.; Scholtz, V.; Khun, J.; Holada, K.

2018-01-01

Plasma-activated water (PAW) was prepared by exposure to nonthermal plasma produced by a positive dc corona discharge in a transient spark regime. The activation of water was performed in atmosphere of various surrounding gases (air, nitrogen, carbon dioxide, and argon). This PAW retains its biological activity, measured on the mouse neuroblastoma cells culture, even after storage for more than one year. The highest hydrogen peroxide content was found for PAWs prepared in the atmospheres of argon or carbon dioxide, whereas the PAWs prepared in air and nitrogen exhibited lower hydrogen peroxide content. The acidity of PAWs mediated by nitric and nitrous acid formation displayed an opposite trend. It is concluded that the long-lasting biological effect of PAW is mediated by hydrogen peroxide in acid milieu only, whereas other possible active components decompose rapidly.

Acclimation of mechanical and hydraulic functions in trees: impact of the thigmomorphogenetic process

PubMed Central

Badel, Eric; Ewers, Frank W.; Cochard, Hervé; Telewski, Frank W.

2015-01-01

The secondary xylem (wood) of trees mediates several functions including water transport and storage, mechanical support and storage of photosynthates. The optimal structures for each of these functions will most likely differ. The complex structure and function of xylem could lead to trade-offs between conductive efficiency, resistance to embolism, and mechanical strength needed to count for mechanical loading due to gravity and wind. This has been referred to as the trade-off triangle, with the different optimal solutions to the structure/function problems depending on the environmental constraints as well as taxonomic histories. Thus, the optimisation of each function will lead to drastically different anatomical structures. Trees are able to acclimate the internal structure of their trunk and branches according to the stress they experience. These acclimations lead to specific structures that favor the efficiency or the safety of one function but can be antagonistic with other functions. Currently, there are no means to predict the way a tree will acclimate or optimize its internal structure in support of its various functions under differing environmental conditions. In this review, we will focus on the acclimation of xylem anatomy and its resulting mechanical and hydraulic functions to recurrent mechanical strain that usually result from wind-induced thigmomorphogenesis with a special focus on the construction cost and the possible trade-off between wood functions. PMID:25954292

Uncovering the determinants of a highly perturbed tyrosine pKa in the active site of ketosteroid isomerase.

PubMed

Schwans, Jason P; Sunden, Fanny; Gonzalez, Ana; Tsai, Yingssu; Herschlag, Daniel

2013-11-05

Within the idiosyncratic enzyme active-site environment, side chain and ligand pKa values can be profoundly perturbed relative to their values in aqueous solution. Whereas structural inspection of systems has often attributed perturbed pKa values to dominant contributions from placement near charged groups or within hydrophobic pockets, Tyr57 of a Pseudomonas putida ketosteroid isomerase (KSI) mutant, suggested to have a pKa perturbed by nearly 4 units to 6.3, is situated within a solvent-exposed active site devoid of cationic side chains, metal ions, or cofactors. Extensive comparisons among 45 variants with mutations in and around the KSI active site, along with protein semisynthesis, (13)C NMR spectroscopy, absorbance spectroscopy, and X-ray crystallography, was used to unravel the basis for this perturbed Tyr pKa. The results suggest that the origin of large energetic perturbations are more complex than suggested by visual inspection. For example, the introduction of positively charged residues near Tyr57 raises its pKa rather than lowers it; this effect, and part of the increase in the Tyr pKa from the introduction of nearby anionic groups, arises from accompanying active-site structural rearrangements. Other mutations with large effects also cause structural perturbations or appear to displace a structured water molecule that is part of a stabilizing hydrogen-bond network. Our results lead to a model in which three hydrogen bonds are donated to the stabilized ionized Tyr, with these hydrogen-bond donors, two Tyr side chains, and a water molecule positioned by other side chains and by a water-mediated hydrogen-bond network. These results support the notion that large energetic effects are often the consequence of multiple stabilizing interactions rather than a single dominant interaction. Most generally, this work provides a case study for how extensive and comprehensive comparisons via site-directed mutagenesis in a tight feedback loop with structural analysis can greatly facilitate our understanding of enzyme active-site energetics. The extensive data set provided may also be a valuable resource for those wishing to extensively test computational approaches for determining enzymatic pKa values and energetic effects.

Uncovering the Determinants of a Highly Perturbed Tyrosine pKa in the Active Site of Ketosteroid Isomerase†

PubMed Central

Schwans, Jason P.; Sunden, Fanny; Gonzalez, Ana; Tsai, Yingssu; Herschlag, Daniel

2013-01-01

Within the idiosyncratic enzyme active site environment, side chain and ligand pKa values can be profoundly perturbed relative to their values in aqueous solution. Whereas structural inspection of systems has often attributed perturbed pKa values to dominant contributions from placement near to charged groups or within hydrophobic pockets, Tyr57 of a P. putida ketosteroid isomerase (KSI) mutant, suggested to have a pKa perturbed by nearly 4 units to 6.3, is situated within a solvent-exposed active site devoid of cationic side chains, metal ions, or cofactors. Extensive comparisons among 45 variants with mutations in and around the KSI active site, along with protein semi-synthesis, 13C NMR spectroscopy, absorbance spectroscopy, and x-ray crystallography, was used to unravel the basis for this perturbed Tyr pKa. The results suggest that the origin of large energetic perturbations are more complex than suggested by visual inspection. For example, the introduction of positively charged residues near Tyr57 raises its pKa rather than lowers it; this effect, and part of the increase in the Tyr pKa from introduction of nearby anionic groups arise from accompanying active site structural rearrangements. Other mutations with large effects also cause structural perturbations or appear to displace a structured water molecule that is part of a stabilizing hydrogen bond network. Our results lead to a model in which three hydrogen bonds are donated to the stabilized ionized Tyr, with these hydrogen bond donors, two Tyr side chains and a water molecule, positioned by other side chains and by a water-mediated hydrogen bond network. These results support the notion that large energetic effects are often the consequence of multiple stabilizing interactions, rather than a single dominant interaction. Most generally, this work provides a case study for how extensive and comprehensive comparisons via site-directed mutagenesis in a tight feedback loop with structural analysis can greatly facilitate our understanding of enzyme active site energetics. The extensive dataset provided may also be a valuable resource for those wishing to extensively test computational approaches for determining enzymatic pKa values and energetic effects. PMID:24151972

The Centrality of the "Mediation" Concept in the Participatory Management of Water Resources

ERIC Educational Resources Information Center

dos Santos, Irenilda Angela; Berlinck, Christian Niel; de Santana Araujo, Symone Christine; Steinke, Ercilia Torres; Steinke, Valdir Adilson; Pianta, Taissa Ferreira; Graebner, Ivete Teresinha; Saito, Carlos Hiroo

2005-01-01

This work presents questions related to the viability and the requirements for the implementation of a National Policy of Water Resources in Brazil, and identifies the means to bring about active participation by the population in the management of water resources. While social inequalities may be an impediment to the implementation of full…

"To Mediate Relevantly": A Response to James Simpson

ERIC Educational Resources Information Center

Waters, Alan

2009-01-01

In Waters (2009), it was contended that, because of its ideological orientation, a good deal of applied linguistics for language teaching (ALLT) fails to "mediate relevantly" between academic and practitioner perspectives. James Simpson's rejoinder to my article (Simpson 2009) attempts to refute its claims. However, in my view, it fails to do so,…

A template-free solvent-mediated synthesis of high surface area boron nitride nanosheets for aerobic oxidative desulfurization.

PubMed

Wu, Peiwen; Zhu, Wenshuai; Chao, Yanhong; Zhang, Jinshui; Zhang, Pengfei; Zhu, Huiyuan; Li, Changfeng; Chen, Zhigang; Li, Huaming; Dai, Sheng

2016-01-04

Hexagonal boron nitride nanosheets (h-BNNs) with rather high specific surface area (SSA) are important two-dimensional layer-structured materials. Here, a solvent-mediated synthesis of h-BNNs revealed a template-free lattice plane control strategy that induced high SSA nanoporous structured h-BNNs with outstanding aerobic oxidative desulfurization performance.

A Model of Sexual Abuse's Effects on Suicidal Behavior and Delinquency: The Role of Emotions as Mediating Factors

ERIC Educational Resources Information Center

Sigfusdottir, Inga Dora; Asgeirsdottir, Bryndis Bjork; Gudjonsson, Gisli H.; Sigurdsson, Jon Fridrik

2008-01-01

Drawing on Agnew's general strain theory, we examined whether depressed mood and anger mediated the effects of sexual abuse on suicidal behavior and delinquency. Participants included 9,113 students attending high schools in Iceland. Structural equation modeling showed that, while controlling for family structure and parental education, being…

Testing Mediation in Structural Equation Modeling: The Effectiveness of the Test of Joint Significance

ERIC Educational Resources Information Center

Leth-Steensen, Craig; Gallitto, Elena

2016-01-01

A large number of approaches have been proposed for estimating and testing the significance of indirect effects in mediation models. In this study, four sets of Monte Carlo simulations involving full latent variable structural equation models were run in order to contrast the effectiveness of the currently popular bias-corrected bootstrapping…

The Mediating Role of Intercultural Wonderment: Connecting Programmatic Components to Global Outcomes in Study Abroad

ERIC Educational Resources Information Center

Engberg, Mark E.; Jourian, T. J.; Davidson, Lisa M.

2016-01-01

This study examines the mediating role of intercultural wonderment in relation to students' development of a global perspective. We utilize both confirmatory factor analysis and structural equation modeling to validate the intercultural wonderment construct and test the direct and indirect effects of the structural pathways in the model,…

The Origin and Early Evolution of Membrane Proteins

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Schweighofer, Karl; Wilson, Michael A.

2005-01-01

Membrane proteins mediate functions that are essential to all cells. These functions include transport of ions, nutrients and waste products across cell walls, capture of energy and its transduction into the form usable in chemical reactions, transmission of environmental signals to the interior of the cell, cellular growth and cell volume regulation. In the absence of membrane proteins, ancestors of cell (protocells), would have had only very limited capabilities to communicate with their environment. Thus, it is not surprising that membrane proteins are quite common even in simplest prokaryotic cells. Considering that contemporary membrane channels are large and complex, both structurally and functionally, a question arises how their presumably much simpler ancestors could have emerged, perform functions and diversify in early protobiological evolution. Remarkably, despite their overall complexity, structural motifs in membrane proteins are quite simple, with a-helices being most common. This suggests that these proteins might have evolved from simple building blocks. To explain how these blocks could have organized into functional structures, we performed large-scale, accurate computer simulations of folding peptides at a water-membrane interface, their insertion into the membrane, self-assembly into higher-order structures and function. The results of these simulations, combined with analysis of structural and functional experimental data led to the first integrated view of the origin and early evolution of membrane proteins.

Electrochemical Water Oxidation and Stereoselective Oxygen Atom Transfer Mediated by a Copper Complex.

PubMed

Kafentzi, Maria-Chrysanthi; Papadakis, Raffaello; Gennarini, Federica; Kochem, Amélie; Iranzo, Olga; Le Mest, Yves; Le Poul, Nicolas; Tron, Thierry; Faure, Bruno; Simaan, A Jalila; Réglier, Marius

2018-04-06

Water oxidation by copper-based complexes to form dioxygen has attracted attention in recent years, with the aim of developing efficient and cheap catalysts for chemical energy storage. In addition, high-valent metal-oxo species produced by the oxidation of metal complexes in the presence of water can be used to achieve substrate oxygenation with the use of H 2 O as an oxygen source. To date, this strategy has not been reported for copper complexes. Herein, a copper(II) complex, [(RPY2)Cu(OTf) 2 ] (RPY2=N-substituted bis[2-pyridyl(ethylamine)] ligands; R=indane; OTf=triflate), is used. This complex, which contains an oxidizable substrate moiety (indane), is used as a tool to monitor an intramolecular oxygen atom transfer reaction. Electrochemical properties were investigated and, upon electrolysis at 1.30 V versus a normal hydrogen electrode (NHE), both dioxygen production and oxygenation of the indane moiety were observed. The ligand was oxidized in a highly diastereoselective manner, which indicated that the observed reactivity was mediated by metal-centered reactive species. The pH dependence of the reactivity was monitored and correlated with speciation deduced from different techniques, ranging from potentiometric titrations to spectroscopic studies and DFT calculations. Water oxidation for dioxygen production occurs at neutral pH and is probably mediated by the oxidation of a mononuclear copper(II) precursor. It is achieved with a rather low overpotential (280 mV at pH 7), although with limited efficiency. On the other hand, oxygenation is maximum at pH 8-8.5 and is probably mediated by the electrochemical oxidation of an antiferromagnetically coupled dinuclear bis(μ-hydroxo) copper(II) precursor. This constitutes the first example of copper-centered oxidative water activation for a selective oxygenation reaction. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

One- and two-dimensional divalent copper coordination polymers based on kinked organodiimine and long flexible aliphatic dicarboxylate ligands

NASA Astrophysics Data System (ADS)

Mallika Krishnan, Subhashree; Supkowski, Ronald M.; LaDuca, Robert L.

2008-11-01

Hydrothermal synthesis under acidic conditions has afforded a pair of divalent copper coordination polymers containing the kinked dipodal tethering organodiimine 4,4'-dipyridylamine (dpa) and flexible long-chain aliphatic dicarboxylate ligands. The new materials were characterized by single crystal X-ray structure determination, infrared spectroscopy, and thermogravimetric analysis. [CuCl(suberate) 0.5(dpa)] ( 1) manifests 1-D ladder-like motifs aggregated into 3-D through hydrogen bonding and copper-mediated supramolecular interactions. Extension of the aliphatic chain within the dicarboxylate ligand by one methylene unit resulted in {[Cu(azelate)(dpa)(H 2O)] · 3H 2O} ( 2), a (4,4) rhomboid grid 2-D coordination polymer encapsulating acyclic water molecule trimers.

IFACEwat: the interfacial water-implemented re-ranking algorithm to improve the discrimination of near native structures for protein rigid docking

PubMed Central

2014-01-01

Background Protein-protein docking is an in silico method to predict the formation of protein complexes. Due to limited computational resources, the protein-protein docking approach has been developed under the assumption of rigid docking, in which one of the two protein partners remains rigid during the protein associations and water contribution is ignored or implicitly presented. Despite obtaining a number of acceptable complex predictions, it seems to-date that most initial rigid docking algorithms still find it difficult or even fail to discriminate successfully the correct predictions from the other incorrect or false positive ones. To improve the rigid docking results, re-ranking is one of the effective methods that help re-locate the correct predictions in top high ranks, discriminating them from the other incorrect ones. In this paper, we propose a new re-ranking technique using a new energy-based scoring function, namely IFACEwat - a combined Interface Atomic Contact Energy (IFACE) and water effect. The IFACEwat aims to further improve the discrimination of the near-native structures of the initial rigid docking algorithm ZDOCK3.0.2. Unlike other re-ranking techniques, the IFACEwat explicitly implements interfacial water into the protein interfaces to account for the water-mediated contacts during the protein interactions. Results Our results showed that the IFACEwat increased both the numbers of the near-native structures and improved their ranks as compared to the initial rigid docking ZDOCK3.0.2. In fact, the IFACEwat achieved a success rate of 83.8% for Antigen/Antibody complexes, which is 10% better than ZDOCK3.0.2. As compared to another re-ranking technique ZRANK, the IFACEwat obtains success rates of 92.3% (8% better) and 90% (5% better) respectively for medium and difficult cases. When comparing with the latest published re-ranking method F2Dock, the IFACEwat performed equivalently well or even better for several Antigen/Antibody complexes. Conclusions With the inclusion of interfacial water, the IFACEwat improves mostly results of the initial rigid docking, especially for Antigen/Antibody complexes. The improvement is achieved by explicitly taking into account the contribution of water during the protein interactions, which was ignored or not fully presented by the initial rigid docking and other re-ranking techniques. In addition, the IFACEwat maintains sufficient computational efficiency of the initial docking algorithm, yet improves the ranks as well as the number of the near native structures found. As our implementation so far targeted to improve the results of ZDOCK3.0.2, and particularly for the Antigen/Antibody complexes, it is expected in the near future that more implementations will be conducted to be applicable for other initial rigid docking algorithms. PMID:25521441

Effects of climate change on snowpack, glaciers, and water resources in the Northern Rockies Region [Chapter 4

Treesearch

Charles H. Luce

2018-01-01

Water is critical to life, and the effects of climate change on ecosystems are mediated through changes in hydrology. Changes in how snow accumulates and melts are one of the more consistently noted climate-induced changes to water in the western United States (Barnett et al. 2005; Service 2004), and these changes affect when water will be available for forests and...

Effect of apoA-I Mutations in the Capacity of Reconstituted HDL to Promote ABCG1-Mediated Cholesterol Efflux.

PubMed

Daniil, Georgios; Zannis, Vassilis I; Chroni, Angeliki

2013-01-01

ATP binding cassette transporter G1 (ABCG1) mediates the cholesterol transport from cells to high-density lipoprotein (HDL), but the role of apolipoprotein A-I (apoA-I), the main protein constituent of HDL, in this process is not clear. To address this, we measured cholesterol efflux from HEK293 cells or J774 mouse macrophages overexpressing ABCG1 using as acceptors reconstituted HDL (rHDL) containing wild-type or various mutant apoA-I forms. It was found that ABCG1-mediated cholesterol efflux was severely reduced (by 89%) when using rHDL containing the carboxyl-terminal deletion mutant apoA-I[Δ(185-243)]. ABCG1-mediated cholesterol efflux was not affected or moderately decreased by rHDL containing amino-terminal deletion mutants and several mid-region deletion or point apoA-I mutants, and was restored to 69-99% of control by double deletion mutants apoA-I[Δ(1-41)Δ(185-243)] and apoA-I[Δ(1-59)Δ(185-243)]. These findings suggest that the central helices alone of apoA-I associated to rHDL can promote ABCG1-mediated cholesterol efflux. Further analysis showed that rHDL containing the carboxyl-terminal deletion mutant apoA-I[Δ(185-243)] only slightly reduced (by 22%) the ABCG1-mediated efflux of 7-ketocholesterol, indicating that depending on the sterol type, structural changes in rHDL-associated apoA-I affect differently the ABCG1-mediated efflux of cholesterol and 7-ketocholesterol. Overall, our findings demonstrate that rHDL-associated apoA-I structural changes affect the capacity of rHDL to accept cellular cholesterol by an ABCG1-mediated process. The structure-function relationship seen here between rHDL-associated apoA-I mutants and ABCG1-mediated cholesterol efflux closely resembles that seen before in lipid-free apoA-I mutants and ABCA1-dependent cholesterol efflux, suggesting that both processes depend on the same structural determinants of apoA-I.

Association between Body Image Dissatisfaction and Self-Rated Health, as Mediated by Physical Activity and Eating Habits: Structural Equation Modelling in ELSA-Brasil.

PubMed

de Oliveira da Silva, Patricia; Miguez Nery Guimarães, Joanna; Härter Griep, Rosane; Caetano Prates Melo, Enirtes; Maria Alvim Matos, Sheila; Del Carmem Molina, Maria; Maria Barreto, Sandhi; de Jesus Mendes da Fonseca, Maria

2018-04-18

This study investigated whether the association between body image dissatisfaction and poor self-rated health is mediated by insufficient physical activity and unhealthy eating habits. The participants were 6727 men and 8037 women from the baseline (2008–2010) of the Longitudinal Study of Adult Health (Estudo Longitudinal de Saúde do Adulto, ELSA-Brasil). Structural equation modelling was used. Associations were found between body image dissatisfaction and poor self-rated health in both sexes. Insufficient physical activity was a mediator. However, unhealthy eating habits were found to exert a mediator effect only via insufficient physical activity. Body image dissatisfaction was found to associate, both directly and possibly indirectly, with poor self-rated health, mediated by insufficient physical activity and unhealthy eating habits. Accordingly, encouraging physical activity and healthy eating can contribute to reducing body image dissatisfaction and favour better self-rated health.

Effects of different black mediators on the shear strength of orthodontic bracket to the enamel treated with Nd-Yag laser

NASA Astrophysics Data System (ADS)

Huang, Shun-Te; Lin, I.-Shueng; Tsai, Chi-Cheng

1995-04-01

The Nd:YAG laser has ablation, crack, and crater effects on the dental enamel through black mediators which are very similar to the acid etching effects of phosphoric acid. This study was designed for searching how the different black mediators influence the shear strengths of the brackets bound to the enamel surfaces which were treated with the Nd:YAG laser. 90 bovine enamels divided into 5 groups were painted with 5 kinds of black mediators including Chinese ink, oil ink, black ball pen, water ink and black transfer paper. The enamel surfaces painted with black mediators were then radiated by Nd:YAG laser (ADL; American Dental Laser 300dl, power: 20 pps, 87.5 mj). Orthodontic brackets were bonded to the radiated surfaces. Then the shear strengths of the brackets to the enamels were measured by Instron. The results showed that the Chinese ink group and oil ink group has the strongest shear strength, ball pen group and water ink group showed the second strength, and the transfer paper group has the lowest shear strength. In addition, scanning electronic microscope also was used to observe the topographic changes of the enamel surfaces induced by the laser ablation.

Why and for Whom May Coping Planning Have Adverse Effects? A Moderated Mediation Analysis.

PubMed

Inauen, Jennifer; Stocker, Andrea; Scholz, Urte

2018-05-09

Coping planning, the formation of plans to overcome behavioral barriers is assumed to promote health behavior maintenance, but the literature on this is inconsistent. In this study, we aimed to investigate the mechanisms of a coping planning intervention that adversely affected maintained safe water consumption. We also explored perceived behavioral difficulty as a potential moderator of coping planning interventions. In the second phase of a cluster-randomised trial, households (N = 177 analyzed) were randomly allocated to a coping planning intervention or a comparison group (repetition of interventions from first intervention phase). Safe water consumption, the mechanisms of coping planning, and perceived difficulty were measured pre-post. The data were analyzed using mediation and moderated mediation analysis. Changes in behavioral intention mediated the intervention effects on behavioral maintenance (b = -0.36, 95% CI [-0.91, -0.03]). Changes in perceived coping planning (b = 0.08, 95% CI [-0.12, 0.34]), and maintenance self-efficacy (b = -0.13, 95% CI [-0.45, 0.01]) did not mediate the effects. Prior perceived difficulty moderated the coping planning intervention effects on maintenance via intention. Coping planning may decrease motivation for health behavior maintenance for persons who experienced few barriers prior to the planning intervention. © 2018 The International Association of Applied Psychology.

Building Adaptive Capacity with the Delphi Method and Mediated Modeling for Water Quality and Climate Change Adaptation in Lake Champlain Basin

NASA Astrophysics Data System (ADS)

Coleman, S.; Hurley, S.; Koliba, C.; Zia, A.; Exler, S.

2014-12-01

Eutrophication and nutrient pollution of surface waters occur within complex governance, social, hydrologic and biophysical basin contexts. The pervasive and perennial nutrient pollution in Lake Champlain Basin, despite decades of efforts, exemplifies problems found across the world's surface waters. Stakeholders with diverse values, interests, and forms of explicit and tacit knowledge determine water quality impacts through land use, agricultural and water resource decisions. Uncertainty, ambiguity and dynamic feedback further complicate the ability to promote the continual provision of water quality and ecosystem services. Adaptive management of water resources and land use requires mechanisms to allow for learning and integration of new information over time. The transdisciplinary Research on Adaptation to Climate Change (RACC) team is working to build regional adaptive capacity in Lake Champlain Basin while studying and integrating governance, land use, hydrological, and biophysical systems to evaluate implications for adaptive management. The RACC team has engaged stakeholders through mediated modeling workshops, online forums, surveys, focus groups and interviews. In March 2014, CSS2CC.org, an interactive online forum to source and identify adaptive interventions from a group of stakeholders across sectors was launched. The forum, based on the Delphi Method, brings forward the collective wisdom of stakeholders and experts to identify potential interventions and governance designs in response to scientific uncertainty and ambiguity surrounding the effectiveness of any strategy, climate change impacts, and the social and natural systems governing water quality and eutrophication. A Mediated Modeling Workshop followed the forum in May 2014, where participants refined and identified plausible interventions under different governance, policy and resource scenarios. Results from the online forum and workshop can identify emerging consensus across scales and sectors and be simulated in adaptation scenarios within integrated models. Comparing interventions and scenarios to existing and planned policy and governance systems in Lake Champlain Basin allows for new feedback to build adaptive capacity to identify key leverage points in the coupled natural and human system.

Aortic Stiffness, Increased White Matter Free Water, and Altered Microstructural Integrity: A Continuum of Injury.

PubMed

Maillard, Pauline; Mitchell, Gary F; Himali, Jayandra J; Beiser, Alexa; Fletcher, Evan; Tsao, Connie W; Pase, Matthew P; Satizabal, Claudia L; Vasan, Ramachandran S; Seshadri, Sudha; DeCarli, Charles

2017-06-01

Previous reports from the Framingham Heart Study have identified cross-sectional associations of arterial stiffness, as reflected by carotid-femoral pulse wave velocity (CFPWV) and systolic blood pressure with vascular brain injury. The purpose of this study is to examine free water (FW), fractional anisotropy (FA), and white matter hyperintensities (WMH) in relation to arterial stiffness among subjects of the Framingham Offspring and Third-Generation cohorts. In 2422 participants aged 51.3±11.6 years, FA, FW, and WMH were related to CFPWV using voxel-based linear and generalized linear regressions, adjusting for relevant covariables. Mean FW, mean FA, and WMH burden (log transformed) were computed within white matter (WM) region and related to systolic blood pressure and CFPWV using multiple mediation analyses. CFPWV was found to be associated with higher FW, lower FA, and higher WMH incidence in WM areas covering, respectively, 356.1, 211.8, and 10.9 mL of the WM mask. Mediation analyses revealed that the effect of systolic blood pressure on FW was mediated by CFPWV (direct and indirect effects: a=0.040; P <0.001, and a'=0.020; P >0.05). Moreover, the effect of CFPWV on FA was mediated by FW (direct and indirect effects: b=-0.092; P <0.001, and b'=0.012; P >0.05), whose effect on WMH was, in turn, mediated by FA (direct and indirect effects: c=0.246; P <0.001, and c'=0.116; P >0.05). From these data, we propose a biomechanical hypothesis designed for future research experiments to explain how hemodynamic alteration may lead to WM injury by impacting cerebral water content and more subtly WM integrity, to finally lead to WMH development. © 2017 American Heart Association, Inc.

The mediator complex in genomic and non-genomic signaling in cancer.

PubMed

Weber, Hannah; Garabedian, Michael J

2018-05-01

Mediator is a conserved, multi-subunit macromolecular machine divided structurally into head, middle, and tail modules, along with a transiently associating kinase module. Mediator functions as an integrator of transcriptional regulatory activity by interacting with DNA-bound transcription factors and with RNA polymerase II (Pol II) to both activate and repress gene expression. Mediator has been shown to affect multiple steps in transcription, including chromatin looping between enhancers and promoters, pre-initiation complex formation, transcriptional elongation, and mRNA splicing. Individual Mediator subunits participate in regulation of gene expression by the estrogen and androgen receptors and are altered in a number of endocrine cancers, including breast and prostate cancer. In addition to its role in genomic signaling, MED12 has been implicated in non-genomic signaling by interacting with and activating TGF-beta receptor 2 in the cytoplasm. Recent structural studies have revealed extensive inter-domain interactions and complex architecture of the Mediator-Pol II complex, suggesting that Mediator is capable of reorganizing its conformation and composition to fit cellular needs. We propose that alterations in Mediator subunit expression that occur in various cancers could impact the organization and function of Mediator, resulting in changes in gene expression that promote malignancy. A better understanding of the role of Mediator in cancer could reveal new approaches to the diagnosis and treatment of Mediator-dependent endocrine cancers, especially in settings of therapy resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Bacterial Mercury Methylation At The Sediment-Water Interface Of Mercury Contaminated Sediments

EPA Science Inventory

Bench scale experiments were conducted to improve our understanding of bacterial mediation of mercury transformation (methylation), specifically those factors which govern the production of methyl mercury (MeHg) at the sediment-water interface. The greatest cause for concern re...

Leader Empowering Behaviours and Work Engagement: The Mediating Role of Structural Empowerment.

PubMed

Cziraki, Karen; Laschinger, Heather

2015-09-01

Reports of poor working conditions persist amid ongoing healthcare restructuring. Simultaneously, nursing shortage threats continue as the nursing population ages. Leadership strategies that create empowering working conditions are likely to retain nurses who are eligible to retire, and attract future nurses to the profession. Several studies have focused on leader behaviours and structural empowerment in recent years and how these impact the work environment and staff engagement. Correlations among leader empowering behaviours, structural empowerment and work engagement have been demonstrated (Laschinger et al. 1999; Peachey 2002); however, there is a gap in the empirical literature as to how leader empowering behaviours influence nurses' work engagement by creating structurally empowering work environments. Kanter's (1977, 1993) structural empowerment theory was used to test this proposition using data from a cross-sectional study of 322 Ontario staff nurses. Mediation analysis revealed that structural empowerment partially mediated the influence of leader empowering behaviours on work engagement. The implications for healthcare managers and leaders are discussed with a view to the recruitment and retention of nursing staff, by fostering greater work engagement. Copyright © 2015 Longwoods Publishing.

Youth Experiences of Family Violence and Teen Dating Violence Perpetration: Cognitive and Emotional Mediators

ERIC Educational Resources Information Center

Jouriles, Ernest N.; McDonald, Renee; Mueller, Victoria; Grych, John H.

2012-01-01

This article describes a conceptual model of cognitive and emotional processes proposed to mediate the relation between youth exposure to family violence and teen dating violence perpetration. Explicit beliefs about violence, internal knowledge structures, and executive functioning are hypothesized as cognitive mediators, and their potential…

Estimating Causal Effects in Mediation Analysis Using Propensity Scores

ERIC Educational Resources Information Center

Coffman, Donna L.

2011-01-01

Mediation is usually assessed by a regression-based or structural equation modeling (SEM) approach that we refer to as the classical approach. This approach relies on the assumption that there are no confounders that influence both the mediator, "M", and the outcome, "Y". This assumption holds if individuals are randomly…

Multilevel SEM Strategies for Evaluating Mediation in Three-Level Data

ERIC Educational Resources Information Center

Preacher, Kristopher J.

2011-01-01

Strategies for modeling mediation effects in multilevel data have proliferated over the past decade, keeping pace with the demands of applied research. Approaches for testing mediation hypotheses with 2-level clustered data were first proposed using multilevel modeling (MLM) and subsequently using multilevel structural equation modeling (MSEM) to…

Affect Regulation as a Mediator of Attachment and Deliberate Self-Harm

ERIC Educational Resources Information Center

Kimball, Joan S.; Diddams, Margaret

2007-01-01

The authors used structural equation modeling to test the mediational role of affect regulation on attachment and deliberate self-harm in 216 undergraduates. Results suggest that affect regulation mediates the relationship between attachment and deliberate self-harm, providing support for the theoretical importance of attachment and affect…

Participation in Athletics and Female Sexual Risk Behavior: The Evaluation of Four Causal Structures.

ERIC Educational Resources Information Center

Dodge, Tonya; Jaccard, James

2002-01-01

Compared sexual risk behavior of female athletes and nonathletes. Examined mediation, reverse mediation, spurious effects, and moderated causal models, using as potential mediators physical development, educational aspirations, self-esteem, attitudes toward pregnancy, involvement in a romantic relationship, age, ethnicity, and social class. Found…

A General Approach to Causal Mediation Analysis

ERIC Educational Resources Information Center

Imai, Kosuke; Keele, Luke; Tingley, Dustin

2010-01-01

Traditionally in the social sciences, causal mediation analysis has been formulated, understood, and implemented within the framework of linear structural equation models. We argue and demonstrate that this is problematic for 3 reasons: the lack of a general definition of causal mediation effects independent of a particular statistical model, the…

Near-membrane electric field calcium ion dehydration.

PubMed

Barger, James P; Dillon, Patrick F

2016-12-01

The dehydration of ion-water complexes prior to ion channel transit has focused on channel protein-mediated dissociation of water. Ion dehydration by the membrane electric field has not previously been considered. Near membrane electric fields have previously been shown to cause the disassociation of non-covalently bound small molecule-small molecule, small molecule-protein, and protein-protein complexes. It is well known that cosmotropic, structure making ions such as calcium and sodium significantly bind multiple water ions in solution. It is also known that these ions are often not hydrated as they pass through membrane ion channels. Using capillary electrophoresis, the range of electric fields needed to strip water molecules from calcium ions has been measured. Ion migration velocity is a linear function of the electric field. At low electric fields, the migration rate of calcium ion was shown to be linearly related to the applied electric field. Using a form of the Stoke's equation applicable to ion migration, the hydrated calcium radius was found to be 0.334nm, corresponding to a water hydration shell of 5.09 water molecules. At higher electric fields, the slope of the calcium migration velocity as a function of the electric field increased, which was modeled as a decrease in the radius of the migrating ion as the water was removed. Using a tanh function to model the transition of the ion from a hydrated to a stripped state, the transition had a midpoint at 446V/cm, and was 88% complete at 587V/cm with a correlation coefficient of 0.9996. The migration velocity of the stripped calcium ion was found to be a function of both the decrease in radius and an increase in the effective, electronic viscosity of the dipole medium through which the dehydrated ion moved. The size of the electric field needed to dehydrate calcium occurs 6-7nm from the cell membrane. Calcium ions within this distance from the membrane will be devoid of water molecules when they reach the calcium selective channel pore entrances, all known to be approximately 1-2nm from the membrane. No matter what the calcium pore structure, calcium ions reaching the channel entrance will be devoid of a water shell. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tripartite ATP-independent Periplasmic (TRAP) Transporters Use an Arginine-mediated Selectivity Filter for High Affinity Substrate Binding*

PubMed Central

Fischer, Marcus; Hopkins, Adam P.; Severi, Emmanuele; Hawkhead, Judith; Bawdon, Daniel; Watts, Andrew G.; Hubbard, Roderick E.; Thomas, Gavin H.

2015-01-01

Tripartite ATP-independent periplasmic (TRAP) transporters are secondary transporters that have evolved an obligate dependence on a substrate-binding protein (SBP) to confer unidirectional transport. Different members of the DctP family of TRAP SBPs have binding sites that recognize a diverse range of organic acid ligands but appear to only share a common electrostatic interaction between a conserved arginine and a carboxylate group in the ligand. We investigated the significance of this interaction using the sialic acid-specific SBP, SiaP, from the Haemophilus influenzae virulence-related SiaPQM TRAP transporter. Using in vitro, in vivo, and structural methods applied to SiaP, we demonstrate that the coordination of the acidic ligand moiety of sialic acid by the conserved arginine (Arg-147) is essential for the function of the transporter as a high affinity scavenging system. However, at high substrate concentrations, the transporter can function in the absence of Arg-147 suggesting that this bi-molecular interaction is not involved in further stages of the transport cycle. As well as being required for high affinity binding, we also demonstrate that the Arg-147 is a strong selectivity filter for carboxylate-containing substrates in TRAP transporters by engineering the SBP to recognize a non-carboxylate-containing substrate, sialylamide, through water-mediated interactions. Together, these data provide biochemical and structural support that TRAP transporters function predominantly as high affinity transporters for carboxylate-containing substrates. PMID:26342690

Reduction of Sodium Arsenite-Mediated Adverse Effects in Mice using Dietary Supplementation of Water Hyacinth (Eichornia crassipes) Root Powder.

PubMed

Sarker, Rim Sabrina Jahan; Ahsan, Nazmul; Hossain, Khaled; Ghosh, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Akhand, Anwarul Azim

2012-07-01

In this study, we evaluated the protective effects of water Hyacinth Root Powder (HRP) on arsenic-mediated toxic effects in mice. Swiss albino mice, used in this study, were divided into four different groups (for each group n=5). The control group was supplied with normal feed and water, Arsenic group (As-group) was supplied with normal feed plus arsenic (sodium arsenite)-containing water, and arsenic+hyacinth group (As+Hy group) was supplied with feed supplemented with HRP plus arsenic water. The remaining Hy-group was supplied with feed supplemented with HRP plus normal water. Oral administration of arsenic reduced the normal growth of the mice as evidenced by weight loss. Interestingly, tip of the tails of these mice developed wound that caused gradual reduction of the tail length. Supplementation of HRP in feed significantly prevented mice growth retardation and tail wounding in As+Hy group mice. However, the growth pattern in Hy-group mice was observed to be almost similar to that of the control group indicating that HRP itself has no toxic or negative effect in mice. Ingested arsenic also distorted the shape of the blood cells and elevated the serum enzymes such as lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and serum glutamic pyruvic transaminase (SGPT). Importantly, elevation of these enzymes and distortion of blood cell shape were partially reduced in mice belong to As+Hy group, indicating HRP-mediated reduction of arsenic toxicity. Therefore, the preventive effect of hyacinth root on arsenic-poisoned mice suggested the future application of hyacinth to reduce arsenic toxicity in animal and human.

Reduction of Sodium Arsenite-Mediated Adverse Effects in Mice using Dietary Supplementation of Water Hyacinth (Eichornia crassipes) Root Powder

PubMed Central

Sarker, Rim Sabrina Jahan; Ahsan, Nazmul; Hossain, Khaled; Ghosh, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Akhand, Anwarul Azim

2012-01-01

Background In this study, we evaluated the protective effects of water Hyacinth Root Powder (HRP) on arsenic-mediated toxic effects in mice. Methods Swiss albino mice, used in this study, were divided into four different groups (for each group n=5). The control group was supplied with normal feed and water, Arsenic group (As-group) was supplied with normal feed plus arsenic (sodium arsenite)-containing water, and arsenic+hyacinth group (As+Hy group) was supplied with feed supplemented with HRP plus arsenic water. The remaining Hy-group was supplied with feed supplemented with HRP plus normal water. Results Oral administration of arsenic reduced the normal growth of the mice as evidenced by weight loss. Interestingly, tip of the tails of these mice developed wound that caused gradual reduction of the tail length. Supplementation of HRP in feed significantly prevented mice growth retardation and tail wounding in As+Hy group mice. However, the growth pattern in Hy-group mice was observed to be almost similar to that of the control group indicating that HRP itself has no toxic or negative effect in mice. Ingested arsenic also distorted the shape of the blood cells and elevated the serum enzymes such as lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and serum glutamic pyruvic transaminase (SGPT). Importantly, elevation of these enzymes and distortion of blood cell shape were partially reduced in mice belong to As+Hy group, indicating HRP-mediated reduction of arsenic toxicity. Conclusion Therefore, the preventive effect of hyacinth root on arsenic-poisoned mice suggested the future application of hyacinth to reduce arsenic toxicity in animal and human. PMID:23407303

Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water

PubMed Central

Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

2015-01-01

Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury. PMID:26316710

Death receptor and mitochondria-mediated hepatocyte apoptosis underlies liver dysfunction in rats exposed to organic pollutants from drinking water.

PubMed

Yang, Guanghong; Zhou, Zhiwei; Cen, Yanli; Gui, Xiaolin; Zeng, Qibing; Ao, Yunxia; Li, Qian; Wang, Shiran; Li, Jun; Zhang, Aihua

2015-01-01

Persistent organic pollutants in drinking water impose a substantial risk to the health of human beings, but the evidence for liver toxic effect and the underlying mechanism is scarce. This study aimed to examine the liver toxicity and elucidate the molecular mechanism of organic pollutants in drinking water in normal human liver cell line L02 cells and rats. The data showed that organic extraction from drinking water remarkably impaired rat liver function, evident from the increase in the serum level of alanine aminotransferase, aspartate aminotransferase, and cholinesterase, and decrease in the serum level of total protein and albumin. Organic extraction dose-dependently induced apoptotic cell death in rat liver and L02 cells. Administration of rats with organic extraction promoted death receptor signaling pathway through the increase in gene and protein expression level of Fas and FasL. Treatment of rats with organic extraction also induced mitochondria-mediated apoptosis via increasing the expression level of proapoptotic protein, Bax, but decreasing the expression level of antiapoptotic protein, Bcl-2, resulting in an upregulation of cytochrome c and activation of caspase cascade at both transcriptional and post-transcriptional levels. Moreover, organic extraction enhanced rat liver glutathione S-transferases activity and reactive oxygen species generation, and upregulated aryl hydrocarbon receptor and glutathione S-transferase A1 at both transcriptional and translational levels. Collectively, the results indicate that organic extraction from drinking water impairs liver function, with the involvement of death receptor and mitochondria-mediated apoptosis in rats. The results provide evidence and molecular mechanisms for organic pollutants in drinking water-induced liver dysfunction, which may help prevent and treat organic extraction-induced liver injury.

Membraneless organelles can melt nucleic acid duplexes and act as biomolecular filters

NASA Astrophysics Data System (ADS)

Nott, Timothy J.; Craggs, Timothy D.; Baldwin, Andrew J.

2016-06-01

Membraneless organelles are cellular compartments made from drops of liquid protein inside a cell. These compartments assemble via the phase separation of disordered regions of proteins in response to changes in the cellular environment and the cell cycle. Here we demonstrate that the solvent environment within the interior of these cellular bodies behaves more like an organic solvent than like water. One of the most-stable biological structures known, the DNA double helix, can be melted once inside the liquid droplet, and simultaneously structures formed from regulatory single-stranded nucleic acids are stabilized. Moreover, proteins are shown to have a wide range of absorption or exclusion from these bodies, and can act as importers for otherwise-excluded nucleic acids, which suggests the existence of a protein-mediated trafficking system. A common strategy in organic chemistry is to utilize different solvents to influence the behaviour of molecules and reactions. These results reveal that cells have also evolved this capability by exploiting the interiors of membraneless organelles.

Spiracular air breathing in polypterid fishes and its implications for aerial respiration in stem tetrapods

NASA Astrophysics Data System (ADS)

Graham, Jeffrey B.; Wegner, Nicholas C.; Miller, Lauren A.; Jew, Corey J.; Lai, N. Chin; Berquist, Rachel M.; Frank, Lawrence R.; Long, John A.

2014-01-01

The polypterids (bichirs and ropefish) are extant basal actinopterygian (ray-finned) fishes that breathe air and share similarities with extant lobe-finned sarcopterygians (lungfishes and tetrapods) in lung structure. They are also similar to some fossil sarcopterygians, including stem tetrapods, in having large paired openings (spiracles) on top of their head. The role of spiracles in polypterid respiration has been unclear, with early reports suggesting that polypterids could inhale air through the spiracles, while later reports have largely dismissed such observations. Here we resolve the 100-year-old mystery by presenting structural, behavioural, video, kinematic and pressure data that show spiracle-mediated aspiration accounts for up to 93% of all air breaths in four species of Polypterus. Similarity in the size and position of polypterid spiracles with those of some stem tetrapods suggests that spiracular air breathing may have been an important respiratory strategy during the fish-tetrapod transition from water to land.

Spiracular air breathing in polypterid fishes and its implications for aerial respiration in stem tetrapods.

PubMed

Graham, Jeffrey B; Wegner, Nicholas C; Miller, Lauren A; Jew, Corey J; Lai, N Chin; Berquist, Rachel M; Frank, Lawrence R; Long, John A

2014-01-01

The polypterids (bichirs and ropefish) are extant basal actinopterygian (ray-finned) fishes that breathe air and share similarities with extant lobe-finned sarcopterygians (lungfishes and tetrapods) in lung structure. They are also similar to some fossil sarcopterygians, including stem tetrapods, in having large paired openings (spiracles) on top of their head. The role of spiracles in polypterid respiration has been unclear, with early reports suggesting that polypterids could inhale air through the spiracles, while later reports have largely dismissed such observations. Here we resolve the 100-year-old mystery by presenting structural, behavioural, video, kinematic and pressure data that show spiracle-mediated aspiration accounts for up to 93% of all air breaths in four species of Polypterus. Similarity in the size and position of polypterid spiracles with those of some stem tetrapods suggests that spiracular air breathing may have been an important respiratory strategy during the fish-tetrapod transition from water to land.

DFT investigation on two-dimensional GeS/WS2 van der Waals heterostructure for direct Z-scheme photocatalytic overall water splitting

NASA Astrophysics Data System (ADS)

Ju, Lin; Dai, Ying; Wei, Wei; Li, Mengmeng; Huang, Baibiao

2018-03-01

Recently, extensive attention has been paid to the direct Z-scheme systems for photocatalytic water splitting where carriers migrate directly between the two semiconductors without a redox mediator. In the present work, the electronic structure and related properties of two-dimensional (2D) van de Waals (vdW) GeS/WX2 (X = O, S, Se, Te) heterojunction are systematically investigated by first-principles calculations. Our results demonstrate that, the GeS/WS2 heterojunction could form a direct Z-scheme system for photocatalytic water splitting, whereas the GeS/WX2 (X = O, Se, Te) can't, because of their respective unsuitable electronic structures. For the GeS/WS2 heterojunction, the GeS and WS2 monolayers serve as photocatalysts for the hydrogen evolution reactionand oxygen evolution reaction, respectively. The internal electric field induced by the electron transfer at the interface can promote the separation of photo-generated charge carriers and formation of the interface Z-scheme electron transfer. Remarkably, the designed GeS/WS2 heterojunction not only enhances the hydrogen production activity of GeS and the oxygen production ability of WS2 but also improves the light absorption of the two monolayers by reducing the band gaps. Moreover, it is found that narrowing the interlayer distance could enhance the internal electric field, improving the photocatalytic ability of the vdW heterojunction. This work provides fundamental insights for further design and preparation of emergent metal dichalcogenide catalysts, beneficial for the development in clean energy.

Sink or Swim: Ions and Organics at the Ice-Air Interface.

PubMed

Hudait, Arpa; Allen, Michael T; Molinero, Valeria

2017-07-26

The ice-air interface is an important locus of environmental chemical reactions. The structure and dynamics of the ice surface impact the uptake of trace gases and kinetics of reactions in the atmosphere and snowpack. At tropospheric temperatures, the ice surface is partially premelted. Experiments indicate that ions increase the liquidity of the ice surface but hydrophilic organics do not. However, it is not yet known the extent of the perturbation solutes induce at the ice surface and what is the role of the disordered liquid-like layer in modulating the interaction between solutes and their mobility and aggregation at the ice surface. Here we use large-scale molecular simulations to investigate the effect of ions and glyoxal, one of the most abundant oxygenated volatile organic compounds in the atmosphere, on the structure, dynamics, and solvation properties of the ice surface. We find that the premelted surface of ice has unique solvation properties, different from those of liquid water. The increase in surface liquidity resulting from the hydration of ions leads to a water-mediated attraction of ions at the ice surface. Glyoxal molecules, on the other hand, perturb only slightly the surface of ice and do not experience water-driven attraction. They nonetheless accumulate as dry agglomerates at the ice surface, driven by direct interactions between the organic molecules. The enhanced attraction and clustering of ions and organics at the ice surface may play a significant role in modulating the mechanism and rate of heterogeneous chemical reactions occurring at the surface of atmospheric ice particles.

Unexpected Binding Mode of a Potent Indeno[1,2-b]indole-Type Inhibitor of Protein Kinase CK2 Revealed by Complex Structures with the Catalytic Subunit CK2α and Its Paralog CK2α′

PubMed Central

Hochscherf, Jennifer; Lindenblatt, Dirk; Witulski, Benedict; Birus, Robin; Aichele, Dagmar

2017-01-01

Protein kinase CK2, a member of the eukaryotic protein kinase superfamily, is associated with cancer and other human pathologies and thus an attractive drug target. The indeno[1,2-b]indole scaffold is a novel lead structure to develop ATP-competitive CK2 inhibitors. Some indeno[1,2-b]indole-based CK2 inhibitors additionally obstruct ABCG2, an ABC half transporter overexpressed in breast cancer and co-responsible for drug efflux and resistance. Comprehensive derivatization studies revealed substitutions of the indeno[1,2-b]indole framework that boost either the CK2 or the ABCG2 selectivity or even support the dual inhibition potential. The best indeno[1,2-b]indole-based CK2 inhibitor described yet (IC50 = 25 nM) is 5-isopropyl-4-(3-methylbut-2-enyl-oxy)-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione (4p). Herein, we demonstrate the membrane permeability of 4p and describe co-crystal structures of 4p with CK2α and CK2α′, the paralogs of human CK2 catalytic subunit. As expected, 4p occupies the narrow, hydrophobic ATP site of CK2α/CK2α′, but surprisingly with a unique orientation: its hydrophobic substituents point towards the solvent while its two oxo groups are hydrogen-bonded to a hidden water molecule. An equivalent water molecule was found in many CK2α structures, but never as a critical mediator of ligand binding. This unexpected binding mode is independent of the interdomain hinge/helix αD region conformation and of the salt content in the crystallization medium. PMID:29236079

A template-free solvent-mediated synthesis of high surface area boron nitride nanosheets for aerobic oxidative desulfurization

DOE PAGES

Wu, Peiwen; Zhu, Wenshuai; Chao, Yanhong; ...

2015-10-16

Hexagonal boron nitride nanosheets (h-BNNs) with rather high specific surface area (SSA) are important two-dimensional layer-structured materials. Here in this study, a solvent-mediated synthesis of h-BNNs revealed a template-free lattice plane control strategy that induced high SSA nanoporous structured h-BNNs with outstanding aerobic oxidative desulfurization performance.

Testing Wallace's intuition: water type, reproductive isolation and divergence in an Amazonian fish.

PubMed

Pires, Tiago H S; Borghezan, Elio A; Machado, Valeria N; Powell, Daniel L; Röpke, Cristhiana P; Oliveira, Claudio; Zuanon, Jansen; Farias, Izeni P

2018-06-01

Alfred Russel Wallace proposed classifying Amazon rivers based on their colour and clarity: white, black and clear water. Wallace also proposed that black waters could mediate diversification and yield distinct fish species. Here, we bring evidence of speciation mediated by water type in the sailfin tetra (Crenuchus spilurus), a fish whose range encompasses rivers of very distinct hydrochemical conditions. Distribution of the two main lineages concords with Wallace's water types: one restricted to the acidic and nutrient-poor waters of the Negro River (herein Rio Negro lineage) and a second widespread throughout the remaining of the species' distribution (herein Amazonas lineage). These lineages occur over a very broad geographical range, suggesting that despite occurring in regions separated by thousands of kilometres, individuals of the distinct lineages fail to occupy each other's habitats, hundreds of metres apart and not separated by physical barrier. Reproductive isolation was assessed in isolated pairs exposed to black-water conditions. All pairs with at least one individual of the lineage not native to black waters showed significantly lower spawning success, suggesting that the water type affected the fitness and contributed to reproductive isolation. Our results endorse Wallace's intuition and highlight the importance of ecological factors in shaping diversity of the Amazon fish fauna. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

School Learning Materials on Water Problems of New Mexico and the Southwest.

ERIC Educational Resources Information Center

Buethe, Chris; And Others

Schools typically make no special efforts to prepare students to cope with present and anticipated water problems. Using this as a premise, the objective of this study was to prepare a set of mediated learning packages based upon water problems of New Mexico and the dry regions of the Southwest. These learning materials were prepared and field…

Selective regulation of clathrin-mediated epidermal growth factor receptor signaling and endocytosis by phospholipase C and calcium

PubMed Central

Delos Santos, Ralph Christian; Bautista, Stephen; Lucarelli, Stefanie; Bone, Leslie N.; Dayam, Roya M.; Abousawan, John; Botelho, Roberto J.; Antonescu, Costin N.

2017-01-01

Clathrin-mediated endocytosis is a major regulator of cell-surface protein internalization. Clathrin and other proteins assemble into small invaginating structures at the plasma membrane termed clathrin-coated pits (CCPs) that mediate vesicle formation. In addition, epidermal growth factor receptor (EGFR) signaling is regulated by its accumulation within CCPs. Given the diversity of proteins regulated by clathrin-mediated endocytosis, how this process may distinctly regulate specific receptors is a key question. We examined the selective regulation of clathrin-dependent EGFR signaling and endocytosis. We find that perturbations of phospholipase Cγ1 (PLCγ1), Ca2+, or protein kinase C (PKC) impair clathrin-mediated endocytosis of EGFR, the formation of CCPs harboring EGFR, and EGFR signaling. Each of these manipulations was without effect on the clathrin-mediated endocytosis of transferrin receptor (TfR). EGFR and TfR were recruited to largely distinct clathrin structures. In addition to control of initiation and assembly of CCPs, EGF stimulation also elicited a Ca2+- and PKC-dependent reduction in synaptojanin1 recruitment to clathrin structures, indicating broad control of CCP assembly by Ca2+ signals. Hence EGFR elicits PLCγ1-calcium signals to facilitate formation of a subset of CCPs, thus modulating its own signaling and endocytosis. This provides evidence for the versatility of CCPs to control diverse cellular processes. PMID:28814502

TEMPO-oxidized cellulose nanofibers

NASA Astrophysics Data System (ADS)

Isogai, Akira; Saito, Tsuguyuki; Fukuzumi, Hayaka

2011-01-01

Native wood celluloses can be converted to individual nanofibers 3-4 nm wide that are at least several microns in length, i.e. with aspect ratios >100, by TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidation and successive mild disintegration in water. Preparation methods and fundamental characteristics of TEMPO-oxidized cellulose nanofibers (TOCN) are reviewed in this paper. Significant amounts of C6 carboxylate groups are selectively formed on each cellulose microfibril surface by TEMPO-mediated oxidation without any changes to the original crystallinity (~74%) or crystal width of wood celluloses. Electrostatic repulsion and/or osmotic effects working between anionically-charged cellulose microfibrils, the ζ-potentials of which are approximately -75 mV in water, cause the formation of completely individualized TOCN dispersed in water by gentle mechanical disintegration treatment of TEMPO-oxidized wood cellulose fibers. Self-standing TOCN films are transparent and flexible, with high tensile strengths of 200-300 MPa and elastic moduli of 6-7 GPa. Moreover, TOCN-coated poly(lactic acid) films have extremely low oxygen permeability. The new cellulose-based nanofibers formed by size reduction process of native cellulose fibers by TEMPO-mediated oxidation have potential application as environmentally friendly and new bio-based nanomaterials in high-tech fields.

Surface Tension Mediated Under-Water Adhesion of Rigid Spheres on Soft, Charged Surfaces

NASA Astrophysics Data System (ADS)

Sinha, Shayandev; Das, Siddhartha

2015-11-01

Understanding the phenomenon of surface-tension-mediated under-water adhesion is necessary for studying a plethora of physiological and technical phenomena, such as the uptake of bacteria or nanoparticle by cells, attachment of virus on bacterial surfaces, biofouling on large ocean vessels and marine devices, etc. This adhesion phenomenon becomes highly non-trivial in case the soft surface where the adhesion occurs is also charged. Here we propose a theory for analyzing such an under-water adhesion of a rigid sphere on a soft, charged surface, represented by a grafted polyelectrolyte layer (PEL). We develop a model based on the minimization of free energy that, in addition to considering the elastic and the surface-tension-mediated adhesion energies, also accounts for the PEL electric double layer (EDL) induced electrostatic energies. We show that in the presence of surface charges, adhesion gets enhanced. This can be explained by the fact that the increase in the elastic energy is better balanced by the lowering of the EDL energy associated with the adhesion process. The entire behaviour is further dictated by the surface tension components that govern the adhesion energy.

MDC1: The art of keeping things in focus.

PubMed

Jungmichel, Stephanie; Stucki, Manuel

2010-08-01

The chromatin structure is important for recognition and repair of DNA damage. Many DNA damage response proteins accumulate in large chromatin domains flanking sites of DNA double-strand breaks. The assembly of these structures-usually termed DNA damage foci-is primarily regulated by MDC1, a large nuclear mediator/adaptor protein that is composed of several distinct structural and functional domains. Here, we are summarizing the latest discoveries about the mechanisms by which MDC1 mediates DNA damage foci formation, and we are reviewing the considerable efforts taken to understand the functional implication of these structures.

Controllable assembly and disassembly of nanoparticle systems via protein and DNA agents

DOEpatents

Lee, Soo-Kwan; Gang, Oleg; van der Lelie, Daniel

2014-05-20

The invention relates to the use of peptides, proteins, and other oligomers to provide a means by which normally quenched nanoparticle fluorescence may be recovered upon detection of a target molecule. Further, the inventive technology provides a structure and method to carry out detection of target molecules without the need to label the target molecules before detection. In another aspect, a method for forming arbitrarily shaped two- and three-dimensional protein-mediated nanoparticle structures and the resulting structures are described. Proteins mediating structure formation may themselves be functionalized with a variety of useful moieties, including catalytic functional groups.

Structure of polyhydroxyalkanoate (PHA) synthase PhaC from Chromobacterium sp. USM2, producing biodegradable plastics.

PubMed

Chek, Min Fey; Kim, Sun-Yong; Mori, Tomoyuki; Arsad, Hasni; Samian, Mohammed Razip; Sudesh, Kumar; Hakoshima, Toshio

2017-07-13

Polyhydroxyalkanoate (PHA) is a promising candidate for use as an alternative bioplastic to replace petroleum-based plastics. Our understanding of PHA synthase PhaC is poor due to the paucity of available three-dimensional structural information. Here we present a high-resolution crystal structure of the catalytic domain of PhaC from Chromobacterium sp. USM2, PhaC Cs -CAT. The structure shows that PhaC Cs -CAT forms an α/β hydrolase fold comprising α/β core and CAP subdomains. The active site containing Cys291, Asp447 and His477 is located at the bottom of the cavity, which is filled with water molecules and is covered by the partly disordered CAP subdomain. We designated our structure as the closed form, which is distinct from the recently reported catalytic domain from Cupriavidus necator (PhaC Cn -CAT). Structural comparison showed PhaC Cn -CAT adopting a partially open form maintaining a narrow substrate access channel to the active site, but no product egress. PhaC Cs -CAT forms a face-to-face dimer mediated by the CAP subdomains. This arrangement of the dimer is also distinct from that of the PhaC Cn -CAT dimer. These findings suggest that the CAP subdomain should undergo a conformational change during catalytic activity that involves rearrangement of the dimer to facilitate substrate entry and product formation and egress from the active site.

Identification of conserved lipid/detergent-binding sites in a high-resolution structure of the membrane protein cytochrome c oxidase

PubMed Central

Qin, Ling; Hiser, Carrie; Mulichak, Anne; Garavito, R. Michael; Ferguson-Miller, Shelagh

2006-01-01

Well ordered reproducible crystals of cytochrome c oxidase (CcO) from Rhodobacter sphaeroides yield a previously unreported structure at 2.0 Å resolution that contains the two catalytic subunits and a number of alkyl chains of lipids and detergents. Comparison with crystal structures of other bacterial and mammalian CcOs reveals that the positions occupied by native membrane lipids and detergent substitutes are highly conserved, along with amino acid residues in their vicinity, suggesting a more prevalent and specific role of lipid in membrane protein structure than often envisioned. Well defined detergent head groups (maltose) are found associated with aromatic residues in a manner similar to phospholipid head groups, likely contributing to the success of alkyl glycoside detergents in supporting membrane protein activity and crystallizability. Other significant features of this structure include the following: finding of a previously unreported crystal contact mediated by cadmium and an engineered histidine tag; documentation of the unique His–Tyr covalent linkage close to the active site; remarkable conservation of a chain of waters in one proton pathway (D-path); and discovery of an inhibitory cadmium-binding site at the entrance to another proton path (K-path). These observations provide important insight into CcO structure and mechanism, as well as the significance of bound lipid in membrane proteins. PMID:17050688

Lower Flathead System Fisheries Study, South Bay of Flathead Lake, Volume III, 1983-1987 Final Report.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cross, David; Waite, Ian

1988-06-01

The Lower Flathead System Fisheries Study assessed the effects of Kerr Dam operation on the fisheries of the lower Flathead ecosystem. South Bay, the southern most lobe of Flathead Lake, is the most extensive area of shallow water, and therefore, most effected by changes in lake levels. This study began in January of 1984 and was completed in early 1987. Vegetative and structural cover are relatively limited in South Bay, a condition which could contribute to lower recruitment for some fish species. Our data show that the study area contained 0.04% structural and 5.4% vegetative cover in June at fullmore » pool. Both figures are less than 1.0% at minimum pool. Structural complexity mediates the ecological interactions between littoral zone fish and their prey, and can affect local productivity and growth in fish. Structural complexity may also be important to overwinter survival of young perch in Flathead Lake. Winter conditions, including ice cover and fall drawdown, seasonally eliminate the vegetative portion of most rooted macrophytes in South Bay. This results in substantial loss of what little structural cover exists, depriving the perch population of habitat which has been occupied all summer. The loss of cover from draw-down concentrates and probably exposes perch to greater predation, including cannibalism, than would occur if structural complexity were greater. 33 refs., 10 figs., 5 tabs.« less

High-Potential Electrocatalytic O2 Reduction with Nitroxyl / NOx Mediators: Implications for Fuel Cells and Aerobic Oxidation Catalysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gerken, James B.; Stahl, Shannon S.

2015-07-15

Efficient reduction of O2 to water is a central challenge in energy conversion and aerobic oxidation catalysis. In the present study, we investigate the electrochemical reduction of O2 with soluble organic nitroxyl and nitrogen oxide (NOx) mediators. When used alone, neither organic nitroxyls, such as TEMPO (2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl), nor NOx species, such as sodium nitrite, are effective mediators of electrochemical O2 reduction. The combination of nitroxyl/NOx species, however, mediates sustained O2 reduction at electrochemical potentials of 0.19–0.33 V (vs. Fc/Fc+) in acetonitrile containing trifluoroacetic acid. Mechanistic analysis of the coupled redox reactions supports a process in which the nitrogen oxide catalystmore » drives aerobic oxidation of a nitroxyl mediator to an oxoammonium species, which then is reduced back to the nitroxyl at the cathode. The electrolysis potential is dictated by the oxoammonium/nitroxyl reduction potential. The high potentials observed with this ORR system benefit from the mechanism-based specificity for four-electron reduction of oxygen to water mediated by NOx species, together with kinetically efficient reduction of oxidized NOx species by TEMPO and other organic nitroxyls. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center, funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences.« less

Fasting is a physiological stimulus of vagus-mediated enhancement of nociception in the female rat.

PubMed

Khasar, S G; Reichling, D B; Green, P G; Isenberg, W M; Levine, J D

2003-01-01

The vagus nerve modulates nociception by a mechanism dependent upon gonadal hormones and the adrenal medulla. In the present study we tested the hypothesis that this modulation is dynamically controlled by physiological stimulation of structures innervated by the subdiaphragmatic vagus. Specifically, food deprivation (fasting) was employed to increase activity in the subdiaphragmatic vagus, and the experiments were performed mainly in female rats because our previous observations suggested that baseline activity in the pathway is lower in females than in males. Consistent with the hypothesis, after a 48-h fast, female rats exhibited increased nociceptive behavior in the formalin test. In contrast, fasting had no effect on formalin-evoked nociceptive behavior in male rats. The fasting-induced effect on nociception appears to be mediated by the vagus nerve since it is prevented by subdiaphragmatic vagotomy. Also similar to the previously characterized vagus-mediated modulation, the effect of fasting in the female is blocked by gonadectomy or adrenal medullectomy, and hormone replacement with 17beta-estradiol in gonadectomized female rats restored the effect of fasting. Decreased glucose metabolism apparently does not play a significant role in the effect of fasting on nociception, since the effect was unchanged when 5% glucose was provided in the drinking water throughout the fasting period. On the other hand, increasing the bulk content of the stomach (without providing nutrients) by infusion of petrolatum significantly attenuated the effect of fasting during the interphase period of the formalin response, suggesting that decreased gut distention, and possibly motility, are important in fasting-induced enhancement of nociception. These results indicate that fasting is a physiological activator of the vagus-mediated pain modulation pathway. This suggests the possibility that, especially in females, natural periodic changes in gut distention and motility may control an ongoing vagus-mediated adjustment in the organism's nociceptive sensitivity.